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1. National Toxicology Program, Public Health Service, National Institutes of Health, US Department of Health and Human Services: Toxicology and carcinogenesis studies of o-nitrotoluene sulfone (CAS no. 88-72-2) in F344/N rats and B6C3F(1) mice (feed studies). Natl Toxicol Program Tech Rep Ser; 2002 May;(504):1-357
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  • [Title] Toxicology and carcinogenesis studies of o-nitrotoluene sulfone (CAS no. 88-72-2) in F344/N rats and B6C3F(1) mice (feed studies).
  • Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, rat and mouse bone marrow cells, and mouse peripheral blood erythrocytes.
  • The ratios of o-nitrobenzoic acid to creatinine and of o-nitrobenzylmercapturic acid to creatinine determined at 2 weeks and at 3, 12, and 18 months were linearly related to exposure concentration in males and females.
  • The ratio of o-aminobenzoic acid to creatinine was not related to exposure concentration.
  • The incidences of hematopoietic cell proliferation of the spleen and of hyperplasia of the mandibular lymph node (females) and bone marrow were increased in exposed groups of males at 3 months and/or 2 years and in exposed groups of females at 2 years.
  • The ratios of o-nitrobenzoic acid to creatinine determined at 2 weeks and at 3, 12, and 18 months were linearly related to exposure concentration in males and females.
  • The concentrations of o-nitrobenzylmercapturic acid and o-aminobenzoic acid were below the limit of quantitation at most time points.
  • Pathology Findings: The incidences of hemangiosarcoma in all exposed groups of males and in 5,000 ppm females were significantly greater than those in the controls.
  • GENETIC TOXICOLOGY: o-Nitrotoluene was not mutagenic in any of several strains of S. typhimurium, with or without metabolic activation enzymes (S9).
  • Sister chromatid exchanges were significantly increased in cultured Chinese hamster ovary cells following exposure to o-nitrotoluene in the presence of S9; an equivocal response was seen without S9. o-Nitrotoluene did not induce chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9. o-Nitrotoluene did not induce a significant increase in the frequency of micronuclei in bone marrow polychromatic erythrocytes of male rats or male mice when administered by intraperitoneal injection.
  • CONCLUSIONS: Under the conditions of these studies, there was clear evidence of carcinogenic activity* of o-nitrotoluene in male rats based on increased incidences of malignant mesothelioma, subcutaneous skin neoplasms, mammary gland fibroadenoma, and liver neoplasms.
  • There was clear evidence of carcinogenic activity of o-nitrotoluene in female rats based on increased incidences of subcutaneous skin neoplasms and mammary gland fibroadenoma.
  • There was clear evidence of carcinogenic activity of -o-nitrotoluene in male and female mice based on increased incidences of hemangiosarcoma, carcinoma of the large intestine (cecum), and hepatocellular neoplasms (females only).
  • Exposure to o--nitrotoluene caused increased incidences of nonneoplastic lesions of the mammary gland (females only), liver, bone marrow, spleen, lung, and mandibular lymph node (females only) in male and female rats and of the liver, kidney, and nose in male and female mice.
  • [MeSH-minor] Administration, Oral. Animals. CHO Cells. Carcinogenicity Tests. Cricetinae. Diet. Dose-Response Relationship, Drug. Female. In Vitro Techniques. Injections, Intraperitoneal. Longevity / drug effects. Male. Mice. Mice, Inbred Strains. Mutagenicity Tests. Rats. Rats, Inbred F344

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  • (PMID = 12087420.001).
  • [ISSN] 0888-8051
  • [Journal-full-title] National Toxicology Program technical report series
  • [ISO-abbreviation] Natl Toxicol Program Tech Rep Ser
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Carcinogens; 0 / Mutagens; 3FPU23BG52 / Toluene; 6Q9N88YIAY / 2-nitrotoluene
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2. Yau T, Leong CH, Chan WK, Chan JK, Liang RH, Epstein RJ: A case of mixed adult Wilms' tumour and angiosarcoma responsive to carboplatin, etoposide and vincristine (CEO). Cancer Chemother Pharmacol; 2008 Apr;61(4):717-20
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  • [Title] A case of mixed adult Wilms' tumour and angiosarcoma responsive to carboplatin, etoposide and vincristine (CEO).
  • Here we report an unusual case of mixed Wilms' tumour and angiosarcoma in a 38-year-old female patient who presented with haematuria and right lower back pain.
  • Histopathology revealed differentiated adult Wilms' tumour with renal angiosarcoma, whereas the pathology of the para-aortic lymph node and bone metastasis revealed angiosarcoma only.
  • This case suggests that highly angiogenic tumours such as angiosarcoma may be effectively palliated using agents usually reserved for refractory Wilms' tumour, and supports the view that adult Wilms' tumour is more sensitive to such agents.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Hemangiosarcoma / drug therapy. Kidney Neoplasms / drug therapy. Wilms Tumor / drug therapy
  • [MeSH-minor] Adult. Antineoplastic Agents / administration & dosage. Antineoplastic Agents, Phytogenic / administration & dosage. Carboplatin / administration & dosage. Combined Modality Therapy. Etoposide / administration & dosage. Fatal Outcome. Female. Humans. Magnetic Resonance Imaging. Neoplasm Metastasis. Neoplasm Recurrence, Local. Platelet Count. Tomography, X-Ray Computed. Vincristine / administration & dosage

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  • (PMID = 17571263.001).
  • [ISSN] 0344-5704
  • [Journal-full-title] Cancer chemotherapy and pharmacology
  • [ISO-abbreviation] Cancer Chemother. Pharmacol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Antineoplastic Agents, Phytogenic; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; BG3F62OND5 / Carboplatin
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3. Schlemmer M, Reichardt P, Verweij J, Hartmann JT, Judson I, Thyss A, Hogendoorn PC, Marreaud S, Van Glabbeke M, Blay JY: Paclitaxel in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma group. Eur J Cancer; 2008 Nov;44(16):2433-6
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  • [Title] Paclitaxel in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma group.
  • Paclitaxel appears to induce tumour control in a higher proportion of patients with angiosarcoma, as compared to other sarcomas.
  • METHOD: Clinical data from patients with angiosarcomas of soft tissue treated with single agent paclitaxel were collected from the centres of the soft tissue and bone sarcoma group of EORTC, using a standardised data collection form.
  • Eleven (34%) patients had been irradiated before as treatment for angiosarcoma.
  • In 8 (25%) patients, the angiosarcoma occurred at sites of prior radiation therapy for other malignancies.
  • CONCLUSION: Paclitaxel was found to be an active agent in angiosarcoma of soft tissue in this retrospective analysis.
  • [MeSH-major] Antineoplastic Agents, Phytogenic / therapeutic use. Hemangiosarcoma / drug therapy. Paclitaxel / therapeutic use. Soft Tissue Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Facial Neoplasms / drug therapy. Female. Humans. Male. Middle Aged. Neoplasm Recurrence, Local / drug therapy. Retrospective Studies. Scalp. Skin Neoplasms / drug therapy. Young Adult


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4. Laifenfeld D, Gilchrist A, Drubin D, Jorge M, Eddy SF, Frushour BP, Ladd B, Obert LA, Gosink MM, Cook JC, Criswell K, Somps CJ, Koza-Taylor P, Elliston KO, Lawton MP: The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma. Toxicol Sci; 2010 Jan;113(1):254-66
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  • [Title] The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
  • 2-BE is a hemolytic agent that induces hemangiosarcomas in mice.
  • We hypothesized that the hemolysis induced by 2-BE would result in local tissue hypoxia, a well-documented trigger for endothelial cell proliferation leading to hemangiosarcoma.
  • Gene expression data from bone marrow (BM), liver, and spleen of mice exposed to a single dose (4 h) or seven daily doses of 2-BE were used to develop a mechanistic model of hemangiosarcoma.
  • In addition, the model supports local tissue hypoxia in the liver and spleen, coupled with increased erythropoeitin signaling and erythropoiesis in the spleen and BM, and suppression of mechanisms that contribute to genomic stability, events that could be contributing factors to hemangiosarcoma formation.
  • Together, the results of this study identify molecular mechanisms that initiate hemangiosarcoma, a key step in understanding safety concerns that can impact drug decision processes, and identified hypoxia as a possible contributing factor for 2-BE-induced hemangiosarcoma in mice.
  • [MeSH-major] Bone Marrow / metabolism. Cell Transformation, Neoplastic / metabolism. Hemangiosarcoma / metabolism. Liver / metabolism. Models, Biological. Signal Transduction. Spleen / metabolism. Systems Biology
  • [MeSH-minor] Animals. Cell Cycle. Cell Differentiation. Cell Hypoxia. Cell Proliferation. Disease Models, Animal. Endothelial Cells / metabolism. Erythropoiesis. Erythropoietin / metabolism. Ethylene Glycols. Gene Expression Profiling / methods. Gene Expression Regulation, Neoplastic. Genomic Instability. Hematopoietic Stem Cells / metabolism. Hemolysis. Hepatitis / metabolism. Hepatitis / pathology. Immunohistochemistry. Macrophage Activation. Male. Mice. Time Factors

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  • (PMID = 19812364.001).
  • [ISSN] 1096-0929
  • [Journal-full-title] Toxicological sciences : an official journal of the Society of Toxicology
  • [ISO-abbreviation] Toxicol. Sci.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Ethylene Glycols; 11096-26-7 / Erythropoietin; I0P9XEZ9WV / n-butoxyethanol
  • [Other-IDs] NLM/ PMC2794330
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5. National Toxicology Program: Toxicology and carcinogenesis studies of formamide (Cas No. 75-12-7) in F344/N rats and B6C3F1 mice (gavage studies). Natl Toxicol Program Tech Rep Ser; 2008 Jul;(541):1-192
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  • A significant increase in the incidence of bone marrow hyperplasia occurred in 80 mg/kg males.
  • The incidences of hemangiosarcoma of the liver occurred with a positive trend in males, and the incidences were significantly increased in the 40 and 80 mg/kg groups.
  • In three independent Ames assays, formamide was not mutagenic in any of several strains of S. typhimurium tested with and without rat or hamster liver S9 activation enzymes or in E. coli strain WP uvrA pKM101 tested with and without 10% rat liver S9.
  • There was clear evidence of carcinogenic activity of formamide in male B6C3F1 mice based on increased incidences of hemangiosarcoma of the liver.
  • An increased incidence of bone marrow hyperplasia occurred in male rats.
  • [MeSH-minor] Administration, Oral. Animals. Body Weight / drug effects. Bone Marrow / drug effects. Bone Marrow / pathology. Calcinosis / chemically induced. Calcinosis / pathology. Female. Hyperplasia. Liver Neoplasms / chemically induced. Liver Neoplasms / pathology. Male. Mice. Mice, Inbred Strains. Mutagenicity Tests. Rats. Rats, Inbred F344. Spleen / drug effects. Spleen / pathology. Testis / drug effects. Testis / pathology

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  • (PMID = 18716632.001).
  • [ISSN] 0888-8051
  • [Journal-full-title] National Toxicology Program technical report series
  • [ISO-abbreviation] Natl Toxicol Program Tech Rep Ser
  • [Language] eng
  • [Publication-type] Journal Article; Technical Report
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Environmental Pollutants; 0 / Formamides; 4781T907ZS / formamide
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6. Schulze R, Schulze M, Salomon-Dani A, Weihprecht H, Bohndorf K, Arnholdt H, Schlimok G: [Recurrent hemoptysis. 65-year-old post-kidney transplant patient with bilateral thoracic wall tumors]. Internist (Berl); 2001 Jan;42(1):119-23
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [MeSH-major] Bone Neoplasms / secondary. Heart Atria. Heart Neoplasms / diagnosis. Hemangiosarcoma / secondary. Hemoptysis / etiology. Kidney Transplantation. Postoperative Complications / diagnosis. Ribs. Thoracic Neoplasms / secondary
  • [MeSH-minor] Aged. Biopsy. Cyclosporine / adverse effects. Cyclosporine / therapeutic use. Diagnosis, Differential. Diagnostic Imaging. Humans. Immune Tolerance / drug effects. Immune Tolerance / immunology. Immunosuppressive Agents / adverse effects. Immunosuppressive Agents / therapeutic use. Male. Prednisone / adverse effects. Prednisone / therapeutic use

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  • (PMID = 11271612.001).
  • [ISSN] 0020-9554
  • [Journal-full-title] Der Internist
  • [ISO-abbreviation] Internist (Berl)
  • [Language] ger
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; 83HN0GTJ6D / Cyclosporine; VB0R961HZT / Prednisone
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7. National Toxicology Program: Toxicology and carcinogenesis studies of riddelliine (CAS No. 23246-96-0) in F344/N rats and B6C3F1 mice (gavage studies). Natl Toxicol Program Tech Rep Ser; 2003 May;(508):1-280
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  • Riddelliine was nominated for study by the Food and Drug Administration because of its potential for human exposure and its economic impact on the livestock industry and because the toxicity of other pyrrolizidine alkaloids suggests riddelliine may be carcinogenic.
  • In addition, riddelliine was evaluated in vivo for induction of micronuclei in mouse bone marrow and peripheral blood erythrocytes and for induction of S-phase DNA synthesis and unscheduled DNA synthesis in the liver of rats and mice.
  • The only clinical finding related to riddelliine administration was a general debilitation of the animals prior to death.
  • Use of a single intraperitoneal injection protocol, however, produced a small but significant increase in the frequency of micronucleated eryth-rocytes in peripheral blood of male Swiss mice 48 hours after injection; bone marrow analysis 24 hours after injection demonstrated a small but insignificant increase in the frequency of micronuclei.
  • CONCLUSIONS: Under the conditions of these studies, there was clear evidence of carcinogenic activity of riddelliine in male and female F344/N rats based primarily on increased incidences of hemangiosarcoma in the liver.
  • There was clear evidence of carcinogenic activity of riddelliine in male B6C3F1 mice based on increased incidences of hemangiosarcoma in the liver.
  • [MeSH-minor] Administration, Oral. Animals. Body Weight / drug effects. Carcinogenicity Tests. Female. Kidney / drug effects. Kidney / pathology. Liver / drug effects. Liver / pathology. Male. Mice. Mice, Inbred Strains. Mutagenicity Tests. Rats. Rats, Inbred F344. Sex Factors. Survival Analysis. Time Factors

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  • (PMID = 12844193.001).
  • [ISSN] 0888-8051
  • [Journal-full-title] National Toxicology Program technical report series
  • [ISO-abbreviation] Natl Toxicol Program Tech Rep Ser
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Carcinogens; 0 / Pyrrolizidine Alkaloids; 23246-96-0 / riddelliine
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8. Basile A, Rand T, Lomoschitz F, Toma C, Lupattelli T, Kettenbach J, Lammer J: Trisacryl gelatin microspheres versus polyvinyl alcohol particles in the preoperative embolization of bone neoplasms. Cardiovasc Intervent Radiol; 2004 Sep-Oct;27(5):495-502
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  • [Title] Trisacryl gelatin microspheres versus polyvinyl alcohol particles in the preoperative embolization of bone neoplasms.
  • The aim of this study was to compare the efficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles (PVA) in the preoperative embolization of bone neoplasms, on the basis of intraoperative blood loss quantified by the differences in preoperative and postoperative hematic levels of hemoglobin, hematocrit and erythrocytes count.
  • From January 1997 to December 2002, preoperative embolization of bone tumors (either primary or secondary) was carried out in 49 patients (age range 12/78), 20 of whom were treated with trysacril gelatin microspheres (group A) and 29 with PVA particles (group B).
  • According to the Student's t-test ( p < 0.05), the difference of hematic parameters between patients treated by embospheres and PVA alone were significant; otherwise there was no significant difference between patients treated with only one embolic material (embospheres and PVA) versus those treated with other additional embolic agents in each group.
  • [MeSH-major] Acrylic Resins / therapeutic use. Bone Neoplasms / therapy. Embolization, Therapeutic. Neoadjuvant Therapy / methods. Polyvinyl Alcohol / therapeutic use. Postoperative Hemorrhage / prevention & control
  • [MeSH-minor] Adolescent. Adult. Aged. Biomarkers / blood. Carcinoma, Giant Cell / therapy. Child. Female. Gelatin / therapeutic use. Hemangiosarcoma / therapy. Humans. Leiomyosarcoma / therapy. Male. Microspheres. Middle Aged. Tomography, X-Ray Computed. Treatment Outcome

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  • (PMID = 15383854.001).
  • [ISSN] 0174-1551
  • [Journal-full-title] Cardiovascular and interventional radiology
  • [ISO-abbreviation] Cardiovasc Intervent Radiol
  • [Language] eng
  • [Publication-type] Controlled Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Acrylic Resins; 0 / Biomarkers; 9000-70-8 / Gelatin; 9002-89-5 / Polyvinyl Alcohol; 97930-01-3 / DEAE-Trisacryl
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9. Jori F, Cooper JE: Spontaneous neoplasms in captive African cane rats (Thryonomys swinderianus Temminck, 1827). Vet Pathol; 2001 Sep;38(5):556-8
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  • Despite the increasing importance of cane rat (Thryonomys swinderianus) farming in Africa, diseases of these animals in captivity are not well known.
  • Within a period of 8 months, a chondroma in an adult female, a hemangiosarcoma in a subadult male, and a chondrosarcoma in an elderly female were diagnosed.
  • Neoplasms in rodents might be induced by such factors as a high inbreeding coefficient, an oncogenic virus, or chemical agent intoxication.
  • [MeSH-minor] Animals. Bone Neoplasms / pathology. Bone Neoplasms / veterinary. Chondroma / pathology. Chondroma / veterinary. Female. Gabon / epidemiology. Head and Neck Neoplasms / pathology. Head and Neck Neoplasms / veterinary. Hemangiosarcoma / pathology. Hemangiosarcoma / veterinary. Hindlimb. Inbreeding. Incidence. Male. Osteosarcoma / pathology. Osteosarcoma / veterinary. Risk Factors. Rodentia. Skin Neoplasms / pathology. Skin Neoplasms / veterinary

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  • (PMID = 11572565.001).
  • [ISSN] 0300-9858
  • [Journal-full-title] Veterinary pathology
  • [ISO-abbreviation] Vet. Pathol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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10. Asmane I, Litique V, Heymann S, Marcellin L, M├ętivier AC, Duclos B, Bergerat JP, Kurtz JE: Adriamycin, cisplatin, ifosfamide and paclitaxel combination as front-line chemotherapy for locally advanced and metastatic angiosarcoma. Analysis of three case reports and review of the literature. Anticancer Res; 2008 Sep-Oct;28(5B):3041-5
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  • [Title] Adriamycin, cisplatin, ifosfamide and paclitaxel combination as front-line chemotherapy for locally advanced and metastatic angiosarcoma. Analysis of three case reports and review of the literature.
  • Angiosarcoma represents 1 to 2% of soft tissue tumors.
  • The outcome of angiosarcoma is poor for those patients in whom aggressive surgery cannot be considered.
  • We report three cases of angiosarcoma in which first-line chemotherapy with adriamycin 40 mg/m2 day 1, ifosfamide 3 g/m2 day 1-2, cisplatin 35 mg/m2 day 1-2 and paclitaxel 175 mg/m2 day 3 led to clinically meaningful responses.
  • We emphasize the need for designing trials specifically dedicated to angiosarcomas, as this rare and severe condition may be a target for new antiangiogenic drugs.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Neoplasms / drug therapy. Breast Neoplasms / drug therapy. Hemangiosarcoma / drug therapy. Soft Tissue Neoplasms / drug therapy

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  • (PMID = 19031953.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Greece
  • [Chemical-registry-number] 80168379AG / Doxorubicin; P88XT4IS4D / Paclitaxel; Q20Q21Q62J / Cisplatin; UM20QQM95Y / Ifosfamide
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11. Rihova B: Clinical experience with anthracycline antibiotics-HPMA copolymer-human immunoglobulin conjugates. Adv Drug Deliv Rev; 2009 Nov 12;61(13):1149-58
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  • Four of six monitored patients attained stabilization of disease (liver ultrasound scan and bone computer tomography) with a very good quality of life lasting from seven up to 18 months.
  • A stable or elevated number of peripheral blood reticulocytes together with activation of natural killer (NK) cells and lymphokine-activated killer (LAK) cells supports the data previously obtained in experimental animals pointing to a dual role, i.e. the cytotoxic and immunomobilizing character of doxorubicin-HPMA conjugates.
  • [MeSH-major] Antibiotics, Antineoplastic / administration & dosage. Doxorubicin / analogs & derivatives. Epirubicin / administration & dosage. Immunoglobulin G / administration & dosage. Polymethacrylic Acids / administration & dosage
  • [MeSH-minor] Acrylamides / chemistry. Adult. Animals. Biomarkers, Tumor / blood. Breast Neoplasms / drug therapy. Drug Carriers / chemistry. Drug Delivery Systems. Drug Resistance, Neoplasm. Female. Hemangiosarcoma / drug therapy. Humans. Immunoglobulins, Intravenous / administration & dosage. Immunoglobulins, Intravenous / immunology. Immunologic Factors / administration & dosage. Immunologic Factors / immunology. Middle Aged. Neoplasm Metastasis. Quality of Life. Treatment Outcome

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  • (PMID = 19682512.001).
  • [ISSN] 1872-8294
  • [Journal-full-title] Advanced drug delivery reviews
  • [ISO-abbreviation] Adv. Drug Deliv. Rev.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Acrylamides; 0 / Antibiotics, Antineoplastic; 0 / Biomarkers, Tumor; 0 / Drug Carriers; 0 / Immunoglobulin G; 0 / Immunoglobulins, Intravenous; 0 / Immunologic Factors; 0 / Polymethacrylic Acids; 0 / doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate; 21442-01-3 / N-(2-hydroxypropyl)methacrylamide; 3Z8479ZZ5X / Epirubicin; 80168379AG / Doxorubicin
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12. Cohen SM, Storer RD, Criswell KA, Doerrer NG, Dellarco VL, Pegg DG, Wojcinski ZW, Malarkey DE, Jacobs AC, Klaunig JE, Swenberg JA, Cook JC: Hemangiosarcoma in rodents: mode-of-action evaluation and human relevance. Toxicol Sci; 2009 Sep;111(1):4-18
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  • [Title] Hemangiosarcoma in rodents: mode-of-action evaluation and human relevance.
  • Although rarely occurring in humans, hemangiosarcomas (HS) have become important in evaluating the potential human risk of several chemicals, including industrial, agricultural, and pharmaceutical agents.
  • An overall framework is presented, including direct and indirect actions on endothelial cells, paracrine effects in local tissues, activation of bone marrow endothelial precursor cells, and tissue hypoxia.
  • [MeSH-major] Hemangiosarcoma / pathology
  • [MeSH-minor] Animals. Carcinogens / toxicity. DNA / drug effects. Dogs. Humans. Mice. Neovascularization, Pathologic / pathology. Neovascularization, Physiologic / physiology. Peroxisome Proliferator-Activated Receptors / agonists. Rats. Risk Assessment. Species Specificity. Vinyl Chloride / toxicity


13. Herman JR, Dethloff LA, McGuire EJ, Parker RF, Walsh KM, Gough AW, Masuda H, de la Iglesia FA: Rodent carcinogenicity with the thiazolidinedione antidiabetic agent troglitazone. Toxicol Sci; 2002 Jul;68(1):226-36
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  • [Title] Rodent carcinogenicity with the thiazolidinedione antidiabetic agent troglitazone.
  • Hypertrophy and hyperplasia of brown adipose tissue was observed in both species at all doses, and fatty change and hypocellularity of bone marrow was noted in mice at all doses and in female rats at 50 and 200 mg/kg.
  • In mice, the incidence of hemangiosarcoma was increased in females at 400 mg/kg and in both sexes at 800 mg/kg.
  • No tumors of any type were increased in rats at exposures up to 47 times therapeutic exposure.
  • [MeSH-major] Carcinogens / toxicity. Chromans / toxicity. Hypoglycemic Agents / toxicity. Thiazoles / toxicity. Thiazolidinediones
  • [MeSH-minor] Adipose Tissue, Brown / drug effects. Adipose Tissue, Brown / pathology. Administration, Oral. Animals. Area Under Curve. Bone Marrow / drug effects. Bone Marrow / pathology. Carcinogenicity Tests. Carcinoma, Hepatocellular / chemically induced. Carcinoma, Hepatocellular / pathology. Dose-Response Relationship, Drug. Heart / drug effects. Hemangiosarcoma / chemically induced. Hemangiosarcoma / pathology. Liver / drug effects. Liver / pathology. Liver Neoplasms / chemically induced. Liver Neoplasms / pathology. Longevity / drug effects. Mice. Myocardium / pathology. Rats. Rats, Wistar. Species Specificity. Survival Analysis

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  • (PMID = 12075125.001).
  • [ISSN] 1096-6080
  • [Journal-full-title] Toxicological sciences : an official journal of the Society of Toxicology
  • [ISO-abbreviation] Toxicol. Sci.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Carcinogens; 0 / Chromans; 0 / Hypoglycemic Agents; 0 / Thiazoles; 0 / Thiazolidinediones; I66ZZ0ZN0E / troglitazone
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14. Kudva R, Perveen S, Janardhana A: Primary epithelioid angiosarcoma of bone: a case report with immunohistochemical study. Indian J Pathol Microbiol; 2010 Oct-Dec;53(4):811-3
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  • [Title] Primary epithelioid angiosarcoma of bone: a case report with immunohistochemical study.
  • Primary malignant vascular tumors of the bone are exceedingly rare and represent <1% of primary malignant bone tumors.
  • Angiosarcoma is a malignant mesenchymal neoplasm in which the neoplastic cells demonstrate endothelial differentiation.
  • Epithelioid angiosarcoma (EA) is a rare variant of angiosarcoma that is characterized by large cells with an epithelioid morphology.
  • [MeSH-major] Bone Neoplasms / diagnosis. Bone Neoplasms / pathology. Hemangiosarcoma / diagnosis. Hemangiosarcoma / pathology. Sarcoma / diagnosis. Sarcoma / pathology. Tibia / pathology
  • [MeSH-minor] Amputation. Antigens, CD34 / analysis. Antineoplastic Agents / therapeutic use. Drug Therapy / methods. Fatal Outcome. Histocytochemistry. Humans. Immunohistochemistry. Magnetic Resonance Imaging. Male. Microscopy. Middle Aged

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  • (PMID = 21045426.001).
  • [ISSN] 0974-5130
  • [Journal-full-title] Indian journal of pathology & microbiology
  • [ISO-abbreviation] Indian J Pathol Microbiol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] India
  • [Chemical-registry-number] 0 / Antigens, CD34; 0 / Antineoplastic Agents
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15. National Toxicology Program, Public Health Services, National Institutes of Health, US Department of Health and Human Services,: NTP technical report on the toxicology and carcinogenesis studies of Elmiron (Cas No. 37319-17-8) in F344/N rats and B6C3F1 mice (Gavage Studies). Natl Toxicol Program Tech Rep Ser; 2004 May;(512):7-289
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  • [structure--see text] Elmiron, a white powder, is the sodium salt of pentosan polysulfate, a semisynthetic sulfated polyanion composed of beta-D-xylopyranose residues with biological properties similar to heparin.
  • The United States Food and Drug Administration nominated Elmiron for toxicology and carcinogenicity testing by the National Toxicology Program because of its orphan drug status.
  • Male and female F344/N rats and B6C3F1 mice received Elmiron, which met product specifications provided by the manufacturer, in deionized water by gavage for 2 weeks, 3 months, or 2 years.
  • Genetic toxicology studies were conducted in Salmonella typhimurium, rat and mouse bone marrow cells, and mouse peripheral blood erythrocytes.
  • No increases in the frequency of micronucleated polychromatic erythrocytes were seen in bone marrow cells of rats or mice administered Elmiron by gavage three times at 24-hour intervals.
  • There was some evidence of carcinogenic activity of Elmiron in male B6C3F1 mice based on increased incidences of liver hemangiosarcoma.
  • There was some evidence of carcinogenic activity of Elmiron in female B6C3F1 mice based on the increased incidences of liver hemangiosarcoma and hepatocellular neoplasms.
  • [MeSH-major] Anti-Inflammatory Agents, Non-Steroidal / toxicity. Carcinogens / toxicity. Neoplasms, Experimental / chemically induced. Pentosan Sulfuric Polyester / toxicity
  • [MeSH-minor] Adenoma, Liver Cell / chemically induced. Adenoma, Liver Cell / pathology. Administration, Oral. Animals. Body Weight / drug effects. Carcinogenicity Tests. Carcinoma, Hepatocellular / chemically induced. Carcinoma, Hepatocellular / pathology. Dose-Response Relationship, Drug. Female. Hemangiosarcoma / chemically induced. Hemangiosarcoma / pathology. Liver Neoplasms / chemically induced. Liver Neoplasms / pathology. Male. Mice. Mice, Inbred Strains. Mutagenicity Tests. Rats. Rats, Inbred F344. Toxicity Tests, Chronic

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  • (PMID = 15213766.001).
  • [ISSN] 0888-8051
  • [Journal-full-title] National Toxicology Program technical report series
  • [ISO-abbreviation] Natl Toxicol Program Tech Rep Ser
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents, Non-Steroidal; 0 / Carcinogens; 37300-21-3 / Pentosan Sulfuric Polyester
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16. National Toxicology Program: NTP Toxicology and carcinogenesis studies of bromodichloromethane (CAS No. 75-27-4) in male F344/N rats and female B6C3F1 mice (Drinking Water Studies). Natl Toxicol Program Tech Rep Ser; 2006 Feb;(532):1-248
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  • Bromodichloromethane is a by-product of the chlorination of drinking water.
  • It is formed by the halogen substitution and oxidation reactions of chlorine with naturally occurring organic matter (e.g., humic or fulvic acids) in water containing bromide.
  • Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, mouse bone marrow cells, and mouse peripheral blood erythrocytes.
  • There were significant concentration-related decreases in water consumption by groups exposed to 87.5 mg/L or greater throughout the study; these decreases were attributed to poor palatability of the dosed water.
  • The incidences of chronic inflammation in the liver of the 350 and 700 mg/L groups were significantly greater than that in the controls; however, the biological significance of these increases is uncertain.
  • The incidence of hemangiosarcoma in all organs was significantly decreased in the 350 mg/L group.
  • No increases in the frequency of micronucleated erythrocytes were seen in bone marrow of male B6C3F1 mice administered bromodichloromethane by intraperitoneal injection for 3 days.
  • [MeSH-minor] Animals. Body Composition / drug effects. Body Weight / drug effects. Dose-Response Relationship, Drug. Female. Male. Mice. Mice, Inbred Strains. Mutagens / toxicity. Neoplasms / chemically induced. Neoplasms / epidemiology. Nutritional Physiological Phenomena. Organ Size / drug effects. Quality Control. Rats. Rats, Inbred F344. Trihalomethanes / toxicity. Water Supply / analysis

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  • (PMID = 16741555.001).
  • [ISSN] 0888-8051
  • [Journal-full-title] National Toxicology Program technical report series
  • [ISO-abbreviation] Natl Toxicol Program Tech Rep Ser
  • [Language] eng
  • [Publication-type] Journal Article; Technical Report
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Carcinogens; 0 / Mutagens; 0 / Trihalomethanes; 7LN464CH2O / bromodichloromethane
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