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)

Four patients with glioblastoma and one patient with astrocytoma (grade III) were treated with recombinant IFN ( rIFN -alpha A, Ro 22-8181) and the effect of IFN on clinical symptoms, CT findings and side effects of IFN were studied. Neurological symptoms were improved in one patient, stable in one patient and worsened in three patients. In all cases, there was no remarkable change of CT findings but in one case a slight decrease in tumor size was recognized. With regards to IFN side effects general malaise, anorexia, fever, nausea and vomiting were observed clinically, decrease of leukocytes, platelets, erythrocytes, hematocrit, hemoglobin and increase of GOT, GPT, LDH, AL-P were noted in the laboratory findings. These symptoms and change in laboratory findings were not serious, and they recovered spontaneously during or after IFN therapy. In one patient, an increase in IFN neutralizing antibody titer was detected. Since the biological activity of IFN may be diminished and anti-tumor effect cannot be expected in such a patient, the appearance of IFN neutralizing antibody may indicate an important problem in IFN therapy.
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PMID:[rInterferon-alpha A (Ro 22-8181) therapy for patients with malignant brain tumors]. 632 84

Fourteen patients with advanced malignant melanoma were treated with a combination chemotherapy consisting of ACNU 100 mg/m2 i.v. on Day 1 in 6 week intervals and DTIC 200 mg/m2 i.v. on Days 1 to 5 at 3 week intervals. Four patients had prior chemotherapy and 2 had prior immunotherapy. Excluding 4 patients received the regimen for adjuvant chemotherapy, 10 of 14 patients were evaluable for response. There were 3 patients of partial responses, 3 minor responses, 1 no change, and 3 progressive diseases. The durations of partial responses were 1, 1, and 8 months, respectively, while the survival times in these patients were 5, 21, and 10 months, respectively. Leukopenia less than 4,000/cmm occurred in 10 of 14 patients (71%) and thrombocytopenia less than 100 X 10(3)/cmm in 9 of 14 patients (64%), moreover, these hematologic toxicities were cumulative. Serum GOT and GPT elevated to 3,460 mu/ml and 1,365 mu/ml, respectively in one patient, but this returned to a normal level one month later. Nausea and vomiting were mild to severe in 12 of 14 patients, being most marked on Day 1 and decreasing intensity during the next several days. Other non-hematologic toxicities including skin rash, fever, and phlebitis were noted in each one patient, respectively. Hematologic toxicity of this regimen was a dose limiting toxicity; therefore, intensive supportive therapy to prevent infection and hemorrhage is essential for the management of the patients during this chemotherapy.
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PMID:[A combination chemotherapy of ACNU and DTIC for advanced malignant melanoma]. 696 41

Intravenous (IV) acetylcysteine, cysteamine, and methionine treatments were compared in patients with severe acetaminophen poisoning; a control group consisted of patients receiving supportive therapy only. Acetylcysteine proved the safest and most effective mode of treatment. Acetylcysteine was effective in preventing liver damage, hepatic failure, renal damage, and death when given eight to ten hours after poisoning. When treatment was delayed for ten to 24 hours, results were the same as in the supportive-therapy group. The alanine aminotransferase (ALT) activity remained normal in 76% of the patients treated within ten hours, as compared with 40% in both cysteamine- and methionine-treated groups and with 16% in the supportive-therapy group. The ingestion-treatment interval for complete protection with all three drugs was eight hours; beyond that time, the incidence of damage increased steadily. After 15 hours, all treatments were pointless. Based on my experience, IV administration is preferable, since nausea and vomiting may limit the effectiveness of oral therapy.
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PMID:Treatment of severe acetaminophen poisoning with intravenous acetylcysteine. 746 30

The antiemetic effect, safety and usefulness of once daily administration of tropisetron 5 mg capsule for 3 to 5 consecutive days was investigated in 37 cases of 12 stations in total, suffering from nausea and vomiting induced by a lower multiple dose of cisplatin. The efficacy ratings assessed every 24 hours on day 1, 2, 3, 4 and 5 were 88.6%, 85.7%, 82.9%, 74.1% and 76.9%, respectively. The final efficacy rating was 82.9% (29/35 cases). Although no adverse event was observed, increases in GOT and GPT, whose cause and relation to the investigational drug were unknown, were noted in 2 cases. Cases rated as useful or better were 82.9% (29/35 cases) of the overall. The above results reveal that tropisetron 5 mg capsule is significantly effective and highly safe in the treatment of nausea and vomiting induced by lower multiple dose of cisplatin. Tropisetron 5 mg capsule is thus deemed extremely useful antiemetic drug.
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PMID:[The antiemetic effect, safety and usefulness of tropisetron capsule in the treatment of nausea and vomiting induced by lower multiple dose of cisplatin]. 761 59

A comparative clinical trial of tropisetron capsule was conducted in three dose groups to investigate its optimal dose on nausea and vomiting induced by anti-cancer drugs, including cisplatin. The doses were randomized by the central registration office. In the assessment of clinical efficacy, cases rated as "effective" or better accounted for 61.5% of the 2.5 mg group (16/26), 80.8% of the 5.0mg group (21/26) and 80.0% of the 10mg group (24/30), respectively; the ratings for the 5mg and 10mg groups were almost equivalent, which was higher than that for the 2.5mg group. Adverse events observed were fever, diarrhea, drowsiness, headache and/or facial erythema in 4 out of 97 cases. Abnormal laboratory findings noted were 6 cases of increased GOT, GPT, LDH, total bilirubin and/or creatinine, but none of these was serious or clinically problematic in particular. On the basis of the above results, the optimal dose of Tropisetron (capsule) is considered to be 5mg once daily.
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PMID:[Clinical phase II study of tropisetron capsule in the treatment of nausea and vomiting induced by anti-cancer drugs]. 761 60

The clinical phase I study of TNP-351, an antifolate drug having a novel structure, was performed through a multicenter cooperative program in 40 patients with solid tumors. The test drug was used on dosage schedules of single and daily doses for 5 or 3 days (by intravenous drip over 30 minutes, respectively). From the daily administration for 5 days, severe adverse reactions such as myelosuppression, became manifest at 5 mg/m2 (1n). This schedule was then switched to daily administration for 3 days. Administration of the test drug was initiated at a dose of 5 mg/m2. On a single-dose schedule, the dose was increased up to 100 mg/m2 (20 n), and on the 3-day daily administration schedule, up to 10.8 mg/m2 (2.2 n). Consequently, 26 of the study patients received single doses; three of them the 5-day daily administration, and 11 the 3-day daily administration. The dose-limiting factors were leukopenia and thrombopenia on both the single-dose and 3-day daily administration schedules. MTD was 100 mg/m2, and MAD, 75 mg/m2 for the single-dose schedule; and 10.8 mg/m2 and 9 mg/m2 for the 3-day daily administration schedule. WBC and platelet counts fell to nadirs at 1-2 weeks on either the single-dose or 3-day daily administration schedule, and it took the respective parameters about 1 week to recover. Subjective and objective adverse reactions to the test drug consisted of digestive tract disorders manifested as stomatitis, anorexia, nausea and vomiting; and laboratory abnormalities such as elevations of GOT and GPT in addition to the myelosuppression. Many of these adverse reactions subsided within 3 weeks after initiation of TNP-351 treatment. On the single-dose schedule, the test drug occurred chiefly in unchanged form in the blood, and in this form it disappeared from the blood biphasically with an alpha phase of 0.29-0.95 hours, and a beta phase of 7.8-14.4 hours. This disappearance pattern did not vary with an increase in dose. The 24-hour urinary excretion rate of the unchanged form amounted to 42-62% of the administered doses. On the 3-day daily administration schedule, the test drug was not accumulated in vivo. In the present study, two patients with malignant fibrous histiocytoma responded to the test drug with tumor regression. The results suggested that the recommended dosage regimen for the clinical early phase II study of the test drug should comprise a course of 9 mg/m2/day (by intravenous drip infusion over 30 minutes) every day for 3 days, which should be repeated every 3 weeks.
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PMID:[The clinical phase I study of TNP-351. The TNP-351 Research Committee]. 785 2

In the present multi-center cooperative phase II study, in which 16 institutions participated, PJ-203 and mitomycin C were concomitantly infused into the hepatic artery of patients with metastatic liver cancer and the tumor response and safety of the combined therapy were examined. Of 81 patients treated with PJ-203, 52 patients were complete cases in which bidimensionally measurable lesions could be assessed for anticancer effect in accordance with the Direct Evaluation Criteria of Chemotherapy. The number of treatments given to the complete cases until the assessment of therapeutic effect ranged from 1 to 11 times, with the mean of 3.1 times. The overall response rate was 48.1% (25/52). The response rate for each primary lesion was 68.8% (11/16) for stomach cancer, 40.7% (11/27) for colorectal cancer and 33.3% (3/9) for other types of cancer including the gallbladder. The 25 patients with CR or PR, a 50% decrease in tumor size was confirmed after the treatment ranged from 1 to 5 times, with the treatment periods of 2 to 3 weeks. Adverse reactions were found in 56 (69.1%) out of 81 patients assessed for safety. Relatively frequent symptoms were pain in 49.4% (40/81), nausea and vomiting in 33.3% (27/81), fever in 30.9% (25/81) and anorexia in 6.2% (5/81). Principal abnormal laboratory values included a transient elevation of GOT (26.3%), GPT (22.5%), LDH (12.7%) and Al-p (8.8%). Blockade of blood flow could be observed by angiography when the amount of PJ-203 infused was in the range from 180 to 900 mg as degradable starch microspheres. The blood flow blockade could be observed most frequently at the amount of 600 mg (37.7%). The period attaining over 50% of tumor response in 25 complete cases was 42 days as a median. After the treatment was initiated in 81 patients, 50% survival duration and one-year survival rate averaged 277 days and 35.7%, respectively. The corresponding figures for each primary cancer were 419 days and 51.0% for patients with liver cancer metastasized from colorectal cancer, against 239 days and 11.8% for those with liver cancer metastasized from stomach cancer.
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PMID:[Multi-center cooperative phase II study of combined infusion of PJ-203 (degradable starch microspheres) into hepatic artery in metastatic liver cancer]. 821 76

The clinical and bacteriological efficacy of imipenem/cilastatin (IPM/CS) was evaluated in 30 cases of serious infections associated with hematological malignancies. 1. Among 28 evaluable cases, excellent efficacy was obtained in 6 cases and good effectiveness in 10 cases, resulting in a high clinical efficacy rate (57.1%). The clinical effectiveness of IPM/CS was not dependent on neutrophil count in peripheral blood. A 53.8% efficacy rate was observed in 26 cases which had received pretreatment with other antibiotics. 2. Antibacterial activities of IPM/CS have so far been evaluated against organisms isolated in 20 of 28 cases: 2 strains of coagulase-negative Staphylococcus, 2 strains of methicillin-resistant Staphylococcus aureus, 2 strains of Enterococcus faecalis, 9 strains of Enterobacter cloacae, and 8 other strains. 3. Among 3 evaluable cases treated with IPM/CS alone, response was good in 1 case. Among 25 patients receiving IPM/CS in combination with an aminoglycoside or a penicillin, the efficacy rate was 60%. 4. Five patients had IPM/CS-related adverse events; nausea and vomiting in 2 cases, seizures in 1 case, small increases in GOT and GPT in 2 cases, and the appearance of casts in urine sediment in 1 case. These patients, however, tolerated the complete course of therapy with IPM/CS except the 2 cases with nausea and vomiting. These results indicate that chemotherapy with IPM/CS is effective for the treatment of severe infectious diseases accompanied by hematological disorders.
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PMID:[Chemotherapy with imipenem/cilastatin for severe infections accompanied by malignant hematological disorders]. 851 Mar 23

The experience with single-agent gemcitabine in advanced or metastatic breast cancer is reviewed. In all studies, gemcitabine was administered as a 30 min intravenous infusion in cycles once a week for 3 weeks followed by 1 week of rest. In the first European study (gemcitabine 800 mg/m2/week), of 40 evaluable patients, 14 were chemo-naive, 7 had received adjuvant chemotherapy, and 19 had received chemotherapy for metastatic disease. There were 3 complete responders and 7 partial responders (all independently validated by an external Oncology Review Board) for an overall response rate of 25.0% (95% CI: 12.7%-41.2%). The median time to declaration of response was 1.9 months and the median duration of survival for all 40 efficacy-evaluable patients was 11.5 months. Haematological and non-haematological toxicities were particularly mild. WHO grade 3 and 4 toxicities included leukopenia (6.8% and 2.3% of patients), neutropenia (23.3% and 7.0%), AST (6.8% and 2.3%), ALT (18.2% and 0%), infection (0% and 2.3%), nausea and vomiting (25.0% and 2.3%), alopecia (2.3% and 0%). There was no grade 3 or 4 creatinine, proteinuria or haematuria. In the smaller US study (18 evaluable patients, all but one having received prior chemotherapy for stage IV disease) there were no responders. However, the mean dose delivered was very low (577 mg/m2/injection). In an ongoing European trial, with a starting dose of 1000 mg/m2, a number of partial responders have been seen in soft tissue, lung and liver. Gemcitabine's modest toxicity profile and single-agent activity make it an attractive candidate for trial in combination therapy in advanced breast cancer where treatment is currently given to palliate symptoms and improve quality of life.
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PMID:Gemcitabine in advanced breast cancer. 871 26

This paper reviews the toxicity profile of gemcitabine, a novel anticancer drug. Gemcitabine has been administered using two different treatment schedules: once weekly or twice weekly for 3 weeks followed by a week of rest (one cycle). It was well tolerated and alopecia was not a problem. Toxicity was greater in the twice-weekly schedule. Comparing the once-weekly with the twice-weekly schedule, WHO grade 3 or 4 thrombocytopenia was reported in 4.7 and 25.6% of patients, respectively. Other hematological toxicity was minimal. Transient WHO grade 3 or 4 elevations of ALT and AST occurred in 9.2 and 7.2% of patients, respectively, in the once-weekly schedule. For the twice-weekly schedule the corresponding percentages were 12.2 and 13.8%. Symptomatic toxicity was greater in patients who received twice-weekly gemcitabine. Nausea and vomiting was mild and generally well controlled without 5HT3 antagonists. However, there was a greater incidence of nausea and vomiting on the twice-weekly schedule. Flu-like symptoms were documented in 19.8% of patients receiving once-weekly and 63.3% of patients receiving twice-weekly gemcitabine. Peripheral edema, not related to cardiac, hepatic or renal failure, was seen more often in patients on twice-weekly treatment. As the efficacy of gemcitabine in non-small cell lung cancer was equivalent when using both regimens, the better tolerated and more easily administered once-weekly schedule is recommended.
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PMID:Gemcitabine: once-weekly schedule active and better tolerated than twice-weekly schedule. 879 11


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