Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of cutaneous malignancies and non-Hodgkin lymphomas is higher in transplant recipients than in the general population. From 1968 to 1984, 200 kidney grafts were transplanted to 180 patients with end-stage renal disease. All patients were on azathioprine (Aza) and prednisolone. In selected cases ALG and/or small doses of CsA were added. Six patients developed malignant tumors (two Kaposi sarcoma, one squamous cell and one squamous plus basal cell skin cancers, one reticulosarcoma, and one glioma). Mean age of patients was 43 years (range 35-53 years), and mean time of appearance of the tumor after transplantation was 62 months (range 24-98 months). Treatment consisted of reduction of the dosage of Aza, surgical removal or local irradiation of the tumor, and chemotherapy in case of systemic involvement (two cases). Three patients died (one Kaposi sarcoma, one reticulosarcoma, and one glioma) 3 to 6 months after diagnosis, and all three had previously been on high doses of Aza. The remaining three cases (one Kaposi) were cured by stopping or decreasing Aza, by excision, and/or local irradiation of the tumor. It seems that late diagnosis and Aza in high dosage are the main factors leading to the rapid dissemination of the initially localized tumor.
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PMID:Cancer in renal transplant recipients. 352 17

Isoprene, the monomeric unit of natural rubber and naturally occurring terpenes and steroids, is primarily obtained as a by-product of naphtha cracking for ethylene production. It is emitted from plants and trees, has been detected in tobacco smoke and automobile exhaust, and was identified as a major endogenous hydrocarbon in human breath. Isoprene was selected for toxicologic evaluation because of its structural similarity to 1,3-butadiene, a potent, multi-organ, rodent carcinogen, and the potential for human exposure due to its large annual production volume. A previous 26-week inhalation study followed by a 26-week recovery period provided clear evidence of carcinogenic activity of isoprene in male B6C3F1 mice. A similar study in male F344/N rats was inconclusive. Male and female F344/N rats were exposed to isoprene (99% pure) by whole body inhalation for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, mouse bone marrow and peripheral blood cells, and rat lung fibroblasts. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female F344/N rats were exposed to 220, 700, or 7,000 ppm isoprene by inhalation, 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights: Survival rates and mean body weights of exposed male and female rats were similar to those of the chamber controls throughout the study. Urinary Vinyl Lactic Acid - Biomarker of Exposure: At 3, 6, 12, and 18 months, the concentrations of vinyl lactic acid normalized to creatinine in the urine increased with increasing exposure concentration in all exposed groups of male and female rats; however, these increases were not proportional to isoprene exposure concentrations, indicating nonlinear metabolism over this range of exposure concentrations. Pathology Findings: Exposure-related increases in the incidences of mam mary gland fibroadenoma were observed in male rats in all groups. The incidences of fibroadenoma in 7,000 ppm males and in all groups of exposed females were significantly greater than those in the chamber control groups. The incidences of fibroadenoma in all exposed groups of males and females and of multiple fibroadenoma in 7,000 ppm males and in all groups of exposed females exceeded the historical control ranges. In addition, the finding of mammary gland carcinoma in exposed male rats was noteworthy because this neoplasm rarely occurs in control male rats. The incidences of renal tubule adenoma in 700 and 7,000 ppm males and of renal tubule hyperplasia in 7,000 ppm males were significantly greater than those in the chamber controls. The severity of kidney nephropathy was slightly increased in 7,000 ppm males when compared to chamber controls. An exposure-related increase in the incidences of interstitial cell adenoma of the testis was observed in male rats. The incidences of bilateral interstitial cell adenoma and of unilateral and bilateral interstitial cell adenoma (combined) of the testis in 700 and 7,000 ppm males were significantly greater than those in the chamber controls. The incidences of interstitial cell adenoma in 700 and 7,000 ppm males exceeded the historical control range. Several rare neoplasms including benign astrocytoma, malignant glioma, malignant medulloblastoma be nign meningeal granular cell tumor, and meningeal sarcoma were observed in the brain of exposed female rats. These neoplasms have seldom or never occurred in historical chamber controls. The incidences of splenic fibrosis in 700 and 7,000 ppm males were significantly greater than that in the chamber control group. GENETIC TOXICOLOGY: Isoprene was not mutagenic in S. typhimurium and did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells with or without exogenous metabolic activation; however, in mice, isoprene induced increases in the frequency of sister chromatid exchanges in bone marrow cells and in the frequency of micronucleated erythrocytes in peripheral blood. The cell cycle duration of proliferating bone marrow cells of mice f mice exposed to 7,000 ppm isoprene was significantly lengthened. No increases in the frequency of chromosomal aberrations were observed in bone marrow cells of male mice after 12 days of exposure to isoprene, and lung fibroblasts of male and female rats exposed to isoprene for 4 weeks showed no increase in the frequency of micronuclei. CONCLUSIONS: Under the conditions of this 2-year inhalation study, there was clear evidence of carcinogenic activity of isoprene in male F344/N rats based on increased incidences of mammary gland fibroadenoma and carcinoma, renal tubule adenoma, and testicular interstitial cell adenoma. There was some evidence of carcinogenic activity of isoprene in female F344/N rats based on increased incidences and multiplicity of mammary gland fibroadenoma. A low incidence of rare brain neoplasms in exposed female rats may have been due to exposure to isoprene. Exposure to isoprene by inhalation for 2 years resulted in increased incidences of renal tubule hyperplasia and splenic fibrosis in male rats. Synonyms: Isopentadiene; b-methylbivinyl; 2-methyl-1,3-butadiene
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PMID:NTP Toxicology and Carcinogenesis Studies of Isoprene (CAS No. 78-79-5) in F344/N Rats (Inhalation Studies). 1257 89

4-Hexylresorcinol, which is used as an anthelmintic and antiseptic, was nominated by the National Cancer Institute for study. Toxicology and carcinogenesis studies were conducted by administering 4-hexylresorcinol (greater than 99% pure) in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 13 weeks, or 2 years. Sixteen-Day and Thirteen-Week Studies: In the 16-day studies, groups of five rats and five mice of each sex were administered 0, 31.3, 62.5, 125, 250, or 500 mg/kg 4-hexylresorcinol. Survival was not affected. Decreased body weights were seen in male rats that received 250 or 500 mg/kg 4-hexylresorcinol. No other effects were observed. In the 13-week studies, groups of 10 rats and 10 mice of each sex were administered 0, 62.5, 125, 250, 500, or 1,000 mg/kg of the chemical, 5 days per week. All rats and male mice and 9/10 female mice that received 1,000 mg/kg died before the end of the studies. Final mean body weights of male rats that received 250 or 500 mg/kg were 22% or 38% lower than that of the vehicle controls; final mean body weights of female rats that received 250 or 500 mg/kg were 16% or 9% lower. No compound-related gross or microscopic pathologic effects were observed in rats. No body weight effects were observed for mice. Mild to moderate nephropathy was dose related in male and female mice. Based on these results, 2-year toxicology and carcinogenesis studies of 4-hexylresorcinol were conducted by administering 0, 62.5, or 125 mg/kg to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex, 5 days per week. Body Weight and Survival in the Two-Year Studies: Mean body weights of high dose male rats were 7%-11% lower than those of the vehicle controls throughout the study. Mean body weights of low dose male and dosed female rats were similar to those of the vehicle controls. The body weights of dosed male and dosed female mice were comparable to those of vehicle controls except during the last 16 weeks of the studies, when body weights were 6%-16% lower in the dosed groups. No significant differences in survival were observed between any groups of rats or mice of either sex (male rats: vehicle control, 30/50; low dose, 29/50; high dose, 33/50; female rats: 28/50; 32/50; 30/50; male mice: 36/50; 26/50; 30/50; female mice: 35/50; 32/50; 35/50). Nonneoplastic and Neoplastic Lesions in the Two-Year Studies: Two astrocytomas and an oligodendroglioma were observed in high dose male rats, a glioma was observed in one low dose male rat, and an oligodendroglioma was observed in one vehicle control male rat. These neoplasms were not considered to be related to 4-hexylresorcinol administration. Focal medullary hyperplasia of the adrenal gland was observed at increased incidences in dosed male mice (5/50; 16/50; 10/49). Pheochromocytomas in male mice occurred with a marginal upward trend (1/50; 2/50; 5/49). Historically, these neoplasms are observed in about 1% of corn oil vehicle control B6C3F1 male mice. The incidences of neoplasms of the harderian gland in male mice were slightly increased over those in the vehicle controls (adenomas or carcinomas, combined: 0/50; 4/50; 3/50). Decreases were observed in the incidences of mononuclear cell leukemia in dosed male (12/49; 7/50; 1/50) and female (16/50; 3/50; 2/50) rats, hepatocellular adenomas or carcinomas (combined) in dosed male mice (21/50; 9/50; 9/50), and circulatory system tumors in male (10/50; 4/50; 2/50) and female (6/50; 2/49; 0/50) mice. These decreased incidences of tumors in rats and mice are considered to be possibly related to 4-hexylresorcinol administration. The incidences and severity of nephropathy (male: 39/50; 43/50; 47/50; female: 7/50; 40/49; 47/50) and incidences of osteosclerosis (male: 5/50; 5/50; 15/50; female: 21/50; 25/49; 40/50) were increased in both dosed male and female mice and are considered to be related to chemical exposure. Genetic Toxicology: 4-Hexylresorcinol was not mutagenic for Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without S9 metabolic activation. 4-Hexylre, TA1535, or TA1537 with or without S9 metabolic activation. 4-Hexylresorcinol induced forward mutations at the TK locus in mouse L5178Y cells in the presence of S9; no response was observed in the absence of metabolic activation. In cytogenetic assays with cultured Chinese hamster ovary (CHO) cells, 4-hexylresorcinol caused an increase in the frequency of sister chromatid exchanges (SCEs) in the absence of metabolic activation; no induction of SCEs was observed in the presence of S9. Chromosomal aberrations were not induced in CHO cells with or without metabolic activation. Data Audit: The data, documents, and pathology materials from the 2-year studies of 4-hexylresorcinol were audited at the NTP Archives. The audit findings show that the conduct of the studies is documented appropriately and support the data and results given in this Technical Report. Conclusions: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of 4-hexylresorcinol for male or female F344/N rats given doses of 62.5 or 125 mg/kg. There was equivocal evidence of carcinogenic activity of 4-hexylresorcinol for male B6C3F1 mice, as shown by marginally increased incidences of pheochromocytomas (and hyperplasia) of the adrenal medulla and of harderian gland neoplasms. There was no evidence of carcinogenic activity for female B6C3F1 mice given doses of 62.5 or 125 mg/kg 4-hexylresorcinol. Decreased incidences of three tumors types were considered related to 4-hexylresorcinol administration: mononuclear cell leukemia in male and female rats, hepatocellular neoplasms in male mice, and circulatory system tumors in male and female mice. Synonyms: 4-hexyl-1,3-benzenediol; 4-hexyl-1,3-dihydroxybenzene
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PMID:NTP Toxicology and Carcinogenesis Studies of 4-Hexylresorcinol (CAS No. 136-77-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1273 6

Renal transplantation is method of choice for treatment of patients with end-stage renal disease without contraindications for immunosuppressive therapy. Neurological complications occur frequently in renal transplant recipients. They may be the consequence of immunosuppressive treatment, but more often evolve as the consequence of previous disturbances which developed during the state of uraemia and treatment with dialysis. The most pronounced neurotoxic effect has calcineurin inhibitors tacrolimus and cyclosporine. The spectrum of neurological disturbances caused by calcineurin inhibitors range from very mild symptoms as paraesthesiae, tremor, headache or flushing, to severe changes that may cause lethal outcome. Peripheral neuropathies in renal transplant recipients may occur in the form of mononeuropathy or polyneuropathy. Cerebrovascular diseases are consequence of changes on blood vessels caused by uraemia, dialysis and side effects of immunosuppressive drugs. They cause death in 8% of renal transplant recipients. Central nervous system (CNS) infections usually occur during the first posttransplant year. Unclear symptomatology frequently postpones the diagnosis. Diagnostic evaluation should include magnetic resonance imaging for localization of the process, as well as lumbal puncture in cases without contraindications for the procedure, in order to determine the causative agent. Regarding the ominous prognosis of CNS infections in the immunocompromised host, only timely diagnosis may improve survival. The most common causative agents are Cryptococcus neoformans, Listeria monocytogenes and Aspergillus funigatus. Viral infections also occur, and are commonly caused by herpes virideae, varicella-zoster virus and papova virus. CNS infections clinically present as meningitis, progressive dementia or focal neurological defect. The most common primary brain tumors are B-cell lymphomas, but glioblastoma, hemangioblastoma, leiomyosarcoma or glioma may also occur. In cases of neurological posttransplant complications, optimal treatment should be guided by neurologist, nephrologist and infectologist, in some cases also by neurosurgeons.
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PMID:[Neurological complications in renal transplant recipients]. 1857 36