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)

The occurrence of ERBB-2 (HER-2/NEU) oncogene amplification was studied in 203 DNA samples obtained from 175 cancer patients. Amplification of ERBB-2 oncogene was established in 14 out of 63 (22%) patients with breast cancer, 1 out of 23 cases of ovarian tumor, 1 out of 19 cases of large bowel cancer and 1 out of 27 patients with cancer of the thyroid. Patients with lung cancer (34), soft tissue sarcoma (6) and malignant melanoma (3) failed to reveal any changes in the above oncogene. A tendency was established for ERBB-2 oncogene amplification to be associated with lymph node involvement in female patients with breast cancer: amplification was observed in 9 out of 28 patients presenting with lymph node metastases and only in 5 out of 29 metastases-free cases. To summarize, ERBB-2 oncogene is fairly often activated in human tumors but a high occurrence of the gene amplification was observed in female patients with breast cancer only.
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PMID:[The search for amplification of the ERBB-2 oncogene in human tumors]. 130 Jul 65

The etiology of cancer is a complex interplay of various factors, including genetic alterations. Multiple studies have been carried out to identify and characterize mutations that frequently occur during tumorigenesis. In human breast cancer, amplification of proto-oncogenes (c-myc, c-erbB-2/neu) and chromosome 11q13, mutation of p53 and loss of heterozygosity (chromosomes 1, 3p, 6q, 7q, 11p, 13q, 16q, 17, 18q and 22q) represent the major types of genetic abnormalities that have been frequently observed in tumor DNAs. The genetic deletions and mutations could inactivate tumor-suppressor genes. In some studies, specific alterations have been associated with some clinical parameters. Recently, linkage analyses, on large families with a predisposition to breast cancer, have been performed to map putative breast cancer susceptibility genes. The survey of high risk patients should be organised to make an earlier diagnosis.
Bull Cancer 1992
PMID:[Molecular analysis of breast cancers: recent developments]. 130 32

Among the various factors reported as having significant prognostic value in primary breast cancers, the author discusses the value of well established "classical" prognostic factors used routinely and "new" prognostic factors developed over recent years as a result of progress in cell and molecular biology. The presence of axillary lymph node metastases remains the most important prognostic factor of recurrence, justifying post-surgical adjuvant therapy. However, in patients with negative axillary nodes (N-), the size of the tumour, Scarff-Bloom-Richardson (SBR and MSBR) histological grade, certain particular histological types (carcinoma in situ and tubular, colloid or pure papillary cancer) and hormone receptors (ER and PR) appear to be well established prognostic factors allowing the identification, within this group of N- patients who generally have a good prognosis, those patients with a low risk of recurrence and therefore not requiring adjuvant therapy. In contrast, the proliferative activity (ploidy and S phase, Thymidine Labeling Index, antibody Ki67), cathepsin D, thymidine kinase, EGF receptors, several genes including oncogene HER-2/neu, are recently developed prognostic factors whose significance needs to be confirmed by further studies.
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PMID:[Prognostic factors in breast cancer]. 134 Jan 64

HER-2/neu oncogene protein, epidermal growth factor receptor, progesterone receptor, and estrogen receptor were examined immunohistochemically in specimens of normal and neoplastic endometrium. Tissues obtained at the time of hysterectomy were snap-frozen at liquid nitrogen temperature and serially sectioned at 4 microns. Normal endometrial epithelial cells stained with anti-epidermal growth factor receptor and anti-HER-2/neu with intensities graded from 0 to 3+. Of the 49 endometrial malignancies studied, seven (14%) contained tissue exhibiting HER-2/neu staining in excess (4+) of any of the normal tissues or the other 42 cancer specimens. Expression of both HER-2/neu and steroid receptors was heterogeneous within these seven tumors. To examine this heterogeneity more closely, sections of these and other tumors were double-stained for HER-2/neu and progesterone receptor. It was found that the cells exhibiting 4+ HER-2/neu staining were progesterone receptor-negative. Conversely, cells that were progesterone receptor-positive within the same specimen exhibited HER-2/neu immunostaining equal to or less than 3+. All specimens containing 4+ HER-2/neu tissue were graded 1 or 2 adenocarcinomas, stage I. Thus, there is an inverse relationship between overexpression of HER-2/neu and progesterone receptor in endometrial cancer. On the other hand, overexpression of HER-2/neu in endometrial cancer does not seem to be related to loss of other differentiated characteristics. The prognostic value of these observations awaits continued study.
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PMID:Immunohistochemical study of HER-2/neu, epidermal growth factor receptor, and steroid receptor expression in normal and malignant endometrium. 134 72

Overexpression of the c-erbB-2/neu protooncogene has recently been shown in ovarian tumors collected from the United States. It is known that environmental and cultural factors may contribute to certain types of cancer, therefore, we examined expression of c-erbB-2/neu in ovarian tumors collected from China by immunohistochemical staining. Out of 81 tumor specimens, 57 (70.4%) were found to be immunopositive, whereas only one out of 17 (5.9%) normal ovarian tissue samples was slightly positive. Our results indicate that overexpression of c-erbB-2/neu is a general phenomenon for ovarian cancer regardless of different population. To search for a c-erbB/neu overexpressing cell line for future study on molecular mechanism, we also analyzed 13 cancer cell lines from the female genital tract for expression of c-erbB-2/neu. The c-erbB-2/neu RNA was found to be overexpressed at least 100-fold in one of the four ovarian cancer cell lines examined. An aberrant c-erbB-2/neu RNA was also found to be overexpressed in this cell line. Southern blot analysis indicated that the c-erbB-2/neu was amplified 2-4-fold in this line, and some of these alleles have structural alteration which may account for expression of the aberrant c-erbB-2/neu RNA. Since the 2-4-fold gene amplification is not proportional to the greater than 100-fold overexpression in RNA, other mechanisms such as transcriptional or posttranscriptional control must be involved in overexpression of this gene in ovarian cancer.
Cancer Lett 1992 Jan 10
PMID:Aberrant expression of the c-erbB-2/neu protooncogene in ovarian cancer. 134 99

Of 221 patients with breast cancer of known epidermal growth factor receptor (EGFR) and oestrogen receptor (ER) status, 99 had developed recurrences during the period of follow-up (range 3-60 months, median 24 months). Of these, 72 received endocrine therapy as first-line treatment for relapse. Immunohistochemical assessment of c-erbB-2 protein product expression was made using paraffin-embedded tumour tissue from 65 of these 72 patients. Including patients whose disease remained stable for more than 6 months with those showing an objective response (CR or PR for more than 3 months), only one (7%) of 14 c-erbB-2 positive tumours responded to endocrine manipulation compared with 19 (37%) of 51 c-erbB-2 negative tumours (P less than 0.05). Coexpression of c-erbB-2 reduced the response rate of ER positive patients from 48% to 20% and of ER negative cases from 27% to 0% (P less than 0.01). EGFR and c-erbB-2 protein appeared to have additive effects in reducing the likelihood of response, and none of eight patients with EGFR positive, c-erbB-2 positive tumours derived benefit from endocrine therapy. The results of this study suggest that c-erbB-2 protein overexpression, a marker of poor prognosis in breast cancer, is associated with a lack of response to endocrine therapy on relapse, and particularly in combination with EGFR may be useful in directing therapeutic choices.
Br J Cancer 1992 Jan
PMID:Relationship between c-erbB-2 protein product expression and response to endocrine therapy in advanced breast cancer. 134 66

Sixty-eight patients with advanced breast cancer were treated with mitoxantrone and clinical responses assessed. Expression of c-erbB-2 protein and cytosolic glutathione S-transferase (GST) isoenzymes pi, alpha and mu by the primary tumours of these patients was determined immunohistochemically, and correlated with treatment response. Tumours overexpressing c-erbB-2 (n = 16, 23%) showed a lower response rate (50% vs 58%) and shorter duration of response to treatment, compared with c-erbB-2 negative tumours. These associations were not statistically significant but survival following start of treatment was significantly shorter in the c-erbB-2 positive group. For each GST isoenzyme, the response rate and duration of response of the group showing enzyme expression did not differ significantly from those with negatively staining tumours. These data do not support a role for expression of GSTs alone in resistance to mitoxantrone monotherapy in advanced breast cancer. The poorer post treatment survival of patients with c-erbB-2 positive tumours suggests they could be selected for more intensive treatment regimens.
Br J Cancer 1992 Feb
PMID:Response to mitoxantrone in advanced breast cancer: correlation with expression of c-erbB-2 protein and glutathione S-transferases. 134 48

To develop an efficient strategy for the targeting of anti-tumor effector cells, we prepared bispecific antibody (BsAb) containing anti-CD3 and an anti-c-erbB-2 proto-oncogene product. The prepared BsAb specifically reacts with both c-erbB-2-positive tumor cells and CD3+ CTL. Human CD4+ helper/killer T cells, induced from peripheral-blood mononuclear cells by activation with immobilized anti-CD3 monoclonal antibody (MAb) plus IL-2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4+ helper/killer cells with the BsAb caused the induction of specific cytotoxicity against c-erbB-2-positive tumor cells. CD4+ helper/killer cells also produced significant amounts of IL-2 during co-culture with c-erbB-2-positive tumor cells in the presence of the BsAb. Moreover, by combination with the BsAb, CD4+ helper/killer cells showed a strong in vivo anti-tumor effect against c-erbB-2 transfectant or human colon-cancer cells implanted in nude mice. Our results strongly suggest that the c-erbB-2 proto-oncogene product on human tumor cells may be a good target for BsAb-directed adoptive tumor immunotherapy.
Int J Cancer 1992 Mar 12
PMID:Human c-erbB-2 proto-oncogene product as a target for bispecific-antibody-directed adoptive tumor immunotherapy. 134 16

The expressions of epidermal growth factors (EGF), epidermal growth factor receptors (EGFR), and the c-erbB-2 oncoprotein were immunohistochemically examined in 25 cases of human pancreatic carcinoma and epineoplastic pancreatitis and in 10 non-cancerous/non-inflammatory pancreatic tissues. The positive rates of EGF, EGFR, and the c-erbB-2 oncoprotein in cancer tissues were 72%, 36%, and 28%, respectively. EGF was stained mainly in the cytoplasm and partly on the surfaces of the cancer cells. EGFR and the c-erbB-2 oncoprotein were stained mainly on the surfaces of the cancer cells and partly in the cytoplasm. The expressions of these 3 products correlated significantly with tumor invasion into the anterior and posterior areas surrounding the pancreas. In the EGF, EGFR, and c-erbB-2 positive cancer tissues, some stromal cells, that is fibroblasts and endothelial cells, were also positive. In the adjacent pancreatic tissues with inflammation, these products were noted in some ductal cells, acinar cells, fibroblasts and endothelial cells. No distinct staining was detected in non-cancerous/non-inflammatory tissues. The survival period for patients who tested positive for these three proteins was statistically shorter than for those who tested negative. These results suggest that the coexpression of EGF and EGFR and the expression of the c-erbB-2 oncoprotein are related to the existence of the invasion of human pancreatic cancer. Furthermore, an immunohistochemical examination of these three products is useful in forming a prognosis for pancreatic cancer patients.
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PMID:The immunohistochemical expressions of epidermal growth factors, epidermal growth factor receptors and c-erbB-2 oncoprotein in human pancreatic cancer. 134 73

The HER-2/neu oncogene encodes a Mr 185,000 transmembrane phosphoglycoprotein which is overexpressed in 25-35% of breast and ovarian neoplasms and portends a poor prognosis. We have studied the feasibility of targeting this oncoprotein, designated p185, with radioiodinated murine monoclonal antibodies (muMABs) 4D5 and 7C2, which recognize distinct epitopes on its extracellular domain. The rates of internalization and catabolism of these antibodies were analyzed by cellular radioimmunoassay and electron microscopy. After binding to NIH3T3 HER-2/neu cells, which show high surface expression of p185, the muMABs were endocytosed via coated pits, routed to lysosomes, and degraded. Approximately 44% of 125I-4D5 and 39% of 125I-7C2 were catabolized by tumor cells after 24 h. The biodistribution of radiolabeled 4D5 and 7C2 were evaluated in beige/nude mice bearing s.c. NIH3T3 HER-2/neu grafts. A high specificity of localization was seen with tumor:organ ratios of activity generally ranging from 5:1 to 30:1. However, the percentage injected dose of radioactivity per gram of tumor declined sharply from 25% at 24 h to 5% at 120 h postinjection. Treating the animals with 400-700 muCi 131I-4D5 caused a marked inhibition of tumor growth, although no mice were cured. Unlabeled 4D5 had no effect on tumor progression in this model, but administering 400-700 muCi of 131I-DA4-4, an isotype-matched irrelevant muMAB, resulted in an intermediate degree of growth retardation. Analysis of kinetic blood data and whole-body time-activity curves indicated that the irrelevant conjugate remained in the body 2-3 times longer than 131I-4D5. Radioiodinated anti-HER-2/neu muMABs are attractive agents for radioimmunodiagnosis and radioimmunotherapy of aggressive HER-2/neu-positive breast and ovarian carcinomas, but effective strategies for retarding intratumoral catabolism may be necessary to optimize their clinical utility.
Cancer Res 1992 Apr 01
PMID:Radiolabeled antibody targeting of the HER-2/neu oncoprotein. 134 16


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