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)

Taxanes are effective in the treatment of metastatic breast cancer. Docetaxel has been shown to be more potent than paclitaxel in inducing bcl-2 phosphorylation and apoptosis and is clinically active in some paclitaxel-resistant breast tumors. HER-2/neu overexpression has been shown to correlate with resistance to hormonal therapy as well as chemotherapy. Using a HER-2/neu transfected MCF-7 human breast cancer cell line, we investigated the role of HER-2/neu overexpression on resistance to paclitaxel and docetaxel treatment. A control vector transfected MCF-7 human breast cancer cell line (MCF/neo) and a HER-2/neu transfected MCF-7 line (MCF/18) were treated with various concentrations of docetaxel or paclitaxel. Cell number was assessed using the MTT tetrazolium dye assay. In the control vector transfected MCF/neo cell line, paclitaxel and docetaxel gave similar dose-dependent growth inhibition ( p = 0.175). In HER-2/neu transfected MCF/18 cells, docetaxel treatment resulted in a dose-dependent inhibition similar to that seen in MCF/neo cells. Paclitaxel, however, gave significantly less growth inhibition than docetaxel in the HER-2/neu overexpressing MCF/18 cells (p = 0.0003). These data suggest that HER-2/neu overexpression may contribute to paclitaxel resistance. In contrast, the cytotoxic effects of docetaxel in these breast carcinoma cells are not affected by HER-2/neu expression. Therefore, docetaxel may be the preferred taxane therapy in HER-2/neu overexpressing breast tumors.
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PMID:Decreased response to paclitaxel versus docetaxel in HER-2/neu transfected human breast cancer cells. 1257 25

Elevated levels of the extracellular domain of HER-2/neu in serum (sHER-2/neu) have been shown to be of prognostic importance. In this phase II study with weekly paclitaxel in metastatic breast cancer, we investigated the predictive quality of this serum oncoprotein by correlating the outcome of therapy to sHER-2/neu levels. Paclitaxel (90 mg/m2 weekly x6, q9w) was administered to 35 patients with complete outcome assessment and biochemical follow-up. sHER-2/neu was measured using standardized enzyme-linked immunoassays. We found that 62.9% (22/35) of the patients had elevated levels (> or = 15 ng/ml) of sHER-2/neu. The overall response rate (RR) to weekly paclitaxel was 40.0% (14/35). There was no difference in RR between sHER-2/neu-positive patients (40.9%) and sHER-2/neu-negative patients (38.5%; p = 0.4). The progression-free interval was longer for sHER-2/neu-negative patients (53.2 weeks) in comparison to sHER-2/neu-positive patients (31.2 weeks; p = 0.098). Responses were significantly more durable in sHER-2/neu-negative patients (65.2 weeks) than in the sHER-2/neu-positive subgroup (25.7 weeks; p = 0.042). Introducing hypothetical cut-offs into the sHER-2/neu-positive subset, we found that in patients with a sHER-2/neu level of greater than 22 ng/ml, the progression-free survival decreased significantly with increasing sHER-2/neu levels (p < or = 0.022). Considering the high impact of progression-free survival and duration of response as outcome parameters, the sHER-2/neu status is a predictive indicator for benefit from paclitaxel chemotherapy.
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PMID:Serum HER-2/neu as a prediction and monitoring parameter in a phase II study with weekly paclitaxel in metastatic breast cancer. 1516 Oct 43

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

Subclinical doses of Paclitaxel (PTX) given 1day prior to a HER-2/neu (neu)-targeted, granulocyte-macrophage colony stimulating factor (GM-CSF)-secreting whole-cell vaccine enhances neu-specific T cell responses and slows neu(+) tumor growth in tolerized HER-2/neu (neu-N) mice. We demonstrate that co-administration of PTX and Cyclophosphamide (CY) synergizes to slow tumor growth, and that in vitro, DC precursors exposed to PTX before LPS maturation results in greater co-stimulatory molecule expression, IL-12 production, and the ability to induce CD8(+) T cells with enhanced lytic activity against neu(+) tumors. PTX treatment also enhances maturation marker expression on CD11c(+) DCs isolated from vaccine-draining lymph nodes. Ex vivo, these DCs activate CD8(+) T cells with greater lytic capability than DC's from vaccine alone-treated neu-N mice. Finally, PTX treatment results in enhanced antigen-specific, IFN-gamma-secreting CD8(+) T cells in vivo. Thus, administration of PTX with a tumor vaccine improves T cell priming through enhanced maturation of DC.
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PMID:Paclitaxel enhances early dendritic cell maturation and function through TLR4 signaling in mice. 2034 45