Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects and adverse drug reaction (ADR) of intermittent cisplatin therapy (ICDDPT) on advanced ovarian cancer patients (OCP). Most OCPs had undergone surgical removal of primary lesion and induction chemotherapy, and histopathological analysis indicated epithelial tumors. Five OCPs were stage III, six were stage IV and one stage II (n = 12). After surgical treatment and induction chemotherapy, ICDDPT was initiated with a 25-30 mg/day dose of CDDP for 5 days, every 3 months. During the intervals, maintenance immunochemotherapy of Tegafur and OK-432 was applied. Following ICDDPT, all patients except one are alive. The longest survival, to date is 5 years 7 months, while the decreased case survived 4 years. ADR was analysed according to the total dose of CDDP i.e. under 500 mg, over 500 mg-under 1,000 mg, 1,000 mg-under 1,500 mg, and 1,500 mg and over. Abnormal laboratory findings were observed for WBC, platelet (thrombocytopenia), Hb, GOT and GPT. The abnormal values except for GOT and GPT reverted to normal just before next administration. Thereafter ADR of CDDP with regard to the renal tubulus were studied by observing urinary NAG and urinary and serum beta 2 microglobulin. These values, however, were restored to within normal limits after 1 week of CDDP administration. These ADR were no greater with the increasing dose, such that accumulative toxicity was not observed. Study of the histological concentration of platinum showed a high level in liver tissue. Therefore, liver damage should be noted as on ADR of CDDP. In conclusion, ICDDPT for OCP was seen to be effective because of a good survival rate and low ADR.
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PMID:[The effect on prognosis and the adverse drug reaction of intermittent cisplatin therapy in advanced ovarian cancer patients]. 207 85

Cefuzonam (CZON) which has a broad spectrum on both Gram-negative and Gram-positive bacteria including methicillin-resistant Staphylococcus aureus was evaluated in severe infections associated with hematological disorders. Sixty five patients were treated with CZON. Among them, 56 patients were evaluable for effectiveness. Nine patients were not evaluable because 3 patients were treated with combination of other antibiotics such as ceftizoxime, norfloxacin, ofloxacin, 1 patient was subjected to additional therapy of G-CSF and gamma-globulin, 4 were the patients with other disease than hematologic disorder (3 malignant mesotheliomas, 1 ovarian cancer), and the remaining one was prophylactically treated. Excellent responses were observed in 21 (37.5%) patients, good responses in 11 (19.6%) patients, with an overall efficacy rate of 57.1%. The efficacy rate in septic patients was 80% (4/5), and that in patient whose peripheral granulocytes were continuously below 100/microliters was 60% (3/5). Three patients who suffered from malignant mesothelioma, one patient who suffered from ovarian cancer, one patient who was treated prophylactically were included in the final evaluation of side effects. Side effects were observed in 2 patients (2/61, 3.3%). In a patient of 7 years, mild liver disfunction (GOT/GPT, 46/55) was found in 10 days after CZON treatment was started. In a patient of 65 years, mild appetite loss was identified in 2 days after CZON administration was begun. The liver disfunction was improved soon after the cessation of the treatment. The mild appetite loss disappeared while the treatment was continued. These results showed that CZON was an effective and safe antibiotic for the treatment of severe infections in patients with hematological disorders.
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PMID:[Clinical evaluation of cefuzonam of severe infections in leukemia and related disorders]. 228 6

We examined the effects of intermittent cisplatin therapy (ICDDPT) on advanced ovarian cancer patients (OCP). Most OCPs had received surgical removal of primary lesion, and histopathological analysis indicated epithelial tumors. Four OCPs were stage 3, three were stage 4 and one was stage 2 (n = 8). After surgical treatment and induction chemotherapy, ICDDPT with 20-25 mg/day CDDP was given for 3 or 5 days, every 3 months. During the intervals, maintenance immunochemotherapy with Tegafur and OK-432 was given. Following ICDDPT all patients are alive, the longest survival time being 3 years and 10 months. Three have survived at least 3 years, 1 for at least 2 years and 3 for at least 1 year. Adverse drug reaction (ADR) was analysed with reference to the total dose of CDDP, i.e. under 500 mg, over 500 mg-under 1,000 mg and over 1,000 mg. Abnormal laboratory findings in platelets (thrombocytopenia), Hb, BUN, Creatinine, GOT and GPT were observed at the all doses. These ADR were not increased with the increasing dose so that accumulative toxicity was not observed. Therefore ICDDPT was seen to be effective in treating OCP.
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PMID:[Clinical evaluation of intermittent administration of CDDP in advanced ovarian cancer]. 249 40

Linkage analysis was conducted in 17 families identified by the familial occurrence of breast and ovarian cancer using a series of 17 serologic and biochemical markers. Lod scores suggestive of linkage of breast/ovarian cancer susceptibility to the RH blood group locus on chromosome 1p were obtained. When the presence of fibrocystic disease of the breast in a first-degree relative of an affected family member was added as an indicator of susceptibility, the evidence for linkage increased. No evidence of linkage to GPT or ABO, both previously suggested to be linked to breast cancer susceptibility, was seen in this study.
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PMID:A genetic linkage study of familial breast-ovarian cancer. 272 Jun 37

Lycobetaine (AT-1840), developed by our institute, is a new chemotherapeutic agent with relatively high percentage of remission on the treatment of ovary cancer and stomach cancer; no remarkable changes in blood picture, EKG and GPT, were observed. Early examination of the structure activity relationship of lycobetaine gave the following results: 1. A potential betaine and a methylenedioxy group in this compound may be critical for exhibiting antitumor activity; 2. Fission of the five membered ring of lycobetaine will not affect its antitumor activity. In order to see whether the distance between the phenolic oxygen and quaternary nitrogen affects its antitumor activity, compounds 7a-c, 8a-b were synthesized and screened against tumor in mice bearing EAC Preliminary experimental results showed that among the open ring analogs of lycobetaine, 7a, 7b and 8d possessed marked antitumor activity and 7c did not. The results indicate that changes in the distance of the betaine in lycobetaine obviously influence its antitumor activity.
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PMID:[Structure-activity-relationship study of the new anticancer drug lycobetaine (AT-1840)]. 281 92

A four-fold (P less than 0.001) mean increase in iron levels was found in 18 patients (a total of 36 courses of therapy) with ovarian cancer at the end of a 5-day course of cisplatin (40 mg/m2 per day every 4-5 weeks). The kinetics of these modifications began very early (24-48 h after initiation of therapy): they reached their maximum on the 4th-5th day, coinciding with the last drug administration, and basal levels were recovered after the 10th day. A subsequent eight-fold average increase (P less than 0.001) in ferritin serum levels, beginning 2 days after the iron changes, was observed, but showed a slower regression (after the 15th day). Reticulocyte counts were lowered (P less than 0.001) with the same time-course of the iron increases, but returned to pretreatment levels within 2 weeks. Total bilirubin and serum glutamate-pyruvate transaminase showed significantly delayed increases compared with iron. The results are in keeping with a reduced iron utilization by the erythroid precursors, but other mechanisms cannot be excluded. There is no statistical correlation between the early iron increases and the subsequent hemoglobin nadir values.
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PMID:Changes in serum iron levels following very high-dose cisplatin. 358 20

Chromosomal locations of hypothetical alleles which increase susceptibility to human breast cancer in some families were investigated by genetic linkage analysis. In 7 families with primarily premenopausal breast cancer and (in 5 families) ovarian cancer, a dominant susceptibility allele may be linked to the genetic marker glutamicpyruvic transaminase or alanine aminotransferase (GPT; lod score 1.95 at zero recombination). The most positive lod score for linkage to a recessive susceptibility allele was for acid phosphatase (ACP; lod score 0.78 at 40% recombination), but ACP was informative in ony 1 family. In 3 families with primarily postmenopausal breast cancer, none of 21 genetic markers provided any evidence for linkage to either dominant or recessive susceptibility alleles. In the families with the possible GPT linkage, women who carry the hypothetical susceptibility allele would be at high risk of breast cancer, whereas their relatives who do not carry that allele would have no increased risk. GPT genotype is not associated with breast cancer risk in the general population, so GPT linkage cannot be used as a screening test for breast cancer.
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PMID:Genetic epidemiology of breast cancer and associated cancers in high-risk families. II. Linkage analysis. 657 21

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

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

Fifty-one patients with histologically confirmed epithelial stage III or IV ovarian cancer were entered into a study in which gemcitabine 800 mg/m2 was given as a 30 min intravenous infusion in a cycle once a week for 3 weeks followed by a week of rest. Patients were aged 58 years (range 23-70 years) with WHO performance status 0-2, and had received up to two different chemotherapy regimens. Thirty-eight patients had received only one prior platinum-containing chemotherapy regimen whereas 9 had received a first-line regimen on more than one occasion. A further 3 patients had received two different regimens. Of 42 patients evaluable for response, 8 (19%; 95% CI: 9%-34%) were partial responders. Seven of the 8 responders were resistant to first-line platinum-based therapy. Median duration of response was 8.1 months (range 4.4-12.5 months). Median progression-free survival was 2.8 months (range 0.2-12.5 months). Haematological toxicity with gemcitabine was modest, with grade 3 leukopenia (11 patients) and grades 3 and 4 thrombocytopenia (6 patients). Grade 3 non-haematological toxicity included nausea/vomiting (6 patients) and elevated AST/ALT (1 patient), while dose-limiting non-haematologic toxicity consisted of flu-like symptoms (2 patients), peripheral oedema (1 patient) and lethargy (1 patient). The activity and modest haematological and non-haematological toxicity seen with gemcitabine suggest that this agent should be further evaluated in the treatment of patients with ovarian cancer and in combination chemotherapy regimens, primarily in combination with platinum.
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PMID:Phase II study of gemcitabine in previously platinum-treated ovarian cancer patients. 871 27


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