National Cancer Institute®
Last Modified: November 21, 2001
UI - 20389780
AU - Symbas NP; Townsend MF; El-Galley R; Keane TE; Graham SD; Petros JA
TI - Poor prognosis associated with thrombocytosis in patients with renal cell carcinoma.
SO - BJU Int 2000 Aug;86(3):203-7
AD - Department of Urology, Emory University School of Medicine, Atlanta, Georgia, and The Virginia Medical Center, USA.
OBJECTIVES: To better define the relationship between platelet count and survival using a retrospective analysis in patients with thrombocytosis and metastatic renal cell carcinoma (RCC), some of whom had a shorter life expectancy than those with a normal platelet count. PATIENTS AND METHODS: The records were reviewed of patients with stage IV RCC who had undergone a variety of adjuvant therapies after nephrectomy between 1972 and 1992. Entry criteria included a tissue diagnosis of RCC, at least one platelet count and a complete follow-up until the time of death. Of 350 patients available for review, 259 met the entry criteria. Patients were divided into two groups: group 1 included 112 patients whose platelet counts remained at < 4 x 105/microL between the time of nephrectomy and the time of death; group 2 included 147 patients with at least one platelet count of > 4 x 105/microL (mean age in each group 57 years). RESULTS: The mean (SD) survival for group 1 was 151 (34) months, compared with 92 (18) months for those in group 2. Using the log-rank chi-square test the difference in survival between the groups was significant (P = 0.005). Controlling for established prognostic indicators of pathological stage, nuclear grade and cell type, using Cox's regression technique, the difference in survival between the groups remained significant (P = 0.015). CONCLUSIONS: These results suggest that patients with metastatic RCC who receive adjuvant therapy and have a persistently normal platelet count have a 64% longer life expectancy than those with thrombocytosis. The difference is highly statistically significant when controlled for nuclear grade, cell type and pathological stage.
UI - 21230212
AU - Val-Bernal JF; Pinto J; Gomez-Roman JJ; Mayorga M; Villoria F
TI - Papillary adenoma of the kidney with mucinous secretion.
SO - Histol Histopathol 2001 Apr;16(2):387-92
AD - Department of Anatomical Pathology, Marques de Valdecilla University Hospital, Medical Faculty, University of Cantabria, Santander, Spain. email@example.com
Although infrequently, mucin secretion has previously been reported in papillary renal cell carcinoma. We here investigate the presence of mucin in a series of 93 renal papillary adenomas in 58 patients. Acid mucin was present in four cases (4.3% of the tumors; 6.9% of the patients), in which basophilic mucin secretion was evident with hematoxylin-eosin. To the best of our knowledge mucin secretion has not been reported in renal papillary adenoma. We describe two different types of mucin secretion: intracytoplasmic and luminal. The secretion was intracellular in numerous scattered tumor cells in two cases, focal luminal in one case, and mixed intracellular and luminal in another case. Mucin production, despite its low frequency, can be considered as an additional feature of renal papillary adenoma. Mucin production suggests that renal papillary adenoma and papillary renal cell carcinoma are actually not two independent biological processes, but a continuum of one biological process.
UI - 21256513
AU - Guarino M; Zuccoli E; Garda E; Cristofori E; Pallotti F; Nebuloni M;
TI - Giordano F Extracellular matrix globules in renal oncocytoma.
SO - Pathol Res Pract 2001;197(4):245-52
AD - Departments of Anatomical Pathology of D. Cotugno Hospital, Naples, Italy.
Extracellular hyaline globules resulting from abnormal accumulation of matrix components have been described in several pathological conditions, including renal tumors. We studied 16 renal oncocytomas and observed these bodies in 11 of them. In these tumors, they showed a homogeneous texture as well as roundish, smooth contours, and were easily detected in hematoxylin-eosin sections in five cases. PAS staining greatly facilitated the identification of globules in the remaining six cases, where they were fewer in number. Immunohistochemically, they appeared to be composed primarily of basement membrane material, being strongly reactive to antibodies for type IV collagen, laminin, and heparan sulphate proteoglycan. In addition, a weak immunoreactivity for type I and type III collagen, and fibronectin was observed in some cases, whereas no globule stained for tenascin. We also analyzed 89 renal cell carcinomas, and found somewhat similar bodies in 10 of them. However, they were more scanty in the latter tumors, and displayed a more irregular configuration with granular or smudged contours. We conclude that, although the mere presence of extracellular hyaline globules does not justify a distinction between renal oncocytoma and renal cell carcinoma, the detection of a large number of well-demarcated, roundish extracellular bodies with smooth contours suggests renal oncocytoma.
UI - 21336420
AU - Marumo K; Satomi Y; Miyao N; Hasegawa M; Tomita Y; Igarashi T; Onishi T;
TI - Nakazawa H; Fukuda M; Ozono S; Terachi T; Tsushima T; Nakamoto T; Kawamura J; The Japanese Society of Renal Cancer The prevalence of renal cell carcinoma: a nation-wide survey in Japan in 1997.
SO - Int J Urol 2001 Jul;8(7):359-65
AD - Department of Urology, School of Medicine, Keio University, Tokyo, Japan. firstname.lastname@example.org
BACKGROUND: The present study was conducted to investigate the incidence of renal cell carcinoma by sex, age group and different regions in Japan. METHODS: The survey was conducted from the beginning of January prefectures throughout Japan were requested to register cases. RESULTS: There were 6358 persons with renal cell carcinoma, consisting of 4372 men and 1986 women. The age-specific incidence rates showed a peak in the age group of 65-70 years in both men and women. The crude incidence rates per 100 000 population for men and women were 7.1 and 3.1, respectively, and age-standardized incidence rates per 100 000 population for men and women were 4.9 and 1.8, respectively. The incidence rates in the Hokkaido region were significantly higher than in other regions (P < 0.05), among which there was no significant difference in incidence rates. CONCLUSIONS: The present study showed that the incidence rates of renal cell carcinoma in Japan were approximately the same as among Japanese in Los Angeles. The rates were, however, lower than North American and European countries, but higher than China, Central or South American countries and African countries. The reasons for the high incidence of renal cancer in the Hokkaido region are not entirely clear. Further epidemiologic research is required.
UI - 21336424
AU - Kong C; Zhang X; Takenaka I
TI - Apoptotic cell death and Smad4 expression in transitional cell carcinoma of the renal pelvis and ureter.
SO - Int J Urol 2001 Jul;8(7):386-90
AD - Department of Urology, Kagawa Medical University, Kagawa, Japan.
PURPOSE: To investigate the frequency of apoptosis and the expression of Smad4 protein as well as their roles in transitional cell carcinoma (TCC) of the renal pelvis and ureter. METHODS: Apoptosis was detected by using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) technique in 34 formalin-fixed and paraffin-embedded specimens of renal pelvic and ureteral TCC. The expression of Smad4 was immunohistochemically studied. RESULTS: The incidence of apoptosis ranged from 1.10 to 3.75% with a median of 2.50% in TCC of the renal pelvis and ureter. The incidence of apoptosis was noted to be closely related to histologic grade but not to pathologic stage of the cancer. The expression of Smad4 was detected in six of 34 cases (17.6%). Regarding subcellular distribution, Smad4 protein was localized both in cytoplasm and nucleus of the cancer cells. In comparing the incidence of apoptosis with the expression of Smad4, no significant associations were seen between them. The expression of Smad4 was not related to the tumor grade nor stage of the cancer. CONCLUSIONS: The present study demonstrated close association of the incidence of apoptosis with the tumor grade of TCC of the renal pelvis and ureter. Significance of Smad4 expression was not noted in the study. It suggests that apoptotic cell death may play an important role in the tumor progression of renal pelvic and ureteral TCC.
UI - 21336431
AU - Pantuck AJ; Zisman A; Belldegrun A
TI - Gene and immune therapy for renal cell carcinoma.
SO - Int J Urol 2001 Jul;8(7):S1-4
AD - Division of Urologic Oncology, Department of Urology, University of California School of Medicine, Los Angeles, California, USA. email@example.com
Conventional therapy for metastatic renal cell carcinoma is associated with a poor response rate and few patients are long-term survivors. The occurrence of spontaneous regression and the prolonged latency period between primary tumor removal and the appearance of metastases in some patients suggest the existence of important host immune responses to autologous tumor cells. With the advent of molecular gene transfer techniques and increased knowledge of the basic pathways of immune activation, the field of cancer immunotherapy has finally begun to develop novel and effective approaches for harnessing the immune system as a therapeutic agent. Current immunotherapy and gene therapy strategies, including methods of cytokine delivery and tumor-cell-based vaccines, are presented.
UI - 21338550
AU - Zekri J; Ahmed N; Coleman RE; Hancock BW
TI - The skeletal metastatic complications of renal cell carcinoma.
SO - Int J Oncol 2001 Aug;19(2):379-82
AD - YCR Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, S10 2SJ, UK.
Of the 103 patients with advanced renal cell carcinoma 31 (30%) developed symptomatic radiologically confirmed skeletal metastases. These were typically lytic, predominantly affecting the axial skeleton and associated with considerable skeletal morbidity. Solitary bone lesions occurred in 14 (45%) of patients. The median survival of patients with bone metastases was 12 months. Hypercalcaemia was common in patients both with (29%) and without (44%) bone metastases. The number and rate of skeletal related events was similar to that seen from bone metastases from breast cancer. It would therefore be appropriate to evaluate the effectiveness of bisphosphonate treatment for reducing skeletal morbidity in advanced renal cell cancer with bone metastases.
UI - 21340679
AU - Mickisch GH
TI - Urologic approaches to metastatic renal cell carcinoma.
SO - Onkologie 2001 Apr;24(2):122-6
AD - Department of Urology, Erasmus University and Academic Hospital, Rotterdam. firstname.lastname@example.org
The treatment of choice for nondisseminated disease is surgery. However, the 5-year survival rates for all stages do not exceed 60%, even in contemporary series. Further improvement will most likely have to await the development of a more effective systemic therapy and the application of combined treatment modalities to counter the relatively high number of patients presenting with advanced stages. Treatment options in metastatic disease include nephrectomy alone, sometimes in combination with metastasectomy in selected cases, or cytoreductive surgery followed by immunotherapy. Alternatively, one may apply immunotherapy initially and perform adjuvant nephrectomy in the case of a response, or proceed with immunotherapy as a monotherapy. Nevertheless, long-term survival rates range merely from 5 to 10%, depending strongly on patient selection criteria. Concepts and progress in this field appear to be of major interest for modern urooncologists following the advent of immunotherapeutic strategies that require a surgical intervention at some stage of the treatment cascade. Copyright 2001 S. Karger GmbH, Freiburg
UI - 21381870
AU - Flanigan RC; Yonover PM
TI - The role of resection for patients with renal carcinoma.
SO - Curr Oncol Rep 2001 Sep;3(5):424-32
AD - Department of Urology, Cardinal Bernardin Cancer Center, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA. email@example.com
Metastatic renal cancer is responsive in some cases to immunotherapeutic agents. Indications for nephrectomy in the face of metastatic disease have traditionally included palliation of symptoms caused by the primary tumor, and nephrectomy combined with metastatectomy in patients with resectable metastases. Recent findings from a Southwest Oncology Group trial strongly suggest that cytoreductive nephrectomy, combined with immunotherapy, may also result in improved survival in patients with unresectable metastases.
UI - 21381871
AU - Hayes-Lattin BM; Maziarz RT; Beer TM
TI - Allogeneic stem-cell transplantation in renal-cell carcinoma.
SO - Curr Oncol Rep 2001 Sep;3(5):433-7
AD - Division of Hematology and Medical Oncology, Oregon Health Sciences University, Mail Code L586, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.
Metastatic renal-cell carcinoma (RCC) remains resistant to nearly all standard cytotoxic therapies, but immune-based cytokine therapies benefit a small minority of patients with advanced RCC. Nonmyeloablative allogeneic stem-cell transplantation is a novel approach to harnessing the immune system to combat this cancer. The strategy relies on a T-cell graft-versus-malignancy effect mediated by donor T cells. Preliminary work in using nonmyeloablative allogeneic stem-cell transplant in RCC has identified a graft-versus-RCC effect and yielded encouraging clinical responses.
UI - 21382675
AU - Grady B; Goharderakhshan R; Chang J; Ribeiro-Filho LA; Perinchery G;
TI - Franks J; Presti J; Carroll P; Dahiya R Frequently deleted loci on chromosome 9 may harbor several tumor suppressor genes in human renal cell carcinoma.
SO - J Urol 2001 Sep;166(3):1088-92
AD - Department of Urology, Veterans Affairs Medical Center and University of California-San Francisco, San Francisco, CA, USA.
PURPOSE: Loss of various loci on chromosome 9 has been reported in various cancers. To determine the frequency of deletions at different loci of chromosome 9 in renal cell carcinoma microdissected samples of normal renal epithelium and carcinoma from the same patients were analyzed. MATERIALS AND METHODS: DNA was isolated from microdissected sections of normal and tumor cells of 60 renal specimens, amplified by polymerase chain reaction and analyzed for loss of heterozygosity on chromosome 9 using the 16 microsatellite markers D9S178, D9S157, D9S274, D9S168, D9S285, D9S156, D9S1839, D9S162, IFNA, D9S736, D9S171, D9S1749, D9S273D9S270, D9S153 and D9S170. Loss of heterozygosity was analyzed by a polymerase chain reaction based technique developed at our laboratory. RESULTS: This study showed a high incidence of loss of heterozygosity on chromosome 9 in renal cell carcinoma. Of 60 cases 44 (73%), 24 (40%) and 14 (23%) showed loss of heterozygosity at a minimum of 1, at a minimum of 3 and at 4 or more loci, respectively. The main deletion was found on the 9p21 region at loci DS171 in 38% of cases, D9S1749 in 42% and DS270 in 14%. Overall deletion on chromosome 9p21 was noted in 57% of renal cancer cases. Other deleted regions were on chromosome 9p'0022 to 23 at loci D9S157 in 37% of cases, D9S274 in 20%, D9S168 in 27%, D9S285 in 20%, D9S156 in 12%, D9S1839 in 17% and D9S162 in 24%. Overall deletion at chromosome 9q32 to 33 was noted in 46% of renal cell carcinoma cases. Chromosome 9q32 to 33 also showed deletion at locus D9S170 in 22% of renal cell carcinoma cases. When we compared the incidence of deletion at various loci on chromosome 9 according to renal cell carcinoma grade, we found a higher rate of deletion in advanced grades of renal cell carcinoma. A candidate target tumor suppressor gene, p16 (MTS-1/CDKN2), has been identified within the 9p21 deleted region in various cancers. In our study the expression of p16 protein was absent or low in renal cell cancer samples, suggesting that loss of the p16 gene may be involved in renal cell carcinogenesis. CONCLUSIONS: Our study demonstrates a high incidence of loss of heterozygosity on chromosome 9, mainly 9p21 and 9p22 to 23, in renal cell carcinoma, suggesting several putative tumor suppressor genes on these regions. The identification of other tumor suppressor genes on the 9p21 and 9p22 to 23 regions warrants further studies.
UI - 21382598
AU - Ramdave S; Thomas GW; Berlangieri SU; Bolton DM; Davis I; Danguy HT;
TI - Macgregor D; Scott AM Clinical role of F-18 fluorodeoxyglucose positron emission tomography for detection and management of renal cell carcinoma.
SO - J Urol 2001 Sep;166(3):825-30
AD - Department of Nuclear Medicine and Centre for PET, Department of Nephrology, Oncology Unit, Ludwig Institute for Cancer Research, Austin & Repatriation Medical Centre, Heidelberg, Australia.
PURPOSE: We evaluate the accuracy of F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) for staging and management of renal cell carcinoma. MATERIALS AND METHODS: FDG-PET was performed in 25 patients with known or suspected primary renal tumors and/or metastatic disease and compared with conventional imaging techniques, including computerized tomography (CT). Histopathological confirmation was obtained in 18 patients and confirmation of the disease was by followup in the remainder. The impact of FDG-PET on disease management was also assessed. RESULTS: Of the 17 patients with known or suspected primary tumors FDG-PET was true positive in 15, true negative in 1 and false-negative in 1. Comparative CT was true positive in 16 patients and false-positive in 1. The accuracy of FDG-PET and CT was similar (94%). All patients would have undergone radical nephrectomy after conventional imaging findings but FDG-PET results altered treatment decisions for 6 (35%), of whom 3 underwent partial nephrectomy and 3 avoided surgery due to confirmation of benign pathology or detection of unsuspected metastatic disease. Of the 8 cases referred for evaluation of local recurrence and/or metastatic disease FDG-PET changed treatment decisions in 4 (50%), with disease up staged in 3 and recurrence excluded in 1. Compared with CT, FDG-PET was able to detect local recurrence and distant metastases more accurately and differentiated recurrence from radiation necrosis. CONCLUSIONS: FDG-PET accurately detected local disease spread and metastatic disease in patients with renal cell carcinoma and altered treatment in 40%. FDG-PET may have a role in the diagnostic evaluation of patients with renal cell carcinoma preoperatively and staging of metastatic disease.
UI - 21382599
AU - Bohm M; Ittenson A; Philipp C; Rohl FW; Ansorge S; Allhoff EP
TI - Complex perioperative immuno-dysfunction in patients with renal cell carcinoma.
SO - J Urol 2001 Sep;166(3):831-6
AD - Department of Urology, Institute of Experimental Internal Medicine, Otto-von-Guericke-University, Magdeburg, Germany.
PURPOSE: Patients with renal cell carcinoma have an impaired function of the immune system, which is the basis for different approaches of immunotherapy. We address perioperative changes of several parameters of the immune system in these patients. MATERIALS AND METHODS: Parameters of cellular and humoral immunity, including differential blood count, T cell markers CD2, 3, 4 and 8, B cell markers CD19 and 20, monocyte markers CD13 and 14, natural killer cell marker CD16, activation markers CD25, CD26 and HLA-DR, and cytokines interleukin-1 (IL-1) receptor antagonist, IL-2, soluble IL-2 receptor, IL-6, IL-10 and transforming growth factor-beta, were measured in the venous blood of patients who underwent renal surgery extracorporeal shock wave lithotripsy (ESWL, Dornier Medical Systems, Inc., Marietta, Georgia). Patients were grouped and age matched, and 37 underwent tumor nephrectomy, 20 open renal surgery for nonmalignant reasons and 24 ESWL. A group consisting of 39 controls received no treatment. RESULTS: Little change was detected in controls and those patients who received ESWL. Patients who underwent open renal surgery had increased leukocyte and granulocyte counts until postoperative day 3 but had low T cell counts. The postoperative decrease in CD25 expressing cells corresponded to an increase in the soluble IL-2-receptor. Cytokines IL-6 and 10, which also have immunosuppressive properties, were markedly increased postoperatively. These changes were more noted (p <0.01) in those patients who underwent tumor nephrectomy than open renal surgery for nonmalignant reasons and remained detectable when paired patients with similar surgical trauma were compared. In tumor nephrectomy cases renal venous IL-6 was higher than peripheral venous levels. CONCLUSIONS: Patients with renal cell carcinoma suffer from selective immuno-dysfunction, indicating a rationale for perioperative immunomodulation.
UI - 21418986
AU - Reutzel D; Mende M; Naumann S; Storkel S; Brenner W; Zabel B; Decker J
TI - Genomic imbalances in 61 renal cancers from the proximal tubulus detected by comparative genomic hybridization.
SO - Cytogenet Cell Genet 2001;93(3-4):221-7
AD - Children's Hospital, University of Mainz, Mainz, Germany.
Comparative genomic hybridization (CGH) has been applied to characterize 61 primary renal cell carcinomas derived histogenetically from the proximal tubulus. The tumor samples comprised 46 clear-cell renal cell carcinomas (ccRCCs) and 15 papillary renal cell carcinomas (pRCCs). Changes in the copy number of entire chromosomes or subregions were detected in 56 tumors (92%). In ccRCCs, losses of chromosome 3 or 3p (63%); 14q (30%); 9 (26%); 1 and 6 or 6q (17% each); 4 and 8 or 8p (15% each); 22 (11%); 2 or 2q and 19 (9% each); 7q, 10, 16, 17p, 18, and Y (7% each); and 5, 11, 13, 15, and 21 (4% each) were detected. Most frequent genomic gains in ccRCC were found on chromosome 5 (63%); 7 (35%); 1 or 1q (33%); 2q (24%); 8 or 8q, 12, and 20 (20% each); 3q (17%); 16 (15%); 19 (13%); 6 and 17 or 17q (11% each); and 4, 10, 11, 21, and Y (9% each). In pRCCs, gains in the copy number of chromosomes 7 and 17 (7/15, each) and 16 and 20 (6/15, each) were frequent. One pRCC showed amplification of subchromosome regions 2q22-->q33, 16q, 17q and the entire X chromosome. In pRCC, losses were less frequently seen than gains. Losses of chromosomes 1, 14, 15, and Y (3/15 each) and 2, 4, 6, and 13 (2/15 each) were observed. In ccRCCs, statistical evaluation revealed significant correlations of chromosomal imbalances with tumor stage and grade, i.e., a gain in copy number of chromosome 5 correlated positively with low tumor grade, whereas a gain of chromosomes 10 and 17 correlated positively with high tumor grade. Furthermore, loss of chromosome 4 correlated positively with high tumor stage. Copyright 2001 S. Karger AG, Basel
UI - 21434724
AU - Les KA; Nicholas RW; Rougraff B; Wurtz D; Vogelzang NJ; Simon MA;
TI - Peabody TD Local progression after operative treatment of metastatic kidney cancer.
SO - Clin Orthop 2001 Sep;(390):206-11
AD - William Beaumont Hospital, Rose Cancer Center, Royal Oak, MI, USA.
The cases of 78 patients with osseous metastases from kidney cancer were reviewed to determine the rate of local progression after operative resection as compared with more traditional intralesional procedures. Group I consisted of 41 (53%) patients who were treated with intralesional procedures involving internal fixation with or without curettage or polymethylmethacrylate. Of the 41 patients, additional operations were recommended for 17 (41%) of the patients who had local osseous progression. Fourteen additional procedures including nine wide resections with reconstruction, three amputations, and two mass excisions were done. Group II consisted of 37 (47%) patients who were treated with marginal or wide resection with or without reconstruction. In this group, only one patient required additional operative intervention for local osseous progression. Median survival of patients in Group I was 20 months compared with 35 months for patients in Group IL This study shows that despite shorter average survival, patients who undergo intralesional surgery are at high risk of reoperation for local progression. Resectional surgery should be considered in patients with skeletal metastases from kidney cancer to lessen the risk of reoperation for local progression.
UI - 21439596
AU - Bernard J; Treton D; Vermot-Desroches C; Boden C; Horellou P; Angevin E;
TI - Galanaud P; Wijdenes J; Richard Y Expression of interleukin 13 receptor in glioma and renal cell carcinoma: IL13Ralpha2 as a decoy receptor for IL13.
SO - Lab Invest 2001 Sep;81(9):1223-31
AD - INSERM U 131, Institut Paris-Sud sur les Cytokines, Clamart, France.
Glioma and renal cell carcinoma (RCC) cells express high affinity interleukin 13 (IL13) binding sites, but only RCC cell proliferation was inhibited by IL13. Both of these two cell types are IL2-receptor (gamma)c chain-negative. We thus used these cell models to investigate the patterns of expression of IL13Ralpha1, IL13Ralpha2, and IL4Ralpha chains and the role of IL13Ralpha2 in the response to IL13. Using new specific antibodies and flow cytometry, we observed a similar surface expression of IL4Ralpha and IL13Ralpha1 chains in most RCC and glioma cells, whereas IL13Ralpha2 was only present on five of six glioma cell lines. In all glioma cell lines, the amount of IL13Ralpha2 expression was 10 to 30 times higher than that of the two other chains. Although there was no surface or intracellular expression of IL13Ralpha2, its mRNA was detected in three of seven RCC cell lines. The expression on RCC cells of IL13Ralpha2 mRNA and/or that of high-affinity IL13 binding sites is not sufficient to predict IL13Ralpha2 protein expression. Blocking experiments showed that IL4 and IL13 strongly inhibited RCC cell proliferation through a unique receptor composed of IL4Ralpha and IL13Ralpha1 chains. Using RCC cells stably transfected with IL13Ralpha2 cDNA, we showed that the overexpression of IL13Ralpha2 decreased the response to IL13 but not that to IL4. Our results demonstrate that IL13Ralpha2 acts as a decoy receptor for IL13 and that it may exert a tight regulation of IL13 activity without impairing the IL4 response of the same cell target.
UI - 21190900
AU - Atkins MB; Redman B; Mier J; Gollob J; Weber J; Sosman J; MacPherson BL;
TI - Plasse T A phase I study of CNI-1493, an inhibitor of cytokine release, in combination with high-dose interleukin-2 in patients with renal cancer and melanoma.
SO - Clin Cancer Res 2001 Mar;7(3):486-92
AD - Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
CNI-1493, an inhibitor of proinflammatory cytokines, was studied in a Phase I trial in melanoma and renal cancer patients receiving high-dose interleukin 2 (IL-2). Objectives of the study were to define the maximum tolerated dose (MTD) and toxicity of CNI-1493, to assess its pharmacological effects, and to define its pharmacokinetics. Twenty-four patients were treated in sequential cohorts with CNI-1493 doses from 2 through 32 mg/m2 daily. Patients first received only CNI-1493 daily for 5 days. After a 9-day rest, patients received two 5-day courses of IL-2 of 600,000 IU/kg every 8 h for up to 14 doses/course plus daily CNI-1493; courses were separated by a 9-day rest period. CNI-1493 administered alone was well tolerated at doses through 32 mg/m2; MTD was not reached. The only clinical toxicity attributed to CNI-1493 was occasional injection-site phlebitis. Grade 1 creatinine increases occurred in 1 of 7 patients at 4 mg/m2, in 1 of 1 patients at 25 mg/m2, and in 3 of 6 patients at 32 mg/m2 CNI-1493 alone. In combination with high-dose IL-2, CNI-1493 at > or = 25 mg/m2 seemed to exacerbate IL-2-induced nephrotoxicity: grade 3 or 4 creatinine increases developed in 3 of 6 patients at 25 or 32 mg/m2, as compared with 1 of 16 patients at doses < or = 16 mg/m2. The MTD for CNI-1493 given with high-dose IL-2 was 16 mg/m2. The dose-limiting toxicity of IL-2 was hypotension in 63% of patients; overall tolerance to IL-2 was not improved by CNI-1493. However, relative to changes seen in a reference group receiving high-dose IL-2 alone, at doses > or = 4 mg/m2 CNI-1493 did show evidence of pharmacological activity as an inhibitor of tumor necrosis factor production.
UI - 21190906
AU - Sabo E; Boltenko A; Sova Y; Stein A; Kleinhaus S; Resnick MB
TI - Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma.
SO - Clin Cancer Res 2001 Mar;7(3):533-7
AD - Department of Pathology, Carmel Medical Center and Technion-Bruce Rappaport Faculty of Medicine, Haifa, Israel.
The objective of this study was to evaluate the utility of measuring microvessel fractal dimension (MFD) as a parameter of architectural microvascular complexity in localized renal cell carcinoma (RCC). Forty-nine patients with low-stage clear cell RCC were assessed in a 9-year follow-up retrospective study. Tumor vessels were visualized with the endothelial marker CD34. Tumor microvessel density (MVD) was measured by computerized morphometry. Fractal analysis of the RCC microvascular network was performed and the MFD was computed in each case. Correlation between tumor vascular parameters, histological grade, extent of tumor necrosis and patient survival were tested by uni- and multivariate analyses. A significant correlation was found between tumor grade and decreased survival (P = 0.04). The extent of macroscopic tumor necrosis also significantly correlated with poor prognosis (P = 0.0001). Survival analysis revealed a significantly higher MVD in patients who survived longer than 5 years as compared with those who died before the end of the 5-year follow-up period (MVD = 10.8 +/- 4.7% versus 6.4 +/- 3.7%; P = 0.03). MVD was also inversely associated with the extent of tumor necrosis (P = 0.03). Microvessel fractal dimension was significantly higher in low- as compared with high-grade tumors (1.55 +/- 0.11 versus 1.45 +/- 0.15; P = 0.03). Survival analysis revealed a significantly higher MFD in those who lived >5 years as compared with those who died earlier (1.56 +/- 0.11 versus 1.46 +/- 0.15; P = 0.02). The MFD was inversely associated with the extent of tumor necrosis (P = 0.01). Multivariate analysis revealed that the MFD was the only significant factor to correlate with tumor necrosis, and that tumor necrosis was the only independent predictor of patient survival. These results indicate that the analysis of MFD as a marker of tumor microvascular complexity may provide important prognostic information as well as novel insight into the biology of tumor angiogenesis.
UI - 21268706
AU - Heinzer H; Huland E; Huland H
TI - Systemic chemotherapy and chemoimmunotherapy for metastatic renal cell cancer.
SO - World J Urol 2001 Apr;19(2):111-9
AD - Department of Urology, University Clinic Eppendorf, Martinistrasse 52, University of Hamberg, 20246 Hamburg, Germany. firstname.lastname@example.org
We review the current literature on systemic therapy for patients with metastatic renal cell carcinoma. Metastatic renal cell carcinoma remains highly resistant to chemotherapy and hormonal agents not justifying its use as a single agent. Interleukin-2 immunotherapy is the most effective treatment for metastatic renal cell carcinoma available today. There is evidence that interleukin-2 improves survival and yields long-lasting remissions in selected patients; the optimal dose and schedule still need to be defined. Response rates in patients treated with subcutaneous interleukin-2 are similar to those achieved with high-dose bolus intravenous applications. Questions remain concerning quality of life and benefit-to-risk ratio with respect to immunotherapy in individual patients. Different routes of administration of interleukin-2 such as local application, promise to improve quality of life and survival times.
UI - 21384893
AU - Phillips JL; Pavlovich CP; Walther M; Ried T; Linehan WM
TI - The genetic basis of renal epithelial tumors: advances in research and its impact on prognosis and therapy.
SO - Curr Opin Urol 2001 Sep;11(5):463-9
AD - Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. email@example.com
The genetics of renal cell carcinoma continues to elucidate the pathways of kidney tumorigenesis. The relationship between the VHL gene and clear cell carcinoma, MET and papillary carcinoma, and the families of genes that they regulate, continues to be unraveled. New hereditary kidney cancer syndromes, like familial oncocytoma and the Birt-Hogg-Dube syndrome, have been identified and the search for the genes that cause them is under way. Researching the genetics of these disorders is essential for an understanding of sporadic kidney cancer genetics. This chapter will review the current knowledge of the hereditary kidney cancer syndromes, the genes that cause them, new advances in genetic research and techniques, and how this information impacts upon diagnostic, prognostic, and therapeutic methods of the future.
UI - 21384898
AU - Childs R; Drachenberg D
TI - Allogeneic stem cell transplantation for renal cell carcinoma.
SO - Curr Opin Urol 2001 Sep;11(5):495-502
AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1501, USA. firstname.lastname@example.org
Although the prognosis for patients with metastatic kidney cancer remains poor, a number of promising immunotherapeutic approaches for the treatment of metastatic disease have been developed over the past decade. The response of some patients to cytokines such as interleukin-2 and interferon-alpha, and more recently, vaccination with dendritic cell/tumor fusions has laid the ground work for ongoing immune-based investigational approaches. Allogeneic stem cell transplantation is a potent form of immunotherapy capable of delivering potentially curative immune-mediated anti-tumor effects against a number of different hematological malignancies. Knowledge of renal cell carcinoma's unusual susceptibility to immune attack has led to the hypothesis that tumor rejection, mediated through immunocompetent donor T-cells, might be generated against this solid tumor following the transplantation of an allogeneic immune system. Although clinical trials are early and ongoing, the recent observation of metastatic disease regression following non-myeloablative stem cell transplantation has identified renal cell carcinoma as being susceptible to a graft-versus-tumor effect. Disease responses following such therapy have ranged from partial to complete and have been observed even in patients who have failed conventional cytokine based strategies. This article reviews the design, methodology and early clinical results of studies investigating the use of allogeneic stem cell transplantation in metastatic renal cell carcinoma.
UI - 21418816
AU - Jiang Y; Xu W; Lu J; He F; Yang X
TI - Invasiveness of hepatocellular carcinoma cell lines: contribution of hepatocyte growth factor, c-met, and transcription factor Ets-1.
SO - Biochem Biophys Res Commun 2001 Sep 7;286(5):1123-30
AD - Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China
To understand the mechanism of invasion and metastasis of hepatocellular carcinoma (HCC), the expression of c-met and Ets-1, and the effect of HGF on these cell's motility and invasion ability were examined in four hepatoma cell lines. The analysis revealed that the overexpression of c-met and Ets-1 is closely connected with the motility and invasion ability of the HCC cell lines. Invasion activity of HepG2 and HLE cells were enhanced by the addition of HGF to medium. HGF regulated c-met transcription in HepG2 and Bel-7402 cells, HGF also induced Ets-1 transcription in Bel-7402 cell. Bel-7402 cells stably transduced with the human Ets-1 gene showed significantly increased invasion potentials compared to parental and mock-transfected cells. The expression level of c-met, MMP1, MMP9, and u-PA in Bel-7402 cells transfected with Ets-1 were markedly increased, and as a consequence of c-met expression increase. Bel-7402 cells transfected with Ets-1 were more responsive to exogenous HGF stimulation in invasiveness and motility ability. In addition, conditioned by antisense Ets-1 oligonucleotide-treat-Bel-7402 cells transfected with Ets-1 gene and HLE hepatoma cells showed markedly reduced invasion activity, and down-regulated the transcription of Ets-1, c-met, u-PA, MMP-1, and MMP-9. These results strongly suggest that Ets-1 has a crucial role in the invasive property in hepatoma cell lines, and there may exist a loop to enhance the invasive ability of hepatoma cell lines. Copyright 2001 Academic Press.
UI - 21443299
AU - Ibrahim EC; Guerra N; Lacombe MJ; Angevin E; Chouaib S; Carosella ED;
TI - Caignard A; Paul P Tumor-specific up-regulation of the nonclassical class I HLA-G antigen expression in renal carcinoma.
SO - Cancer Res 2001 Sep 15;61(18):6838-45
AD - CEA, Service de Recherches en Hemato-Immunologie, DSV/DRM, Hopital Saint-Louis, Centre Hayem, 75010 Paris, France.
HLA-G is a nonclassical class I antigen mainly expressed at the maternofetal interface during pregnancy where it is thought to down-modulate maternal immune response against the semiallogeneic fetus. Recent studies indicate that ectopic up-regulation of HLA-G expression on melanoma cells may also favor their escape from antitumor immune response. HLA-G expression was here investigated on paraffin-embedded tumor and adjacent normal renal tissues of 18 renal cell carcinoma (RCC) patients. We provide evidence that HLA-G antigen is differentially expressed in carcinoma and normal renal cells and that up-regulation of this antigen in the tumor cells is more frequent than alterations of other MHC class I or class II antigens. We also demonstrated that HLA-G cell surface expression and secretion is maintained in a tumor cell line (DM) established from an HLA-G-positive RCC lesion. Furthermore, we show that type I (alpha and beta) and, in particular, type II (gamma) IFN treatment enhances steady-state mRNA levels and cell surface expression of HLA-G in the DM cell line. As several studies suggest that HLA-G displays various functional features that allow down-modulation of immune response in vitro, we propose that selective in vivo expression of HLA-G may participate in the impairment of antitumor immunity in RCC.
UI - 21277276
AU - Pachucki J; Ambroziak M; Tanski Z; Luczak J; Nauman J; Nauman A
TI - Type I 5'-iodothyronine deiodinase activity and mRNA are remarkably reduced in renal clear cell carcinoma.
SO - J Endocrinol Invest 2001 Apr;24(4):253-61
AD - Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Poland. email@example.com
The purpose of this study was to compare thyroid hormone metabolism between non-cancerous tumor-surrounding human kidney tissues and renal clear cell carcinomas (RCCC). The material consisted of samples taken from 10 RCCC patients of both sexes and three grades of differentiation, G1 to G3. We showed that, similar to rat tissue, type I 5' monodeiodinase (5'DI) expression is heterogeneous within the human kidney. We also found a poor correlation between 5'DI activity and mRNA level in non-cancerous tumor-surrounding tissue suggesting significant post-transcriptional regulation of 5'DI expression by an unidentified process in the human kidney. In all RCCC tissues both 5'DI activity and mRNA levels were undetectable. This suggests either loss of human 5'DI gene expression during neoplastic transformation or the origination of RCCC from a tubular cell type that does not express 5'DI.
UI - 21287658
AU - Cicco A; Salomon L; Hoznek A; Saint F; Alame W; Gasman D; Antiphon P;
TI - Chopin DK; Abbou CC Results of retroperitoneal laparoscopic radical nephrectomy.
SO - J Endourol 2001 May;15(4):355-9; discussion 375-6
AD - Service d'Urologie, Hjpital Henri Mondor, Creteil, France.
PURPOSE: To analyze the retroperitoneal approach to laparoscopic radical nephrectomy in terms of feasibility, safety, morbidity, and cancer control. PATIENTS AND METHODS: We reviewed the records of 50 consecutive patients with renal cancer underwent radical nephrectomy via the retroperitoneal laparoscopic approach from 1995 through 1999. RESULTS: The mean operative time was 139 minutes (range 60-330 minutes) with a mean of 149.78-mL operative blood loss (0-1500 mL). The mean renal size was 100 mm (70-150 mm) with a mean tumor size of 38.6 mm (20-90 mm). The postoperative hospital was 6 days (2-13 days). Three open conversions were necessary: one for laparoscopically uncontrolled bleeding and two because obesity interfered with surgery. We noted two major complication and two minor complications. Two disease progression have been noted to date. One patient with a pT3 grade 2 renal-cell carcinoma had a local recurrence with liver metastasis 9 months after the procedure and died 19.7 months after radical nephrectomy. Another patient with a pT3aN+M+ cancer died 23.1 months after the procedure. CONCLUSION: Retroperitoneal laparoscopic nephrectomy for kidney cancer requires further assessment. It seems to have several advantages over open radical nephrectomy and to be effective and safe for small (<50-mm) renal tumors.
UI - 21287660
AU - Kozlowski PM; Winfield HN
TI - Laparoscopic partial nephrectomy and wedge resection for the treatment of renal malignancy.
SO - J Endourol 2001 May;15(4):369-74; discussion 375-6
AD - Department of Urology, Stanford University, California 94305-5118, USA.
The widespread use of abdominal ultrasonography, CT, and MRI has led to an increase in the number of incidentally detected renal masses, some of which are malignant. Numerous studies suggest that partial nephrectomy or wedge resection of these lesions yield cure rates similar to those obtained with radical surgery. Laparoscopic nephron-sparing surgery is one of the more challenging minimally invasive surgical techniques, and its use is largely restricted to specialized medical centers. The techniques and available results are described.
UI - 21287661
AU - Liatsikos EN; Dinlenc CZ; Kapoor R; Smith AD
TI - Transitional-cell carcinoma of the renal pelvis: ureteroscopic and percutaneous approach.
SO - J Endourol 2001 May;15(4):377-83; discussion 397
AD - Department of Urology, Albert Einstein College of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11042, USA.
There are a variety of publications advocating the ureteroscopic or the percutaneous approach for the treatment of transitional cell carcinoma of the renal pelvis. The diagnostic tool of choice for the upper urinary tract and collecting system is the flexible ureteroscope. One of the major concerns about ureteroscopic management of renal disease initially was the lack of flexibility of the instruments and therefore the inability to deal with demanding sites. The advent of new ureteroscopic techniques, as well as the continuous evolution of the technology, have paved the way for safe and effective access to the upper urinary tract. In the hands of an experienced urologist, such procedures can provide reliable treatment options for small upper urinary tract lesions. Coupling minimal morbidity with ever-improving optics and flexibility, the ureteroscope of today leaves no area of the urinary tract unseen. In patients with bulky tumors or in whom easy access and resection is not possible ureteroscopically, the percutaneous approach to the renal pelvis, although more invasive, provides a better working environment. Clearly, the most difficult aspect of ureteroscopic access to the lower pole is not just visibility but the loss of deflection caused by passage of various instruments through the working channel. Direct access via percutaneous approach with a large resectoscope avoids these problems.
UI - 21366208
AU - Saito T; Oda Y; Itakura E; Shiratsuchi H; Kinoshita Y; Oshiro Y; Tamiya
TI - S; Hachitanda Y; Iwamoto Y; Tsuneyoshi M Expression of intercellular adhesion molecules in epithelioid sarcoma and malignant rhabdoid tumor.
SO - Pathol Int 2001 Jul;51(7):532-42
AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
We clinicopathologically evaluated 31 cases of epithelioid sarcoma (ES; 25 'classical' type and six 'proximal variant' type) and six cases of malignant rhabdoid tumor (MRT; three extrarenal and three renal). We also did immunohistochemical studies on 12 classical and three proximal variant cases of ES, and six cases of