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1. Kast RE: Evidence that amphotericin B mediates reactivation of latent Epstein-Barr virus in Hodgkin's lymphoma allowing cytotoxicity by acyclovir. Yonsei Med J; 2006 Apr 30;47(2):287-90
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  • [Title] Evidence that amphotericin B mediates reactivation of latent Epstein-Barr virus in Hodgkin's lymphoma allowing cytotoxicity by acyclovir.
  • This brief communication focuses on aspects of a recent case report (Yonsei Med J 2005;46:425-30) on a full and sustained remission of Hodgkin's lymphoma (HL) after a single day of chemotherapy.
  • A septic episode required stopping chemotherapy and starting amphotericin B and acyclovir.
  • A review of research supporting the notion that amphotericin B can reactivate latent Epstein-Barr virus and thus allow acyclovir to kill infected HL cells is given.
  • If successful, amphotericin B and acyclovir treatment could be extended to other EBV-driven cancers such as Burkitt's lymphoma, nasopharyngeal carcinoma and the occasional EBV-related epithelial cancer of the breast, colon, prostate, and others.
  • [MeSH-major] Acyclovir / therapeutic use. Amphotericin B / pharmacology. Drug Synergism. Herpesvirus 4, Human / metabolism. Hodgkin Disease / drug therapy. Hodgkin Disease / virology
  • [MeSH-minor] Anti-Bacterial Agents / pharmacology. Burkitt Lymphoma / virology. Ganciclovir / therapeutic use. Humans. Remission Induction. Tumor Necrosis Factor-alpha / metabolism. Virus Activation

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  • (PMID = 16642564.001).
  • [ISSN] 0513-5796
  • [Journal-full-title] Yonsei medical journal
  • [ISO-abbreviation] Yonsei Med. J.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 0 / Anti-Bacterial Agents; 0 / Tumor Necrosis Factor-alpha; 7XU7A7DROE / Amphotericin B; P9G3CKZ4P5 / Ganciclovir; X4HES1O11F / Acyclovir
  • [Other-IDs] NLM/ PMC2687644
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2. Benekli M, Baumann H, Wetzler M: Targeting signal transducer and activator of transcription signaling pathway in leukemias. J Clin Oncol; 2009 Sep 10;27(26):4422-32
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  • Signal transducer and activator of transcription (STAT) proteins comprise a seven-member family of latent cytoplasmic transcription factors that are activated through tyrosine phosphorylation by a variety of cytokines and growth factors.
  • A better understanding of the mechanisms of dysregulation of the STAT pathway and understanding of the cause and effect relationship in leukemogenesis may serve as a basis for designing novel therapeutic strategies directed against STATs.
  • Mechanisms of STAT activation, the potential role of STAT signaling in leukemogenesis, and recent advances in drug discovery targeting the STAT pathway are the focus of this review.

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  • (PMID = 19667270.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P30 CA016056; United States / NCI NIH HHS / CA / CA16056; United States / NCI NIH HHS / CA / CA85580; United States / NCI NIH HHS / CA / CA99238; United States / NCI NIH HHS / CA / R01 CA085580; United States / NCI NIH HHS / CA / R21 CA099238
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / STAT Transcription Factors; 0 / STAT1 Transcription Factor; 0 / STAT3 Transcription Factor
  • [Number-of-references] 118
  • [Other-IDs] NLM/ PMC2744278
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3. Hsieh TC, Wu JM: Cell growth and gene modulatory activities of Yunzhi (Windsor Wunxi) from mushroom Trametes versicolor in androgen-dependent and androgen-insensitive human prostate cancer cells. Int J Oncol; 2001 Jan;18(1):81-8
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  • [Title] Cell growth and gene modulatory activities of Yunzhi (Windsor Wunxi) from mushroom Trametes versicolor in androgen-dependent and androgen-insensitive human prostate cancer cells.
  • The incidence of prostate cancer varies greatly throughout the world; it is highest in African-Americans and lowest in the Asian populations of China, India, and Japan.
  • Geographical differences in both prevalence of latent prostate cancer and mortality have been postulated to be influenced by diverse tumor-promoting and protective factors, both environmental and dietary.
  • Prostate cancer is a tumor with an extremely long latency; the pattern of prostate tumorigenesis, in terms of the display and sequence of appearance of particular molecular or biochemical features, or morphological changes, characterizing different stages of the carcinogenic process, is expected to be heterogeneous.
  • The present study aims to investigate whether hormone-responsive LNCaP and androgen-refractory JCA-1, PC-3, and DU-145 prostate cancer cells are responsive to Yunzhi (YZ), a proprietary dietary supplement prepared from extracts of Trametes versicolor, also known as Coriolus versicolor (a mushroom consumed by Chinese for its purported health benefits), and to elucidate its mechanism of action.
  • In androgen-unresponsive prostate cancer cells, YZ had a much less pronounced suppressive effect on proliferation of PC-3 and DU-145 cells, compared to LNCaP, and was inactive against JCA-1 cells.
  • Western blot analyses show that the expression of Rb, a key regulatory protein in G1/S transition, and PCNA, integrally involved in mammalian cell DNA replication, were significantly reduced by treatment with YZ in PC-3 and DU-145 cells, respectively.
  • In contradiction, none of these biochemical parameters were affected in JCA-1 cells under identical treatment conditions.
  • The greater sensitivity of LNCaP cells to this polysaccharopeptide raises the possibility that YZ may be considered as an adjuvant therapy in the treatment of hormone responsive prostate cancer; additionally, it may have chemopreventive potential to restrict prostate tumorigenic progression from the hormone-dependent to the hormone-refractory state.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Drugs, Chinese Herbal / pharmacology. Gene Expression Regulation, Neoplastic / drug effects. Polyporales / chemistry. Prostatic Neoplasms / drug therapy
  • [MeSH-minor] Androgens / metabolism. Cell Cycle Proteins / biosynthesis. Cell Cycle Proteins / genetics. Cell Division / drug effects. DNA-Binding Proteins / biosynthesis. DNA-Binding Proteins / genetics. Humans. Male. Prostate-Specific Antigen / biosynthesis. Prostate-Specific Antigen / genetics. STAT1 Transcription Factor. Trans-Activators / biosynthesis. Trans-Activators / genetics. Tumor Cells, Cultured


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4. Fujimoto N, Suzuki T, Honda H, Kitamura S: Estrogen enhancement of androgen-responsive gene expression in hormone-induced hyperplasia in the ventral prostate of F344 rats. Cancer Sci; 2004 Sep;95(9):711-5
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  • [Title] Estrogen enhancement of androgen-responsive gene expression in hormone-induced hyperplasia in the ventral prostate of F344 rats.
  • It has been postulated that, in addition to the crucial role of androgens, estrogens may be involved in development of prostate hyperplasia and cancer.
  • In rats, combined administration of estrogen and androgen synergistically increases ventral prostate weight, and continued treatment results in the development of glandular hyperplasia.
  • Prostate adenocarcinoma can be induced by chemical carcinogens in rats, and estrogen given together with an androgen generally shortens the latent period or increases the incidence and/or multiplicity of carcinomas.
  • In the present study, we examined the combined effects of 17beta-estradiol (E2) and testosterone (T) on gene expression in an early stage of prostate hyperplasia in an F344 rat model.
  • ERalpha expression, which has been suggested to contribute to development of prostatic hyperplasia, was increased by the combined treatment with T and E2, while it was suppressed by T alone.
  • Expression levels of two androgen-responsive genes, probasin and kallikrein S3, were increased in the ventral prostate of rats treated with T plus E2 for 4 weeks in a dose-dependent manner, while short-term treatment did not alter the expression.
  • These results suggested that enhancing effects of E2 on transcription of androgen-responsive genes, as well as an increased level of ERalpha may play roles in the synergistic effects of E2 on T-induced prostate hyperplasia.
  • [MeSH-minor] Androgen-Binding Protein / genetics. Androgen-Binding Protein / metabolism. Animals. Antineoplastic Combined Chemotherapy Protocols. Body Weight / drug effects. Carrier Proteins. Cell Division / drug effects. Drug Synergism. Drug Therapy, Combination. LIM Domain Proteins. Male. Proteins / metabolism. RNA, Messenger / metabolism. Rats. Rats, Inbred F344. Reverse Transcriptase Polymerase Chain Reaction. Tissue Kallikreins / genetics. Tissue Kallikreins / metabolism

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  • (PMID = 15471555.001).
  • [ISSN] 1347-9032
  • [Journal-full-title] Cancer science
  • [ISO-abbreviation] Cancer Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Androgen-Binding Protein; 0 / CRIP1 protein, human; 0 / Carrier Proteins; 0 / Estrogen Receptor alpha; 0 / Estrogen Receptor beta; 0 / LIM Domain Proteins; 0 / Proteins; 0 / RNA, Messenger; 0 / Receptors, Androgen; 0 / probasin; 3XMK78S47O / Testosterone; 4TI98Z838E / Estradiol; EC 3.4.21.35 / Tissue Kallikreins
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5. Howard EW, Leung SC, Yuen HF, Chua CW, Lee DT, Chan KW, Wang X, Wong YC: Decreased adhesiveness, resistance to anoikis and suppression of GRP94 are integral to the survival of circulating tumor cells in prostate cancer. Clin Exp Metastasis; 2008;25(5):497-508
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  • [Title] Decreased adhesiveness, resistance to anoikis and suppression of GRP94 are integral to the survival of circulating tumor cells in prostate cancer.
  • The presence of circulating tumor cells (CTC) is common in prostate cancer patients, however until recently their clinical significance was unknown.
  • The CTC stage is essential for the formation of distant metastases, and their continuing presence after radical prostatectomy has been shown to predict recurrent or latent disease.
  • A novel CTC cell line from the bloodstream of an orthotopic mouse model of castration-resistant prostate cancer was established and compared with the primary tumor using attachment assays, detachment culture, Western blot, flow cytometry and 2D gel electrophoresis.
  • Decreased adhesiveness and expression of adhesion molecules E-cadherin, beta4-integrin and gamma-catenin, together with resistance to detachment and drug-induced apoptosis and upregulation of Bcl-2 were integral to the development of CTC and their survival.
  • GRP94 was also shown to be suppressed in a tissue microarray study of 79 prostate cancer patients, indicating its possible role in prostate cancer progression.
  • Overall, this study suggests molecular alterations accounting for the release and survival of CTC, which may be used as drug targets for either anti-metastatic therapy or the suppression of latent disease.
  • We also indicate the novel involvement of GRP94 suppression in prostate cancer metastasis.
  • [MeSH-minor] Animals. Blotting, Western. Cell Adhesion / physiology. Cell Line, Tumor. Cell Survival / physiology. Flow Cytometry. Humans. Immunohistochemistry. Male. Mice. Reverse Transcriptase Polymerase Chain Reaction. Tissue Array Analysis

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  • (PMID = 18340425.001).
  • [ISSN] 0262-0898
  • [Journal-full-title] Clinical & experimental metastasis
  • [ISO-abbreviation] Clin. Exp. Metastasis
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / HSP70 Heat-Shock Proteins; 0 / Membrane Proteins; 0 / glucose-regulated proteins
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6. Sun LC, Luo J, Mackey LV, Fuselier JA, Coy DH: A conjugate of camptothecin and a somatostatin analog against prostate cancer cell invasion via a possible signaling pathway involving PI3K/Akt, alphaVbeta3/alphaVbeta5 and MMP-2/-9. Cancer Lett; 2007 Feb 8;246(1-2):157-66
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A conjugate of camptothecin and a somatostatin analog against prostate cancer cell invasion via a possible signaling pathway involving PI3K/Akt, alphaVbeta3/alphaVbeta5 and MMP-2/-9.
  • It was found that, in addition to blocking migration and invasion of highly invasive prostate cancer PC-3 cells, this conjugate also inhibited in vitro capillary-like tube formation of endothelial cells and in vivo angiogenesis in C57B1/6N female mice.
  • This conjugate also inactivated phosphorylation of protein kinase B (PKB/Akt), down-regulated the expression of latent matrix metalloproteinase (MMP) -2 and MMP-9, but had little effect on MMP-3/-10.
  • Meanwhile, membrane type-1 matrix metalloproteinase (MT1-MMP) and the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) were not detectable in PC-3 cells. alphaVbeta3/alphaVbeta5 and MMP-2/-9 are known to be highly expressed in many tumor cells and play an important role in tumor progression.
  • Our results support that this conjugate could possibly inhibit prostate cancer PC-3 cell invasion through a signaling pathway involving PI3K/Akt, alphaVbeta3/alphaVbeta5 and MMP-2/-9, and this SSA could be used as an efficient vector to deliver CPT or other cytotoxic agents to target sites for cancer therapy.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Camptothecin / pharmacology. Cell Movement / drug effects. Signal Transduction / drug effects. Somatostatin / pharmacology
  • [MeSH-minor] Amino Acid Sequence. Animals. Blotting, Western. Cell Adhesion / drug effects. Cell Line, Tumor. Female. Humans. Integrin alphaVbeta3 / metabolism. Integrins / metabolism. Male. Matrix Metalloproteinase 2 / metabolism. Matrix Metalloproteinase 9 / metabolism. Mice. Mice, Inbred C57BL. Neoplasm Invasiveness. Neovascularization, Pathologic / pathology. Neovascularization, Pathologic / prevention & control. Phosphatidylinositol 3-Kinases / metabolism. Phosphorylation / drug effects. Prostatic Neoplasms / metabolism. Prostatic Neoplasms / pathology. Prostatic Neoplasms / physiopathology. Proto-Oncogene Proteins c-akt / metabolism. Receptors, Vitronectin / metabolism

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  • (PMID = 16644105.001).
  • [ISSN] 0304-3835
  • [Journal-full-title] Cancer letters
  • [ISO-abbreviation] Cancer Lett.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Ireland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Integrin alphaVbeta3; 0 / Integrins; 0 / JF-10-81; 0 / Receptors, Vitronectin; 0 / integrin alphaVbeta5; 51110-01-1 / Somatostatin; EC 2.7.1.- / Phosphatidylinositol 3-Kinases; EC 2.7.11.1 / Proto-Oncogene Proteins c-akt; EC 3.4.24.24 / Matrix Metalloproteinase 2; EC 3.4.24.35 / Matrix Metalloproteinase 9; XT3Z54Z28A / Camptothecin
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7. Amanatullah DF, Reutens AT, Zafonte BT, Fu M, Mani S, Pestell RG: Cell-cycle dysregulation and the molecular mechanisms of prostate cancer. Front Biosci; 2000 Apr 1;5:D372-90
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Cell-cycle dysregulation and the molecular mechanisms of prostate cancer.
  • Prostate cancer is the most common cause of non-cutaneous cancer in men and although frequently latent is the second commonest cause of death.
  • Screening for the disease was historically based on symptoms of urethral obstruction, clinical examination of the prostate gland and serum measurements of prostate specific antigen.
  • As prostate cancer growth in the early stages is enhanced by androgens, the mainstay of therapy has been androgen ablation by pharmaco-therapeutic or surgical means.
  • The subsequent development of androgen therapy resistant prostate cancer in many patients, for whom therapeutic options remain limited, has led researchers to focus attention on understanding the molecular genetics of prostate cancer.
  • The array of genetic abnormalities observed in prostate tumors, which include changes in components of the cell cycle, suggest the disease is quite heterogeneous and may require further sub-classification based on genetic markers.
  • Such analyses may lead to identification of relevant new prognostic and therapeutic indicators.
  • The advent of transgenic mouse models of prostate cancer may provide a critical tool for the implementation of rational genetic based therapeutics and alternate drug design.

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  • (PMID = 10762592.001).
  • [ISSN] 1093-9946
  • [Journal-full-title] Frontiers in bioscience : a journal and virtual library
  • [ISO-abbreviation] Front. Biosci.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R01 CA77552; United States / NCI NIH HHS / CA / R01CA75503; United States / NCI NIH HHS / CA / R29CA70897; etc
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Cell Adhesion Molecules; 0 / Cyclins; 0 / Cytokines; 0 / Oncogene Proteins; 0 / Receptors, Calcitriol; 0 / Tumor Suppressor Proteins; EC 3.1.3.- / Phosphoric Monoester Hydrolases; EC 3.1.3.48 / PTEN protein, human; EC 3.1.3.67 / PTEN Phosphohydrolase
  • [Number-of-references] 186
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8. Sternberg CN: Highlights of contemporary issues in the medical management of prostate cancer. Crit Rev Oncol Hematol; 2002 Aug;43(2):105-21
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Highlights of contemporary issues in the medical management of prostate cancer.
  • This paper highlights contemporary issues in the medical management of prostate cancer.
  • Controversies surrounding adjuvant and neo-adjuvant hormonal therapy in localized prostate cancer are reviewed, as well as the use of chemohormonal therapy in high risk localized disease.
  • The latent period of asymptomatic biochemical progression prior to clinical progression is an opportunity to evaluate new non-toxic therapies.
  • In patients with advanced metastatic disease hormonal therapy and new alternatives are discussed.
  • Chemotherapy in hormone refractory prostate cancer (HRPC) is extensively covered as well as the emerging role of molecular-targeted therapies.
  • [MeSH-major] Prostatic Neoplasms / therapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Antineoplastic Agents, Hormonal / therapeutic use. Bone Neoplasms / drug therapy. Bone Neoplasms / secondary. Disease Management. Drug Resistance, Neoplasm. Humans. Male. Palliative Care / methods

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  • (PMID = 12191733.001).
  • [ISSN] 1040-8428
  • [Journal-full-title] Critical reviews in oncology/hematology
  • [ISO-abbreviation] Crit. Rev. Oncol. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Ireland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Antineoplastic Agents, Hormonal
  • [Number-of-references] 142
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9. Manservigi R, Argnani R, Marconi P: HSV Recombinant Vectors for Gene Therapy. Open Virol J; 2010;4:123-56
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  • [Title] HSV Recombinant Vectors for Gene Therapy.
  • These include delivery and expression of human genes to cells of the nervous systems, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases, and targeted infection to specific tissues or organs.
  • Replication-defective recombinant vectors are non-toxic gene transfer tools that preserve most of the neurotropic features of wild type HSV-1, particularly the ability to express genes after having established latent infections, and are thus proficient candidates for therapeutic gene transfer settings in neurons.
  • A replication-defective HSV vector for the treatment of pain has recently entered in phase 1 clinical trial.
  • This review briefly summarizes the obstacle encountered in the delivery of HSV vectors and examines the various strategies developed or proposed to overcome such challenges.

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  • (PMID = 20835362.001).
  • [ISSN] 1874-3579
  • [Journal-full-title] The open virology journal
  • [ISO-abbreviation] Open Virol J
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Netherlands
  • [Other-IDs] NLM/ PMC2936037
  • [Keywords] NOTNLM ; HSV / cancer / gene therapy / neurodegenerative disorders / oncolytic vectors / targeting / vaccines. / viral vectors
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10. Miller GJ, Torkko KC: Natural history of prostate cancer--epidemiologic considerations. Epidemiol Rev; 2001;23(1):14-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Natural history of prostate cancer--epidemiologic considerations.
  • Multicentricity, heterogeneity, and sampling error complicate the study of the natural history of prostate cancer.
  • Carcinomas previously termed "latent" are probably similar to those detected clinically.
  • Estimates of grade and stage made at the time of detection are prone to sampling error and are likely to change following examination of radical prostatectomy specimens.
  • In regions with lower life expectancies, the problem of prostate cancer becomes a lower priority due to its association with aging.
  • However, in view of the high worldwide prevalence of the disease, further epidemiologic studies of prostate cancer are warranted.
  • [MeSH-minor] Developed Countries. Epidemiologic Studies. Humans. Male. Precancerous Conditions / epidemiology. Precancerous Conditions / pathology. Prostate / abnormalities. United States / epidemiology

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  • (PMID = 11588839.001).
  • [ISSN] 0193-936X
  • [Journal-full-title] Epidemiologic reviews
  • [ISO-abbreviation] Epidemiol Rev
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 53520; United States / NCI NIH HHS / CA / CA 66161
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] United States
  • [Number-of-references] 52
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11. Sooriakumaran P: Management of prostate cancer. Part 1: chemoprevention. Expert Rev Anticancer Ther; 2006 Mar;6(3):419-25
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Management of prostate cancer. Part 1: chemoprevention.
  • Numerous agents have been investigated in prostate cancer prevention.
  • Some are postulated to even affect downstream targets, such as cyclooxygenase-2, which has been shown to be elevated in prostate cancer by most investigators.
  • In addition, the current lack of ability to accurately differentiate clinically important prostate cancer from latent disease makes chemoprevention in this setting even more challenging.
  • Currently, no reliable biomarkers that can act as surrogate endpoints for the development of clinically relevant prostate cancer exist, which makes performing large chemoprevention trials expensive.
  • At present, there is little to suggest that the urologist or General Practitioner should be recommending any particular chemopreventive agent to either the general population or those deemed to be at higher risk of contracting prostate cancer.
  • [MeSH-minor] Anti-Inflammatory Agents, Non-Steroidal / pharmacology. Anti-Inflammatory Agents, Non-Steroidal / therapeutic use. Cell Proliferation / drug effects. Clinical Trials as Topic. Cyclooxygenase Inhibitors / pharmacology. Cyclooxygenase Inhibitors / therapeutic use. Dietary Fats. Gonadal Steroid Hormones / antagonists & inhibitors. Gonadal Steroid Hormones / physiology. Humans. Male

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  • (PMID = 16503858.001).
  • [ISSN] 1744-8328
  • [Journal-full-title] Expert review of anticancer therapy
  • [ISO-abbreviation] Expert Rev Anticancer Ther
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents, Non-Steroidal; 0 / Cyclooxygenase Inhibitors; 0 / Dietary Fats; 0 / Gonadal Steroid Hormones
  • [Number-of-references] 96
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12. Rusu D, Rusu V, Răileanu I, Stefănescu C: [PSA as a marker for prostate cancer progression]. Rev Med Chir Soc Med Nat Iasi; 2010 Jul-Sep;114(3):792-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [PSA as a marker for prostate cancer progression].
  • Monitoring the evolution of prostate cancer has crucial importance since this tip of neoplasia has a variable biology, ranging from latent cancers to extremely aggressive tumors.
  • At the moment, PSA (prostate specific antigen) values point out to either successful or unsuccessful prostate cancer therapy.
  • Depending on therapeutic strategies, biochemical recurrence (BCR) is differently defined.
  • After external beam therapy, PSA is slowly decreasing reaching up the nadir of 0.2-0.5 ng/mL in months or years; BCR: PSA = nadir + 2 ng/mL.
  • After hormonal therapy, PSA declines in 3-6 months, maintains low values for 18-24 months, then increases, settling for hormone independency.
  • After chemotherapy, PSA is considered normal at values < 2 ng/mL; the response of PSA represents a confirmed decreasing from the second test at 4 or more weeks after the initial decline; the length of the response is the period between first decline with 50 % of PSA to 50 % increase from nadir; the progression of PSA is shown in the increase with 25 % in comparison to the basic level.
  • [MeSH-major] Biomarkers, Tumor / blood. Prostate-Specific Antigen / blood. Prostatic Neoplasms / diagnosis
  • [MeSH-minor] Chemotherapy, Adjuvant. Disease Progression. Humans. Male. Predictive Value of Tests. Prostatectomy. Radiotherapy, Adjuvant. Sensitivity and Specificity. Severity of Illness Index


13. Denmeade SR, Jakobsen CM, Janssen S, Khan SR, Garrett ES, Lilja H, Christensen SB, Isaacs JT: Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer. J Natl Cancer Inst; 2003 Jul 2;95(13):990-1000
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer.
  • BACKGROUND: Standard anti-proliferative chemotherapy is relatively ineffective against slowly proliferating androgen-independent prostate cancer cells within metastatic sites.
  • However, thapsigargin's mechanism of action indicates that it is unlikely to be selective for cancer cells or prostate cells.
  • METHODS: We coupled a chemically modified form of thapsigargin, L12ADT, to a peptide carrier that is a substrate for the prostate-specific antigen (PSA) protease to produce a soluble, cell-impermeant latent prodrug that is specifically activated extracellularly within metastatic prostate cancer sites by PSA.
  • We analyzed the kinetics of PSA hydrolysis of the prodrug, the in vitro cytotoxicity of the prodrug against PSA-producing LNCaP human prostate cancer and PSA non-producing HCT-116 human colon cancer cells, and the in vivo pharmacokinetics of the prodrug in mice.
  • We also analyzed antitumor efficacy of the prodrug in nude mice xenograft models of prostate cancer (using LNCaP cells) and renal carcinoma (using human SN12C cells).
  • RESULTS: The L12ADT peptide prodrug was hydrolyzed efficiently by PSA, was selectively toxic to PSA-producing prostate cancer cells in vitro, and was stable in human plasma.
  • Levels of prodrug and liberated L12ADT in prostate cancer xenograft tumors were approximately eightfold and sixfold, respectively, higher than the in vitro LD50s.
  • Prostate cancer xenograft tumors in mice treated with prodrug by intravenous administration were growth-inhibited without substantial host toxicity.
  • Continuous subcutaneous prodrug administration in mice produced complete growth inhibition of established PSA-producing prostate cancer xenograft tumors but had no effect on PSA non-producing renal carcinoma xenograft tumors.
  • CONCLUSION: Further development of PSA-activated thapsigargin prodrugs as therapy for metastatic prostate cancer is warranted.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Prodrugs / therapeutic use. Prostate-Specific Antigen / drug effects. Prostatic Neoplasms / drug therapy. Prostatic Neoplasms / immunology. Thapsigargin / therapeutic use
  • [MeSH-minor] Animals. Disease Models, Animal. Humans. Hydrolysis / drug effects. Male. Mice. Mice, Nude. Transplantation, Heterologous. Treatment Outcome






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