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)

The notification rate of tuberculosis in Japan was 31.0 per 100,000 in 2000. The rate was especially high among the elderly population, reaching 85.5 per 100,000 among those over 65 years of age. We conducted a study of preventive therapy in middle-aged and elderly persons selected from the population-based screening by the mass miniature radiography. The eligible criteria were 50-79 years of age, fibrous lesion which were compatible with healed tuberculosis and showed no change for at least one year, no previous treatment for tuberculosis, normal liver function tests, and no serious disease at the time of study. The eligible criteria for liver function tests in this study was less than 50 IU/L of AST and ALT value, and less than 1.5 mg/dl of T-bil level. A total of 13,219 people underwent TB screening in 4 cities in 1997 and 2 cities in 1998. Among them, 440 persons fulfilled the above criteria based on the screening records and chest X-ray films. The municipal offices sent letters to 418 people, except 22 whose addresses were unknown, to obtain permission to use their addresses and results of screening in our study. Permission was obtained from 137 persons and we sent them invitation letters for cost-free physical checkup service. Ninety-five persons visited us, and we offered them physical checkup and explained about our study. After obtaining the informed consent, we performed chest X-ray and sputum examination for 3 consecutive days. Finally 29 people were enrolled in the study. They were divided into 4 groups by sex and age, and were randomly assigned to one of two treatment groups. One group took 300 mg of INH per day for 6 months and the other group was only followed up by chest X-ray. Fourteen out of 29 persons began to take INH and received monthly liver function test. All the subjects were scheduled to follow by medical checkup every 6 months for 5 years. The proportion of taking INH tablets was estimated to range from 94% to 100%, based on the calendar for record of taking medication and the number of remaining tablets each month. Six (42.9%) of 14 persons reported adverse reactions. Two of 6 persons complained some of diarrhea, vomiting and gastrointestinal disturbance within 2 weeks, and discontinued taking INH, although none of them showed abnormal liver function tests. Two of 6 persons who reported some kinds of symptoms and 2 of 8 persons who did not complain of any symptoms showed abnormal liver function tests. The abnormal liver function tests had developed from 2 months after the beginning of INH taking in most of the persons and the abnormality improved after the completion of 6-month treatment. We have followed them for a maximum duration of 2.5 years, and 3 cases dropped out from the study. These defaulted cases had completed 6 months of INH. One person (69 y.o. male) was diagnosed as active TB by his chest X-ray film at the 6th month medical checkup, although it was not confirmed bacteriologically. One person (62 y.o. female) had the mastectomy for breast cancer 7 months before the entry to this study and relapsed at the 8th month after the entry. One person (73 y.o. female) was diagnosed as lung cancer at the medical checkup on 2.5 years. Besides them, 4 persons were suspected of worsening the abnormal shadows on chest X-ray films; one was from the INH group and three were from the follow-up group. However none of them was diagnosed clinically and bacteriologically as active tuberculosis.
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PMID:[Preventive therapy in middle-aged and elderly persons selected from the population-based screening by mass miniature radiography--methodological aspect and adverse reactions]. 1244 Jan 39

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing doxorubicin and human immunoglobulin as an actively/passively targeting moiety was used in four patients with generalized breast cancer resistant to standard cytotoxic chemotherapy. The dose and time schedule were deduced from a Phase I clinical trial in which doxorubicin bound to HPMA copolymer carrier (PK1) was tested. It was confirmed that the Dox-HPMA-HuIg conjugate is stable and doxorubicin remains in the peripheral blood with a small amount also in the urine, mostly in its polymer-bound form. More than 116 biochemical, immunological and hematological parameters were determined for blood samples taken from patients 24 h, 48 h, 72 h and 1 to 11 weeks after treatment. Depending on the patient, some parameters decreased permanently or temporarily to the normal level (CRP, C3, CA 72-4, beta(2)-microglobulin, ferritin, CEA, CA 125, CD4, CD8, CE19, CD16(+)56(+), leu, ery) and some moved markedly towards physiological values (AST, ALT, ALP, GMT, CA 15-3, NSE, AFP). While the number of peripheral blood reticulocytes was significantly decreased after treatment with the classical free drug, their number was not affected or was even elevated after treatment with Dox-HPMA-HuIg. Increased absolute numbers of CD16(+)56(+) and CD4(+) cells in the peripheral blood and activation of NK and LAK cells in all patients support data obtained in experimental animals, pointing to a dual, i.e. cytostatic and immunomobilizing character of Dox-HPMA conjugates containing a targeting immunoglobulin moiety.
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PMID:Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data. 1293 33

Synthetic coumarin (benzopyrone) was launched in France in 1988 for the adjuvant therapy of lymphoedema of the upper limb following radiosurgical treatment of breast cancer. Further to the reporting of hepatic reactions, a national survey has been carried out. The survey dealt with 22 cases reported to the pharmacovigilance regional centres and 20 to Knoll France company (five duplicate cases) up to June 1996. Thirty-four cases corresponding to an elevation of ALT over 2N and/or alkaline phosphatase over 1.5N (criteria chosen for selection in this survey) had been taken into account. Among these cases, a causal relationship was considered likely or probable for 15 of them. Two positive rechallenges were reported. The hepatic reactions observed between 2 to 6 months of treatment in two-thirds of the cases (average dose: 90 mg/day; i.e. recommended dose) was essentially cytolytic in 85% of the cases, with jaundice in 14 cases and hyperbilirubinaemia reported in five other cases. In 23 cases (68%), the increase of ALT exceeded 10N. Of the patients 41% were hospitalized. Severe liver failure with encephalopathy justified liver transplantation once and likely led to encephalopathy and fatal evolution in two other cases. The evolution was favourable in the other cases. The drug was prescribed for other uses than the registered indication in more than 50% of these cases. No risk factors could be identified in the survey. This survey provides a strong signal for potential hepatotoxicity of coumarin (likely due to the production of a reactive metabolite in some patients exhibiting a coumarin 7-hydroxylation deficiency).
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PMID:French pharmacovigilance survey evaluating the hepatic toxicity of coumarin. 1507 59

Reactivation of hepatitis B virus (HBV) after cytotoxic chemotherapy is a serious problem, and it occurred to 41% of breast cancer patients carrying HBV. Previous studies have demonstrated that lamivudine was effective for HBV flare-up during cytotoxic chemotherapy. We aimed to monitor the HBV status of breast cancer patients undergoing chemotherapy with preemptive lamivudine over time. Six breast cancer patients carrying hepatitis B surface antigen (HBsAg) were monitored during chemotherapy, five in the adjuvant setting and one with metastatic disease. Preemptive lamivudine was given throughout the chemotherapy course. HBsAg, HBV envelope antigen (HBeAg), anti-HBV envelope antibody (HBe Ab), serial serum alanine transaminase (ALT), quantitative HBV viral DNA analysis, and HBV DNA precore promoter and precore sequence were monitored. One patient carried wild type and the other five precore mutant strain of HBV by examination of HBV sequence in precore promoter and precore region. No evident HBV reactivation developed, and all patients tolerated lamivudine well. During the 6-to-8-month follow-up after cessation of cytotoxic therapy and withdrawal of lamivudine, serum ALT remained unchanged, although an increase of HBV DNA levels in four patients was found. No emergence of the tyrosine-methionine-aspartate-aspartate (YMDD) lamivudine-selective resistant strain was observed in the six patients. Preemptive use of lamivudine can effectively prevent reactivation of HBV in breast cancer patients receiving postoperative adjuvant chemotherapy. Lamivudine can be discontinued safely without emergence of lamivudine-resistant HBV strain or rebound HBV flare-up. The candidate for the use of preemptive lamivudine in HBV carriers who need short-term chemotherapy remained to be investigated
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PMID:Preemptive use of lamivudine in breast cancer patients carrying hepatitis B virus undergoing cytotoxic chemotherapy: a longitudinal study. 1507 16

Novel ruthenium(II) organo-metallic compounds are active in ovarian cancer models [Aird RE, Cummings J, Ritchie AA, Muir M, Morris RE, Chen H, et al. In vitro and in vivo activity and cross resistance profiles of novel ruthenium(II) organometallic arene complexes in human ovarian cancer. Br J Cancer 2002;86(10):1652-7]. [(eta6-C6H5C6H5)Ru(en)Cl]+ (as a PF6 salt, where en=ethylenediamine (RM175)) has been evaluated in a 13-cell line panel. Particular sensitivity (approximately 10-fold lower than mean IC50) was noted in breast cancer and non-small cell lung cancer cell lines. In addition, IC50 in the A549 was 2 microM and RM175 (25 mg kg-1, days 1 and 5, i.p.) caused a significant (p=0.004) growth delay in a xenograft model. HC11 [(eta6-tetrahydroanthracene)Ru(en)Cl]PF6 was more potent in the A549 cell line (IC50 0.5 microM). HC11 (25 mg kg-1, days 1, 8 and 15, i.p.) was also active in vivo. Following RM175 25 mg kg-1, days 1 and 5, and 15 mg kg-1, days 1-5, HC11 25 and 40 mg kg-1, day 1, elevated alanine transaminase levels were detected, suggesting hepatotoxicity. No changes were observed in kidney or haematological parameters. In liver sections, multi-focal hepatic necrosis was seen, becoming confluent at high doses of HC11. In vitro studies confirmed that HC11 was more toxic than RM175 to fresh human hepatocytes and equitoxic to mithramycin. Liver toxicity may be related to the arene ligand and modification may reduce the potential for hepatic toxicity, while maintaining the anti-tumour activity seen.
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PMID:Anti-tumour activity in non-small cell lung cancer models and toxicity profiles for novel ruthenium(II) based organo-metallic compounds. 1636 Jun 45

A 40-year-old Chinese-American woman with breast carcinoma metastatic to her lungs presented with a 3-month history of erosions on her inner thighs (Figure 1) and medial left shoulder. Faint livedo reticularis was evident on her legs as well. She had difficulty in walking and raising her shoulders. Her cutaneous examination was also notable for cuticular erythema (Figure 2) and mild periorbital erythema and edema. She had no systemic or rheumatologic complaints other than some difficulty in swallowing. Her blood chemistry values were notable for a creatinine kinase of 564 IU/L (5-200 IU/L), alanine aminotransferase 161 U/L (0-40 U/L) and aspartate aminotransferase 93 U/L (0-40 U/L), and an antinuclear antibody titer of 1:2560. Other blood chemistries and antibody serologies (anti-Jo-1, anti-Mi-2 and other anti-tRNA synthetase, anti-Ro/SSA, anti-U1RNP, anti-PM/Scl, and anti-Ku) were within normal limits. A biopsy specimen was obtained from an area of intact skin close to a right thigh ulceration that showed subtle vacuolar alteration at the dermo-epidermal junction with occasional necrotic keratinocyte (Figure 3). Melanophages and telangiectases were present. Within the subcutis there was fibrin deposition and neutrophils. A diagnosis of dermatomyositis was made. The patient received oral prednisone 20 mg three times a day, and her ulcerations resolved. Her creatinine kinase, alanine aminotransferase, and aspartate aminotransferase values returned to normal over the course of 3 weeks, but her antinuclear antibody was unchanged. Radiographic studies concurrently noted that her breast cancer had recurred in her lungs; plans were made to treat her with chemotherapy. The patient was lost to close follow-up, but it was learned that her erosions had reoccurred while her prednisone was tapered and resolved when her dosage of prednisone was increased.
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PMID:Ulcerative paraneoplastic dermatomyositis secondary to metastatic breast cancer. 1660 44

Propolis, a natural beehive product has been known for centuries for a variety of beneficial traditional medicinal properties. The present study was conducted to ascertain the antineoplastic potential of propolis along with paclitaxel against experimental mammary carcinogenesis. Female Sprague Dawley rats at 55 days of age were treated with dimethylbenz(a)anthracene to induce breast cancer. Paclitaxel at a dose of 33 mg/kg body mass intraperitoneally and propolis 50 mg/kg body weight orally was administered to the experimental animals, immediately after the carcinogen treatment and continued until the termination of the study. At the end of the treatment activities of phase I and II xenobiotic metabolizing enzymes and liver marker enzymes were measured. A significant increase in carcinogen activating enzymes, cytochrome P(450), cytochrome b(5) and NADPH cytochrome C reductase with concomitant decrease in phase II enzymes, glutathione transferase and UDP-glucuronyl transferase were observed in animals with mammary cancer. Furthermore there was a significant decrease in alanine aminotransferase, aspartate aminotransferase with a sharp increase in alkaline phosphatase, acid phosphatase and 5' nucleotidase. Propolis treatment caused the activity of these enzymes return to almost normal control levels, indicating the protective effect of propolis against dimethyl benz(a) anthracene induced carcinogenesis. On the basis of the observed results propolis can be considered a promising chemotherapeutic agent and can be administered as an adjuvant with paclitaxel chemotherapy.
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PMID:Therapeutic effect of propolis and paclitaxel on hepatic phase I and II enzymes and marker enzymes in dimethylbenz(a)anthracene-induced breast cancer in female rats. 1672 Jan 5

We investigated the time it took to develop fatty liver and changes in serum aspartate aminotransferase and alanine aminotransferase levels in patients with breast cancer treated with adjuvant tamoxifen. Liver sonography to detect fatty liver and measurement of serum aspartate and alanine aminotransferase levels were performed regularly for patients with early breast cancer. The results were compared in groups of patients with and without adjuvant tamoxifen as well as those on chemotherapy. Eighty-two of 156 patients treated with tamoxifen developed fatty liver, compared with eight of 62 patients not taking it. Fatty liver appeared as early as 3 months after beginning tamoxifen and was detected within 2 years in most cases. It persisted for 48 months after discontinuing tamoxifen in 17 of the 82 patients who developed it. The incidence of fatty liver in patients receiving both chemotherapy and tamoxifen was the same as that in patients receiving tamoxifen alone. While 115 patients had elevations of aspartate aminotransferase, alanine aminotransferase or both, the magnitude of the elevation was clinically significant in only 32 patients. Patients on both chemotherapy and tamoxifen had a higher incidence of elevated transaminases than those on tamoxifen alone. Adjuvant tamoxifen increases the incidence of fatty liver, but has only a minimal effect on aspartate aminotransferase and alanine aminotransferase. Fatty liver may appear as early as 3 months after beginning tamoxifen and may persist for more than 4 years after discontinuing it. Therefore, long-term follow-up is warranted. Chemotherapy is not clearly associated with fatty liver, but may cause a greater degree of hepatocellular damage than does tamoxifen.
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PMID:Fatty liver and transaminase changes with adjuvant tamoxifen therapy. 1691 17

We evaluated the feasibility of doxorubicin plus cyclophosphamide (AC) followed by weekly paclitaxel (wT) as adjuvant therapy for node-positive breast cancer in a variety of practice settings. Forty-seven patients received AC at either doses of 40 mg/m(2)+400 mg/m(2) (A(40)C(400), 33 patients) or 50 mg/m(2)+500 mg/m(2) (A(50)C(500), 14 patients) every 3 weeks for 4 cycles followed by wT at a dose of 80 mg/m(2)for 12 cycles with a week pause after 3 consecutive weekly administrations. Mean relative dose-intensities were 98.8% for A(40)C(400), 90.7% for wT after A(40)C(400), 91.3% for A(50)C(500), and 89.2% for wT after A(50)C(500). Grade 4 toxicity included neutropenia (3.0% for A(40)C(400), 14.3% for A(50)C(500)). Grade 3 toxicity included neutropenia (18.2% for A(40)C(400), 28.6% for A(50)C(500), 6.7% for wT), thrombocytopenia (2.2% for wT), nausea/vomiting (6.1% for A(40)C(400)), anorexia (3.0% for A(40)C(400), 2.2% for wT), fatigue (3.0% for A(40)C(400)), AST/ALT elevation (7.1% for A(50)C(500)), allergic reaction (4.4% for wT). There were six (12.8%) treatment discontinuations, including two allergic reactions to paclitaxel. AC followed by wT can be administered safely in the community at doses of 50 mg/m(2), 500 mg/m(2), and 80 mg/m(2), respectively,with minimal toxicity.
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PMID:[Adjuvant doxorubicin and cyclophosphamide followed by weekly paclitaxel for Japanese women with node-positive breast cancer: a multi-institutional feasibility study in a variety of practice settings in Kyushu]. 1703 30

Tamoxifen, the widely prescribed drug in the prevention and therapy of breast cancer, may cause side effects which may be influenced by gender. The present study was undertaken to investigate the impact of gender on tamoxifen-induced toxic and biochemical changes following oral administration of tamoxifen at high dose level of 20 mg/kg once daily for a 2-week period in both male and female rats. The results showed marked increases in serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in female rats. In contrast, treatment with tamoxifen in male animals significantly decreased the activity of ALT, with a tendency for a decrease in serum AST levels. In female rats, a significant reduction in the serum activity of acid phosphatase (ACP) was noted, compared with a non-significant decrease in males. Non-significant changes in serum levels of alkaline phosphatase (ALP) were seen in both sexes. Tamoxifen lowered serum contents of total lipid and total cholesterol in both male and female rats. Serum levels of triglycerides were reduced in female rats as compared to a non-significant decrease in male animals. The serum albumin concentration was decreased in both male and female rats, while total protein was decreased only in female animals. Tamoxifen markedly increased serum levels of creatinine in female rats, compared with a non-significant rise in males. Total serum contents of calcium were similarly reduced in both males and females. This is the first study which points to gender-related differences in tamoxifen-induced toxic and metabolic changes in rats. The results indicated that females are more susceptible than males to tamoxifen toxicity, probably due to the ability of tamoxifen to antagonize the action of estrogen in females.
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PMID:Influence of gender on tamoxifen-induced biochemical changes in serum of rats. 1727 26


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