Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.
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PMID:[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group]. 794 92

An 87-year-old woman, who had been suffering from hypothyroidism and had been treated as an outpatient at our department since 1982, noticed left cervical swelling toward the end of November 1992. Because ultrasonic examination revealed a mass in her thyroid gland, she was admitted for a closer examination and additional treatment. Biopsy of thyroid gland revealed non-Hodgkin's lymphoma (NHL; the diffuse small cell type, B-cell origin). A part from the swelling of thyroid gland and the left cervical lymph node, performance of various examinations did not detected any other NHL lesions. Therefore, it was classified as stage II NHL according to the Ann Arbor classification. Laboratory data on admission were as follows; WBC 4,400/microliters, Hb 13.6 g/dl, platelet count 10.1 x 10(4)/microliters, GOT 51 IU/l, GPT 31 IU/l, TSH 1.17, free-T4 1.03, free-T3 2.04, and microsome test 1,600 x. Those data indicated marked hypothyroidism. In addition, stage IIa and IIc gastric cancers were detected by the examination with gastric endoscopy performed for stage classification. Both were adenocarcinomas. Because polyps were found in her sigmoid colon with colonoscopy, polypectomy was performed. The polyps were diagnose histologically as moderately differentiated adenocarcinoma. On July 20, COP-BLAM therapy was started (CPM 600 mg div, VCR 1.2 mg iv, ADR 30 mg iv on day 1, PDN 40 mg p.o and PCZ 100 mg p.o. on days 1-10, BLM 7.5 mg div on day 14). Subsequently, the left cervical lymph node swelling disappeared, and shrinkage of the mass in the thyroid gland was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of elderly Hashimoto disease presenting malignant lymphoma, gastric cancer and colon cancer]. 829 59

A phase II study of Paclitaxel in patients with ovarian cancer by 3-hour intravenous infusion was undertaken by a cooperative study group of 30 institutes. Of 66 cases enrolled, 57 cases were evaluable for efficacy, and 63 cases were evaluable for safety. In spite of the fact that all cases for efficacy evaluation were previously treated with chemotherapy including platinum-based drugs, 2 cases of complete response (CR) and 15 cases of partial response (PR) were observed, with a response rate of 29.8% (The 95% confidence interval of response rate was 18.4-43.4%). Paclitaxel also showed 28.2% (11/39) response rate in patients refractory to treatment by platinum-based drugs. Histologically, the response rates were 28.9% (11/38) in serous adenocarcinoma, 40.0% (2/5) in clear cell adenocarcinoma and 25.0% (1/4) in mucinous adenocarcinoma. As the major laboratory abnormalities, leukopenia, neutropenia and decrease in hemoglobin were observed with incidence rates of 98.4% (62/63), 95.2% (59/62) and 85.7% (54/63), respectively. However, these abnormalities were clinically manageable by either withdrawal of medication, administration of antibiotics, G-CSF or metachysis etc. In addition, thrombocytopenia, elevation in GOT and GPT were seen with moderate incidence. Peripheral neuropathy was a major adverse symptom with an incidence of 79.4% (50/63), followed by alopecia, myalgia, arthralgia and fever. However, the majority of these adverse reactions were less than grade 3. From these findings, we confirmed that 3-hour intravenous infusion of Paclitaxel was a clinically useful chemotherapeutic agent in patients with ovarian cancer.
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PMID:[Phase II study of paclitaxel (BMS-181339) in patients with ovarian cancer by 3-hour intravenous infusion]. 871 25

CA 19-9 is a tumour marker which has been used widely in patients with pancreatic adenocarcinoma. Elevated levels are associated with advanced disease at presentation and disease progression during follow-up. CA19-9 levels may also be elevated in a variety of other malignant and benign conditions. This study examined the significance and implications of elevated CA19-9 levels. An analysis of all CA19-9 measurements performed over a 4 yr period was undertaken and 204 patients with elevated CA19-9 levels were identified. One hundred and thirty patients (63.7 per cent) had malignant conditions and 74 (36.3 per cent) had benign conditions or no definite cause was found. There was a significant correlation between CA19-9 levels and CEA (r = 0.3137; P < 0.001) as well as alkaline phosphatase, ALT, AST, bilirubin, gamma glutamyl transpeptidase and lactate dehydrogenase. CA19-9 levels were significantly lower in patients with benign pathology than those with malignant pathology. Similar differences were observed for CEA. CA19-9 levels were in fact highest in patients with pancreatic carcinoma (P < 0.05) while no significant differences were observed for CEA. In conclusion CA19-9 may be elevated in both benign as well as malignant conditions and interpretation of CA19-9 results must be made in light of the clinical condition of the patient.
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PMID:Are elevated levels of the tumour marker CA19-9 of any clinical significance?--an evaluation. 1042 94

Based on the results of our previous pilot study, we conducted a multi-institutional phase II study of combination chemotherapy consisting of oral UFT (Taiho Pharmaceutical Co. Ltd, Tokyo) plus cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). UFT capsule containing 100 mg tegafur and 224 mg uracil was orally administered in two divided doses on days 1 through 21 making the total tegafur dose 400 mg/m(2)/day (maximum 600 mg/body). CDDP was administered by drip infusion at a dose of 20 mg/m(2) on a 5-day schedule from day 8 to 12. Treatment was repeated every 4 weeks as long as the criteria for initiation of therapy were still met. Between April 1995 and March 1997, 51 patients were entered into the study. The mean age of all 50 eligible patients was 64 years(range: 40-78). There were 21 patients with clinical stage IIIB disease and 29 patients with IV disease. Thirty-two patients had adenocarcinoma, 14 had epidermoid carcinoma, and four had large cell carcinoma. Of the 47 assessable patients, 18 achieved a partial response with an overall response rate of 38.3% (95% confidence interval: 24.4-52.2%). The median response duration was 113 days. The median survival time of the eligible patients was 12.8 months, and the 1-year survival rate was 54%. Among the 51 patients enrolled, grade 3 or 4 leukopenia developed in one patient (2%), neutropenia in six patients (11. 8%), thrombocytopenia in six patients (11. 8%), and anemia in three patients (5. 9%). Non-hematological grade 3 or 4 toxicities included anorexia in 10 patients (19.6%), nausea in ten (19.6%), vomiting in two (3.9%), and diarrhea in two (3. 9%). Grade 3 abnormal laboratory data included bilirubinemia in four (7. 8%), GPT elevation in one (2.0%), and hematuria in one (2.0%). In conclusion, combination of CDDP plus oral UFT is efficacious, with low toxicity, in the treatment of advanced NSCLC. In particular, the low hematological toxicity may warrant application of this regimen to the treatment of elderly patients and in trials of concurrent chemoradiotherapy in patients with locally advanced NSCLC.
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PMID:A phase II trial of oral UFT plus cisplatin (CDDP) in patients with non-small cell lung cancer (NSCLC). 1116 9

This is, to our knowledge, the first report of papillary adenocarcinoma originating in the subvesical bile duct. A 77-year-old man was referred to our hospital for further evaluation of liver dysfunction. Serum liver function test results on admission included: aspartate aminotransferase, 99 IU/l; alanine aminotransferase, 149 IU/l; lactate dehydrogenase, 438 IU/l; alkaline phosphatase, 992 IU/l; leucine aminopeptidase, 320 IU/l; and gamma-glutamyl transpeptidase, 593 IU/l. Serum carbohydrate antigen (CA) 19-9 value was high (80 U/ml). Abdominal ultrasonogram, computed tomographic scan, and percutaneous transhepatic cholangiogram demonstrated a mass in the common hepatic duct, and dilatation of the intrahepatic bile ducts. A laparotomy was performed on May 14, 1997. The tumor originated in the dilated subvesical duct that joined the common hepatic duct, and projected into the common hepatic duct. The patient underwent cholecystectomy, resection of the subvesical duct and the common hepatic duct, dissection of regional pericholedochal lymph nodes, and Roux-en-Y hepaticojejunostomy. The resected tumor presented macroscopically as a papillary mass measuring 4.0 x 2.0 cm. The pathological diagnosis was papillary adenocarcinoma. The immunostaining positivity rates for MIB-1 and p53 protein were 49.6% and 33.8%, respectively.
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PMID:Papillary adenocarcinoma of the subvesical duct. 1170 63

Metastatic carcinomas are the largest group of malignant tumors of the liver. But parenchymal liver metastasis from cystic ovarian adenocarcinoma is very rare. We report a case in which the resection of metastatic liver neoplasm from ovarian serous cystadenocarcinoma was done 7 yr after initial treatment. A 48-yr-old oriental housewife complained of easy fatigability and right lower quadrant discomfort. The hepatic mass was detected by ultrasonographic examination. Serum albumin, bilirubin, and aspartate aminotransferase/alanine aminotransferase were normal. Alkaline phosphatase level was slightly increased at 146 IU/L. A tumor marker study showed alpha-fetoprotein 0.97 IU/mL, carcinoembryonic antigen 0.965 ng/mL, cancer antigen 125 1,267 ng/mL and CA 19-9 106.1 ng/mL. The operation involved cholecystectomy and segmentectomy VI and VII of the liver. The patient recovered from the surgery without any complication. On the 10th postoperative day, the patient received a single-regimen chemotherapy with paclitaxel (Taxol, 155 mg/m(2) BSA) and was discharged. She has been carefully followed-up without any evidence of recurrence after completion of the remaining 5 cycles of chemo-therapy, at intervals of three weeks.
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PMID:Hepatic resection of metastatic tumor from serous cystadenocarcinoma of the ovary. 1206 51

1,2,3-Trichloropropane is a colorless liquid used as a paint and varnish remover, solvent, and degreasing agent, and as a crosslinking agent in the synthesis of polysulfides and hexafluoropropylene. 1,2,3-Trichloropropane may be found as an impurity in certain nematocides and soil fumigants and as a contaminant of drinking and ground water. Studies on the toxic and carcinogenic effects of 1,2,3-trichloropropane were initiated because of the close structural relationship of this chemical to other short-chain halogenated compounds that were demonstrated to be carcinogenic in experimental animals, and because of the potential for human exposure. Toxicology and carcinogenicity studies were conducted by administering 1,2,3-trichloropropane (greater than 99% pure) in corn oil by gavage to groups of F344/N rats and B6C3FI mice for 17 weeks and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium strains, mouse lymphoma cells, and Chinese hamster ovary cells. 17-Week Studies: Groups of 20 male and 20 female rats received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg body weight 5 days per week for up to 17 weeks; 30 male and 30 female rats received corn oil alone and served as controls. Animals were evaluated at 8 or 17 weeks. All rats in the 250 mg/kg groups died by week 5. One male and four female rats in the 125 mg/kg groups died during the study. The mean body weight gains and final mean body weights of males receiving 63 mg/kg and of males and females receiving 125 mg/kg were lower than those of the controls. Hematocrit values, hemoglobin concentrations, and erythrocyte counts decreased with dose in males and females. Serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase activities were significantly increased in some female rats receiving 125 mg/kg. Serum pseudocholinesterase activity decreased with dose in females. Increases in kidney and liver weights were related to chemical administration. The principal toxic lesions associated with the administration of 1,2,3-trichloropropane to rats were hepatocellular necrosis, karyomegaly, and biliary hyperplasia of the liver; renal tubule necrosis, regeneration, and karyomegaly of the kidney; and necrosis and inflammation of the nasal olfactory and respiratory epithelium. Groups of 20 male and 20 female mice received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg 5 days per week for up to 17 weeks; 30 male and 30 female mice received corn oil alone and served as controls. Sixteen male and seven female mice in the 250 mg/kg groups died by week 4. The final mean body weights and mean body weight gains of dosed mice were similar to those of the controls, except those of 250 mg/kg males, which were lower than those of controls. The principal toxic lesions associated with the administration of 1,2,3-trichloropropane were hepatocellular necrosis and karyomegaly of the liver; necrosis, regeneration, and hyperplasia of the bronchiolar epithelium in the lung; and acanthosis (hyperplasia) and hyperkeratosis of the forestomach epithelium. 2-Year Studies: Groups of 60 male and 60 female rats received 0, 3, 10, or 30 mg 1,2,3-trichloropropane/kg body weight in corn oil by gavage 5 days per week for up to 104 weeks. Selection of 30 mg/kg as the high dose in these studies was based on the following chemical-related effects in the 17-week studies: deaths and liver and kidney lesions at 125 and 250 mg/kg and reduced final mean body weights and mean body weight gains at 63 mg/kg or greater. Groups of 60 male and 60 female mice received 0, 6, 20, or 60 mg 1,2,3-trichloropropane/kg body weight in corn oil by gavage 5 days per week for up to 104 weeks. Selection of 60 mg/kg as the high dose was based on chemical-related deaths and lesions of the liver, lung, and forestomach at 125 and 250 mg/kg in the 17-week studies. 15-Month Interim Evaluations: Up to 10 rats and 10 mice from each dose group were evaluated at 15 months. Absolute and relative liver and kidned kidney weights of dosed rats were significantly greater than those of the controls. Chemical-related nonneoplastic lesions and neoplasms of the forestomach, oral mucosa, pancreas (males), kidney, mammary gland (females), preputial gland, and clitoral gland were observed in dosed rats. Chemical-related nonneoplastic lesions and neoplasms of the forestomach and liver (females) were observed in dosed mice. Survival and Body Weight in the 2-Year Studies: Survival of male and female rats receiving 10 or 30 mg/kg 1,2,3-trichloropropane was significantly lower than that of controls. Two-year survival rates of male rats were: control, 34/50; 3 mg/kg, 32/50; 10 mg/kg, 14/49; 30 mg/kg, 0/52; and of females were: 31/50, 30/49, 8/52, 0/52. At 30 mg/kg, survival was markedly reduced due to chemical-related neoplasms, and survivors were killed in weeks 67 (females) or 77 (males). Final mean body weights of 30 mg/kg rats were 13&percnt; lower for males and 12&percnt; lower for females than those of controls; mean body weights of 3 and 10 mg/kg rats were similar to controls. Survival rates of mice receiving 6, 20, or 60 mg/kg 1,2,3-trichloropropane were also significantly lower than those of controls. Two-year survival rates of male mice were: 42/52, 18/51, 0/54, 0/56; and of female mice were: 41/50, 13/50, 0/51, 0/55. Because of reduced survival at 20 and 60 mg/kg due to chemical-related neoplasms, survivors were killed in weeks 73 (60 mg/kg females), 79 (60 mg/kg males), or 89 (20 mg/kg males and females). Final mean body weights were 16&percnt; lower for 60 mg/kg males, 18~ lower for 60 mg/kg females, and 13&percnt; lower for 20 mg/kg males than those of controls. Final mean body weights of 6 mg/kg males and females and 20 mg/kg females were similar to controls. Neoplasms and Nonneoplastic Lesions in the 2-Year Studies: Administration of 1,2,3-trichloropropane to rats induced benign and malignant neoplasms of the oral mucosa (pharynx and tongue), forestomach, and preputial and clitoral glands in males and females; benign neoplasms of the exocrine pancreas and kidney in males, and malignant neoplasms of the mammary gland in females. The incidences of squamous cell papillomas and carcinomas of the oral mucosa were significantly increased in 10 and 30 mg/kg rats, while the incidences of squamous cell papillomas or carcinomas (combined) of the forestomach were significantly increased in all dosed groups. The incidence of pancreatic acinar adenoma was significantly increased in dosed males, but not in dosed females. Similarly, the incidence of adenoma of the kidney was significantly increased in 10 and 30 mg/kg male rats only. The incidences of adenoma or carcinoma (combined) of the preputial gland in 30 mg/kg males and of the clitoral gland in 10 and 30 mg/kg females (homologous organs) were significantly increased. The incidence of adenocarcinoma of the mammary gland was significantly increased in the 10 and 30 mg/kg females. The incidences of Zymbal's gland carcinomas were increased in 30 mg/kg males and females. Adenocarcinomas of the intestine occurred in small numbers of dosed rats and may have been chemical related. In mice, the incidence of squamous cell carcinoma of the oral mucosa was significantly increased only in 60 mg/kg females. In contrast, the incidences of squamous cell papilloma and carcinoma of the forestomach were significantly increased in all groups of dosed mice. The incidences of hepatocellular adenoma or carcinoma (combined) were significantly increased in all dosed groups of males and 60 mg/kg females. The incidences of harderian gland adenoma were significantly increased in 20 mg/kg males and in 60 mg/kg males and females. The incidences of uterine adenoma, adenocarcinoma, and stromal polyp were significantly increased in 60 mg/kg females. Genetic Toxicology: 1,2,3-Trichloropropane was mutagenic in vitro in the presence of S9 metabolic activation. At two laboratories, positive responses were obtained for mutagenicity in Salmonella typhimurium strains TA97, TA98, TA100, and TA1535 in the presence of S9; no mutagenic activity was observed in TA1537, with or without S9. 1,2,3-Trichloropropane induced trifluorothymidine resistance in L5178Y mouse lymphoma cells with, but not without, S9. In cultured Chinese hamster ovary cells, sister chromatid exchanges and chromosomal aberrations were induced by 1,2,3-trichloropropane; however, significant increases in the endpoints of both cytogenetic effects occurred only in the presence of S9. Conclusions: Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in male F344/N rats based on increased incidences of squamous cell papillomas and carcinomas of the oral mucosa and forestomach, adenomas of the pancreas and kidney, adenomas or carcinomas of the preputial gland, and carcinomas of the Zymbal's gland. Adenomatous polyps and adenocarcinomas of the intestine may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in female F344/N rats based on increased incidences of squamous cell papillomas and carcinomas of the oral mucosa and forestomach, adenomas or carcinomas of the clitoral gland, adenocarcinomas of the mammary gland, and carcinomas of the Zymbal's gland. Adenocarcinomas of the intestine may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in male B6C3F1 mice based on increased incidences of squamous cell papillomas and carcinomas of the forestomach, hepatocellular adenomas or carcinomas of the liver, and harderian gland adenomas. Squamous cell papillomas of the oral mucosa may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in female B6C3F1, mice based on increased incidences of squamous cell carcinomas of the oral mucosa, squamous cell papillomas and carcinomas of the forestomach, hepatocellular adenomas or carcinomas of the liver, harderian gland adenomas, and uterine adenomas, adenocarcinomas, and stromal polyps. Nonneoplastic lesions associated with exposure to 1,2,3-trichloropropane included increased severity of nephropathy in male rats and increased incidences of basal cell and squamous hyperplasia of the forestomach, acinar hyperplasia of the pancreas, renal tubule hyperplasia, and preputial or clitoral gland hyperplasia in male and female rats. Increased incidences of squamous hyperplasia of the forestomach and eosinophilic foci in the liver in male and female mice were chemical related. Synonyms: Allyl trichloride, glycerol tnchlorohydrin, glyceryl tnchlorohydrin, trichlorohydrin
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PMID:NTP Toxicology and Carcinogenesis of 1,2,3-Trichloropropane (CAS No. 96-18-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1269 52

Recent studies have emphasized the importance of patient selection for the surgical resection of pancreatic adenocarcinoma based on reproducible prognostic factors. The aim of the study was to investigate the prognostic factors affecting long-term survival in patients with resectable and nonresectable pancreatic cancer and to evaluate their prognostic value. Forty six patients (25 women, 21 men, aged 44-80) with ductal adenocarcinoma of the pancreas were reviewed. Primary tumor size and regional enlargement of lymph nodes was assessed with enhanced CT scan. 13 patients were treated conservatively, 9 with standard Whipple procedure (pancreatoduodenectomy) and 24 - with palliative surgery. Survival probabilities were computed using univariate Kaplan-Meier analysis. Log-rank test was used to compare survival between groups. Overall median survival was 6 months with a 4 years survival of 2.2%. There was no difference in survival time (ST) between patients aged 65 years or younger and older (p=0.71). MeanST in patients after Whipple procedure was 10.3, after palliative surgery - 9.4 and after conservative treatment - 4.4 months (p<0.05). Thirty-day surgical mortality was 9.4%. ST was significantly longer in patients with tumors 3 cm or less of diameter compared with larger ones (p<0.05). Presenting signs and symptoms, like jaundice, diabetes, alkaline phosphatase, aspartate and alanine aminotransferase elevation and history of cholecystectomy did not have any significant impact on survival. The only significant independent factors improving survival were: operative treatment and tumor size smaller than 3 cm.
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PMID:Prognostic factors in the operative and palliative treatment of pancreatic cancer. 1462 94

Eight cases of feline pancreatic adenocarcinoma and two cases of pancreatic adenoma were reviewed. The adenomas were incidental findings. Most cats with adenocarcinomas had anorexia (75%) and vomiting (63%), while 38% had abdominal pain, a palpable abdominal mass, and/or jaundice. Diagnostic abnormalities included leukocytosis, hyperglycemia, increased alanine aminotransferase activity, poor serosal detail on abdominal radiography, and an abdominal mass effect on ultrasonography. The majority of cats with carcinomas had metastases (mostly to liver, lung, and small intestine), and all were euthanized or died within 7 days of diagnosis. Clinically, feline pancreatic carcinoma may be difficult to distinguish from feline pancreatitis.
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PMID:Exocrine pancreatic neoplasia in the cat: a case series. 1513 Nov 6


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