Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background. - Trastuzumab is known as an active agent in HER2/neu overexpressing advanced breast cancer. In the prospective study we investigated efficacy, safety and toxicity of trastuzumab and paclitaxel in advanced breast cancer progressing on previous therapy. Patients and methods. - Seventeen patients with histologically confirmed disease were accrued. Inclusion criteria were as follows: Karnofsky performance status >/= 60 %, age < 75, pretreatment with at least two regimens; HER2/neu by immunohistochemistry 3+ or 2+, adequate organ function. Trastuzumab was given 4 mg/kg i.v. as a loading dose followed by 2mg/kg i.v. weekly. Paclitaxel was given 80 mg/m2 i.v. weekly. Both drugs were given until disease progression or unacceptable toxicity. We assessed the response rate (RR), the time to progression (TTP), the overall survival (OS) and toxicity. Results. RR in the intent to treat population was 59 % (10 out of 17), including 2 complete responses. In the median follow up of 4,3 years median TTP was 9 month and median OS 23 month. In total 710 cycles including 528 full dose cycles of trastuzumab and paclitaxel were administered. One patient developed hypersensitivity reaction after the first trastuzumab infusion and discontinued from study. Trastuzumab infusion related pyretic reaction was observed in 6 patients. Left ventricular ejection fraction decline occurred in 2 patients (grade 2 and grade 3). Five patients experienced grade 3 neuropathy. Hematological toxicity was very modest: 1 episode of grade 4 neutropenia and grade 3 anemia. Other grade 3/4 toxicity: 4 episodes of grade 3 infection without neutropenia, grade 3 elevation of liver function tests in 1 patient, 1 episode of grade 3 hyperglycemia, and 1 episode of grade 3 weight gain. Other grade 3 or 4 toxicity was not detected. Conclusion. - Trastuzumab and paclitaxel have shown activity and good tolerability in HER-2/neu overexpressing advanced breast cancer patients.
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PMID:4-years results of weekly trastuzumab and paclitaxel in the treatment of women with HER2/neu overexpressing advanced breast cancer: single institution prospective study. 1558 95

Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include DAF-2 and InR and their homologues in mammals, and inactivation of the corresponding genes is followed by increased life span in nematodes, fruit flies and mice. It is possible that the life-prolonging effects of calorie restriction are due to decreasing IGF-1 levels. A search of pharmacological modulators of insulin/IGF-1 signaling pathway (which mimetic effects of life span extending mutations or calorie restriction) could be a perspective direction in regulation of longevity. The chronic treatment of female transgenic HER-2/neu mice with metformin (100 mg/kg in drinking water) slightly decreased the food consumption but failed in reducing the body weight or temperature, slowed down the age-related rise in blood glucose and triglycerides level, as well as the age-related switch-off of estrous function, prolonged the mean life span by 8% (p < 0.05), the mean life span of last 10% survivors by 13.1%, and the maximum life span by 1 month in comparison with control mice. The demographic aging rate represented by the estimate of respective Gompertz's parameter was decreased 2.26 times. The metformin-treatment significantly decreased the incidence and size of mammary adenocarcinomas in mice and increased the mean latency of the tumors.
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PMID:Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. 1612 52