Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary tumors originating from cells of the glial lineage usually affect predominantly the white matter of the brain. Only rarely do gliomas destroy the surrounding bone by invasion of the extracellular matrix, especially without prior surgery. This paper describes the unusual case of a 66-year-old female patient with a left-sided intra- and extracranial tumor involving the temporal lobe, destroying the underlying skull base, and growing into the paranasal sinuses, orbit, and temporal bone. Biopsy revealed glioblastoma multiforme with strong GFAP positivity. Molecular biologic investigations of the p53, EGFR, and mdm2 genes showed functional inactivation of the p53 gene but no overexpression of oncogenes. Because the tumor was considered inoperable, palliative irradiation was carried out. The patient died 7 months after diagnosis. The causes of this phenomenon are discussed and the literature reviewed.
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PMID:Local invasivity of glioblastoma multiforme with destruction of skull bone. Case report and review of the literature. 887 8

Spinal cord injury (SCI) patients are at high risk of developing cystitis, and vesical neoplasia. As abnormal growth regulation of urothelium may be a predisposing factor for cystitis and vesical neoplasia, we studied alterations if any, in the expression and localization of epidermal growth factor receptor (EGRF) in the vesical urothelium by an immuno-histochemical technique, using monoclonal mouse anti-human epidermal growth factor receptor antibody (DAKO-EGFRI) in cold-cup biopsies taken from the trigone of the urinary bladder in 18 adult SCI patients who had a neuropathic bladder. Abnormal localisation of EGFR-p, i.e. cytoplasmic, was noted in 13 patients. A linear localization of EGFR-p along the cell membrane of the urothelium, considered as an essential requirement for effective function, was observed in only three cases. Combined cytoplasmic and cell membrane location of EGFR-p was seen in two patients. The three patients with cell membrane location of EGFR-p showed a strong expression of EGFR-p (2+, 2-3+, and 4+, respectively); the intensity of EGFR-p expression in cases of cytoplasmic immunostaining varied considerably. Histopathology revealed denuding cystitis in one; follicular cystitis in four; active inflammatory infiltrate in three; lymphocytic infiltrate in three; squamous metaplasia in six; and intestinal metaplasia in three biopsy specimens. The three specimens showing cell membrane location of EGFR-p were from patients who did not have an indwelling urethral catheter (a paraplegic man practising intermittent self-catheterisation, a tetraplegic patient on penile condom drainage, and a tetraplegic woman with reflex voiding), and histopathology revealed very little inflammatory infiltrate. In contrast, the biopsies from all the nine patients, who were on indwelling urethral catheter drainage and in whom the bladder biopsy revealed varying degree of cystitis, showed only cytoplasmic location of EGFR-p. Similarly, the biopsies from patients with bladder stone (n = 6) showed only cytoplasmic localisation of EGFR-p. In conclusion, abnormalities in vesical urothelial expression in EGFR in SCI patients may play a role in the pathogenesis of cystitis, vesical urothelial metaplasia, dysplasia and neoplasia.
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PMID:Epidermal growth factor receptor in the vesical urothelium of paraplegic and tetraplegic patients: an immunohistochemical study. 889 22

The genetic basis of spontaneous melanoma formation in spotted dorsal (Sd) Xiphophorus platyfish-swordtail hybrids has been studied for decades, and is adequately explained by a two-gene inheritance model involving a sex-linked oncogene, Xmrk, and an autosomal tumor suppressor, DIFF. The Xmrk oncogene encodes a receptor tyrosine kinase related to EGFR; the nature of the DIFF tumor suppressor gene is unknown. We analyzed the gentic basis of UV-B-induced melanoma formation in closely related, spotted side platyfish-swordtail hybrids, which carry a different sex-linked pigment pattern locus, Sp. We UV-irradiated spotted side Xiphophorus platyfish-swordtail backcross hybrids to induce melanomas at frequencies 6-fold higher than occur spontaneously in unirradiated control animals. To identify genetic determinants of melanoma susceptibility in this UV-inducible Xiphophorus model, we genotyped individual animals from control and UV-irradiated experimental regimes using allozyme and DNA restriction fragment length polymorphisms and tested for joint segregation of genetic markers with pigmentation phenotype and UV-induced melanoma formation. Joint segregation results show linkage of a CDKN2-like DNA polymorphism with UV-B-induced melanoma formation in these hybrids. The CDKN2-like polymorphism maps to Xiphophorus linkage group V and exhibits recombination fractions with ES1 and MDH2 allozyme markers consistent with previous localization of the DIFF tumor suppressor locus. Our results indicate that the CDKN2-like sequence we have cloned and mapped is a candidate for the DIFF tumor suppressor gene.
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PMID:A CDKN2-like polymorphism in Xiphophorus LG V is associated with UV-B-induced melanoma formation in platyfish-swordtail hybrids. 891 41

Various molecular genetic abnormalities have been reported in esophageal carcinoma. These include amplification of the chromosome 11q13 region containing cyclin D1, EXP1 and EMS1 genes, and the oncogenes, the epidermal growth factor receptor gene, EGFR/c-ERBB1, and c-myc. Loss of heterozygosity (LOH) at several chromosome loci and point mutation of the p53 and p16/CDKN2 tumor suppressor genes have also been described. Mutations of p53 gene and LOH at 3p and 9q loci were investigated in esophageal epithelial dysplasia. In contrast, amplification of cyclin D1, EGFR, c-myc and other genes was accumulated in advanced tumors with invasion. Cyclin D1 amplification is found more in metastatic lesions than in primary tumors.
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PMID:[Genetic events during development of esophageal squamous cell carcinoma]. 892 Jun 74

Genomic alterations and expression of the p53 tumor suppressor gene and the epidermal factor receptor gene (EGFR) were investigated in 22 patients with primary World Health Organization (WHO) grade II gliomas that on recurrence had progressed to malignant gliomas of WHO grades III or IV. Mutations of the p53 gene (exons 5 to 8) were found in 12 of 22 primary tumors (10 of 13 astrocytomas, 1 of 7 oligodendrogliomas, 1 of 2 oligoastrocytomas). In each of these cases identical p53 mutations were present in the respective malignant recurrences. In all instances in which the p53 mutation was associated with p53 protein accumulation (10 of 12 cases) the percentage of p53 immunopositive tumor cells had increased from the primary to the recurrent tumor. None of the primary low-grade and none of the recurrent high-grade tumors (7 anaplastic astrocytomas, 10 anaplastic oligodendrogliomas, 4 anaplastic oligoastrocytomas, and 5 glioblastomas) showed evidence of EGFR gene amplification. Our results thus demonstrate p53 is mutated in a high fraction of low-grade astrocytomas with progression to anaplastic astrocytomas and glioblastomas and that progression in such cases is frequently associated with an increase in the fraction of p53 immunopositive tumor cells. The general absence of EGFR amplification in our tumor series supports the hypothesis that the significance of p53 mutation and EGFR amplification may be different in glioblastomas that developed by progression from low-grade astrocytomas (secondary glioblastomas) compared to glioblastomas that developed rapidly in a de novo manner without a history of previous low-grade tumor (primary glioblastomas).
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PMID:Analysis of p53 mutation and epidermal growth factor receptor amplification in recurrent gliomas with malignant progression. 896 97

Hypopharyngeal squamous cell carcinomas (HPC) has an extremely poor prognosis. Characteristics of cell lines of head and neck squamous cell carcinomas including HPC were studied by various methods, e.g., chemosensitivity test and the immunohistochemistry staining method, to determine whether this poor prognosis is due to the biological behavior of this cancer. An HPC cell line was found to be resistant to anti tumor drugs, i.e., PEP, MTX and CPM and moderately sensitive to CDDP, 5-FU and ADM. Thermoresistance to hyperthermatic treatment and weak expression of ICAM-1 on the HPC cell line were observed. DNA synthesis by the HPC cell line was induced by stimulation with a low concentration of EGF and the amount of EGFR on these HPC cells was very high. In addition, cyclinD1 overexpression was found in the HPC cell line. Based on the above findings, further analysis of hypopharyngeal carcinoma cells and the development of a new treatment modality to control tumor growth and metastatic factors influencing the poor outcome are necessary to improve the prognosis of this cancer.
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PMID:[Biological behavior of hypopharyngeal carcinoma]. 903 77

Tumour angiogenesis is an important prognostic factor in non-small cell lung cancer. Recently, EGFR and c-erbB-2 protein was found to regulate cell adhesion and the invasive growth of cancer through its association with the cadherin-catenin complex. The role of c-erbB-2 protein in cell migration has been also reported. In this study we investigate the combined role of tumoral neoangiogenesis and c-erbB-2/EGFR expression in the metastatic behaviour and prognosis of operable non-small cell lung cancer. 107 tumour samples from patients suffering from operable non small cell lung cancer were examined. EGFR and c-erbB-2 were not correlated with each other. C-erbB-2 expression was associated with low angiogenesis, approaching statistical significance in adenocarcinomas (p = 0.08). The absence of expression of both c-erbB-2 and EGFR oncogenes in tumours with high angiogenesis, was most frequently observed in node negative cases (p = 0.04). C-erbB-2 overexpression defined a subgroup of node negative patients with low angiogenesis and prognosis similar to patients with tumours bearing high angiogenesis. These findings support the hypothesis that expression of the erb genes is a mechanism activated in non-small cell lung cancer to enable cancer cell migration. This pathway seems to be activated mainly in tumours with poor vasculature presumably lading to an unfavourable intratumoral nutritional and oxygen ambience.
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PMID:Non-small cell lung cancer: c-erbB-2 overexpression correlates with low angiogenesis and poor prognosis. 904 64

Monoclonal antibody (mAb) L8A4, specific for the tumor-associated mutant epidermal growth factor receptor variant III (EGFRvII), is internalized and degraded after cell binding. Four paired-label experiments were performed in athymic mice bearing EGFRvIII-positive xenografts to determine the suitability of N-succinimidyl 3-iodo-5-pyridinecarboxylate (SIPC) for labeling this internalizing mAb. In mice with HC2 20 d2 xenografts, tumor uptake reached a maximum of 32.7 +/- 2.0% injected dose/g when labeled using SIPC, a value significantly higher (P < 0.05, paired t test) than that observed when L8A4 was labeled using lodogen (24.4 +/- 2.2% injected dose/g). The specificity of mAb uptake in HC2 20 d2 and U87MG(delta)EGFR xenografts was measured in separate experiments by coadministration of L8A4 and nonspecific, isotype-matched P3X63Ag8 mAb, both radioiodinated using SIPC. Tumor localization indices were approximately 10 or more by 72 h, a degree of specificity 3-4 times higher than that reported previously when labeling was performed using the tyramine cellobiose (TCB) method. In a final study directly comparing L8A4 labeled using SIPC and TCB, similar tumor levels were obtained (SIPC, 33.7 +/- 6.1% injected dose/g at 24 h; TCB, 37.8 +/- 6.7% injected dose/g at 24 h); however, tumor-to-tissue ratios for the liver, spleen, and kidneys were 3 times higher with SIPC at later time points. These results suggest that SIPC is a promising method for labeling this anti-EGFRvIII mAb and possibly other mAbs that internalize after binding.
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PMID:Improved targeting of an anti-epidermal growth factor receptor variant III monoclonal antibody in tumor xenografts after labeling using N-succinimidyl 5-iodo-3-pyridinecarboxylate. 910 53

TNF induces cytotoxicity in human tumor cells through a receptor-mediated process with unknown signaling characteristics. Evidence suggests that overexpression of transmembrane growth factor receptors with intrinsic tyrosine kinase activity may suppress the antiproliferative or cytotoxic activity of TNF, suggesting antagonism between these two signaling pathways in tumor cells. To investigate TNF cytotoxic signal transduction, ME-180 cervical carcinoma cell variants were isolated that expressed complete cytotoxic sensitivity (ME-180S) or resistance (ME-180R) to TNF but identical levels of p55 TNF receptor expression. ME-180R cells expressed threefold higher EGFR than the ME-180S cell line and TNF treatment stimulated EGFR tyrosine phosphorylation only in resistant cells. Activation of tyrosine phosphorylation in ME-180R cells was TNF concentration dependent and maximally stimulated (three- to-five-fold) after 10-15 minutes of treatment. Other tyrosine phosphoproteins were not affected by TNF incubation demonstrating specific TNF-stimulated tyrosine phosphomodulation of EGFR. Pretreatment with the tyrosine kinase inhibitor tryphostin before incubation with TNF resulted in partial reversal of TNF cytotoxic resistance in ME-180R cells and enhanced TNF responsiveness in ME-180S cells, suggesting a "protective" role for tyrosine phosphorylation in TNF-induced cytotoxicity. Together these results demonstrate that TNF-mediated tyrosine phosphorylation is differentially regulated in sensitive and resistant tumor cells and may play a critical role in the cytotoxic signaling process through differential expression or regulation of tyrosine protein kinases and phosphatases.
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PMID:Activation of epidermal growth factor receptor tyrosine phosphorylation by tumor necrosis factor correlates with loss of cytotoxic activity. 916 24

We have previously shown that human bladder tumor cell lines may be adapted to grow in the complete absence of serum or any other growth supplement and that this can be explained on the basis of autocrine stimulation. In the present study we have extended the number of cell lines that could be established as serum-free cultures and found this capacity to be correlated with tumor malignancy. We also used the receptor blocking monoclonal antibody, mAb 528, to study its effect on tumor cell growth. Inhibition was observed in all of seven bladder carcinoma cell lines tested. A similar effect was observed in two colon carcinoma cell lines but not in a melanoma line. The results show that the EGFR is involved in autocrine growth stimulation and that the acquirement of autonomous growth capacity is likely to be an important factor in the oncogenesis of bladder tumors.
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PMID:The epidermal growth factor receptor is involved in autocrine growth of human bladder carcinoma cell lines. 921 46


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