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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA derived from medulloblastoma biopsies was analyzed to determine if deletions of the 17p region, mutations of the TP53 gene, or amplification of the c-myc, N-myc, EGFR (epidermal growth factor receptor), or MDM2 (murine double-minute-2) genes was indicative of a poor prognosis. Loss of heterozygosity for 17p, observed in 8/28 (29%) paired samples, was associated with a shortened survival period (p = 0.045 by the logrank test). TP53 mutations occurred in 2/46 (4.3%) tumor samples. c-myc Amplification was seen in 3/43 (6.9%) cases, while none of the tumors contained amplified N-myc, EGFR, or MDM2 genes. These results demonstrate that, while only rare medulloblastomas contain TP53 gene mutations or amplification of the c-myc gene, loss of heterozygosity on chromosome 17p is indicative of a significantly worse prognosis among patients with these tumors. Further, these results provide a strong impetus for a prospective analysis of loss of heterozygosity in a cooperative group setting, which would include tumor staging, a selection of treatment modalities, and multivariate analyses.
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PMID:Prognostic implications of chromosome 17p deletions in human medulloblastomas. 852 74

Recent advances in molecular genetics have disclosed oncogenes playing a significant role in the development of malignant gliomas. Amplification of the c-erb gene which code EGFR and aberration of P53 oncogene play a significant role in the development of most malignant gliomas. Karyotype analysis of malignant gliomas revealed gains of chromosome 7, loss of chromosome 10, double minutes and loss of heterozygosity. The development of the tumors appear to result from the accumulation of those multiple genetic alterations. Although many cases of familiar malignant gliomas have been reported the role of hereditary factors in familial transmission still remains controversial. Chromosomal abnormalities seemed to be confined to the tumor cell, and no alteration in karyotype of peripheral blood, which indicated germ line mutation, was demonstrated. However, several authors indicated that the frequency of malignant gliomas in the relatives of patients was estimated more than ten times to the controls. Some hereditary factors might play a role in malignant gliomas.
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PMID:[Malignant glioma]. 853 25

Gliomas affect 15,000 to 17,000 Americans every year and carry a dismal prognosis. The potential of immunologically mediated diagnosis and therapy, although greatly enhanced since the advent of monoclonal antibodies, has not been fully realized due to significant problems, most especially the challenge of identifying antigenic molecules specific to glial tumors. Other problematic issues include antigen-associated factors such as heterogeneity, modulation, shedding, and cross-reactivity with normal cells, and factors associated with therapeutic agent delivery, typically variable tumor perfusion and unfavorable diffusional forces in tumor microenvironment. An understanding of these problems called for the delineation of operationally specific antigens (tumor-associated antigens not expressed by the normal central nervous system) combined with the use of compartmental therapeutic approaches to increase the specificity of therapy. Numerous antigens have been identified and are classified as extracellular/matrix-associated, membrane-associated, and intracellular antigens. Nevertheless, only a few have been demonstrated to be of significant therapeutic and diagnostic utility. These few include the extracellular matrix-associated antigens tenascin and GP 240, defined by the monoclonal antibodies 81C6 and Mel-14, both of which are now in Phase I clinical trials, and membrane-associated ganglioside molecules, primarily 3', 6'-isoLD1, defined by the antibody DMAb-22. Recent identification of the overexpression of a deletion variant of the epidermal growth factor receptor (EGFRvIII) in up to 50% of the more malignant glial tumors and the subsequent creation of monoclonal antibodies that are specific to this molecule and do not recognize the wild-type EGFR provide the most exciting development yet in the design of specific antiglioma immunoconjugates. In addition, the tumor-specific nature of EGFRvIII combined with improved knowledge of immune mechanisms, especially in the context of the central nervous system, will facilitate the design of highly selective cell-mediated therapeutic approaches with a view toward obtaining tumor-specific immunity.
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PMID:Tumor antigens in astrocytic gliomas. 858 61

Gene amplification or structural alteration of different erbB genes exerts a transforming effect in a variety of human neoplasms. Overexpression of the EGF receptor is associated with tumor initiation and progression of renal cell carcinoma (RCC). However, the role of erbB-2 in these processes remains unknown. We investigated 34 renal cell carcinomas for gene amplification and expression of the EGFR and erbB-2 genes at the mRNA and protein level and their relationship to pathological and clinical parameters. No amplification of both genes has been observed. However, high expression of the EGF receptor protein and p185erbB2 was frequent in RCC and statistically significantly related to higher tumor grades. We could demonstrate a close correlation of p185erbB2 overexpression with high EGF receptor levels. Co-overexpression of both receptor types was significantly associated with metastatic disease. Our results suggest a synergistic involvement of both EGF receptor and p185erbB2 in the progression of RCC.
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PMID:Concomitant overexpression of the EGFR and erbB-2 genes in renal cell carcinoma (RCC) is correlated with dedifferentiation and metastasis. 860 53

Recent observations suggest that transforming growth factor alpha (TGF-alpha), which binds to the epidermal growth factor (EGF) receptor (EGFR), may induce neoplastic growth of the colonic mucosa through an autocrine mechanism. To assess the functional role of TGF-alpha in colonic carcinogenesis the present investigation examines the changes in TGF-alpha-and EGF-induced activation of intrinsic tyrosine kinase (Tyr-k) activity of EGFR in the colonic mucosa of rats after administration of the colonic carcinogen azoxymethane (AOM; 20 mg/kg body wt). Five days after a single injection of AOM to 4- to 5-month old rats proliferative activity (as assessed by 5-bromo-2'-deoxyuridine immunoreactivity) in the colonic mucosa was increased by approximately 700% over the corresponding saline-injected controls. This was accompanied by: (i) a marked rise in autophosphorylation of a number of mucosal proteins, including one with a M(r) of 170 kDa, a molecular mass that corresponds to EGFR; (ii) a 110-130% increase in basal EGFR Tyr-k activity. Despite this rise in basal EGFR Tyr-k activity, exposure of isolated colonocytes or detergent-solubilized colonic mucosa from AOM-treated animals to either 1 x 10(-8) M TGF-alpha or EGF caused a further 90-160% increase in EGFR Tyr-k activity over the corresponding basal levels. In contrast, bombesin produced no apparent change in EGFR Tyr-k activity. We conclude that increased ligand-induced activation of EGFR Tyr-k may be an important event for development of the hyperproliferative state associated with induction of colorectal neoplasia.
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PMID:Azoxymethane enhances ligand-induced activation of EGF receptor tyrosine kinase in the colonic mucosa of rats. 862 44

Relationships between the incidence of metastatic spread and microvessel density, expression of proto-oncogene products, or expression of resistance-related proteins were investigated in human ovarian carcinomas by immunohistochemistry. Ovarian carcinomas with a high microvessel density showed a significantly increased formation of metastases (P = 0.005). Tumors with positive immunoreactivity of c-jun and c-myc products had a higher metastatic spread; however, these results were not statistically significant. A marginally significant correlation existed between the expression of erbB1 (EGFR) and metastatic spread (P = 0.05). No significant relationship was found between the expression of the resistance-related proteins P-glycoprotein or glutathione S-transferase-pi and the incidence of metastases. Furthermore, no correlation was detected between expression of the heat shock protein 70 and the occurrence of metastases.
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PMID:Microvessel density, expression of proto-oncogenes, resistance-related proteins and incidence of metastases in primary ovarian carcinomas. 867 74

Although c-erbB-2 oncoprotein immunohistochemical expression has been thoroughly studied in a variety of human tumors, its prognostic significance remains unclear. Moreover, differences in assessment criteria further complicate the evaluation of c-erbB-2 as a prognostic marker. In the present study we examined the expression of c-erbB-2 protein in 107 patients suffering from operable (T 1,2-N0, 1 staged) non-small cell lung cancer (30 adenocarcinomas and 69 squamous cell carcinomas) treated with surgery alone. A 3-7 year of follow up (median 45 months) was available for all patients. Paraffin embedded sections were stained with the NCL-CB11 monoclonal antibody using the immunoperoxidase technique. Analysis was based on cytoplasmic reactivity as membrane staining was impossible to assess against this background. Strong positive cytoplasmic staining was identified in 20/107 (19%) of cases, weak in 30/107 (20%) and negative in 57/107 (53%). Results were correlated with patient variables (age,sex) and tumor parameters (T,N-stage, grade, histology, Ki67 proliferation index, p53 and EGFR expression). C-erbB-2 expression was not related to any of these factors. Although c-erbB-2 defined a worse prognosis, univariate analysis of survival did not confirm any statistically significant difference between the c-erbB-2 staining groups (p=0.5). T,N-stage were the only statistically significant prognostic variables. Any contribution of c-erbB-2 to the development of tumour aggressive behaviour in non-small cell lung cancer requires assessment in the specific subgroups of patients.
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PMID:C-erbB-2 oncoprotein expression in operable non-small cell lung cancer. 868 65

The prognostic factors for esophageal cancer from the viewpoint of molecular biology are reviewed. Among several oncogenes and suppressor genes erbB, int2/hst1/Cyclin D1 and MDM2 gene amplifications are significant prognostic factors for esophageal cancer. The value of p53 mutation, and expression of matrix metalloproteinase (MMPs) in the prediction of patients' survival are controversial, so further research is needed. High expression of tumor proliferation-related factors (Ki67, PCNA, and AgNOR), abnormalities of adhesion molecule (E-Cadherin, alpha-Catenin), activation of autocrine mechanism of growth factor (EGFR-TGF alpha, EGF), and DNA ploidy pattern, which is thought to be the result of an accumulation of genomic abnormalities are also prognostic factors for esophageal cancer.
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PMID:[Prognostic factors for esophageal cancer--from the viewpoint of molecular biology]. 868 32

Tumour angiogenesis is an important factor for tumour growth and metastasis. Although some recent reports suggest that microvessel counts in non-small cell lung cancer are related to a poor disease outcome, the results were not conclusive and were not compared with other molecular prognostic markers. In the present study, the vascular grade was assessed in 107 (T1,2-N0,1) operable non-small cell lung carcinomas, using the JC70 monoclonal antibody to CD31. Three vascular grades were defined with appraisal by eye and by Chalkley counting: high (Chalkley score 7-12), medium (5-6), and low (2-4). There was a significant correlation between eye appraisal and Chalkley counting (P < 0.0001). Vascular grade was not related to histology, grade, proliferation index (Ki67), or EGFR or p53 expression. Tumours from younger patients had a higher grade of angiogenesis (P = 0.05). Apart from the vascular grade, none of the other factors examined was statistically related to lymph node metastasis (P < 0.0001). A univariate analysis of survival showed that vascular grade was the most significant prognostic factor (P = 0.0004), followed by N-stage (P = 0.001). In a multivariate analysis, N-stage and vascular grade were not found to be independent prognostic factors, since they were strongly related to each other. Excluding N-stage, vascular grade was the only independent prognostic factor (P = 0.007). Kaplan-Meier survival curves showed a statistically significant worse prognosis for patients with high vascular grade, but no difference was observed between low and medium vascular grade. These data suggest that angiogenesis in operable non-small cell lung cancer is a major prognostic factor for survival and, among the parameters tested, is the only factor related to cancer cell migration to lymph nodes. The integration of vascular grading in clinical trials on adjuvant chemotherapy and/or radiotherapy could substantially contribute in defining groups of operable patients who might benefit from cytotoxic treatment.
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PMID:Prognostic value of angiogenesis in operable non-small cell lung cancer. 869 50

The significance of prognostic factors that may predict the clinical outcome of patients with head and neck cancer was discussed. Many indicators can be grouped into three categories, patient factors, tumor factors and treatment factors. The most significant indicator of prognosis seems to be pathological nodal stage. Factors such as clinical stage, resectability, and depth of invasion may also affect the patient outcome. Recent research development has revealed biological phenotypes of cancer cells to predict the effect of cancer treatment and the clinical course in head and neck cancer. Possible predictive indicators include DNA ploidy, Tpot, EGFR and cyclin D1. C erbB2 and p53 may not predict the survival of patients with head and neck cancer.
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PMID:[Clinico-pathological predictive indicators in squamous cell carcinoma of the head and neck]. 871 16


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