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1. Sabbatani S, Fulgaro C, Latini G, Burzi M, Manfredi R: Associated actinomycosis and rhinopharyngeal adenocarcinoma during HIV infection: diagnostic and therapeutic issues. Infez Med; 2008 Sep;16(3):164-72
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  • [Title] Associated actinomycosis and rhinopharyngeal adenocarcinoma during HIV infection: diagnostic and therapeutic issues.
  • An extremely infrequent episode of nasopharyngeal actinomycosis associated with squamous adenocarcinoma occurred in an HIV-infected male patient with a previous diagnosis of AIDS, treated with combined antiretroviral therapy taken with insufficient adherence, such that a satisfactory immune system recovery (as expressed by a CD4 lymphocyte count persistently above 400 cells/mcl), contrasted with a low-level persistence of detectable HIV viraemia, and enlarged genotypic resistance mutations.
  • Despite appropriate and timely diagnostic assessment carried out with repeated, combined computerized tomography, magnetic resonance imaging, and fiberoptic rhinoscopy with biopsy and histopathologic studies, the final diagnosis of a combined dual infectious-neoplastic pathology occurred only after a demolishing surgical intervention and subsequent pathology studies.
  • Despite proper antimicrobial therapy, and an associated radiotherapy and cytotoxic chemotherapy schedule, rapid dissemination of multiple secondary lesions to the brain rapidly led to our patient's death.
  • The imaging and histopathological diagnostics of the dual illnesses of our HIV-infected patient, and its therapeutic and outcome features, are presented and discussed on the basis of the evidence from the available literature.
  • To the best of our knowledge, this is the first described case of actinomycosis associated with a local, underlying squamous cell adenocarcinoma of the same ear, nose, and throat district in either HIV-infected or HIV-non-infected subjects.
  • [MeSH-major] AIDS-Related Opportunistic Infections / complications. Acquired Immunodeficiency Syndrome / complications. Actinomycosis / complications. Carcinoma, Squamous Cell / complications. Nasopharyngeal Neoplasms / complications. Sinusitis / complications
  • [MeSH-minor] Administration, Inhalation. Anti-Bacterial Agents / therapeutic use. Antiretroviral Therapy, Highly Active. Brain Neoplasms / secondary. Cocaine-Related Disorders / complications. Combined Modality Therapy. Fatal Outcome. Heroin Dependence / complications. Humans. Male. Middle Aged. Patient Compliance. Smoking / adverse effects. Substance Abuse, Intravenous / complications. Tomography, X-Ray Computed


2. Lepelletier Y, Camara-Clayette V, Jin H, Hermant A, Coulon S, Dussiot M, Arcos-Fajardo M, Baude C, Canionni D, Delarue R, Brousse N, Benaroch P, Benhamou M, Ribrag V, Monteiro RC, Moura IC, Hermine O: Prevention of mantle lymphoma tumor establishment by routing transferrin receptor toward lysosomal compartments. Cancer Res; 2007 Feb 1;67(3):1145-54
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  • Mantle cell lymphoma (MCL) is one of the most frequent of the newly recognized non-Hodgkin's lymphomas.
  • The major problem of MCL therapy is the occurrence of relapse and subsequent resistance to chemotherapy and immunotherapy in virtually all cases.
  • Here, we show that one injection of anti-human transferrin receptor (TfR) monoclonal antibody A24 totally prevented xenografted MCL tumor establishment in nude mice.
  • In vitro, A24 induced up to 85% reduction of MCL cell proliferation (IC(50) = 3.75 nmol/L) independently of antibody aggregation, complement-dependent or antibody-dependent cell-mediated cytotoxicity.
  • A24 induced MCL cell apoptosis through caspase-3 and caspase-9 activation, either alone or synergistically with chemotherapeutic agents.
  • Therefore, A24-based therapies alone or in association with classic chemotherapies could provide a new alternative strategy against MCL, particularly in relapsing cases.
  • [MeSH-major] Antibodies, Monoclonal / pharmacology. Immunization, Passive / methods. Lymphoma, Mantle-Cell / prevention & control. Lysosomes / metabolism. Receptors, Transferrin / metabolism
  • [MeSH-minor] Animals. Apoptosis / drug effects. Cell Cycle / drug effects. Cell Growth Processes / drug effects. Cell Line, Tumor. Endocytosis / drug effects. Female. Humans. Lymph Nodes / metabolism. Lymph Nodes / pathology. Mice. Mice, Nude. Xenograft Model Antitumor Assays

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  • (PMID = 17283149.001).
  • [ISSN] 0008-5472
  • [Journal-full-title] Cancer research
  • [ISO-abbreviation] Cancer Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Receptors, Transferrin
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3. Hess G, Flohr T, Huber C, Kolbe K, Derigs HG, Fischer T: Safety and feasibility of CHOP/rituximab induction treatment followed by high-dose chemo/radiotherapy and autologous PBSC-transplantation in patients with previously untreated mantle cell or indolent B-cell-non-Hodgkin's lymphoma. Bone Marrow Transplant; 2003 May;31(9):775-82
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  • [Title] Safety and feasibility of CHOP/rituximab induction treatment followed by high-dose chemo/radiotherapy and autologous PBSC-transplantation in patients with previously untreated mantle cell or indolent B-cell-non-Hodgkin's lymphoma.
  • Patients with no prior chemotherapy and with advanced and progressive follicular lymphoma (FCL) or mantle cell lymphoma (MCL) were enrolled into a treatment protocol combining CHOP/rituximab-CHOP therapy with subsequent consolidation high-dose therapy (HDT) to evaluate the safety and feasibility of this treatment.
  • Overall, 15 patients were enrolled and 13 patients completed the entire treatment protocol without major toxicities or increased infectious complications.
  • One patient was taken off study with signs of disease progression after induction treatment.
  • Follow-up of immune reconstitution displayed transient severe combined immunodeficiency with slow normalization of the cellular and humoral compartments without a significant increase of infectious complications.
  • Taken together, high-dose chemotherapy can be safely given following treatment with CHOP+rituximab.
  • Efficacy in this small cohort of patients was encouraging with sustained remissions in both FCL and MCL patients.
  • Upfront HDT should be considered as a therapeutic option especially in young and/or high-risk patients.
  • [MeSH-major] Antibodies, Monoclonal / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lymphoma, B-Cell / therapy. Lymphoma, Mantle-Cell / therapy. Peripheral Blood Stem Cell Transplantation / methods


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4. Kiss TL, Mollee P, Lazarus HM, Lipton JH: Stem cell transplantation for mantle cell lymphoma: if, when and how? Bone Marrow Transplant; 2005 Oct;36(8):655-61
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  • [Title] Stem cell transplantation for mantle cell lymphoma: if, when and how?
  • Although the prognosis for mantle cell lymphoma (MCL) patients has improved in recent years, the outlook for those with advanced or recurrent disease remains poor.
  • High-dose chemotherapy and autografting performed early in responding patients appears to be a method to extend progression-free survival (PFS) and overall survival (OS).
  • The use of monoclonal antibody therapy added into the initial therapy and in the peritransplant period may improve on these results.
  • Myeloablative allogeneic transplant appears to be a modality capable of providing curative therapy, but is plagued by a high treatment-related mortality, especially in older patients.
  • Trials designed to look at newly diagnosed patients with MCL examining the outcomes after planned autologous and allogeneic transplant as part of the initial management are needed to confirm the role of these various modalities in the overall therapy of this poor-outcome lymphoma.
  • [MeSH-major] Lymphoma, Mantle-Cell / therapy. Stem Cell Transplantation / methods

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  • (PMID = 16007106.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 48
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5. Klapper W, Szczepanowski M, Heidorn K, Müschen M, Liedtke S, Sotnikova A, Andersen NS, Greeve J, Parwaresch R: Immunoglobulin class-switch recombination occurs in mantle cell lymphomas. J Pathol; 2006 Jun;209(2):250-7
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  • [Title] Immunoglobulin class-switch recombination occurs in mantle cell lymphomas.
  • Mantle cell lymphoma (MCL) is an IgM-expressing B cell lymphoma that originates from naive B cells and responds poorly to chemotherapy.
  • Similar to the situation in normal B cells, in vitro stimulation of MCL cell lines with CD40 ligand (CD40L) and interleukin-4 induced expression of activation-induced cytidine deaminase (AID) and germline transcription at the immunoglobulin heavy chain gene locus.
  • Additionally, the occurrence of switch-circle transcripts and mature IgG transcripts after stimulation indicated ongoing class-switch recombination in mantle cell lymphoma cell lines.
  • Furthermore, stimulation of primary MCL cells in vitro induced expression of class-switched IgG mRNA in the tumour cells.
  • Our data indicate that mantle cell lymphomas have retained the ability to undergo class-switch recombination if appropriate stimuli, such as the CD40 ligand, are provided.
  • [MeSH-major] Immunoglobulin Class Switching / genetics. Lymphoma, Mantle-Cell / genetics
  • [MeSH-minor] Antigens, CD40 / immunology. Cell Line, Tumor. Cytidine Deaminase / immunology. Dendritic Cells, Follicular / immunology. Genes, Immunoglobulin Heavy Chain / genetics. Genes, Immunoglobulin Heavy Chain / immunology. Humans. Immunoglobulin G / genetics. Immunoglobulin G / immunology. Immunohistochemistry / methods. Interleukin-4 / immunology. Mutation / genetics. Mutation / immunology. RNA, Messenger / analysis. RNA, Neoplasm / analysis. Recombination, Genetic / genetics. Recombination, Genetic / immunology. Reverse Transcriptase Polymerase Chain Reaction / methods. Transcription, Genetic / genetics. Transcription, Genetic / immunology

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  • [Copyright] Copyright (c) 2006 Pathological Society of Great Britain and Ireland.
  • (PMID = 16508921.001).
  • [ISSN] 0022-3417
  • [Journal-full-title] The Journal of pathology
  • [ISO-abbreviation] J. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD40; 0 / Immunoglobulin G; 0 / RNA, Messenger; 0 / RNA, Neoplasm; 207137-56-2 / Interleukin-4; EC 3.5.4.5 / Cytidine Deaminase
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6. Linehan WM, Pinto PA, Bratslavsky G, Pfaffenroth E, Merino M, Vocke CD, Toro JR, Bottaro D, Neckers L, Schmidt LS, Srinivasan R: Hereditary kidney cancer: unique opportunity for disease-based therapy. Cancer; 2009 May 15;115(10 Suppl):2252-61
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  • [Title] Hereditary kidney cancer: unique opportunity for disease-based therapy.
  • Kidney cancer is not a single disease; it is comprised of several different types of cancer, each with a different histology, with a different clinical course, caused by a different gene, and responding differently to therapy.
  • The VHL gene is the gene for the hereditary cancer syndrome, von Hippel-Lindau, as well as for the common form of sporadic, noninherited, clear cell kidney cancer.
  • Hereditary papillary renal carcinoma (HPRC) is a hereditary renal cancer syndrome in which affected individuals are at risk for the development of bilateral, multifocal, type 1 papillary renal cell carcinoma.
  • The genetic defect underlying HPRC is MET, the cell surface receptor for hepatocyte growth factor.
  • Mutations of MET also have been identified in a subset of tumors from patients with sporadic type 1 papillary renal cell carcinoma (RCC).
  • Clinical trials targeting the MET pathway are currently underway in patients with HPRC and in patients with sporadic (nonhereditary) papillary kidney cancer.
  • The BHD gene (also known as folliculin or FLCN) is the gene for Birt-Hogg-Dube syndrome, an autosomal-dominant genodermatosis associated with a hereditary form of chromophobe and oncocytic, hybrid RCC.
  • Preclinical studies are underway targeting the BHD gene pathway in preparation for clinical trials in Birt-Hogg-Dube and sporadic chromophobe RCC.
  • Patients with hereditary leiomyomatosis RCC (HLRCC) are at risk for developing cutaneous and uterine leiomyomas and a very aggressive type of RCC.
  • HLRCC is characterized by germline mutation of the Krebs cycle enzyme, fumarate hydratase (FH).
  • Studies of the tricarboxylic acid cycle and the VHL-HIF pathways have provided the foundation for therapeutic approaches in patients with HLRCC-associated kidney cancer as well as other hereditary and sporadic forms of RCC.


7. Yoong Y, Kurtin PJ, Allmer C, Geyer S, Habermann TM, Nagorney DM, Witzig TE: Efficacy of splenectomy for patients with mantle cell non-Hodgkin's lymphoma. Leuk Lymphoma; 2001 Nov-Dec;42(6):1235-41
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  • [Title] Efficacy of splenectomy for patients with mantle cell non-Hodgkin's lymphoma.
  • The purpose of this study was to define the role of splenectomy in patients (pts) with mantle cell lymphoma (MCL) with regard to improving cytopenias and symptoms of splenomegaly.
  • 26 pts with MCL underwent splenectomy between January 1987 and October 1999 and were followed prospectively for hematologic response and operative morbidity and mortality.
  • A positive response was defined at 1 month of follow-up as: a hemoglobin of > or = 1.0 g/dl in a pt with a preoperative value < 11.0 g/dl; or a platelet count of > or = 100 x 10(9)/L in a pt with a preoperative value < 100 x 10(9)/L.
  • Four (15.4%) pts have not required chemotherapy after splenectomy.
  • Three of these four were previously untreated and they have maintained stable disease for eight years after splenectomy without chemotherapy.
  • Eight additional pts did not require chemotherapy for > 13 months after splenectomy.
  • These results suggest that splenectomy may provide durable remission in selected pts with refractory cytopenias or symptoms related to splenomegaly in pts with MCL.
  • There is a subset of pts that have prolonged disease stabilization without the requirement for immediate chemotherapy after splenectomy.
  • [MeSH-major] Lymphoma, Mantle-Cell / surgery. Splenectomy

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  • (PMID = 11911404.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Switzerland
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8. Zhang L, Qian Z, Cai Z, Sun L, Wang H, Bartlett JB, Yi Q, Wang M: Synergistic antitumor effects of lenalidomide and rituximab on mantle cell lymphoma in vitro and in vivo. Am J Hematol; 2009 Sep;84(9):553-9
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  • [Title] Synergistic antitumor effects of lenalidomide and rituximab on mantle cell lymphoma in vitro and in vivo.
  • Rituximab (RTX), a chimeric anti-CD20 antibody, is associated with direct induction of apoptosis and antibody-dependent cell-mediated cytotoxicity (ADCC) with clinical efficacy in mantle cell lymphoma (MCL).
  • Our study attempted to elucidate the mechanism of LEN-enhanced RTX-mediated cytotoxicity of MCL cells.
  • We found that LEN and RTX induced growth inhibition of both cultured and fresh primary MCL cells.
  • LEN enhanced RTX-induced apoptosis via upregulating phosphorylation of c-Jun N-terminal protein kinases (JNK), Bcl-2, Bad; increasing release of cytochrome-c; enhancing activation of caspase-3, -8, -9 and cleavage of PARP.
  • Whole PBMCs but not NK cell-depleted PBMCs treated with LEN augmented 30% of RTX-dependent cytotoxicity.
  • Daily treatment with LEN increased NK cells by 10-folds in SCID mice, and combination of LEN and RTX decreased tumor burden and prolonged survival of MCL-bearing SCID mice.
  • Taken together, our study demonstrates that LEN plus RTX provides a synergistically therapeutic effect on MCL cells by enhancing apoptosis and RTX-dependent NK cell-mediated cytotoxicity and may be an optimal combination in the clinical trial of relapsed or refractory MCL.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lymphoma, Mantle-Cell / drug therapy
  • [MeSH-minor] Animals. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal / pharmacology. Antibodies, Monoclonal, Murine-Derived. Apoptosis / drug effects. Apoptosis Regulatory Proteins / metabolism. Blood Cells / drug effects. Cell Line, Tumor. Cell Proliferation / drug effects. Cells, Cultured. Drug Synergism. Humans. Killer Cells, Natural / drug effects. Leukocytes, Mononuclear / drug effects. MAP Kinase Kinase 4 / metabolism. Mice. Mice, SCID. Neoplasms, Experimental / drug therapy. Phosphorylation / drug effects. Rituximab. Thalidomide / administration & dosage. Thalidomide / analogs & derivatives. Thalidomide / pharmacology

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  • [Copyright] 2009 Wiley-Liss, Inc.
  • (PMID = 19565649.001).
  • [ISSN] 1096-8652
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Apoptosis Regulatory Proteins; 4F4X42SYQ6 / Rituximab; 4Z8R6ORS6L / Thalidomide; EC 2.7.12.2 / MAP Kinase Kinase 4; F0P408N6V4 / lenalidomide
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9. Hedley BD, Winquist E, Chambers AF: Therapeutic targets for antimetastatic therapy. Expert Opin Ther Targets; 2004 Dec;8(6):527-36
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Therapeutic targets for antimetastatic therapy.
  • Metastases are responsible for most cancer deaths.
  • Despite dramatic advances in cancer therapy, the presence of metastases implies a significantly shortened survival and reduced quality of remaining life.
  • Aside from prevention of cancer altogether, or significant improvements in early detection for most cancers, effective novel therapeutic strategies targeting metastasis should provide the greatest clinical benefit.
  • Metastasis research has shown that many of the initial steps in metastasis are completed with a high degree of efficiency and may have occurred by the time of clinical diagnosis.
  • Therefore, targeting the later stages of metastasis may offer a more promising therapeutic approach for the development of antimetastatic therapies.
  • Dormancy of solitary single cells, seen clinically and experimentally, may be an explanation for cancer recurrence.
  • However, little is known about what makes cancer cells dormant and, therefore, a greater knowledge of the mechanisms of dormancy is needed.
  • This review discusses potential biological targets, as defined by the steps in the metastatic process, for antimetastatic therapies and provides examples of clinical strategies for preventing or treating successful metastasis.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Neoplasm Metastasis / drug therapy
  • [MeSH-minor] Angiogenesis Inhibitors / pharmacology. Angiogenesis Inhibitors / therapeutic use. Bone Neoplasms / drug therapy. Bone Neoplasms / secondary. Disease Progression. Drug Design. Female. Humans. Male. Neoplasm Proteins / antagonists & inhibitors. Neoplasm Proteins / physiology. Neoplastic Cells, Circulating. Neoplastic Stem Cells / drug effects. Neoplastic Stem Cells / physiology. Neovascularization, Pathologic / drug therapy. Randomized Controlled Trials as Topic

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  • (PMID = 15584860.001).
  • [ISSN] 1744-7631
  • [Journal-full-title] Expert opinion on therapeutic targets
  • [ISO-abbreviation] Expert Opin. Ther. Targets
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Antineoplastic Agents; 0 / Neoplasm Proteins
  • [Number-of-references] 108
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10. Dreger P, Martin S, Kuse R, Sonnen R, Glass B, Kröger N, Parwaresch R, Kneba M, Schmitz N, Haas R: The impact of autologous stem cell transplantation on the prognosis of mantle cell lymphoma: a joint analysis of two prospective studies with 46 patients. Hematol J; 2000;1(2):87-94
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  • [Title] The impact of autologous stem cell transplantation on the prognosis of mantle cell lymphoma: a joint analysis of two prospective studies with 46 patients.
  • INTRODUCTION: The purpose of this analysis was to investigate if early sequential high-dose therapy with autologous stem cell transplantation (ASCT) can improve the poor prognosis of patients with disseminated mantle cell lymphoma (MCL).
  • Both were characterized by a sequential high-dose therapy consisting of an intensive chemotherapy ('HAM' or 'Dexa-BEAM') for mobilization of peripheral blood stem cells and induction of minimal disease followed by a total body irradiation-containing myeloablative regimen and ASCT.
  • Forty-six patients with reference panel-confirmed stage III/IV MCL were included.
  • RESULTS: All patients were in remission after mobilization chemotherapy and proceeded to ASCT; there were no exclusions due to poor response, poor mobilization, or patient refusal.
  • With a follow-up of 24 (2-73) months post transplant, the event-free and overall survival probabilities at 2 years were 77 and 100% for the upfront ASCT group compared to 30% (P=0.0007) and 54% (P=0.0016) for the delayed ASCT group.
  • CONCLUSION: ASCT is not curative but may improve the prognosis of patients with MCL if performed as part of an intensive first-line treatment strategy.

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  • (PMID = 11920175.001).
  • [ISSN] 1466-4860
  • [Journal-full-title] The hematology journal : the official journal of the European Haematology Association
  • [ISO-abbreviation] Hematol. J.
  • [Language] ENG
  • [Publication-type] Clinical Trial; Comparative Study; Controlled Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; 9PHQ9Y1OLM / Prednisolone; Q41OR9510P / Melphalan; U68WG3173Y / Carmustine; VB0R961HZT / Prednisone
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11. Tobinai K: 4. Antibody therapy for malignant lymphoma. Intern Med; 2007;46(2):99-100
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  • [Title] 4. Antibody therapy for malignant lymphoma.
  • Rituximab, a genetically engineered, chimeric anti-CD20 monoclonal antibody, induces the apoptosis of B-lymphoma cells, in addition to the lyses by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), as shown in Fig.
  • 1. A Japanese phase I study of rituximab in relapsed or refractory patients with B-cell non-Hodgkin's lymphoma (B-NHL) showed an overall response rate (ORR) of 64% (7/11) with minimal toxicities.
  • In the subsequent phase II study, 90 relapsed or refractory patients with indolent B-NHL or mantle cell lymphoma (MCL) were treated with rituximab at 375 mg/m2x4 weekly infusions.
  • ORRs in indolent B-NHL and MCL were 61% (37/61) and 46% (6/13), respectively.
  • In this presentation, the results of clinical trials of antibody therapy of malignant lymphoma are summarized, focusing on the two recent Japanese multicenter trials of rituximab and a Japanese feasibility study of anti-CD20 radioimmunotherapy with yttrium-90-lableled ibritumomab tiuxetan.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Lymphoma / drug therapy
  • [MeSH-minor] Antibodies, Monoclonal, Murine-Derived. Antigens, CD20 / immunology. Humans. Lymphoma, B-Cell / drug therapy. Lymphoma, B-Cell / radiotherapy. Lymphoma, Mantle-Cell / drug therapy. Lymphoma, Mantle-Cell / radiotherapy. Lymphoma, Non-Hodgkin / drug therapy. Lymphoma, Non-Hodgkin / radiotherapy. Radioimmunotherapy. Rituximab. Yttrium Radioisotopes

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  • (PMID = 17220608.001).
  • [ISSN] 1349-7235
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antigens, CD20; 0 / Yttrium Radioisotopes; 0 / ibritumomab tiuxetan; 4F4X42SYQ6 / Rituximab
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12. Romaguera JE: Mantle cell lymphoma: Frontline and salvage therapy. Curr Hematol Malig Rep; 2008 Oct;3(4):204-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Mantle cell lymphoma: Frontline and salvage therapy.
  • Mantle cell lymphoma (MCL) is a therapeutic challenge because of its lower cure rate when compared with other lymphomas such as diffuse large cell lymphoma.
  • The current emphasis in the treatment of newly diagnosed MCL has been on intensifying chemotherapy, but there is no consensus on the need to consolidate with autologous stem cell transplantation.
  • Newer strategies include the use of models to aid in tailoring therapy.
  • Likewise, autologous stem cell consolidation does not cure relapsed disease.
  • Because of its known graft-versus-lymphoma effect, allogeneic stem cell transplantation offers a potentially curative option for relapsed MCL.
  • New insights into resistance pathways and new drugs created to inhibit them offer great promise in the treatment of newly diagnosed and previously treated MCL.
  • [MeSH-major] Lymphoma, Mantle-Cell / therapy. Salvage Therapy
  • [MeSH-minor] Clinical Trials as Topic. Drug Therapy, Combination. Humans. Neoplasm, Residual. Recurrence. Stem Cell Transplantation. Transplantation, Autologous. Transplantation, Homologous

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  • (PMID = 20425467.001).
  • [ISSN] 1558-822X
  • [Journal-full-title] Current hematologic malignancy reports
  • [ISO-abbreviation] Curr Hematol Malig Rep
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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13. Kravchenko AV, Miroshnichenko AV, Beliaeva VV, Serebrovskaia LV, Bogoslovskaia EV, Sitdykova IuR: [Antiretroviral therapy of acute HIV-infection]. Ter Arkh; 2004;76(4):15-8
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  • [Title] [Antiretroviral therapy of acute HIV-infection].
  • [Transliterated title] Antiretrovirusnaia terapiia ostroĭ VICh-infektsii.
  • AIM: To study efficacy of a short course of highly active antiretroviral therapy (HAART).
  • MATERIAL AND METHODS: Acute HIV infection was verified in 16 infected subjected basing either on seroconversion (by immunoblotting) or a documented negative result 6-12 months before registration of a positive result for HIV antibodies.
  • The number of CD+ lymphocytes (by median) 1 month after the treatment increased by 185 cells/mcl, 3 months after the treatment--by 215 cells/mcl.
  • After 1-month therapy viral load (median) diminished by 2.02 log10 copy/ml, after 3 months--by 2.31 log10 copy/ml.
  • Therefore, it is necessary to consult the patients for preparing them for treatment and to maintain compliance.
  • [MeSH-major] Anti-HIV Agents / administration & dosage. HIV Infections / drug therapy. Lamivudine / administration & dosage. Nevirapine / administration & dosage. Zidovudine / administration & dosage
  • [MeSH-minor] Adult. Antiretroviral Therapy, Highly Active. Drug Combinations. Female. HIV Seropositivity / immunology. Humans. Lymphocyte Count. Male. Viral Load

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  • (PMID = 15174313.001).
  • [ISSN] 0040-3660
  • [Journal-full-title] Terapevticheskiĭ arkhiv
  • [ISO-abbreviation] Ter. Arkh.
  • [Language] rus
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Russia
  • [Chemical-registry-number] 0 / Anti-HIV Agents; 0 / Drug Combinations; 0 / lamivudine, zidovudine drug combination; 2T8Q726O95 / Lamivudine; 4B9XT59T7S / Zidovudine; 99DK7FVK1H / Nevirapine
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14. Rosato RR, Almenara JA, Kolla SS, Maggio SC, Coe S, Giménez MS, Dent P, Grant S: Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions. Mol Cancer Ther; 2007 Feb;6(2):692-702
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  • [Title] Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions.
  • The mechanism and functional significance of XIAP and Mcl-1 down-regulation in human leukemia cells exposed to the histone deacetylase inhibitor vorinostat and the cyclin-dependent kinase inhibitor flavopiridol was investigated.
  • Combined exposure of U937 leukemia cells to marginally toxic concentrations of vorinostat and flavopiridol resulted in a marked increase in mitochondrial damage and apoptosis accompanied by pronounced reductions in XIAP and Mcl-1 mRNA and protein.
  • Down-regulation of Mcl-1 and XIAP expression by vorinostat/flavopiridol was associated with enhanced inhibition of phosphorylation of RNA polymerase II and was amplified by caspase-mediated protein degradation.
  • Chromatin immunoprecipitation analysis revealed that XIAP and Mcl-1 down-regulation were also accompanied by both decreased association of nuclear factor-kappaB (XIAP) and increased E2F1 association (Mcl-1) with their promoter regions, respectively.
  • Ectopic expression of Mcl-1 but not XIAP partially protected cells from flavopiridol/vorinostat-mediated mitochondrial injury at 48 h, but both did not significantly restored clonogenic potential.
  • Flavopiridol/vorinostat-mediated transcriptional repression of XIAP, Mcl-1-enhanced apoptosis, and loss of clonogenic potential also occurred in primary acute myelogenous leukemia (AML) blasts.
  • Together, these findings indicate that transcriptional repression of XIAP and Mcl-1 by flavopiridol/vorinostat contributes functionally to apoptosis induction at early exposure intervals and raise the possibility that expression levels may be a useful surrogate marker for activity in current trials.
  • [MeSH-minor] Apoptosis / drug effects. Apoptosis Inducing Factor / metabolism. Blast Crisis. Blotting, Western. Butyrates / pharmacology. Caspases / metabolism. Chromatin Immunoprecipitation. Cyclin-Dependent Kinases / antagonists & inhibitors. Cytochromes c / metabolism. Down-Regulation. Drug Interactions. Histone Deacetylase Inhibitors. Humans. Leukemia, Myeloid, Acute / drug therapy. Leukemia, Myeloid, Acute / metabolism. Membrane Potential, Mitochondrial / drug effects. Myeloid Cell Leukemia Sequence 1 Protein. RNA, Messenger / genetics. RNA, Messenger / metabolism. Reverse Transcriptase Polymerase Chain Reaction. Transcription, Genetic / drug effects. Tumor Stem Cell Assay. U937 Cells / drug effects

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  • (PMID = 17308065.001).
  • [ISSN] 1535-7163
  • [Journal-full-title] Molecular cancer therapeutics
  • [ISO-abbreviation] Mol. Cancer Ther.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 100866; United States / NCI NIH HHS / CA / CA 63753; United States / NCI NIH HHS / CA / CA 93738
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / AIFM1 protein, human; 0 / Antineoplastic Agents; 0 / Apoptosis Inducing Factor; 0 / Butyrates; 0 / Flavonoids; 0 / Histone Deacetylase Inhibitors; 0 / Hydroxamic Acids; 0 / Myeloid Cell Leukemia Sequence 1 Protein; 0 / Neoplasm Proteins; 0 / Piperidines; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / RNA, Messenger; 0 / X-Linked Inhibitor of Apoptosis Protein; 0 / XIAP protein, human; 45AD6X575G / alvocidib; 58IFB293JI / vorinostat; 9007-43-6 / Cytochromes c; EC 2.7.11.22 / Cyclin-Dependent Kinases; EC 3.4.22.- / Caspases
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15. Visser HP, Tewis M, Willemze R, Kluin-Nelemans JC: Mantle cell lymphoma proliferates upon IL-10 in the CD40 system. Leukemia; 2000 Aug;14(8):1483-9
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  • [Title] Mantle cell lymphoma proliferates upon IL-10 in the CD40 system.
  • Mantle cell lymphoma (MCL) is a B cell non-Hodgkin's lymphoma, characterized by a poor response to therapy and short survival.
  • To assess the proliferative capacity, we cultured MCL cells, using irradiated 3T6 mouse fibroblasts transfected with human CD40L ('CD40 system') in the presence of different cytokines.
  • Thirteen out of 16 MCL cases proliferated well in the CD40 system.
  • CFSE staining of cells before and after culture showed an increased number of cell divisions in the IL-10/CD40L stimulated cells.
  • The MCL cells remained CD5+CD19+.
  • Neither plasma cell differentiation nor isotype switching was seen.
  • IL-1beta, IL-2, IL-6, G-CSF and GM-CSF did not stimulate MCL proliferation.
  • Autocrine IL-10 production by the MCL cells was detected in eight of 10 cases tested.
  • In conclusion, MCL can successfully be cultured upon CD40 stimulation if 3T6 CD40L+ cells are used.
  • This culture system may be useful to test new treatment strategies for this, thus far, therapy-resistant lymphoma.
  • [MeSH-major] Antigens, CD40 / immunology. Cell Division / drug effects. Interleukin-10 / pharmacology. Lymphoma, Mantle-Cell / pathology
  • [MeSH-minor] Animals. Dose-Response Relationship, Drug. Humans. Immunoglobulin Class Switching. Immunophenotyping. Mice. Receptors, Interleukin / antagonists & inhibitors. Receptors, Interleukin-10. Tumor Cells, Cultured

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  • (PMID = 10942246.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] ENGLAND
  • [Chemical-registry-number] 0 / Antigens, CD40; 0 / Receptors, Interleukin; 0 / Receptors, Interleukin-10; 130068-27-8 / Interleukin-10
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16. Neumeyer JL, Bidlack JM, Zong R, Bakthavachalam V, Gao P, Cohen DJ, Negus SS, Mello NK: Synthesis and opioid receptor affinity of morphinan and benzomorphan derivatives: mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine dependence. J Med Chem; 2000 Jan 13;43(1):114-22
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  • [Title] Synthesis and opioid receptor affinity of morphinan and benzomorphan derivatives: mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine dependence.
  • This report concerns the synthesis and preliminary pharmacological evaluation of a novel series of kappa agonists related to the morphinan (-)-cyclorphan (3a) and the benzomorphan (-)-cyclazocine (2) as potential agents for the pharmacotherapy of cocaine abuse.
  • We describe the synthesis and chemical characterization of a series of morphinans 3a-c, structural analogues of cyclorphan [(-)-3-hydroxy-N-cyclopropylmethylmorphinan S(+)-mandelate, 3a], the 10-ketomorphinans 4a,b, and the 8-ketobenzomorphan 1b.
  • Binding experiments demonstrated that the cyclobutyl analogue 3b [(-)-3-hydroxy-N-cyclobutylmethylmorphinan S(+)-mandelate, 3b, MCL-101] of cyclorphan (3a) had a high affinity for mu, delta, and kappa opioid receptors in guinea pig brain membranes.
  • [MeSH-major] Benzomorphans / chemical synthesis. Morphinans / chemical synthesis. Receptors, Opioid, kappa / drug effects. Receptors, Opioid, mu / drug effects
  • [MeSH-minor] Acetic Acid. Animals. Brain / metabolism. Dose-Response Relationship, Drug. Ethylketocyclazocine / analogs & derivatives. Ethylketocyclazocine / pharmacology. Guinea Pigs. In Vitro Techniques. Injections, Intraventricular. Male. Mice. Mice, Inbred ICR. Morphine / antagonists & inhibitors. Narcotic Antagonists / chemical synthesis. Narcotic Antagonists / pharmacology. Pain / chemically induced. Pain / drug therapy. Pain Measurement. Reaction Time / drug effects

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  • (PMID = 10633042.001).
  • [ISSN] 0022-2623
  • [Journal-full-title] Journal of medicinal chemistry
  • [ISO-abbreviation] J. Med. Chem.
  • [Language] eng
  • [Grant] United States / NIDA NIH HHS / DA / DA00360; United States / NIDA NIH HHS / DA / K05-DA00101; United States / NIDA NIH HHS / DA / U-19-DA11007
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Benzomorphans; 0 / Morphinans; 0 / Narcotic Antagonists; 0 / Receptors, Opioid, kappa; 0 / Receptors, Opioid, mu; 58640-84-9 / Ethylketocyclazocine; 6IO4IG518S / ketazocine; 76I7G6D29C / Morphine; Q40Q9N063P / Acetic Acid
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17. Garnock-Jones KP: Bendamustine: a review of its use in the management of indolent non-Hodgkin's lymphoma and mantle cell lymphoma. Drugs; 2010 Sep 10;70(13):1703-18
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  • [Title] Bendamustine: a review of its use in the management of indolent non-Hodgkin's lymphoma and mantle cell lymphoma.
  • Bendamustine (bendamustine hydrochloride) is an alkylating agent indicated in several countries for the treatment of indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma (MCL).
  • Bendamustine monotherapy was effective in treatment-refractory (including rituximab-refractory) indolent NHL or MCL.
  • Moreover, bendamustine-based combination treatment was at least as effective as cyclophosphamide-based treatment, and bendamustine plus rituximab was at least as effective as cyclophosphamide, doxorubicin, vincristine plus prednisone (CHOP) plus rituximab, as first-line therapy in patients with indolent NHL or MCL.
  • Treatment-refractory disease also appeared to respond favourably to bendamustine-containing combination treatment.
  • In general, bendamustine was associated with a high overall response rate and a durable response.
  • Regimens that included bendamustine were also associated with a very low rate of alopecia compared with regimens that included other antineoplastic drugs.
  • In conclusion, bendamustine is a unique alkylating agent, which in clinical trials has demonstrated consistent efficacy and acceptable tolerability in patients with indolent NHL or MCL.
  • It may be a particularly useful treatment option in patients with rituximab-refractory disease, but has also demonstrated efficacy as part of a first-line combination treatment.
  • While further research is necessary to firmly establish the best place for bendamustine in the management of indolent NHL and MCL, it is a valuable addition to the pool of available treatments for these diseases.
  • [MeSH-major] Lymphoma, Mantle-Cell / drug therapy. Lymphoma, Non-Hodgkin / drug therapy. Nitrogen Mustard Compounds / therapeutic use
  • [MeSH-minor] Animals. Antineoplastic Agents / adverse effects. Antineoplastic Agents / pharmacokinetics. Antineoplastic Agents / therapeutic use. Bendamustine Hydrochloride. Clinical Trials as Topic. Humans

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  • (PMID = 20731477.001).
  • [ISSN] 1179-1950
  • [Journal-full-title] Drugs
  • [ISO-abbreviation] Drugs
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] New Zealand
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Nitrogen Mustard Compounds; 981Y8SX18M / Bendamustine Hydrochloride
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18. Gotlib J, Berubé C, Growney JD, Chen CC, George TI, Williams C, Kajiguchi T, Ruan J, Lilleberg SL, Durocher JA, Lichy JH, Wang Y, Cohen PS, Arber DA, Heinrich MC, Neckers L, Galli SJ, Gilliland DG, Coutré SE: Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation. Blood; 2005 Oct 15;106(8):2865-70
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  • [Title] Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation.
  • The majority of patients with systemic mast cell disease express the imatinib-resistant Asp816Val (D816V) mutation in the KIT receptor tyrosine kinase.
  • Limited treatment options exist for aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL).
  • We evaluated whether PKC412, a small-molecule inhibitor of KIT with a different chemical structure from imatinib, may have therapeutic use in advanced SM with the D816V KIT mutation.
  • We treated a patient with MCL (with an associated myelodysplastic syndrome (MDS)/myeloproliferative disorder [MPD]) based on in vitro studies demonstrating that PKC412 could inhibit D816V KIT-transformed Ba/F3 cell growth with a 50% inhibitory concentration (IC50) of 30 nM to 40 nM.
  • In addition, PKC412 treatment resulted in a significant decline in the percentage of peripheral blood mast cells and serum histamine level and was associated with a decrease in KIT phosphorylation and D816V KIT mutation frequency.
  • The patient died after 3 months of therapy due to progression of her MDS/MPD to acute myeloid leukemia (AML).

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  • (PMID = 15972446.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA66996; United States / NIDDK NIH HHS / DK / DK50654; United States / NHLBI NIH HHS / HL / K23HL04409; United States / NIAID NIH HHS / AI / AI-41995; United States / NIAID NIH HHS / AI / AI-23990; United States / NCI NIH HHS / CA / CA-72074
  • [Publication-type] Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Protein Kinase Inhibitors; 120685-11-2 / 4'-N-benzoylstaurosporine; 30KYC7MIAI / Aspartic Acid; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit; H88EPA0A3N / Staurosporine
  • [Other-IDs] NLM/ PMC1895309
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19. Dubay RA, Rose PG, O'Malley DM, Shalodi AD, Ludin A, Selim MA: Evaluation of concurrent and adjuvant carboplatin with radiation therapy for locally advanced cervical cancer. Gynecol Oncol; 2004 Jul;94(1):121-4
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  • [Title] Evaluation of concurrent and adjuvant carboplatin with radiation therapy for locally advanced cervical cancer.
  • OBJECTIVE: To analyze the toxicity profile and long-term outcomes of patients receiving carboplatin with concurrent radiation for locally advanced cervical cancer.
  • METHODS: A retrospective study was performed to identify patients treated with carboplatin and concurrent radiation therapy for locally advanced cervical cancer with a minimum follow-up period of 24 months.
  • Records were reviewed for demographic data, chemotherapy doses, toxicities, and survival outcomes.
  • Specifically reviewed were hematologic, gastrointestinal, and renal toxicities and the need for dose modification and treatment delays.
  • RESULTS: Twenty-one patients with cervical carcinoma Stage IIB (7), III (13), or IVA (1) treated with carboplatin chemotherapy from 1993 to 2001 were identified.
  • Carboplatin at a dose of 300 mg/m(2) administered every 3 weeks for an intended six courses was initiated at the start of radiation therapy.
  • No grade 3 or 4 thrombocytopenia or renal toxicity was observed.
  • Nine patients had delays in chemotherapy administration and/or received a 25% reduction in the dose of chemotherapy based on one or more of the following: thrombocytopenia (platelet count <100000 cells/mcl) (n = 3), granulocytopenia (ANC <1.0) (n = 4), or anemia (hemoglobin <10.0 g/dl) (n = 5).
  • Six patients developed recurrent disease (five local and one distant) with a pelvic control rate of 76% and an overall survival of 71%.
  • CONCLUSION: Carboplatin at a dose of 300 mg/m(2) (equivalent to an AUC of 3.9) on an every 3-week schedule is tolerable with concurrent pelvic radiation therapy for locally advanced cervical cancer.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Carboplatin / therapeutic use. Uterine Cervical Neoplasms / drug therapy. Uterine Cervical Neoplasms / radiotherapy
  • [MeSH-minor] Adult. Aged. Chemotherapy, Adjuvant. Drug Administration Schedule. Female. Humans. Middle Aged. Neoplasm Staging. Radiotherapy / adverse effects. Retrospective Studies. Treatment Outcome


20. Li R, Zang Y, Li C, Patel NS, Grandis JR, Johnson DE: ABT-737 synergizes with chemotherapy to kill head and neck squamous cell carcinoma cells via a Noxa-mediated pathway. Mol Pharmacol; 2009 May;75(5):1231-9
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  • [Title] ABT-737 synergizes with chemotherapy to kill head and neck squamous cell carcinoma cells via a Noxa-mediated pathway.
  • Overexpression of Bcl-X(L), an antiapoptotic Bcl-2 family member, occurs in a majority of head and neck squamous cell carcinomas (HNSCCs) and correlates with chemotherapy resistance in this disease.
  • As a single agent, ABT-737 was largely ineffective at promoting HNSCC cell death.
  • By contrast, ABT-737 strongly synergized with the chemotherapy drugs cisplatin and etoposide to promote HNSCC cell death and loss of clonogenic survival.
  • Synergism between ABT-737 and chemotherapy was associated with synergistic activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase.
  • Treatment with ABT-737 plus chemotherapy resulted in dramatic up-regulation of proapoptotic Noxa protein, and small interfering RNA (siRNA)-mediated inhibition of Noxa up-regulation partially attenuated cell death by the synergistic combination.
  • Treatment with cisplatin or etoposide, alone or in combination with ABT-737, resulted in substantial down-regulation of Mcl-1L, a known inhibitor of ABT-737 action.
  • Further down-regulation of Mcl-1L using siRNA failed to enhance killing by the cisplatin/ABT-737 synergistic combination, indicating that chemotherapy treatment of HNSCC cells is sufficient to remove this impediment to ABT-737.
  • Together, our results demonstrate potent synergy between ABT-737 and chemotherapy drugs in the killing of HNSCC cells and reveal an important role for Noxa in mediating synergism by these agents.

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  • (PMID = 19246337.001).
  • [ISSN] 1521-0111
  • [Journal-full-title] Molecular pharmacology
  • [ISO-abbreviation] Mol. Pharmacol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P50 CA097190; United States / NCI NIH HHS / CA / P50-CA097190-01A1
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / ABT-737; 0 / Antineoplastic Agents; 0 / Biphenyl Compounds; 0 / Boronic Acids; 0 / Myeloid Cell Leukemia Sequence 1 Protein; 0 / Nitrophenols; 0 / PMAIP1 protein, human; 0 / Piperazines; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / Pyrazines; 0 / Sulfonamides; 0 / bcl-X Protein; 69G8BD63PP / Bortezomib; Q20Q21Q62J / Cisplatin
  • [Other-IDs] NLM/ PMC2672802
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21. Decaudin D, Brousse N, Brice P, Haioun C, Bourhis JH, Morel P, Van Hoof A, Souleau B, Quesnel B, Gisselbrecht C: Efficacy of autologous stem cell transplantation in mantle cell lymphoma: a 3-year follow-up study. Bone Marrow Transplant; 2000 Feb;25(3):251-6
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  • [Title] Efficacy of autologous stem cell transplantation in mantle cell lymphoma: a 3-year follow-up study.
  • This study was designed to evaluate the efficacy of therapeutic intensification with autologous stem cell transplantation (ASCT) for mantle cell lymphomas (MCL) in terms of response rate, duration of response, and event-free and overall survivals.
  • Twenty-four patients with confirmed MCL responding to chemotherapy received a high-dose chemo-radiotherapy regimen followed by ASCT.
  • Transplantation was performed during first-line therapy in nine cases, second-line in 13 cases and third-line in two cases.
  • At the time of ASCT, eight patients were in complete remission (33%).
  • One patient died from Pneumocystis carinii interstitial pneumonitis and five patients developed secondary malignancies.
  • With a median follow-up after transplantation of 34 months, the 3-year event-free survival was 55% and the 3-year overall survival was 68%.
  • These results indicate that therapeutic intensification with ASCT might be an effective treatment for mantle cell lymphomas.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lymphoma, Mantle-Cell / complications. Lymphoma, Mantle-Cell / therapy
  • [MeSH-minor] Adult. Bacterial Infections / etiology. Carmustine / administration & dosage. Carmustine / toxicity. Combined Modality Therapy / adverse effects. Cyclophosphamide / administration & dosage. Cyclophosphamide / toxicity. Cytarabine / administration & dosage. Cytarabine / toxicity. Etoposide / administration & dosage. Etoposide / toxicity. Female. Follow-Up Studies. Hematopoietic Stem Cell Transplantation / adverse effects. Humans. Male. Melphalan / administration & dosage. Melphalan / toxicity. Middle Aged. Neoplasms, Second Primary / etiology. Recurrence. Survival Rate. Transplantation, Autologous / adverse effects. Treatment Outcome. Whole-Body Irradiation / adverse effects

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  • (PMID = 10673695.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study
  • [Publication-country] ENGLAND
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 6PLQ3CP4P3 / Etoposide; 8N3DW7272P / Cyclophosphamide; Q41OR9510P / Melphalan; U68WG3173Y / Carmustine; BAEC protocol; BEAM regimen
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22. Ferrer A, Marcé S, Bellosillo B, Villamor N, Bosch F, López-Guillermo A, Espinet B, Solé F, Montserrat E, Campo E, Colomer D: Activation of mitochondrial apoptotic pathway in mantle cell lymphoma: high sensitivity to mitoxantrone in cases with functional DNA-damage response genes. Oncogene; 2004 Nov 25;23(55):8941-9
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  • [Title] Activation of mitochondrial apoptotic pathway in mantle cell lymphoma: high sensitivity to mitoxantrone in cases with functional DNA-damage response genes.
  • Mantle cell lymphoma (MCL) is a mature B-cell proliferation characterized by the presence of translocation t(11;14)(q13;q32), an aggressive clinical course, and poor response to chemotherapy.
  • The majority of drugs currently used in the treatment of lymphoproliferative disorders induce cell death by triggering apoptosis, but few data concerning drug-induced apoptosis in MCL have been reported.
  • We have analysed the mechanisms of drug-induced cell death in four cell lines with the t(11;14) and in primary cells from 10 patients with MCL.
  • Mitoxantrone, a topoisomerase II inhibitor, induced a strong cytotoxic effect in three cell lines (JVM-2, REC-1, and Granta 519), and in primary MCL cells.
  • However, no cytotoxic effect was detected after incubation with DNA-damaging agents in the NCEB-1 cell line, carrying p53 and ATM alterations, despite the presence of functional mitochondrial machinery.
  • These results support that mitoxantrone can be effective in the treatment of MCL but that this activity requires the integrity of functional DNA-damage response genes.
  • [MeSH-major] Apoptosis. Cyclophosphamide / analogs & derivatives. Lymphoma, Mantle-Cell / pathology. Mitochondria / pathology. Mitoxantrone / pharmacology. Vidarabine / analogs & derivatives
  • [MeSH-minor] Annexin A5 / pharmacology. Antineoplastic Agents / pharmacology. Cell Cycle. Cell Death. Cell Line, Tumor. Cell Survival. Coloring Agents / pharmacology. DNA Damage. Enzyme Inhibitors / pharmacology. Flow Cytometry. Genes, p53. Humans. In Situ Hybridization, Fluorescence. Leukocytes, Mononuclear / metabolism. Membrane Potentials. Proteins / chemistry. Reactive Oxygen Species. Staurosporine / pharmacology. Time Factors. Translocation, Genetic. Tumor Suppressor Protein p53 / metabolism. Tumor Suppressor Protein p53 / physiology

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  • (PMID = 15480431.001).
  • [ISSN] 0950-9232
  • [Journal-full-title] Oncogene
  • [ISO-abbreviation] Oncogene
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Annexin A5; 0 / Antineoplastic Agents; 0 / Coloring Agents; 0 / Enzyme Inhibitors; 0 / Proteins; 0 / Reactive Oxygen Species; 0 / Tumor Suppressor Protein p53; 5970HH9923 / mafosfamide; 8N3DW7272P / Cyclophosphamide; BZ114NVM5P / Mitoxantrone; FA2DM6879K / Vidarabine; H88EPA0A3N / Staurosporine; P2K93U8740 / fludarabine
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23. Intragumtornchai T, Rojnuckarin P, Sutcharitchan P, Wannakrairot P: Mantle cell lymphoma in Thai patients. J Med Assoc Thai; 2004 Sep;87(9):1071-5
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  • [Title] Mantle cell lymphoma in Thai patients.
  • Mantle cell lymphoma (MCL) is a disease entity recently introduced into the new lymphoma classification, therefore, the clinical features as well as therapeutic outcomes in Thai patients with MCL has never been described The authors herein retrospectively analysed 21 newly diagnosed patients with MCL at King Chulalongkorn Memorial Hospital from January 1997 to December 2002.
  • With a median follow-up of 13 months (range, 1-62 months), the rates of overall, progression-free and disease-free survivals were 32%, 9% and 20%, respectively.
  • In conclusion, the clinical features as well as the outcomes of Thai patients with MCL were comparable to patients in Western countries.
  • Newly diagnosed patients should be treated with novel modalities other than conventional CHOP chemotherapy in order to improve the outcomes.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lymphoma, Mantle-Cell / drug therapy
  • [MeSH-minor] Adult. Aged. Cyclophosphamide / therapeutic use. Doxorubicin / therapeutic use. Female. Humans. Male. Middle Aged. Prednisone / therapeutic use. Retrospective Studies. Thailand / epidemiology. Treatment Outcome. Vincristine / therapeutic use

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  • (PMID = 15516008.001).
  • [ISSN] 0125-2208
  • [Journal-full-title] Journal of the Medical Association of Thailand = Chotmaihet thangphaet
  • [ISO-abbreviation] J Med Assoc Thai
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Thailand
  • [Chemical-registry-number] 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; VB0R961HZT / Prednisone; CHOP protocol; COP protocol 2
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24. Méhes L, Telek B, Udvardy M, Schlammadinger A, és Rejto L: [Mantle cell lymphoma: case report]. Orv Hetil; 2008 Aug 3;149(31):1471-4
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  • [Title] [Mantle cell lymphoma: case report].
  • Mantle cell lymphoma (MCL) is a moderately aggressive disease, which is not curable with chemo-immunotherapy.
  • Most of the patients have advanced stage disease at the time of diagnosis.
  • Fifty percent of the patients show infiltration of the bone marrow, in 25% of the MCL patients the gastrointestinal tract is involved, in 25% of patients leukaemic transformation occurs.
  • The tumor cells express pan-B-cell markers and the T-cell marker CD5.
  • The overexpression of cyclin D1 was found as another marker for mantle cell lymphoma.
  • Combined chemotherapy, chemo-immunotherapy, autologous peripheral stem cell (and allogenous) transplantation is the treatment of choice.
  • Our two patients had prolonged survival, in spite of missing the best first line therapy.
  • The survival time after the complex treatment (chemo-immunotherapy, irradiation, surgical intervention, autologous stem cell transplantation) was 80 and 90 months, respectively.
  • In addition to the history of two patients, authors review the current treatment options in mantle cell lymphoma.
  • [MeSH-major] Lymphoma, Mantle-Cell / diagnosis. Lymphoma, Mantle-Cell / therapy
  • [MeSH-minor] Aged. Combined Modality Therapy. Female. Humans. Male. Middle Aged. Treatment Outcome


25. Dumontet C, Morschhauser F, Solal-Celigny P, Bouafia F, Bourgeois E, Thieblemont C, Leleu X, Hequet O, Salles G, Coiffier B: Gemcitabine as a single agent in the treatment of relapsed or refractory low-grade non-Hodgkin's lymphoma. Br J Haematol; 2001 Jun;113(3):772-8
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  • [Title] Gemcitabine as a single agent in the treatment of relapsed or refractory low-grade non-Hodgkin's lymphoma.
  • Thirty-six patients were enrolled onto the study, including 11 cases of mantle cell lymphoma (MCL), 10 cases of chronic lymphocytic leukaemia (CLL)/lymphocytic lymphoma, nine cases of follicular lymphoma, four cases of lymphoplasmacytic lymphoma and two cases of T-cell lymphoma.
  • Gemcitabine 1 g/m(2) was administered as a 30-min infusion on d 1, 8 and 15 of a 28-d schedule, up to a maximum of six cycles.
  • Complete responses were observed in two patients with MCL, and partial responses were observed in seven patients, including three patients with CLL/lymphocytic lymphoma, two patients with T-cell lymphoma, one patient with MCL and one patient with follicular lymphoma.
  • Minor responses were observed in three patients, including two patients with MCL and one patient with CLL.
  • The median duration of response was 150 d and the overall progression-free survival was 342 d.
  • Severe non-haematological toxicity included one case of fatal veno-occlusive disease, one case of thrombotic microangiopathy leading to terminal renal failure, one case of capillary leak syndrome, one case of myocardial infarction and drug-induced fever in two patients.
  • These data suggest that gemcitabine displays activity in patients with MCL and CLL/lymphocytic lymphoma.
  • [MeSH-major] Antimetabolites / therapeutic use. Deoxycytidine / therapeutic use. Lymphoma, Non-Hodgkin / drug therapy
  • [MeSH-minor] Adult. Aged. Capillary Leak Syndrome / chemically induced. Disease-Free Survival. Drug Administration Schedule. Female. Fever / chemically induced. Humans. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy. Leukemia, Lymphocytic, Chronic, B-Cell / mortality. Leukopenia / chemically induced. Lymphoma, Follicular / drug therapy. Lymphoma, Follicular / mortality. Lymphoma, Mantle-Cell / drug therapy. Lymphoma, Mantle-Cell / mortality. Lymphoma, T-Cell / drug therapy. Lymphoma, T-Cell / mortality. Male. Middle Aged. Myocardial Infarction / chemically induced. Pulmonary Veno-Occlusive Disease / chemically induced. Recurrence. Renal Insufficiency / chemically induced. Survival Rate. Thrombocytopenia / chemically induced. Time Factors

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  • (PMID = 11380469.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites; 0W860991D6 / Deoxycytidine; B76N6SBZ8R / gemcitabine
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26. Villela L, García M, Caballero R, Borbolla-Escoboza JR, Bolaños-Meade J: Rapid complete response using intrathecal rituximab in a patient with leptomeningeal lymphomatosis due to mantle cell lymphoma. Anticancer Drugs; 2008 Oct;19(9):917-20
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  • [Title] Rapid complete response using intrathecal rituximab in a patient with leptomeningeal lymphomatosis due to mantle cell lymphoma.
  • Mantle cell lymphoma (MCL) is a B-cell lymphoid tumor that expresses CD20 and is associated with a poor prognosis.
  • We report a 62-year-old male with MCL and meningeal lymphomatosis.
  • Systemic therapy consisted of R-HyperCVAD alternating with rituximab, high-dose methotrexate, and cytarabine every 21 days, with IT-R on day 1 of each chemotherapy cycle.
  • The patient was consolidated with an autologous stem cell transplant and remains in remission 23 months later.
  • The use of IT-R and conventional intrathecal chemotherapy in MCLs is discussed here.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Lymphoma, Mantle-Cell / drug therapy. Meningeal Neoplasms / drug therapy
  • [MeSH-minor] Antibodies, Monoclonal, Murine-Derived. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Humans. Injections, Spinal. Male. Middle Aged. Rituximab

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  • (PMID = 18766006.001).
  • [ISSN] 0959-4973
  • [Journal-full-title] Anti-cancer drugs
  • [ISO-abbreviation] Anticancer Drugs
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P30 CA006973
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 4F4X42SYQ6 / Rituximab
  • [Other-IDs] NLM/ NIHMS737074; NLM/ PMC4703051
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27. Singleton DC, Li D, Bai SY, Syddall SP, Smaill JB, Shen Y, Denny WA, Wilson WR, Patterson AV: The nitroreductase prodrug SN 28343 enhances the potency of systemically administered armed oncolytic adenovirus ONYX-411(NTR). Cancer Gene Ther; 2007 Dec;14(12):953-67
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  • An Escherichia coli nitroreductase (NTR) gene (nfsB) was introduced into the E3B region of the systemically active CRAd ONYX-411, to produce ONYX-411(NTR), which had single agent oncolytic activity equivalent to unarmed virus in vitro and in vivo.
  • A fluorogenic probe (SN 29884) developed to monitor NTR expression revealed robust, durable NTR expression in ONYX-411(NTR) infected neoplastic but not primary human cell lines.
  • A novel NTR prodrug, the 3,5-dinitrobenzamide-2-bromomustard SN 27686, was shown to be more dose potent and selective than CB 1954 and provided a superior bystander effect in 3D multicellular layer cultures.
  • A single intravenous dose of ONYX-411(NTR) (10(8) PFU) to nude mice bearing large H1299 xenografts (>350 mm(3)) resulted in tumor-specific NTR expression which increased over time.
  • [MeSH-major] Adenoviridae. Antineoplastic Agents / pharmacology. Escherichia coli Proteins / biosynthesis. Neoplasms / therapy. Nitrogen Mustard Compounds / pharmacology. Nitroreductases / biosynthesis. Oncolytic Virotherapy. Oncolytic Viruses. Prodrugs / pharmacology. Transduction, Genetic
  • [MeSH-minor] Animals. Aziridines / pharmacology. Gene Expression. Humans. Mice. Mice, Mutant Strains. Time Factors. Virus Replication / drug effects. Virus Replication / genetics. Xenograft Model Antitumor Assays

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  • (PMID = 17975564.001).
  • [ISSN] 1476-5500
  • [Journal-full-title] Cancer gene therapy
  • [ISO-abbreviation] Cancer Gene Ther.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Aziridines; 0 / Escherichia coli Proteins; 0 / Nitrogen Mustard Compounds; 0 / Prodrugs; 0 / SN 28343; 7865D5D01M / tretazicar; EC 1.7.- / NfsB protein, E coli; EC 1.7.- / Nitroreductases
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28. Fisher B, Seiferheld W, Schultz C, DeAngelis L, Nelson D, Schold SC, Curran W, Mehta M: Secondary analysis of Radiation Therapy Oncology Group study (RTOG) 9310: an intergroup phase II combined modality treatment of primary central nervous system lymphoma. J Neurooncol; 2005 Sep;74(2):201-5
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  • [Title] Secondary analysis of Radiation Therapy Oncology Group study (RTOG) 9310: an intergroup phase II combined modality treatment of primary central nervous system lymphoma.
  • PURPOSE: To determine whether a lower dose of hyperfractionated whole brain radiation reduces central nervous system morbidity without compromising survival for primary CNS lymphoma (PCNSL) patients receiving combined modality treatment.
  • MATERIALS AND METHODS: One hundred and two patients received a course of pre-radiation chemotherapy, followed by whole brain radiation, followed by cytosine-arabinoside.
  • Initial radiation dose was 45 Gy/25 fractions (RT) then the study was amended to reduce this dose for complete responders to induction chemotherapy to 36 Gy/30 fractions/3 weeks (HFX).
  • MMSE scores and survival for the 40 patients who received radiotherapy after complete response to chemotherapy (27 RT and 13 HFX) were compared.
  • There were no notable differences in pre-treatment patient characteristics between the RT and HFX groups.
  • RESULTS: Neurotoxicity: By 4 years, there were 8/82 (10%) grade 5 neurotoxicities which included 2/16 (13%) grade 5 encephalopathies and 0/27 in the RT group of complete responders to chemotherapy.
  • Survival: There was no statistically significant difference in overall or progression-free survival (PFS) between the chemotherapy-complete responders who received RT and HFX.
  • Cognitive function testing: MMSE scores improved at 8 months across both treatment groups.
  • [MeSH-major] Brain Neoplasms / drug therapy. Brain Neoplasms / radiotherapy. Lymphoma / drug therapy. Lymphoma / radiotherapy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Brain / radiation effects. Cognition. Combined Modality Therapy. Disease Progression. Dose Fractionation. Humans. Leucovorin / administration & dosage. Methotrexate / administration & dosage. Procarbazine / administration & dosage. Radiation Injuries / mortality. Radiation Injuries / pathology. Survival Rate. Vincristine / administration & dosage

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  • [ISSN] 0167-594X
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Grant] United States / PHS HHS / / U 32115; United States / NCI NIH HHS / CA / U10 CA 21661; United States / NCI NIH HHS / CA / U10 CA 37422
  • [Publication-type] Clinical Trial, Phase II; Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 35S93Y190K / Procarbazine; 5J49Q6B70F / Vincristine; Q573I9DVLP / Leucovorin; YL5FZ2Y5U1 / Methotrexate
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29. Schrader C, Meusers P, Brittinger G, Teymoortash A, Siebmann JU, Janssen D, Parwaresch R, Tiemann M: Topoisomerase IIalpha expression in mantle cell lymphoma: a marker of cell proliferation and a prognostic factor for clinical outcome. Leukemia; 2004 Jul;18(7):1200-6
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  • [Title] Topoisomerase IIalpha expression in mantle cell lymphoma: a marker of cell proliferation and a prognostic factor for clinical outcome.
  • Mantle cell lymphoma (MCL) is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3-4 years.
  • Treatment usually consists of combination chemotherapy, often including topoisomerase (topo) inhibitors such as doxorubicin, etoposide and mitoxantrone.
  • Topo IIalpha is an enzyme that is needed whenever uncoiling of DNA is necessary during the cell cycle.
  • The enzyme is a marker of cell proliferation.
  • We analyzed the expression of topo IIalpha in relation to Ki-67 and the clinical outcome in patients with MCL.
  • Patients with low (0-10%) topo IIalpha expression had a median overall survival time of 49.0 months, compared to 17.0 months for patients with high (more than 10%) topo IIalpha expression.
  • The Kaplan-Meier analysis showed a significant difference in the overall survival time related to the percentage of topo IIalpha (P<0.001) and Ki-67 (P<0.001) positive tumor cells.
  • Multivariate Cox regression analysis revealed the expression of topo IIalpha as the most important prognostic factor (P<0.001) in MCL superior to the international prognostic index (IPI), the Ki-67 index and other clinical characteristics.
  • [MeSH-major] DNA Topoisomerases, Type II / analysis. Lymphoma, Mantle-Cell / enzymology
  • [MeSH-minor] Antigens, Neoplasm. Antineoplastic Agents / therapeutic use. Biomarkers / analysis. Cell Division. DNA-Binding Proteins. Female. Humans. Immunohistochemistry. Ki-67 Antigen / analysis. Male. Middle Aged. Prognosis. Regression Analysis. Survival Analysis. Treatment Outcome

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  • [CommentIn] Leukemia. 2004 Aug;18(8):1347-9 [15201855.001]
  • (PMID = 15116121.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / Antineoplastic Agents; 0 / Biomarkers; 0 / DNA-Binding Proteins; 0 / Ki-67 Antigen; EC 5.99.1.3 / DNA Topoisomerases, Type II; EC 5.99.1.3 / DNA topoisomerase II alpha
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30. Till BG, Gooley TA, Crawford N, Gopal AK, Maloney DG, Petersdorf SH, Pagel JM, Holmberg L, Bensinger W, Press OW: Effect of remission status and induction chemotherapy regimen on outcome of autologous stem cell transplantation for mantle cell lymphoma. Leuk Lymphoma; 2008 Jun;49(6):1062-73
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  • [Title] Effect of remission status and induction chemotherapy regimen on outcome of autologous stem cell transplantation for mantle cell lymphoma.
  • We analysed the outcomes of autologous stem cell transplantation (ASCT) following high-dose therapy with respect to remission status at the time of transplantation and induction regimen used in 56 consecutive patients with mantle cell lymphoma (MCL).
  • Twenty-one patients received induction chemotherapy with HyperCVAD with or without rituximab (+/-R) followed by ASCT in first complete or partial remission (CR1/PR1), 15 received CHOP (+/-R) followed by ASCT in CR1/PR1 and 20 received ASCT following disease progression.
  • The hazard of mortality among patients transplanted with relapsed/refractory disease was 6.09 times that of patients transplanted in CR1/PR1 (P = 0.006).
  • These results suggest that ASCT in CR1/PR1 leads to improved survival outcomes for patients with MCL compared to ASCT with relapsed/refractory disease, and a HyperCVAD (+/-R) induction regimen may be associated with an improved PFS among patients transplanted in CR1/PR1.

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  • [CommentIn] Leuk Lymphoma. 2008 Jun;49(6):1017-8 [18452075.001]
  • (PMID = 18452065.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA044991-21; United States / NCI NIH HHS / CA / K23 CA085479; United States / NCI NIH HHS / CA / P01 CA44991; United States / NCI NIH HHS / CA / P01 CA044991; United States / NCI NIH HHS / CA / K23CA85479; United States / NCI NIH HHS / CA / K23 CA085479-06; United States / NCI NIH HHS / CA / CA085479-06; United States / NCI NIH HHS / CA / CA044991-21
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 4F4X42SYQ6 / Rituximab; 5J49Q6B70F / Vincristine; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; VB0R961HZT / Prednisone
  • [Other-IDs] NLM/ NIHMS147578; NLM/ PMC2769072
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31. Weide R, Hess G, Köppler H, Heymanns J, Thomalla J, Aldaoud A, Losem C, Schmitz S, Haak U, Huber C, Unterhalt M, Hiddemann W, Dreyling M, German Low Grade Lymphoma Study Group: High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Leuk Lymphoma; 2007 Jul;48(7):1299-306
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  • [Title] High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG).
  • On the basis of a preceding phase I study, the current trial explored bendamustine in combination with mitoxantrone and rituximab (BMR) in patients with stage III/IV relapsed or refractory indolent lymphomas and mantle cell lymphoma (MCL) with or without prior rituximab containing chemo-immunotherapy (R-chemo) treatment.
  • Therapy consisted of bendamustine 90 mg/m(2) days 1 + 2, mitoxantrone 10 mg/m(2) day 1, rituximab 375 mg/m(2) day 8.
  • Treatment was repeated on day 29 for a total of four cycles.
  • Between 3 April and 04 July, 57 patients were recruited from 24 participating institutions, 39% of whom had received prior R-chemo therapy.
  • Lymphoma subtypes were 29 follicular (FL), 18 MCL, and 10 other indolent lymphomas.
  • After a median observation time of 27 months (1 - 43), the estimated median progression free survival is 19 months.
  • The 2 year overall survival is 60% for patients with FL and MCL.
  • Treatment related toxicities of grade 3/4 comprised a reversible myelosuppression (10% anemia, 78% leukocytopenia, 46% granulocytopenia, 16% thrombocytopenia).
  • BMR is a very effective new outpatient immuno-chemotherapy with low toxicity for patients with relapsed/refractory FL, MCL and other indolent lymphomas.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lymphoma, Mantle-Cell / drug therapy. Lymphoma, Non-Hodgkin / drug therapy. Nitrogen Mustard Compounds / administration & dosage
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Murine-Derived. Bendamustine Hydrochloride. Female. Humans. Lymphoma, Follicular / complications. Lymphoma, Follicular / drug therapy. Lymphoma, Follicular / mortality. Male. Middle Aged. Mitoxantrone / administration & dosage. Remission Induction. Rituximab. Salvage Therapy / methods. Survival Analysis. Treatment Outcome

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  • [CommentIn] Leuk Lymphoma. 2007 Jul;48(7):1264-6 [17613752.001]
  • (PMID = 17613757.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Nitrogen Mustard Compounds; 4F4X42SYQ6 / Rituximab; 981Y8SX18M / Bendamustine Hydrochloride; BZ114NVM5P / Mitoxantrone
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32. Goy A, Feldman T: Expanding therapeutic options in mantle cell lymphoma. Clin Lymphoma Myeloma; 2007 Aug;7 Suppl 5:S184-91
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Expanding therapeutic options in mantle cell lymphoma.
  • Mantle cell lymphoma (MCL) still carries a poor prognosis.
  • Chemoimmunotherapy (combination with rituximab) is the routine first-line therapy, although data strongly suggest a benefit from intensification through high-dose therapy with stem cell transplantation consolidation or dose-intense chemotherapy with HyperCVAD (fractionated cyclophosphamide/vincristine/doxorubicin/dexamethasone)/rituximab.
  • Unfortunately, most patients still experience relapse, and a multitude of novel agents are currently being tested in this setting, including proteasome inhibitors with bortezomib (the first of its class and first Food and Drug Administration-approved drug in MCL), mammalian target of rapamycin inhibitors, Bcl-2 inhibitors, and antiangiogenesis agents, among others.
  • Because of the relative rarity of the disease-MCL represents 6% of non-Hodgkin lymphoma-an obvious effort is needed to enroll patients on clinical trials.
  • Not surprisingly, as in other non-Hodgkin lymphomas, MCL appears more and more as a heterogeneous disease, which might impact future clinical trial design through pharmacogenomics and hopefully help us develop smaller "molecular" relevant trials.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lymphoma, Mantle-Cell / drug therapy
  • [MeSH-minor] Animals. Combined Modality Therapy. Humans. Radioimmunotherapy

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  • (PMID = 17877843.001).
  • [ISSN] 1557-9190
  • [Journal-full-title] Clinical lymphoma & myeloma
  • [ISO-abbreviation] Clin Lymphoma Myeloma
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 90
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33. Dreger P, Laport GG: Controversies in lymphoma: the role of hematopoietic cell transplantation for mantle cell lymphoma and peripheral T cell lymphoma. Biol Blood Marrow Transplant; 2008 Jan;14(1 Suppl 1):100-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Controversies in lymphoma: the role of hematopoietic cell transplantation for mantle cell lymphoma and peripheral T cell lymphoma.
  • Mantle cell lymphoma (MCL) and peripheral T cell lymphoma (PTCL) are distinct lymphoma subtypes that each comprise about approximately 10% of the non-Hodgkin lymphomas.
  • Although both subtypes are characterized by high remission rates to frontline chemotherapy, the prognosis is generally poor because of inevitable relapse within 1-2 years or less, depending on the specific histology.
  • Patients with MCL who achieve a complete remission with upfront conventional chemotherapy currently have several options for consolidative therapy including maintenance therapy with rituximab, autologous hematopoietic cell transplantation (HCT), and more recently, allogeneic HCT utilizing a reduced intensity conditioning (RIC) regimen.
  • In the autologous HCT setting, the added efficacy of rituximab is under active investigation as a method of in vivo purging during hematopoietic cell mobilization, as part of the conditioning regimen and as post-HCT maintenance therapy.
  • This review summarizes the current role of HCT for patients with MCL in first remission and for patients with PTCL as consolidation and for relapsed/refractory disease.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / methods. Lymphoma, Mantle-Cell / surgery. Lymphoma, T-Cell, Peripheral / surgery
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Humans. Transplantation Conditioning / methods

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  • [ErratumIn] Biol Blood Marrow Transplant. 2008 Nov;14(11):1317-8
  • (PMID = 18162229.001).
  • [ISSN] 1523-6536
  • [Journal-full-title] Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • [ISO-abbreviation] Biol. Blood Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 59
  • [General-notes] NLM/ Original DateCompleted: 20080104
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34. Hon C, Chan RT, Ma ES, Shek TW, Yau K, Au WY: Lymphomatous proptosis as a novel feature of mantle cell lymphoma. Leuk Lymphoma; 2006 Jan;47(1):71-5
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  • [Title] Lymphomatous proptosis as a novel feature of mantle cell lymphoma.
  • We describe eight cases of acute proptosis due to mantle cell lymphoma (MCL), among 26 consecutive MCL cases.
  • The median time of onset was 29 months (range 0-102) from diagnosis.
  • Two cases presented initially with orbital masses while five as sudden disease progression after multiple courses of chemotherapy.
  • In each case, there was dramatic loss of vision and severe proptosis, which uniformly responded to radiotherapy and/or further chemotherapy.
  • The high incidence, as well as bilateral and recurrent nature, of orbital involvement suggested a homing mechanism of MCL to this site.
  • Apart from lymphomatous polyposis of the gut, MCL cells also show predilection to ocular presentation, and must be considered as a differential diagnosis to maltoma in the two anatomical sites.
  • [MeSH-major] Exophthalmos / etiology. Lymphoma, Mantle-Cell / diagnosis
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Combined Modality Therapy. Disease Progression. Fatal Outcome. Female. Humans. Male. Middle Aged. Orbital Neoplasms / diagnosis. Orbital Neoplasms / therapy. Recurrence. Survival Rate. Treatment Outcome

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  • (PMID = 16321830.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
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35. Obukhova TN, Lorie IuIu, Vodinskaia LA, Alimova GA, Nikitin EA, Samoĭlova RS, Kaplanskaia IB, Domracheva EV: [Cytogenetics of mantle cell lymphoma]. Ter Arkh; 2004;76(7):70-7
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  • [Title] [Cytogenetics of mantle cell lymphoma].
  • AIM: To determine the type and rate of secondary chromosomal aberrations and role in pathogenesis of mantle cell lymphoma (MCL).
  • Deletions 6q15-q23 were seen in patients with privalent lesions of lymph nodes.
  • Monosomy 20 was found only in patients with large cell transformations.
  • Thus, deletions 6q, 11q23, 13q14 and 9p21 are typical for MCL.
  • Deletions 9p21 and 17p13 are more characteristic for large cell variants of the tumor.
  • Deletion 17p13 occurs at the terminal stage of the disease in rapidly growing tumor mass and resistance to chemotherapy.
  • FISH technique is effective in detection of submicroscopic rearrangements especially small deletions.
  • No significant differences were found between transformed and de novo blastoid cases.
  • CONCLUSION: Progression and transformation of MCL are related to mutation of proapoptotic genes and genes proteins of which are inhibitors of active complexes of D1 cycline.
  • [MeSH-major] Chromosome Aberrations. Lymphoma, Mantle-Cell / genetics

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  • (PMID = 15379132.001).
  • [ISSN] 0040-3660
  • [Journal-full-title] Terapevticheskiĭ arkhiv
  • [ISO-abbreviation] Ter. Arkh.
  • [Language] rus
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Russia
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36. Haritunians T, Mori A, O'Kelly J, Luong QT, Giles FJ, Koeffler HP: Antiproliferative activity of RAD001 (everolimus) as a single agent and combined with other agents in mantle cell lymphoma. Leukemia; 2007 Feb;21(2):333-9
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  • [Title] Antiproliferative activity of RAD001 (everolimus) as a single agent and combined with other agents in mantle cell lymphoma.
  • Mantle cell lymphoma (MCL) is an aggressive form of B-cell non-Hodgkin's lymphoma, with a mean survival of only 3-5 years and suboptimal therapeutic options.
  • MCL is characterized by a balanced translocation t(11;14)(q13;q32), resulting in overexpression of cyclin D1, a G(1) cyclin regulated by the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway.
  • As improved therapy for MCL is required and the mTOR pathway may be involved in its pathophysiology, the antiproliferative effects of RAD001 (everolimus), an mTOR inhibitor, against three MCL cell lines were investigated.
  • As a single agent, RAD001 inhibited proliferation in MCL cell lines (Jeko1, SP49 and NCEB1) approximately 40-65% compared to diluent control cells.
  • This was associated with G(1) cell-cycle arrest and reduced phosphorylation of the mTOR downstream target, 4E-BP1.
  • Furthermore, combination drug studies revealed predominantly synergistic cytotoxicity with RAD001 and several secondary agents, including doxorubicin, vincristine or rituximab (components of the standard MCL regimen), as well as paclitaxel, vorinostat and bortezomib.
  • These data indicate that single agent RAD001 is effective in inhibiting growth of MCL cells in vitro and combination studies with secondary agents further demonstrate synergistic cytotoxicity.
  • Thus, these findings support future clinical studies of RAD001 in the treatment of MCL.
  • [MeSH-major] Antibiotics, Antineoplastic / pharmacology. Lymphoma, Mantle-Cell / pathology. Sirolimus / analogs & derivatives
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / pharmacology. Cell Division / drug effects. Cell Line, Tumor. Dimethyl Sulfoxide / pharmacology. Everolimus. Humans


37. Michaux L, Wlodarska I, Theate I, Stul M, Scheiff JM, Deneys V, Ferrant A, Hagemeijer A: Coexistence of BCL1/CCND1 and CMYC aberrations in blastoid mantle cell lymphoma: a rare finding associated with very poor outcome. Ann Hematol; 2004 Sep;83(9):578-83
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  • [Title] Coexistence of BCL1/CCND1 and CMYC aberrations in blastoid mantle cell lymphoma: a rare finding associated with very poor outcome.
  • A patient with mantle cell lymphoma (MCL) of the pleomorphic blastoid subtype is reported.
  • The disease was clinically aggressive and refractory to chemotherapy, and the patient survived only 2 months.
  • Cytogenetically, a t(11;19;14)(q13;q13;q32) was found.
  • In addition, subclonal abnormalities of the region 8q24 manifested either as a t(8;22)(q24;q11)/CMYC rearrangement or trisomy 8 were identified.
  • The pathogenetic impact of this very uncommon association of BCL1/CCND1 and CMYC rearrangements in MCL is discussed and the literature is reviewed.
  • [MeSH-major] Cyclin D1 / genetics. Lymphoma, Mantle-Cell / genetics. Lymphoma, Mantle-Cell / pathology. Proto-Oncogene Proteins c-myc / genetics. Translocation, Genetic / genetics. Trisomy / genetics
  • [MeSH-minor] Aged. Chromosomes, Human / genetics. DNA, Neoplasm / genetics. Female. Humans. Immunohistochemistry. In Situ Hybridization, Fluorescence. Male. Middle Aged. Treatment Outcome

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  • (PMID = 15138714.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / DNA, Neoplasm; 0 / Proto-Oncogene Proteins c-myc; 136601-57-5 / Cyclin D1
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38. Schaffel R, Hedvat CV, Teruya-Feldstein J, Persky D, Maragulia J, Lin D, Portlock CS, Moskowitz CH, Zelenetz AD: Prognostic impact of proliferative index determined by quantitative image analysis and the International Prognostic Index in patients with mantle cell lymphoma. Ann Oncol; 2010 Jan;21(1):133-9
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  • [Title] Prognostic impact of proliferative index determined by quantitative image analysis and the International Prognostic Index in patients with mantle cell lymphoma.
  • BACKGROUND: The proliferative index (PI) is a powerful prognostic factor in mantle cell lymphoma (MCL); however, its utility is hampered by interobserver variability.
  • The mantle cell international prognostic index (MIPI) has been reported to have prognostic importance.
  • In this study, we determined the prognostic value of the PI as determined by quantitative image analysis in MCL.
  • PATIENTS AND METHODS: Eighty-eight patients with adequate tissue were included in this analysis.
  • Patients were treated with one of two treatment programs: sequential therapy with high-dose therapy consolidation or radioimmunotherapy followed by combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone.
  • By univariate analysis, intensive treatment and a low PI were associated with a superior progression-free survival (PFS); only PI was associated with overall survival.
  • By multivariate analysis, both intensive treatment and PI correlated with PFS.
  • CONCLUSIONS: PI is the most important prognostic factor in MCL.
  • The cut-off of 30% is clinically meaningful and can be used to tailor the intensity of therapy in future clinical trials.

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  • (PMID = 20019090.001).
  • [ISSN] 1569-8041
  • [Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology
  • [ISO-abbreviation] Ann. Oncol.
  • [Language] ENG
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Ki-67 Antigen
  • [Other-IDs] NLM/ PMC2795614
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39. Rasmussen P, Sjö LD, Prause JU, Ralfkiaer E, Heegaard S: Mantle cell lymphoma in the orbital and adnexal region. Br J Ophthalmol; 2009 Aug;93(8):1047-51
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  • [Title] Mantle cell lymphoma in the orbital and adnexal region.
  • AIMS: To characterise clinicopathological features of mantle cell lymphoma (MCL) in the orbital and adnexal region.
  • METHODS: Data on lymphoid lesions were retrieved searching the Danish Ocular Lymphoma Database 1980-2005.
  • Specimens were collected from Danish pathological departments and re-evaluated with a panel of monoclonal antibodies.
  • For all patients with confirmed MCL the complete clinical files were collected and reviewed.
  • RESULTS: Twenty-one patients with MCL in the orbital and adnexal region were identified comprising 9% (21/230) of all lymphoma in the ocular region.
  • Orbital and adnexal region MCL as first presenting symptom comprised 67% of the patients.
  • Secondary MCL comprised 33% of the patients.
  • Patients receiving anti-CD20 (rituximab)-containing chemotherapy had a significantly better 5-year overall survival (OS) rate (83%) than patients in treatment regimes without rituximab (5-year OS rate, 8%).
  • CONCLUSIONS: Orbital and adnexal region MCL presents in elderly males.
  • There is a very high proportion of systemic involvement in general with MCL of the orbital and adnexal region.
  • Most patients presented with stage IV disease and had multiple relapses and short survival time.
  • Treatment with rituximab-containing chemotherapy improved survival significantly compared with combination chemotherapy without rituximab.
  • [MeSH-major] Eye Neoplasms / pathology. Lymphoma, Mantle-Cell / pathology
  • [MeSH-minor] Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Neoplasm Staging. Orbital Neoplasms / pathology. Orbital Neoplasms / therapy. Prognosis. Survival Analysis. Treatment Outcome

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  • (PMID = 19429588.001).
  • [ISSN] 1468-2079
  • [Journal-full-title] The British journal of ophthalmology
  • [ISO-abbreviation] Br J Ophthalmol
  • [Language] eng
  • [Publication-type] Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
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40. Habermann TM, Lossos IS, Justice G, Vose JM, Wiernik PH, McBride K, Wride K, Ervin-Haynes A, Takeshita K, Pietronigro D, Zeldis JB, Tuscano JM: Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol; 2009 May;145(3):344-9
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  • [Title] Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma.
  • Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma with a poor prognosis following first relapse.
  • We present a subgroup analysis of an open-label phase II trial investigating the efficacy and safety of lenalidomide in patients with relapsed or refractory MCL.
  • Among 15 patients with MCL with a median disease duration of 5.1 years and a median of four prior treatments, the ORR was 53%.
  • In conclusion, oral lenalidomide monotherapy is well tolerated and active in relapsed or refractory MCL.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Lymphoma, Mantle-Cell / drug therapy. Thalidomide / analogs & derivatives
  • [MeSH-minor] Administration, Oral. Aged. Aged, 80 and over. Disease-Free Survival. Drug Administration Schedule. Female. Humans. Kaplan-Meier Estimate. Leukopenia / chemically induced. Lymphoma, B-Cell / drug therapy. Lymphoma, B-Cell / mortality. Male. Middle Aged. Neutropenia / chemically induced. Recurrence. Thrombocytopenia / chemically induced. Treatment Outcome

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  • (PMID = 19245430.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 4Z8R6ORS6L / Thalidomide; F0P408N6V4 / lenalidomide
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41. Pilichowska ME, Smouse JH, Dorfman DM: Concurrent herpes simplex viral lymphadenitis and mantle cell lymphoma: a case report and review of the literature. Arch Pathol Lab Med; 2006 Apr;130(4):536-9
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  • [Title] Concurrent herpes simplex viral lymphadenitis and mantle cell lymphoma: a case report and review of the literature.
  • We report a case of localized herpes simplex virus lymphadenitis in a patient with mantle cell lymphoma (MCL).
  • A 43-year-old woman with a 2-month history of lymphadenitis and peripheral lymphocytosis received a diagnosis of stage IV MCL based on histologic, flow cytometric, and immunohistochemical findings.
  • One week after completion of chemotherapy, she presented with rapidly enlarging bilateral cervical lymph nodes, a retropharyngeal mass, and incipient respiratory compromise.
  • Multiple biopsies of the cervical nodes and oropharynx that were submitted for morphologic, flow cytometric, and immunohistochemical studies revealed involvement by MCL with superimposed herpes simplex virus lymphadenitis.
  • The recognition of herpes simplex virus infection with MCL is important for treatment as well as to rule out transformation of MCL to a higher-grade lesion.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Herpes Simplex / pathology. Lymphadenitis / pathology. Lymphoma, Mantle-Cell / pathology
  • [MeSH-minor] Adult. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Murine-Derived. Antiviral Agents / therapeutic use. Cyclophosphamide / therapeutic use. Dexamethasone / therapeutic use. Doxorubicin / therapeutic use. Female. Ganciclovir / therapeutic use. Humans. Neoplasm Staging. Rituximab. Vincristine / therapeutic use

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  • (PMID = 16594747.001).
  • [ISSN] 1543-2165
  • [Journal-full-title] Archives of pathology & laboratory medicine
  • [ISO-abbreviation] Arch. Pathol. Lab. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antiviral Agents; 4F4X42SYQ6 / Rituximab; 5J49Q6B70F / Vincristine; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; P9G3CKZ4P5 / Ganciclovir; CVAD protocol
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42. Dreger P, Rieger M, Seyfarth B, Hensel M, Kneba M, Ho AD, Schmitz N, Pott C: Rituximab-augmented myeloablation for first-line autologous stem cell transplantation for mantle cell lymphoma: effects on molecular response and clinical outcome. Haematologica; 2007 Jan;92(1):42-9
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  • [Title] Rituximab-augmented myeloablation for first-line autologous stem cell transplantation for mantle cell lymphoma: effects on molecular response and clinical outcome.
  • BACKGROUND AND OBJECTIVES: Autologous stem cell transplantation (ASCT) is effective in mantle cell lymphoma (MCL).
  • We investigated whether incorporation of rituximab into the high-dose regimen might further improve the results of ASCT in patients with MCL.
  • DESIGN AND METHODS: In a prospective phase II study, patients with newly diagnosed MCL were treated with a sequential dose-escalating therapy comprising standard chemotherapy for remission induction, intensive ara-C-containing chemotherapy for mobilization of stem cells, and myeloablative therapy followed by ASCT.
  • Outcome parameters (toxicity, clinical and molecular response as assessed by allele-specific IGH real-time quantitative polymerase chain reaction (RQ-PCR), event-free survival, and overall survival) were compared with those of 34 historical controls treated identically but without rituximab.
  • This was associated with a trend for a superior molecular response rate in 11 study vs. 10 control patients with a marker available (73% vs. 30%, p=0.086) despite similar levels of lymphoma contamination of the stem cell inocula infused.
  • INTERPRETATION AND CONCLUSIONS: Incorporation of two standard doses of rituximab into the myeloablative regimen might improve outcome of up front ASCT for MCL, allowing long-term disease control to an extent previously not reached in this disease.
  • [MeSH-major] Antibodies, Monoclonal / pharmacology. Lymphoma, Mantle-Cell / therapy. Stem Cell Transplantation / methods. Transplantation, Autologous / methods
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal, Murine-Derived. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cyclophosphamide. Disease-Free Survival. Doxorubicin. Female. Humans. Male. Middle Aged. Prednisolone. Proportional Hazards Models. Prospective Studies. Rituximab. Treatment Outcome. Vincristine

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  • (PMID = 17229634.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 4F4X42SYQ6 / Rituximab; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; 9PHQ9Y1OLM / Prednisolone; VAP-cyclo protocol
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43. Rao R, Lee P, Fiskus W, Yang Y, Joshi R, Wang Y, Buckley K, Balusu R, Chen J, Koul S, Joshi A, Upadhyay S, Tao J, Sotomayor E, Bhalla KN: Co-treatment with heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG) and vorinostat: a highly active combination against human mantle cell lymphoma (MCL) cells. Cancer Biol Ther; 2009 Jul;8(13):1273-80
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  • [Title] Co-treatment with heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG) and vorinostat: a highly active combination against human mantle cell lymphoma (MCL) cells.
  • Here, we determined the effects of the more soluble, orally bio-available, geldanamycin analogue 17-NN-dimethyl ethylenediamine geldanamycin (DMAG, Kosan Biosciences Inc.) and/or vorinostat in cultured and primary human MCL cells.
  • While vorinostat induced accumulation in the G(1) phase, treatment with DMAG arrested MCL cells in the G(2)/M phase of the cell cycle.
  • Both agents dose-dependently induced apoptosis of MCL cells.
  • Vorinostat also induced hyperacetylation of hsp90 and disrupted the association of hsp90 with its co-chaperones p23 and cdc37, as well as with its client proteins CDK4 and c-RAF.
  • Treatment of MCL cells with vorinostat or 17-DMAG was associated with the inductionof p21 and p27, as well as with depletion of c-Myc, c-RAF, AKT and CDK4.
  • Compared to treatment with either agent alone, co-treatment with DMAG and vorinostat markedly attenuated the levels of cyclin D1 and CDK4, as well as of c-Myc, c-RAF and AKT.
  • Combined treatment with DMAG and vorinostat synergistically induced apoptosis of the cultured MCL cells, as well as induced more apoptosis of primary MCL cells than either agent alone.
  • Therefore, these findings support the rationale to determine the in vivo efficacy of co-treatment with vorinostat and DMAG against human MCL cells.

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  • (PMID = 19440035.001).
  • [ISSN] 1555-8576
  • [Journal-full-title] Cancer biology & therapy
  • [ISO-abbreviation] Cancer Biol. Ther.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA129962-01A1; United States / NCI NIH HHS / CA / R01 CA129962; United States / NCI NIH HHS / CA / R01 CA129962-01A1
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzoquinones; 0 / Cell Cycle Proteins; 0 / HSP90 Heat-Shock Proteins; 0 / Hydroxamic Acids; 0 / Lactams, Macrocyclic; 001L2FE0M3 / 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin; 58IFB293JI / vorinostat
  • [Other-IDs] NLM/ NIHMS130612; NLM/ PMC2766923
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44. Zhou Y, Zhang L, Romaguera J, Delasalle K, Han X, Du X, Kwak L, Yi Q, Wang M: Immunotherapy in mantle cell lymphoma: anti-CD20-based therapy and beyond. Am J Hematol; 2008 Feb;83(2):144-9
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  • [Title] Immunotherapy in mantle cell lymphoma: anti-CD20-based therapy and beyond.
  • Mantle cell lymphoma (MCL), an aggressive non-Hodgkin's lymphoma characterized by t(11; 14)(q13;.
  • Recent advances in biology, genetics, and immunology have supported the development of immunotherapy in MCL.
  • Rituximab monotherapy in MCL has limited activity.
  • It is more effective when used in combination with chemotherapy such as R-CHOP, R-hyperCVAD/MTX-Ara-C, or R-FCM as front-line or salvage therapy for mantle cell lymphoma.
  • Although most results have suggested that combining autologous stem cell transplantation with Rituximab may lead to durable remission, the sample size was not sufficient to declare survival benefit.
  • Anti-CD20 radioimmunoconjugates (RICs) (90)Yttrium-ibritumomab tiuxetan and (131)Iodine-tositumomab have been used in mantle cell lymphoma even when patients are relatively resistant to Rituximab-based therapy.
  • Allogeneic stem cell transplantation is a treatment modality in advanced or relapsed MCL, particularly using reduced-intensity conditioning.
  • MCL may have high response rates and sustained remissions after donor lymphocyte infusion.
  • Dendritic cells (DCs) fused with MCL cells for immunostimulation have preliminarily shown anti-lymphoma effects as well.
  • Idiotype vaccination in MCL patients following Rituximab-containing chemotherapy induced tumor-specific T-cell immunity in the absence of B cells.
  • A Phase I/II study is ongoing to determine the maximum tolerated dose (MTD) and the efficacy of lenalidomide in combination with Rituximab for relapsed/refractory MCL.
  • This review summarizes the latest and exciting advances in MCL.
  • [MeSH-major] Antigens, CD20 / immunology. Immunotherapy / methods. Lymphoma, Mantle-Cell / therapy
  • [MeSH-minor] Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Murine-Derived. Antigens, CD / immunology. Antineoplastic Agents / therapeutic use. Cancer Vaccines / therapeutic use. Dendritic Cells / immunology. Graft vs Tumor Effect. Humans. Rituximab


45. Shishodia S, Amin HM, Lai R, Aggarwal BB: Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochem Pharmacol; 2005 Sep 1;70(5):700-13
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  • [Title] Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma.
  • Human mantle cell lymphoma (MCL), an aggressive B cell non-Hodgkin's lymphoma, is characterized by the overexpression of cyclin D1 which plays an essential role in the survival and proliferation of MCL.
  • Because of MCL's resistance to current chemotherapy, novel approaches are needed.
  • Since MCL cells are known to overexpress NF-kappaB regulated gene products (including cyclin D1), we used curcumin, a pharmacologically safe agent, to target NF-kappaB in a variety of MCL cell lines.
  • All four MCL cell lines examined had overexpression of cyclin D1, constitutive active NF-kappaB and IkappaB kinase and phosphorylated forms of IkappaBalpha and p65.
  • On treatment of cells with curcumin, however, downregulated constitutive active NF-kappaB and inhibited the consitutively active IkappaBalpha kinase (IKK), and phosphorylation of IkappaBalpha and p65.
  • Consequently, the expression of all NF-kappaB-regulated gene products, were downregulated by the polyphenol leading to the suppression of proliferation, cell cycle arrest at the G1/S phase of the cell cycle and induction of apoptosis as indicated by caspase activation, PARP cleavage, and annexin V staining.
  • That NF-kappaB activation is directly linked to the proliferation of cells, is also indicated by the observation that peptide derived from the IKK/NEMO-binding domain and p65 suppressed the constitutive active NF-kappaB complex and inhibited the proliferation of MCL cells.
  • Overall, our results indicate that curcumin inhibits the constitutive NF-kappaB and IKK leading to suppression of expression of NF-kappaB-regulated gene products that results in the suppression of proliferation, cell cycle arrest, and induction of apoptosis in MCL.
  • [MeSH-major] Apoptosis / drug effects. Curcumin / pharmacology. G1 Phase / drug effects. Lymphoma, Mantle-Cell / drug therapy. NF-kappa B / antagonists & inhibitors. S Phase / drug effects
  • [MeSH-minor] Active Transport, Cell Nucleus / drug effects. Cell Line, Tumor. Cell Proliferation / drug effects. Humans. I-kappa B Proteins / metabolism. Phosphorylation. Tumor Necrosis Factor-alpha / analysis. Tumor Necrosis Factor-alpha / antagonists & inhibitors


46. Hess G: Temsirolimus for the treatment of mantle cell lymphoma. Expert Rev Hematol; 2009 Dec;2(6):631-40
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Temsirolimus for the treatment of mantle cell lymphoma.
  • Although recent progress has been made in the treatment of mantle cell lymphoma (MCL) the majority of patients experience relapse and ultimately die of their disease.
  • The translocation t(11;14) is a prerequisite for the diagnosis of MCL and results in overexpression of cyclin D1.
  • Its protein translation is controlled by mTOR, a key element of the PI3K/Akt pathway, and mTOR constitutes an attractive therapeutic target.
  • Temsirolimus, a specific inhibitor of mTOR, has been evaluated in two Phase II trials in patients with relapsed MCL, and promising response rates up to 40% were found.
  • This adds temsirolimus to the therapeutic armamentarium for the treatment of MCL.
  • Further developments target combination therapy in MCL and other lymphoid neoplasms.
  • [MeSH-major] Antineoplastic Agents. Cyclin D1 / analysis. Cyclin D1 / metabolism. Intracellular Signaling Peptides and Proteins / metabolism. Lymphoma, Mantle-Cell. Sirolimus / analogs & derivatives. TOR Serine-Threonine Kinases / antagonists & inhibitors
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Clinical Trials as Topic. Disease-Free Survival. Drug Administration Schedule. Female. Humans. Male. Middle Aged. Remission Induction. Secondary Prevention


47. Vaughn JE, Gopal AK: Relapsed mantle cell lymphoma presenting as "sister Mary joseph nodule". Case Rep Med; 2010;2010:708348
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  • [Title] Relapsed mantle cell lymphoma presenting as "sister Mary joseph nodule".
  • We report a case of relapsed mantle cell lymphoma (MCL) presenting as a Sister Mary Joseph's nodule.
  • Although the few reports of lymphoma exhibiting umbilical metastasis suggest that patients may still expect a reasonable response to chemotherapy, this patient experienced multiple relapses, despite aggressive chemotherapy regimens.
  • This clinical course is characteristic of the mantle cell form of non-hodgkin's lymphoma and illustrates a need to seek out more effective therapies.

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  • (PMID = 20396390.001).
  • [ISSN] 1687-9635
  • [Journal-full-title] Case reports in medicine
  • [ISO-abbreviation] Case Rep Med
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC2852603
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48. Lenz G, Hiddemann W, Dreyling M: The role of fludarabine in the treatment of follicular and mantle cell lymphoma. Cancer; 2004 Sep 1;101(5):883-93
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  • [Title] The role of fludarabine in the treatment of follicular and mantle cell lymphoma.
  • Advanced-stage follicular lymphoma (FL) and mantle cell lymphoma (MCL) cannot be cured using conventional chemotherapy.
  • Fludarabine, the most widely used purine analog, exhibits a particularly high level of activity against small lymphocytic lymphoma and chronic lymphocytic leukemia (CLL).
  • Numerous studies have investigated the efficacy of fludarabine as a single agent or in combination with other cytostatic compounds in the treatment of FL and MCL.
  • Fludarabine monotherapy has proven to be particularly effective in the treatment of FL; however, complete responses (CRs) are observed in only approximately 20-40% of all cases.
  • In a randomized trial, an immunochemotherapy regimen consisting of a fludarabine-containing combination and rituximab resulted in superior remission and survival rates compared with the fludarabine-containing combination alone.
  • In summary, fludarabine has proven to be a safe and effective agent in the treatment of indolent lymphoma.
  • Consequently, current research efforts have focused on the use of fludarabine-containing combinations in the first-line treatment of FL and MCL.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Lymphoma, Follicular / drug therapy. Lymphoma, Mantle-Cell / drug therapy. Vidarabine / analogs & derivatives. Vidarabine / therapeutic use

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  • [Copyright] Copyright 2004 American Cancer Society.
  • (PMID = 15329894.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; EC 2.1.1.37 / DNA (Cytosine-5-)-Methyltransferase; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
  • [Number-of-references] 74
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49. Incani RN, Hernández M, González ME: Hyperinfection by Strongyloides stercoralis probably associated with Rituximab in a patient with mantle cell lymphoma and hyper eosinophilia. Rev Inst Med Trop Sao Paulo; 2010 Jul-Aug;52(4):221-4
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  • [Title] Hyperinfection by Strongyloides stercoralis probably associated with Rituximab in a patient with mantle cell lymphoma and hyper eosinophilia.
  • The first report to our knowledge, of hyperinfection by Strongyloides stercoralis (HS) and hypereosinophilia, associated to immune suppression by Rituximab (the only drug received for the last one year and 10 months), in a patient with mantle-cell lymphoma (MCL), is presented.
  • The patient has a 3-year history of MCL, and developed two accesses of HS during 2008, including meningitis, pneumonia and presence of larvae of S. stercoralis in the lungs.
  • We had a unique chance to look at cytotoxicity of filariform larvae in the expectoration after Ivermectin treatment, showing immobilization and death of larvae, associated with eosinophils attached to the cuticle of the parasite.
  • [MeSH-minor] Animals. Antiparasitic Agents / therapeutic use. Female. Humans. Hypereosinophilic Syndrome / immunology. Ivermectin / therapeutic use. Lymphoma, Mantle-Cell / drug therapy. Lymphoma, Mantle-Cell / immunology. Middle Aged. Rituximab

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  • (PMID = 21748232.001).
  • [ISSN] 1678-9946
  • [Journal-full-title] Revista do Instituto de Medicina Tropical de São Paulo
  • [ISO-abbreviation] Rev. Inst. Med. Trop. Sao Paulo
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Brazil
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antineoplastic Agents; 0 / Antiparasitic Agents; 4F4X42SYQ6 / Rituximab; 70288-86-7 / Ivermectin
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51. Straten Pt, Andersen MH: The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens. Oncotarget; 2010 Aug;1(4):239-45
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  • Anti-apoptotic members of the Bcl-2 family (Bcl-2, Bcl-X(L) and Mcl-2) are pivotal regulators of apoptotic cell death.
  • They are all highly overexpressed in cancers of different origin in which they enhance the survival of the cancer cells.
  • Consequently, they represent prime candidates for anti-cancer therapy and specific antisense oligonucleotides or small molecule inhibitors have shown broad anti-cancer activities in pre-clinical models and are currently tested in clinical trials.
  • In addition, immune-mediated tumor destruction is emerging as an interesting modality to treat cancer patients.
  • Notably, spontaneous cellular immune responses against the Bcl-2 family proteins have been identified as frequent features in cancer patients underscoring that these proteins are natural targets for the immune system.
  • Thus, Bcl-2 family may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies, alone or in the combination with conventional therapy.
  • Here, we summarize the current knowledge of Bcl-2 family proteins as T-cell antigens, which has set the stage for the first explorative trial using these antigens in therapeutic vaccinations against cancer, and discuss future opportunities.
  • [MeSH-major] Antigens, Neoplasm. Neoplasms / therapy. Proto-Oncogene Proteins c-bcl-2 / immunology. bcl-X Protein / immunology
  • [MeSH-minor] Apoptosis. Cancer Vaccines / therapeutic use. Combined Modality Therapy. Drug Discovery. Genes, bcl-2. Humans. Myeloid Cell Leukemia Sequence 1 Protein. Oligonucleotides, Antisense / therapeutic use

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  • (PMID = 21304176.001).
  • [ISSN] 1949-2553
  • [Journal-full-title] Oncotarget
  • [ISO-abbreviation] Oncotarget
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / Cancer Vaccines; 0 / Myeloid Cell Leukemia Sequence 1 Protein; 0 / Oligonucleotides, Antisense; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / bcl-X Protein
  • [Other-IDs] NLM/ PMC3248102
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52. Rolland D, Raharijaona M, Barbarat A, Houlgatte R, Thieblemont C: Inhibition of GST-pi nuclear transfer increases mantle cell lymphoma sensitivity to cisplatin, cytarabine, gemcitabine, bortezomib and doxorubicin. Anticancer Res; 2010 Oct;30(10):3951-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Inhibition of GST-pi nuclear transfer increases mantle cell lymphoma sensitivity to cisplatin, cytarabine, gemcitabine, bortezomib and doxorubicin.
  • PURPOSE: Mantle cell lymphoma (MCL) is a chemoresistant lymphoma overexpressing the class pi glutathione-S-transferase (GST-pi).
  • The nuclear localisation of GST-pi is induced by chemotherapy and is correlated to cell resistance.
  • In this study, the effect of the Agaricus bisporus lectin (ABL), a GST-pi nuclear transfer inhibitor, on the chemosensitivity of MCL cells was investigated.
  • METHODS: The proliferation of three MCL cell lines was evaluated in the presence of doxorubicin (DOX), cisplatin (CDDP), cytarabine (Ara-C), gemcitabine (GEM) or bortezomib with or without ABL pre-treatment.
  • RESULTS: The cytotoxic activities of CDDP, Ara-C, GEM and bortezomib were increased in all cell lines.
  • The DOX cytotoxic activity was enhanced in two of three cell lines.
  • The inhibition of GST-pi nuclear transfer led to the potentialisation of all drug combinations.
  • CONCLUSION: The inhibition of the nuclear transfer of GST-pi increases the MCL sensitivity to DOX, CDDP, Ara-C, GEM and bortezomib, alone or in combination.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Antineoplastic Combined Chemotherapy Protocols / pharmacology. Glutathione S-Transferase pi / antagonists & inhibitors. Lymphoma, Mantle-Cell / drug therapy. Lymphoma, Mantle-Cell / enzymology
  • [MeSH-minor] Active Transport, Cell Nucleus / drug effects. Boronic Acids / administration & dosage. Boronic Acids / pharmacology. Bortezomib. Cell Growth Processes / drug effects. Cell Line, Tumor. Cisplatin / administration & dosage. Cisplatin / pharmacology. Cytarabine / administration & dosage. Cytarabine / pharmacology. Deoxycytidine / administration & dosage. Deoxycytidine / analogs & derivatives. Deoxycytidine / pharmacology. Doxorubicin / administration & dosage. Doxorubicin / pharmacology. Drug Screening Assays, Antitumor. Humans. Lectins / administration & dosage. Lectins / pharmacology. Pyrazines / administration & dosage. Pyrazines / pharmacology


53. Hagemeister FB: Mantle cell lymphoma: non-myeloablative versus dose-intensive therapy. Leuk Lymphoma; 2003;44 Suppl 3:S69-75
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  • [Title] Mantle cell lymphoma: non-myeloablative versus dose-intensive therapy.
  • Mantle cell lymphoma (MCL) is now recognized as an aggressive lymphoma, in which there is frequent development of resistance to chemotherapy and a median survival period of 3-4 years.
  • In recent years, the use of the chimeric monoclonal antibody rituximab, which is directed against the CD20 antigen, has provided new possibilities for the treatment of MCL.
  • Rituximab alone produces overall response rates of 30-33% in patients with MCL, and is also effective at inducing complete responses in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
  • Furthermore, the addition of rituximab to the regimen of fractionated Hyper-CVAD/MTX-AraC (cyclophosphamide/doxorubicin:vincristine/dexamethasone alternated with methotrexate/cytarabine) has been found to produce responses and relapse-free and overall survival in younger patients that are comparable to those seen with Hyper-CVAD/MTX-AraC plus stem cell transplantation.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Lymphoma, Mantle-Cell / therapy
  • [MeSH-minor] Disease-Free Survival. Hematopoietic Stem Cell Transplantation. Humans

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  • (PMID = 15202528.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 29
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54. Cerovecki T, Bojanic I, Brcic L, Radic B, Vukoja I, Seiwerth S, Sikiric P: Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. J Orthop Res; 2010 Sep;28(9):1155-61
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  • [Title] Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat.
  • We improved medial collateral ligament (MCL) healing throughout 90 days after surgical transection.
  • We introduced intraperitoneal, per-oral (in drinking water) and topical (thin cream layer) peptide therapy always given alone, without a carrier.
  • Previously, as an effective peptide therapy, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide effective in inflammatory bowel disease therapy (PL 14736)) particularly improved healing of transected tendon and muscle and wound healing effect including the expression of the early growth response 1 (egr-1) gene.
  • After MCL transection BPC 157 was effective in rats when given once daily intraperitoneally (10 microg or 10 ng/kg) or locally as a thin layer (1.0 microg dissolved in distilled water/g commercial neutral cream) at the site of injury, first application 30 min after surgery and the final application 24 h before sacrifice.
  • Thus, we suggest BPC 157 improved healing of acute ligament injuries in further ligament therapy.
  • [MeSH-major] Medial Collateral Ligament, Knee / drug effects. Medial Collateral Ligament, Knee / injuries. Peptide Fragments / pharmacology. Proteins / pharmacology. Wound Healing / drug effects
  • [MeSH-minor] Administration, Oral. Animals. Collagen Type I / metabolism. Collagen Type III / metabolism. Contracture / prevention & control. Disease Models, Animal. Male. Motor Activity / drug effects. Neutrophils / physiology. Rats. Rats, Wistar. Recovery of Function / drug effects

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  • [Copyright] (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
  • (PMID = 20225319.001).
  • [ISSN] 1554-527X
  • [Journal-full-title] Journal of orthopaedic research : official publication of the Orthopaedic Research Society
  • [ISO-abbreviation] J. Orthop. Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Collagen Type I; 0 / Collagen Type III; 0 / Peptide Fragments; 0 / Proteins; 137525-51-0 / BPC 157
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55. Obrador-Hevia A, Fernández de Mattos S, Villalonga P, Rodríguez J: Molecular biology of mantle cell lymphoma: from profiling studies to new therapeutic strategies. Blood Rev; 2009 Sep;23(5):205-16
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  • [Title] Molecular biology of mantle cell lymphoma: from profiling studies to new therapeutic strategies.
  • Mantle cell lymphoma (MCL) is a well-defined lymphoid malignancy characterized by a rapid clinical evolution and poor response to current therapeutic protocols.
  • The hallmark genetic alteration of MCL is the t(11;14)(q13;32) chromosomal translocation that leads to the overexpression of cyclin D1.
  • Recently, new molecular alterations of major importance in the pathogenic mechanisms of this disease have been discovered, and have revealed the biological heterogeneity of MCL.
  • In the second section we revise new therapeutic strategies based on new drug families that target key molecular pathways of major relevance in this malignancy.
  • We analyze emerging agents that are already producing significant results in different models of human cancers, including MCL.
  • Based on the current knowledge and recent studies, we suggest that the encouraging results described here should provide a rationale platform for the design of new treatments that may overcome the resistance of this aggressive lymphoma to conventional therapy and improve patient prognosis.
  • [MeSH-major] Apoptosis / physiology. Cyclin D1 / metabolism. Lymphoma, Mantle-Cell / drug therapy. Lymphoma, Mantle-Cell / genetics
  • [MeSH-minor] Animals. Cell Cycle / drug effects. Cell Cycle / physiology. DNA Damage / physiology. Enzyme Inhibitors / therapeutic use. Gene Expression Profiling. Humans. Immunologic Factors / therapeutic use. Protein Kinase Inhibitors / therapeutic use

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  • (PMID = 19362399.001).
  • [ISSN] 1532-1681
  • [Journal-full-title] Blood reviews
  • [ISO-abbreviation] Blood Rev.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Enzyme Inhibitors; 0 / Immunologic Factors; 0 / Protein Kinase Inhibitors; 136601-57-5 / Cyclin D1
  • [Number-of-references] 141
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56. Geisler C, Kolstad A, Laurell A, Räty R, Nordic Lymphoma Group, Mantle Cell Lymphoma Subcommittee: Mantle cell lymphoma - does primary intensive immunochemotherapy improve overall survival for younger patients? Leuk Lymphoma; 2009 Aug;50(8):1249-56
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  • [Title] Mantle cell lymphoma - does primary intensive immunochemotherapy improve overall survival for younger patients?
  • MCL is a rare entity of non-Hodgkin lymphoma, hitherto considered incurable.
  • There is no standard therapy, but the current treatment results do seem to have led to a prolongation of the median survival from 3 to 5 years.
  • Following CHOP-like induction, high-dose radiochemotherapy, and autologous stem cell transplantation (ASCT) chemotherapy has been shown in a controlled trial to be superior in younger patients, but does not, however, lead to long-term freedom from disease.
  • Results of recent prospective but uncontrolled trials of more intensive frontline immunochemotherapy containing cytarabine and rituximab followed by ASCT, however, now for the first time indicate plateaus of the curves of event-free, progression-free and overall survival, suggesting cure, but more studies and longer follow-up is needed.
  • Following relapse, autologous stem-cell transplantation does not seem to be of value, but graft-versus-lymphoma effect has been documented, and allogeneic stem cell transplantation with reduced-intensity conditioning is emerging as the treatment of choice in this setting.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lymphoma, Mantle-Cell / therapy
  • [MeSH-minor] Age Factors. Aged. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Murine-Derived. B-Lymphocyte Subsets / pathology. Clinical Trials as Topic / statistics & numerical data. Combined Modality Therapy. Cyclophosphamide / administration & dosage. Cytarabine / administration & dosage. Disease-Free Survival. Doxorubicin / administration & dosage. Female. Follow-Up Studies. Genes, bcl-1. Hematopoietic Stem Cell Transplantation. Humans. Immunophenotyping. Male. Middle Aged. Prednisone / administration & dosage. Prognosis. Prospective Studies. Rituximab. Salvage Therapy. Survival Analysis. Transplantation Conditioning. Vincristine / administration & dosage

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  • (PMID = 19562619.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 04079A1RDZ / Cytarabine; 4F4X42SYQ6 / Rituximab; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; VB0R961HZT / Prednisone; CHOP protocol
  • [Number-of-references] 50
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57. Kikuchi T, Asano N, Noguchi T, Nomura E, Uchimi K, Kagaya H, Suzuki S, Suzuki M, Kayaba Y, Tateno H, Onodera H: [A case of primary gastric mantle cell lymphoma]. Nihon Shokakibyo Gakkai Zasshi; 2009 Aug;106(8):1168-76
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  • [Title] [A case of primary gastric mantle cell lymphoma].
  • Endoscopic examination of a 60-year-old man revealed multiple erosions in the gastric antrum.
  • After 20 months, the gastroduodenal erosions developed into mucosal ulcers, and the systemic lymph node swelling progressed.
  • Histological examination of the neck lymph node showed mantle cell lymphoma (MCL).
  • This case was diagnosed as recurrent primary gastric MCL in other areas, with systemic lymph node metastasis and bone marrow invasion.
  • Hyper-CVAD (cyclophosphamide, doxorubicin, vincristine, and dexamethasone), high-dose methotrexate and cytarabine in combination with Rituximab and stem cell transplantation was performed.
  • The gastroduodenal lesions and atypical cells in the bone marrow disappeared after 2 cycles of the chemotherapy.
  • Metastatic lymph node swelling regressed after stem cell transplantation.
  • Primary gastric MCL is very rare and cyclin D1 immunohistochemistry and FISH assay were very useful for the diagnosis of MCL.
  • [MeSH-major] Lymphoma, Mantle-Cell / pathology. Stomach Neoplasms / pathology
  • [MeSH-minor] Combined Modality Therapy. Hematopoietic Stem Cell Transplantation. Humans. Male. Middle Aged


58. Singh AT, Evens AM, Anderson RJ, Beckstead JA, Sankar N, Sassano A, Bhalla S, Yang S, Platanias LC, Forte TM, Ryan RO, Gordon LI: All trans retinoic acid nanodisks enhance retinoic acid receptor mediated apoptosis and cell cycle arrest in mantle cell lymphoma. Br J Haematol; 2010 Jul;150(2):158-69
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  • [Title] All trans retinoic acid nanodisks enhance retinoic acid receptor mediated apoptosis and cell cycle arrest in mantle cell lymphoma.
  • Mantle cell lymphoma (MCL) is characterized by translocation t(11;14)(q13;q32), aggressive clinical behaviour, and poor patient outcomes following conventional chemotherapy.
  • New treatment approaches are needed that target novel biological pathways.
  • The present study evaluated cell killing effects of ATRA-enriched nanoscale delivery particles, termed nanodisks (ND), on MCL cell lines.
  • Results show that ATRA-ND induced cell death more effectively than naked ATRA (dimethyl sulphoxide) or empty ND.
  • At ATRA concentrations that induced apoptosis, expression levels of retinoic acid receptor-alpha (RARalpha) and retinoid X receptor-gamma (RXRgamma) were increased.
  • Compared to naked ATRA, ATRA-ND significantly stimulated transcriptional activity of RARA in a model carcinoma cell line.
  • Furthermore, the RAR antagonist, Ro 41-5253, inhibited ATRA-ND induced ROS generation and prevented ATRA-ND induced cell growth arrest and apoptosis.
  • In summary, incorporation of ATRA into ND enhanced the biological activity of this retinoid in cell culture models of MCL.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Lymphoma, Mantle-Cell / pathology. Receptors, Retinoic Acid / drug effects. Tretinoin / pharmacology
  • [MeSH-minor] Apoptosis / drug effects. Benzoates / pharmacology. Cell Cycle / drug effects. Cell Cycle Proteins / biosynthesis. Cell Cycle Proteins / drug effects. Chromans / pharmacology. Drug Delivery Systems. Drug Evaluation, Preclinical. Guanine Nucleotide Exchange Factors / biosynthesis. Guanine Nucleotide Exchange Factors / drug effects. Humans. Nanoparticles. Neoplasm Proteins / biosynthesis. Neoplasm Proteins / drug effects. Nuclear Proteins / biosynthesis. Nuclear Proteins / drug effects. Reactive Oxygen Species / metabolism. Retinoid X Receptors / drug effects. Retinoid X Receptors / metabolism. Transcription, Genetic / drug effects. Tumor Cells, Cultured

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  • (PMID = 20507312.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R01 CA121192; United States / NHLBI NIH HHS / HL / R37 HL064159; United States / NCI NIH HHS / CA / R43 CA141904-01; United States / NHLBI NIH HHS / HL / R01 HL064159-12; United States / NCI NIH HHS / CA / 1R43CA141904; United States / NCI NIH HHS / CA / P30 CA060553; United States / NHLBI NIH HHS / HL / HL-64159; United States / NHLBI NIH HHS / HL / R01 HL064159; United States / NCI NIH HHS / CA / R43 CA141904; United States / NCI NIH HHS / CA / R01 CA121192-05; United States / NCI NIH HHS / CA / CA121192
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzoates; 0 / Cell Cycle Proteins; 0 / Chromans; 0 / Guanine Nucleotide Exchange Factors; 0 / Neoplasm Proteins; 0 / Nuclear Proteins; 0 / RCC1 protein, human; 0 / Reactive Oxygen Species; 0 / Receptors, Retinoic Acid; 0 / Retinoid X Receptors; 144092-31-9 / Ro 41-5253; 5688UTC01R / Tretinoin
  • [Other-IDs] NLM/ NIHMS212465; NLM/ PMC2907750
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59. Paoluzzi L, Gonen M, Bhagat G, Furman RR, Gardner JR, Scotto L, Gueorguiev VD, Heaney ML, Manova K, O'Connor OA: The BH3-only mimetic ABT-737 synergizes the antineoplastic activity of proteasome inhibitors in lymphoid malignancies. Blood; 2008 Oct 1;112(7):2906-16
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  • Overexpression of antiapoptotic members of the Bcl-2 family is observed in approximately 80% of B-cell lymphomas, contributing to intrinsic and acquired drug resistance.
  • Nullifying the antiapoptotic influence of these proteins can potentially overcome this resistance, and may complement conventional chemotherapy.
  • In vitro, ABT-737 exhibited concentration-dependent cytotoxicity against a broad panel of lymphoma cell lines including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL).
  • ABT-737 showed synergism when combined with the proteasome inhibitors bortezomib or carfilzomib in select lymphoma cell lines and induced potent mitochondrial membrane depolarization and apoptosis when combined with either.
  • ABT-737 plus bortezomib also induced significant apoptosis in primary samples of MCL, DLBCL, and chronic lymphocytic leukemia (CLL) but no significant cytotoxic effect was observed in peripheral blood mononuclear cells from healthy donors.
  • In severe combined immunodeficient beige mouse models of MCL, the addition of ABT-737 to bortezomib enhanced efficacy compared with either drug alone and with the control.
  • Collectively, these data suggest that ABT-737 alone or in combination with a proteasome inhibitor represents a novel and potentially important platform for the treatment of B-cell malignancies.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Biphenyl Compounds / pharmacology. Enzyme Inhibitors / pharmacology. Lymphoma / enzymology. Lymphoma / pathology. Molecular Mimicry / drug effects. Nitrophenols / pharmacology. Proteasome Inhibitors. Sulfonamides / pharmacology
  • [MeSH-minor] Animals. Boronic Acids / pharmacology. Bortezomib. Cell Death / drug effects. Cell Line, Tumor. Dose-Response Relationship, Drug. Drug Resistance, Neoplasm / drug effects. Drug Synergism. Health. Humans. Leukemia, Lymphocytic, Chronic, B-Cell / pathology. Leukocytes, Mononuclear / drug effects. Lymphoma, Large B-Cell, Diffuse / pathology. Lymphoma, Mantle-Cell / pathology. Membrane Potential, Mitochondrial / drug effects. Mice. Microscopy, Confocal. Piperazines / pharmacology. Proto-Oncogene Proteins c-bcl-2 / metabolism. Pyrazines / pharmacology. Tissue Donors. Xenograft Model Antitumor Assays

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  • (PMID = 18591385.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / ABT-737; 0 / Antineoplastic Agents; 0 / Biphenyl Compounds; 0 / Boronic Acids; 0 / Enzyme Inhibitors; 0 / Nitrophenols; 0 / Piperazines; 0 / Proteasome Inhibitors; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / Pyrazines; 0 / Sulfonamides; 69G8BD63PP / Bortezomib
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60. Sohn SK, Baek JH, Kim DH, Jung JT, Kwak DS, Park SH, Suh JS, Lee KB: Successful allogeneic stem-cell transplantation with prophylactic stepwise G-CSF primed-DLIs for relapse after autologous transplantation in mantle cell lymphoma: a case report and literature review on the evidence of GVL effects in MCL. Am J Hematol; 2000 Sep;65(1):75-80
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  • [Title] Successful allogeneic stem-cell transplantation with prophylactic stepwise G-CSF primed-DLIs for relapse after autologous transplantation in mantle cell lymphoma: a case report and literature review on the evidence of GVL effects in MCL.
  • Mantle cell lymphoma (MCL) is a distinctive clinicopathologic entity and represents 2-8% of all non-Hodgkin's lymphomas.
  • The median survival of patients with MCL is only 3 years, and none of the available conventional chemotherapy regimens appears curative.
  • Encouraging results have been reported with high-dose chemotherapy with autologous stem-cell transplantation (autoSCT).
  • However, a plateau in disease-free survival was not observed in relapsed MCL on the autoSCT trials.
  • Donor lymphocyte infusions (DLIs), by virtue of a GVL effect, have been shown to induce durable remissions in a few cases with refractory MCL that recur after alloSCT.
  • In this article, we review the literature on the evidence of the GVL effects in MCL and describe a patient with relapsed MCL shortly after high-dose chemotherapy with autoSCT.
  • G-CSF-primed cryopreserved DLIs were then infused on D+64 and D+92 to enhance the GVL effect.
  • Grade 3 intestinal GVHD developed 20 days after the 2(nd) DLI and was partially controlled with the combination of cyclosporin, prednisone, and mycophenolate mofetil.
  • Our findings suggest that alloSCT followed by prophylactic DLIs may offer a curative approach to refractory MCL.
  • [MeSH-major] Graft vs Tumor Effect. Granulocyte Colony-Stimulating Factor / pharmacology. Hematopoietic Stem Cell Transplantation. Intestinal Neoplasms / therapy. Lymphocyte Transfusion. Lymphoma, Mantle-Cell / therapy
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Blood Donors. Humans. Male. Recurrence. Transplantation, Homologous. Treatment Outcome

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  • [Copyright] Copyright 2000 Wiley-Liss, Inc.
  • (PMID = 10936869.001).
  • [ISSN] 0361-8609
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 143011-72-7 / Granulocyte Colony-Stimulating Factor
  • [Number-of-references] 33
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61. Kella VK, Constantine R, Parikh NS, Reed M, Cosgrove JM, Abo SM, King S: Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions--case report and review of literature. World J Surg Oncol; 2009;7:60
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  • [Title] Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions--case report and review of literature.
  • BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin's lymphoma that originates from small to medium sized lymphocytes located in the mantle zone of the lymph node.
  • Extra nodal involvement is present in the majority of cases, with a peculiar tendency to invade the gastro-intestinal tract in the form of multiple lymphomatous polyposis.
  • MCL can be accurately diagnosed with the use of the highly specific marker Cyclin D1.
  • Few cases of mantle cell lymphoma presenting with intussuception have been reported.
  • Here we present a rare case of multiple intussusceptions caused by mantle cell lymphoma and review the literature of this disease.
  • Laparoscopy confirmed multiple intussusceptions involving ileo-colic and ileo-ileal segments of gastrointestinal tract.
  • The histology and immuno-histochemistry of the excised small and large bowel revealed mantle cell lymphoma with multiple lymphomatous polyposis and positivity to Cyclin D1 marker.
  • The patient was successfully treated with Rituximab-CHOP chemotherapy and remains in complete remission at one-year follow-up.
  • CONCLUSION: This is a rare case of intestinal lymphomatous polyposis due to mantle cell lymphoma presenting with multiple small bowel intussusceptions.
  • Our case highlights laparoscopic-assisted bowel resection as a potential and feasible option in the multi-disciplinary treatment of mantle cell lymphoma.
  • [MeSH-major] Gastrointestinal Neoplasms / complications. Ileal Diseases / etiology. Intussusception / etiology. Lymphoma, Mantle-Cell / complications


62. Garcia M, Romaguera JE, Inamdar KV, Rassidakis GZ, Medeiros LJ: Proliferation predicts failure-free survival in mantle cell lymphoma patients treated with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with rituximab plus high-dose methotrexate and cytarabine. Cancer; 2009 Mar 1;115(5):1041-8
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  • [Title] Proliferation predicts failure-free survival in mantle cell lymphoma patients treated with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with rituximab plus high-dose methotrexate and cytarabine.
  • BACKGROUND: It has been demonstrated that the tumor proliferation index has prognostic significance in patients with mantle cell lymphoma (MCL).
  • Patients in most of studies, however, have been treated with relatively traditional chemotherapy regimens.
  • At the authors' institution, patients with MCL received an aggressive chemotherapy regimen: rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with rituximab plus high-dose methotrexate and cytarabine (R-hyper-CVAD).
  • METHODS: The authors assessed the proliferation rate of MCL using immunohistochemistry and an antibody specific for Ki-67 in 71 untreated patients who subsequently received R-hyper-CVAD.
  • The study group included 59 patients who had classic MCL and 12 patients who had the blastoid variant of MCL.
  • RESULTS: For the entire study group and for the group of patients with classic MCL, a proliferation index of >20% Ki-67-positive cells was correlated significantly with shorter failure-free survival.
  • CONCLUSIONS: The current results indicated that the proliferation index in patients with MCL predicted prognosis in those who uniformly received the R-hyper-CVAD chemotherapy regimen.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lymphoma, Mantle-Cell / drug therapy
  • [MeSH-minor] Antibodies, Monoclonal. Antibodies, Monoclonal, Murine-Derived. Cyclophosphamide / administration & dosage. Cytarabine / administration & dosage. Dexamethasone / administration & dosage. Disease-Free Survival. Doxorubicin / administration & dosage. Drug Administration Schedule. Female. Humans. Ki-67 Antigen / metabolism. Male. Methotrexate / administration & dosage. Middle Aged. Prognosis. Rituximab. Survival Analysis. Vincristine / administration & dosage

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  • [Copyright] (c) 2009 American Cancer Society.
  • (PMID = 19170236.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Ki-67 Antigen; 04079A1RDZ / Cytarabine; 4F4X42SYQ6 / Rituximab; 5J49Q6B70F / Vincristine; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; YL5FZ2Y5U1 / Methotrexate
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63. Ladetto M, Magni M, Pagliano G, De Marco F, Drandi D, Ricca I, Astolfi M, Matteucci P, Guidetti A, Mantoan B, Bodoni CL, Zanni M, Boccadoro M, Gianni AM, Tarella C: Rituximab induces effective clearance of minimal residual disease in molecular relapses of mantle cell lymphoma. Biol Blood Marrow Transplant; 2006 Dec;12(12):1270-6
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  • [Title] Rituximab induces effective clearance of minimal residual disease in molecular relapses of mantle cell lymphoma.
  • Molecular remission (MR) is associated with improved outcome in mantle cell lymphoma (MCL).
  • The 4 patients received rituximab-supplemented, high-dose sequential chemotherapy and autologous stem cell transplantation as induction treatment and achieved clinical remission and MR.
  • Minimal residual disease was monitored by qualitative and real-time quantitative PCR.
  • No clinical relapses were recorded at 3, 6, 18, and 62 months from treatment, although 1 patient had a second M-rel that was sensitive to rituximab.
  • Our results indicate that rituximab is active against residual MCL cells and suggest that molecularly tailored maintenance therapy needs to be investigated in clinical trials.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Lymphoma, Mantle-Cell / drug therapy. Salvage Therapy
  • [MeSH-minor] Adult. Antibodies, Monoclonal, Murine-Derived. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Chromosomes, Human, Pair 11 / genetics. Chromosomes, Human, Pair 11 / ultrastructure. Chromosomes, Human, Pair 14 / genetics. Chromosomes, Human, Pair 14 / ultrastructure. Combined Modality Therapy. Cyclophosphamide / administration & dosage. Cytarabine / administration & dosage. Doxorubicin / administration & dosage. Drug Evaluation. Follow-Up Studies. Gene Rearrangement, B-Lymphocyte, Heavy Chain. Genes, Immunoglobulin. Humans. Immunoglobulin Heavy Chains / genetics. Male. Melphalan / administration & dosage. Middle Aged. Mitoxantrone / administration & dosage. Neoplasm, Residual. Peripheral Blood Stem Cell Transplantation. Polymerase Chain Reaction. Prednisone / administration & dosage. Recurrence. Remission Induction. Retrospective Studies. Rituximab. Translocation, Genetic. Transplantation, Autologous. Vincristine / administration & dosage

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  • (PMID = 17162208.001).
  • [ISSN] 1083-8791
  • [Journal-full-title] Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • [ISO-abbreviation] Biol. Blood Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Immunoglobulin Heavy Chains; 04079A1RDZ / Cytarabine; 4F4X42SYQ6 / Rituximab; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; BZ114NVM5P / Mitoxantrone; Q41OR9510P / Melphalan; VB0R961HZT / Prednisone
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64. Bodet-Milin C, Touzeau C, Leux C, Sahin M, Moreau A, Maisonneuve H, Morineau N, Jardel H, Moreau P, Gallazini-Crépin C, Gries P, Gressin R, Harousseau JL, Mohty M, Moreau P, Kraeber-Bodere F, Le Gouill S: Prognostic impact of 18F-fluoro-deoxyglucose positron emission tomography in untreated mantle cell lymphoma: a retrospective study from the GOELAMS group. Eur J Nucl Med Mol Imaging; 2010 Aug;37(9):1633-42
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  • [Title] Prognostic impact of 18F-fluoro-deoxyglucose positron emission tomography in untreated mantle cell lymphoma: a retrospective study from the GOELAMS group.
  • PURPOSE: (18)F-fluorodeoxyglucose (FDG) PET is a non-invasive imaging technique recommended for the management of both diffuse large B-cell and Hodgkin's lymphomas.
  • This retrospective study investigated the value of FDG PET for initial staging and its prognostic impact on patients with mantle cell lymphoma (MCL).
  • METHODS: A total of 44 untreated MCL patients assessed by both conventional evaluations (CE) and FDG PET for initial staging were included.
  • The maximum standardized uptake value (SUV(max)) in the most intense pathological area was recorded for each patient.
  • Disease status after chemotherapy completion was assessed according to the International Workshop Criteria (IWC) for non-Hodgkin's lymphoma (NHL) response and IWC+PET.
  • With a median follow-up of 21 months, only the International Prognostic Index (IPI) and IWC+PET modified both event-free survival (EFS) (p = .02 and .0001, respectively) and overall survival (p = .03 and .05, respectively) duration.
  • CONCLUSION: In MCL, FDG PET at diagnosis is complementary to CE, but BM and GI biopsies remain mandatory.
  • [MeSH-major] Fluorodeoxyglucose F18. Lymphoma, Mantle-Cell / diagnostic imaging. Positron-Emission Tomography
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Neoplasm Staging. Prognosis. Retrospective Studies. Treatment Outcome

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  • (PMID = 20428863.001).
  • [ISSN] 1619-7089
  • [Journal-full-title] European journal of nuclear medicine and molecular imaging
  • [ISO-abbreviation] Eur. J. Nucl. Med. Mol. Imaging
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0Z5B2CJX4D / Fluorodeoxyglucose F18
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65. Hsieh YC, Lin CL, Tsao CJ, Hsieh PP, Tzeng CC, Chuang SS: Aberrant expression of CD19 and CD43 in a patient with therapy-related acute myeloid leukemia and a history of mantle cell lymphoma. Kaohsiung J Med Sci; 2009 Jul;25(7):389-94
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  • [Title] Aberrant expression of CD19 and CD43 in a patient with therapy-related acute myeloid leukemia and a history of mantle cell lymphoma.
  • Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with frequent involvement of the gastrointestinal tract and peripheral blood (PB).
  • In addition to the B cell markers, the neoplastic cells express CD5 and CD43.
  • In patients with a prior history of MCL with PB involvement, the appearance of leukemic cells after chemotherapy usually heralds a relapse, particularly if the leukemic cells express B cell markers and CD43.
  • We report a patient with MCL who presented with multiple lymphomatous polyposis of the intestine.
  • Three years after chemotherapy, thrombocytopenia with the appearance of rare leukemic cells in the PB was noted.
  • Detailed cytomorphological and immunophenotypic studies unveiled the myeloid nature of these leukemic cells, and a diagnosis of therapy-related acute myeloid leukemia was made.
  • This case illustrates the importance of morphologic examination and performing a complete antibody panel in the diagnosis of a suspected relapse in patients with a prior history of lymphoma.
  • [MeSH-major] Antigens, CD19 / immunology. Antigens, CD43 / immunology. Gene Expression Regulation, Neoplastic. Leukemia, Myeloid, Acute / etiology. Leukemia, Myeloid, Acute / immunology. Lymphoma, Mantle-Cell / immunology

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  • (PMID = 19605331.001).
  • [ISSN] 1607-551X
  • [Journal-full-title] The Kaohsiung journal of medical sciences
  • [ISO-abbreviation] Kaohsiung J. Med. Sci.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] China (Republic : 1949- )
  • [Chemical-registry-number] 0 / Antigens, CD19; 0 / Antigens, CD43
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66. Lefrère F, Delmer A, Suzan F, Levy V, Belanger C, Djabarri M, Arnulf B, Damaj G, Maillard N, Ribrag V, Janvier M, Sebban C, Casasnovas RO, Bouabdallah R, Dreyfus F, Verkarre V, Delabesse E, Valensi F, McIntyre E, Brousse N, Varet B, Hermine O: Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study. Leukemia; 2002 Apr;16(4):587-93
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  • [Title] Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study.
  • Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor prognosis.
  • We have conducted a prospective study in patients with MCL to evaluate a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if CHOP failed to induce complete remission.
  • Responding patients then proceeded to an intensification therapy with autologous peripheral blood stem cell transplantation (APBSCT).
  • Twenty-eight consecutive patients with newly diagnosed aggressive MCL were included.
  • The twenty-three responding patients received high-dose therapy (TAM8 regimen: TBI-cytarabine-melphalan) followed by APBSCT.
  • (1) CHOP regimen induces a low CR rate in MCL;.
  • (2) CHOP plus DHAP appears to be much more efficient and allows a large proportion of patients to proceed to high-dose therapy in CR;.
  • (3) consolidation therapy including TBI and high-dose Arac-C followed by APBSCT may improve event-free survival.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cisplatin / therapeutic use. Cyclophosphamide / therapeutic use. Cytarabine / therapeutic use. Dexamethasone / therapeutic use. Doxorubicin / therapeutic use. Hematopoietic Stem Cell Transplantation / methods. Lymphoma, Mantle-Cell / therapy. Prednisone / therapeutic use. Vincristine / therapeutic use
  • [MeSH-minor] Adult. Disease-Free Survival. Female. Follow-Up Studies. Humans. Immunophenotyping. Male. Middle Aged. Neoplasm Recurrence, Local. Prospective Studies. Survival Rate. Treatment Outcome


67. He H, Cheng L, Weiss LM, Chu PG: Clinical outcome of incidental pelvic node malignant B-cell lymphomas discovered at the time of radical prostatectomy. Leuk Lymphoma; 2007 Oct;48(10):1976-80
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  • [Title] Clinical outcome of incidental pelvic node malignant B-cell lymphomas discovered at the time of radical prostatectomy.
  • Incidental pelvic node malignant B-cell lymphomas diagnosed at the time of radical prostatectomy are rare.
  • Of 13 cases, 9 were chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 3 marginal zone B-cell lymphoma (MZL) and 1 mantle cell lymphoma (MCL).
  • All 13 patients did not receive radiation or chemotherapy; and five of 13 cases showed hematologic evidence of lymphoma progression between 1 and 5 months after radical prostatectomy.
  • After progression, the mantle cell lymphoma patient received aggressive chemotherapy and had systemic dissemination.
  • Two of 13 cases had recurrent prostate carcinoma.
  • None of 13 patients had died from lymphoma or prostate carcinoma at the last follow-up.
  • In conclusion, most incidental pelvic node lymphomas (8/13) showed no evidence of systemic dissemination to peripheral blood or bone marrow after a mean 42.8 weeks of follow-up despite the fact that no additional treatment was given.
  • Strong consideration should be given to withholding further treatment in patients diagnosed with pelvic low-grade B-cell lymphoma at the time of radical prostatectomy until disease progression occurs.
  • [MeSH-major] Lymphoma, B-Cell / immunology. Lymphoma, B-Cell / therapy. Neoplasms, Second Primary / therapy. Prostatic Neoplasms / surgery. Prostatic Neoplasms / therapy
  • [MeSH-minor] Aged. Antineoplastic Agents / therapeutic use. Disease-Free Survival. Follow-Up Studies. Humans. Male. Middle Aged. Models, Biological. Neoplasm Metastasis. Prognosis. Prostatectomy. Time Factors. Treatment Outcome

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  • (PMID = 17917966.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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68. Montaner JS, Schutz M, Schwartz R, Jayaweera DT, Burnside AF, Walmsley S, Saag MS: Efficacy, safety and pharmacokinetics of once-daily saquinavir soft-gelatin capsule/ritonavir in antiretroviral-naive, HIV-infected patients. MedGenMed; 2006;8(2):36
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  • CONTEXT: Once-daily HIV treatment regimens are being used in clinical practice with the objective of improving patient acceptance and adherence.
  • MAIN OUTCOME MEASURE: Proportion of patients with HIV-RNA levels < 50 copies/mL.
  • In the on-treatment (OT) population, 73% (38/52) and 93% (54/58) of patients in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, had effective viral suppression < 50 copies/mL (P = .5015, 95% 1-sided CI = -33.4%).
  • Mean CD4+ cell counts increased by 239 and 204 cells/microliters (mcL), in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, in the OT analysis (P = .058).
  • Gastrointestinal adverse effects were commonly associated with treatment failure in the saquinavir-SGC/ritonavir arm of the study.
  • [MeSH-minor] Adult. Benzoxazines. Capsules. Drug Administration Schedule. Drug Therapy, Combination. Female. Gelatin. HIV Infections. Humans. Male. Middle Aged

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  • (PMID = 16926775.001).
  • [ISSN] 1531-0132
  • [Journal-full-title] MedGenMed : Medscape general medicine
  • [ISO-abbreviation] MedGenMed
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Anti-HIV Agents; 0 / Benzoxazines; 0 / Capsules; 0 / HIV Protease Inhibitors; 0 / Oxazines; 9000-70-8 / Gelatin; JE6H2O27P8 / efavirenz; L3JE09KZ2F / Saquinavir; O3J8G9O825 / Ritonavir
  • [Other-IDs] NLM/ PMC1785231
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69. Bramwell VH: Osteosarcomas and other cancers of bone. Curr Opin Oncol; 2000 Jul;12(4):330-6
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  • The results of several studies suggest that alterations in various cell cycle regulatory genes are involved in the pathogenesis of osteosarcomas.
  • Experiments in animal models provide preliminary data on the feasibility of gene therapy in osteosarcoma and chondrosarcoma.
  • Prediction of response to chemotherapy remains a major focus of imaging research.
  • Several clinicopathologic studies have explored the mechanisms underlying multidrug resistance in osteosarcoma patients receiving neoadjuvant chemotherapy.
  • HER2/erbB2 expression, linked to poor prognosis, has been proposed as a therapeutic target in osteosarcoma.
  • A retrospective analysis showed no value for dose intensification of doxorubicin/cisplatin, but the results of a prospective trial should be more informative.
  • Recent evidence confirms that secondary osteosarcomas and malignant fibrous histiocytomas of bone should be treated with aggressive chemotherapy regimens, similar to those used for osteosarcomas.


70. Andersen NS, Pedersen L, Elonen E, Johnson A, Kolstad A, Franssila K, Langholm R, Ralfkiaer E, Akerman M, Eriksson M, Kuittinen O, Geisler CH, Nordic Lymphoma Group: Primary treatment with autologous stem cell transplantation in mantle cell lymphoma: outcome related to remission pretransplant. Eur J Haematol; 2003 Aug;71(2):73-80
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  • [Title] Primary treatment with autologous stem cell transplantation in mantle cell lymphoma: outcome related to remission pretransplant.
  • OBJECTIVES: The aim of the first Nordic mantle cell lymphoma (MCL) protocol was to study the clinical significance of an augmented CHOP induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) and to examine the prognostic significance of stem cell contamination rates in newly diagnosed patients with MCL.
  • Responders underwent stem cell mobilization with a fourth course of CHOP, stem cell harvest and ASCT.
  • Stem cell purging was optional in the protocol and followed the routine of each participating centre.
  • RESULTS: Induction therapy led to complete remission (CR) in 11 of 41 patients (27%), partial remission (PR) in 20 of 41 patients (49%) and no response in nine patients (22%), whereas one patient was not evaluable.
  • CONCLUSION: In MCL, an important strategy to improve the outcome will be to intensify the induction chemotherapy.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lymphoma, Mantle-Cell / therapy. Peripheral Blood Stem Cell Transplantation / methods
  • [MeSH-minor] Adult. Blood Component Removal / methods. Cyclophosphamide / administration & dosage. Female. Humans. Immunomagnetic Separation. Male. Middle Aged. Neoplastic Cells, Circulating. Prednisone / administration & dosage. Remission Induction. Survival Analysis. Transplantation, Autologous. Treatment Outcome. Vincristine / administration & dosage

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  • (PMID = 12890145.001).
  • [ISSN] 0902-4441
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Denmark
  • [Chemical-registry-number] 5J49Q6B70F / Vincristine; 8N3DW7272P / Cyclophosphamide; VB0R961HZT / Prednisone
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71. Dreyling M, Hoster E, Bea S, Hartmann E, Horn H, Hutter G, Salaverria I, Pott C, Trneny M, Le Gouill S, Cortelazzo S, Szymczyk M, Jurczak W, Shpilberg O, Ribrag V, Hermine O, European MCL Network: Update on the molecular pathogenesis and clinical treatment of Mantle Cell Lymphoma (MCL): minutes of the 9th European MCL Network conference. Leuk Lymphoma; 2010 Sep;51(9):1612-22
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  • [Title] Update on the molecular pathogenesis and clinical treatment of Mantle Cell Lymphoma (MCL): minutes of the 9th European MCL Network conference.
  • Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma which is characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in constitutional overexpression of cyclin D1 and cell cycle dysregulation in virtually all cases.
  • Clinically, MCL shows an aggressive clinical course with a continuous relapse pattern and a median survival of only 3-5 years.
  • However, recently a subset of 15% long-term survivors has been identified with a rather indolent clinical course, even after conventional treatment strategies only.
  • Advanced stage disease is usually apparent already at first clinical manifestation; thus, conventional chemotherapy is only palliative, and the median duration of remissions is only 1-2 years.
  • Emerging strategies including proteasome inhibitors, immune modulatory drugs (IMiDs), mTOR inhibitors, and others are based on the dysregulated control of cell cycle machinery and impaired apoptotic pathways.
  • Monotherapy of these compounds achieves efficacy comparable to conventional chemotherapy in relapsed MCL, and combination strategies are currently being investigated in numerous trials; however, their introduction into clinical practice and current treatment algorithms remain a challenge.
  • In 2000 the European MCL Network ( http://www.european-mcl.net ) was founded, consisting of 15 national lymphoma study groups supplemented by experts in histopathology and molecular genetics.
  • During the past decade, the European consortium has successfully initiated the largest phase III trials in MCL worldwide, with a current annual recruitment of almost 200 patients per year in first-line studies.
  • In detail, in prospective randomized studies, the addition of a B-lymphocyte specific antibody doubled the median progression-free survival from 14 to 28 months, and a dose-intensified consolidation with high-dose radiochemotherapy and subsequent autologous stem cell transplant resulted in superior response duration (3.7 vs. 1.6 years) and even improved overall survival in a recent analysis.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lymphoma, Mantle-Cell / etiology. Lymphoma, Mantle-Cell / therapy. Stem Cell Transplantation
  • [MeSH-minor] Clinical Trials as Topic. Combined Modality Therapy. Congresses as Topic. Humans


72. Lenz G, Dreyling M, Unterhalt M, Hiddemann W: [Current strategies in the treatment of advanced stage mantle cell lymphoma]. Dtsch Med Wochenschr; 2004 Nov 5;129(45):2429-33
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  • [Title] [Current strategies in the treatment of advanced stage mantle cell lymphoma].
  • Advanced stage mantle cell lymphoma (MCL) with a median survival of only three years and virtually no long-term survivors represents the lymphoma subtype with the poorest prognosis and remains incurable with conventional chemotherapy.
  • Recently two randomized trials of the German Low Grade Lymphoma Study Group (GLSG) demonstrated the superiority of a combined immunochemotherapy with the anti-CD20 antibody rituximab in first-line therapy (R-CHOP) as well as in relapsed disease (R-FCM).
  • In addition, in a trial of the European MCL Network, intensified-consolidation with high-dose radiochemotherapy followed by autologous stem cell transplantation significantly improved the progression-free survival in patients up to 65 years of age.
  • However, the vast majority of patients with MCL will eventually relapse.
  • Thus, new strategies such as allogenic transplantation after dose-reduced conditioning or novel molecular targeting agents (e. g. proteasome inhibitors or radiolabeled antibodies) are urgently warranted to further improve the long-term outcome of MCL.
  • [MeSH-major] Lymphoma, Mantle-Cell / therapy
  • [MeSH-minor] Age Factors. Aged. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Murine-Derived. Antineoplastic Agents / administration & dosage. Antineoplastic Agents / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Clinical Trials, Phase II as Topic. Clinical Trials, Phase III as Topic. Combined Modality Therapy. Cyclophosphamide / therapeutic use. Disease-Free Survival. Doxorubicin / therapeutic use. Female. Humans. Immunotherapy. Male. Middle Aged. Prednisone / therapeutic use. Prognosis. Proteasome Inhibitors. Radiotherapy Dosage. Randomized Controlled Trials as Topic. Recurrence. Risk Factors. Rituximab. Stem Cell Transplantation. Survival Analysis. Time Factors. Transplantation, Autologous. Vincristine / therapeutic use

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  • (PMID = 15529247.001).
  • [ISSN] 0012-0472
  • [Journal-full-title] Deutsche medizinische Wochenschrift (1946)
  • [ISO-abbreviation] Dtsch. Med. Wochenschr.
  • [Language] ger
  • [Publication-type] Comparative Study; English Abstract; Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antineoplastic Agents; 0 / Proteasome Inhibitors; 4F4X42SYQ6 / Rituximab; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; VB0R961HZT / Prednisone; CHOP protocol
  • [Number-of-references] 48
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73. Maddika S, Ande SR, Panigrahi S, Paranjothy T, Weglarczyk K, Zuse A, Eshraghi M, Manda KD, Wiechec E, Los M: Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist Updat; 2007 Feb-Apr;10(1-2):13-29
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  • [Title] Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy.
  • The partial cross-utilization of molecules and pathways involved in opposing processes like cell survival, proliferation and cell death, assures that mutations within one signaling cascade will also affect the other opposite process at least to some extent, thus contributing to homeostatic regulatory circuits.
  • Thus, we discuss the role of cyclins in the apoptotic process, and in the regulation of cell proliferation.
  • Bcl2, Bcl-X(L) Mcl-1(L); Bax, Bok/Mtd, Bak, and Bcl-X(S); Bad, Bid, Bim(EL), Bmf, Mcl-1(S)) are highlighted both for their apoptosis-regulating capacity and also for their effect on the cell cycle progression.
  • The PI3-K/Akt cell survival pathway is shown as regulator of cell metabolism and cell survival, but examples are also provided where aberrant activity of the pathway may contribute to the induction of apoptosis.
  • Finally, we reflect on novel therapeutic approaches that would involve redirecting over-active survival and proliferation pathways towards induction of apoptosis in cancer cells.
  • [MeSH-major] Apoptosis / physiology. Cell Cycle / physiology. Cell Survival / physiology. Cyclins / physiology. Neoplasms / drug therapy
  • [MeSH-minor] Antineoplastic Agents / pharmacology. Antineoplastic Agents / therapeutic use. Cell Proliferation. Cyclin-Dependent Kinase Inhibitor Proteins / physiology. Cyclin-Dependent Kinases / physiology. Drug Delivery Systems. Drug Design. Humans. Proto-Oncogene Proteins c-bcl-2 / physiology


74. Atwell GJ, Yang S, Pruijn FB, Pullen SM, Hogg A, Patterson AV, Wilson WR, Denny WA: Synthesis and structure-activity relationships for 2,4-dinitrobenzamide-5-mustards as prodrugs for the Escherichia coli nfsB nitroreductase in gene therapy. J Med Chem; 2007 Mar 22;50(6):1197-212
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  • [Title] Synthesis and structure-activity relationships for 2,4-dinitrobenzamide-5-mustards as prodrugs for the Escherichia coli nfsB nitroreductase in gene therapy.
  • A series of 2,4-dinitrobenzamide mustards were prepared from 5-chloro-2,4-dinitrobenzoic acid or the corresponding 5-dimesylate mustard as potential prodrugs for gene-directed enzyme prodrug therapy (GDEPT) with the E. coli nfsB nitroreductase (NTR).
  • The compounds, including 32 new examples, were evaluated in four pairs of NTR+ve/-ve cell lines for selective cytotoxicity (IC50 and IC50 ratios), in multicellular layer (MCL) cultures for bystander effects, and for in vivo activity against tumors grown from stably NTR transfected EMT6 and WiDr cells in nude mice.
  • Bystander effects in the MCL assay also correlated positively with logP and negatively with leaving group reactivity, presumably reflecting the transcellular diffusion/reaction properties of the activated metabolites.
  • [MeSH-minor] Animals. Bystander Effect. Cell Line, Tumor. Drug Screening Assays, Antitumor. Enzyme Activation. Female. Genetic Therapy. Humans. Least-Squares Analysis. Male. Mice. Mice, Nude. Multivariate Analysis. Quantitative Structure-Activity Relationship. Transplantation, Heterologous

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  • (PMID = 17326614.001).
  • [ISSN] 0022-2623
  • [Journal-full-title] Journal of medicinal chemistry
  • [ISO-abbreviation] J. Med. Chem.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / 2,4-dinitrobenzamide nitorgen mustard; 0 / Antineoplastic Agents, Alkylating; 0 / Escherichia coli Proteins; 0 / Nitrogen Mustard Compounds; 0 / Prodrugs; EC 1.7.- / NfsB protein, E coli; EC 1.7.- / Nitroreductases
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75. Kaufmann H, Raderer M, Wöhrer S, Püspök A, Bankier A, Zielinski C, Chott A, Drach J: Antitumor activity of rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma. Blood; 2004 Oct 15;104(8):2269-71
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  • [Title] Antitumor activity of rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma.
  • We evaluated a treatment strategy targeting both lymphoma cells (by rituximab) and the microenvironment (by thalidomide) in 16 patients with relapsed/refractory mantle cell lymphoma (MCL).
  • Rituximab was administered at 375 mg/m(2) for 4 weekly doses concomitantly with thalidomide (200 mg daily, with a dose increment to 400 mg on day 15), which was continued as maintenance therapy until progression/relapse.
  • In patients achieving a complete response, PFS after rituximab plus thalidomide was longer than PFS after the preceding chemotherapy.
  • Severe adverse events included 2 thromboembolic events and 1 grade IV neutropenia associated with thalidomide.
  • Our results suggest that rituximab plus thalidomide has marked antitumor activity in relapsed/refractory MCL and a low toxicity profile, which warrants further evaluation in MCL.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents / therapeutic use. Lymphoma, Mantle-Cell / drug therapy. Lymphoma, Mantle-Cell / pathology. Thalidomide / therapeutic use

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  • (PMID = 15166030.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antineoplastic Agents; 4F4X42SYQ6 / Rituximab; 4Z8R6ORS6L / Thalidomide
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76. O'Connor OA, Czuczman MS: Novel approaches for the treatment of NHL: Proteasome inhibition and immune modulation. Leuk Lymphoma; 2008;49 Suppl 1:59-66
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  • [Title] Novel approaches for the treatment of NHL: Proteasome inhibition and immune modulation.
  • Proteasome inhibitors and immunomodulatory drugs (IMiDs) have demonstrated clinical potential as novel therapies for non-Hodgkin lymphoma (NHL).
  • Single-agent bortezomib is effective in several lymphoid malignancies, and is recommended for second-line treatment of mantle-cell lymphoma (MCL).
  • Ongoing trials are investigating the combination of bortezomib with chemotherapy, and with agents that target Bcl-2 proteins.
  • Although proteasome inhibitors are potentially potent anti-tumor drugs, the pleotropic nature of their biological effects means that further research is required to elucidate the optimal combinations, doses and schedules.
  • These drugs inhibit cell growth and proliferation by several mechanisms, including blocking the effect of growth factors and stimulating T cells and natural killer cells.
  • Lenalidomide is particularly effective in lymphoproliferative disorders such as multiple myeloma, and is active in patients with various forms of NHL, with a favourable side-effect profile.
  • Complimentary clinical and pharmacological features suggest that lenalidomide may be effective when combined with monoclonal antibodies.
  • [MeSH-major] Immunologic Factors / therapeutic use. Lymphoma, Non-Hodgkin / drug therapy. Protease Inhibitors / therapeutic use
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Boronic Acids / therapeutic use. Bortezomib. Humans. Pyrazines / therapeutic use. Thalidomide / analogs & derivatives. Thalidomide / therapeutic use

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  • (PMID = 18821434.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Boronic Acids; 0 / Immunologic Factors; 0 / Protease Inhibitors; 0 / Pyrazines; 4Z8R6ORS6L / Thalidomide; 69G8BD63PP / Bortezomib; F0P408N6V4 / lenalidomide
  • [Number-of-references] 48
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77. Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W, German Low Grade Lymphoma Study Group (GLSG): Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood; 2006 Dec 15;108(13):4003-8
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  • [Title] Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG).
  • In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab (R) improves the prognosis when combined with chemotherapy.
  • The present study investigated R-maintenance after R-chemotherapy.
  • Patients with recurring or refractory FL and MCL were randomized to 4 courses of fludarabine, cyclophosphamide, and mitoxantrone (FCM) alone or combined with R (R-FCM).
  • Responding patients underwent a second randomization for R-maintenance comprising 2 further courses of 4-times-weekly doses of R after 3 and 9 months.
  • This beneficial effect was also observed when analyzing FL (P = .035) and MCL (P = .049) separately.
  • Hence, R-maintenance is effective after salvage with R-chemotherapy and significantly prolongs response duration in patients with recurring or refractory FL or MCL.
  • [MeSH-major] Lymphoma, Follicular / drug therapy. Lymphoma, Mantle-Cell / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Murine-Derived. Antineoplastic Combined Chemotherapy Protocols. Cyclophosphamide / administration & dosage. Disease-Free Survival. Female. Germany. Humans. Male. Middle Aged. Mitoxantrone / administration & dosage. Prospective Studies. Recurrence. Remission Induction. Rituximab. Salvage Therapy / methods. Survival Rate. Vidarabine / administration & dosage. Vidarabine / analogs & derivatives


78. Hiddemann W, Dreyling M: Mantle cell lymphoma: therapeutic strategies are different from CLL. Curr Treat Options Oncol; 2003 Jun;4(3):219-26
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  • [Title] Mantle cell lymphoma: therapeutic strategies are different from CLL.
  • In contrast to the typical course of chronic lymphocytic lymphoma and despite an indolent lymphoma-like presentation, the clinical outcome of mantle cell lymphoma (MCL) is dismal, with a median survival time of 3 years and virtually no long-term survivors.
  • Although clinical studies did not prove a clear superiority of anthracyclin-containing combinations, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like regimens represent the standard therapeutic approach in MCL.
  • Recent randomized studies have shown a benefit of a combined immunochemotherapy strategy (chemotherapy plus rituximab) increasing the complete and overall response rates, whereas further follow-up is pending for evaluation of the progression-free and overall survival.
  • In patients younger than 65 years, a dose-intensive consolidation comprising high-dose radiochemotherapy and subsequent autologous stem cell transplantation after a CHOP-like induction results in an improved progression-free survival.
  • However, despite the benefits of this multimodal approach, most patients relapse even after high-dose therapy.
  • The only curative approach is allogeneic stem cell transplantation, which may be adapted to the elderly MCL patient cohort by modified dose-reduced conditioning regimens.
  • Prospective randomized trials remain critical to further improve the clinical course of MCL with the addition of newer treatment modalities, such as radioactively labeled antibodies and targeted therapies (eg, flavopiridol and PS-341).
  • [MeSH-major] Leukemia, Lymphocytic, Chronic, B-Cell / therapy. Lymphoma, Mantle-Cell / therapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Humans. Immunophenotyping. Immunotherapy. Stem Cell Transplantation / methods

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  • (PMID = 12718799.001).
  • [ISSN] 1527-2729
  • [Journal-full-title] Current treatment options in oncology
  • [ISO-abbreviation] Curr Treat Options Oncol
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 46
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79. Wang X, Chen W, Zeng W, Bai L, Tesfaigzi Y, Belinsky SA, Lin Y: Akt-mediated eminent expression of c-FLIP and Mcl-1 confers acquired resistance to TRAIL-induced cytotoxicity to lung cancer cells. Mol Cancer Ther; 2008 May;7(5):1156-63
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  • [Title] Akt-mediated eminent expression of c-FLIP and Mcl-1 confers acquired resistance to TRAIL-induced cytotoxicity to lung cancer cells.
  • However, TRAIL can also stimulate the proliferation and metastasis of TRAIL-resistant cancer cells.
  • Thus, acquired TRAIL resistance during TRAIL therapy would shift the patient's treatment from beneficial to detrimental.
  • In this study, we focused on the acquired TRAIL resistance mechanism and showed that the elevated expression of the antiapoptotic factor cellular FLICE-like inhibitory protein (c-FLIP) and the prosurvival Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) underlie the main mechanism of this type of TRAIL resistance in lung cancer cells.
  • Chronic exposure to TRAIL resulted in lung cancer cell resistance to TRAIL-induced cytotoxicity, and this resistance was associated with the increase in the cellular levels of c-FLIP(L) and Mcl-1(L).
  • Overexpresssion of c-FLIP(L) suppressed recruitment of caspase-8 to the death-inducing signaling complex, whereas increased Mcl-1(L) expression blunted the mitochondrial apoptosis pathway.
  • The elevation of c-FLIP(L) and Mcl-1(L) expression was due to Akt-mediated stabilization of these proteins in TRAIL-resistant cells.
  • Importantly, suppressing c-FLIP(L) and Mcl-1(L) expression by RNA interference collectively alleviated acquired TRAIL resistance.
  • Taken together, these results identify c-FLIP(L) and Mcl-1(L) as the major determinants of acquired TRAIL resistance and could be molecular targets for improving the therapeutic value of TRAIL against lung cancer.

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  • (PMID = 18483303.001).
  • [ISSN] 1535-7163
  • [Journal-full-title] Molecular cancer therapeutics
  • [ISO-abbreviation] Mol. Cancer Ther.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R03 CA125796; United States / NCI NIH HHS / CA / R03 CA125796-01A1; United States / NCI NIH HHS / CA / CA125796-01A1; United States / NCI NIH HHS / CA / R03CA125796; United States / NCI NIH HHS / CA / R03 CA125796-02; United States / NCI NIH HHS / CA / CA125796-02
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / CASP8 and FADD-Like Apoptosis Regulating Protein; 0 / Death Domain Receptor Signaling Adaptor Proteins; 0 / Myeloid Cell Leukemia Sequence 1 Protein; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / TNF-Related Apoptosis-Inducing Ligand; EC 2.7.11.1 / Proto-Oncogene Proteins c-akt; EC 3.4.22.- / Caspase 8
  • [Other-IDs] NLM/ NIHMS123493; NLM/ PMC2715176
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80. Rassidakis GZ, Jones D, Lai R, Ramalingam P, Sarris AH, McDonnell TJ, Medeiros LJ: BCL-2 family proteins in peripheral T-cell lymphomas: correlation with tumour apoptosis and proliferation. J Pathol; 2003 Jun;200(2):240-8
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  • [Title] BCL-2 family proteins in peripheral T-cell lymphomas: correlation with tumour apoptosis and proliferation.
  • The present study investigated expression levels of the anti-apoptotic proteins BCL-2, BCL-XL and MCL-1 and the pro-apoptotic proteins BAX and BCL-XS in a series of 112 peripheral T-cell lymphomas (PTCLs) classified according to the WHO classification.
  • Using immunohistochemical methods and a 10% cut-off, each protein was detected in a subset of PTCLs: BCL-2 in 46%, BCL-XS in 49%, BAX in 57%, BCL-XL in 57%, and MCL-1 in 65%.
  • The mean percentage of positive cells for these proteins varied significantly among the PTCL types.
  • Only two types of PTCL, ALK-positive anaplastic large cell lymphoma (ALCL) and enteropathy-type T-cell lymphoma, had a distinctive pattern of expression; all were BCL-2-negative and MCL-1-positive.
  • The mean percentage of BAX-positive and BCL-XS-positive tumour cells was higher in ALK-positive ALCL than in ALK-negative ALCL or other types of PTCL (p = 0.06 and p = 0.01, respectively, Kruskal-Wallis test).
  • MCL-1 was detected significantly more frequently (p = 0.01, chi-square test) and at higher levels (p = 0.0001, Kruskal-Wallis test) in ALK-positive ALCL and ALK-negative ALCL than in other PTCL types.
  • The proliferation index, assessed by the MIB-1 antibody, correlated with expression levels of MCL-1 (R = 0.42, p = 0.003), BCL-2 (R = 0.32, p = 0.027), BAX (R = 0.33, p = 0.014), and BCL-XL (R = 0.34, p = 0.015) (Spearman rank).
  • In conclusion, BCL-2 family proteins are expressed by a subset of PTCLs and their levels correlate with some histological types, apoptotic rate, and proliferation index.
  • Expression of these proteins may explain the poor response of many types of PTCL to standard chemotherapy.
  • These proteins may also provide novel targets for experimental therapy.
  • [MeSH-major] Apoptosis. Lymphoma, T-Cell, Peripheral / metabolism. Proto-Oncogene Proteins c-bcl-2 / metabolism
  • [MeSH-minor] Cell Division. Humans. Myeloid Cell Leukemia Sequence 1 Protein. Neoplasm Proteins / metabolism. Protein Array Analysis / methods. Protein-Tyrosine Kinases / metabolism. Proto-Oncogene Proteins / metabolism. Receptor Protein-Tyrosine Kinases. bcl-2-Associated X Protein. bcl-X Protein

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  • [Copyright] Copyright 2003 John Wiley & Sons, Ltd.
  • (PMID = 12754745.001).
  • [ISSN] 0022-3417
  • [Journal-full-title] The Journal of pathology
  • [ISO-abbreviation] J. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / BAX protein, human; 0 / BCL2L1 protein, human; 0 / Myeloid Cell Leukemia Sequence 1 Protein; 0 / Neoplasm Proteins; 0 / Proto-Oncogene Proteins; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / bcl-2-Associated X Protein; 0 / bcl-X Protein; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.10.1 / Receptor Protein-Tyrosine Kinases; EC 2.7.10.1 / anaplastic lymphoma kinase
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81. Valent P, Akin C, Sperr WR, Mayerhofer M, Födinger M, Fritsche-Polanz R, Sotlar K, Escribano L, Arock M, Horny HP, Metcalfe DD: Mastocytosis: pathology, genetics, and current options for therapy. Leuk Lymphoma; 2005 Jan;46(1):35-48
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  • [Title] Mastocytosis: pathology, genetics, and current options for therapy.
  • Mast cell disorders are defined by an abnormal accumulation of tissue mast cells (MCs) in one or more organ systems.
  • Cutaneous mastocytosis (CM) is a benign disease of the skin and may regress spontaneously.
  • The WHO discriminates five categories of SM: indolent SM (ISM), aggressive SM (ASM), SM with associated clonal hematological non-MC-lineage disease (AHNMD), and mast cell leukemia (MCL).
  • In SM-AHNMD, additional genetic abnormalities have been reported, whereas no additional defects are yet known for ASM or MCL.
  • Patients with ISM and CM are treated with "mediator-targeting" drugs, whereas patients with ASM or MCL are candidates for cytoreductive therapy.
  • However, the D816V mutation of c-kit is associated with relative resistance against STI571.
  • Therefore, these patients require alternative targeted drugs or new drug-combinations.
  • In patients with SM-AHNMD, separate treatment plans for the SM-component and the AHNMD should be established.
  • Examples include the use of STI571 in patients with SM plus hypereosinophilic syndrome (SM-HES) and the FIPL1/PDGFRA fusion gene target, or chemotherapy for eradication of AML in patients with SM-AML.

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  • (PMID = 15621779.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 122
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82. Wang M, Zhang L, Han X, Yang J, Qian J, Hong S, Samaniego F, Romaguera J, Yi Q: Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways. Blood; 2007 Jun 15;109(12):5455-62
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  • [Title] Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways.
  • This study was undertaken to evaluate the therapeutic efficacy of atiprimod on mantle cell lymphoma (MCL) and elucidate the mechanism by which it induces cell apoptosis.
  • Atiprimod inhibited the growth and induced apoptosis of MCL cell lines and freshly isolated primary tumor cells in vitro.
  • Atiprimod activated c-Jun N-terminal protein kinases (JNK) and up-regulated the level of Bax, Bad, and phosphorylated Bcl-2, resulting in release of apoptosis-inducing factor (AIF) and cytochrome c from mitochondria and activation and cleavage of caspase-9, caspase-3, and PARP.
  • However, AIF, but not activation of caspases or PARP, was responsible for apoptosis in MCL cells because an AIF inhibitor, but not pan-caspase or paspase-9 inhibitors, completely abrogated atiprimod-induced apoptosis.
  • Taken together, our results demonstrate that atiprimod displays a strong anti-MCL activity.
  • Cell apoptosis was induced mainly via activation of the AIF pathway.
  • These results support the use of atiprimod as a potential agent in MCL chemotherapy.
  • [MeSH-major] Apoptosis / drug effects. Cell Proliferation / drug effects. Lymphoma, Mantle-Cell / drug therapy. Mitochondria / drug effects. Spiro Compounds / pharmacology
  • [MeSH-minor] Animals. Apoptosis Regulatory Proteins / drug effects. Drug Evaluation, Preclinical. Mice. Mitochondrial Proteins / drug effects

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  • (PMID = 17317853.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Apoptosis Regulatory Proteins; 0 / Mitochondrial Proteins; 0 / Spiro Compounds; 123018-47-3 / azaspirane
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83. Miglietta L, Franzone P, Centurioni MG, Boni L, Tacchini L, Cosso M, Boccardo F, Ferrarini M, Bruzzone M: A phase II trial with cisplatin-paclitaxel cytotoxic treatment and concurrent external and endocavitary radiation therapy in locally advanced or recurrent cervical cancer. Oncology; 2006;70(1):19-24
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  • [Title] A phase II trial with cisplatin-paclitaxel cytotoxic treatment and concurrent external and endocavitary radiation therapy in locally advanced or recurrent cervical cancer.
  • BACKGROUND: Five randomized studies have demonstrated a beneficial effect of adding cisplatin-based chemotherapy to radiation therapy in the treatment of cervical carcinoma.
  • In the present phase II study, we evaluated the response and toxicity of cisplatin-Taxol chemotherapy combined with concomitant radiotherapy in patients with locally advanced cervical carcinoma (LACC) and locally recurrent cervical carcinoma (LRCC).
  • PATIENTS AND METHODS: In 2000, this phase II study was initiated with a chemotherapy regimen of cisplatin (75 mg/m(2)) and Taxol (175 mg/m(2)) every 21 days, for four cycles, concomitant with external radiotherapy and high-dose-rate brachytherapy.
  • Pelvic radiotherapy was started 2 weeks after the first chemotherapy cycle, while the first brachytherapy insertion was carried out during the fourth chemotherapy cycle.
  • SCC marker was determined before treatment and after every chemotherapy cycle.
  • Two patients with LACC experienced distant recurrence 22 and 24 months after complete response, respectively, and 1 patient with LRCC had local progression 6 months after the end of radiotherapy.
  • Although generally tolerable, neutropenia grade 3-4 in 4 patients and anemia grade 3 in 2 patients were observed, and 1 patient experienced grade 2 neurotoxicity; toxicity due to radiotherapy was moderate.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Brachytherapy. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / radiotherapy. Uterine Cervical Neoplasms / drug therapy. Uterine Cervical Neoplasms / radiotherapy
  • [MeSH-minor] Adult. Aged. Carcinoma / drug therapy. Carcinoma / radiotherapy. Carcinoma / surgery. Chemotherapy, Adjuvant. Cisplatin / administration & dosage. Drug Administration Schedule. Feasibility Studies. Female. Humans. Middle Aged. Neoplasm Staging. Paclitaxel / administration & dosage. Prospective Studies. Radiotherapy, Adjuvant / methods. Treatment Outcome


84. Tobinai K: Monoclonal antibody therapy for B-cell lymphoma: clinical trials of an anti-CD20 monoclonal antibody for B-cell lymphoma in Japan. Int J Hematol; 2002 Dec;76(5):411-9
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  • [Title] Monoclonal antibody therapy for B-cell lymphoma: clinical trials of an anti-CD20 monoclonal antibody for B-cell lymphoma in Japan.
  • Twelve patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma (B-NHL) were enrolled in a phase I study of rituximab; 4 received rituximab 250 mg/m2 and 8 received rituximab 375 mg/m2 once weekly for 4 weeks.
  • Grade 1 or 2 infusion-related toxicity was observed.
  • The elimination half-life (T1/2) of rituximab was 445 +/- 361 hours, and serum rituximab levels were detectable at 3 months.
  • Thereafter, 90 relapse patients with indolent B-NHL or mantle cell lymphoma (MCL) were enrolled in a phase II study and treated with rituximab at 375 mg/m2 per infusion in 4 weekly infusions.
  • The overall response rates (ORR) in indolent B-NHL and MCL were 61% (37 of 61 patients) and 46% (6 of 13 patients), respectively.
  • Factors affecting response and progression-free survival (PFS) were analyzed for 77 patients whose histopathology was centrally confirmed as indolent B-NHL or MCL.
  • The ORR in patients receiving 1 prior chemotherapy regimen was higher than the ORR in those receiving > or = 2 regimens (P < .05).
  • The median PFS was shorter in MCL patients, in those with extranodal disease, and in those receiving > or = 2 prior chemotherapy regimens (P < .01).
  • The PFS of patients with higher serum rituximab levels (> or = 70 microg/mL) immediately before the third infusion was longer than that of other patients (P < .01).
  • Several pretreatment factors and serum rituximab levels are useful for predicting the efficacy of rituximab monotherapy.
  • Rituximab re-treatment was well tolerated in 13 patients with no grade 3 or 4 nonhematological toxicities.
  • A partial response was observed in 5 patients (38%), and the median PFS after re-treatment was 5.1 months.
  • In conclusion, rituximab is a highly effective agent in relapsed indolent and aggressive B-NHL and MCL and has acceptable toxicities.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Lymphoma, B-Cell / drug therapy
  • [MeSH-minor] Antibodies, Monoclonal, Murine-Derived. Antigens, CD20 / immunology. Antineoplastic Agents / therapeutic use. Clinical Trials as Topic. Humans. Japan. Rituximab

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  • (PMID = 12512835.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antigens, CD20; 0 / Antineoplastic Agents; 4F4X42SYQ6 / Rituximab
  • [Number-of-references] 29
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85. Vranovsky A, Ladicka M, Lakota J: Autologous stem cell transplantation in first-line treatment of high-risk aggressive non-Hodgkin's lymphoma. Neoplasma; 2008;55(2):107-12
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  • [Title] Autologous stem cell transplantation in first-line treatment of high-risk aggressive non-Hodgkin's lymphoma.
  • A single center, retrospective analysis evaluating the outcome of patients with poor-risk aggressive non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT) as a part of firstline therapy.
  • Forty-seven patients younger than 65 years with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL) or alk-negative anaplastic large cell lymphoma (ALCL) underwent ASCT between July 1997 and November 2005.
  • All patients were transplanted after MACOP-B induction therapy followed by 2 courses of DHAP and myeloablative chemotherapy BEM or CBV.
  • The complete response rate to the high-dose therapy was 79% with an estimated 5-year progression-free survival of 66%.
  • There were 4 treatment-related deaths.
  • Our results confirm the efficacy of high-dose therapy with ASCT during first-line treatment of patients with poor-prognosis aggressive lymphoma, with substantial number of patients cured by using this treatment approach.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Lymphoma, Non-Hodgkin / therapy
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bleomycin / therapeutic use. Cisplatin / therapeutic use. Combined Modality Therapy. Cyclophosphamide / therapeutic use. Cytarabine / therapeutic use. Dexamethasone / therapeutic use. Doxorubicin / therapeutic use. Female. Humans. Male. Methotrexate / therapeutic use. Middle Aged. Prednisolone / therapeutic use. Retrospective Studies. Transplantation, Autologous. Vincristine / therapeutic use

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  • (PMID = 18652043.001).
  • [ISSN] 0028-2685
  • [Journal-full-title] Neoplasma
  • [ISO-abbreviation] Neoplasma
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Slovakia
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 11056-06-7 / Bleomycin; 5J49Q6B70F / Vincristine; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; 9PHQ9Y1OLM / Prednisolone; Q20Q21Q62J / Cisplatin; YL5FZ2Y5U1 / Methotrexate; DHAP protocol; MACOP-B regimen
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86. Lenz G, Dreyling M, Hoster E, Wörmann B, Dührsen U, Metzner B, Eimermacher H, Neubauer A, Wandt H, Steinhauer H, Martin S, Heidemann E, Aldaoud A, Parwaresch R, Hasford J, Unterhalt M, Hiddemann W: Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol; 2005 Mar 20;23(9):1984-92
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  • [Title] Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).
  • PURPOSE: Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years.
  • In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL.
  • PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62).
  • Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFNalpha).
  • RESULTS: R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131).
  • Toxicity was acceptable, with no major differences between the two therapeutic groups.
  • CONCLUSION: The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone.
  • Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cyclophosphamide / therapeutic use. Doxorubicin / therapeutic use. Interferon-alpha / therapeutic use. Lymphoma, Mantle-Cell / drug therapy. Prednisone / therapeutic use. Vincristine / therapeutic use
  • [MeSH-minor] Aged. Antibodies, Monoclonal, Murine-Derived. Female. Germany. Humans. Male. Middle Aged. Rituximab. Stem Cell Transplantation. Treatment Failure

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  • [CommentIn] J Clin Oncol. 2005 Sep 20;23(27):6802; author reply 6802-3 [16170194.001]
  • (PMID = 15668467.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Interferon-alpha; 4F4X42SYQ6 / Rituximab; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; VB0R961HZT / Prednisone; CHOP protocol
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87. Pfaffenroth EC, Linehan WM: Genetic basis for kidney cancer: opportunity for disease-specific approaches to therapy. Expert Opin Biol Ther; 2008 Jun;8(6):779-90
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  • [Title] Genetic basis for kidney cancer: opportunity for disease-specific approaches to therapy.
  • BACKGROUND: Kidney cancer is not a homogenous entity; it is comprised of many different tumor types, with different biologies and molecular mechanisms leading to disease and therefore different treatment approaches.
  • OBJECTIVE: To describe the genetic basis and biochemical pathways underlying inherited forms of renal cancer, specifically in four described syndromes (von Hippel-Lindau [VHL], hereditary papillary renal cancer [HPRC], Birt-Hogg-Dubé [BHD] and hereditary leiomyomatosis renal cell carcinoma [HLRCC]), and to elucidate how the understanding of these diseases enables the possibility of disease-specific approaches to therapy.
  • METHODS: A systematic review of the published literature on inherited and sporadic forms of renal cancer was performed.
  • CONCLUSION: Understanding of the biology and mechanisms of different forms of kidney cancer provides an opportunity for development of new treatment options.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Genes, Tumor Suppressor. Kidney Neoplasms / genetics. Neoplastic Syndromes, Hereditary / genetics. Proto-Oncogenes
  • [MeSH-minor] Carcinoma, Renal Cell / genetics. Carcinoma, Renal Cell / therapy. Drug Design. Fumarate Hydratase / deficiency. Fumarate Hydratase / genetics. Fumarate Hydratase / physiology. Genetic Predisposition to Disease. Humans. Leiomyomatosis / genetics. Leiomyomatosis / therapy. Neoplasm Proteins / antagonists & inhibitors. Neoplasm Proteins / genetics. Neoplasm Proteins / physiology. Neoplasms, Multiple Primary / genetics. Neoplasms, Multiple Primary / therapy. Proto-Oncogene Proteins / antagonists & inhibitors. Proto-Oncogene Proteins / deficiency. Proto-Oncogene Proteins / genetics. Proto-Oncogene Proteins / physiology. Proto-Oncogene Proteins c-met. Receptors, Growth Factor / antagonists & inhibitors. Receptors, Growth Factor / deficiency. Receptors, Growth Factor / genetics. Receptors, Growth Factor / physiology. Tumor Suppressor Proteins / deficiency. Tumor Suppressor Proteins / genetics. Tumor Suppressor Proteins / physiology. Vascular Endothelial Growth Factor A / antagonists & inhibitors. Von Hippel-Lindau Tumor Suppressor Protein / genetics. Von Hippel-Lindau Tumor Suppressor Protein / physiology. von Hippel-Lindau Disease / genetics. von Hippel-Lindau Disease / therapy

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  • (PMID = 18476789.001).
  • [ISSN] 1744-7682
  • [Journal-full-title] Expert opinion on biological therapy
  • [ISO-abbreviation] Expert Opin Biol Ther
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / / Z01 SC006659-25
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / FLCN protein, human; 0 / Neoplasm Proteins; 0 / Proto-Oncogene Proteins; 0 / Receptors, Growth Factor; 0 / Tumor Suppressor Proteins; 0 / VEGFA protein, human; 0 / Vascular Endothelial Growth Factor A; EC 2.7.10.1 / MET protein, human; EC 2.7.10.1 / Proto-Oncogene Proteins c-met; EC 4.2.1.2 / Fumarate Hydratase; EC 6.3.2.19 / VHL protein, human; EC 6.3.2.19 / Von Hippel-Lindau Tumor Suppressor Protein
  • [Number-of-references] 90
  • [Other-IDs] NLM/ NIHMS66250; NLM/ PMC2768039
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88. Thieblemont C, Antal D, Lacotte-Thierry L, Delwail V, Espinouse D, Michallet AS, Traulle C, Bouafia-Sauvy F, Giraud C, Salles G, Guilhot F, Coiffier B: Chemotherapy with rituximab followed by high-dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma. Cancer; 2005 Oct 1;104(7):1434-41
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  • [Title] Chemotherapy with rituximab followed by high-dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma.
  • BACKGROUND: The authors evaluated the efficacy of chemotherapy combined with rituximab followed by high-dose therapy (HDT) plus autologous stem cell transplantation in patients with mantle cell lymphoma (MCL).
  • METHODS: This was a retrospective analysis of 34 patients who were treated in 2 departments of hematology, including 29 patients (85%) who received first-line treatment.
  • Rituximab was administered as 4 injections just before harvest in 25 patients (73%) or simultaneously with chemotherapy in 9 patients (27%).
  • RESULTS: After induction therapy, all patients except one reached a response: There were 14 (41%) complete responses (CR) and 19 (56%) partial responses (PR).
  • Stem cell harvest was successful in all patients but 2, with a median number of 5.9 CD34-positive cells per 10(6)/kg.
  • With a median follow-up at 2.6 years, the estimated median time to disease progression was 3.4 years.
  • Rituximab treatment before harvest did not delay hematopoietic reconstitution: The median time it took patients to recover absolute neutrophil count to > 0.5 G/L was 10 days.
  • CONCLUSIONS: Chemotherapy combined with rituximab followed by HDT improved the overall survival and progression-free survival in patients MCL without adding toxicities.
  • [MeSH-major] Antibodies, Monoclonal / administration & dosage. Lymphoma, Mantle-Cell / mortality. Lymphoma, Mantle-Cell / therapy. Stem Cell Transplantation / methods
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal, Murine-Derived. Combined Modality Therapy. Female. Follow-Up Studies. Graft Survival. Humans. Infusions, Intravenous. Male. Middle Aged. Pulse Therapy, Drug. Remission Induction. Retrospective Studies. Risk Assessment. Rituximab. Severity of Illness Index. Survival Rate. Transplantation, Autologous. Treatment Outcome

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  • (PMID = 16104036.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 4F4X42SYQ6 / Rituximab
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89. Lin TS, Blum KA, Fischer DB, Mitchell SM, Ruppert AS, Porcu P, Kraut EH, Baiocchi RA, Moran ME, Johnson AJ, Schaaf LJ, Grever MR, Byrd JC: Flavopiridol, fludarabine, and rituximab in mantle cell lymphoma and indolent B-cell lymphoproliferative disorders. J Clin Oncol; 2010 Jan 20;28(3):418-23
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