Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies indicate that expression of higher gangliosides in renal cell carcinoma (RCC) is correlated with metastatic potential, particularly in the lung. Out of five major gangliosides in RCC, three disialogangliosides (disialogalactosylgloboside, IV(3)NeuAcIII(6)NeuAcLc(4), and IV(4)GalNAcIV(3)NeuAcIII(6)NeuAcLc(4)) bind strongly to siglec7, which is expressed highly in monocytes and natural killer cells. Out of other gangliosides tested, 2-->6 sialylparagloboside, GD3, GD2, and GT1b, but not other lacto- or ganglio-series gangliosides, showed clear binding to siglec7. In view of preferential metastasis of RCC to the lung, and binding of RCC cell line TOS-1 to lung tissue sections as shown in our previous study, we examined expression of siglec7 in the lung. siglec7 is expressed highly in resident blood cells, but not in parenchymatous cells. TOS-1 cells aggregate together strongly through adhesion with peripheral blood mononuclear cells to form large clumps. This suggests the possibility that such aggregates may form embolisms of microvasculature, particularly in the lung, which initiate metastasis. Other possible roles of higher gangliosides in RCC in promoting metastasis and tumor progression are discussed.
 ...
PMID:Binding specificity of siglec7 to disialogangliosides of renal cell carcinoma: possible role of disialogangliosides in tumor progression. 1138 9

BACKGROUND: Known influence of the immune system on metastases of renal cell cancer (RCC) has led to the development of several therapeutic approaches for further stimulation of the host immune system by cytokines and the retransfusion of tumor-infiltrating lymphocytes (TIL). Based on observations in human prostate adenocarcinomas and transitional cell carcinomas, we have investigated the presence of TIL in different stages of RCC in correlation to vascular endothelial growth factor (VEGF) expression as a parameter for tumor progression and adverse survival in RCC patients. METHODS: Samples from surgically obtained RCC (n = 28) and benign renal parenchyma (n =10) were snap-frozen and processed by double-immunofluorescence staining with CD4/CD8 and VEGF antibodies. RESULTS: In 20 of 28 RCCs a coexpression of TIL-specific markers CD4 and/or CD8 and VEGF was demonstrated. Control tissues were VEGF-negative and showed only negligible infiltration by CD4- or CD8-positive lymphocytes. CONCLUSION: The results indicate that at least 71% of TIL produce VEGF and may promote tumor progression rather than represent an abortive antitumor response of the host immune system. Copyright 2000 S. Karger GmbH, Freiburg
 ...
PMID:Tumor-Infiltrating Lymphocytes Express Vascular Endothelial Growth Factor in Renal Cell Carcinomas. 1144 Dec 41

Previous studies indicate that expression of higher gangliosides in renal cell carcinoma (RCC) is correlated with metastatic potential, particularly in the lung. Out of five major gangliosides in RCC, three disialogangliosides (disialogalactosylgloboside, IV(3)NeuAcIII(6)NeuAcLc(4), and IV(4)GalNAcIV(3)NeuAcIII(6)NeuAcLc(4)) bind strongly to siglec7, which is expressed highly in monocytes and natural killer cells. Out of other gangliosides tested, 2-->6 sialylparagloboside, GD3, GD2, and GT1b, but not other lacto- or ganglio-series gangliosides, showed clear binding to siglec7. In view of preferential metastasis of RCC to the lung, and binding of RCC cell line TOS-1 to lung tissue sections as shown in our previous study, we examined expression of siglec7 in the lung. siglec7 is expressed highly in resident blood cells, but not in parenchymatous cells. TOS-1 cells aggregate together strongly through adhesion with peripheral blood mononuclear cells to form large clumps. This suggests the possibility that such aggregates may form embolisms of microvasculature, particularly in the lung, which initiate metastasis. Other possible roles of higher gangliosides in RCC in promoting metastasis and tumor progression are discussed.
 ...
PMID:Binding specificity of siglec7 to disialogangliosides of renal cell carcinoma: possible role of disialogangliosides in tumor progression. 1152 2

Renal cell carcinoma (RCC) is known to have a wide variation in clinical outcome despite the use of conventional prognostic factors, such as staging or grading. A better knowledge of the biologic aggressiveness of RCC could facilitate the selection of patients at high risk of tumor progression. The aim of this study was to determine if use of measurements of vascular density, cell proliferation, and cell adhesion could better predict the biologic behavior of RCC. We immunohistochemically analyzed CD34, Ki-67, and CD44H expression on formalin-fixed, paraffin-embedded tissues from 73 RCCs for quantifying microvessel density (MVD), Ki-67 labeling index (LI), and CD44H LI, respectively. Univariate cancer-specific survival analysis showed that tumor stage (P < .01), tumor size (P < .001), nuclear grade (P < .01), metastasis (P < .001), MVD (P < .03), Ki-67 LI (P < .001), and CD44H LI (P < .0001) were predictors of tumor-related death. There was a statistical correlation between CD44H LI and both Ki-67 LI (r' = .3) and MVD (r' = -44). Ki-67 LI (P < .04) and CD44H LI (P < .02), as well as metastasis (P < .008), emerged as independent predictors of cancer-specific survival in multivariate analysis in patients with metastases (P < .04 and P < .02, respectively) and in patients without metastases (P < .006 and P < .00001, respectively). Our study suggests that vascular density, cell proliferation, and cell adhesion represent a complex tumor-host interaction that may favor progression of RCC. Cell proliferation and CD44H expression appear to be powerful markers to identify patients with an adverse prognosis.
 ...
PMID:Clinical significance of cell proliferation, microvessel density, and CD44 adhesion molecule expression in renal cell carcinoma. 1461 Jul 54

Local recurrence (LR) of renal cell carcinoma (RCC) after nephrectomy is a rare event with a poor prognosis. The clinical outcome of 15 patients with LR after tumor nephrectomy was analyzed retrospectively. Within a mean follow-up of 28 months (1-110 months) the mean time to recurrence (TTLR) was 23 months. Mean time to further tumor progression (TTP) after surgery was 22.2 months (11-32 months), after surgery and adjunctive therapy 6.8 months (3-15 months+) and after chemoimmunotherapy alone 3.6 months (3-6 months). Tumor specific survival (TSS) rate was 47% at 1 year and 33% at 3 years. Mean TSS after surgery was 62.2 months (38-110 months), after resection and adjunctive treatment 26 months (8-74 months) and after chemoimmunotherapy 9.2 months (7-15 months). In conclusion, surgery is recommended for treatment of LR. Additional benefit is not confirmed for any adjuctive therapy.
 ...
PMID:Therapy of local recurrence of renal cell carcinoma. 1174 81

The INK4a / ARF locus on chromosome 9p21, which encodes two distinct genes, p14(ARF) and p16(INK4a), is frequently altered in human neoplasms. To investigate the potential roles of p14(ARF) and p16(INK4a) genes in human renal cell carcinomas (RCCs), we analyzed 6 human RCC cell lines and 91 primary RCCs for homozygous deletion, promoter hypermethylation and expression of the p14(ARF) and p16(INK4a) gene products using differential PCR, methylation-specific PCR, and immunohistochemistry, respectively. Five cell lines showed homozygous co-deletion of both genes and one demonstrated promoter hypermethylation of the p16(INK4a) gene only. Eight of 91 RCCs showed aberrations of p14(ARF) or p16(INK4a) status and six of these featured gross extension into the renal vein. The results suggest that p14(ARF) and p16(INK4a) aberrations may play roles in the relatively late stage of renal tumorigenesis associated with tumor progression.
 ...
PMID:Aberrations of the p14(ARF) and p16(INK4a) genes in renal cell carcinomas. 1174 94

This study examines the coexpression of MUC1 mucin and trefoil factor 1 (TFF1) and their relationship to progression of renal cell carcinoma (RCC). Immunohistochemistry was performed on tumor and adjacent normal tissue from clear-cell RCC (n = 60) and tissues from normal controls (n = 5) using a set of well-characterized monoclonal antibodies recognizing different epitopes of MUC1 and TFF1. Results of immunohistochemistry were compared with clinical parameters, including tumor grade, tumor size, presence of metastasis, and progression-free survival of patients after surgery. In normal tissue, MUC1 and TFF1 were absent from the normal proximal tubular epithelium but were identified in distal and collecting tubular epithelium. In RCC, increased MUC1 expression positively correlated to tumor progression. MUC1 recognized by HMFG1 was associated with large tumor size (P < .05), distant metastasis (P < .05), and invasion of large veins (P < .05). Expression of the under-glycosylated form of MUC1 recognized by SM3 was found to correlate to time to progression (recurrence, metastasis, or death of patient; P < .001). Expression of TFF1 did not significantly correlate with any prognostic parameters. However, there was a significant correlation (P < .01) between TFF1 and MUC1 expression (HMFG2 epitope) in RCCs. These results are consistent with the following conclusions: (1) MUC1 may be an independent prognostic marker in RCC; (2) TFF1 is frequently coexpressed with MUC1 and may act synergistically; and (3) RCC may originate from distal tubular epithelium.
 ...
PMID:MUC1 mucin and trefoil factor 1 protein expression in renal cell carcinoma: correlation with prognosis. 1182 74

Previously, we described a family with a significantly increased predisposition for renal cell cancer co-segregating with a t(2;3)(q35;q21) chromosomal translocation. Several primary tumors of the clear cell type from different family members were analyzed at a molecular level. Loss of the derivative chromosome 3 was consistently found. In addition, different somatic Von Hippel Lindau (VHL) gene mutations were observed in most of the tumors analyzed, even within the same patient. Based on these results a multistep tumorigenesis model was proposed in which (non-disjunctional) loss of the derivative chromosome 3 represents an early event and somatic mutation of the VHL gene represents a late event related to tumor progression. More recently, however, we noted that these two anomalies were absent in at least one early-stage tumor sample that we tested. Similar results were obtained in another family with renal cell cancer and t(3;6)(q12;q15), thus suggesting that another genetic event may precede these two oncogenetic steps. We speculate that deregulation of a gene(s) located at or near the translocation breakpoint may act as such. In order to identify such genes, a detailed physical map encompassing the 3q21 breakpoint region was constructed. Through a subsequent positional cloning effort we found that this breakpoint targets a hitherto unidentified gene, designated DIRC2 (disrupted in renal cancer 2). Computer predictions of the putative DIRC2 protein showed significant homology to different members of the major facilitator superfamily (MFS) of transporters. Based on additional DIRC2 expression and mutation analyses, we propose that the observed gene disruption may result in haplo-insufficiency and, through this mechanism, in the onset of tumor growth.
 ...
PMID:Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21). 1191 79

To delineate more precisely the somatic von Hippel-Lindau disease (VHL) gene alteration as well as to elucidate its etiologic role in renal tumorigenesis, we examined a total of 240 sporadic renal cell carcinomas (RCCs) for somatic VHL gene alterations by DNA-SSCP followed by sequencing, methylation-specific PCR assay, microsatellite LOH study, and Southern blot analysis. Intragenic mutation of the VHL gene was found exclusively in clear-cell or variant-type RCCs at a frequency of 51% (104/202). Hypermethylation of the VHL promoter region was detected in an additional 11 clear-cell RCCs. Microsatellite analysis demonstrated that LOH of the VHL locus was found in 140/155 (90%) informative clear-cell RCCs. The VHL gene therefore seems to be inactivated in a two-hit manner by intragenic mutation or hypermethylation plus allelic loss in clear-cell RCC. Genomic rearrangement of the VHL gene detected by Southern analysis was not found (0/216 cases); this is in contrast to germ lines in which Southern aberrations consisted of 7-19% of the mutations. Clinicopathologic data demonstrated that VHL mutation/LOH did not vary according to tumor progression in clear-cell RCC, including tumor diameter, stage, grading, distant metastasis, and lymph node metastasis. Interestingly, VHL mutation was significantly less frequent in RCCs occurring in younger (< or = 55 years) than that in older (> or = 56 years) patients. These data suggested that the inactivation of the VHL tumor-suppressor gene is a specific genetic change in clear-cell RCC, and that it may occur at an early or first step in the clear-cell tumorigenic pathway rather than as a late event.
 ...
PMID:Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters. 1192 Dec 83

Previously, we described a family with renal cell carcinoma (RCC) and a constitutional balanced t(2;3) (q35;q21). Based on loss of heterozygosity and von Hippel-Lindau (VHL) gene mutation analyses in five tumor biopsies from three patients in this family, we proposed a multistep model for RCC development in which the familial translocation may act as a primary oncogenic event leading to (nondisjunctional) loss of the translocation-derived chromosome 3, and somatic mutation of the VHL gene as a secondary event related to tumor progression. Here, we describe the cytogenetic and molecular analysis of three novel tumors at early stages of development in two members of this family. Again, loss of derivative chromosome 3 was found in two of these tumors and a VHL mutation in one of them. In the third tumor, however, none of these abnormalities could be detected. These results underline our previous notion that loss of derivative chromosome 3 and VHL gene mutation play critical roles in familial RCC. In addition, they show that both anomalies may occur at relatively early stages of tumor development.
 ...
PMID:Cytogenetic and molecular analysis of early stage renal cell carcinomas in a family with a translocation (2;3)(q35;q21). 1199 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>