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1.
Familial non-syndromic clear cell renal cell carcinoma 总被引:1,自引:0,他引:1
Woodward ER 《Current molecular medicine》2004,4(8):843-848
The diagnosis of familial non-syndromic clear cell renal cell carcinoma is one of exclusion. In families presenting with clear cell RCC a germline VHL mutation and a constitutional translocation of chromosome 3 must be excluded before familial non-syndromic clear cell RCC can be diagnosed. Large familial non-syndromic clear cell RCC kindreds are uncommon and a predisposing gene has not been identified. However inheritance is autosomal dominant in most cases and age at onset is earlier than in sporadic cases. Recognition and appropriate screening of familial non-syndromic clear cell RCC cases will reduce morbidity and mortality. Large scale collaborative linkage studies may provide a basis for the identification of familial non-syndromic clear cell RCC susceptibility gene(s). 相似文献
2.
Human chromophobe cell renal carcinoma 总被引:27,自引:0,他引:27
W Thoenes S St?rkel H J Rumpelt 《Virchows Archiv. B, Cell pathology including molecular pathology》1985,48(3):207-217
3.
Samy L. Habib 《Cell cycle (Georgetown, Tex.)》2014,13(6):869-870
4.
Gouttefangeas C Stenzl A Stevanović S Rammensee HG 《Cancer immunology, immunotherapy : CII》2007,56(1):117-128
Carcinomas of the kidney generally have a poor prognosis and respond minimally to classical radiotherapy or chemotherapy. Immunotherapy constitutes an interesting alternative to these established forms of treatment, and indeed, cytokine-based therapies have been used for many years, leading to favorable clinical responses in a small subset of patients. During the past few years, immunotherapeutical trials targeting renal cell tumor-associated antigens have also been reported, with diverse passive or active approaches using antibodies or aimed at activating tumor-directed T lymphocytes. The following review presents the results and the progress made in the field, including classical cytokine treatments, non-myeloablative stem cell transplantation and antigen specific-based trials, with special focus on T-cell studies. In consideration of the few specific molecular targets described so far for this tumor entity, current strategies which can lead to the identification of new relevant antigens will be discussed. Hopefully these will very soon contribute to an improvement in renal cell carcinoma specific immunotherapy and its evaluation. 相似文献
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6.
Nucleolar organizing regions in renal cell carcinoma, renal oncocytoma and renal adenoma 总被引:1,自引:0,他引:1
Nucleolar organizing regions (NORs), as demonstrated by the silver-colloid staining technique, have been counted in 75 renal cell carcinomas (20 grade 1, 22 grade 2, 17 grade 3 and 16 sarcomatoid), eight renal oncocytomas and nine renal adenomas. Mean NOR counts were 3.27, 6.28, 9.24 and 8.12, respectively, for grades 1, 2, 3 and sarcomatoid tumours, 3.09 for renal oncocytomas and 2.63 for renal adenomas. Analysis of data using the unpaired Student's t-test showed significant difference between NOR counts of grade 1, 2 and 3/sarcomatoid renal cell carcinoma, and grades 2, 3 and sarcomatoid renal cell carcinomas when compared to renal oncocytomas and adenomas. The association between type and grade of tumour, NOR value and tumour proliferation is discussed. 相似文献
7.
Vanessa Drendel Bianca Heckelmann Christoph Schell Lucas Kook Martin L. Biniossek Martin Werner Cordula A. Jilg Oliver Schilling 《Clinical proteomics》2018,15(1):25
Background
Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5–7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns.Methods
We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases.Results
At 1% false discovery rate, we identified?>?3900 proteins, of which?>?2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO.Conclusion
We present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.8.
9.
Nephron-sparing surgery has become an established surgical treatment for patients with renal cell carcinoma (RCC), particularly in situations in which preservation of renal parenchyma is critical. However, due to the fear of local renal fossa recurrence with nephron-sparing surgery, radical nephrectomy has historically been the treatment of choice for patients with unilateral RCC and a normal contralateral kidney. Recently, increased incidence of low-stage, localized, solitary RCC has led to renewed interest in partial nephrectomy. With excellent disease-specific survival and recurrence rates comparable to that achieved with radical nephrectomy, nephron-sparing surgery can be confidently utilized in treating patients with stage T1 RCC lesions (<7 cm) and a normal contralateral kidney. The utility of nephron-sparing surgery in the context of adjunctive systemic immunotherapy remains to be explored. 相似文献
10.
Immunosuppression in murine renal cell carcinoma 总被引:1,自引:0,他引:1
In our companion paper we have reported that cell-mediated immunity of mice bearing renal cell carcinoma is profoundly suppressed. The non-responsiveness of such animals was found to be attributable to Renca cells themselves and to splenic lymphoid cells that down-regulate other fully capable lymphoid cells. In this communication the lymphoid cell source of suppression within Renca-bearing mice has been explored with the aim of identifying phenotypes of the responsible cells, the manner by which suppression is mediated, and initial ways by which suppression may be eliminated. A plastic-adherent cell bearing the Thy1.2 surface marker as well as the Lyt1 and Lyt2 antigens has been found to operate, perhaps in conjunction with macrophages, to down-regulate lymphokine-activated killer (LAK) cell development for natural killer (NK) and non-NK targets that include Renca cells themselves. The splenic suppressor cells lost the capacity to suppress the NK response of normal recipient mice upon shallow irradiation (250 rad) prior to adoptive transfer. Spleen cells, presumably macrophages, from Renca-bearing mice were found to suppress the generation of LAK and NK cells in vitro by synthesizing prostaglandins. Indomethacin, a prostaglandin synthetase inhibitor, blocked the induction of suppression both in vitro and in vivo, suggesting the presence of endogenous prostaglandins in Renca-bearing mice. The suppression seen in Renca-bearing mice that derives from multiple sources and has been prevented by two separate methods has been discussed from the viewpoint of the inter-relatedness of the sources. 相似文献
11.
Amato RJ 《Reviews in urology》2003,5(2):65-71
Several potential vaccines have been evaluated for the treatment of patients with renal cell carcinoma (RCC). They include dendritic cells pulsed with tumor lysate, a dendritic cell-tumor cell hybrid, irradiated tumor cells admixed with adjuvants, and a heat shock protein-peptide complex. Promising results have been obtained in several early clinical trials, but issues of tumor immunosuppression and lack of identified tumor-associated antigens must be addressed before vaccine therapy can be applied successfully in advanced RCC. In this patient population, vaccine therapy will likely be required in combination with other forms of immunotherapy, such as interleukin-2 and thalidomide. In contrast, vaccine therapy alone may be sufficient for high-risk patients in the adjuvant setting. 相似文献
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Summary Four cell-mediated immunological responses related to tumor elimination have been examined in mice injected with a transplantable renal cell carcinoma (Renca). Lymphokine-activated killer (LAK) cells generatedin vitro from spleen cells of normal mice were capable of attacking Renca, EL-4, P815 and YAC-1 targets, but those from mice bearing Renca for 3 weeks could not. Natural killer activity, stimulatedin vivo by administering poly(I) poly(C), was less than 50% of normal in Rencabearing hosts. In addition, development of cytotoxic T lymphocytes to allogeneic targets was markedly inhibited in mice possessing the renal tumor. Finally, the delayed hypersensitivity response to a dermally applied hapten was approximately 70% less than normal in tumor-bearing mice, no matter whether the tumor existed subcutaneously or intrarenally. A kinetic study of the development of nonresponsiveness using the LAK assay showed onset of poor response at 1 week, which became maximal within 3 weeks following receipt of tumor subcutaneously. The immunological depression was seen to be attributable in part to suppressor cells present among spleen cells but not bone marrow cells of tumor-bearing hosts. The suppressor cells preventedin vitro LAK generation by normal spleen cells and, when adoptively transferred to normal mice, they inhibited natural killer stimulation and delayed hypersensitivity generation. Another source of immunological downregulation was provided by Renca cells themselves. Incorporation of Renca cells that had been X-irradiated with 30000 rad into cultures of normal and Renca-derived splenic cells suppressed replication of both almost completely. Furthermore, the presence of X-irradiated Renca cells in cultures of normal spleen cells prevented development of LAK cells. Thus, the suppression seen in Renca-bearing mice derives from multiple sources and whether each is in any way related to the other has been discussed. Identification of the phenotypes of cells responsible for the lymphoid cell-mediated suppression and examination of its elimination are communicated in the companion paper.Offered in partial fulfillment of the requirements for the Ph. D. degree at Cleveland State University by SKG. 相似文献
14.
Prognostic factors in renal cell carcinoma 总被引:2,自引:0,他引:2
We studied 569 cases of renal cell carcinoma in the files of the Department of Pathology of the Norwegian Radium Hospital from 1964 to 1974. A nephrectomy had been performed in all cases. Clinical information on sex, age, survival time and metastases was traced. The histological slides were examined and tumour growth pattern, cell type, cell shape, nuclear atypia, abnormal nucleoli, nuclear grade, vascular invasion and tumour demarcation were all evaluated. Besides well-known prognostic factors such as tumour stage, presence or absence of metastases and vascular invasion, nuclear grade was found to be a useful prognostic factor. Younger patients were found to do better than older, and women better than men. Smaller tumours carried a better prognosis than larger and clear cell tumours had a better prognosis than those composed of eosinophilic or basophilic cells. The presence of spindle cells was a bad prognostic omen. 相似文献
15.
Soini Y Kallio JP Hirvikoski P Helin H Kellokumpu-Lehtinen P Tammela TL Peltoniemi M Martikainen PM Kinnula LV 《Histology and histopathology》2006,21(2):157-165
The aim of the study was to estimate the significance of oxidative/nitrosative damage and expression of antioxidant enzymes in renal cell carcinomas (RCC). For this we investigated immunohistochemically six antioxidant enzymes (AOEs) including MnSOD, ECSOD, thioredoxin, thioredoxin reductase, and gammaglutamyl cysteine synthetase heavy and light chain in 138 RCCs. As an indicator of oxidative/nitrosative damage, sections were stained with an antibody to nitrotyrosine. The extent of apoptosis was evaluated by TUNEL method and proliferation by immunohistochemistry to Ki67. Variable expression of all AOEs could be seen in RCC with expression of MnSOD being strongest. Nitrotyrosine was significantly associated with high grade tumors. MnSOD was associated with tumors of a lower stage. Cases showing ECSOD reactivity had higher and cases expressing thioredoxin lower apoptotic index than other tumors. No association with patient prognosis was observed. According to the results renal cell carcinomas show oxidative/nitrosative damage which, according to nitrotyrosine staining, was higher in high grade tumors. Of AOEs, MnSOD was more abundantly expressed in low stage tumors suggesting that its antioxidant function could play a main role to prevent development of oxidative damage leading to more aggressive tumors. 相似文献
16.
Homogenates of human renal cell carcinomas were tested for glutathione-S-transferase, an enzyme of normal proximal tubule cells. All tumors were positive; mean tumor fraction enzyme activity was 0.040 +/- 0.02 mumol/min/microgram protein. Glutathione-S-transferase activity in homogenates from normal kidney was 0.022 and 0.054 mumol/min/microgram protein. Finding similar levels of a major cytosolic enzyme in tumor and renal cortex confirms the origin of renal cell carcinoma in the proximal nephron. Glutathione-S-transferase, which binds carcinogens and steroids, may play a role in carcinogenesis and serve as a marker for this tumor. 相似文献
17.
Candidate biomarkers in renal cell carcinoma 总被引:1,自引:0,他引:1
Although the human genome has been decoded, the knowledge about the pathogenesis of diseases including cancer is still limited. By focusing on renal cell carcinoma (RCC) we here summarize the data of various research groups analyzing the protein/peptide expression profiles of tumor lesions/cell lines or serum obtained from patients and respective controls. Different powerful approaches such as 2-DE, PROTEOMEX/SERPA/SPEARS, and T cell epitope discovery upon elution of MHC class I-bound peptides in combination with MS/LC-MS/MS revealed 500 differentially expressed proteins. The overlap in target recognition limits the pool to 299 unique protein identities, but only few thereof (12%) have been validated. The management, analysis, and interpretation of the distinct data sets derived from 27 publications required bioinformatic restructuring of the results. However, the comprehensive analysis of the results expands the knowledge about the pathophysiology of RCC in particular of the most prominent clear cell subtype by providing information on the differentially expressed proteins, their regulation status in RCC compared to normal kidney epithelium next to additional information on MHC-presented T cell epitopes and on serological targets. Despite the low number of validated differentially expressed proteins some of them might serve as candidate biomarkers for the diagnosis and/or as therapeutic targets. 相似文献
18.
Kun Liu Rui Gao Hao Wu Zhe Wang Guang Han 《Journal of cellular and molecular medicine》2021,25(9):4260-4274
Renal cell carcinoma (RCC) is one of the leading causes of cancer-related death worldwide. Tumour metastasis and heterogeneity lead to poor survival outcomes and drug resistance in patients with metastatic RCC (mRCC). In this study, we aimed to assess intratumoural heterogeneity (ITH) in mRCC cells by performing a combined analysis of bulk data and single-cell RNA-sequencing data, and develop novel biomarkers for prognosis prediction on the basis of the potential molecular mechanisms underlying tumorigenesis. Eligible single-cell cohorts related to mRCC were acquired using the Gene Expression Omnibus (GEO) dataset to identify potential mRCC subpopulations. We then performed gene set variation analysis to understand the differential function in primary RCC and mRCC samples. Subsequently, we applied weighted correlation network analysis to identify coexpressing gene modules that were related to the external trait of metastasis. Protein-protein interactions were used to screen hub subpopulation-difference (sub-dif) markers (ACTG1, IL6, CASP3, ACTB and RAP1B) that might be involved in the regulation of RCC metastasis and progression. Cox regression analysis revealed that ACTG1 was a protective factor (HR < 1), whereas the other four genes (IL6, CASP3, ACTB and RAP1B) were risk factors (HR > 1). Kaplan-Meier survival analysis suggested the potential prognostic value of these sub-dif markers. The expression of sub-dif markers in mRCC was further evaluated in clinical samples by immunohistochemistry (IHC). Additionally, the genetic features of sub-dif marker expression patterns, such as genetic variation profiles, correlations with tumour-infiltrating lymphocytes (TILs), and targeted signalling pathway activities, were assessed in bulk RNA-seq datasets. In conclusion, we established novel subpopulation markers as key prognostic factors affecting EMT-related signalling pathway activation in mRCC, which could facilitate the implementation of a treatment for mRCC patients. 相似文献
19.
BackgroundF-box proteins play important roles in cell cycle and tumorigenesis. However, its prognostic value and molecular function in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, we established a survival model to evaluate the prognosis of patients with ccRCC using the F-box gene signature and investigated the function of FBXL6 in ccRCC.MethodsComprehensive bioinformatics analyses were used to identify differentially expressed F-box and hub genes associated with ccRCC carcinogenesis. Based on the F-box gene signature, we constructed a risk model and nomogram to predict the overall survival (OS) of patients with ccRCC and assist clinicians in decision-making. Finally, we verified the function and underlying molecular mechanisms of FBXL6 in ccRCC using CCK-8 and EdU assays, flow cytometry, and subcutaneous xenografts.ResultsA risk model based on FBXO39, FBXL6, FBXO1, and FBXL16 was developed. In addition, we drew a nomogram based on the risk score and clinical features to assess the prognosis of patients with ccRCC. Subsequently, we identified FBXL6 as an independent prognostic marker that was highly expressed in ccRCC cell lines. In vivo and in vitro assays revealed that the depletion of FBXL6 inhibited cell proliferation and induced apoptosis. We also demonstrated that SP1 regulated the expression of FBXL6.ConclusionsFBXL6 was first identified as a diagnostic and prognostic marker in patients with ccRCC. Loss of FBXL6 attenuates proliferation and induces apoptosis in ccRCC cells. SP1 was also found to regulate the expression of FBXL6. 相似文献
20.
The function of the kidney, filtering blood and concentrating metabolic waste into urine, takes place in an intricate and functionally elegant structure called the renal glomerulus. Normal glomerular function retains circulating cells and valuable macromolecular components of plasma in blood, resulting in urine with just trace amounts of proteins. Endothelial cells of glomerular capillaries, the podocytes wrapped around them, and the fused extracellular matrix these cells form altogether comprise the glomerular filtration barrier, a dynamic and highly selective filter that sieves on the basis of molecular size and electrical charge. Current understanding of the structural organization and the cellular and molecular basis of renal filtration draws from studies of human glomerular diseases and animal models of glomerular dysfunction.The mammalian kidney orchestrates the excretion of metabolic wastes found in blood, a function intimately related to its essential roles in general fluid homeostasis and osmoregulation. It is also important in the control of blood pressure, synthesis of vitamin D, bone mineralization, and the promotion of erythrocyte development. Despite its modest size (each is approximately the size of a human fist), a mammalian kidney is highly vascularized. A pair of kidneys receives and filters a remarkable volume of blood, estimated to be the equivalent of roughly 20% of total cardiac output (Stein and Fadem, 1978; Munger et al., 2011). In humans, blood filtration by the kidneys generates on average 1 liter of urine per day. Urine is produced and concentrated along the length of nephrons, the basic unit of kidneys (Fig. 1 A). An adult human kidney is known to contain an average of 1 million and up to as many as 2.5 million nephrons (Puelles et al., 2011).Open in a separate windowFigure 1.Anatomical overview of renal filtration. (A) Diagrammatic representation of nephron distribution in the kidney. Glomeruli, the filtration compartments of nephrons, are found within the kidney cortex. (B) Segmental structure of nephrons. The vascularized glomerulus is found at the proximal end and is connected through a series of renal tubules where urinary filtrate composition is refined through resorption and secretion. (C) Cellular organization of the glomeruli. GEC, glomerular endothelial cell; AA, afferent arteriole; EA, efferent arteriole; Pod, podocyte; MC, mesangial cell; PEC, parietal epithelial cell; PT, proximal tubule; DT, distal tubule; LOH, loop of Henle; CD, collecting duct; BS, Bowman’s space.A nephron is functionally subdivided into a filtration unit called the renal corpuscle or glomerulus and a segmented tubular resorption compartment (Fig. 1 B). The glomerulus is an assembly of four different cells: the glomerular endothelial cells (GECs), podocytes, mesangial cells (MCs), and parietal epithelial cells (PECs; Figs. 1 C and and2).2). The word glomerulus is a reference to its intricately tortuous inner capillary tuft formed by GECs, after the Latin word glomus for a ball of yarn (Fig. 2 C). Podocytes are specialized perivascular cells aptly named for their elaborate projections, known as foot processes (FPs) or pedicels, that are intimately wrapped around the exterior of glomerular capillaries (Fig. 2, A and B). GECs and podocytes share a common ECM known as the glomerular basement membrane (GBM). The GECs, the podocytes, and the GBM in between constitute the three distinctive layers of the glomerular filtration barrier (GFB; Fig. 2 E), an elegant sieve that selectively filters blood components, generating a dilute primary urinary filtrate. The mesangium, a stalk-like aggregate of MCs and their ECM called the mesangial matrix, provides the structural reinforcement for the glomerular vasculature. The PECs forms a watertight cuplike enclosure called the Bowman’s capsule. Primary urinary filtrate collects within the Bowman’s capsule and empties through a connected series of epithelial tubules starting from the proximal tubules, the loop of Henle, the distal tubules, and a final collecting duct. The renal tubules of the nephrons and the collecting ducts express various ion and water channels, as well as transporters that help concentrate and adjust the composition of the urinary filtrate by resorption and secretion. This last step is vital for fluid conservation, maintenance of electrolyte balance, and resorption of glucose.Open in a separate windowFigure 2.An ultrastructural overview of podocytes and the glomerular endothelium. (A) Scanning electron micrograph of an exposed glomerulus. In this image, the Bowman’s capsule is broken, permitting a striking view of podocytes (Pod) completely wrapped around the glomerular capillaries. (B) Higher magnification of a podocyte within the glomerulus revealing the interdigitated FPs. (C) A resin cast of the glomerular capillary tuft with the cells corroded to reveal its highly convoluted shape. Image courtesy of F. Hossler (East Tennessee State University, Johnson City, TN). (D) Scanning electron micrograph of an exposed glomerular capillary and its numerous perforations (fenestrae). (E) Simplified diagram of the GFB. The GEC and its fenestrae are lined by a filamentous glycocalyx enriched in negatively charged proteoglycans. The glycocalyx and adsorbed plasma components form the thicker ESL. The GBM is a stratified ECM in between podocytes and GECs. Podocytes form the final layer of the GFB. The interdigitating FPs of podocytes are linked by porous SDs where primary urinary filtrate passes through. Bars: (A) 20 µm; (B and D) 1 µm; (C) 50 µm.