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Renal Carcinoma (renal + carcinoma)
Selected AbstractsModulation of p21-activated kinase 1 alters the behavior of renal cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Gerald C. O'Sullivan Abstract The p21-activated kinase 1 (Pak1) is a serine/threonine kinase whose activity is regulated by both Rho GTPases and AGC kinase family members. It plays a role in cytoskeletal remodeling and cell motility as well as cell proliferation, angiogenesis, tumorigenesis and metastasis. An involvement of Pak1 in renal cell carcinoma (RCC), which remains highly refractory to chemotherapy and radiotherapy, remains to be investigated. Pak1 expression, phosphorylation and kinase activity were examined in RCC cell lines and human tissue from normal and renal carcinoma. We report increased Pak1 expression and constitutive activity in the membrane and nucleus but not the cytoplasm of resected human RCC. To study a role for Pak1 in RCC, we developed 786-0 clones that expressed either a kinase-active Pak1L83,L86 2 different Pak1 dominant negative mutants, Pak1R299 and Pak1L83,L86,R299 or Pak1 siRNA. The expression of Pak1L83,L86 increased 786-0 proliferation, motility and anchorage independent growth, while the dominant negative mutants and Pak1 siRNA abrogated these effects. In addition, Pak1L83,L86 conferred resistance to 5-fluorouracil with a 40% ± 10% increase in cell viability. Conversely, Pak1L83,L86,R299, Pak1R299 and Pak1 siRNA conferred sensitivity with a 65.2% ± 5.5%, 69.2% ± 3.3% and 73.0% ± 8.4% loss in viability, respectively. Finally, Pak1 plays a role in renal tumor growth in vivo. Only 33% of mice developed tumors in the Pak1L83,L86,R299 group and no tumors developed from Pak1R299 cell challenge. Together these findings point to Pak1 as an exciting target for therapy of renal cancer, which remains highly refractory to existing treatments. © 2007 Wiley-Liss, Inc. [source] Response of papillary renal cell carcinoma in a solitary kidney to high dose interleukin therapyINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2005ERIC K DINER Abstract ,Kidney cancer affects 36 000 Americans annually and is responsible for nearly 12 000 deaths every year in the US. Treatment with interleukin-2 (IL-2), the only FDA approved therapy for patients with advanced kidney cancer, is associated with a 10% complete response and a 12% partial response. To date, clear cell renal carcinoma has been the only histological type associated with response to IL-2-based therapy. In the current report, we describe a response to IL-2 therapy in a patient with type I papillary renal carcinoma. [source] Spoke-wheel-like enhancement as an important imaging finding of chromophobe cell renal carcinoma: A retrospective analysis on computed tomography and magnetic resonance imaging studiesINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2004TSUNENORI KONDO Abstract Aim:, Little information has been reported with regard to the radiological features of chromophobe cell renal carcinomas (CCRC). The aim of the present study was to identify imaging characteristics which lead to the histological diagnosis of CCRC. Methods:, The imaging findings of computed tomography (CT) and magnetic resonance imaging (MRI) were retrospectively analyzed in 11 patients with CCRC operated on at Tokyo Women's Medical University, Tokyo, Japan. Results:, None of the factors studied were significant in distinguishing the two variants, typical and eosinophilic variants. Enhanced CT scans showed a spoke-wheel-like enhancement with a central scar in 3 patients (27%). The radiological patterns were classified into two groups. Seven patients (64%) showed pattern 1 in which: (i) a hypodense to isodense enhancement compared to the renal medulla in the corticomedullary phase during dynamic CT; (ii) an isodense mass compared to the renal medulla in unenhanced CT scan; and (iii) a lobulated appearance were typically observed. Four patients (36%) showed pattern 2 that seemed to be similar to the features of clear cell carcinoma, having an alveolar structure including a hyperdense enhancement in the corticomedullary phase and an inhomogeneous appearance. A spoke-wheel-like enhancement was observed only in patients with pattern 1, and was more clearly demonstrated in larger tumors. Conclusions:, The CT and MRI findings in CCRC patients were not uniform, but it was noted that a spoke-wheel-like enhancement with a central stellate scar, which might have been mistaken for oncocytoma, was one of important findings of CCRC. Tumors demonstrating a spoke-wheel-like enhancement with a central scar should be carefully managed, because they could be malignant. [source] Sporadic neoplasms of farmed chinook salmon, Oncorhynchus tshawytscha (Walbaum), from New ZealandJOURNAL OF FISH DISEASES, Issue 7 2003J S Lumsden Abstract Eight separate neoplasms with five distinct morphologies are described in the present report. The spontaneous neoplasms were identified in farmed chinook salmon, Oncorhynchus tshawytscha (Walbaum), during processing. The masses were examined histologically and were classified as teratoma, rhabdosarcoma, biliary and renal cystadenomas, renal carcinoma and three leiomyomas. This represents one neoplasm detected for every 125 000 fish processed during the sampling period. [source] Molecular tumor markers for asbestos-related mesothelioma: Serum diagnostic markersPATHOLOGY INTERNATIONAL, Issue 11 2006Masahiro Maeda Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30,40 years, and the prognosis is dismal. In addition to immunohistochemical markers, recently, serum markers for the diagnosis of mesothelioma have been reported as candidates. In contrast, the expression in renal carcinoma (ERC) gene has been discovered in the Eker rat model (Tsc2 gene mutant), which is a homolog of the human mesothelin/megakaryocyte potentiating factor gene, and a novel ELISA system (N-ERC/mesothelin) has been developed. It has also been found that N-ERC/mesothelin is very stable and plentiful in the blood. In the present paper the potential utility of molecular diagnostic markers is reviewed, including ELISA systems for asbestos-related mesothelioma. [source] Metastasis of renal cell carcinoma to central nervous system hemangioblastoma in two patients with von Hippel,Lindau diseasePATHOLOGY INTERNATIONAL, Issue 12 2001Shuji Hamazaki Here we report tumor-to-tumor metastases identified in two patients with von Hippel,Lindau (VHL) disease. The first patient had bilateral renal carcinomas and multiple cerebellar hemangioblastomas, and the second patient had a renal carcinoma and multiple hemangioblastomas in the retina, cerebellum and spinal cord. A cerebellar lesion from the first patient and a spinal lesion from the second patient contained two distinct components. The inner part of these tumors consisted of a nested mass of polygonal clear cells that expressed cytokeratin and epithelial membrane antigen, while the outer part of the tumors showed proliferation of capillaries and intervening foamy stromal cells that were negative for cytokeratin and epithelial membrane antigen. The tumors were thus considered to be hemangioblastomas complicated by metastatic lesions of renal cell carcinoma of clear cell type. These cases indicate that tumor-to-tumor metastasis should be considered when hemangioblastoma contains a clear cell carcinoma component in the setting of VHL disease, and that immunohistochemical staining for cytokeratin and epithelial membrane antigen is useful for the diagnosis. [source] Matrix vapor deposition/recrystallization and dedicated spray preparation for high-resolution scanning microprobe matrix-assisted laser desorption/ionization imaging mass spectrometry (SMALDI-MS) of tissue and single cellsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 3 2010Werner Bouschen Matrix preparation techniques such as air spraying or vapor deposition were investigated with respect to lateral migration, integration of analyte into matrix crystals and achievable lateral resolution for the purpose of high-resolution biological imaging. The accessible mass range was found to be beyond 5000 u with sufficient analytical sensitivity. Gas-assisted spraying methods (using oxygen-free gases) provide a good compromise between crystal integration of analyte and analyte migration within the sample. Controlling preparational parameters with this method, however, is difficult. Separation of the preparation procedure into two steps, instead, leads to an improved control of migration and incorporation. The first step is a dry vapor deposition of matrix onto the investigated sample. In a second step, incorporation of analyte into the matrix crystal is enhanced by a controlled recrystallization of matrix in a saturated water atmosphere. With this latter method an effective analytical resolution of 2,µm in the x and y direction was achieved for scanning microprobe matrix-assisted laser desorption/ionization imaging mass spectrometry (SMALDI-MS). Cultured A-498 cells of human renal carcinoma were successfully investigated by high-resolution MALDI imaging using the new preparation techniques. Copyright © 2010 John Wiley & Sons, Ltd. [source] Oxidative/nitrosative stress and peroxiredoxin 2 are associated with grade and prognosis of human renal carcinoma,APMIS, Issue 5 2006Y. SOINI Peroxiredoxins (Prxs) 1,6 were assessed in 138 renal cell carcinomas (RCC) using immunohistochemistry and selected samples by Western blotting analysis. Oxidative/nitrosative damage was evaluated using nitrotyrosine immunoreactivity. The expressions of Prxs were correlated with tumor grade and survival and nitrotyrosine reactivity. Non-malignant kidney tubular cells showed positivity with variable intensity for all six Prxs. In RCCs, most cases were positive for Prxs 1 and 2, while only 15,20% of tumors showed expression for Prxs 3 and 4. Prx 2 was associated with tumors of a lower grade (p=0.009) and with a lower frequency of distant metastases (p=0.046). Patients with tumors expressing Prx2 had better prognosis (p=0.027). Instead, nitrotyrosine was significantly associated with high grade tumors (p=0.001). Compared with the non-malignant kidney tubular cells, low Prx expression in the tumor cells can make them more susceptible to oxidative damage. Prx 2 was more abundantly expressed in low grade tumors, suggesting that this protein could play a role in preventing the development of oxidative damage, which in turn can lead to the activation of pathways leading to aggressive tumors. [source] Nephron-sparing surgery: a call for greater application of established techniquesBJU INTERNATIONAL, Issue 10 2008James G. Young OBJECTIVES To examine the results of open partial nephrectomy (OPN) over a 15-year period in a large UK teaching hospital and to compare results with other series including minimally invasive techniques, as nephron-sparing techniques are still under-utilized in the surgical treatment of renal carcinoma. A standardized technique is described that we think minimizes the risk of postoperative urinoma. PATIENTS AND METHODS We retrospectively reviewed a series of 141 patients who underwent OPN performed over a 15-year period in one centre by the senior author (D.M.A.W.). A notable feature of this series compared with others is the high proportion of patients undergoing other major synchronous surgery. RESULTS In all, 141 patients underwent 147 OPNs, with six undergoing bilateral procedures, of which 82 were for imperative indications (single kidney, bilateral synchronous tumours, or pre-existing renal impairment). There were three perioperative deaths, two in patients undergoing other synchronous major surgery. In all, 38 patients had postoperative complications: 28 patients required blood transfusion (four required intervention for their bleeding), five required acute dialysis and three late dialysis. There was a 90% cancer-specific survival rate at a median follow-up of 2 years. CONCLUSIONS This series confirms the trend towards improved outcomes and decreased complications in OPN at a time when its place is challenged by minimally invasive techniques. [source] An epidemiological study of renal pathology in tuberous sclerosis complexBJU INTERNATIONAL, Issue 6 2004Finbar J. O'Callaghan OBJECTIVES To report the frequency of renal symptoms and complications of patients with tuberous sclerosis complex (TSC), to describe the ultrasonographic appearance of the kidneys in a population-based sample, and to investigate the relationship between a history of renal haemorrhage and renal lesions identified by ultrasonography. PATIENTS AND METHODS As part of an epidemiological study, 179 patients with TSC were identified as living in the Wessex Region in the South of England. Patients were interviewed and examined in their homes, to elicit the presence of renal symptoms or a history of renal complications. Renal ultrasonography was used in consenting patients in their homes. RESULTS There was a history of renal complications in 16 (9%) patients; 149 consented to interview and examination, and 19 gave a history of renal symptoms in the previous year; 124 had renal ultrasonography; 86 (69%) had renal angiomyolipomas and 37 (30%) had renal cysts. Large lesions (>3 cm in diameter) were strongly associated with a history of symptomatic bleeding, although significant haemorrhage occurred in a 6-year-old child with small angiomyolipomas. CONCLUSIONS The formation of angiomyolipoma in TSC is common. Polycystic kidney disease, renal carcinoma and renal failure, although rare, occur in TSC. Most patients with angiomyolipomas have neither complications nor symptoms. There was no appreciable difference between the sexes in the risk of developing these lesions. Although less commonly seen in the very young, there is no identifiable relationship after adolescence between age and the risk of having a renal angiomyolipoma. Bleeding tends to occur from large lesions (>3 cm) but most such patients have remained asymptomatic to date. [source] Chromophobe renal cell carcinomaCANCER, Issue 7 2004Analysis of 61 cases Abstract BACKGROUND Chromophobe renal cell carcinoma (CRCC) is often associated with a favorable prognosis. However, to the authors' knowledge, only few clinical data are available regarding this variant of tumor. In the current study, the authors report their experience with CRCC over the last 14 years. METHODS Since 1989, 61 patients have been treated at the study institution for CRCC. Tumor characteristics and patient outcome were analyzed retrospectively. Data were obtained from the patients' medical records. RESULTS The mean age of the patients was 58 years. Of the 61 tumors, 68.8% were discovered incidentally. The mean tumor size was 6.9 cm. Fifty-seven patients (93.4%) were treated with radical nephrectomy and 4 patients (6.6%) underwent partial nephrectomy. According to the 1997 TNM classification, the pathologic tumor stage was T1 in 65.6% of cases, T2 in 31.1% of cases, and T3a in 3.3% of cases. All tumors were staged as N0M0. Nuclear grade was low (1 or 2) in 88.5% of cases. In no case of CRCC was a sarcomatoid component observed. At a mean follow-up of 49.5 months (range, 5,135 months), no patient had experienced tumor recurrence or disease progression, and none had died of renal carcinoma. CONCLUSIONS In the authors' experience, CRCC carries an excellent prognosis, possibly due to the high rate of low-stage and low-grade tumors. Cancer 2004;100:1406,10. © 2004 American Cancer Society. [source] Phase I trial of weekly docetaxel and gemcitabine in patients with refractory malignanciesCANCER, Issue 1 2003M.Sc., Tarek Mekhail M.D. Abstract BACKGROUND A Phase I study using weekly docetaxel and gemcitabine was conducted to investigate toxicity; to determine the maximum tolerated dose (MTD) of each agent; and, in a preliminary fashion, to determine the antitumor activity of the combination. METHODS Docetaxel and gemcitabine were administered intravenously on Days 1, 8, and 15 every 28 days. The dose levels of docetaxel and gemcitabine were as follows: Level I, docetaxel 20 mg/m2and gemcitabine 400 mg/m2; Level II, docetaxel 30 mg/m2and gemcitabine 400 mg/m2; Level III, docetaxel 30 mg/m2and gemcitabine 600 mg/m2; Level IV, docetaxel 36 mg/m2and gemcitabine 600 mg/m2; and Level V, docetaxel 36 mg/m2and gemcitabine 800 mg/m2. RESULTS Thirty-three eligible patients were entered. The diagnoses were as follows: Eleven patients had nonsmall cell lung carcinoma, 3 patients had carcinoma of the bladder, 3 patients had renal carcinoma, 2 patients had adrenal carcinoma, 5 patients had unknown primary tumors, and 9 patients had miscellaneous malignancies. Fifty-nine percent of patients had received prior chemotherapy. The median age was 62 years (range, 27,77 years), and the median Eastern Cooperative Oncology Group performance status was 1 (range, 0,1). Five patients were treated at Dose Levels I and II, 6 patients were treated at Dose Levels III and V, and 11 patients were treated at Dose Level IV. Grade 3,4 toxicities during Cycle I included neutropenia, thrombocytopenia, mucositis, and diarrhea. Dose-limiting toxicity, consisting of neutropenia and thrombocytopenia, occurred in three of six patients at Dose Level V. The combination of docetaxel 36 mg/m2 and gemcitabine 600 mg/m2 (Dose Level IV) was determined as the MTD and was the recommended Phase II dose. Two patients had a partial response: one patient with bladder carcinoma (Dose Level II) and one patient with nonsmall cell lung carcinoma (Dose Level III). CONCLUSIONS Overall, weekly docetaxel and gemcitabine were well tolerated. Further studies using this combination are planned, including a Phase II trial in patients with advanced nonsmall cell lung carcinoma. Cancer 2003;97:170,8. © 2003 American Cancer Society. DOI 10.1002/cncr.10991 [source] Renal carcinogenesis: Genotype, phenotype and dramatypeCANCER SCIENCE, Issue 2 2003Okio Hino Cancer is a heritable disorder of somatic cells. Environment and heredity are both important in the carcinogenic process. The Eker rat model of hereditary renal carcinoma (RC) is an example of a Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal. Forty years after the discovery of the Eker rat in Oslo, we and Knudson's group independently identified a germline retrotransposon insertion in the rat homologue of the human tuberous sclerosis (TSC2) gene. To our knowledge, this was the first isolation of a Mendelian dominantly predisposing cancer gene in a naturally occurring animal model. Recently, we discovered a new hereditary renal carcinoma in the rat. This rat was named the "Ninon''rat and its predisposing (Nihon) gene could be a novel renal tumor suppressor gene. This article will review the utility of these unique models for the study of problems in carcinogenesis; e.g., species-specific differences in tumorigenesis, cell stage and tissue/cell-type specific tumorigene-sis, multistep carcinogenesis, modifier gene(s) in renal carcinogenesis, cancer prevention and the development of therapeutic treatments which can be translated to human patients, as well as how environmental factors interact with cancer susceptibility gene(s). (Cancer Sci 2003; 94: 142,147) [source] A Novel Gene "Niban" Upregulated in Renal Carcinogenesis: Cloning by the cDNA-amplified Fragment Length Polymorphism ApproachCANCER SCIENCE, Issue 9 2000Shuichi Majima A modified AFLP (amplified fragment length polymorphism) method was employed to isolate genes differentially expressed in renal carcinogenesis of Tsc2 gene mutant (Eker) rats. One gene, selected for further investigation, was named "Niban" ("second" in Japanese), because it is the second new gene to be found after Erc (expressed in renal carcinoma) in our laboratory. Importantly, "Niban" is well expressed even in small primary rat Eker renal tumors, more than in progressed cell lines, and is also expressed in human renal carcinoma cells, but not in normal human or rat kidneys. Chromosome assignment was to RNO 13 in the rat, and HSA 1. This "Niban" gene is a candidate as a marker for renal tumor, especially early-stage renal carcinogenesis. [source] Variable phenotypic expression of homozygous familial hypobetalipoproteinaemia due to novel APOB gene mutationsCLINICAL GENETICS, Issue 3 2008E Di Leo Homozygous familial hypobetalipoproteinaemia (Ho-FHBL) is a rare co-dominant disorder characterized by extremely low levels of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB). Most patients with Ho-FHBL have mutations in APOB gene resulting in truncated apoBs. Some patients are asymptomatic, while others have fatty liver, intestinal fat malabsorption and neurological dysfunctions. We investigated three adult subjects with severe hypobetalipoproteinaemia and a family history of FHBL. Proband FHBL-47 had liver cirrhosis with hepatocarcinoma and a renal carcinoma but no clinical manifestations related to FHBL. He was a compound heterozygote for a 7-bp deletion in exon 21 and a base insertion in exon 26 resulting in truncated apoBs (apoB-22.46/apoB-66.51). Proband FHBL-53, with severe hepatic steatosis and fibrosis, had a nonsense mutation in exon 19 resulting in a truncated apoB (apoB-20.61) and a rare nucleotide substitution in intron 14 (c.2068-4T>A). The latter was also present in her daughter, found to have low plasma LDL-C and apoB. Proband FHBL-82 had chronic diarrhoea and steatorrhoea. She was found to be homozygous for a nonsense mutation in exon 24 resulting in a truncated apoB (apoB-26.65). In adult subjects, the presence of chronic liver disease and chronic diarrhoea, when associated with severe hypobetalipoproteinaemia, may lead to the diagnosis of Ho-FHBL. [source] Accidental transplantation of a kidney with a cystic renal cell carcinoma following living donation: management and 1 yr follow-upCLINICAL TRANSPLANTATION, Issue 2 2006Michael Neipp Abstract: Transmission of cancer is a fatal risk in organ transplantation. We present a case of incidental renal carcinoma in a kidney obtained from a living donor. A 56-yr-old father was evaluated for donation for his 28-yr-old daughter. An MRT scan revealed two cysts in the right kidney. Right-sided donor nephrectomy and subsequent transplantation was performed. The wall of the prominent cyst was partially excised prior to transplantation. Histology revealed a high-grade renal clear cell carcinoma 10 d after transplantation. Following careful evaluation the recipient underwent partial nephrectomy. Immunosuppression was switched to rapamune. The graft function remained stable. Donor and recipient are without evidence of tumor recurrence 1 yr after transplantation. Our policy to obtain the kidney presenting anatomical variations proved to be beneficial for the donor. In case of transmission of cancer partial resection preserving graft function might be justified. [source] Malignant pheochromocytoma with progressive paraparesis in von Hippel,Lindau diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2000R. Mössner Pheochromocytomas are a feature of the von Hippel,Lindau disease spectrum, a multisystem disorder of autosomal dominant inheritance. Pheochromocytomas are, however, observed during life with a lower frequency than other features of this disease, such as retinal angiomas, haemangioblastomas of the CNS, and renal carcinomas. We present the highly unusual case of a patient who required an emergency operation for an intradural extramedullary thoracic tumour which was clinically suggestive initially of neurinoma. We present evidence from NMR, histological and isotope scan investigations of this being a pheochromocytoma metastasis and of an additional right-sided paraganglioma at the same height. A detailed history revealed that this patient had suffered from four other pheochromocytomas and two other paragangliomas, in addition to retinal angiomatosis of von Hippel,Lindau disease. This case is extraordinary due to (i) the unusual site of the metastasis, (ii) the neurological requirement for an emergency operation of pheochromocytoma, (iii) metastasis of pheochromocytoma in von Hippel,Lindau disease (only eight previous cases), and (iv) the number of recurrent pheochromocytomas. It clearly demonstrates the necessity for frequent and life-long follow-up in von Hippel,Lindau disease. [source] Spoke-wheel-like enhancement as an important imaging finding of chromophobe cell renal carcinoma: A retrospective analysis on computed tomography and magnetic resonance imaging studiesINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2004TSUNENORI KONDO Abstract Aim:, Little information has been reported with regard to the radiological features of chromophobe cell renal carcinomas (CCRC). The aim of the present study was to identify imaging characteristics which lead to the histological diagnosis of CCRC. Methods:, The imaging findings of computed tomography (CT) and magnetic resonance imaging (MRI) were retrospectively analyzed in 11 patients with CCRC operated on at Tokyo Women's Medical University, Tokyo, Japan. Results:, None of the factors studied were significant in distinguishing the two variants, typical and eosinophilic variants. Enhanced CT scans showed a spoke-wheel-like enhancement with a central scar in 3 patients (27%). The radiological patterns were classified into two groups. Seven patients (64%) showed pattern 1 in which: (i) a hypodense to isodense enhancement compared to the renal medulla in the corticomedullary phase during dynamic CT; (ii) an isodense mass compared to the renal medulla in unenhanced CT scan; and (iii) a lobulated appearance were typically observed. Four patients (36%) showed pattern 2 that seemed to be similar to the features of clear cell carcinoma, having an alveolar structure including a hyperdense enhancement in the corticomedullary phase and an inhomogeneous appearance. A spoke-wheel-like enhancement was observed only in patients with pattern 1, and was more clearly demonstrated in larger tumors. Conclusions:, The CT and MRI findings in CCRC patients were not uniform, but it was noted that a spoke-wheel-like enhancement with a central stellate scar, which might have been mistaken for oncocytoma, was one of important findings of CCRC. Tumors demonstrating a spoke-wheel-like enhancement with a central scar should be carefully managed, because they could be malignant. [source] Deep Hypothermia and Circulatory Arrest in the Surgical Management of Renal Tumors with Cavoatrial ExtensionJOURNAL OF CARDIAC SURGERY, Issue 6 2009Panagiotis Dedeilias M.D. Their intraluminar extension to the cardiac cavities occurs with a tumor-thrombus formation at a percentage of 1%. The aim of this study is to present the principles of "radical" management that should be targeted to excision of the kidney together with the cavoatrial tumor-thrombus. Material: From 2003 through 2008, we treated six patients with renal-cell carcinoma involving the IVC and/or the right cardiac chambers. The main symptoms leading to the diagnosis were hematuria, dyspnea, or lower limb edema. The extension of the tumor was type IV in three cases, type III in two, and type II in one case. Method: Extracorporeal circulation combined with a short period of hypothermic circulatory arrest was the method used. Radical nephrectomy combined with cavotomy and atriotomy was performed to an "en-block" extirpation of the tumor-thrombus and allowed oncologic surgical clearance of the disease. Results: There was no operative death. The mean postoperative course duration was 11 days, apart from one obese patient who presented postoperative pancreatitis and died on the 44th postoperative day due to respiratory failure. During the cumulative postoperative follow-up of 171 months the patients remain free of recurrence. Conclusions: The use of extracorporeal circulation and deep hypothermic circulatory arrest provides a good method for radical excision of renal carcinomas involving the IVC with satisfactory morbidity and long-term survival results. Cooperation of urologists and cardiac surgeons is necessary for this type of operation. [source] Metastasis of renal cell carcinoma to central nervous system hemangioblastoma in two patients with von Hippel,Lindau diseasePATHOLOGY INTERNATIONAL, Issue 12 2001Shuji Hamazaki Here we report tumor-to-tumor metastases identified in two patients with von Hippel,Lindau (VHL) disease. The first patient had bilateral renal carcinomas and multiple cerebellar hemangioblastomas, and the second patient had a renal carcinoma and multiple hemangioblastomas in the retina, cerebellum and spinal cord. A cerebellar lesion from the first patient and a spinal lesion from the second patient contained two distinct components. The inner part of these tumors consisted of a nested mass of polygonal clear cells that expressed cytokeratin and epithelial membrane antigen, while the outer part of the tumors showed proliferation of capillaries and intervening foamy stromal cells that were negative for cytokeratin and epithelial membrane antigen. The tumors were thus considered to be hemangioblastomas complicated by metastatic lesions of renal cell carcinoma of clear cell type. These cases indicate that tumor-to-tumor metastasis should be considered when hemangioblastoma contains a clear cell carcinoma component in the setting of VHL disease, and that immunohistochemical staining for cytokeratin and epithelial membrane antigen is useful for the diagnosis. [source] Reduced Activity of CD13/Aminopeptidase N (APN) in Aggressive Meningiomas Is Associated with Increased Levels of SPARCBRAIN PATHOLOGY, Issue 1 2010Christian Mawrin Abstract Meningiomas are the second most common brain tumors in adults, and meningiomas exhibit a tendency to invade adjacent structures. Compared with high-grade gliomas, little is known about the molecular changes that potentially underlie the invasive behavior of meningiomas. In this study, we examined the expression and function of the membrane alanyl-aminopeptidase [mAAP, aminopeptidase N (APN), CD13, EC3.4.11.2] zinc-dependent ectopeptidase in meningiomas and meningioma cell lines, based on its prior association with tumor invasion in colorectal and renal carcinomas. We found a significant reduction of APNmRNA and protein expression, as well as enzymatic activity, in high-grade meningiomas. While meningioma tumor cell proliferation was not affected by either pharmacologic APN inhibition or siRNA-mediated APN silencing, APN pharmacologic and siRNA knockdown significantly reduced meningioma cell invasion in vitro. Next, we employed pathway-specific cDNA microarray analyses to identify extracellular matrix and adhesion molecules regulated by APN, and found that APN-siRNA knockdown substantially increased the expression of secreted protein, acidic and rich in cysteine (SPARC)/osteonectin. Finally, we demonstrated that SPARC, which has been previously associated with meningioma invasiveness, was increased in aggressive meningiomas. Collectively, these results suggest that APN expression and enzymatic function is reduced in aggressive meningiomas, and that alterations in the balance between APN and SPARC might favor meningioma invasion. [source] Inhibitory effect of c-Met mutants on the formation of branching tubules by a porcine aortic endothelial cell lineCANCER SCIENCE, Issue 12 2006Marino Maemura The association of hepatocyte growth factor (HGF) with its high-affinity receptor (c-Met) has been shown to induce mitogenesis, motogenesis and morphogenesis in a variety of cell types. Various point mutations in c-Met have been identified in hereditary and sporadic papillary renal carcinomas as well as in other carcinomas. In the present study, we examined the effects of c-Met point mutations on the morphology of a porcine aortic endothelial (PAE) cell line. When cultured in three-dimensional collagen gel, PAE cells formed branching tubule structures, and HGF treatment caused breakdown of the structures and induced a scattered morphology. The exogenous expression of c-Met point mutants inhibited the formation of tubules. HGF treatment induced the formation of tubules by PAE cells expressing some c-Met mutants, but it induced the scattering of PAE cells expressing other c-Met mutants. The presence of a low concentration of a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor cancelled the inhibitory effect of the c-Met point mutations on the formation of tubules. These results suggest that c-Met point mutations affect the extracellular signal-regulated kinase (ERK) signaling required for the formation of tubules by PAE cells, and HGF binding changes the conformation of c-Met mutants, leading to the different signals required for formation of tubules and cell scattering. 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