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2. National Toxicology Program: NTP technical report on the toxicology and carcinogenesis studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (CAS No. 1746-01-6) in female Harlan Sprague-Dawley rats (Gavage Studies). Natl Toxicol Program Tech Rep Ser; 2006 Apr;(521):4-232
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds" (DLCs).
  • The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener.
  • This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals based on a common mechanism of action involving an initial binding of DLCs to the AhR.
  • The main sources of TCDD releases into the environment are from combustion and incineration; metal smelting, refining, and processing; chemical manufacturing and processing; biological and photochemical processes; and existing reservoir sources that reflect past releases.
  • HEPATIC CELL PROLIFERATION DATA: To evaluate hepatocyte replication, analysis of labeling of replicating hepatocytes with 5-bromo-2'-deoxyuridine was conducted at the 14-, 31-, and 53-week interim evaluations.
  • DETERMINATIONS OF TCDD CONCENTRATIONS IN TISSUES: The tissue disposition of TCDD was analyzed in the liver, lung, fat, and blood of all animals in each group at the 14-, 31-, and 53-week interim evaluations and in 10 animals per group at the end of the 2-year study (105 weeks).
  • At 2 years, there was a significant increase in toxic hepatopathy characterized by increased incidences of numerous nonneoplastic liver lesions including hepatocyte hypertrophy, multinucleated hepatocytes, altered hepatocellular foci, inflammation, pigmentation, diffuse fatty change, necrosis, portal fibrosis, oval cell hyperplasia, bile duct hyperplasia, bile duct cysts, cholangiofibrosis, and nodular hyperplasia At 2 years, the incidence of hepatocellular adenoma was significantly increased in the 100 ng/kg core study group.
  • The highest incidence of cholangiocarcinoma was seen in the 100 ng/kg core study group and included a significant number of animals with multiple cholangiocarcinomas.
  • The incidence of gingival squamous cell carcinoma of the oral mucosa was significantly increased in the 100 ng/kg core study group at 2 years and was accompanied by an increased incidence of gingival squamous hyperplasia.
  • At 2 years, the incidence of squamous cell carcinoma of the uterus in the 46 ng/kg group was significantly increased, and there were two squamous cell carcinomas in the 100 ng/kg stop-exposure group.
  • At 2 years, one acinar adenoma and two acinar cell carcinomas of the pancreas were seen in the 100 ng/kg core study group; one acinar carcinoma was seen in the 100 ng/kg stop-exposure group.
  • The incidences of acinar cell adenoma or carcinoma (combined) exceeded the historical vehicle control range.
  • [MeSH-minor] Animals. Body Weight / drug effects. Carcinogenicity Tests. Female. Mice. Neoplasms, Experimental / chemically induced. Organ Size / drug effects. Rats. Rats, Sprague-Dawley

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  • (PMID = 16835633.001).
  • [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; DO80M48B6O / Tetrachlorodibenzodioxin
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3. Sugita H, Hirota M, Ichihara A, Furuhashi S, Kihara S, Shimada S: Combined chemotherapy of irinotecan and low-dose cisplatin (I/low-P) against metastatic biliary tract cancer. J Hepatobiliary Pancreat Surg; 2006;13(5):463-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Biliary Tract Neoplasms / drug therapy. Biliary Tract Neoplasms / pathology
  • [MeSH-minor] Adenocarcinoma / drug therapy. Adenocarcinoma / pathology. Adult. Aged. Bile Duct Neoplasms / drug therapy. Bile Duct Neoplasms / pathology. Camptothecin / administration & dosage. Camptothecin / analogs & derivatives. Carcinoma, Squamous Cell / drug therapy. Carcinoma, Squamous Cell / pathology. Cisplatin / administration & dosage. Female. Gallbladder Neoplasms / drug therapy. Gallbladder Neoplasms / pathology. Humans. Infusions, Intravenous. Male. Middle Aged. Neoplasm Metastasis

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  • (PMID = 17013724.001).
  • [ISSN] 0944-1166
  • [Journal-full-title] Journal of hepato-biliary-pancreatic surgery
  • [ISO-abbreviation] J Hepatobiliary Pancreat Surg
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 7673326042 / irinotecan; Q20Q21Q62J / Cisplatin; XT3Z54Z28A / Camptothecin
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4. Suzuki E, Hirai R, Ota T, Shimizu N: Primary adenosquamous carcinoma of the liver: case report. J Hepatobiliary Pancreat Surg; 2002;9(6):769-73
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Primary adenosquamous carcinoma of the liver: case report.
  • We describe a case of adenosquamous carcinoma of the liver, including treatment for the recurrence.
  • It was a yellowish white solid mass without macroscopic invasion of the intrahepatic bile duct.
  • Histological examination of the resected specimen revealed both adenocarcinoma and squamous cell carcinoma.
  • We also review 41 cases of adenosquamous carcinoma of the liver reported in the Japanese and English language literature, including the present case.
  • [MeSH-major] Carcinoma, Adenosquamous / surgery. Hepatectomy. Liver Neoplasms / surgery
  • [MeSH-minor] Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cisplatin / administration & dosage. Fatal Outcome. Fluorouracil / administration & dosage. Humans. Infusions, Intra-Arterial. Male. Neoplasm Recurrence, Local / drug therapy

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  • (PMID = 12658415.001).
  • [ISSN] 0944-1166
  • [Journal-full-title] Journal of hepato-biliary-pancreatic surgery
  • [ISO-abbreviation] J Hepatobiliary Pancreat Surg
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] Q20Q21Q62J / Cisplatin; U3P01618RT / Fluorouracil
  • [Number-of-references] 28
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5. National Toxicology Program: Toxicology and carcinogenesis studies of 2,3',4,4',5-pentachlorobiphenyl (PCB 118) (CAS No. 31508-00-6) in female harlan Sprague-Dawley rats (gavage studies). Natl Toxicol Program Tech Rep Ser; 2010 Nov;(559):1-174
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds"(DLCs).
  • The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener.
  • This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR.
  • Manufacture and use of these chemicals were stopped because of increased PCB residues in the environment, but they continue to be released into the environment through the use and disposal of products containing PCBs, as by-products during the manufacture of certain organic chemicals, during combustion of some waste materials, and during atmospheric recycling.
  • In general, exposure to PCB 118 lead to dose-dependent decreases in the concentrations of serum total thyroxine (T4) and free T4 in all dosed groups.
  • There were increases in hepatic cell proliferation in the 4,600 g/kg group at 14, 31, and 53 weeks.
  • At 2 years, a significant dose-related increase in hepatic toxicity was observed and was characterized by increased incidences of numerous lesions including hepatocyte hypertrophy, inflammation, oval cell hyperplasia, pigmentation, multinucleated hepatocyte, eosinophilic and mixed cell foci, diffuse fatty change, toxic hepatopathy, nodular hyperplasia, necrosis, bile duct hyperplasia and cyst, and cholangiofibrosis.
  • Incidences of bronchiolar metaplasia of the alveolar epithelium were significantly increased in the groups administered 460 g/kg or greater, and the incidence of squamous metaplasia was significantly increased in the 4,600 g/kg core study group.
  • The incidence of carcinoma of the uterus in the 4,600 g/kg stop-exposure group was significantly greater than those in the vehicle control and 4,600 g/kg core study groups at 2 years.
  • A marginal increase in squamous cell carcinoma occurred in the 220 g/kg group.
  • At 2 years, there were marginally increased incidences of exocrine pancreatic adenoma or carcinoma in the 460, 1,000, and 4,600 g/kg core study groups.
  • Numerous nonneoplastic effects were seen in other organs including: adrenal cortical atrophy and cytoplasmic vacuolization, pancreatic acinar cell cytoplasmic vacuolization and arterial chronic active inflammation, follicular cell hypertrophy of the thyroid gland, inflammation and respiratory epithelial hyperplasia of the nose, and kidney pigmentation.
  • Occurrences of carcinoma in the uterus were considered to be related to the administration of PCB 118.
  • Occurrences of squamous cell carcinoma of the uterus and acinar neoplasms of the pancreas may have been related to administration of PCB 118.
  • [MeSH-minor] Animals. Carcinogenicity Tests. Dose-Response Relationship, Drug. Female. Humans. Male. Rats. Rats, Sprague-Dawley. Tetrachlorodibenzodioxin / toxicity

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  • (PMID = 21383778.001).
  • [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] 31508-00-6 / 2,3',4,4',5-pentachlorobiphenyl; DFC2HB4I0K / Polychlorinated Biphenyls; DO80M48B6O / Tetrachlorodibenzodioxin
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6. National Toxicology Program: Toxicology and carcinogenesis studies of 3,3',4,4'-tetrachloroazobenzene (TCAB) (CAS No. 14047-09-7) in Harlan Sprague-Dawley rats and B6C3F1 mice (gavage studies). Natl Toxicol Program Tech Rep Ser; 2010 Nov;(558):1-206
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  • 3,3',4,4'-Tetrachloroazobenzene (TCAB) is not commercially manufactured but is formed as an unwanted by-product in the manufacture of 3,4-dichloroaniline and its herbicidal derivatives Propanil, Linuron, and Diuron.
  • It occurs from the degradation of chloroanilide herbicides (acylanilides, phenylcarbamates, and phenylureas) in soil by peroxide-producing microorganisms; and is formed by the photolysis and biolysis of 3,4-dichloroaniline.
  • TCAB was nominated by the United States Environmental Protection Agency for toxicity and carcinogenicity testing based on its structural and biological similarity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the potential for human exposure from the consumption of crops contaminated with 3,4-dichloroaniline-derived herbicides.
  • Hematopoietic cell proliferation occurred in most males administered 3 mg/kg or greater and most females administered 10 mg/kg or greater.
  • In the lung, significantly increased incidences of bronchiolar metaplasia of the alveolar epithelium and interstitial mononuclear cell infiltration occurred in 10, 30, and 100 mg/kg males.
  • The incidence of interstitial mononuclear cell infiltration was also significantly increased in 100 mg/kg females.
  • Significantly increased incidences of hematopoietic cell proliferation of the spleen occurred in males administered 10 mg/kg or greater.
  • Significantly increased incidences of pigmentation, alveolar epithelium squamous metaplasia (except 10 mg/kg females), and alveolar epithelium bronchiolar metaplasia occurred in all dosed groups of males and females.
  • A significant dose-related increase in hepatic toxicity was observed in dosed rats and was characterized by increased incidences of numerous lesions including hepatocyte hypertrophy, centrilobular degeneration, hepatocellular necrosis, pigmentation, fatty change, bile duct hyperplasia, oval cell hyperplasia, nodular hyperplasia, hematopoietic cell proliferation, eosinophilic focus, mixed cell focus, multinucleated hepatocytes, bile duct cyst, toxic hepatopathy, and cholangiofibrosis.
  • Significantly increased incidences of gingival squamous cell carcinoma within the oral mucosa occurred in 10 mg/kg males and 100 mg/kg males and females.
  • The incidences of gingival squamous hyperplasia and cystic keratinizing hyperplasia in dosed groups of males and females were generally significantly increased.
  • The incidences of follicular cell adenoma (single or multiple) of the thyroid gland in 30 and 100 mg/kg males were significantly greater than that in the vehicle control group.
  • The incidences of follicular cell hypertrophy, follicular cell hyperplasia, and inflammation were significantly increased in 30 and 100 mg/kg males.
  • Three incidences of single or multiple squamous cell papilloma of the forestomach occurred in 100 mg/kg females, and single incidences of squamous cell carcinoma of the forestomach occurred in 10 and 100 mg/kg females.
  • [MeSH-minor] Animals. Body Weight / drug effects. Carcinogenicity Tests. Dose-Response Relationship, Drug. Female. Humans. Male. Mice. Mice, Inbred Strains. Organ Size / drug effects. Rats. Rats, Sprague-Dawley

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  • (PMID = 21383777.001).
  • [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 / Azo Compounds; 0 / Chlorobenzenes; 14047-09-7 / 3,4,3',4'-tetrachloroazobenzene
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7. Lien HC, Lu YS, Shun CT, Yao YT, Chang WC, Cheng AL: Differential expression of glucocorticoid receptor in carcinomas of the human digestive system. Histopathology; 2008 Feb;52(3):314-24
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  • GR expression was strong in oesophageal squamous epithelia, pancreatic islet cells and hepatocytes, but generally weak or negative in non-squamous epithelia.
  • Consistently, GR expression was found in a high percentage of oesophageal squamous cell carcinomas (SCC) (98.1%) and hepatocellular carcinomas (HCC) (92.9%), but rarely in gastric adenocarcinomas (7.4%) and not at all in colorectal adenocarcinomas (0%).
  • The general lack of GR in adenocarcinomas contrasts with the high percentage of SCCs and HCCs expressing GR, and, along with the generation of chemoresistance by DEX, warrants prospective study of the effects of steroids on these cancers.
  • [MeSH-major] Adenocarcinoma / metabolism. Biomarkers, Tumor / metabolism. Carcinoma, Basosquamous / metabolism. Carcinoma, Squamous Cell / metabolism. Digestive System Neoplasms / metabolism. Receptors, Glucocorticoid / metabolism
  • [MeSH-minor] Ampulla of Vater / metabolism. Ampulla of Vater / pathology. Antineoplastic Combined Chemotherapy Protocols / pharmacology. Bile Ducts, Intrahepatic / metabolism. Bile Ducts, Intrahepatic / pathology. Cell Line, Tumor. Cell Survival / drug effects. Cholangiocarcinoma / metabolism. Cholangiocarcinoma / mortality. Cholangiocarcinoma / pathology. Common Bile Duct Neoplasms / metabolism. Common Bile Duct Neoplasms / mortality. Common Bile Duct Neoplasms / pathology. DNA, Neoplasm / analysis. Dexamethasone / pharmacology. Drug Resistance, Neoplasm / drug effects. Humans. Immunoenzyme Techniques. Sequence Analysis, DNA. Survival Rate

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  • (PMID = 18269582.001).
  • [ISSN] 1365-2559
  • [Journal-full-title] Histopathology
  • [ISO-abbreviation] Histopathology
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / DNA, Neoplasm; 0 / Receptors, Glucocorticoid; 7S5I7G3JQL / Dexamethasone
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8. National Toxicology Program: NTP toxicology and carcinogenesis studies of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) (CAS No. 57465-28-8) in female Harlan Sprague-Dawley rats (Gavage Studies). Natl Toxicol Program Tech Rep Ser; 2006 Jan;(520):4-246
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds" (DLCs).
  • The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD that is the most potent congener.
  • This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR.
  • Manufacture and use of the chemical was stopped because of increased PCB residues in the environment, but it continues to be released into the environment through the use and disposal of products containing PCBs, as by-products during the manufacture of certain organic chemicals, and during combustion of some waste materials.
  • Bioaccumulation of PCB 126 results in persistent levels in animal and human tissues and the biological responses to PCB 126 are similar to those of TCDD, a known human carcinogen.
  • HEPATIC CELL PROLIFERATION DATA: To evaluate hepatocyte replication, analysis of labeling of replicating hepatocytes with 5-bromo-2'-deoxyuridine was conducted at the 14-, 31-, and 53-week interim evaluations.
  • At 2 years, a significant dose-related increase in hepatic toxicity was observed and was characterized by increased incidences of numerous lesions including hepatocyte hypertrophy, multinucleated hepatocytes, diffuse fatty change, bile duct hyperplasia, bile duct cyst, oval cell hyperplasia, necrosis, pigmentation, inflammation, nodular hyperplasia, portal fibrosis, cholangiofibrosis, and toxic hepatopathy.
  • At 2 years, treatment related increases in the incidences of cystic keratinizing epithelioma and squamous cell carcinomas were observed.
  • In addition, dose-related increases in the incidences of bronchiolar metaplasia of the alveolar epithelium and squamous metaplasia were also observed.
  • The incidence of gingival squamous cell carcinoma of the oral mucosa was significantly increased in the 1,000 ng/kg core study group at 2 years.
  • Gingival squamous cell carcinoma, although reduced in incidence as compared to the 1,000 ng/kg core study group, was still present in the 1,000 ng/kg stop-exposure group.
  • [MeSH-minor] Animals. Body Weight / drug effects. Carcinogenicity Tests. Cell Proliferation / drug effects. Chemistry, Pharmaceutical. Female. Hepatocytes / drug effects. Liver / pathology. Male. Neoplasms / chemically induced. Neoplasms / pathology. Nutritional Physiological Phenomena. Organ Size / drug effects. Quality Control. Rats. Rats, Sprague-Dawley. Survival Analysis. Thyroid Hormones / blood

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  • (PMID = 16628245.001).
  • [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 / Thyroid Hormones; DFC2HB4I0K / Polychlorinated Biphenyls; TSH69IA9XF / 3,4,5,3',4'-pentachlorobiphenyl
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