Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diallyl sulfide (DAS) is a principal thioether of garlic (Allium sativum) accounting, in part, for the flavor and fragrance of this herb. Previous studies have shown that DAS is a potent inhibitor of experimentally induced colon cancer in mice. Metabolic studies of other garlic-derived substances suggested that DAS could prevent tumorigenicity of other hepatic activated carcinogens. The present study was designed to determine whether DAS could inhibit the DNA-damaging and tumorigenic effects of N-nitrosomethylbenzylamine in rat esophagus. A dose of 200 mg/kg of DAS given p.o. 3 h prior to N-nitrosomethylbenzylamine administration was found to inhibit the carcinogen-induced nuclear toxicity by 64% to 56% at the two doses (3 and 5 mg/kg) of NMBA tested. These results suggested that the compound was potentially anticarcinogenic. In the carcinogenicity experiment it was found that DAS totally inhibited tumor formation in rats treated with a carcinogenic dose of NMBA (100% inhibition of papilloma and squamous cell carcinoma incidence, P less than 0.0001). Additionally DAS was found to substantially reduce hepatic microsomal metabolism of the carcinogen. These data demonstrate that DAS is unique in its anticarcinogenic activity. It strongly suppresses the tumorigenic effects of potent, metabolically activated monoalkylating carcinogens in the gastrointestinal tract.
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PMID:Chemoprevention of N-nitrosomethylbenzylamine-induced esophageal cancer in rats by the naturally occurring thioether, diallyl sulfide. 318 95

Cancer risk was studied in 781 male Seventh-Day Adventists (SDA) and 808 male members of other temperance societies. Standardized morbidity ratios for all cancers were 0.69 among SDA and 1.05 among other temperants. Significantly decreased risks of cancers were noted among SDA for cancer of the colon [observed/expected (O/E): 0.13], cancer of the respiratory system (O/E: 0.17), cancer of the lung (O/E: 0.15), and cancer of the bladder including papilloma (O/E: 0.13). No significant deviations from expectations were noted among members of other temperance societies. Thus risks of tobacco-associated cancers were markedly decreased among SDA. The risk of alcohol-associated cancers (cancers of the oral cavity, pharynx, esophagus, and larynx) taken together was also decreased (O/E: 0.7), although not significantly so. When the results were compared with those of a previous study of Danish brewery workers who had a high average daily beer intake, the present investigation provides further support that the alleged association between beer consumption and the occurrence of rectal cancer is of a noncausal nature. The explanation for the decreased risk of colon cancer should probably be sought in the dietary practices of SDA.
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PMID:Cancer risk among Danish male Seventh-Day Adventists and other temperance society members. 657 68

To study the antitumor effect of local production of interleukin-2 (IL-2) from tumor cells, the poorly immunogenic murine colon cancer cells, colon26, was transfected with murine IL-2 cDNA in a bovine papilloma virus vector. IL-2 gene transfectants (mIL2 + colon26) did not alter their growth rate compared with parental colon26 cells in vitro, but reduced their tumorigenicity in vivo. Immunization with mIL2 + colon26 cells could induce protective immunity against parental colon26 cells. Following intravenous challenges, the colonies of lung metastasis were also inhibited. Moreover, inoculation of mIL2 + colon26 cells slowed the growth of challenged renal cell carcinoma cells, RenCa. Intraperitoneal inoculation of IL-2 gene transfectants generated a large number of peritoneal exudate cells and these cells had a highly cytolytic activity against colon26 and YAC-1. These results suggest that inoculation with IL-2 transfected tumor cells can stimulate not only cytotoxic T lymphocytes but also natural killer cells, and that these cells will act as antitumor effector cells in host animals.
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PMID:Induction of tumor-specific cytotoxic T lymphocytes and natural killer cells by tumor cells transfected with the interleukin-2 gene. 782 64

1-Amino-2,4-dibromoanthraquinone is an anthraquinone-derived vat dye, a member of a class of insoluble dyes that are impregnated into textile fibers. Five anthraquinone-derived dyes with representative and diverse structures, as well as the parent chemical, anthraquinone, were selected for NTP Toxicology and Carcinogenesis evaluation. Similar to the benzidine dye initiative, the rationale for selecting these vat dyes was to generate sufficient toxicologic data to permit more reliable predictions of carcinogenicity to be made on other chemicals in this class, thereby eliminating or reducing the need to study every anthraquinone dye. 1-Amino-2,4-dibromoanthraquinone is the last anthraquinone-derived dye in this group to be studied. Groups of male and female F344/N rats and B6C3F1 mice were exposed to 1-amino-2,4-dibromoanthraquinone (87% to 97% pure) for 13 weeks or for 9, 15, or 24 months. Because 1-amino-2,4-dibromoanthraquinone was predicted to be carcinogenic, these studies were designed to evaluate the potential for tumor progression and regression. Absorption and excretion studies were carried out in male F344/N rats. Genetic toxicity was determined in vitro using Salmonella typhimurium and cultured Chinese hamster ovary cells. Extensive chemical analyses were performed to identify and characterize impurities of the 1-amino-2,4-dibromoanthraquinone used in these studies. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were given 0, 2,500, 5,000, 10,000, 25,000, or 50,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 13 weeks. These levels correspond to approximately 150 to 3,200 mg 1-amino-2,4-dibromoanthraquinone/kg body weight per day for males and to approximately 170 to 3,200 mg/kg for females. Chemical-related mortality was limited to one male and one female in the 50,000 ppm groups. Final mean body weights and body weight gains of all exposed groups of rats were significantly lower than those of the controls. Feed consumption by all exposed groups was less than that by the controls throughout the study and generally decreased with increasing exposure concentration. Pink-red staining of the fur and tail was observed in all exposed groups. Absolute and relative liver weights of all exposed groups were generally significantly greater than those of the controls. Chemical-related lesions were present in the liver, kidney, and spleen of male and female rats. Nonneoplastic lesions in the liver included foci of hepatocellular alteration, diffuse hepatocellular hypertrophy (cytomegaly), hepatocellular cytoplasmic vacuolation, bile duct hyperplasia, inflammation, and pigmentation. These differences were observed primarily in the 25,000 and 50,000 ppm groups of males and females; the spectrum of proliferative lesions of the bile ducts (hyperplasia, fibrosis, and necrotizing cholangitis) in the 25,000 and 50,000 ppm groups was morphologically consistent with the lesion described as cholangiofibrosis. Pigmentation was present in the renal tubule epithelium of all groups of exposed rats; nuclear enlargement (karyomegaly) was also present in the renal tubule epithelium in some of the exposed rats. Accumulation of hyaline droplets in the cytoplasm of the renal tubule epithelium and tubule lumina was present in 2,500, 5,000, 10,000, and 25,000 ppm males. Incidences of hematopoiesis of the spleen in exposed groups of males and females were increased compared to those in the controls. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were given 0, 2,500, 5,000, 10,000, 25,000, or 50,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 13 weeks. These levels correspond to approximately 500 to 10,600 mg 1-amino-2,4-dibromoanthraquinone/kg body weight per day for males and approximately 660 to 11,700 mg/kg per day for females. There was no chemical-related mortality. Feed consumption and final mean body weights of exposed groups were similar to those of the controls. Red staining of the fur was observed in all exposed groups. Absolute and relative liver weights of the exposed groups were greater than those er than those of the controls except for the absolute liver weight of 2,500 ppm males. Absolute and relative kidney weights of 25,000 and 50,000 ppm males were lower than those of the controls. Chemical-related lesions were limited to the livers of males and consisted of pigmentation of hepatocytes at all exposure concentrations and centrilobular hepatocellular hypertrophy at 10,000, 25,000, and 50,000 ppm. Minimal pigment was present in the liver of one female in the 25,000 ppm group and in one female in the 50,000 ppm group. 2-YEAR STUDY IN RATS: Groups of 70 male and 70 female rats were given 0, 5,000, or 10,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 103 weeks. In addition, groups of 50 male and 50 female rats were given 2,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 104 weeks. These exposure concentrations were approximately equal to 90, 240, or 490 mg 1-amino-2,4-dibromoanthraquinone/kg body weight for males and 110, 285, or 600 mg/kg for females. Ten animals from each group were evaluated for histopathology at 9 months. Additional groups of 10 animals from the 0 and 10,000 ppm groups were evaluated for histopathology at 15 months. Survival, Body Weights, Feed Consumption, and Clinical Findings In the 2-year study, survival of the 10,000 ppm males and females was significantly lower than that of the controls. Survival of the 2,000 and 5,000 ppm groups was similar to that of the controls. During the last year of the study, the mean body weights of exposed males were 80% to 91% those of controls, and the mean body weights of exposed females were 67% to 84% those of controls. Feed consumption among exposed groups was generally similar, but was less than that by controls. The fur and urine of all exposed male and female groups were discolored. Pathology Findings In the 2-year study, 1-amino-2,4-dibromoanthraquinone was associated with significant chemical-related increases in the incidences of benign and malignant neoplasms in the liver, large intestine, kidney, and urinary bladder of males and females. Chemical-related nonneoplastic proliferative and degenerative lesions occurred in the liver, kidney, urinary bladder, and forestomach of males and females. The incidences of foci of hepatocellular alteration and pigmentation in the liver of males and females were increased at the 9-month interim evaluation, and a hepatocellular adenoma was present in one 5,000 ppm male. At the 15-month interim evaluation, hepatocellular adenoma or carcinoma (combined) occurred in all males and nine females in the 10,000 ppm groups. By the end of the 2-year study, hepatocellular adenoma, carcinoma, cholangioma, or cholangiocarcinoma were observed in males and females in the 5,000 and 10,000 ppm groups. In the 2,000 ppm groups, similar liver neoplasms were present in 63% of the males and in 83% of the females. Of the hepatocellular carcinomas in the 5,000 and 10,000 ppm groups of males and females, 31% to 49% were metastatic to the lungs or other sites. Increases in the incidences of foci of hepatocellular alteration (basophilic, eosinophilic, and clear cell) and pigmentation of the liver were also observed in exposed groups of males and females. Adenomatous polyps (adenoma) of the large intestine were present in six 10,000 ppm males at the 15-month interim evaluation. Incidences of adenomatous polyp (adenoma) and carcinoma of the large intestine were significantly increased in exposed groups of males and females after 2 years; multiple benign and malignant intestinal neoplasms were observed in many of these rats. In the kidney, incidences of renal tubule adenoma and carcinoma were significantly increased in exposed groups of males and females after 2 years. Renal tubule adenomas were present in two 10,000 ppm males at 15 months. There were also chemical-related increases in the incidences and severities of renal tubule epithelial hyperplasia, pigmentation, and transitional cell hyperplasia in the kidney of males and females. Hyaline droplet accumulation was present in all exposed male rats at 9 months. Incidences of transitional cell papilloma and carcinoma of the urinary bladder were increased at 2 years in males and females in the 10,000 ppm groups. Transitional cell hyperplasia was observed in exposed males and females at the 15-month interim evaluation. Other nonneoplastic lesions observed in the urinary bladder at 2 years included metaplasia of the transitional epithelium and submucosal stromal tissue. In the forestomach, the incidences and severities of inflammation, ulceration, hyperkeratosis, and hyperplasia of the squamous mucosa were increased in all exposed groups of males and females at 2 years, but not at the 9- or 15-month interim evaluations. In exposed males and females, the incidences of mononuclear cell leukemia were significantly decreased. The incidences of atrophy of the seminal vesicle were increased in exposed male rats in the 2-year study. Stop-Exposure Evaluation in Rats Groups of 40 male and 40 female rats were given 20,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 9 or 15 months. At 9 months, 10 males and 10 females were evaluated for histopathology (9-month interim evaluation groups). After 9 months of exposure, an additional 10 males and 10 females were fed control diet until the end of the 15-month evaluation (9-month stop-exposure groups), and 20 males and 20 females continued to receive 20,000 ppm 1-amino-2,4-dibromoanthraquinone until the end of the evaluation (15-month exposure groups). The approximate daily consumption of 1-amino-2,4-dibromoanthraquinone was 1,335 mg/kg for males and 1,790 mg/kg for females in the 9-month stop-exposure groups and 1,115 mg/kg for males and 1,435 mg/kg for females in the 15-month exposure groups. Survival was similar among groups except for the females in the 15-month exposure group; the survival of this group was lower than that of the controls. Lower mean body weights were related to increased exposure duration. The mean body weights of exposed males were 76% to 82% that of controls, and the mean body weights of exposed females were 73% to 84% that of controls. For the stop-exposure evaluation, similar chemical-related neoplasms and nonneoplastic lesions were observed in the same sites as in the 2-year study: liver, large intestine, kidney, urinary bladder, and forestomach. After 9 months of dietary exposure to a concentration of 20,000 ppm 1-amino-2,4-dibromoanthraquinone, hepatocellular adenoma and carcinoma occurred in males and females. Nonneoplastic chemical-related lesions in the liver of exposed rats included pigmentation, focal hepatocellular alteration, and bile duct hyperplasia. Neoplasms at other sites in males included one adenomatous polyp (adenoma) in the large intestine and one transitional cell papilloma in the urinary bladder. Hyaline droplet accumulation was present in the kidney of exposed males at 9 months. In the stop-exposure groups examined at 15 months, hepatocellular adenoma and carcinoma were present in most males and females. Adenomatous polyp (adenoma) of the colon, renal tubule cell adenoma, and urinary bladder transitional cell papilloma and carcinoma also occurred in males and females. Nonneoplastic chemical-related lesions included foci of hepatocellular alteration in the liver and hyperplasia of the renal tubule epithelium and urinary bladder transitional epithelium. Hyperplasia, hyperkeratosis, inflammation, and ulceration were observed in the forestomach of some male and female rats continuously exposed for 15 months. 2-YEAR STUDY IN MICE: Groups of 60 male and 60 female mice were given 0, 10,000, or 20,000 ppm 1-amino-2,4-dibromoanthraquinone in feed for 104 weeks. The daily compound consumption was approximately 1,690 or 3,470 mg 1-amino-2,4-dibromoanthraquinone/kg body weight for males and 1,950 or 4,350 mg/kg for females. Ten animals from each group were evaluated for histopathology at 15 months. Survival, Body Weights, Feed Consumption, and Clinical Findings In the 2-year study, survival of exposed males was significantly lower than that of the controls. Survival of exposed females was similar to that of the controls. The final mean body weights of exposed males were 83% to 85% that of controls, and the final mean body weights of exposed females were 81% to 86% that of controls. Feed consumption by exposed groups was generally similar to that by controls. Discoloration of the fur, urine, and feces was observed in all exposed groups. Pathology Findings In the 2-year study, 1-amino-2,4-dibromoanthraquinone was associated with significant chemical-related increases in the incidences of benign and malignant neoplasms in the liver, forestomach, and lung of males and females. Incidences of hepatocellular adenoma and carcinoma were increased in exposed groups at the 15-month interim evaluation and at 2 years. At 2 years, there were significant increases in the incidences of multiple hepatocellular adenoma and carcinoma in males and females and in the incidences of hepatoblastoma in males. Centrilobular hypertrophy of hepatocytes in males and foci of hepatocellular alteration and pigmentation in the liver of males and females were also chemical-related changes. Sqamous cell papilloma of the forestomach mucosa occurred in 10,000 ppm females and 20,000 ppm males and females at the 15-month interim evaluation, and the incidences of squamous cell papilloma and carcinoma were significantly increased in exposed groups of males and females at 2 years. Chemical-related hyperplasia of forestomach epithelium was also present at 15 months and at 2 years. Alveolar/bronchiolar adenomas were present only in the exposed groups of males and females at 15 months, and the incidences of alveolar/bronchiolar adenoma were significantly increased in exposed males and females at 2 years. The incidences of multiple alveolar/bronchiolar adenomas were also increased in exposed males. In the kidney, pigmentation was present in the renal tubules of most mice after 2 years of exposure. DISPOSITION AND METABOLISM STUDIES: Adult male F344/N rats were given [14C]-labeled 1-amino-2,4-dibromoanthraquinone as a single intravenous dose of 0.4 mg/kg body weight or as a single oral dose of 2, 23, 118, 814, or 1,473 mg/kg. A 6-hour bile cannulation study was also performed. From day 0 through day 3 after intravenous administration, about 50% of the 14C was excreted in the feces, 15% in the urine, and 6% in expired air. Unmetabolized 1-amino-2,4-dibromoanthraquinone accounted for less than 3% of the excreted 14C after intravenous administration. For oral doses administered, the amount of the dose that was absorbed fit the equation: absorbed dose = 6.6 x log(dose). After intravenous administration, the metabolites of 1-amino-2,4-dibromoanthraquinone in blood were primarily in the plasma fraction (blood:plasma ratio of approximately 0.5:1). The highest concentrations of 14C in tissues 15 minutes after intravenous dosing were in excretory organs, lung, kidney, small intestine, liver, adipose tissue, and adrenal gland. GENETIC TOXICOLOGY: 1-Amino-2,4-dibromoanthraquinone was mutagenic in Salmonella typhimurium strains TA98 and TA1537 in the absence of S9; with S9, an equivocal response was observed in TA1537. 1-Amino-2,4-dibromoanthraquinone resulted in an equivocal response in TA100 with and without S9, and no mutagenic activity was detected with strain TA1535. In cultured Chinese hamster ovary cells, 1-amino-2,4-dibromoanthraquinone induced sister chromatid exchanges with and without S9; chromosomal aberrations were induced in the absence of S9. CONCLUSIONS: Under the conditions of these 2-year feed studies, there was clear evidence of carcinogenic activity of 1-amino-2,4-dibromoanthraquinone in male and female F344/N rats based on increased incidences of neoplasms in the liver, large intestine, kidney, and urinary bladder. There was clear evidence of carcinogenic activity of 1-amino-2,4-dibromoanthraquinone in male and female B6C3F1 mice based on increased incidences of neoplasms in the liver, forestomach, and lung. Exposure of male and female rats to 1-amino-2,4-dibromoanthraquinone for 2 years was associated with basophilic focus (males only), clear cell focus, eosinophilic focus, and pigmentation in the liver; renal tubule hyperplasia, renal tubule pigmentation, and transitional cell hyperplasia in the kidney; transitional cell hyperplasia, squamous metaplasia, and stromal metaplasia (females only) in the urinary bladder; squamous hyperplasia, hyperkeratosis, ulceration, and inflammation of the forestomach mucosa; and seminal vesicle atrophy. Exposure of male and female mice to 1-amino-2,4-dibromoanthraquinone for 2 years was associated with centrilobular hepatocellular hypertrophy (males only), basophilic focus, clear cell focus (females only), eosinophilic focus, and pigmentation in the liver; pigmentation in the kidney; and hyperplasia, basal cell hyperplasia, hyperkeratosis, and inflammation of the forestomach mucosa. Synonym: ADBAQ
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PMID:NTP Toxicology and Carcinogenesis Studies of 1-Amino-2,4-Dibromoanthraquinone (CAS No. 81-49-2) in F344/N Rats and B6C3F1 Mice (Feed Studies). 1269 53

The absorption of water, sodium, and potassium from isolated segments of the large intestine has been studied in 11 patients. In eight control segments adjacent to a carcinoma of the colon, absorption of water and sodium and secretion of potassium occurred. In five segments of intestine containing a villous papilloma, water, sodium, and potassium were secreted. The difference is mainly due to an increase in exsorption of sodium and water, insorption being relatively unaffected.
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PMID:THE ABSORPTION OF WATER, SODIUM, AND POTASSIUM IN THE LARGE INTESTINE WITH PARTICULAR REFERENCE TO THE EFFECTS OF VILLOUS PAPILLOMAS. 1408 49

Human papilloma viruses (HPVs) are the main tumor viruses in humans and have been identified in gynecological malignancies, especially carcinomas of the uterine cervix and their precursor lesions. In addition, they are frequently observed in other anogenital tumors such as vulva/vagina, anal and penis carcinoma. Furthermore, the potential association with head and neck cancer, in particular tonsillar carcinoma, is now well documented. However, there are controversial reports on the detection of HPV in various other tumors; these are summarized in the present report. Data revealed that apart from the heart and the kidney, the virus has been found in all other organs that have been analyzed so far, i.e., prostate, urinary bladder, oral cavity, larynx, esophagus, stomach, colon, liver, vagina/vulva, endometrium, ovary, breast, penis, anus, skin, and lung. Some of the detection rates are remarkable, e.g., colon cancer up to 97%, lung cancer 80%, and breast cancer 74%. They point to geographical differences in the incidence of HPV in different populations, but also highlight the need for validation of the results. HPV is nevertheless an important biomarker in molecular tumor diagnostics. Firstly, it is useful for the differentiation of a secondary squamous cell carcinoma from a metastasis. Secondly, HPV-positive carcinomas not only have a distinct etiology but also a particular morphological phenotype. Overall, they are characterized by different tumor biology, such as, for example, increased sensitivity to radiotherapy.
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PMID:[HPV in non-gynecological tumors]. 1903 15

Microbiome studies show altered microbiota in head and neck squamous cell carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity. These studies utilized a traditional bioinformatics methodology, which allows for accurate taxonomic assignment down to the genus level, but cannot accurately resolve species level membership. We applied Resphera Insight, a high-resolution methodology for 16S rRNA taxonomic assignment that is able to provide species-level context in its assignments of 16S rRNA next generation sequencing (NGS) data. Resphera Insight applied to saliva samples from HNSCC patients and healthy controls led to the discovery that a subset of HNSCC saliva samples is significantly enriched with commensal species from the vaginal flora, including Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus vaginalis (52x higher in saliva). These species were not observed in normal saliva from Johns Hopkins patients, nor in 16S rRNA NGS saliva samples from the Human Microbiome Project (HMP). Interestingly, both species were only observed in saliva from Human Papilloma Virus (HPV) positive and HPV negative oropharyngeal cancer patients. We confirmed the representation of both species in HMP data obtained from mid-vagina (n=128) and vaginal introitus (n=121) samples. Resphera Insight also led to the discovery that Fusobacterium nucleatum, an oral cavity flora commensal bacterium linked to colon cancer, is enriched (600x higher) in saliva from a subset of HNSCC patients with advanced tumors stages. Together, these high-resolution analyses on 583 samples suggest a possible role for bacterial species in the therapeutic outcome of HPV positive and HPV negative HNSCC patients.
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PMID:High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and chemo-radiation. 2934 28