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

We evaluated 28 patients with advanced renal cell carcinoma for the initial expression of P-glycoprotein (MDR1 gene product) employing immunocytochemistry. Tumor specimens were obtained upon primary tumor nephrectomy. In all patients, progression-free survival time following nephrectomy was evaluated and correlated statistically with the staining results. Progression-free survival of patients with no or very few (< 1%) P-glycoprotein-positive tumor cells (n = 8, median survival 27.0 months) was significantly extended (p < 0.04) as compared to patients with 1% or more P-glycoprotein-positive tumor cells (n = 20, median survival 4.0 months). Correlations with histopathological tumor characteristics were insignificant. These results suggest a potential role for P-glycoprotein as a biologic parameter predictive of tumor progression in renal cell carcinoma patients.
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PMID:Immunocytochemical detection of P-glycoprotein: initial expression correlates with survival in renal cell carcinoma patients. 791 63

We described a patient with Beckwith-Wiedemann syndrome associated with rhabdomyosarcoma (RMS), and renal cell carcinoma (RCC). Karyotypes of peripheral lymphocytes and RMS cells were normal. DNA analyses showed maternal loss of heterozygosity (LOH) at 11p15 region in RMS but not in RCC. The insulin-like growth factor II gene (IGF2) was found to be expressed at a moderate level in RMS but not in RCC by in situ hybridization. Each of parental allele-derived IGF2 transcript was detected in RCC, while maternal allele-derived transcript was weak in RMS because of maternal LOH. These results suggest that (1) loss of imprinting (LOI) of IGF2 might be responsible for BWS, (2) on the other hand, LOI itself might not induce tumor occurrence in tissues where the control of tissue-specific expression of IGF2 is maintained, (3) increased expression of IGF2 due to maternal loss of a putative controller gene for IGF2 at 11p15 might predispose to sustaining tumorigenic mutations and tumor progression, (4) loss of a putative onco-suppressor gene at 11p15 might induce RMS occurrence. The cause of RCC was thought to be different from that of RMS.
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PMID:Molecular analysis of a patient with Beckwith-Wiedemann syndrome, rhabdomyosarcoma and renal cell carcinoma. 808 40

Aberrant and elevated ganglioside expression has been observed in neoplasms, and has been shown to be an important marker of tumor progression. We therefore studied the gangliosides of renal cell carcinoma (RCC) by analyzing gangliosides from 18 RCC biopsies, 10 RCC lines and 5 normal kidney biopsies. A comparison of tumor with normal tissue revealed a significant difference in individual ganglioside expression in which the former consistently expressed eight major gangliosides, GM3, GM2, GM1, GD3, GD1A, GD2, GD1B and GT1B, according to the nomenclature of Svennerholm. There was a notable significant mean increase in the expression of GM2, GM1 and GD1A and a significant decrease in the expression of GD3 in tumor tissue compared with normal kidney tissue. Compared with tumor biopsy tissue, RCC cell lines showed a significant decrease in the expression of GM3, but a significant increase in GM2, GM1 and GD2. There was a marked increase in a pathway gangliosides (GM2, GM1, and GD1a) in RCC biopsies and cell lines compared with normal kidney. These studies indicating that RCC have markedly aberrant ganglioside expression similar to neural origin tumors may relate to the activation of a ganglioside pathway enzymes. Gangliosides expressed on RCC tumors may be important markers of tumor progression and target antigens for immunotherapy.
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PMID:Aberrant expression of gangliosides in human renal cell carcinomas. 823 May 55

Allelic loss on the short arm of chromosome 3 (3p) is considered to be one of the early detectable events in the pathogenesis of renal cell carcinoma (RCC). Conflicting reports, however, suggest that this event may be absent in some renal tumors. The present study attempts to further define subgroups of renal tumors associated with 3p deletions. In addition, we have also attempted to identify late genetic events associated with tumorigenesis and tumor progression. Eighty-two primary renal tumors (69 RCC and 13 oncocytic tumors) were analyzed by restriction fragment length polymorphism analysis directed at chromosomes 3, 11p, 17p, and 18q. Results were correlated with histopathological information. Deletions of 3p were seen in nonpapillary RCC of all cell types, but were absent in oncocytic and most papillary tumors. Among the 60 nonpapillary RCC, significant correlations were seen between deletion of 17p and tumor grade (P = 0.037), P stage (P = 0.027), and nodal metastases (P = 0.042). We therefore conclude that 3p deletions, although not specific to any cell type or histological pattern of RCC, are seen in a majority of clear cell nonpapillary RCC but are absent in oncocytic and most papillary tumors. Additional allelic losses on chromosome 17p are associated with advanced disease and, therefore, may be related to tumor progression. Further studies on larger series of patients with extended follow-up will be necessary to investigate the prognostic value of molecular genetic markers in RCC.
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PMID:Allelic deletions in renal tumors: histopathological correlations. 824 36

Hereditary renal carcinoma (RC) in the rat, originally reported by R. Eker in 1954, is an example of a Mendelian dominant predisposition to a specific cancer in an experimental animal. At the histologic level, RCs develop through multiple stages from early preneoplastic lesions (e.g., atypical tubules) to adenomas in virtually all heterozygotes by the age of 1 year. The homozygous mutant condition is lethal at approximately 10 days of fetal life. Ionizing radiation induces additional tumors in a linear dose-response relationship, suggesting that in heterozygotes two events (one inherited, one somatic) are necessary to produce tumors, and that the predisposing gene is a tumor suppressor gene. No genetic linkage has yet been found between the Eker mutation and rat DNA sequences homologous to those in human chromosome 3p, the presumed site of the putative tumor suppressor gene responsible for human RC. Nonrandom loss of rat chromosome 5 in RC-derived cell lines is sometimes associated with homozygous deletion of the interferon gene loci at rat chromosome bands 5q31-q33. Since this locus is not linked with the predisposing inherited gene in the Eker rat, it probably represents a second tumor suppressor gene involved in tumor progression.
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PMID:Spontaneous and radiation-induced renal tumors in the Eker rat model of dominantly inherited cancer. 841 37

Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI. The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation. In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day. Two oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested. All administered dosages of CAI yielded plasma concentration at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitro and in preclinical models (1 microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia. CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day liquid CAI dose level. No evidence of cumulative end organ damage or central nervous system injury was observed. Disease stabilization and improvement in performance status was observed. Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI. Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months). The recommended Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100 mg/m2/day in the gelatin capsule formation.
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PMID:Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. 856 73

During a 10-year period, 17 patients with segmentally destructive bone lesions of the humeral diaphysis in disseminated malignancies resulting in impending fracture (8 patients), pathologic fracture (6 patients), or failure of attempted internal fixation techniques (3 patients) were treated with resection of the involved diaphyseal segment and reconstruction with a cemented modular intercalary humeral spacer. Fourteen patients had metastatic cancer, 2 had multiple myeloma, and 1 had lymphoma. Breast and renal carcinoma were the most common pathologic diagnoses. The involved site was within the middle 1/3 in 8 patients, in the proximal-middle junction in 5, in the middle-distal junction in 2, and within the proximal and distal 1/3 in 1 patient each. Early pain relief was successful in 88% of patients. Early in the postoperative hospital course, patients generally were able to use the ipsilateral hand to assist feeding. Radiographic analysis revealed that the limited selection of stem lengths led to 76% of the distal stems and 47% of the proximal stems being shorter than the ideal length. The complication rate independent of disease progression was 29%. The most common complication was temporary radial nerve injury (3 patients). There were 3 implant failures, most commonly due to disengagement of the male-female junction. Two periprosthetic fractures occurred, 1 proximally (due to tumor progression) and 1 distally. Suggestions are given for modification of the implants to improve the major problems of limited versatility in intramedullary stem length and inadequate mating at the junction.
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PMID:Intercalary spacers in the treatment of segmentally destructive diaphyseal humeral lesions in disseminated malignancies. 859 62

Aberrant glycosylation expressed in specific types of human cancer may define stage, direction, and fate of tumor progression. Well-studied examples are expression of sialosyl-Lewis(x) or sialosyl-Lewis(a) in colorectal carcinoma and histo-blood group A and H/Le(y) in lung cancer. In renal cell carcinoma (RCC), expression of sialosyl-Lewis(x) has no correlation with metastatic potential. Clinicopathological studies have revealed that the degree of expression of disialosyl galactosylgloboside (DSGG) and monosialosyl galactosylgloboside is correlated with metastatic potential (to lung and lymph nodes) of RCC and inversely correlated with patient survival. In the present study, we compared the adhesion of RCC lines to sections of various tissues measured by Stamper-Woodruff assay and other similar assays under dynamic flow conditions. Of the eight RCC lines tested, only TOS-1 (which expresses DSGG) bound strongly to lung tissue sections. TOS-1 did not bind to sections of liver, kidney, or lymph nodes. In the same eight RCC lines, we also compared expression of DSGG and monosialosyl galactosylgloboside (reflected by reactivity with RM1 and RM2), overall ganglioside patterns, and correlation with lung tissue-binding ability. Under both static and dynamic flow conditions, the binding of TOS-1 cells to lung alveolar tissue was correlated with their DSGG expression, i.e., the binding was inhibited by RM2 but not by RM1. This binding was also inhibited by sialidase but not by EDTA (i.e., it was CA 2+ independent). The other seven cell lines (TOS-2, TOS-M, SMKT-R1, -R2, -R3, and -R4, and ACHN), which do not express DSGG, showed much weaker adhesion to lung tissue. None of the eight cell lines showed E- or P-selectin-dependent adhesion. These results suggest the existence of a yet-uncharacterized sialoadhesive receptor++ that specifically recognizes DSGG. This receptor could be the binding target in RCC metastasis to lung.
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PMID:Disialosyl galactosylgloboside as an adhesion molecule expressed on renal cell carcinoma and its relationship to metastatic potential. 862 May 16

In addition to the commonly used pathologic staging systems such as the TNM classification, the grading and demographic features have been reported to affect survival following surgical extirpation of renal cell carcinoma (RCC). These features, especially the pathologic stage, are well established as prognostic factors. However, several cellular and molecular variables, although potentially important in the ultimate outcome, are not taken into consideration by these criteria. Thus patients with different prognoses may be classified as belonging to the same stages. Attempts are now made to use cytogenetic and molecular findings to predict long-term survival of RCC patients. Chromosome 16 q and 14 q aberrations may play an important role in the future by identifying the high-risk groups of patients with papillary and nonpapillary RCC, resp. In nonpapillary RCC, mutations of the von Hippel-Lindau gene have been implicated as the initial step of carcinogenesis. However, the subsequent steps remain to be elucidated and the search for genetic markers associated with tumor progression is under way. The distinction between patients with high and low risk of progression will become increasingly important as more effective adjuvant therapies are available.
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PMID:[Traditional and future criteria for progression in renal cell carcinoma. Molecular biology and clinical aspects]. 871 34

Circulating immune markers sICAM-1, sELAM-1, sMHC-I, beta 2-MG, sCD4 and sCD8 were evaluated prior to and during immunotherapy with biologically active doses of interferon gamma (IFN-gamma) in 16 patients with advanced renal cell carcinoma (RCC) over a period of 12 months. Compared to 20 healthy controls, significantly (P < 0.01) elevated baseline levels of circulating adhesion molecules sICAM-1 (mean 1166 vs 230 ng/ml) and sELAM-1 (70 vs 17 ng/ml) were found in all patients. Compared to responders (n = 2) or patients with stable disease (n = 2), progressive disease during therapy (n = 12) was associated with significantly (P < 0.05) higher mean concentrations of sICAM-1 (1574 vs 962 ng/ml) and sELAM-1 (86 vs 46 ng/ml). Pretherapeutic and intratherapeutic levels of sMHC-I among the RCC patients were significantly (P < 0.05) lower than among the controls (0.41 vs 0.8 ng/ml). sCD4 levels clearly showed the same tendency (24 vs 33 U/l). sCD8 baseline levels, by contrast, were significantly (P < 0.05) elevated (564 vs 336 U/l), reflecting either activation of the NK-cell subset or increased synthesis of CD8+ T-suppressor cells. Again, significantly (P < 0.05) higher intratherapeutic sCD8 concentrations were observable with progressive disease than with response to therapy or stable disease (721 vs 355 U/l). Interestingly, although the biologically active dose of IFN-gamma was defined by an increase in beta 2-MG release of at least 30% within 48 h after injection, none of the other markers showed any significant alteration following IFN-gamma administration, suggesting that IFN-gamma in vivo does not produce changes in circulating markers of activation that might be expected on the basis of its effects in vitro. The finding of significantly elevated concentrations of sICAM-1, sELAM-1 and sCD8 in the presence of low sCD4 and sMHC-I levels might be of clinical significance for indicating ongoing tumor progression.
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PMID:Circulating immune markers in advanced renal cell carcinoma during immunotherapy with interferon gamma. 874 Sep 79


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