Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with breast cancer developed severe asthenia, accompanied with progressively increasing transaminases, during adjuvant chemotherapy with CMF (cyclophosphamide, methotrexate and 5-fluorouracil). Additional blood tests and imaging were negative. A liver biopsy revealed a grade II toxic hepatitis. Because methotrexate was suspected to be the cause of the hepatotoxicity, the administration of this drug was stopped and mitoxantrone was given instead. A recovery of clinical symptoms and normalisation of the liver function tests was observed afterwards. In that sense, mitoxantrone appears to be a valuable alternative to methotrexate in cases of hepatotoxicity in patients with breast cancer. An overview of the literature regarding methotrexate hepatotoxicity is presented.
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PMID:Methotrexate-associated liver toxicity in a patient with breast cancer: case report and literature review. 1236 78

The multisubunit transcription elongation factor NELF (for negative elongation factor) acts together with DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) sensitivity-inducing factor (DSIF)/human Spt4-Spt5 to cause transcriptional pausing of RNA polymerase II (RNAPII). NELF activity is associated with five polypeptides, A to E. NELF-A has sequence similarity to hepatitis delta antigen (HDAg), the viral protein that binds to and activates RNAPII, whereas NELF-E is an RNA-binding protein whose RNA-binding activity is critical for NELF function. To understand the interactions of DSIF, NELF, and RNAPII at a molecular level, we identified the B, C, and D proteins of human NELF. NELF-B is identical to COBRA1, recently reported to associate with the product of breast cancer susceptibility gene BRCA1. NELF-C and NELF-D are highly related or identical to the protein called TH1, of unknown function. NELF-B and NELF-C or NELF-D are integral subunits that bring NELF-A and NELF-E together, and coexpression of these four proteins in insect cells resulted in the reconstitution of functionally active NELF. Detailed analyses using mutated recombinant complexes indicated that the small region of NELF-A with similarity to HDAg is critical for RNAPII binding and for transcriptional pausing. This study defines several important protein-protein interactions and opens the way for understanding the mechanism of DSIF- and NELF-induced transcriptional pausing.
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PMID:Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex. 1261 62

One of the major challenges in medical domain is the extraction of comprehensible knowledge from medical diagnosis data. In this paper, a two-phase hybrid evolutionary classification technique is proposed to extract classification rules that can be used in clinical practice for better understanding and prevention of unwanted medical events. In the first phase, a hybrid evolutionary algorithm (EA) is utilized to confine the search space by evolving a pool of good candidate rules, e.g. genetic programming (GP) is applied to evolve nominal attributes for free structured rules and genetic algorithm (GA) is used to optimize the numeric attributes for concise classification rules without the need of discretization. These candidate rules are then used in the second phase to optimize the order and number of rules in the evolution for forming accurate and comprehensible rule sets. The proposed evolutionary classifier (EvoC) is validated upon hepatitis and breast cancer datasets obtained from the UCI machine-learning repository. Simulation results show that the evolutionary classifier produces comprehensible rules and good classification accuracy for the medical datasets. Results obtained from t-tests further justify its robustness and invariance to random partition of datasets.
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PMID:Evolutionary computing for knowledge discovery in medical diagnosis. 1263 76

Comprehensibility is very important for any machine learning technique to be used in computer-aided medical diagnosis. Since an artificial neural network ensemble is composed of multiple artificial neural networks, its comprehensibility is worse than that of a single artificial neural network. In this paper, C4.5 Rule-PANE which combines artificial neural network ensemble with rule induction by regarding the former as a preprocess of the latter, is proposed. At first, an artificial neural network ensemble is trained. Then, a new training data set is generated by feeding the feature vectors of the original training instances to the trained ensemble and replacing the expected class labels of the original training instances with the class labels output from the ensemble. Additional training data may also be appended by randomly generating feature vectors and combining them with their corresponding class labels output from the ensemble. Finally, a specific rule induction approach, i.e., C4.5 Rule, is used to learn rules from the new training data set. Case studies on diabetes, hepatitis, and breast cancer show that C4.5 Rule-PANE could generate rules with strong generalization ability, which profits from artificial neural network ensemble, and strong comprehensibility, which profits from rule induction.
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PMID:Medical diagnosis with C4.5 Rule preceded by artificial neural network ensemble. 1267 17

Breast cancer is a rapidly increasing problem in many developing countries, and cytotoxic chemotherapy is now an integral part of its management. In several developing countries, the carriage of hepatitis B virus (HBV) in cancer patients may be as high as 12%, and such patients are at risk of developing fatal HBV reactivation during chemotherapy. HBV reactivation is well recognized in patients with hematological malignancies, but limited data are available on patients with other, more common, cancers, such as breast cancer. Recent data have suggested that increased viral replication, an indication of HBV reactivation, may precede clinical hepatitis. In the absence of serial HBV DNA monitoring, HBV reactivation during chemotherapy may have been underestimated. In this prospective study, breast cancer patients who were hepatitis B surface antigen (HBsAg) seropositive were followed up during chemotherapy. The main objectives were to determine the incidence of HBV reactivation in breast cancer patients undergoing conventional chemotherapy; to investigate whether "serial HBV DNA monitoring" improves the accuracy of diagnosing HBV reactivation when compared with previous schema that only measured HBV DNA at the time of clinical hepatitis ("conventional monitoring"); and to assess the clinical consequences as a result of developing the condition. The secondary objective was to identify risk factors associated with this condition. Over an 18-month period, 41 patients were studied. Ten developed HBV reactivation by conventional monitoring criteria, but with serial HBV DNA monitoring, seven additional patients were diagnosed when increased HBV DNA levels were detected before, but not concomitant with, clinical hepatitis. Thus, a total of 17 patients (41%) developed HBV reactivation. Premature termination of chemotherapy or delay in treatment schedules occurred in 71% of the patients who developed viral reactivation, as compared with 33% in those who did not develop the condition (P = 0.019). No risk factors associated with the development of HBV reactivation could be identified. Serial monitoring of HBV DNA, in addition to liver function, increases the sensitivity of diagnosing of HBV reactivation, and helps explain some cases that would otherwise be labeled as "cryptogenic hepatitis," for which concomitant HBV DNA measured at the time of hepatitis was undetectable. The present study highlights the importance of monitoring HBsAg-seropositive patients who are receiving chemotherapy for common solid tumors such as breast cancer.
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PMID:Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy: a prospective study. 1508 99

The results of lamivudine therapy in 4 patients with chemotherapy-induced hepatitis B virus (HBV) reactivation are reported. Cancer chemotherapy-induced reactivation is a known complication in patients with chronic HBV infection or history of HBV infection with recovery. Reactivation of HBV infection has a broad spectrum of manifestations ranging from mild elevation of aminotransferase levels to fatal fulminant hepatitis. Lamivudine is a nucleoside analogue and a potent inhibitor of HBV reverse transcription. The 4 patients treated with lamivudine included 1 woman with breast cancer and 3 men with non-Hodgkin lymphoma, ranging from 41 to 63 years of age. All 4 patients were undergoing standard, multi-agent chemotherapy when they presented with HBV reactivation manifested by sudden onset of fatigue, jaundice, and HBV serology consistent with active HBV infection (detectable serum HBV DNA) in the absence of other known causes of acute hepatitis. Lamivudine therapy (100 mg/d in 3 patients and 150 mg/d in 1 patient) was initiated from 1 to 18 days following the diagnosis of HBV reactivation. All 4 patients showed rapid decrease in aminotransferase levels within 2 weeks after initiating lamivudine therapy. Unfortunately, hepatic synthetic function failed to improve in 2 patients, who both died. The remaining 2 patients had suppression of HBV DNA to undetectable levels after 1 and 4 months of treatment and had biochemical and clinical improvement. The 2 patients who died received lamivudine therapy for 8 days and for 3 weeks. There have been no randomized clinical trials to study the role of lamivudine for prophylaxis or treatment of HBV reactivation associated with chemotherapy. However, based on our limited experience, lamivudine may be efficacious in suppressing potentially fatal HBV reactivation secondary to chemotherapy in patients with chronic HBV infection or prior infection with recovery. Patients who undergo chemotherapy should be screened for the presence of markers of chronic hepatitis B infection or previous HBV infection. We recommend that patients with chronic HBV infection (positive HBV DNA and/or positive HBsAg) or history of HBV infection with recovery (positive hepatitis B core antibody with or without HBsAb) be considered for prophylactic lamivudine use to prevent chemotherapy-induced HBV reactivation.
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PMID:Prophylaxis against chemotherapy-induced reactivation of hepatitis B virus infection with Lamivudine. 1281 Dec 13

Drug-induced hepatotoxicity accounts for more than a third of the cases of acute liver failure in the United States. In complex medical conditions, the diagnosis of drug-induced liver injury may be confounding and, specifically, the potential hepatotoxicity of chemotherapeutic agents may be easily overlooked. Two fatal cases of cholestatic hepatotoxicity have been previously reported, clearly implicating gemcitabine therapy. We report a third fatal case of cholestatic liver failure that we think is strongly linked to the use of gemcitabine. This chemotherapeutic agent is a fluorine analog with broad-spectrum antitumor activity commonly used in the treatment of breast, lung, prostate, and cervical cancer. The case we report is of a 45-year-old woman with a history of metastatic breast cancer to her spine. The patient was in remission for two years before she presented with a compensated mixed hepatitis of mild to moderate severity. Inpatient work-up found metastases to the right humerus and inferior pubic ramus, but none in the liver. Gemcitabine and carboplatin therapy was initiated for relapse of breast cancer. The patient's liver enzyme elevation diminished, but did not normalize before the start of chemotherapy. She received four courses of gemcitabine/carboplatin and subsequently presented with decompensated, severe cholestatic hepatitis. Transjugular liver biopsy displayed marked cholestasis and hepatocellular injury consistent with drug-induced hepatoxicity. Gemcitabine has been extensively studied in the oncology literature and at this time is thought to be a low-risk hepatotoxin causing hepatic adaptation and transient, reversible liver enzyme elevation, rarely leading to termination of gemcitabine therapy for solid tumors. We believe that gemcitabine therapy, particularly in the setting of preexisting liver injury or metastases to the liver, increases the relative risk of severe and potentially fatal hepatic injury possibly by idiosyncratic and dose-dependent mechanisms. We recommend careful monitoring and dose adjustment of gemcitabine in patients with abnormal liver function tests or evidence of hepatic metastases until further study clarifies this issue.
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PMID:Fatal cholestatic liver failure associated with gemcitabine therapy. 1456 Oct 5

Herbal remedies generate more than 1.8 billion dollars in annual sales in the United States. Herbal products have been associated with a wide spectrum of hepatic toxicities. With the recent Women's Health Initiative Study demonstrating increased risk of breast cancer and cardiovascular events associated with hormone therapy, many women may resort to herbal remedies for persistent menopause symptoms. We report a case of autoimmune hepatitis likely triggered by the use of black cohosh (Actaea racemosa), an agent marketed to treat menopause symptoms. Given this case report, we recommend close monitoring of women using this herbal preparation.
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PMID:Autoimmune hepatitis associated with the use of black cohosh: a case study. 1535 12

In parts of Asia, about 10% of the population have chronic hepatitis B virus (HBV) infection, and cancer patients who are HBV carriers are frequently complicated by HBV reactivation while receiving cytotoxic chemotherapy. The condition may result in varying degrees of liver damage, causing disruption in chemotherapy and compromising the patients' prognosis. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Recent reports have suggested that the anti-viral agent, lamivudine, may reduce HBV reactivation and its associated morbidity. However, most studies are based on small series of lymphoma patients, while information on the other high risk population, namely breast cancer patients, has been lacking. In this study, we studied the role of lamivudine in preventing HBV reactivation and its associated morbidity in breast cancer patients with chronic HBV infection who were planned for chemotherapy. Two groups were studied. One group consisted of 31 patients who received 'prophylactic lamivudine' prior to and until 8 weeks after discontinuing chemotherapy. The other comprised of 61 historical controls who underwent chemotherapy without prophylactic lamivudine. The outcomes, in terms of the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity during chemotherapy were compared. The results revealed that in the prophylactic lamivudine group, despite a significantly higher proportion receiving anthracyclines, there was significantly fewer incidences of hepatitis (12.9 vs. 59.0%, p < 0.001), less HBV reactivation (6.5. vs. 31.1%, p=0.008), and less disruption of chemotherapy (16.1% vs. 45.9%, p=0.006). We conclude that prophylactic lamivudine significantly reduces the incidence of HBV reactivation and the overall morbidity of breast cancer patients undergoing chemotherapy.
Breast Cancer Res Treat 2004 Dec
PMID:Use of lamivudine to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patients. 1598 Sep 97

Physalis angulata (PA) is employed in herbal medicine around the world. It is used to treat diabetes, hepatitis, asthma and malaria in Taiwan. We have evaluated PA as a cancer chemopreventive agent in vitro by studying the role of PA in regulation of proliferation, cell cycle and apoptosis in human breast cancer cell lines. PA inhibited cell proliferation and induced G2/M arrest and apoptosis in human breast cancer MAD-MB 231 and MCF-7 cell lines. In this study, under treatment with various concentrations of PA in MDA-MB 231 cell line, we checked mRNA levels for cyclin A and cyclin B1 and the protein levels of cyclin A and cyclin B1, Cdc2 (cyclin-dependent kinases), p21(waf1/cip1) and P27(Kip1) (cyclin-dependent kinase inhibitors), Cdc25C, Chk2 and Wee1 kinase (cyclin-dependent kinase relative factors) in cell cycle G2/M phase. From those results, we determined that PA arrests MDA-MB 231 cells at the G2/M phase by (i) inhibiting synthesis or stability of mRNA and their downstream protein levels of cyclin A and cyclin B1, (ii) increasing p21(waf1/cip1) and P27(kip1) levels, (iii) increasing Chk2, thus causing an increase in Cdc25C phosphorylation/inactivation and inducing a decrease in Cdc2 levels and an increase in Wee1 level. According to the results obtained, PA appears to possess anticarcinogenic properties; these results suggest that the effect of PA on the levels of phosphorylated/inactivated Cdc25C are mediated by Chk2 activation, at least in part, via p21(waf1/cip1) and P27(kip1) cyclin-dependent kinase inhibitors pathway to arrest cells at G2/M phase in breast cancer carcinoma cells.
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PMID:Physalis angulata induced G2/M phase arrest in human breast cancer cells. 1642 78


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