Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Interleukin-6 (IL-6) is a cytokine that was initially recognized as a regulator of immune and inflammatory responses, but it also regulates the growth of many tumour cells, including prostrate carcinoma. Overexpression of the growth-factor receptors ErbB2/neu and ErbB3 has been implicated in the neoplastic transformation of prostate carcinoma. Here we show that treatment of the prostate cancer cell line LNCaP with IL-6 induces tyrosine phosphorylation of ErbB2 and ErbB3, but not ErbB1/EGFR. We also show that ErbB2 forms a complex with the gp130 subunit of the IL-6 receptor in an IL-6-dependent manner. This association is important because the inhibition of ErbB2 activity results in abrogation of IL-6-induced MAPK activation. Thus ErbB2 is a critical component of IL-6 signalling through the MAP kinase pathway. These data show how a cytokine receptor can diversify its signalling pathways by engaging with a growth-factor receptor kinase.
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PMID:Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. 959 Jun 94

Tumor size, axillary nodal status, histologic grading and the hormonal receptor status are the established prognostic factors for breast carcinoma. Concurrent to these factors the clinical validation of the new innovative tumor characteristics from molecular biology is difficult to achieve. Clinicians are more and more interested in indicators of response to particular treatments (predictive factors) and less in prognostic factors relevant for the natural course. The hormonal receptor status is the best known predictive factor with regard to the response to hormonal treatment. Among the innovative parameters the tumor suppressor gene p53 and the oncogene Her2/neu show a good correlation to sensitivity to cytostatic treatment. The detection of more and more molecular mechanisms of tumor growth and tumor spread raise hopes that innovative treatment approaches will lead to an antineoplastic effect. The molecular tumor parameters then may play the role of predictive factors for a specific treatment. For the present the established tumor factors should be used as the base for a treatment plan and the available already known predictive factors should be taken into consideration.
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PMID:[Relative indicators for disease outcome in breast carcinoma]. 960 45

The ability of interleukin (IL)-12 to prevent tumors when administered to individuals with a genetic risk of cancer was studied in two lines of transgenic mice expressing rat HER-2/neu oncogene in the mammary gland. Female BALB/c (H-2(d)) mice carrying the activated HER-2/ neu oncogene show no morphological abnormalities of the mammary gland until 3 wk of age. They then progress through atypical hyperplasia to in situ lobular carcinoma and at 33 wk of age all 10 mammary glands display invasive carcinomas. Adult FVB mice (H-2(q)) carrying the HER-2/neu protooncogene develop mammary carcinomas with a longer latency (38-49 wk) and a lower multiplicity (mean of 2.6 tumors/mice). Treatment with IL-12 (5 daily intraperitoneal injections, 1 wk on, 3 wk off; the first course with 50 ng IL-12/day, the second with 100 ng IL-12/day) begun at 2 wk of age in BALB/c mice and at 21 wk of age in FVB mice markedly delayed tumor onset and reduced tumor multiplicity. Analogous results were obtained in immunocompetent and permanently CD8(+) T lymphocyte-depleted mice. In both transgenic lines, tumor inhibition was associated with mammary infiltration of reactive cells, production of cytokines and inducible nitric oxide synthase, and reduction in microvessel number, in combination with a high degree of hemorrhagic necrosis.
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PMID:Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice. 968 35

The HER2/neu oncogene encodes a cell surface protein which plays a role in growth factor-stimulated mitogenic signaling. HER2/neu is overexpressed in 30-40% of human breast carcinomas. This study tested the hypothesis that inhibiting HER2/neu expression using a phosphorothioate antisense (AS) oligonucleotide would inhibit the growth of breast cancer cells that overexpress this gene. A human breast carcinoma cell line, BT474, which overexpresses the HER2/neu oncogene was exposed to AS, sense (S), or scrambled antisense (SC) phosphorothioate oligonucleotides in tissue culture. Treatment with AS oligonucleotides specifically downregulated HER2/neu mRNA expression and resulted in lower levels of the HER2/neu protein product, p185; control oligonucleotides had no such effect. AS oligonucleotide treatment significantly inhibited the in vitro growth of BT474 cells, whereas S and SC controls had little effect on BT474 growth. HER2/neu AS oligonucleotide treatment had no effect on the growth of a distinct breast cancer line, MCF7, which expresses low levels of the HER2/neu oncogene. Breast carcinoma cells which overexpress the HER2/neu gene appear to be dependent on continued expression of this oncogene for cell growth. AS oligonucleotide pharmaceuticals which interfere with the expression of the HER2/neu oncogene may be of use in the therapy of some patients with breast carcinoma.
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PMID:Antisense oligonucleotides specific for the HER2/neu oncogene inhibit the growth of human breast carcinoma cells that overexpress HER2/neu. 969 39

Transgenic mice carrying the HER-2/neu proto-oncogene under tissue-specific transcriptional control of a mammary tumor virus long terminal repeat (Tg-MMTVneu mice) spontaneously develop mammary carcinomas. HER-2/neu is a tumor antigen that can be recognized by cytotoxic T lymphocytes if tumor cells present the appropriate major histocompatibility complex (MHC) class I glycoproteins. The purpose of this work was to assess whether mammary carcinomas arising in Tg-MMTVneu mice correctly expressed MHC (H-2q) class I gene products. We analyzed by flow cytometry 51 primary tumors from 19 transgenic mice. About one-half of the tumors showed a reduced expression of class I antigens. All tumors were highly positive for membrane neu. Some mice had multiple mammary carcinomas with widely different MHC expression levels, and most mice had at least one tumor with a low expression. Treatment with gamma-interferon of carcinoma cells cultured in vitro induced a strong reexpression of H-2q antigens. Our results suggest that the immune response activated in vivo by HER-2/neu-positive tumors can lead to the emergence of escape variants characterized by a down-regulation of MHC class I products.
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PMID:Down regulation of major histocompatibility complex class I expression in mammary carcinoma of HER-2/neu transgenic mice. 971 68

We identified an NH2-terminally truncated HER-2/neu product of M(r) 95,000 with in vitro kinase activity by Western blotting and immunoprecipitations using domain-specific antibodies. p95 levels correlated with the extracellular domain (ECD) shed from different cells under varied conditions. Both ECD and p95 were at approximately 20-fold lower levels in SKOV3 ovarian carcinoma cells, as compared to BT474 breast carcinoma cells. Both were stimulated by treatment of cells with the phorbol ester tumor promoter phorbol 12-myristate 13-acetate and the lysosomotrophic agent chloroquine. The hydroxamate inhibitor of metalloproteases, TAPI, suppressed both p95 and ECD in a dose-dependent fashion, with maximal inhibition at < or = 10 microM in BT474 cells. Cancer tissues were analyzed by Western blotting and scored for p95HER-2/neu and for p185HER-2/neu expression. Breast and ovarian cancer tissues were both found to express p95HER-2/neu in addition to p185HER-2/neu. Of 161 breast cancer tissues, 22.4% expressed p95, 21.7% overexpressed p185, and 14.3% were p95 positive and overexpressed p185. A higher proportion of node-positive patients (23 of 78) than node-negative patients (9 of 63) expressed p95 in all tumors combined (P = 0.032). In the group that overexpressed p185, those that contained p95 were associated with node-positive patients (15 of 21), whereas those that were p95 negative were associated with node-negative patients (8 of 11; P = 0.017). Neither p95- nor p185-rich patients significantly correlated with tumor size or with hormone receptor status in this study. Our findings show that breast cancers, which express the HER-2/neu oncogene, are heterogeneous with respect to HER-2/neu protein products. p95HER-2/neu appears to distinguish tumors that have metastasized to the lymph nodes from those in node-negative patients.
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PMID:NH2-terminally truncated HER-2/neu protein: relationship with shedding of the extracellular domain and with prognostic factors in breast cancer. 982 22

We have previously shown that neu oncogene-initiated rat mammary carcinomas uniquely over-express neu-related lipocalin (NRL), a member of the calycin protein superfamily. Here, we characterize the putative human homolog of NRL, neutrophil gelatinase-associated lipocalin (NGAL). ngal gene expression was found at moderate levels in only 2 of 17 human tissues examined, breast and lung. When breast cancers were examined for NGAL mRNA and protein levels, they were found to exhibit heterogeneous expression. NGAL levels varied in these tumors from undetectable to exceeding those in normal breast parenchyma. Immuno-histochemical analysis confirmed the presence of NGAL within breast carcinoma cells but detected only low levels of this protein in normal ductal epithelium. In contrast, large amounts of the protein were localized to the lumen of normal breast ducts in the vicinity of NGAL-expressing tumors. Interestingly, unlike NRL in rat mammary carcinomas, no significant association between NGAL expression and HER-2/neu activation was found in human breast tumors. In contrast, a significant correlation between NGAL expression in breast cancer was found with several other markers of poor prognosis, including estrogen and progesterone receptor-negative status and high proliferation (S-phase fraction). NGAL levels were stratified as high or low in breast cancers from a cohort of node-positive patients with known outcome. No significant association between NGAL expression and disease-free or overall survival was observed.
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PMID:Heterogeneous expression of the lipocalin NGAL in primary breast cancers. 984 63

erbB2/neu, an overexpressed oncogene product, has been proposed as a human cancer vaccine target. In the present study, transgenic (rat neuNT oncogene) FVB/neu mice, developing metastasizable mammary carcinoma, were immunized with a plasmid DNA encoding are not tolerant to the self antigen and sequences. We report that transgenic tumour-bearing mice, like some breast cancer patients erbB2 + X, develop anti-neu autoimmune responses, which can be boosted and skewed to a Th1 phenotype by DNA immunization. Intramuscular injections of neuNT plasmid drastically reduced (or even prevented in a small number of treated mice) the outgrowth of mammary neoplasms as well as their metastatic penetrance. Furthermore, DNA immunization caused haemorrhagic necrosis of established cancer nests, leaving a greatly reduced portion of the tumour burden for the host to cope with. The antitumour activities we obtained, in this very challenging model for cancer immunotherapy, lay the foundation for DNA-based immunization to control erbB2/neu-overexpressing neoplasms.
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PMID:Genetic immunization against neu/erbB2 transgenic breast cancer. 987 70

Male breast carcinoma (MBC) accounts for only 1% of total mammary carcinomas. Controversy exists about whether MBC differs clinically and pathologically from female breast carcinoma (FBC). We compared 10 archival cases with 75 stage-matched FBCs. Clinical data, histologic details, immunostains for mammary lineage markers, and results of several putative "prognostic" analyses were addressed, including DNA ploidy and expression of c-erbB-2 (neu) oncoprotein and p53 protein. Cumulative literature data on 2,530 MBCs were contrasted with information from 135 institutional cases of FBC. A statistically significant difference in grade 3 lesions at low stage persisted when MBCs of all stages were compared with similar FBCs. For stages I and IIA, 5-year survival was 60% and 86% for MBCs and FBCs, respectively (also statistically significant). This difference disappeared when all stages were compared. A similar number of MBCs and FBCs, regardless of stage, demonstrated DNA aneuploidy with or without synthesis of S-100 protein, gross cystic disease fluid protein-15, c-erbB-2 protein, and p53 protein. Hormone receptor positivity was more common in MBC than in FBC at high tumor stages. Low-stage MBC and FBC differ biologically; MBCs tend to manifest at a higher grade with lessened 5-year survival. However, aside from distinctions in hormone receptor proteins, broader comparison of MBC and FBC at stages IIB and higher shows no significant differences in 5-year survival or expression of breast cancer-associated gene products.
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PMID:Low-stage carcinoma of the male breast. A histologic, immunohistochemical, and flow cytometric comparison with localized female breast carcinoma. 989 55


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