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

We investigated the dynamics of the genetic changes that are associated with two types of glioma recurrence, that is, progression from a lower-grade to a high-grade tumor (7 cases) and development of a same high-grade recurrence (15 cases). Each pair of tumors was analyzed for TP53 mutation, EGFR amplification, and loss of heterozygosity for tumor suppressor genes (TP53, RB1, CDKN2A, PTEN, DMBT1) and tumor suppressor gene regions (1p36, 19q13, 11p15, 10p15) known to be frequently implicated in glioma tumorigenesis. By comparing the genetic changes in the primary and corresponding secondary tumors, we found that additional loss of CDKN2A and/or RB1, encoding important components of the cell cycle regulatory pathway, was the most frequent genetic change in both types of recurrence development (10 of 22 cases, 45%). Additional loss of heterozygosity for the 10p15 region, for PTEN, and/or for DMBT1 in the recurrent tumor was noted in 7 of 22 cases (32%), suggesting that additional inactivation of tumor suppressor genes on chromosome 10 is another important feature of glioma relapse. Less frequent additional losses were detected for chromosome regions 11p15 and 19q13 (3 of 22 cases, 14%, each). We conclude that glioma recurrences are characterized by an increased involvement of tumor suppressor genes, even in those cases in which the primary and secondary tumor are of the same high malignancy grade.
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PMID:Dynamics of genetic alterations associated with glioma recurrence. 973 18

Conventional histopathological criteria based on light microscopy are used in pulmonary oncologic pathology in order to establish the diagnosis of tumor, but most frequently they are insufficient, accurate diagnosis requiring ultrastructural and immunohistochemical investigations. The method of immunostaining allowed some molecular marker to be evaluated. Some of them seem to be important in carcinogenesis as a general process, while others have high specificity for lung tumors. Estimation of EGFR and c-erbB-2 protein immunoreactivity showed a significantly stronger staining with NSCLC and was correlated to the poor differentiation of the tumors, undergoing an aggressive biological behavior and an unfavorable prognosis. The expression of p53 protein was found in 19 cases by immunostaining with DO-7 antibody. Immunotracing of more than 50% of the tumoral cells was a predictive factor for the progression of the disease. The growing rate of tumoral proliferative activity was evaluated by immunotracing technique (MIB-1), allowing the Ki-67 index of labeling to be calculated.
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PMID:Immunohistochemical markers in the morphological diagnosis of lung carcinoma. 974 20

The presented classification of astrocytic gliomas follows the system adopted by the WHO which was last published in 1993. The nosographic position of each tumour type is discussed in relation to previous positions and the rationale of changes is provided. The biology and pathology of anaplasia, leading from astrocytoma to glioblastoma, are discussed briefly. The increasing genotypic and phenotypic heterogeneity is described in its progressive stages. A series of genetic changes are associated with the main histologic features of malignancy , such as TP53 mutations, EGFR amplification, CDKN2 deletion, etc. The genetic differences between primary and secondary glioblastomas are emphasised. Tumour-associated biological events are presented: cell invasion and spread, necrosis and apoptosis and angiogenesis are all discussed in some detail. Of each event a short survey on the principal phenotypic and molecular features is given with emphasis on their significance to pathogenesis. Each tumour type is briefly summarised from epidemiological, clinical and pathological standpoints.
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PMID:Classification and biology of astrocytic gliomas. 975 90

Rearrangements of EGFR are known to occur in a significant fraction of glioblastomas, the most common and malignant form of central nervous system tumor. Although the consequences of these alterations have been described at the mRNA and protein level, little is known about human EGFR genomic sequence or organization at the rearrangement sites. To investigate one group of alterations in glioblastoma, we used long-range PCR to synthesize a segment of the gene near its 3' end, which is frequently rearranged in tumors with EGFR amplification. The sequence of this PCR product provided a precise map for the five 3'-terminal exons of EGFR, designated as exons 22-26. Ten tumors were identified with rearrangements in this part of the gene, most of which resulted in the loss of 325 coding bases that constitute exons 23-25. No two tumors shared identical donor or acceptor rearrangement sites, and the examination of sequences at these sites failed to support homologous recombination as a mechanism responsible for any of the rearrangements. However, examination of the entire exon 22-26 region for sequence motifs associated with genomic instability identified two large, CA-rich tracts in intron 25.
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PMID:3' end structure and rearrangements of EGFR in glioblastomas. 979 May 6

Approximately 30% of ovarian and breast cancers overexpress p185(c-erbB-2) with as many as 10(6) receptors/cell. Normal cells have as few as 10(4) receptors/cell. We have examined the susceptibility of SKOv3 human ovarian cancer cells to anti-c-erbB2 antibodies and immunotoxins as a function of c-erbB-2 density on the cell surface. A panel of SKOv3 clones that expressed different densities of p185(c-erbB-2) receptor were generated through transfection with the c-erbB-2 gene. A significant correlation was found between p185(c-erbB-2) density and susceptibility to killing by anti-p185(c-erbB-2)-ricin A chain (anti-p185(c-erbB-2)-RTA) immunotoxins. With 10(5) copies/cell of p185(c-erbB-2), <10% of clonogenic ovarian cancer cells could be eliminated, whereas in clones that expressed 10(6) copies/cell of p185(c-erbB-2), 99.9% of clonogenic tumor cells were killed. In cell lines that overexpressed p185(c-erbB-2) and also expressed p170(EGFR), anti-p185(cerbB-2)-RTA and anti-p170(EGFR)-RTA immunotoxins exerted synergistic cytotoxicity. Treatment with the two immunotoxins could eliminate 99.99% of clonogenic cells. Importantly, tumor cells that had survived first treatment with anti-p185(c-erbB2)-RTA alone still retained sensitivity to repeat treatment with the same immunotoxin and also proved susceptible to the synergistic cytotoxicity of anti-p185(cerbB-2)-RTA in combination with anti-p170(EGFR)-RTA. Growth characteristics of the clones expressing various levels of p185(c-erbB-2) were also studied. No correlation was found between p185(c-erbB-2) expression levels and the rate of anchorage-dependent growth, anchorage-independent growth, or in vivo growth in nude mice.
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PMID:Cell surface density of p185(c-erbB-2) determines susceptibility to anti-p185(c-erbB-2)-ricin A chain (RTA) immunotoxin therapy alone and in combination with anti-p170(EGFR)-RTA in ovarian cancer cells. 979 89

We previously reported that schwannoma-derived growth factor (SDGF), a member of heparin-binding epidermal growth factor (EGF) family, participates in autocrine pathways and promotes rat glioma cell growth. To investigate the potential role of similar molecules in human gliomas, we examined 7 human glioma cell lines and 11 glioblastoma specimens for expression of the human homologue of SDGF, amphiregulin (AR), as well as heparin-binding EGF-like growth factor (HB-EGF). Northern blot analysis revealed that only one cell line and no tumor specimens expressed AR mRNA. In contrast, HB-EGF mRNA was expressed in all human glioma cell lines and its level of expression was two- to five-fold higher than that of control brain tissues in 8 of 11 glioblastoma cases. Immunohistochemistry demonstrated that membrane-anchored HB-EGF (proHB-EGF) and EGFR were co-expressed in 44% of 34 human malignant gliomas. Introduction of exogenous HB-EGF (10 ng/ml) increased human glioma cell proliferation, and anti-HB-EGF blocking antibodies reduced the growth of glioma cells by 30-40%, confirming the presence of an autocrine loop. When added to the medium, transforming growth factor-alpha, basic fibroblast growth factor, or HB-EGF rapidly induced HB-EGF mRNA expression. These results indicate that HB-EGF and proHB-EGF contribute to the growth of human malignant glioma cells, most likely through autocrine and juxtacrine mechanisms.
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PMID:Heparin-binding epidermal growth factor-like growth factor stimulates mitogenic signaling and is highly expressed in human malignant gliomas. 979 95

Experimental data suggest that dysregulation of growth factors and the cognate receptors may play an important role in hepatocarcinogenesis. The objective of the present study was to characterize the expression of two hepatotrophic growth factor/receptor systems [transforming growth factor-alpha/epidermal growth factor receptor (TGF-alpha/EGFR) and hepatocyte growth factor/c-met receptor (HGF/c-met)], both of which are implicated in the development of human liver tumors. In addition, we have analyzed the expression of transforming growth factor-beta receptor type II (TGF-beta-RII) and p53, genes associated with growth inhibition and tumor suppression, respectively. Surgical biopsy specimens from 86 human hepatocellular carcinomas were analyzed. TGF-alpha was overexpressed in 17%, equally expressed in 21%, and down-regulated in 62% of the hepatocellular carcinomas when compared to the surrounding hepatic tissue. No major changes were found with EGFR expression. HGF was over-expressed in 33% and down-regulated in 21% of the tumors. The c-met receptor was overexpressed in 20%, equally expressed in 48%, and down-regulated in 32% of the neoplasms. In contrast, TGF-beta-RII was overexpressed in only 8%, equal in 42%, and down-regulated in 50% of tumors. Nuclear staining of p53, indicative of a mutation(s), was observed in the great majority of the tumors (80%), whereas no nuclear p53 was detected in peritumoral tissues. Interestingly, simultaneous down-regulation of c-met and TGF-beta-RII was observed in 23% of the hepatocellular carcinomas, 85% of which also showed nuclear p53 staining. Taken together, our data suggest that down-regulation of c-met and TGF-beta-RII may, together with p53 mutations, play a significant role in human liver carcinogenesis.
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PMID:Analysis of transforming growth factor (TGF)-alpha/epidermal growth factor receptor, hepatocyte growth Factor/c-met,TGF-beta receptor type II, and p53 expression in human hepatocellular carcinomas. 981 84

Tumor necrosis factor (TNF)-alpha has a broad range of biological activities, which depend heavily on cell type and physiological condition. In a panel of human tumor cell lines we analyzed expression of the receptor tyrosine kinases EGFR, ErbB2 and ErbB3, and the response to TNF-alpha. Among the cell lines tested those resistant to TNF-alpha were found to express high levels of either EGFR, or ErbB2 and ErbB3. In TNF-sensitive breast and cervical carcinoma cells activation of EGFR or ErbB2 by the exogenous growth factors EGF and heregulin beta1 resulted in a significant increase in the number of cells surviving TNF-alpha treatment. In contrast, inhibition of EGFR activation in TNF-resistant breast carcinoma cells by the novel antagonistic anti-EGFR antibody 14E1 sensitized the cells to the cytotoxic effects of TNF-alpha. A bacterially expressed fusion protein consisting of a 14E1 single-chain (sc) Fv antibody fragment linked to human TNF-alpha retained TNF-alpha activity. This scFv(14E1)-TNF-alpha molecule localized specifically to EGFR on the surface of tumor cells and activated the NF-kappaB pathway in co-cultured T cells, as demonstrated by electrophoretic mobility shift assays.
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PMID:Activation of EGF receptor family members suppresses the cytotoxic effects of tumor necrosis factor-alpha. 982 42

The expression of epidermal growth factor (EGF) and its receptor (EGFR) was studied immunohistochemically in fifty-seven Chinese patients with primary invasive ductal carcinoma (IDC) of the pancreas. The frequency of expression of EGF and EGFR was 73.7% and 68.4%, respectively. The frequency of their co-expression was 61.4%. No significant relationships were seen between the expression of EGF and its receptor and the patients' age, gender, site of the tumor, stage, and grade. Positive co-expression of EGF and EGFR was significantly associated with the poor prognosis. The median survival of the EGF(-)EGFR(-) group for 17.2 months was longer than that of the EGF(+)EGFR(+) group for 9.7 months (p = 0.02), as well as that of the other groups of EGR(+)EGFR(-), EGF(-)EGFR(+), and EGF(+)EGFR(+) for 9.9 month (p = 0.03). These results suggested that EGF and EGFR were frequently expressed in Chinese patients with IDC of the pancreas. Their co-expression may be a useful prognostic indicator for pancreatic cancer.
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PMID:Epidermal growth factor and its receptor as prognostic indicators in Chinese patients with pancreatic cancer. 989 28

Incidence rates have risen rapidly for esophageal and gastric cardia adenocarcinomas. These cancers, arising at and around the gastroesophageal junction (GEJ), share a poor prognosis. In contrast, there is no consensus with respect to clinical staging resulting in possible adverse effects on treatment and survival. The goal of this study was to provide more insight into the genetic changes underlying esophageal and gastric cardia adenocarcinomas. We have used comparative genomic hybridization for a genetic analysis of 28 adenocarcinomas of the GEJ. Eleven tumors were localized in the distal esophagus and related to Barrett's esophagus, and 10 tumors were situated in the gastric cardia. The remaining seven tumors were located at the junction and could not be classified as either Barrett-related, or gastric cardia. We found alterations in all 28 neoplasms. Gains and losses were distinguished in comparable numbers. Frequent loss (> or = 25% of all tumors) was detected, in decreasing order of frequency, on 4pq (54%), 14q (46%), 18q (43%), 5q (36%), 16q (36%), 9p (29%), 17p (29%), and 21q (29%). Frequent gain (> or = 25% of all tumors) was observed, in decreasing order of frequency, on 20pq (86%), 8q (79%), 7p (61%), 13q (46%), 12q (39%), 15q (39%), 1q (36%), 3q (32%), 5p (32%), 6p (32%), 19q (32%), Xpq (32%), 17q (29%), and 18p (25%). Nearly all patients were male, and loss of chromosome Y was frequently noted (64%). Recurrent high-level amplifications (> 10% of all tumors) were seen at 8q23-24.1, 15q25, 17q12-21, and 19q13.1. Minimal overlapping regions could be determined at multiple locations (candidate genes are in parentheses): minimal regions of overlap for deletions were assigned to 3p14 (FHIT, RCA1), 5q14-21 (APC, MCC), 9p21 (MTS1/CDKN2), 14q31-32.1 (TSHR), 16q23, 18q21 (DCC, P15) and 21q21. Minimal overlapping amplified sites could be seen at 5p14 (MLVI2), 6p12-21.1 (NRASL3), 7p12 (EGFR), 8q23-24.1 (MYC), 12q21.1, 15q25 (IGF1R), 17q12-21 (ERBB2/HER2-neu), 19q13.1 (TGFB1, BCL3, AKT2), 20p12 (PCNA), 20q12-13 (MYBL2, PTPN1), and Xq25. The distribution of the imbalances revealed similar genetic patterns in the three GEJ tumor groups. However, loss of 14q31-32.1 occurred significantly more frequent in Barrett-related adenocarcinomas of the distal esophagus, than in gastric cardia cancers (P = 0.02). The unclassified, "pure junction" group displayed an intermediate position, suggesting that these may be in part gastric cardia tumors, whereas the others may be related to (short-segment) Barrett's esophagus. In conclusion, this study has, fist, provided a detailed comparative genomic hybridization-map of GEJ adenocarcinomas documenting new genetic changes, as well as candidate genes involved. Second, genetic divergence was revealed in this poorly understood group of cancers.
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PMID:Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of 14Q31-32.1 discriminates between esophageal (Barrett's) and gastric cardia adenocarcinomas. 997 27


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