Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 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

Breast cancer is the most common malignant tumor among women, comprising an estimated 24% of all cancer cases and 18% of all cancer deaths. At least half of the patients with primary breast cancer will ultimately die by metastatic disease. The tumor characteristics, the natural course of the disease and the response to therapy vary strongly. A number of recently detected cell biological parameters such as oncogenes/suppressor genes, growth factors and secretory proteins are more or less important prognostic factors, because they influence the characteristics and behavior of a tumor with respect to metastatic pattern, extent of cellular differentiation, growth rate and response to treatment. However, there is no clear consensus how best to identify patients at high or low risk. In our experience c-myc amplification and pS2 protein are strong prognosticators for relapse rate, while in advanced disease (apart from a negative estrogen/progesterone receptor/pS2 status) amplification of HER2/neu is a good prognosticator for failure to endocrine therapy. In the diagnosis of breast cancer, in vivo imaging of tumors by labeled hormones or other factors also forms a new development which might have implications for treatment too. With respect to treatment both endocrine and chemotherapy can cure a minority of patients with micrometastases, but in patients with advanced disease only a prolongation of (progression-free) survival can be reached. Response rates decrease with increasing tumor load. In the past decade a number of interesting new endocrine agents has been developed such as new (pure) (anti)steroidal agents, vitamins, aromatase inhibitors, analogs of peptide hormones, prolactin inhibitors and growth factor antagonists. However, less is known on the (potential) interaction between hormones, chemotherapeutic agents, retinoids, cytokins, growth factor antagonists and irradiation. Rapid detection of new powerful combination therapies are needed to improve treatment results during the nineties.
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PMID:Clinical breast cancer, new developments in selection and endocrine treatment of patients. 144 97

Fifty patients with typical infiltrating ductal adenocarcinoma of the breast were studied for amplification of the c-erb B-2 (neu/HER-2) oncogene within the tumor DNA. Amplification, ranging from 4 to greater than 50 copies per cell, was observed in 17 (34%) of the samples. The presence of c-erb B-2 gene amplification was not significantly correlated with patient survival, metastases, recurrence, or overall histologic grade. However, amplification was significantly associated with increased mitotic activity. Also, amplification of c-erb B-2 showed a significantly negative association with both progesterone and estrogen receptor presence. Progesterone receptor presence correlated significantly with survival.
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PMID:Amplification of the c-erb B-2 oncogene and prognosis of breast adenocarcinoma. 196 29

The human homolog of the rat neu oncogene, HER2 (also termed c-erbB2) has been demonstrated in amplified form in human breast tumors with poor prognosis. Although amplification of the gene correlates with expression of a 185-kDa transmembrane glycoprotein, no extensive information is available regarding the extent of tissue and tumor specificity of this gene product. We have addressed this issue by immunohistochemically evaluating the expression of p185 HER2 in normal tissue and various tumors using monoclonal antibodies (MAbs) to distinct epitopes of its extracellular domain. No detectable levels of p185 HER2 were found in fetal tissues analyzed, with the exception of renal tubules in 2 out of 3 specimens tested and in intestinal epithelium. In adult tissues, detectable levels of this glycoprotein were found in a restricted number of cell types, the expression being heterogeneous among individuals and cell histotypes. Among the neoplasms assayed p185 HER2 was expressed in 46% of primary breast cancers, in 28% of ovarian tumors and in 30% of colon rectum malignancies. No male breast adenocarcinomas were p185-positive. A large number of other tumors tested revealed only a low incidence of expression of the p185. In metastatic breast tumors p185 HER2 was demonstrated homogeneously among multiple autologous lesions and almost invariably (80%) the expression of p185 in the primary lesion correlated with that of the deriving metastases. Our findings indicate that the expression of the p185 HER2 represents a tumor marker of clinical relevance in breast cancer. Whether this holds true for other malignancies remains to be explored.
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PMID:Expression of the p185 encoded by HER2 oncogene in normal and transformed human tissues. 196 37

Prompted by recent findings on the amplification of c-erbB-2 (HER-2, neu) oncogene in salivary gland tumours, the present study was conducted to analyse the expression of c-erbB-2 in both benign and malignant salivary gland tumours, with special emphasis on its prognostic significance and relevance to clinical data. A series of 219 salivary gland tumours (with pertinent clinical data), including 103 malignant and 116 benign tumours, were analysed immunohistochemically using a monoclonal antibody to c-erbB-2 protein. Smoking was not a risk factor for malignant tumours, smokers being equally represented in both groups: 18.4 and 21.6% in malignant and benign series, respectively. Multi-variate analysis of the extensive clinical data did not disclose any other risk factors either. Cellular membrane staining for c-erbB-2 was present in 36 (35.0%) carcinomas and 41 (35.3%) benign tumours. Among the malignant tumours, c-erbB-2 expression was most frequent in adenoid cystic carcinomas (57.7%) followed by adenocarcinomas (39.3%). Among the benign tumours, 47% of Warthin's tumours and 33.3% of the pleomorphic adenomas showed staining for c-erbB-2. The highest prevalence of c-erbB-2 immunoreactivity was seen in adenocarcinomas of the parotid gland (81.8%), followed by undifferentiated carcinomas (75%) and adenoid cystic carcinomas (73.3%) in that location. Age at diagnosis, number of recurrences, analysis as well as time to relapse or metastases were similar in c-erbB-2-positive and -negative malignant tumours. Also mortality in c-erbB-2-positive and -negative salivary gland cancers was similar.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:c-erbB-2 oncogene expression in salivary gland tumours. 791 30

For the integration of new cell biological prognostic factors in daily clinical practice, we need to know not only their prognostic power with respect to prediction of relapse free and overall survival, but also their possible relation to response to endocrine therapy or chemotherapy in order to select adequate treatment for each patient. A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficult to predict the response to treatment accurately. A valuable prognostic factor can be a worthless predictive factor for endocrine therapy or chemotherapy, and vice versa. High tumour levels of ER, PGR, AR and PS2 protein predict a relatively good response to endocrine therapy, whereas EGFR positivity, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high u-PA levels indicate a good chance of a poor response to endocrine therapy in metastatic breast cancer. With respect to chemotherapy, a high proliferation rate and HER2/neu amplification predict a good response to therapy in metastatic disease, whereas MDR gene expression and possibly c-myc amplification are related to a worse response. In conclusion, the newer cell biological parameters can be used to select high and low risk patients and type of systemic treatment and can be used as targets for new treatment modalities.
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PMID:Prognostic factors and response to therapy in breast cancer. 801 96

A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficulty accurately to predict the response to treatment. A valuable prognostic factor can be a poor predictive factor for response, and vice versa. High tumor levels of ER, PgR, AR and pS2 predict a relatively good response to endocrine therapy, while EGF-R positively, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high uPA levels indicate a high chance of poor response to endocrine therapy in metastatic breast cancer. With respect to chemotherapy, a high proliferation rate and HER2/neu amplification predict a good response to therapy in metastatic disease, while MDR gene expression and possibly c-myc amplification are related to a worse response. In conclusion, the newer cell biological parameters can be used to select high and low-risk patients, type of systemic treatment, and as targets for new treatment modalities.
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PMID:Cell biological factors associated with the response of breast cancer to systemic treatment. 848 34

The management of metastatic breast cancer continues to provide enormous challenges. The taxanes have significant activity in patients with resistant disease, and combination regimens are being evaluated as first-line therapy. The combination of paclitaxel and doxorubicin appears to have substantial activity, but troublesome cardiac toxicity has been noted in a recently reported study. Docetaxel has been shown to be very active in initial phase II evaluation, notably in women with anthracycline-resistant disease. The controversy over high-dose therapy continues, and its role in the management of metastatic breast cancer outside the confines of clinical trials remains unclear. The HER-2 protein appears to be a predictive factor for patients with metastatic disease. Antibody therapy directed at this target can produce responses in a proportion of patients. Bisphosphonates appear to be beneficial to patients with lytic bony metastases when administered in conjunction with cytotoxic or hormonal therapy.
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PMID:Metastatic breast cancer. 897 68

The HER2/neu gene, which is overexpressed in 20-30% of human breast tumors, encodes a receptor tyrosine kinase that functions through multiple signaling pathways to regulate the activity of nuclear transcription factors. We have reported that PEA3, an Ets family transcription factor, is overexpressed in HER2/Neu-induced breast tumors and their metastases. To account for the increased levels of PEA3 in these tumors we have suggested that HER2/Neu enhances PEA3 transcriptional activity, which then acts to stimulate expression of the PEA3 gene. This hypothesis is consistent with the occurrence of PEA3 binding sites in the PEA3 promoter and with the ability of PEA3 to transactivate this promoter. To learn whether HER2/Neu indeed regulates PEA3 activity we measured the capacity of constitutively-activated HER2/Neu to affect PEA3-dependent reporter gene expression. Coexpression of PEA3 and HER2/Neu stimulated PEA3-dependent reporter gene expression to a much greater extent than did either protein alone suggesting that HER2/Neu upregulates the transcriptional activity of PEA3. To define the pathway whereby HER2/Neu functions we employed dominant-negative mutants of signaling proteins known to be downstream of HER2/Neu. Overexpression of Rap1a, a Ras-related protein capable of antagonizing Ras function, completely inhibited the ability of HER2/Neu to stimulate PEA3-dependent gene expression. Ras is known to stimulate at least two mitogen-activated protein kinase (MAPK) cascades, the extracellular-regulated kinase (ERK) cascade and the stress-activated kinase (SAPK) or Jun kinase (JNK) cascade. Similarly, HER2/Neu activated both ERKs and SAPKs/JNKs in a Ras-dependent fashion. Dominant-inhibitory mutants in either the ERK or SAPK/JNK cascades partially inhibited HER2/Neu activation of PEA3-dependent gene expression. These findings suggest that HER2/Neu regulates PEA3 activity through two different Ras-dependent MAPK pathways.
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PMID:The PEA3 Ets transcription factor is a downstream target of the HER2/Neu receptor tyrosine kinase. 946 55

The clinicopathologic features of 32 metaplastic carcinomas with heterologous osteocartilaginous elements are reported. Each neoplasm consisted of invasive adenocarcinoma accompanied by a cartilaginous or osseous component. In 10 neoplasms, this consisted of cartilage and in 2 the heterologous element was osteoid or bone exclusively. The remaining 20 neoplasms contained a mixture of cartilaginous and osseous components. All patients were women; mean age was 56 years. Twenty-four patients were treated using mastectomy and eight by local excision. Twenty-six patients underwent axillary lymph node dissection. Lymph node metastases were detected in 6 of the 26 (23%) patients who underwent axillary dissection. Clinical follow-up was available for 29 of 32 patients (91%). Local recurrence or distant metastases developed in 6 patients (21%) within 2 years of initial treatment, and 4 of these patients died of metastatic carcinoma. The overall 5-year survival rate was 60%. When compared with control patients with infiltrating duct carcinoma, the group with metaplastic carcinoma tended to have a more favorable prognosis after adjustment for nodal status and tumor size. The prognosis of patients with metaplastic mammary carcinoma with heterologous osteocartilaginous elements is dependent on tumor stage at diagnosis. Immunohistochemical studies for 34BE12, p53, retinoblastoma protein, HER/2neu (polyclonal), epidermal growth factor receptor, and cyclin D1 were performed in 18 cases. Positive immunohistochemical staining was found as follows: 34BE12: n = 13 (72%); p53: n = 11 (61%); retinoblastoma protein: n = 12 (66%); HER2/neu: n = 2 (11%); epidermal growth factor receptor: n = 7 (38%); and cyclin Dm: n = 5 (28%). Positive staining for 34BE12 was observed in the carcinomatous component in 5 (38%) of the neoplasms, in the metaplastic component in 2 (15%), and in both elements in 6 (64%). A p53 staining was observed in the carcinomatous component exclusively in 4 (36%) of 11 p53-positive tumors. No disparity in p53 staining was noted between the epithelial and metaplastic elements in the other p53-positive tumors. Expression of these markers did not correlate with clinicopathologic features such as patient age, tumor size, tumor type, relative proportion of metaplastic elements, and axillary nodal status and was not predictive of disease-free survival.
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PMID:Metaplastic carcinoma of the breast with osteocartilaginous heterologous elements. 950 Feb 19


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