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

Ab-mediated signaling in tumor cells and Ab-dependent cell-mediated cytotoxicity (ADCC) are both considered as relevant effector mechanisms for Abs in tumor therapy. To address potential interactions between these two mechanisms, we generated HER-2/neu- and CD19-derived chimeric target Ags, which were expressed in experimental tumor target cells. HER-2/neu-directed Abs were documented to mediate effective ADCC with both mononuclear cells (MNCs) and polymorphonuclear granulocytes (PMNs), whereas Abs against CD19 were effective only with MNCs and not with PMNs. We generated cDNA encoding HER-2/CD19 or CD19/HER-2 (extracellular/intracellular) chimeric fusion proteins by combining cDNA encoding extracellular domains of HER-2/neu or CD19 with intracellular domains of CD19 or HER-2/neu, respectively. After transfecting wild-type HER-2/neu or chimeric HER-2/CD19 into Raji Burkitt's lymphoma cells and wild-type CD19 or chimeric CD19/HER-2 into SK-BR-3 breast cancer cells, target cell lines were selected for high membrane expression of transfected Ags. We then investigated the efficacy of tumor cell lysis by PMNs or MNCs with CD19- or HER-2/neu-directed Ab constructs. MNCs triggered effective ADCC against target cells expressing wild-type or chimeric target Ag. As expected, PMNs killed wild-type HER-2/neu-transfected, but not wild-type CD19-transfected target cells. Interestingly, however, PMNs were also effective against chimeric CD19/HER-2-transfected, but not HER-2/CD19-transfected target cells. In conclusion, these results demonstrate that intracellular domains of target Ags contribute substantially to effective Ab-mediated tumor cell killing by PMNs.
 ...
PMID:Intracellular domains of target antigens influence their capacity to trigger antibody-dependent cell-mediated cytotoxicity. 1190 82

The cytotoxic effect of trastuzumab in combination with oral fluoropyrimidine S-1 on human epidermal growth factor receptor 2 (HER2)-overexpressing human pancreatic cancer cell line TRG in vitro and in vivo was investigated. HER2 expression in TRG was analyzed by RT-PCR and flow cytometry. For in vitro experiments, 5-fluorouracil (5-FU) was used instead of S-1. In vivo studies were conducted with TRG xenografts in athymic mice. Trastuzumab (10 mg/kg) was administered intraperitoneally once a week for 4 weeks. S-1 (10 mg/kg) was administered orally 5 days a week for 4 weeks. The results showed that TRG cells were positive for HER2 mRNA and overexpressed HER2 protein. Either trastuzumab or 5-FU concentration-dependently inhibited the growth of TRG cells. The combination of trastuzumab and 5-FU resulted in a significant inhibition of growth of TRG cells compared to either agent alone (P<0.001). Incubation of TRG cells with peripheral blood mononuclear cells after treatment with trastuzumab enhanced the antiproliferative effect of trastuzumab, which could be the result of antibody-dependent cellular cytotoxicity. The combination of trastuzumab and S-1 resulted in a significant reduction in xenograft volume compared to each agent alone (P<0.0001). In conclusion, this study showed that combination therapy with trastuzumab and S-1 may be effective for HER2-overexpressing pancreatic cancer patients.
 ...
PMID:Antitumor activity of a combination of trastuzumab (Herceptin) and oral fluoropyrimidine S-1 on human epidermal growth factor receptor 2-overexpressing pancreatic cancer. 1761 67

The human epidermal growth factor (EGF) receptor (HER) family consists of four receptors that bind to ligands sharing an EGF-like motif. The HER family of receptor tyrosine kinases and their ligands (EGF family) are known to play a significant role in gastrointestinal cancer. In particular, the EGF receptor, HER1, is one of the main candidates for the molecular-targeted therapy of colon cancer, and HER2 is a candidate for the treatment of gastric cancer which overexpresses HER2. In contrast, the role of the HER and EGF families in malignant lymphoma has not been fully elucidated. In this study, we investigated the expression and function of the HER and EGF families in lymphoma cell lines and tumor samples. Reverse transcription polymerase chain reaction revealed that the ligands for HER1 were mainly expressed in gastric cancer and colon cancer cell lines, but not in lymphoma cell lines. On the other hand, the EGF family member, neuregulin (NRG) 4, was highly expressed in lymphoma cell lines. Immunohistochemical analyses of malignant lymphoma clinical samples revealed that NRG4 and HER4 were mainly expressed in mucosa-associated lymphoid tissue (MALT) and follicular lymphoma. Immunoprecipitation of Raji and Daudi cell lines revealed that recombinant NRG4 induced the tyrosine phosphorylation of HER4. Additionally, recombinant NRG4 activated the proliferation of lymphoma cell lines. These findings suggest that the NRG4-HER4 axis plays a major role in the proliferation of malignant lymphoma cells in the gastrointestinal tract.
 ...
PMID:The role of neuregulin4 and HER4 in gastrointestinal malignant lymphoma. 2180 36