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)

Because the crucial role of angiogenesis has been demonstrated in tumor growth and metastasis, the present study was undertaken to characterize the relative expression of vascular endothelial growth factors VEGF (vascular endothelial growth factor), VEGF-B, VEGF-C, and their receptors KDR (kinase insert domain-containing receptor), FLT-1 (fms-like tyrosine kinase), and FLT-4 in human colonic cancers, in relation to the Astler-Coller pathological classification, and to prognosis. VEGF and VEGF-B gene expression was quantified by Northern blot in 72 tumor samples matched with control tissues. VEGF gene expression was 1.4 times higher in adenocarcinomas than in control tissues (p = 0.02), but did not increase further between Astler-Coller tumor stages A and D, and did not correlate with disease recurrence for patients at stages B2 or C. In adenomas, VEGF mRNA levels were not significantly different from those in the paired control colonic mucosa. The expression pattern of VEGF isoforms, mainly identified by RT-PCR (reverse-transcriptase-coupled polymerase chain reaction) as VEGF121 and VEGF165 and to a lesser extent VEGF189, was comparable in tumor and control tissues. VEGF-B mRNA levels were unchanged during the neoplastic progression of colonic mucosa. In contrast to KDR and FLT-4, the expression of VEGF-C and FLT-1 genes increased in some pathological tissues. These results provide evidence that the early and sustained increase in VEGF transcripts and the expression of multiple angiogenic factors and receptors contribute to the development of colon cancer, and thus constitute a putative target for anti-angiogenic drug therapy.
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PMID:Vegf, Vegf-B, Vegf-C and their receptors KDR, FLT-1 and FLT-4 during the neoplastic progression of human colonic mucosa. 1073 43

Epstein-Barr virus (EBV)-associated smooth muscle tumors following solid organ transplantation are extremely rare, with only 12 cases reported in the literature thus far. The exact pathogenetic role of EBV infection in the oncogenesis of these soft tissue tumors in immunodeficient patients and the biologic behavior of such tumors is still unclear. We report a 26-year-old man in whom multiple smooth muscle tumors developed 36 to 51 months after heart transplantation. All tumors, two synchronous liver nodules, two subsequently occurring paravertebral tumors, and a single tumor in a vein at the left ankle were surgically resected. The tumor tissue was processed for routine histology and immunohistochemical (IHC) stains. Additionally, competitive polymerase-chain-reaction (PCR), reverse-transcriptase PCR (RT-PCR), as well as in situ hybridization (ISH) were used for EBV particle quantification and gene transcription analysis. The histologic features and immunohistochemical profiles were consistent with leiomyosarcoma in all tumor nodules. EBV infection was detected in >95% of tumor cell nuclei by EBER 1/2 ISH. Competitive PCR revealed 3105 EBV particles per milligram of tumor tissue. The EBV gene expression pattern analyzed by RT-PCR and IHC corresponded to the latency type III with specific expression of EBNA1, EBNA2, LMP1, and LMP2A genes. Under continuous antiviral therapy (famcyclovir) the patient currently shows no evidence of disease. Our data indicate that EBV infection plays a causal role in the development of smooth muscle tumors following organ transplantation. A latency type III, identical to EBV-associated posttransplant lymphoproliferative disorders, was identified and suggests a common pathogenetic mechanism in the development of these histogenetically distinct neoplasms. The fact that the patient currently shows no evidence of disease may be the result of the continuous administration of antiviral therapy because the soft tissue recurrences of the leiomyosarcoma occurred while the patient was not receiving antiviral prophylaxis.
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PMID:Epstein-Barr virus-associated multicentric leiomyosarcoma in an adult patient after heart transplantation: case report and review of the literature. 1075 11

Glucose utilisation by cancer cells is greatly enhanced when compared with that by normal tissue. Glucose is taken up by cells and then phosphorylated to glucose-6-phosphate. Facilitative hexose uptake is achieved by five transmembrane transporters, termed glut1-5, which are protein products of their respective GLUT genes. Glut types differ in their kinetics, which are tailored to the requirements of the cell type they serve, although more than one glut may be expressed by a particular cell type. Herein are reviewed the results from approximately 30 studies which examined glut expression in human cancer tissue. These studies measured GLUT messenger RNA (mRNA) either using the reverse-transcriptase polymerase chain reaction or by Northern blot analysis, or detected glut proteins using the appropriate antibodies. Tumour tissue is frequently associated with the abnormal and/or over-expression of gluts, especially glut1. Some tumour cells express specific GLUT mRNA but not the respective protein. Some studies have reported associations between glut expression and proliferative indices, whilst others suggest that glut may be of prognostic significance, especially in lung cancer.
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PMID:Facilitative glucose transporter expression in human cancer tissue. 1079 74

The tyrosine kinase receptor c-kit and its ligand [kit ligand (KL) or stem cell factor (SCF)] exert a broad range of biological activities during organogenesis and normal cell development. Recent studies have revealed that altered c-kit levels occur in a variety of malignancies and cancer cell lines. KL has also been shown to stimulate the growth of malignant cells, as well as to promote chemotaxis. We had previously reported expression of KL in stroma cells of normal human prostate. The present study was undertaken in order to analyze the patterns of expression of c-kit and KL in a well characterized set of prostatic tissues, including normal prostate (n=4), benign prostatic hyperplasia (BPH) (n=53) and adenocarcinoma (n=46) samples. The distribution of c-kit and KL proteins was studied by immunohistochemical analyses, while transcript levels were determined by in situ hybridization with specific RNA probes on a subset of the benign and malignant tissues referred above. In addition, reverse-transcriptase polymerase chain reaction (RT-PCR) was performed to determine levels of c-kit and KL expression in cultures of epithelial and stroma cells, as well as in the prostate cancer cell lines LNCaP, DU145 and PC3. c-kit protein in normal prostate was exclusively detected in mast cells by immunohistochemistry and in situ hybridization. However, c-kit transcripts, but not c-kit protein, were detected in low levels and with an heterogeneous pattern in basal epithelial cells of ducts and acini. c-kit in BPH was detected in epithelial cells in 9 of 53 (17%) specimens. c-kit protein expression in malignant epithelial cells was identified in 1 of 46 (2%) tumors. However, c-kit transcripts were detected in low levels by in situ hybridization in most of the tumors analyzed. KL protein and transcripts in normal prostate were detected in high levels in stroma cells. However, epithelial cells were unreactive for anti-KL antibody, but showed low levels of KL transcripts mainly in cells of the basal layer. Basal epithelial cells in hyperplastic glands showed KL expression in 13 of 53 (24%) specimens. KL protein in tumor cells was noted in 18 of 46 (39%) cases. c-kit transcripts were not found in normal prostate and in the 3 cancer cell lines analyzed by RT-PCR, however, it was present in cultured epithelial cells of BPH, and in cultures of stroma cells from both normal and BPH. The majority of cultured cell lines of epithelial and stromal origin displayed considerable levels of KL. In addition all prostate cell lines studied showed significant levels of KL transcripts. In summary, co-expression of c-kit and KL in a subset of BPH cases may suggest an autocrine mode of signaling. Data from this study reveals that altered patterns of c-kit and KL expression are associated with BPH and adenocarcinoma of prostate. It appears that KL induces mast cells proliferation and maturation and enhances their release of protease. This could explain the accumulation of mast cells at tumor sites, a phenomenon that was not observed in normal prostate or BPH samples.
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PMID:Expression of c-kit and kit-ligand in benign and malignant prostatic tissues. 1080 54

While pituitary tumors can be induced in rats by the administration of estrogen, susceptibility to such tumors is highly strain dependent. In this study, 21-day-old male rats of two strains-Fischer 344 (F344) strain, which is particularly susceptible to pituitary tumors, and Sprague-Dawley (SD) strain, which is relatively resistant, were treated with diethylstilbestrol (DES) over a period of 10 days. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to analyze the expression levels of two tumor suppressor genes, p53 and rb, in the pituitaries. In SD rats, both p53 and rb mRNA appeared to increase in response to DES treatment, while in F344 rats they remained undetectable. Western blot analysis revealed that protein levels of cyclin D, which is a cell cycle regulating protein thought to be a potential oncogene, decreased in response to DES treatment in F344 rats but remained constant in SD rats. The observed differences in the expression levels of p53, rb and cyclin D suggest that they might be involved in the primary process of estrogen-induced pituitary tumor development prior to detectable tumor growth.
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PMID:Potential involvement of tumor suppressor gene expression in the formation of estrogen-inducible pituitary tumors in rats. 1081 Dec 86

A case of clear cell sarcoma (CCS) arising in the transverse colon is presented. The tumor consisted of sheets or small nests of epithelioid malignant cells possessing pleomorphic nuclei with one or more prominent nucleoli and ample clear or slightly eosinophilic cytoplasm. Some of the tumor cells contained various amounts of melanin pigments that were confirmed by histochemical and ultrastructural examinations. Immunohistochemical examination showed a positive immunoreactivity for HMB45 and S-100 protein. A metastatic nodule, which was found 9 months after surgery, showed similar histological findings to those of the primary one but lacked melanin pigments. Reverse transcriptase- polymerase chain reaction using total ribonucleic acid obtained from metastatic nodule demonstrated the presence of EWS-ATF-1 fusion gene. Based on these findings, the present case tumor is a CCS of the colon.
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PMID:Clear cell sarcoma arising in the transverse colon. 1084 31

The presence of axillary lymph node metastasis in patients with breast cancer is a major prognostic factor and also determines the use of adjuvant chemotherapy. Micrometastasis has been arbitrary defined as deposits of < 2 mm dimension. Earlier studies of micrometastases failed to demonstrate prognostic relevance. However, when larger numbers of patients were followed up for longer periods, micrometastasis was shown to be a significantly poor prognostic parameter with patients having a survival rate similar to those with macrometastasis or nodal disease. There are no compelling reasons to retain the term "micrometastasis" in the light of these findings and our understanding of tumor biology. Routine histological examination of axillary lymph nodes is a notoriously inaccurate method for the detection of metastases. When serial or multilevel sectioning and/or immunohistochemical staining for cytokeratin were employed, detection rates increased by as much as 33%. Reverse transcriptase-polymerase chain reaction and Southern blotting for CK19 may be a more accurate method of examination. However, there are inherent technical problems associated with this method, and the recent finding of a pseudogene with great homology to CK19 in normal peripheral blood nucleated cells further emphasises the need for caution in this approach. It is not cost-effective to employ serial sectioning and immunohistochemistry when examining the axillary contents. However, the introduction of sentinel-node biopsy may allow detailed examination of the single node most likely to harbour a metastatic tumor.
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PMID:The prognostic dilemma of nodal micrometastases in breast carcinoma. 1089 73

Malignant mesothelioma characteristically shows epithelial and/or sarcomatous morphology, this phenotypic differentiation being correlated to the prognosis. The present study was undertaken to see whether proteoglycan (PG) expression influences mesothelioma differentiation. To assess this hypothesis, we studied a mesothelioma model, where the cells were induced to differentiate into epithelial or fibroblast-like morphology, mimicking the biphasic growth of this sarcoma. Series of PGs were analyzed in parallel by semiquantitative reversed transcriptase polymerase chain reaction, showing increased expression of syndecan-2, syndecan-4, and hyaluronan synthase in the epithelial phenotype, whereas the fibroblast-like cells expressed more matrix PGs: versican, decorin, and biglycan. Western blotting confirms these differences and provides evidence of extensive shedding and rapid turnover of cell membrane PGs. Experimental down-regulation of the studied syndecans by antisense targeting resulted in a change in shape from polygonal to spindle-like morphology, while syndecan-1 and -4, but not syndecan-2, could be associated with cell aggregation, indicating distinct functions of different syndecans. The PG profile is thus closely associated with the morphology and biological behavior of tumor cells, mesotheliomas showing a different profile than true epithelial tumors.
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PMID:Differentiation of mesothelioma cells is influenced by the expression of proteoglycans. 1091 83

Disruption of the function of tumor suppressor proteins occasionally can be dependent on their subcellular localization. In about 40% of the breast cancer tissues, p53 is found in the cytoplasm as opposed to the nucleus, where it resides in normal breast cells. This means that the regulation of subcellular location of p53 is an important mechanism in controlling its function. The transport factors required for the nuclear export of p53 and the mechanisms of their nuclear export have been extensively characterized. However, little is known about the mechanism of nuclear import of p53. p53 contains putative nuclear localization signals (NLSs) which would interact with a nuclear transport factor, importin alpha. In this report we demonstrate that importin alpha binds to NLSI in p53 and mediates the nuclear import of p53. Reverse transcriptase-polymerase chain reaction and sequencing analyses showed that a truncated importin alpha deleted the region encoding the putative NLS-binding domain of p53, suggesting that it could not bind to NLSs of p53 proteins. Binding of importin alpha to p53 was confirmed by using yeast two-hybrid assay. When expressed in CHO-K1 cells, the truncated importin alpha predominantly localized to the cytoplasm. In truncated importin alpha expressing cells, p53 preferentially localized to cytoplasmic sites as well. A significant increase in the p21(waf1/cip1) mRNA level and induction of apoptosis were also observed in importin alpha overexpressing cells. These results strongly suggest that importin alpha functions as a component of the NLS receptor for p53 and mediates nuclear import of p53.
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PMID:Truncated form of importin alpha identified in breast cancer cell inhibits nuclear import of p53. 1093 Apr 27

Tumor cells can reach every anatomic district, organ and tissue through the peripheral blood circulation. Tumor cell shedding is considered an early event in the multi-phase process of metastasis, and the possibility of detecting tumor cells in the bloodstream and/or bone marrow before clinical evidence of distant metastases needs to be explored. The use of new sophisticated diagnostic and investigative techniques has boosted the study of tumor cell contamination of bone marrow and peripheral blood. Molecular techniques, such as reverse-transcriptase polymerase chain reaction, may be useful tools to reach this target, but, today, immunocytochemistry is still considered the gold standard to assess new techniques to detect isolated tumor cells in hematopoietic tissue. Little is known about the biology of isolated tumor cells in the peripheral blood or bone marrow. Two crucial points need to be evaluated: the identification of specific markers of breast cancer cells with clonogenic potential and their biologic properties, and the prognostic impact of the detection of isolated tumor cells in the bone marrow or peripheral blood stem cell collections.
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PMID:Detection of breast cancer cells in the bone marrow or peripheral blood: methods and prognostic significance. 1093 95


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