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)

To investigate the possibility that the epidermal growth factor (EGF) receptor functions as an oncogene product, we have determined the levels of EGF receptor protein and RNA in a variety of malignant and normal human cells, using a specific polyclonal antibody to the EGF receptor and a cDNA clone (plasmid pE7) that encodes the EGF receptor, respectively. Besides A431 epidermoid carcinoma cells, which are known to make large amounts of EGF receptor, cell lines from two ovarian cancers, two cervical cancers, and one kidney cancer were found to contain substantial amounts of receptor protein (11-22% of A431). Normal human fibroblasts (Detroit 551), a human lymphocyte line (IM-9), and a leukemic lymphocyte line (CEM) contained low or undetectable levels of EGF receptor. RNA blot analysis showed that among the human cell lines examined the levels of a 10- and a 5.6-kilobase species of pE7-specific RNA generally correlated with the amount of the EGF receptor protein. Genomic DNA blot analysis revealed that except for A431 none of these cell lines expressing high levels of EGF receptor protein possessed amplified receptor gene sequences. A431 cells are known to secrete a truncated form of the EGF receptor. An abundant 2.9-kilobase RNA is found only in A431 cells; it could encode the truncated form of the EGF receptor.
 ...
PMID:Characterization of epidermal growth factor receptor gene expression in malignant and normal human cell lines. 609 84

The epidermal growth factor (EGF) receptor and its ligand transforming growth factor-alpha (TGF-alpha) are overexpressed in human renal cell carcinoma (RCC). The chimeric anti-EGF receptor monoclonal antibody C225 was used to determine the effects of blocking the EGF receptor on RCC growth both in vitro and in vivo. A panel of RCC cell lines all tested positive at various levels for EGF receptor cell surface expression. C225 inhibited DNA synthesis of cultured A498, Caki-1, SK-RC-4, SK-RC-29, and SW839 cells in a dose-dependent manner, ranging from 20 to 45% inhibition compared with untreated controls. C225 also inhibited exogenous ligand-stimulated tyrosine phosphorylation of EGF receptor on RCC cells. The antitumor effects of C225 on RCC tumor growth were evaluated in ascites, s.c., and orthotopic RCC xenograft models. Mice treated with C225 in a Caki-1 ascites xenograft model showed a significant increase in survival (P = 0.002). All control mice died with ascites tumors by week 9, whereas >70% of C225-treated mice survived beyond 12 weeks. C225 also inhibited the growth of s.c. SK-RC-29 tumors in a dose-dependent manner. Mice treated with C225 (1 mg/dose) displayed a significant decrease in tumor volume compared with mice treated with control antibody (P < 0.05) or vehicle alone (P < 0.01). Lastly, C225 inhibited the growth and metastasis of RCC tumors growing orthotopically in the renal subcapsule of nude mice. Histological examination of RCC tumors from mice treated with C225 showed a substantial decrease in proliferating cell nuclear antigen staining and an increase in tumor cell apoptosis. These data suggest that C225 affects growth of RCC tumors by inhibiting EGF receptor-dependent proliferation and demonstrate the potential for therapeutic application of C225 in the treatment of human renal cancer.
 ...
PMID:Mouse-human chimeric anti-epidermal growth factor receptor antibody C225 inhibits the growth of human renal cell carcinoma xenografts in nude mice. 986 6

HER-2/neu is a tumor-associated antigen overexpressed in a large variety of human tumors. Eight HER-2/neu peptides displaying HLA-A*0201 anchoring motifs were selected and tested for their binding affinity to HLA-A*0201 and their capacity to elicit cytotoxic T lymphocyte (CTL) responses in both HLA-A*0201 transgenic mice and in HLA-A*0201(+) healthy donors. Two high-affinity (p5 and p48) and one intermediate-affinity (p1023) peptides triggered CTL responses in both transgenic mice and humans, comparable to those observed for the well-known HER2/neu dominant peptide p369. CTL induced in transgenic mice lysed HLA-A*0201(+) RMA cells infected with recombinant HER-2/neu but not cells infected with wild-type vaccinia virus. Human CTL lysed HLA-A*0201(+) HER-2/neu(+) tumor cells of different origins (breast, colon, lung and renal cancer) irrespective of the expression levels of HER-2/neu. Importantly, primed CTL specific for these epitopes were detected in freshly isolated tumor-infiltrating lymphocytes from three renal cell carcinoma patients. Therefore, the HER-2/neu peptides p5, p48 and p1023 may be good candidates for immunotherapy of a broad spectrum of tumors, including renal cell carcinoma.
 ...
PMID:Identification of HER-2/neu immunogenic epitopes presented by renal cell carcinoma and other human epithelial tumors. 1174 43