Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development

DEFF Research Database (Denmark)

Robdrup Tinning, Anne; Jensen, Boye L; Johnsen, Iben

2016-01-01

Postnatal inhibition or deletion of angiotensin II (ANG II) AT1 receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary....... In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg·kg(-1)·day(-1)) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria...... for the development of the renal medullary microcirculation. Endothelial cell-specific immunolabeling of kidney sections from rats showed immature vascular bundles at postnatal day (P) 10 with subsequent expansion of bundles until P21. Medullary VEGF protein abundance coincided with vasa recta bundle formation...

Renal medullary AA amyloidosis, hepatocyte dissociation and multinucleated hepatocytes in a 14-year-old free-ranging lioness (Panthera leo

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J.H. Williams

2005-06-01

Full Text Available A 14-year-old lioness, originating from Etosha in Namibia, and a member of a pride in Pilanesberg National Park since translocation in 1994, was euthanased due to fight-related vertebral fracture and spinal injury, incurred approximately 6-8 weeks previously. Blood specimens collected at the time of death showed mild anaemia and a leukogram reflecting stress and chronic infection. Necropsy conducted within 2 hours of death was on a dehydrated, emaciated animal with hindquarter wasting and chronic traumatic friction injuries from dragging her hindlegs. There was cellulitis in the region of bite-wounds adjacent to the thoraco-lumbar vertebral fracture, at which site there was spinal cord compression, and there was marked intestinal helminthiasis. The outer renal medullae appeared pale and waxy and the liver was macroscopically unremarkable. Histopathology and electron microscopy of the kidneys revealed multifocal to coalescing deposits of proximal medullary interstitial amyloid, which fluoresced strongly with thioflavine T, and was sensitive to potassium permanganate treatment prior to Congo Red staining, thus indicating inflammatory (AA origin. There was diffuse hepatocyte dissociation, as well as numerous binucleated and scattered multinucleated (up to 8 nuclei/cell hepatocytes, with swollen hepatocyte mitochondria, in liver examined light microscopically. Ultrastructurally, the mono-, bi- and multinucleated hepatocytes contained multifocal irregular membrane-bound accumulations of finely-granular, amorphous material both intra-cytoplasmically and intra-nuclearly, as well as evidence of irreversible mitochondrial injury. The incidence and relevance in cats and other species of amyloidosis, particularly with renal medullary distribution, as well as of hepatocyte dissociation and multinucleation, as reported in selected literature, is briefly overviewed and their occurrence in this lioness is discussed.

MR imaging of medullary streaks in osteosclerosis: a case report

International Nuclear Information System (INIS)

Lee, Hak Soo; Joo, Kyung Bin; Park, Tae Soo; Song, Ho Taek; Kim, Yong Soo; Park, Dong Woo; Park, Choong Ki

2000-01-01

We present a case of medullary sclerosis of the appendicular skeleton in a patient with chronic renal insufficiency for whom MR imaging findings were characteristic. T1- and T2-weighted MR images showed multiple vertical lines (medullary streaks) of low signal intensity in the metaphyses and diaphyses of the distal femur and proximal tibia

Proximal Tubular Injury in Medullary Rays Is an Early Sign of Acute Tacrolimus Nephrotoxicity

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Diane Cosner

2015-01-01

Full Text Available Tacrolimus (FK506 is one of the principal immunosuppressive agents used after solid organ transplantations to prevent allograft rejection. Chronic renal injury induced by tacrolimus is characterized by linear fibrosis in the medullary rays; however, the early morphologic findings of acute tacrolimus nephrotoxicity are not well characterized. Kidney injury molecule-1 (KIM-1 is a specific injury biomarker that has been proven to be useful in the diagnosis of mild to severe acute tubular injury on renal biopsies. This study was motivated by a patient with acute kidney injury associated with elevated serum tacrolimus levels in whom KIM-1 staining was present only in proximal tubules located in the medullary rays in the setting of otherwise normal light, immunofluorescent, and electron microscopy. We subsequently evaluated KIM-1 expression in 45 protocol and 39 indicated renal transplant biopsies to determine whether higher serum levels of tacrolimus were associated with acute segment specific injury to the proximal tubule, as reflected by KIM-1 staining in the proximal tubules of the cortical medullary rays. The data suggest that tacrolimus toxicity preferentially affects proximal tubules in medullary rays and that this targeted injury is a precursor lesion for the linear fibrosis seen in chronic tacrolimus toxicity.

Renal papillary necrosis

Science.gov (United States)

... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

Individual renal function study using dynamic computed tomography

International Nuclear Information System (INIS)

Fukuda, Yutaka; Kiya, Keiichi; Suzuki, Yoshiharu

1990-01-01

Dynamic CT scans of individual kindneys were obtained after an intravenous bolus injection of contrast agent. Time-density curves measured from the renal cortex, medulla and pelvis revealed the changes in density produced by the contrast agent reflecting the differential phase of renal function. Renal cortical density increased rapidly after bolus administration and then renal medullary and pelvic density increased continuously. In analyzing time-density curve, the cortico-medullary junction time, which is the time when the cortical and medullary curves cross was 57±8 seconds in patients with normal renal function. The cortico-medullary junction time was delayed in patient with decreased glomerular filtration rate. The cortico-pelvic junction time, which is the time when the cortical and pelvic curves cross was 104±33 seconds in patients with normal renal function. The cortico-pelvic junction time was delayed in patients with declined urinary concentrating capacity. In patients with unilateral renal agenesis and patients who were treated surgically by ureteral sprits, the relationship between individual renal functions and these junction times was examined. As a result of study there were inversely significant correlations between C-M junction time and unilateral GFR and between C-P junction time and urinary concentrating capacity. These studies indicate that dynamic CT scanning is an effective way that individual renal function can be monitored and evaluated. (author)

Nitric oxide, prostaglandins and angiotensin II in the regulation of renal medullary blood flow during volume expansion.

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Moreno, Carol; Llinás, María T; Rodriguez, Francisca; Moreno, Juan M; Salazar, F Javier

2016-03-01

Regulation of medullary blood flow (MBF) is essential in maintaining renal function and blood pressure. However, it is unknown whether outer MBF (OMBF) and papillary blood flow (PBF) are regulated independently when extracellular volume (ECV) is enhanced. The aim of this study was to determine whether OMBF and PBF are differently regulated and whether there is an interaction between nitric oxide (NO), prostaglandins (PGs) and angiotensin II (Ang II) in regulating OMBF and PBF when ECV is enhanced. To achieve these goals, OMBF and PBF were measured by laser-Doppler in volume-expanded rats treated with a cyclooxygenase inhibitor (meclofenamate, 3 mg/kg) and/or a NO synthesis inhibitor (L-nitro-arginine methyl ester (L-NAME), 3 μg/kg/min) and/or Ang II (10 ng/kg/min). OMBF was unchanged by NO or PGs synthesis inhibition but decreased by 36 % (P blood flows to the outer medulla and renal papilla are differently regulated and showing that there is a complex interaction between NO, PGs and Ang II in regulating OMBF and PBF when ECV is enhanced.

Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats.

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Schulman, Ivonne Hernandez; Zhou, Ming-Sheng; Treuer, Adriana V; Chadipiralla, Kiranmai; Hare, Joshua M; Raij, Leopoldo

2010-01-01

The susceptibility to fibrosis and progression of renal disease is mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized that activation of the intrarenal RAS predisposes to renal fibrosis in aging. Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2 (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle-aged), and 24-month-old (old) male Sprague-Dawley rats. Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT(1)R /AT(2)R ratios were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH oxidase activity was increased (2-fold), whereas antioxidant capacity and expression of the mitochondrial enzyme manganese superoxide dismutase (cortical -40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were decreased in old rats. Age-related intrarenal activation of the RAS preceded the development of severe renal fibrosis, suggesting that it contributes to the increased susceptibility to renal injury observed in the elderly. Copyright © 2010 S. Karger AG, Basel.

The normal and pathologic renal medulla: a comprehensive overview.

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López, José I; Larrinaga, Gorka; Kuroda, Naoto; Angulo, Javier C

2015-04-01

The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an extensive review of the literature on the renal medulla, in both normal and pathologic conditions. We set out in detail the points of key interest to pathologists: normal and pathological development, physiology, microscopic anatomy, histology and immunohistochemistry; and the specific and most common other types of disease associated with this part of the kidney: developmental abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive polycystic kidney diseases, medullary cystic kidney disease), inflammatory conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors, chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma, other carcinomas, renal medullary fibroma and metastatic tumors). This condensed overview of the origin, function and pathology of the renal medulla, both in terms of development, inflammation and neoplastic processes, should help focus the interest of clinical pathologists on this widely overlooked part of the kidney. Copyright © 2014 Elsevier GmbH. All rights reserved.

The renin-angiotensin system; development and differentiation of the renal medulla

DEFF Research Database (Denmark)

Madsen, Kirsten; Robdrup Tinning, Anne; Marcussen, Niels

2013-01-01

on mechanisms of postnatal development the renal medulla and putting medullary developmental lesions into perspective with regard to the programming effect. Moreover, the renin-angiotensin system is critically involved in mammalian kidney development and signaling disorders give rise to developmental renal...... disturbances reaching into adulthood. A review of current knowledge of the role of the renin-angiotensin system for renal medullary development will be given. Acta Physiologica © 2013 Scandinavian Physiological Society....... lesions that has been associated with hypertension later in life. A consistent finding in both experimental animal models and in human case reports is atrophy of the renal medulla with developmental lesions to both medullary nephron segments and vascular development with concomitant functional...

MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

Science.gov (United States)

Wentland, Andrew L; Artz, Nathan S; Fain, Sean B; Grist, Thomas M; Djamali, Arjang; Sadowski, Elizabeth A

2012-01-01

Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all three parameters of kidney function in a single MRI examination and to evaluate the relationships between these functional parameters is potentially useful for evaluating the state of the human kidneys in situ in future studies.

Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

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Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

1990-09-01

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

Sorting the Alphabet Soup of Renal Pathology: A Review.

Science.gov (United States)

Curran-Melendez, Sheilah M; Hartman, Matthew S; Heller, Matthew T; Okechukwu, Nancy

2016-01-28

Diseases of the kidney often have their names shortened, creating an arcane set of acronyms which can be confusing to both radiologists and clinicians. This review of renal pathology aims to explain some of the most commonly used acronyms within the field. For each entity, a summary of the clinical features, pathophysiology, and radiological findings is included to aid in the understanding and differentiation of these entities. Discussed topics include acute cortical necrosis, autosomal dominant polycystic kidney disease, angiomyolipoma, autosomal recessive polycystic kidney disease, acute tubular necrosis, localized cystic renal disease, multicystic dysplastic kidney, multilocular cystic nephroma, multilocular cystic renal cell carcinoma, medullary sponge kidney, paroxysmal nocturnal hemoglobinuria, renal papillary necrosis, transitional cell carcinoma, and xanthogranulomatous pyelonephritis. Copyright © 2016 Mosby, Inc. All rights reserved.

Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies

OpenAIRE

Sgouralis, Ioannis; Kett, Michelle M.; Ow, Connie P. C.; Abdelkader, Amany; Layton, Anita T.; Gardiner, Bruce S.; Smith, David W.; Lankadeva, Yugeesh R.; Evans, Roger G.

2016-01-01

Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2. Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2. Both intravenous infusion of [Phe2,Ile3,Orn8]-vasopressin and infusion of NG-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8–1...

Retrograde Renal Cooling to Minimize Ischemia

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Janet L. Colli

2013-01-01

Full Text Available Objective: During partial nephrectomy, renal hypothermia has been shown to decrease ischemia induced renal damage which occurs from renal hilar clamping. In this study we investigate the infusion rate required to safely cool the entire renal unit in a porcine model using retrograde irrigation of iced saline via dual-lumen ureteral catheter. Materials and Methods: Renal cortical, renal medullary, bowel and rectal temperatures during retrograde cooling in a laparoscopic porcine model were monitored in six renal units. Iced normal saline was infused at 300 cc/hour, 600 cc/hour, 1000 cc/hour and gravity (800 cc/hour for 600 seconds with and without hilar clamping. Results: Retrograde cooling with hilar clamping provided rapid medullary renal cooling and significant hypothermia of the medulla and cortex at infusion rates ≥ 600 cc/hour. With hilar clamping, cortical temperatures decreased at -0.9° C/min. reaching a threshold temperature of 26.9° C, and medullary temperatures decreased at -0.90 C/min. reaching a temperature of 26.1° C over 600 seconds on average for combined data at infusion rates ≥ 600 cc/hour. The lowest renal temperatures were achieved with gravity infusion. Without renal hilum clamping, retrograde cooling was minimal at all infusion rates. Conclusions: Significant renal cooling by gravity infusion of iced cold saline via a duel lumen catheter with a clamped renal hilum was achieved in a porcine model. Continuous retrograde irrigation with iced saline via a two way ureteral catheter may be an effective method to induce renal hypothermia in patients undergoing robotic assisted and/or laparoscopic partial nephrectomy.

Expression of receptor-type protein tyrosine phosphatase in developing and adult renal vasculature.

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Keiko Takahashi

Full Text Available Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTPμ, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTPμ were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTPμ promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5 and postnatal (P0, P3, P7 kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage, and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTPμ immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1 VE-PTP and PTPμ are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2 their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3 peritubular capillary VE-PTP expression

Sonographic findings in primary diseases of renal pyramids

International Nuclear Information System (INIS)

Rao, B.K.

1987-01-01

Primary pathologic processes involving the renal pyramids such as papillary necrosis, drug-induced necrosis or calcinosis, cysts, neoplasms, and medullary nephrocalcinosis are rare. Thirty-four patients with primary renal pyramid diseases underwent US evaluation for altered morphology; a 5-MHz transducer was used. In 20 patients site-specific changes in the pyramid (e.g., papillary necrosis at the apex, small cysts at the base in medullary cystic disease, tubular calcification in MSK, corticomedullary hyperechogenicity in oxalosis) were noted on US. Sonographic delineation of the site and pattern of pathologic changes in the renal pyramid may help to identify specific diseases

Medullary sponge kidney and isolated hemihyperplasia

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P S Priyamvada

2014-01-01

Full Text Available The term hemihyperplasia refers to an enlargement of body parts beyond the normal asymmetry. Hemihyperplasia can be isolated or associated with various well-described malformation syndromes. Medullary sponge kidney (MSK has been described with isolated and syndromic hemihyperplasia; the actual prevalence is not known The hemi hypertrophy can be so subtle that it may be easily overlooked. MSK need not be limited to the side of hemihyperplasia - most often it is bilateral. Around 33 cases has been reported from different parts of the world of which 15 cases are isolated hemi hyperplasia (IHH, the remaining occurring in the context of various malformation syndromes So far only one case has been reported from India. We report a case of IHH involving right side of the body, recurrent renal stones, incomplete distal renal tubular acidosis hypercalciuria and imaging showing bilateral MSKs.

Thyroid cancer - medullary carcinoma

Science.gov (United States)

Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

Assessment of renal fibrosis in chronic kidney disease using diffusion-weighted MRI

International Nuclear Information System (INIS)

Zhao, J.; Wang, Z.J.; Liu, M.; Zhu, J.; Zhang, X.; Zhang, T.; Li, S.; Li, Y.

2014-01-01

Aim: To assess the performance of diffusion-weighted magnetic resonance imaging (MRI) for the assessment of renal fibrosis in chronic kidney disease (CKD), with histopathology as a reference standard. Materials and methods: Forty patients with CKD and 30 healthy volunteers were recruited for the study. All participants underwent diffusion-weighted MRI. Renal biopsy was performed in 25 patients with CKD. Mean renal medullary and cortical apparent diffusion coefficient (ADC) values were compared between CKD patients and the healthy volunteers. Pearson's correlation coefficient was calculated to investigate the relationship between ADC values, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), 24 h urinary protein (24h-UPRO), and renal histopathological scores. Results: Cortical and medullary ADC values in the CKD group were significantly lower compared to those in the healthy controls. In the CKD group, a significant negative correlation was found between cortical ADC values and SCr/24h-UPRO, and significant positive correlation was found between cortical ADC and eGFR. There was also a significant negative correlation between medullary ADC values and SCr. Both cortical and medullary ADC values were significantly correlated with histopathological fibrosis score. Conclusion: Renal ADC values strongly correlate with histological measures of fibrosis, and have the potential to enhance the non-invasive monitoring of chronic kidney disease. - Highlights: • Renal ADC values in the CKD patients were lower than those in controls. • Renal ADC values were strongly correlated with histological fibrosis score. • Renal ADC values have the potential to enhance the noninvasive monitoring of CKD

Application of Color Doppler Ultrasound in Renal Medullary Calcium%彩色多普勒超声在肾髓质钙质沉着症中的应用分析

Institute of Scientific and Technical Information of China (English)

金丽梅

2016-01-01

目的：分析彩色多普勒超声在肾髓质钙沉着症中的应用价值。方法回顾性分析2011—2015年期间在该院行彩色多普勒超声诊断肾髓质钙沉着症的68例患者的临床资料，观察患者的超声诊断特点以及血流动力学改变。结果68例行彩色多普勒超声诊断肾髓质钙沉着症的患者中，诊断阳性共65例，阴性3例，诊断的准确率为95.6%，65例肾髓质钙沉着症患者中包括皮质型30例，髓质型32例，混合型3例，患者的两侧肾脏大小正常，形态对称，包膜光滑，皮质和髓质界限较为清楚，肾脏的皮质厚度和回声均正常，在患者的髓质内，有密集点状的强回声，形态和椎体的形态基本一致，有一侧有弱声影。结论彩色多普勒超声在肾髓质钙沉着症中应用，准确率较高，可以有效的显示内部的形态、血流变化等指标，具有重要的临床诊断价值。%Objective To analyze the value of color Doppler ultrasound in the renal medulla of calcium applications. Methods Convenient selection a retrospective analysis of clinical data by color Doppler ultrasound diagnosis of renal medullary calcinosis disease 68 patients were retrospectively analyzed the period from 2011 to 2015, observed in patients with ultrasonic diagnostic characteristics and hemodynamic change. Results 68 patients with routine color Doppler ultra-sound diagnosis of renal medullary calcinosis disease, the diagnosis of a total of65 positive cases, negative in 3 cases, the diagnostic accuracy was 95.6%, 65 cases of renal medullary calcinosis patients included cortical 30 cases, 32 cases of medullary, mixed three cases, both sides of the patient's normal kidney size, shape symmetry, smooth coated, cortex and medulla boundaries more clearly, renal cortical thickness and echo were normal in patients within the medulla, a strong e-cho dense point-like, form and shape of the vertebral body are basically the same, there is one

A new perspective on the pathogenesis of chronic renal disease in captive cheetahs (Acinonyx jubatus).

Science.gov (United States)

Mitchell, Emily P; Prozesky, Leon; Lawrence, John

2018-01-01

The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the

Incorporation of radioactive sulfate (Na235SO4) by mouse adrenal medullary cells as shown by radioautography

International Nuclear Information System (INIS)

Munhoz, C.O.G.; Merzel, J.

1977-01-01

Preliminary radioautographic results, observed in the adreno-medullary cells of mice injected with radiosulfate, suggested that the cells might synthetize sulfur-containing compounds. Only further studies could make-clear if sulfate groups are linked to carbohydrate molecules and/or chromaffin granules [pt

Constitutive Activation of Smoothened in the Renal Collecting Ducts Leads to Renal Hypoplasia, Hydronephrosis, and Hydroureter.

Science.gov (United States)

Gupta, Deepak Prasad; Hwang, Jae-Won; Cho, Eui-Sic; Kim, Won; Song, Chang Ho; Chai, Ok Hee

2017-01-01

Sonic Hedgehog (Shh) signaling plays a major role in and is essential for regulation, patterning, and proliferation during renal development. Smoothened (Smo) plays a pivot role in transducing the Shh-glioma-associated oncogene Kruppel family member. However, the cellular and molecular mechanism underlying the role of sustained Smo activation in postnatal kidney development is still not clearly understood. Using a conditional knockin mouse model that expresses a constitutively activated form of Smo (SmoM2) upon Homeobox-B7-mediated recombination (Hoxb7-Cre), the effects of Shh signaling were determined in postnatal kidney development. SmoM2;Hoxb7-Cre mutant mice showed growth retardation with a reduction of body weight. Constitutive activation of Smo in the renal collecting ducts caused renal hypoplasia, hydronephrosis, and hydroureter. The parenchymal area and glomerular numbers were reduced, but the glomerular density was increased in SmoM2;Hoxb7-Cre mutant mice. The expression of Patched 1, the receptor of Shh and a downstream target gene of the Shh signaling pathway, was highly restricted and it was upregulated in the inner medullary collecting ducts of the kidney. The proliferative cells in the mesenchyme and collecting ducts were decreased in SmoM2;Hoxb7-Cre mutant mice. This study showed for the first time that sustained Smo inhibits postnatal kidney development by suppressing the proliferation of the mesenchyme and medullary collecting ducts in mice. © 2017 S. Karger AG, Basel.

Adrenal medullary regulation of rat renal cortical adrenergic receptors

International Nuclear Information System (INIS)

Sundaresan, P.R.; Guarnaccia, M.M.; Izzo, J.L. Jr.

1987-01-01

The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particular fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of [ 3 H]prazosin, [ 3 H]rauwolscine, and [ 125 I]iodocyanopindolol were used to quantitate α 1 -, α 2 -, and β-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (B max , per milligram membrane protein) for α 1 -, and α 2 -, and β-adrenergic receptors were increased by 22, 18.5, and 25%, respectively. No differences were found in the equilibrium dissociation constants (K D ) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation, renal cortical epinephrine was not detectable in control or demedullated animals. The results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine

Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients

Energy Technology Data Exchange (ETDEWEB)

Chen, Xiao; Zhou, Hao; Duan, Na; Liu, Yongkang; Wang, Zhongqiu [Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing (China); Zhu, Qingqiang [Medical School of Yangzhou University, Department of Medical Imaging, Subei People' s Hospital, Yangzhou (China); Li, Baoxin [Gulou Hospital, Department of Radiology, Nanjing (China); Cui, Wenjing [Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing (China); Nanjing University Medical School, Department of Radiology, Jinling Hospital, Nanjing (China); Kundra, Vikas [The University of Texas, M.D. Anderson Cancer Center, Department of Radiology, Houston, TX (United States)

2017-02-15

To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. (orig.)

Investigations on renal organic and inorganic solutes, in vivo

International Nuclear Information System (INIS)

Wolff, S.D.

1989-01-01

A basic question in renal physiology is how do the cells of the renal medulla survive the high concentrations of sodium chloride and urea which occur with antidiuresis. The problem is two-fold: (1) urea, being highly permeable to cell membranes, should enter the cell and adversely affect protein function; and (2) inorganic ions, being in much higher concentration extracellularly than intracellularly should dehydrate the cell. If these organic solutes exist in response to high concentrations of sodium chloride and urea, then their content should vary with diuretic state. Two protocols were developed to test the validity of this hypothesis. The first protocol used 31 P-NMR in vivo to monitor GPC content before, during, and after acute diuresis in an exteriorized rabbit kidney model. Changes in sodium distribution and tissue structure were monitored dynamically with 23 Na- and 1 H-NMR imaging, respectively. The second protocol used HPLC to quantitate each of the four organic solutes in renal inner medullary homogenates. Here, the effect of diuretic state and acute diuresis on organic solute content was assessed

Renal cell carcinoma in patient with crossed fused renal ectopia

Directory of Open Access Journals (Sweden)

Ozgur Cakmak

2016-01-01

Full Text Available Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vasculature is essential for preservation of the uninvolved renal units.

Frequency and clinical significance of transient hyperechoic renal medulla in neonates

International Nuclear Information System (INIS)

Cho, Sung Shick; Kim, Jung Hoon; Hong, Hyun Sook; Shin, Ji Hoon; Hwang, Jung Hwa; Goo, Dong Erk; Kwon, Kui Hyang; Choi, Deuk Lin

2001-01-01

To evaluate the clinical significance of transient hyperechogenicity of the renal medulla in neonates by comparing the clinical features, urinalysis and follow-up ultrasonographic examination of the control group. One hundred ten neonates were divided into 2 groups, hyperechoic and normal renal medulla groups, and all of them underwent abdominal ultrasound with a 7.5 MHz linear transducer (Sonoace 8800MT, Medicine, Korea) from November 1999 to January 2000. Whether there was any difference in clinical features including birth weight, body surface area, gestational age, sex, date of examination and mode of delivery between two groups was evaluated. In addition, any difference in their urinary osmolarity, albumin, uric acid and calcium in 41 neonates who underwent urinalysis was evaluated. In ten neonates with hyperechoic renal medulla underwent follow-up study, the follow-up ultrasonographic findings were compared with the initial study. In 67 of 110 (61%) neonates, ultrasonography demonstrated hyperechoic renal medulla. There was no difference in clinical features between the hyperechoic renal medullary group and normal group. In 41 neonates, there was no significant difference in urinalysis between two groups. (Osmolarity=146.46 ± 68.4 mOsml/KgH 2 O in the hyperechoic renal medullary group vs. 149.8 ± 77.7 mOsml/KgH 2 O in the normal group; albumin=13.9 ± 10.2 mg/ml vs. 17.6 ± 13.6 mg/dl; uric acid=50.0 ± 23.3 mg/dl vs. 44.9 ± 34.1 mg/dl; calcium=1.38 ± 3.0 mg/ dl vs. 0.44 ± 0.07 mg/dl.) Ten neonates who underwent follow-up ultrasonography within 20 days after the initial study showed the normal medullary echogenicity. There were no significant difference between the hyperechoic renal medullary group and the normal echogenic group in their clinical features and urinalysis. Therefore, the hyperechoic renal medullar in neonate is considered as an usual and transient finding which disappears on follow-up study.

Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia.

Science.gov (United States)

Saad, Ahmed; Wang, Wei; Herrmann, Sandra M S; Glockner, James F; Mckusick, Michael A; Misra, Sanjay; Bjarnason, Haraldur; Lerman, Lilach O; Textor, Stephen C

2016-11-01

Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF), ultimately leading to kidney hypoxia and inflammation. Insulin-like growth factor binding protein-7 (IGFBP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) are biomarkers of cell cycle arrest, often increased in ischemic conditions and predictive of acute kidney injury (AKI). This study sought to examine the relationships between renal vein levels of IGFBP-7, TIMP-2, reductions in RBF and postcontrast hypoxia as measured by blood oxygen level-dependent (BOLD) magnetic resonance imaging. Renal vein levels of IGFBP-7 and TIMP-2 were obtained in an ARAS cohort (n= 29) scheduled for renal artery stenting and essential hypertensive (EH) healthy controls (n = 32). Cortical and medullary RBFs were measured by multidetector computed tomography (CT) immediately before renal artery stenting and 3 months later. BOLD imaging was performed before and 3 months after stenting in all patients, and a subgroup (N = 12) underwent repeat BOLD imaging 24 h after CT/stenting to examine postcontrast/procedure levels of hypoxia. Preintervention IGFBP-7 and TIMP-2 levels were elevated in ARAS compared with EH (18.5 ± 2.0 versus 15.7 ± 1.5 and 97.4 ± 23.1 versus 62.7 ± 9.2 ng/mL, respectively; Pblood flow (r = -0.59, P= 0.004). These data demonstrate elevated IGFBP-7 and TIMP-2 levels in ARAS as a function of the degree of reduced RBF. Elevated baseline IGFBP-7 levels were associated with protection against postimaging hypoxia, consistent with 'ischemic preconditioning'. Despite contrast injection and stenting, AKI in these high-risk ARAS subjects with elevated IGFBP-7/TIMP-2 was rare and did not affect long-term kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Stages of Renal Cell Cancer

Science.gov (United States)

... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

Bilateral papillary renal cell carcinoma

International Nuclear Information System (INIS)

Gossios, K.; Vazakas, P.; Argyropoulou, M.; Stefanaki, S.; Stavropoulos, N.E.

2001-01-01

Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. (orig.)

CT differentiation of infiltrating renal cell carcinoma and renal urothelial tumor

International Nuclear Information System (INIS)

Choi, Hyo Kyeong; Goo, Dong Erk; Bang, Sun Woo; Lee, Moon Gyu; Cho, Kyoung Sik; Auh, Yong Ho

1994-01-01

It may be difficult to differentiate renal cell carcinoma involving collecting system from renal urothelial tumor invading into renal parenchyma. The purpose of this study was to assess the differences of CT findings between two conditions. CT findings of 5 cases of renal cell carcinoma involving the renal collecting systems and 10 cases of renal urothelial tumors invading the renal parenchyma were compared, and analyzed about the presence or absence of hydronephrosis, normal or abnormal CT nephrogram, renal contour changes due to mass and tentative diagnosis. The diagnoses were confirmed at surgery. Renal cell carcinoma showed hydronephrosis in only 20% and normal CT nephrogram and outward contour bulging in all cases. In contrast, renal urothelial tumor showed hydronephrosis(70%), abnormal CT nephrogram(60%), and preservation of reinform shape(100%). Renal contour changes and CT nephrogram may be useful in distinguishing both disease entities

Basolateral P2X receptors mediate inhibition of NaCl transport in mouse medullary thick ascending limb (mTAL)

DEFF Research Database (Denmark)

Marques, Rita D; de Bruijn, Pauline I.A.; Sørensen, Mads Vaarby

2012-01-01

Extracellular nucleotides regulate epithelial transport via luminal and basolateral P2 receptors. Renal epithelia express multiple P2 receptors, which mediate significant inhibition of solute absorption. Recently, we identified several P2 receptors in the medullary thick ascending limb (m...

CT differentiation of renal tumor invading parenchyma and pelvis: renal cell carcinoma vs transitional cell carcinoma

International Nuclear Information System (INIS)

Lee, Chang Hee; Cho, Seong Beum; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung

1994-01-01

The differentiation between renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) is important due to the different methods of treatment and prognosis. But occasionally it is difficult to draw a distinction between the two diseases when renal parenchyma and renal collecting systems are invaded simultaneously. We reviewed CT scans of 37 cases of renal cell carcinoma and 12 cases of transitional cell carcinoma which showed involvement of renal parenchyma and renal sinus fat on CT. Retrospective analysis was performed by 3 abdominal radiologists. Check points were renal contour bulging or reinform shape, location of mass center, intact parenchyma overlying the tumor, cystic change, calcification, LN metastasis, vessel invasion, and perirenal extention. There were renal contour bulging due to the tumor mass in 33 out of 37 cases of renal cell carcinoma, where a and nine of 12 cases of transitional cell carcinoma maintained the reinform appearance. This is significant statiscal difference between the two(P<0.005). Center of all TCCs were located in the renal sinus, and 24 out of 35 cases of RCC were located in the cortex(P<0.005). Thirty-six out of 37 cases of RCC lost the overlying parenchyma, where as 4 out of 9 cases of well enhanced TCC had intact overlying parenchyma(P<0.005) RCC showed uptic change within the tumor mags in 31 cases which was significanity higher than the 4 cases in TCC(P<0.05). CT findings of renal cell carcinoma are contour bulging, peripheral location, obliteration of parenchyma, and cystic change. Findings of transitional cell carcinoma are reinform appearance, central location within the kidney, intact overlying parenchyma, and rare cystic change

Somatostatin Receptor Scintigraphy in Medullary Thyroid Cancer

NARCIS (Netherlands)

van der Horst-Schrivers, Anouk N. A.; Brouwers, Adrienne; Links, Thera; Hubalewska‐Dydejczyk, Alicja; Signore, Alberto; de Jong, Marion; Dierckx, Rudi A.; Buscombe, John; Van de Wiele, Christophe

2015-01-01

Medullary thyroid cancer (MTC) is a neuroendocrine tumor originating from the calcitonin‐secreting C cells. Surgery, consisting of a total thyroidectomy and an extensive lymph node dissection, is the only effective treatment in MTC; however, metastases are frequently found in the regional cervical

Enamel renal syndrome: A rare case report

Directory of Open Access Journals (Sweden)

S V Kala Vani

2012-01-01

Full Text Available Enamel renal syndrome is a very rare disorder associating amelogenesis imperfecta with nephrocalcinosis. It is known by various synonyms such as amelogenesis imperfecta nephrocalcinosis syndrome, MacGibbon syndrome, Lubinsky syndrome, and Lubinsky-MacGibbon syndrome. It is characterized by enamel agenesis and medullary nephrocalcinosis. This paper describes enamel renal syndrome in a female patient born in a consanguineous family.

Schwannosis induced medullary compression in VACTERL syndrome.

LENUS (Irish Health Repository)

Treacy, A

2011-10-21

A 7-year-old boy with a history of VACTERL syndrome was found collapsed in bed. MRI had shown basilar invagination of the skull base and narrowing of the foramen magnum. Angulation, swelling and abnormal high signal at the cervicomedullary junction were felt to be secondary to compression of the medulla. Neuropathologic examination showed bilateral replacement of the medullary tegmentum by an irregularly circumscribed cellular lesion which was composed of elongated GFAP\\/S 100-positive cells with spindled nuclei and minimal atypia. The pathologic findings were interpreted as intramedullary schwannosis with mass effect. Schwannosis, is observed in traumatized spinal cords where its presence may represent attempted, albeit aberrant, repair by inwardly migrating Schwann cells ofperipheral origin. In our view the compressive effect of the basilar invagination on this boy\\'s medulla was of sufficient magnitude to have caused tumoral medullary schwannosis with resultant intermittent respiratory compromise leading to reflex anoxic seizures.

Renal cystic disease: A practical overview

International Nuclear Information System (INIS)

Hartman, D.S.

1987-01-01

Renal cystic disease includes a group of lesions with extremely diverse clinical, radiographic, and pathologic findings. The recent development of multiple imaging systems to study renal cystic disease has resulted in considerable interest in correlating the images obtained by different modalities with each other and with the underlying gross pathology. A thorough knowledge of the disturbed morphology and natural history of these diseases will lead to a better understanding of their appearance on radiologic imaging. This refresher course correlates disturbed morphology with appearances on diagnostic imaging, urography, US, angiography, CT, and MR imaging. The advantages and limitations of each imaging method are detailed. A practical classification emphasizing differential features is presented. The presentation is divided into two parts. In the first part typical and atypical cystic masses, including acquired cystic disease (from dialysis), Von Hippel-Lindau disease, and the cystic disease of tuberous sclerosis are discussed. In the second part, polycystic kidney disease (dominant and recessive), medullary cystic disease, medullary sponge kidney, multicycle-dysplastic kidney, renal sinus cysts (peripelvic), and pluricystic kidney disease are discussed

Evaluation of Renal Oxygenation Level Changes after Water Loading Using Susceptibility-Weighted Imaging and T2* Mapping.

Science.gov (United States)

Ding, Jiule; Xing, Wei; Wu, Dongmei; Chen, Jie; Pan, Liang; Sun, Jun; Xing, Shijun; Dai, Yongming

2015-01-01

To assess the feasibility of susceptibility-weighted imaging (SWI) while monitoring changes in renal oxygenation level after water loading. Thirty-two volunteers (age, 28.0 ± 2.2 years) were enrolled in this study. SWI and multi-echo gradient echo sequence-based T2(*) mapping were used to cover the kidney before and after water loading. Cortical and medullary parameters were measured using small regions of interest, and their relative changes due to water loading were calculated based on baseline and post-water loading data. An intraclass correlation coefficient analysis was used to assess inter-observer reliability of each parameter. A receiver operating characteristic curve analysis was conducted to compare the performance of the two methods for detecting renal oxygenation changes due to water loading. Both medullary phase and medullary T2(*) values increased after water loading (p T2(*) changes (p > 0.05). Interobserver reliability was excellent for the T2(*) values, good for SWI cortical phase values, and moderate for the SWI medullary phase values. The area under receiver operating characteristic curve of the SWI medullary phase values was 0.85 and was not different from the medullary T2(*) value (0.84). Susceptibility-weighted imaging enabled monitoring changes in the oxygenation level in the medulla after water loading, and may allow comparable feasibility to detect renal oxygenation level changes due to water loading compared with that of T2(*) mapping.

General Information about Renal Cell Cancer

Science.gov (United States)

... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

Treatment Option Overview (Renal Cell Cancer)

Science.gov (United States)

... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

Receptor stimulated formation of inositol phosphates in cultures of bovine adrenal medullary cells: the effects of bradykinin, bombesin and neurotensin.

Science.gov (United States)

Bunn, S J; Marley, P D; Livett, B G

1990-04-01

The ability of a number of drugs and neuropeptides to stimulate phosphoinositide metabolism in cultured bovine adrenal medullary cells has been assessed. Low concentrations (10 nM) of angiotensin II, bradykinin, histamine, arginine-vasopressin, and bombesin, and high (10 microM) concentrations of oxytocin, prostaglandins E1, and E2, beta-endorphin, and neurotensin stimulated significant accumulation of [3H]inositol phosphates in adrenal medullary cells preloaded with [3H)]inositol. Bradykinin stimulated a significant response at concentration as low as 10pM, with an EC50 of approximately 0.5 nM. The response was markedly inhibited by the bradykinin B2 antagonist [Thi5,8,D-Phe7] bradykinin but not the B1 antagonist [Des-Arg9,Leu8] bradykinin. Higher concentrations of bombesin and neurotensin were required to elicit a response (10 nM and 10 microM respectively). The bombesin response was sensitive to inhibition by the bombesin antagonist [D-Arg1,D-Pro2,D-Trp7,9Leu11]-substance P. In contrast, the neurotensin response was not reduced by the NT1 antagonist [D-Trp11]-neurotensin. These results indicate there are a number of agents that can stimulate phosphatidylinositide hydrolysis in the adrenal medullary cells by acting on different classes of receptors. Such a range of diverse agonists that stimulate inositol phosphate formation will facilitate further analysis of the phosphatidylinositide breakdown in chromaffin cell function.

Medullary compression syndrome

International Nuclear Information System (INIS)

Barriga T, L.; Echegaray, A.; Zaharia, M.; Pinillos A, L.; Moscol, A.; Barriga T, O.; Heredia Z, A.

1994-01-01

The authors made a retrospective study in 105 patients treated in the Radiotherapy Department of the National Institute of Neoplasmic Diseases from 1973 to 1992. The objective of this evaluation was to determine the influence of radiotherapy in patients with medullary compression syndrome in aspects concerning pain palliation and improvement of functional impairment. Treatment sheets of patients with medullary compression were revised: 32 out of 39 of patients (82%) came to hospital by their own means and continued walking after treatment, 8 out of 66 patients (12%) who came in a wheelchair or were bedridden, could mobilize by their own after treatment, 41 patients (64%) had partial alleviation of pain after treatment. In those who came by their own means and did not change their characteristics, functional improvement was observed. It is concluded that radiotherapy offers palliative benefit in patients with medullary compression syndrome. (authors). 20 refs., 5 figs., 6 tabs

Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal

DEFF Research Database (Denmark)

Mitchell, Thomas J.; Turajlic, Samra; Rowan, Andrew

2018-01-01

Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the...

ERK Regulates Renal Cell Proliferation and Renal Cyst Expansion in inv Mutant Mice

International Nuclear Information System (INIS)

Okumura, Yasuko; Sugiyama, Noriyuki; Tanimura, Susumu; Nishida, Masashi; Hamaoka, Kenji; Kohno, Michiaki; Yokoyama, Takahiko

2009-01-01

Nephronophthisis (NPHP) is the most frequent genetic cause of end-stage kidney disease in children and young adults. Inv mice are a model for human nephronophthisis type 2 (NPHP2) and characterized by multiple renal cysts and situs inversus. Renal epithelial cells in inv cystic kidneys show increased cell proliferation. We studied the ERK pathway to understand the mechanisms that induce cell proliferation and renal cyst progression in inv kidneys. We studied the effects of ERK suppression by administering PD184352, an oral mitogen-activated protein kinase kinase (MEK) inhibitor on renal cyst expansion, extracellular signal-regulated protein kinase (ERK) activity, bromo-deoxyuridine (BrdU) incorporation and expression of cell-cycle regulators in invΔC kidneys. Phosphorylated ERK (p-ERK) level increased along with renal cyst enlargement. Cell-cycle regulators showed a high level of expression in invΔC kidneys. PD184352 successfully decreased p-ERK level and inhibited renal cyst enlargement. The inhibitor also decreased expression of cell-cycle regulators and BrdU incorporation in renal epithelial cells. The present results showed that ERK regulated renal cell proliferation and cyst expansion in inv mutants

New non-renal congenital disorders associated with medullary sponge kidney (MSK) support the pathogenic role of GDNF and point to the diagnosis of MSK in recurrent stone formers.

Science.gov (United States)

Ria, Paolo; Fabris, Antonia; Dalla Gassa, Alessandra; Zaza, Gianluigi; Lupo, Antonio; Gambaro, Giovanni

2017-08-01

Medullary sponge kidney (MSK) is a congenital renal disorder. Its association with several developmental abnormalities in other organs hints at the likelihood of some shared step(s) in the embryogenesis of the kidney and other organs. It has been suggested that the REarranged during Transfection (RET) proto-oncogene and the Glial cell line-Derived Neurotrophic Factor (GDNF) gene are defective in patients with MSK, and both RET and GDNF are known to have a role in the development of the central nervous system, heart, and craniofacial skeleton. Among a cohort of 143 MSK patients being followed up for nephrolithiasis and chronic kidney disease at our institution, we found six with one or more associated non-renal anomalies: one patient probably has congenital hemihyperplasia and hypertrophic cardiomyopathy with adipose metaplasia and mitral valve prolapse; one has Marfan syndrome; and the other four have novel associations between MSK and nerve and skeleton abnormalities described here for the first time. The discovery of disorders involving the central nervous system, cardiovascular system and craniofacial skeleton in MSK patients supports the hypothesis of a genetic alteration on the RET-GDNF axis having a pivotal role in the pathogenesis of MSK, in a subset of patients at least. MSK seems more and more to be a systemic disease, and the identification of extrarenal developmental defects could be important in arousing the suspicion of MSK in recurrent stone formers.

Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct.

Science.gov (United States)

Yu, Ming-Jiun; Miller, R Lance; Uawithya, Panapat; Rinschen, Markus M; Khositseth, Sookkasem; Braucht, Drew W W; Chou, Chung-Lin; Pisitkun, Trairak; Nelson, Raoul D; Knepper, Mark A

2009-02-17

We used a systems biology-based approach to investigate the basis of cell-specific expression of the water channel aquaporin-2 (AQP2) in the renal collecting duct. Computational analysis of the 5'-flanking region of the AQP2 gene (Genomatix) revealed 2 conserved clusters of putative transcriptional regulator (TR) binding elements (BEs) centered at -513 bp (corresponding to the SF1, NFAT, and FKHD TR families) and -224 bp (corresponding to the AP2, SRF, CREB, GATA, and HOX TR families). Three other conserved motifs corresponded to the ETS, EBOX, and RXR TR families. To identify TRs that potentially bind to these BEs, we carried out mRNA profiling (Affymetrix) in mouse mpkCCDc14 collecting duct cells, revealing expression of 25 TRs that are also expressed in native inner medullary collecting duct. One showed a significant positive correlation with AQP2 mRNA abundance among mpkCCD subclones (Ets1), and 2 showed a significant negative correlation (Elf1 and an orphan nuclear receptor Nr1h2). Transcriptomic profiling in native proximal tubules (PT), medullary thick ascending limbs (MTAL), and IMCDs from kidney identified 14 TRs (including Ets1 and HoxD3) expressed in the IMCD but not PT or MTAL (candidate AQP2 enhancer roles), and 5 TRs (including HoxA5, HoxA9 and HoxA10) expressed in PT and MTAL but not in IMCD (candidate AQP2 repressor roles). In luciferase reporter assays, overexpression of 3 ETS family TRs transactivated the mouse proximal AQP2 promoter. The results implicate ETS family TRs in cell-specific expression of AQP2 and point to HOX, RXR, CREB and GATA family TRs as playing likely additional roles.

Computed tomography of renal cell carcinoma in patients with terminal renal impairment

International Nuclear Information System (INIS)

Ferda, Jiri; Hora, Milan; Hes, Ondrej; Reischig, Tomas; Kreuzberg, Boris; Mirka, Hynek; Ferdova, Eva; Ohlidalova, Kristyna; Baxa, Jan; Urge, Tomas

2007-01-01

Purpose: An increased incidence of renal tumors has been observed in patients with end-stage-renal-disease (ESRD). The very strong association with acquired renal cystic disease (ACRD) and increased incidence of the renal tumors (conventional renal cell carcinoma (CRCC), papillary renal cell carcinoma (PRCC) or papillary renal cell adenoma (PRCA)) was reported. This study discusses the role of computed tomography (CT) in detecting renal tumors in patients with renal impairment: pre-dialysis, those receiving dialysis or with renal allograft transplants. Materials and methods: Ten patients (nine male, one female) with renal cell tumors were enrolled into a retrospective study; two were new dialysis patients, three on long-term dialysis, and five were renal transplant recipients with history of dialysis. All patients underwent helical CT, a total of 11 procedures were performed. Sixteen-row detector system was used five times, and a 64-row detector system for the six examinations. All patients underwent nephrectomy of kidney with suspected tumor, 15 nephrectomies were performed, and 1 kidney was assessed during autopsy. CT findings were compared with macroscopic and microscopic assessments of the kidney specimen in 16 cases. Results: Very advanced renal parenchyma atrophy with small cysts corresponding to ESRD was found in nine patients, chronic pyelonephritis in remained one. A spontaneously ruptured tumor was detected incidentally in one case, patient died 2 years later. In the present study, 6.25% (1/16) were multiple PRCA, 12.5% (2/16) were solitary PRCC, 12.5% tumors (2/16) were solitary conventional renal cell carcinomas (CRCC's), 12.5% tumors (2/16) were multiple conventional renal cell carcinomas (CRCC's), 25% (4/16) were CRCC's combined with multiple papillary renal cell carcinomas with adenomas (PRCC's and PRCA's), and 25% (4/16) of the tumors were multiple PRCC's combined with PRCA's without coexisting CRCC's. Bilateral renal tumors were found in our study

Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER Database.

Science.gov (United States)

Daugherty, Michael; Blakely, Stephen; Shapiro, Oleg; Vourganti, Srinivas; Mollapour, Mehdi; Bratslavsky, Gennady

2016-04-01

The renal cell cancer incidence is relatively low in younger patients, encompassing 3% to 7% of all renal cell cancers. While young patients may have renal tumors due to hereditary syndromes, in some of them sporadic renal cancers develop without any family history or known genetic mutations. Our recent observations from clinical practice have led us to hypothesize that there is a difference in histological distribution in younger patients compared to the older cohort. We queried the SEER (Surveillance, Epidemiology and End Results) 18-registry database for all patients 20 years old or older who were surgically treated for renal cell carcinoma between 2001 and 2008. Patients with unknown race, grade, stage or histology and those with multiple tumors were excluded from study. Four cohorts were created by dividing patients by gender, including 1,202 females and 1,715 males younger than 40 years old, and 18,353 females and 30,891 males 40 years old or older. Chi-square analysis was used to compare histological distributions between the cohorts. While clear cell carcinoma was still the most common renal cell cancer subtype across all genders and ages, chromophobe renal cell cancer was the most predominant type of nonclear renal cell cancer histology in young females, representing 62.3% of all nonclear cell renal cell cancers (p renal cell cancer remained the most common type of nonclear renal cell cancer. It is possible that hormonal factors or specific pathway dysregulations predispose chromophobe renal cell cancer to develop in younger women. We hope that this work provides some new observations that could lead to further studies of gender and histology specific renal tumorigenesis. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

HV1 acts as a sodium sensor and promotes superoxide production in medullary thick ascending limb of Dahl salt-sensitive rats.

Science.gov (United States)

Jin, Chunhua; Sun, Jingping; Stilphen, Carly A; Smith, Susan M E; Ocasio, Hiram; Bermingham, Brent; Darji, Sandip; Guha, Avirup; Patel, Roshan; Geurts, Aron M; Jacob, Howard J; Lambert, Nevin A; O'Connor, Paul M

2014-09-01

We previously characterized a H(+) transport pathway in medullary thick ascending limb nephron segments that when activated stimulated the production of superoxide by nicotinamide adenine dinucleotide phosphate oxidase. Importantly, the activity of this pathway was greater in Dahl salt-sensitive rats than salt-resistant (SS.13(BN)) rats, and superoxide production was enhanced in low Na(+) media. The goal of this study was to determine the molecular identity of this pathway and its relationship to Na(+). We hypothesized that the voltage-gated proton channel, HV1, was the source of superoxide-stimulating H(+) currents. To test this hypothesis, we developed HV1(-/-) null mutant rats on the Dahl salt-sensitive rat genetic background using zinc-finger nuclease gene targeting. HV1 could be detected in medullary thick limb from wild-type rats. Intracellular acidification using an NH4Cl prepulse in 0 sodium/BaCl2 containing media resulted in superoxide production in thick limb from wild-type but not HV1(-/-) rats (Pthick limb and peritoneal macrophages only when HV1 was present. When fed a high-salt diet, blood pressure, outer medullary renal injury (tubular casts), and oxidative stress (4-hydroxynonenal staining) were significantly reduced in HV1(-/-) rats compared with wild-type Dahl salt-sensitive rats. We conclude that HV1 is expressed in medullary thick ascending limb and promotes superoxide production in this segment when intracellular Na(+) is low. HV1 contributes to the development of hypertension and renal disease in Dahl salt-sensitive rats. © 2014 American Heart Association, Inc.

Evaluation of renal oxygenation level changes after water loading using susceptibility-weighted imaging and T2{sup *} mapping

Energy Technology Data Exchange (ETDEWEB)

Ding, Jiule; Xing, Wei; Chen, Jie; Pan, Liang; Sun, Jun; Xing, Shi Jun [Dept. of Radiology, Third Affiliated Hospital of Suzhou University, Changzhou (China); Wu, Dong Mei [Shanghai Key Laboratory of Magnetic Resonance Imaging, East China Normal University, Shanghai (China); Dai, Yong Ming [Philips Healthcare, Shanghai (China)

2015-08-15

To assess the feasibility of susceptibility-weighted imaging (SWI) while monitoring changes in renal oxygenation level after water loading. Thirty-two volunteers (age, 28.0 ± 2.2 years) were enrolled in this study. SWI and multi-echo gradient echo sequence-based T2{sup *} mapping were used to cover the kidney before and after water loading. Cortical and medullary parameters were measured using small regions of interest, and their relative changes due to water loading were calculated based on baseline and post-water loading data. An intraclass correlation coefficient analysis was used to assess inter-observer reliability of each parameter. A receiver operating characteristic curve analysis was conducted to compare the performance of the two methods for detecting renal oxygenation changes due to water loading. Both medullary phase and medullary T2{sup *} values increased after water loading (p < 0.001), although poor correlations were found between the phase changes and the T2{sup *} changes (p > 0.05). Interobserver reliability was excellent for the T2{sup *} values, good for SWI cortical phase values, and moderate for the SWI medullary phase values. The area under receiver operating characteristic curve of the SWI medullary phase values was 0.85 and was not different from the medullary T2{sup *} value (0.84). Susceptibility-weighted imaging enabled monitoring changes in the oxygenation level in the medulla after water loading, and may allow comparable feasibility to detect renal oxygenation level changes due to water loading compared with that of T2{sup *} mapping.

Update on the renal toxicity of iodinated contrast drugs used in clinical medicine

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Andreucci M

2017-05-01

Full Text Available Michele Andreucci,1 Teresa Faga,1 Raffaele Serra,2 Giovambattista De Sarro,3 Ashour Michael1 1Renal Unit, Department of Health Sciences, 2Interuniversity Center of Phlebolymphology (CIFL, International Research and Educational Program in Clinical and Experimental Biotechnology, Department of Medical and Surgical Sciences, 3Pharmacology Unit, Department of Health Sciences, Magna Graecia University, Catanzaro, Italy Abstract: An important side effect of diagnostic contrast drugs is contrast-induced acute kidney injury (CI-AKI; a sudden decrease in renal function occurring 48–72 hours after injection of a contrast drug that cannot be attributed to other causes. Its existence has recently been challenged, because of some retrospective studies in which the incidence of AKI was not different between subjects who received a contrast drug and those who did not, even using propensity score matching to prevent selection bias. For some authors, only patients with estimated glomerular filtration rate <30 mL/min/1.73 m2 are at significant risk of CI-AKI. Most agree that when renal function is normal, there is no CI-AKI risk. Many experimental studies, however, are in favor of the existence of CI-AKI. Contrast drugs have been shown to cause the following changes: renal vasoconstriction, resulting in a rise in intrarenal resistance (decrease in renal blood flow and glomerular filtration rate and medullary hypoxia; epithelial vacuolization and dilatation and necrosis of proximal tubules; potentiation of angiotensin II effects, reducing nitric oxide (NO and causing direct constriction of descending vasa recta, leading to formation of reactive oxygen species in isolated descending vasa recta of rats microperfused with a solution of iodixanol; increasing active sodium reabsorption in the thick ascending limbs of Henle’s loop (increasing O2 demand and consequently medullary hypoxia; direct cytotoxic effects on endothelial and tubular epithelial cells (decrease

STUDIES OF THE RENAL CONCENTRATING MECHANISM IN HUMANS. I. THE EFFECT OF HYPERTHYROIDISM,

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Summary: (1) The maximum urinary osmolality after dehydration and exogenous vasopressin was significantly decreased during thyrotoxicosis in... thyrotoxicosis , TcH2O during a moderate mannitol diuresis was unchanged in most patients. The data suggest that the decreased Umax and normal TcH2O...in thyrotoxic individuals is probably caused by an increase in medullary blood flow with a decrease in medullary osmolality. (2) Renal hemodynamics

Identification of a subpopulation of marrow MSC-derived medullary adipocytes that express osteoclast-regulating molecules: marrow adipocytes express osteoclast mediators.

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Vance Holt

Full Text Available Increased marrow medullary adipogenesis and an associated decrease in bone mineral density, usually observed in elderly individuals, is a common characteristic in senile osteoporosis. In this study we investigated whether cells of the medullary adipocyte lineage have the potential to directly support the formation of osteoclasts, whose activity in bone leads to bone degradation. An in vitro mesenchymal stem cell (MSC-derived medullary adipocyte lineage culture model was used to study the expression of the important osteoclast mediators RANKL, M-CSF, SDF-1, and OPG. We further assessed whether adipocytes at a specific developmental stage were capable of supporting osteoclast-like cell formation in culture. In vitro MSC-derived medullary adipocytes showed an mRNA and protein expression profile of M-CSF, RANKL, and OPG that was dependent on its developmental/metabolic stage. Furthermore, RANKL expression was observed in MSC-derived adipocytes that were at a distinct lineage stage and these cells were also capable of supporting osteoclast-like cell formation in co-cultures with peripheral blood mononuclear cells. These results suggest a connection between medullary adipocytes and osteoclast formation in vivo and may have major significance in regards to the mechanisms of decreased bone density in senile osteoporosis.

Kidney (Renal Cell) Cancer—Health Professional Version

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Kidney cancer has three main types. Renal cell cancer, or renal cell adenocarcinoma, forms in the tubules of the kidney. Transitional cell carcinoma forms in the renal pelvis and ureter. Wilms tumors are common in children. Find evidence-based information on kidney cancer treatment, research, genetics, and statistics.

Dual energy CT monitoring of the renal corticomedullary sodium gradient in swine

International Nuclear Information System (INIS)

Kumar, Rahi; Wang, Zhen J.; Forsythe, Carlos; Fu Yanjun; Chen, Yunn-Yi; Yeh, Benjamin M.

2012-01-01

Objective: To evaluate the feasibility of dual-energy CT (DECT) for monitoring dynamic changes in the renal corticomedullary sodium gradient in swine. Material and methods: This study was approved by our Institutional Animal Care and Use Committee. Four water-restricted pigs were CT-scanned at 80 and 140 kVp at baseline and at 5 min intervals for 30 min during saline or furosemide diuresis. The renal cortical and medullary CT numbers were recorded. A DECT basis material decomposition method was used to quantify renal cortical and medullary sodium concentrations and medulla-to-cortex sodium ratios at each time point based on the measured CT numbers. The sodium concentrations and medulla-to-cortex sodium ratios were compared between baseline and at 30 min diuresis using paired Student t-tests. The medulla-to-cortex sodium ratios were considered to reflect the corticomedullary sodium gradient. Results: At baseline prior to saline diuresis, the mean medullary and cortical sodium concentrations were 103.8 ± 8.7 and 65.3 ± 1.7 mmol/l, respectively, corresponding to a medulla-to-cortex sodium ratio of 1.59. At 30 min of saline diuresis, the medullary and cortical sodium concentrations decreased to 72.3 ± 1.0 and 56.0 ± 1.4 mmol/l, respectively, corresponding to a significantly reduced medulla-to-cortex sodium ratio of 1.29 (P < 0.05). At baseline prior to furosemide diuresis, the mean medullary and cortical sodium concentrations were 110.5 ± 3.6 and 66.7 ± 4.1 mmol/l, respectively, corresponding to a medulla-to-cortex sodium ratio of 1.66. At 30 min of furosemide diuresis, the medullary and cortical sodium concentrations decreased to 68.5 ± 0.3 and 58.9 ± 4.0 mmol/l, respectively, corresponding to a significantly reduced medulla-to-cortex sodium ratio of 1.16 (P < 0.05). One of the 4 pigs developed acute tubular necrosis likely related to prolonged hypoxia during intubation prior to the furosemide diuresis experiment. The medulla-to-cortex sodium ratio for this

Medullary thyroid cancer: RET testing of an archival material

DEFF Research Database (Denmark)

Godballe, Christian; Jørgensen, Gita; Gerdes, Anne-Marie Axø

2010-01-01

Medullary thyroid carcinoma (MTC) might be sporadic (75%) or hereditary (25%). Until the mid nineties the diagnosis of hereditary MTC was based on family history, clinical evaluation, histological detection of C-cell hyperplasia and tumor multifocality. Patients and families with hereditary MTC...

Medullary thyroid cancer: RET testing of an archival material

DEFF Research Database (Denmark)

Godballe, Christian; Jørgensen, Gita; Gerdes, Anne-Marie

2009-01-01

Medullary thyroid carcinoma (MTC) might be sporadic (75%) or hereditary (25%). Until the mid nineties the diagnosis of hereditary MTC was based on family history, clinical evaluation, histological detection of C-cell hyperplasia and tumor multifocality. Patients and families with hereditary MTC...

Apical P2XR contribute to [Ca2+]i signaling and Isc in mouse renal MCD.

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Li, Liuzhe; Lynch, I Jeanette; Zheng, Wencui; Cash, Melanie N; Teng, Xueling; Wingo, Charles S; Verlander, Jill W; Xia, Shen-Ling

2007-08-03

We examined P2X receptor expression and distribution in the mouse collecting duct (CD) and their functional role in Ca(2+) signaling. Both P2X(1) and P2X(4) were detected by RT-PCR and Western blot. Immunohistochemistry demonstrated apical P2X(1) and P2X(4) immunoreactivity in principal cells in the outer medullary CD (OMCD) and inner medullary CD (IMCD). Luminal ATP induced an increase in Ca(2+) signaling in native medullary CD (MCD) as measured by fluorescence imaging. ATP also induced an increase in Ca(2+) signaling in MCD cells grown in primary culture but not in the presence of P2XR antagonist PPNDS. Short circuit current (I(sc)) measurement with mouse IMCD cells showed that P2XR agonist BzATP induced a larger I(sc) than did P2YR agonist UTP in the apical membrane. Our data reveal for the first time that P2X(1) and P2X(4) are cell-specific with prominent immunoreactivity in the apical area of MCD cells. The finding that P2XR blockade inhibits ATP-induced Ca(2+) signaling suggests that activation of P2XR is a key step in Ca(2+)-dependent purinergic signaling. The result that activation of P2XR produces large I(sc) indicates the necessity of P2XR in renal CD ion transport.

Magnetization Transfer Magnetic Resonance Imaging Noninvasively Detects Renal Fibrosis in Swine Atherosclerotic Renal Artery Stenosis at 3.0 T.

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Jiang, Kai; Ferguson, Christopher M; Woollard, John R; Zhu, Xiangyang; Lerman, Lilach O

2017-11-01

Renal fibrosis is a useful biomarker for diagnosis and evaluation of therapeutic interventions of renal diseases but often requires invasive testing. Magnetization transfer magnetic resonance imaging (MT-MRI), which evaluates the presence of macromolecules, offers a noninvasive tool to probe renal fibrosis in murine renal artery stenosis (RAS) at 16.4 T. In this study, we aimed to identify appropriate imaging parameters for collagen detection at 3.0 T MRI and to test the utility of MT-MRI in measuring renal fibrosis in a swine model of atherosclerotic RAS (ARAS). To select the appropriate offset frequency, an MT-MRI study was performed on a phantom containing 0% to 40% collagen I and III with offset frequencies from -1600 to +1600 Hz and other MT parameters empirically set as pulse width at 16 milliseconds and flip angle at 800 degrees. Then selected MT parameters were used in vivo on pigs 12 weeks after sham (n = 8) or RAS (n = 10) surgeries. The ARAS pigs were fed with high-cholesterol diet to induce atherosclerosis. The MT ratio (MTR) was compared with ex vivo renal fibrosis measured using Sirius-red staining. Offset frequencies at 600 and 1000 Hz were selected for collagen detection without direct saturation of free water signal, and subsequently applied in vivo. The ARAS kidneys showed mild cortical and medullary fibrosis by Sirius-red staining. The cortical and medullary MTRs at 600 and 1000 Hz were both increased. Renal fibrosis measured ex vivo showed good linear correlations with MTR at 600 (cortex: Pearson correlation coefficient r = 0.87, P 3.0 T. Therefore, MT-MRI may potentially be clinically applicable and useful for detection and monitoring of renal pathology in subjects with RAS.

A bioartificial renal tubule device embedding human renal stem/progenitor cells.

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Anna Giovanna Sciancalepore

Full Text Available We present a bio-inspired renal microdevice that resembles the in vivo structure of a kidney proximal tubule. For the first time, a population of tubular adult renal stem/progenitor cells (ARPCs was embedded into a microsystem to create a bioengineered renal tubule. These cells have both multipotent differentiation abilities and an extraordinary capacity for injured renal cell regeneration. Therefore, ARPCs may be considered a promising tool for promoting regenerative processes in the kidney to treat acute and chronic renal injury. Here ARPCs were grown to confluence and exposed to a laminar fluid shear stress into the chip, in order to induce a functional cell polarization. Exposing ARPCs to fluid shear stress in the chip led the aquaporin-2 transporter to localize at their apical region and the Na(+K(+ATPase pump at their basolateral portion, in contrast to statically cultured ARPCs. A recovery of urea and creatinine of (20±5% and (13±5%, respectively, was obtained by the device. The microengineered biochip here-proposed might be an innovative "lab-on-a-chip" platform to investigate in vitro ARPCs behaviour or to test drugs for therapeutic and toxicological responses.

Culture in embryonic kidney serum and xeno-free media as renal cell carcinoma and renal cell carcinoma cancer stem cells research model.

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Krawczyk, Krzysztof M; Matak, Damian; Szymanski, Lukasz; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M

2018-04-01

The use of fetal bovine serum hinders obtaining reproducible experimental results and should also be removed in hormone and growth factor studies. In particular hormones found in FBS act globally on cancer cell physiology and influence transcriptome and metabolome. The aim of our study was to develop a renal carcinoma serum free culture model optimized for (embryonal) renal cells in order to select the best study model for downstream auto-, para- or endocrine research. Secondary aim was to verify renal carcinoma stem cell culture for this application. In the study, we have cultured renal cell carcinoma primary tumour cell line (786-0) as well as human kidney cancer stem cells in standard 2D monolayer cultures in Roswell Park Memorial Institute Medium or Dulbecco's Modified Eagle's Medium and Complete Human Kidney Cancer Stem Cell Medium, respectively. Serum-free, animal-component free Human Embryonic Kidney 293 media were tested. Our results revealed that xeno-free embryonal renal cells optimized culture media provide a useful tool in RCC cancer biology research and at the same time enable effective growth of RCC. We propose bio-mimic RCC cell culture model with specific serum-free and xeno-free medium that promote RCC cell viability.

CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion.

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Rogers, Natasha M; Zhang, Zheng J; Wang, Jiao-Jing; Thomson, Angus W; Isenberg, Jeffrey S

2016-08-01

Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

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Hayam Abdel Meguid El Aggan

2013-09-01

Full Text Available Introduction: Chronic allograft nephropathy (CAN is a poorly understood clinico-pathological entity associated with chronic allograft loss due to immunologic and non-immunologic causes. It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs and mesenchymal stem cells (MSCs. Characterization of HSCs includes their multipotency, expression of typical surface markers such as CD34 and CD45, while characterization of MSC includes their multipotency, expression of typical surface markers such as CD90 and CD105, and the absence of hemopoietic lineage markers. Aim & methods: The aim of the present work was to study the role of bone marrow-derived HSCs and MSCs, renal progenitor cells and SCF in chronic renal allograft nephropathy in relation to renal hemodynamics and histopathological changes. We studied 30 patients with kidney transplantation for more than 6 months, divided into 15 patients with stable serum creatinine and 15 patients who developed CAN. Detection of HSCs and MSCs in the peripheral blood using flow cytometry via detection of CD34, CD45, CD117 and CD106, as well as immunohistochemical detection of CD34, CD133, VEGF and αSMA in transplanted kidney biopsies of patients with CAN were done. Results: There was a significant increase in the levels of SCF, number of peripheral blood HSCs and MSCs in both transplanted patient groups than the controls and they were higher in patients of group Ia than patients of group Ib, (F = 39.73, P < 0.001, (F = 13.28, P < 0.001, (F = 11.94, P < 0.001, respectively and this was accompanied by evident expression of markers of renal repair. Conclusion: Stem cells might have a role in renal regeneration in CAN and this may pave the way toward the use of stem cells in correction of CAN. KEYWORDS

Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

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2017-12-11

Adult Acute Myeloid Leukemia in Remission; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndrome; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndrome; Metastatic Renal Cell Cancer; Previously Treated Myelodysplastic Syndrome; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Renal Medullary Carcinoma; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

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Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-01

Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

Blood oxygenation level dependent (BOLD). Renal imaging. Concepts and applications

International Nuclear Information System (INIS)

Nissen, Johanna C.; Haneder, Stefan; Schoenberg, Stefan O.; Michaely, Henrik J.

2010-01-01

Many renal diseases as well as several pharmacons cause a change in renal blood flow and/or renal oxygenation. The blood oxygenation level dependent (BOLD) imaging takes advantage of local field inhomogeneities and is based on a T2 * -weighted sequence. BOLD is a non-invasive method allowing an estimation of the renal, particularly the medullary oxygenation, and an indirect measurement of blood flow without administration of contrast agents. Thus, effects of different drugs on the kidney and various renal diseases can be controlled and observed. This work will provide an overview of the studies carried out so far and identify ways how BOLD can be used in clinical studies. (orig.)

Metastatic renal cell carcinoma management

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Flavio L. Heldwein

2009-06-01

Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

Impact of Mannose-Binding Lectin Deficiency on Radiocontrast-Induced Renal Dysfunction

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Michael Osthoff

2013-01-01

Full Text Available Contrast-induced nephropathy (CIN is the third leading cause of acute renal failure in hospitalized patients. Endothelial dysfunction, renal medullary ischemia, and tubular toxicity are regarded as the most important factors in the pathogenesis of CIN. Mannose-binding lectin (MBL, a pattern recognition protein of the lectin pathway of complement, has been found to aggravate and mediate tissue damage during experimental renal ischemia/reperfusion (I/R injury which was alleviated by inhibition with C1 inhibitor, a potent MBL, and lectin pathway inhibitor. In this paper, we highlight the potential role of MBL in the pathogenesis of human CIN. In experimental I/R models, MBL was previously found to induce tubular cell death independent of the complement system. In addition, after binding to vascular endothelial cells, MBL and its associated serine proteases were able to trigger a proinflammatory reaction and contribute to endothelial dysfunction. In humans, urinary MBL was increased after administration of contrast media and in individuals with CIN. Moreover, individuals with normal/high MBL levels were at increased risk to develop radiocontrast-induced renal dysfunction. Hence, MBL and the lectin pathway seem to be a promising target given that a licensed, powerful, human recombinant inhibitor exits to be added to the scarce armamentarium currently available for prophylaxis of CIN.

NMR studies of renal phosphate metabolites in vivo: Effects of hydration and dehydration

International Nuclear Information System (INIS)

Wolff, S.D.; Eng, C.; Balaban, R.S.

1988-01-01

The present study characterizes the 31 P-nuclear magnetic resonance (NMR) spectrum of rabbit kidneys in vivo and evaluates the effect of hydration on phosphorous metabolites including the organic solute glycerophosphorylcholine (GPC). Cortical phosphorylethanolamine is the predominant component of the phosphomonoester region of the 31 P spectrum. The contribution of blood to the spectrum is mainly from 2,3 diphosphoglycerate, which comprises ∼30% of the inorganic phosphate region. Acute infusion of 0.9% saline decreases the sodium content of the inner medulla by >50% in 15 min as shown by 23 Na imaging. Despite this medullary Na dilution, no change in renal GPC content was observed for >1 h even with the addition of furosemide or furosemide and antidiuretic hormone. However, 20 h of chronic dehydration with 0.45% saline did result in a 30% decrease in renal GPC content when compared with dehydrated animals. These findings are consistent with GPC not playing a role in the short-term regulation of the medullary intracellular milieu in response to acute reductions in medullary Na content

CT staging of renal cell carcinoma

International Nuclear Information System (INIS)

Spina, Juan C.; Garcia, Adriana T.; Rogondino, Jose; Spina, Juan C. h; Vidales, Valeria; Troiani, Guillermo; Iotti, Alejandro; Venditti, Julio

2002-01-01

Objective: To assess the usefulness of computerized tomography (CT) in the characterization of renal masses, in order to stage them, determine their prognosis and their appropriate clinical and/or surgical management. Material and Methods: Between 1988 and 2001, we selected 63 patients with renal tumors that had been examined by pathology. Patient's ages ranged from 16 to 88 years (25 women, 38 men). The studies were performed with a sequential helical CT, using 5 mm thickness sections every 5mm evaluating the cortico medullar and nephrographic phases. Renal tumors were characterized and staged without any knowledge about the pathological findings; subsequently the tomographic characteristics were compared to such findings. The following characteristics were evaluated: 1) mixed solid-cystic nature; 2) size; 3) borders; 4) enhancement; 5) necrosis; 6) hemorrhage; 7) central scar; 8) presence of fat; 9) collecting system; 10) capsular invasion; 11) perirenal fat invasion; 12) vessels; 13) Gerota's fascia; 14) lymph nodes; and 15) local and/or distant metastases. Results: Of the 63 tumors, 2 were complicated cysts; of the 61 remaining tumors, 10 were angiomyolipomas, 1 was a renal lymphoma, 1 was a focal xantogranulomatose pyelonephritis, 1 was a metanephric adenoma, 3 papillary renal cell carcinoma (RCC), 4 transitional cell tumors, 4 oncocytomas, 37 clear cell renal carcinoma. The CT could correctly characterize the 2 cystic tumors as such, as well as the 9 angiomyolipomas and the 4 transitional cell tumors. The 48 other tumors (1 angiomyolipoma, 1 lymphoma, 1 focal xantogranulomatose pyelonephritis, 1 metanephric adenoma, 3 papillary RCC, 4 oncocytomas, and 37 cell renal carcinomas) remaining were characterized as renal adenocarcinomas and CT staged. Conclusion: CT is a useful method to characterize renal masses since it determines their solid-cystic or fatty structure; aiding in many cases to define a surgical treatment. For the CT staging of renal tumors, the

Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels

DEFF Research Database (Denmark)

Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D

2001-01-01

The distribution of voltage-dependent calcium channels in kidney pre- and postglomerular resistance vessels was determined at the molecular and functional levels. Reverse transcription-polymerase chain reaction analysis of microdissected rat preglomerular vessels and cultured smooth muscle cells...... on vascular diameter in the afferent arteriole. We conclude that voltage-dependent L- and T-type calcium channels are expressed and of functional significance in renal cortical preglomerular vessels, in juxtamedullary efferent arterioles, and in outer medullary vasa recta, but not in cortical efferent...

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

Science.gov (United States)

Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-14

Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

Triiodothyronine regulates cell growth and survival in renal cell cancer.

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Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

2016-10-01

Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

How Kidney Cell Death Induces Renal Necroinflammation.

Science.gov (United States)

Mulay, Shrikant R; Kumar, Santhosh V; Lech, Maciej; Desai, Jyaysi; Anders, Hans-Joachim

2016-05-01

The nephrons of the kidney are independent functional units harboring cells of a low turnover during homeostasis. As such, physiological renal cell death is a rather rare event and dead cells are flushed away rapidly with the urinary flow. Renal cell necrosis occurs in acute kidney injuries such as thrombotic microangiopathies, necrotizing glomerulonephritis, or tubular necrosis. All of these are associated with intense intrarenal inflammation, which contributes to further renal cell loss, an autoamplifying process referred to as necroinflammation. But how does renal cell necrosis trigger inflammation? Here, we discuss the role of danger-associated molecular patterns (DAMPs), mitochondrial (mito)-DAMPs, and alarmins, as well as their respective pattern recognition receptors. The capacity of DAMPs and alarmins to trigger cytokine and chemokine release initiates the recruitment of leukocytes into the kidney that further amplify necroinflammation. Infiltrating neutrophils often undergo neutrophil extracellular trap formation associated with neutrophil death or necroptosis, which implies a release of histones, which act not only as DAMPs but also elicit direct cytotoxic effects on renal cells, namely endothelial cells. Proinflammatory macrophages and eventually cytotoxic T cells further drive kidney cell death and inflammation. Dissecting the molecular mechanisms of necroinflammation may help to identify the best therapeutic targets to limit nephron loss in kidney injury. Copyright © 2016 Elsevier Inc. All rights reserved.

OCTREOTIDE FOR MEDULLARY-THYROID CARCINOMA ASSOCIATED DIARRHEA

NARCIS (Netherlands)

SMID, WM; DULLAART, RPF

Medullary thyroid carcinoma associated diarrhoea can be disabling. A 75-yr-old man with metastatic medullary thyroid carcinoma and refractory diarrhoea is described. Subcutaneous administration of the somatostatin analogue, octreotide, 100-mu-g thrice daily, resulted in a sustained improvement in

MEDULLARY THYROID CARCINOMA

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V. S. Medvedev

2013-01-01

Full Text Available Medullary thyroid carcinoma belongs to orphan diseases affecting a small part of the population. Multicenter trials are required to elaborate a diagnostic algorithm, to define treatment policy, and to predict an outcome.

Drugs Approved for Kidney (Renal Cell) Cancer

Science.gov (United States)

... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

Science.gov (United States)

Cheng, Shaun Kian Hong; Chuah, Khoon Leong

2016-06-01

The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

Renal water molecular diffusion characteristics in healthy native kidneys: assessment with diffusion tensor MR imaging.

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Zhenfeng Zheng

Full Text Available BACKGROUND: To explore the characteristics of diffusion tensor imaging (DTI and magnetic resonance (MR imaging in healthy native kidneys. METHODS: Seventy-three patients without chronic kidney disease underwent DTI-MRI with spin echo-echo planar (SE-EPI sequences accompanied by an array spatial sensitivity encoding technique (ASSET. Cortical and medullary mean, axial and radial diffusivity (MD, AD and RD, fractional anisotropy (FA and primary, secondary and tertiary eigenvalues (λ1, λ2, λ3 were analysed in both kidneys and in different genders. RESULTS: Cortical MD, λ2, λ3, and RD values were higher than corresponding medullary values. The cortical FA value was lower than the medullary FA value. Medullary λ1 and RD values in the left kidney were lower than in the right kidney. Medullary λ2, and λ3 values in women were higher than those in men. Medullary FA values in women were lower than those in men. Medullary FA (r = 0.351, P = 0.002 and λ1 (r = 0.277, P = 0.018 positively correlated with eGFR. Medullary FA (r = -0.25, P = 0.033 negatively correlated with age. CONCLUSIONS: Renal water molecular diffusion differences exist in human kidneys and genders. Age and eGFR correlate with medullary FA and primary eigenvalue.

Medullary bone and humeral breaking strength in laying hens

International Nuclear Information System (INIS)

Fleming, R.H.; McCormack, H.A.; McTeir, L.; Whitehead, C.C.

1998-01-01

To test the hypothesis that large amounts of medullary bone in the humeral diaphysis may increase breaking strength, various parameters of bone quality and quantity were examined in two large flocks of hens near end of lay. We conclude that the amount of medullary bone in the humerus of hens during the laying period influences bone strength. This medullary bone may not have any intrinsic strength, but may act by contributing to the fracture resistance of the surrounding cortical bone. Using a quantitative, low dose, radiographic technique, we can predict, from early in the laying period, those birds which will develop large amounts of medullary bone in their humeri by the end of the laying period. The formation of medullary bone in the humeral diaphysis is not at the expense of the surrounding radiographed cortical bone

MR imaging of renal transplant rejection

International Nuclear Information System (INIS)

Hanna, S.; Helenon, O.; Legendre, C.; Chichie, J.F.; Di Stefano, D.; Kreis, H.; Moreau, J.F.; Hopital Necker, 75 - Paris

1991-01-01

The results of 62 consecutive MR examinations were correlated with the subsequent clinical course and histologic results. Twenty-six cases of rejection showed a marked diminution of cortico-medullary differentiation (CMD). The renal parenchymal vascular pattern and visibility of renal sinus fat were not markedly altered in rejection and there was no difference between normal and rejected allograft shape. The ability of MR imaging to diagnose renal transplant rejection is only based on CMD, which, however, is non-specific. In 2 cases of severe rejection, T2 weighted images showed an abnormal signal intensity of the cortex due to renal infarction. Our preliminary results in 8 patients with Gd-DOTA injection showed 2 cases with necrosis seen as areas with absent contrast enhancement. This technique seems to be promising in the detection of perfusion defects. (orig.)

RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

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Elisangela Giachini

2017-06-01

Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

Engineering kidney cells: reprogramming and directed differentiation to renal tissues.

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Kaminski, Michael M; Tosic, Jelena; Pichler, Roman; Arnold, Sebastian J; Lienkamp, Soeren S

2017-07-01

Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons. In addition, culture conditions are also defined that allow the expansion of renal progenitor cells in vitro. Another route towards the generation of kidney cells is direct reprogramming. Key transcription factors are used to directly impose renal cell identity on somatic cells, thus circumventing the pluripotent stage. This complementary approach to stem-cell-based differentiation has been demonstrated to generate renal tubule cells and nephron progenitors. In-vitro-generated renal cells offer new opportunities for modelling inherited and acquired renal diseases on a patient-specific genetic background. These cells represent a potential source for developing novel models for kidney diseases, drug screening and nephrotoxicity testing and might represent the first steps towards kidney cell replacement therapies. In this review, we summarize current approaches for the generation of renal cells in vitro and discuss the advantages of each approach and their potential applications.

[Plasma cell dyscrasias and renal damage].

Science.gov (United States)

Pasquali, Sonia; Iannuzzella, Francesco; Somenzi, Danio; Mattei, Silvia; Bovino, Achiropita; Corradini, Mattia

2012-01-01

Kidney damage caused by immunoglobulin free light chains in the setting of plasma cell dyscrasias is common and may involve all renal compartments, from the glomerulus to the tubulointerstitium, in a wide variety of histomorphological and clinical patterns. The knowledge of how free light chains can promote kidney injury is growing: they can cause functional changes, be processed and deposited, mediate inflammation, apoptosis and fibrosis, and obstruct nephrons. Each clone of the free light chain is unique and its primary structure and post-translation modification can determine the type of renal disease. Measurement of serum free light chain concentrations and calculation of the serum kappa/lambda ratio, together with renal biopsy, represent essential diagnostic tools. An early and correct diagnosis of renal lesions due to plasma cell dyscrasias will allow early initiation of disease-specific treatment strategies. The treatment of free light chain nephropathies is evolving and knowledge of the pathways that promote renal damage should lead to further therapeutic developments.

Medullary Thyroid Carcinoma Program | Center for Cancer Research

Science.gov (United States)

Medullary Thyroid Carcinoma Program Multiple endocrine neoplasia (MEN) types 2A and 2B are rare genetic diseases, which lead to the development of medullary thyroid cancer, usually in childhood. Surgery is the only standard treatment.

Epidemiologic characteristics and risk factors for renal cell cancer

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Loren Lipworth

2009-04-01

Full Text Available Loren Lipworth1,2, Robert E Tarone1,2, Lars Lund2,3, Joseph K McLaughlin1,21International Epidemiology Institute, Rockville, MD, USA; 2Department of Medicine (JKM, RET and Preventive Medicine (LL, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 3Department of Urology, Viborg Hospital, Viborg, DenmarkAbstract: Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches

Culture and Characterization of Circulating Endothelial Progenitor Cells in Patients with Renal Cell Carcinoma.

Science.gov (United States)

Gu, Wenyu; Sun, Wei; Guo, Changcheng; Yan, Yang; Liu, Min; Yao, Xudong; Yang, Bin; Zheng, Junhua

2015-07-01

Although emerging evidence demonstrates increased circulating endothelial progenitor cells in patients with solid tumors, to our knowledge it is still unknown whether such cells can be cultured from patients with highly angiogenic renal cell carcinoma. We cultured and characterized circulating endothelial progenitor cells from patients with renal cell carcinoma. The circulating endothelial progenitor cell level (percent of CD45(-)CD34(+) VEGF-R2(+) cells in total peripheral blood mononuclear cells) was quantified in 47 patients with renal cell carcinoma and 40 healthy controls. Peripheral blood mononuclear cells were then isolated from 33 patients with renal cell carcinoma and 30 healthy controls to culture and characterize circulating endothelial progenitor cells. The circulating endothelial progenitor cell level was significantly higher in patients with renal cell carcinoma than in healthy controls (0.276% vs 0.086%, p cells first emerged significantly earlier in patient than in control preparations (6.72 vs 14.67 days, p culture success rate (87.8% vs 40.0% of participants) and the number of colonies (10.06 vs 1.83) were significantly greater for patients than for controls (each p cell level correlated positively with the number of patient colonies (r = 0.762, p Cells cultured from patients and controls showed a similar growth pattern, immunophenotype, ability to uptake Ac-LDL and bind lectin, and form capillary tubes in vitro. However, significantly more VEGF-R2(+) circulating endothelial progenitor cells were found in preparations from patients with renal cell carcinoma than from healthy controls (21.1% vs 13.4%, p cell colonies, a higher cell culture success rate and more colonies were found for patients with renal cell carcinoma than for healthy controls. Results indicate the important significance of VEGF-R2(+) circulating endothelial progenitors in patients with renal cell carcinoma. Copyright © 2015 American Urological Association Education and Research

Rate of renal cell carcinoma subtypes in different races

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Alexander Sankin

2011-02-01

Full Text Available PURPOSE: We sought to identify racial differences among histological subtypes of renal cell carcinoma (RCC between black and non-black patients in an equal-access health care system. MATERIALS AND METHODS: We established a multi-institutional, prospective database of patients undergoing partial or radical nephrectomy between January 1, 2000 and Sept 31, 2009. For the purposes of this study, data captured included age at diagnosis, race, tumor size, presence of lymphovascular invasion, presence of capsular invasion, margin status, and tumor histology. RESULTS: 204 kidney tumors were identified (Table-1. Of these, 117 (57.4% were in black patients and 87 (42.6% were in non-black patients. Age at surgery ranged from 37 to 87 with a median of 62. Tumor size ranged from 1.0 to 22.0 cm with a median of 5.0 cm. Overall, tumors were composed of clear cell RCC in 97 cases (47.5%, papillary RCC in 65 cases (31.9%, chromophobe RCC in 13 cases (6.4%, collecting duct/medullary RCC in 2 cases (1.0%, RCC with multiple histological subtypes in 8 cases (3.9%, malignant tumors of other origin in 6 cases (2.9%, and benign histology in 13 cases (6.4%. Among black patients, papillary RCC was seen in 56 cases (47.9%, compared to 9 cases (10.3% among non-black patients (p < 0.001 (Table-2. Clear cell RCC was present in 38 (32.5% of black patients and in 59 (67.8% of non-blacks (p < 0.001. CONCLUSIONS: In our study, papillary RCC had a much higher occurrence among black patients compared to non-black patients. This is the first study to document such a great racial disparity among RCC subtypes.

Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

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Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

2014-09-15

Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

The relationship of mast cells and angiogenesis with prognosis in renal cell carcinoma

International Nuclear Information System (INIS)

Guldur, M.E.; Kocarslan, S.; Dincoglu, D.

2014-01-01

Objective: To evaluate the effects of mast cell count and angiogenesis on the prognosis of renal cell carcinoma. Methods: The retrospective study was conducted at the Harran University, Sanliurfa, Turkey, and included 64 cases with diagnosis of renal cell carcinoma between 2002 and 2012. Immunohistochemical analysis was performed on paraffin sections using the standard streptavidin-biotin immunoperoxidase method. CD31 antibodies were used to identify microvessels in tumoural tissues. The microvessel density was calculated using a serological method. The mean vascular density was equivalent to the vascular surface area (in mm) per unit tissue volume (in mm) (MVD=mm). Mast cells tryptase antibody was used to evaluate the mast cell count in tumoural and non-tumoural tissues. The relationship between mast cell count and microvessel density was evaluated and compared with stage, grade, tumour diameter, and age. Results: The mast cell count in the tumoral tissue of renal cell carcinoma was significantly higher compared with non-neoplastic renal tissue (p 0.05). The intratumoural mast cell count in clear cell renal carcinoma was significantly higher compared with non-clear variety (p=0.001). No significant relationship was found between microvessel density, age, stage, diameter, or grade of the tumour and tumoral mast cell count (p>0.05). Conclusion: No significant association was found between the number of mast cells in tumoral tissue and microvessel density. Further studies are needed to demonstrate the effect of mast cells on angiogenesis in renal cell carcinoma. (author)

Extramedullary plasmacytoma of thyroid - a mimicker of medullary carcinoma at fine needle aspiration cytology: A case report

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Vidya Bhat

2014-01-01

Full Text Available A rare case of extra medullary plasmacytoma (EMP of thyroid gland in a 60 year old male, occurring against a background of Hashimoto′s thyroiditis is reported. The fine needle aspiration cytology (FNAC initially done as an outpatient procedure, showed atypical epithelial cells on a background of amyloid. Considering these findings we gave a diagnosis of medullary carcinoma. Histology of the total thyroidectomy specimen showed an extensive infiltration of neoplastic plasma cells against a background of Hashimoto′s thyroiditis, with a bizarre Hurthle cell change. Immunohistochemistry on the histology sections confirmed the diagnosis of solitary plasmacytoma of thyroid against a background of Hashimoto′s thyroiditis.

Asymptomatic renal cell carcinoma incidentally detected by abdominal CT

International Nuclear Information System (INIS)

Yoneda, Fumio; Miyake, Noriaki; Tsujimura, Haruhiro; Nakajima, Mikio; Akiyama, Hajime

1987-01-01

Four cases of renal cell carcinoma that were incidentally detected by abdominal CT are reported. Abdominal CT was performed during gastro-intestinal examination in two patients and for suspected liver disease in the other two. No patient had symptoms of renal cell carcinoma, or hematuria. In all cases, the histopathological diagnosis was renal cell carcinoma of a low stage. (author)

Pazopanib-Induced Hypertension in Patients With Renal Cell Carcinoma Is Associated With Low Urine Excretion of NO Metabolites

DEFF Research Database (Denmark)

Tinning, Anne Robdrup; Bengtsen, Camilla; Jensen, Niels Viggo

2018-01-01

-NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1. With a single-center prospective observational design, patients with metastatic...... increased, whereas heart rate decreased significantly; urine protein/creatinine ratio increased significantly, whereas estimated glomerular filtration rate was unchanged. Urine nitrite/nitrate (NOx) and cGMP/creatinine ratios decreased significantly, whereas urine endothelin-1/creatinine ratio and FENa...

Renal Artery Embolization of Perirenal Hematoma in Hemorrhagic Fever with Renal Syndrome: A Case Report

International Nuclear Information System (INIS)

Choi, Hee Seok; Lee, Yong Seok; Lim, Ji Hyon; Kim, Kyung Soo; Yoon, Yup; Hwang, Jae Cheol

2007-01-01

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease characterized by fever, hemorrhage and renal failure. Among the various hemorrhagic complications of HFRS, spontaneous rupture of the kidney and perirenal hematoma are very rare findings. We report here on a case of HFRS complicated by massive perirenal hematoma, and this was treated with transcatheter arterial embolization. Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease caused by hantavirus. HFRS is clinically characterized by fever, renal failure and hemorrhage in organs such as lung, kidney, spleen and the pituitary gland. Renal medullary hemorrhage is a well-known complication in the kidney, but spontaneous rupture of the kidney and perirenal hematoma in HFRS is rare, and patients showing continuous bleeding and massive perirenal hematoma have often been surgically treated. We report here on a case of HFRS complicated by massive perirenal hematoma, and the patient was treated with transcatheter arterial embolization. In summary, spontaneous rupture of the kidney and perirenal hematoma is a rare complication of HFRS. We report here on a case of HFRS that caused massive perirenal hematoma, and this was treated with superselective renal artery embolization

Renal Artery Embolization of Perirenal Hematoma in Hemorrhagic Fever with Renal Syndrome: A Case Report

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Choi, Hee Seok; Lee, Yong Seok; Lim, Ji Hyon; Kim, Kyung Soo; Yoon, Yup [Dongguk University College of Medicine, Goyang (Korea, Republic of); Hwang, Jae Cheol [Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of)

2007-08-15

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease characterized by fever, hemorrhage and renal failure. Among the various hemorrhagic complications of HFRS, spontaneous rupture of the kidney and perirenal hematoma are very rare findings. We report here on a case of HFRS complicated by massive perirenal hematoma, and this was treated with transcatheter arterial embolization. Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease caused by hantavirus. HFRS is clinically characterized by fever, renal failure and hemorrhage in organs such as lung, kidney, spleen and the pituitary gland. Renal medullary hemorrhage is a well-known complication in the kidney, but spontaneous rupture of the kidney and perirenal hematoma in HFRS is rare, and patients showing continuous bleeding and massive perirenal hematoma have often been surgically treated. We report here on a case of HFRS complicated by massive perirenal hematoma, and the patient was treated with transcatheter arterial embolization. In summary, spontaneous rupture of the kidney and perirenal hematoma is a rare complication of HFRS. We report here on a case of HFRS that caused massive perirenal hematoma, and this was treated with superselective renal artery embolization.

Simultaneous Infiltration of Polyfunctional Effector and Suppressor T Cells into Renal Cell Carcinomas

NARCIS (Netherlands)

Attig, Sebastian; Hennenlotter, Jörg; Pawelec, Graham; Klein, Gerd; Koch, Sven D.; Pircher, Hanspeter; Feyerabend, Susan; Wernet, Dorothee; Stenzl, Arnulf; Rammensee, Hans-Georg; Gouttefangeas, Cécile

2009-01-01

Renal cell carcinoma is frequently infiltrated by cells of the immune system. This makes it important to understand interactions between cancer cells and immune cells so they can be manipulated to bring clinical benefit. Here, we analyze subsets and functions of T lymphocytes infiltrating renal cell

Renal stem cells: fact or science fiction?

Science.gov (United States)

McCampbell, Kristen K; Wingert, Rebecca A

2012-06-01

The kidney is widely regarded as an organ without regenerative abilities. However, in recent years this dogma has been challenged on the basis of observations of kidney recovery following acute injury, and the identification of renal populations that demonstrate stem cell characteristics in various species. It is currently speculated that the human kidney can regenerate in some contexts, but the mechanisms of renal regeneration remain poorly understood. Numerous controversies surround the potency, behaviour and origins of the cell types that are proposed to perform kidney regeneration. The present review explores the current understanding of renal stem cells and kidney regeneration events, and examines the future challenges in using these insights to create new clinical treatments for kidney disease.

Renal epithelioid angiomyolipoma presenting clinically as renal cell ...

African Journals Online (AJOL)

M.S. Johnson

a Detroit Medical Center, Michigan State University School of Osteopathic Medicine, Detroit, MI, USA .... Immunohistochemically, the tumor cells stained strongly positive .... [10] Cao Q, Liu F, Xiao P, Tian X, Li B, Li Z. Coexistence of renal.

H+, Water and Urea Transport in the Inner Medullary Collecting Duct and Their Role in the Prevention and Pathogenesis of Renal Stone Disease

Science.gov (United States)

Wall, Susan M.; Klein, Janet D.

2008-09-01

The inner medullary collecting duct (IMCD) is the final site within the kidney for the reabsorption of urea, water and electrolytes and for the secretion of H+ before the luminal fluid becomes the final urine. Transporters expressed in the IMCD contribute to the generation of the large ion gradients that exist between the interstitium and the collecting duct lumen. Thus, the luminal fluid within the human IMCD can reach an osmolality of 1200 mOsm/kg H2O and a pH of 4. This ability of the human nephron to concentrate and acidify the urine might predispose to stone formation. However, under treatment conditions that predispose to stone formation, such as during hypercalciuria, the kidney mitigates stone formation by reducing solute concentration by reducing H2O reabsorption. Moreover, the kidney attenuates stone formation by tightly controlling acid-base balance, which prevents the bone loss, hypocitraturia and hypercalciuria observed during metabolic acidosis by augmenting net H+ excretion by tightly regulating H+ transporter function and through luminal buffering, particularly with NH3. This article will review the ion transporters present in the mammalian IMCD and their role in the prevention and in the pathogenesis of renal stone formation.

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

Science.gov (United States)

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

2017-02-01

Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

Metastatic renal cell carcinoma in the nasopharynx.

Science.gov (United States)

Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

2013-01-01

Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient's clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

Metastatic renal cell carcinoma in the nasopharynx

Directory of Open Access Journals (Sweden)

Yavuz Atar

2013-01-01

Full Text Available Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient′s clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

Dynamic computed tomography (CT) in the rat kidney and application to acute renal failure models

International Nuclear Information System (INIS)

Ishikawa, Isao; Saito, Tadashi; Ishii, Hirofumi; Bansho, Junichi; Koyama, Yukinori; Tobita, Akira

1995-01-01

Renal dynamic CT scanning is suitable for determining the excretion of contrast medium in the cortex and medulla of the kidney, which is valuable for understanding the pathogenesis of disease processes in various conditions. This form of scanning would be convenient for use, if a method of application to the rat kidney were available. Therefore, we developed a method of applying renal dynamic CT to rats and evaluated the cortical and medullary curves, e.g., the corticomedullary junction time which is correlated to creatinine clearance, in various rat models of acute renal failure. The rat was placed in a 10deg oblique position and a bilateral hilar slice was obtained before and 5, 10, 15, 20, 25, 30, 40, 50, 60, 80, 100, 120, 140, 160 and 180 sec after administering 0.5 ml of contrast medium using Somatom DR. The width of the slice was 4 mm and the scan time was 3 sec. The corticomedullary junction time in normal rats was 23.0±10.5 sec, the peak value of the cortical curve was 286.3±76.7 Hounsfield Unit (HU) and the peak value of the medullary curve was 390.1±66.2 HU. Corticomedullary junction time after exposure of the kidney was prolonged compared to that of the unexposed kidney. In rats with acute renal failure, the excretion pattern of contrast medium was similar in both the glycerol- and HgCl2-induced acute renal failure models. The peak values of the cortical curve were maintained three hours after a clamp was placed at the hilar region of the kidney for one hour, and the peak values of the medullary curve were maintained during the administration of 10μg/kg/min of angiotensin II. Dynamic CT curves in the acute renal failure models examined were slightly different from those in human acute renal failure. These results suggest that rats do not provide an ideal model for human acute renal failure. However, the application of dynamic CT to the rat kidney models was valuable for estimating the pathogenesis of various human kidney diseases. (author)

Prospective MR image alignment between breath-holds: Application to renal BOLD MRI.

Science.gov (United States)

Kalis, Inge M; Pilutti, David; Krafft, Axel J; Hennig, Jürgen; Bock, Michael

2017-04-01

To present an image registration method for renal blood oxygen level-dependent (BOLD) measurements that enables semiautomatic assessment of parenchymal and medullary R2* changes under a functional challenge. In a series of breath-hold acquisitions, three-dimensional data were acquired initially for prospective image registration of subsequent BOLD measurements. An algorithm for kidney alignment for BOLD renal imaging (KALIBRI) was implemented to detect the positions of the left and right kidney so that the kidneys were acquired in the subsequent BOLD measurement at consistent anatomical locations. Residual in-plane distortions were corrected retrospectively so that semiautomatic dynamic R2* measurements of the renal cortex and medulla become feasible. KALIBRI was tested in six healthy volunteers during a series of BOLD experiments, which included a 600- to 1000-mL water challenge. Prospective image registration and BOLD imaging of each kidney was achieved within a total measurement time of about 17 s, enabling its execution within a single breath-hold. KALIBRI improved the registration by up to 35% as found with mutual information measures. In four volunteers, a medullary R2* decrease of up to 40% was observed after water ingestion. KALIBRI improves the quality of two-dimensional time-resolved renal BOLD MRI by aligning local renal anatomy, which allows for consistent R2* measurements over many breath-holds. Magn Reson Med 77:1573-1582, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Architecture of interstitial nodal spaces in the rodent renal inner medulla.

Science.gov (United States)

Gilbert, Rebecca L; Pannabecker, Thomas L

2013-09-01

Every collecting duct (CD) of the rat inner medulla is uniformly surrounded by about four abutting ascending vasa recta (AVR) running parallel to it. One or two ascending thin limbs (ATLs) lie between and parallel to each abutting AVR pair, opposite the CD. These structures form boundaries of axially running interstitial compartments. Viewed in transverse sections, these compartments appear as four interstitial nodal spaces (INSs) positioned symmetrically around each CD. The axially running compartments are segmented by interstitial cells spaced at regular intervals. The pairing of ATLs and CDs bounded by an abundant supply of AVR carrying reabsorbed water, NaCl, and urea make a strong argument that the mixing of NaCl and urea within the INSs and countercurrent flows play a critical role in generating the inner medullary osmotic gradient. The results of this study fully support that hypothesis. We quantified interactions of all structures comprising INSs along the corticopapillary axis for two rodent species, the Munich-Wistar rat and the kangaroo rat. The results showed remarkable similarities in the configurations of INSs, suggesting that the structural arrangement of INSs is a highly conserved architecture that plays a fundamental role in renal function. The number density of INSs along the corticopapillary axis directly correlated with a loop population that declines exponentially with distance below the outer medullary-inner medullary boundary. The axial configurations were consistent with discrete association between near-bend loop segments and INSs and with upper loop segments lying distant from INSs.

Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

Directory of Open Access Journals (Sweden)

Todenhöfer Tilman

2012-03-01

Full Text Available Abstract Background Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma. Case presentation A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable. Conclusions Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.

Giant kidney worms in a patient with renal cell carcinoma.

Science.gov (United States)

Kuehn, Jemima; Lombardo, Lindsay; Janda, William M; Hollowell, Courtney M P

2016-03-07

Dioctophyma renale (D. renale), or giant kidney worms, are the largest nematodes that infect mammals. Approximately 20 cases of human infection have been reported. We present a case of a 71-year-old man with a recent history of unintentional weight loss and painless haematuria, passing elongated erythematous tissue via his urethra. CT revealed a left renal mass with pulmonary nodules and hepatic lesions. On microscopy, the erythematous tissue passed was identified as D. renale. On subsequent renal biopsy, pathology was consistent with renal cell carcinoma. This is the first reported case of concomitant D. renale infection and renal cell carcinoma, and the second reported case of D. renale infection of the left kidney alone. 2016 BMJ Publishing Group Ltd.

MR evaluation of renal function. A preliminary study

Energy Technology Data Exchange (ETDEWEB)

Beomonte Zobel, B; Giammarile, F; Matarese, A; Gallucci, M; Mascicchi, C; Passariello, R; Di Renzi, P; Splendiani, G; Casciani, C U

1988-01-01

The amount of functioning renal parenchyma can be estimated by MRI by considering the ratio between the mean intensities of cortical and medullar zones of the kidney. Fifty-six patients and 5 healthy volunteers were studied by MRI in our department. Scanning was performed with a superconductive magnet system operating at 0.5 Tesla. Pulse sequence was Spin-Echo with TR 300/TE 30 ms. The cortimedullary ratio (CMR) and differentiation (CMD) were standardized and related with creatine blood levels. CMR data ranged from 1.05 to 3.00, while CMD data ranged from 0.04 to 0.50. High values (good cortico-medullary contrast) were observed in subjects with normal renal function. Patients with renal diseases had low CMR and CMD, proportionally to the degree of renal failure, as proved by laboratory findings. Our preliminary study seems to demonstrate that MRI is an useful technique in the follow-up of patients with chronic renal disease. 19 refs.

Dragon (repulsive guidance molecule RGMb) inhibits E-cadherin expression and induces apoptosis in renal tubular epithelial cells.

Science.gov (United States)

Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y; Xia, Yin

2013-11-01

Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45-66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo.

Genetics Home Reference: hereditary leiomyomatosis and renal cell cancer

Science.gov (United States)

... Home Health Conditions HLRCC Hereditary leiomyomatosis and renal cell cancer Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary leiomyomatosis and renal cell cancer ( HLRCC ) is a disorder in which affected individuals ...

Recovery of Dysphagia in Lateral Medullary Stroke

Directory of Open Access Journals (Sweden)

Hitesh Gupta

2014-01-01

Full Text Available Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function.

Recovery of Dysphagia in lateral medullary stroke.

Science.gov (United States)

Gupta, Hitesh; Banerjee, Alakananda

2014-01-01

Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function.

Recovery of Dysphagia in Lateral Medullary Stroke

Science.gov (United States)

Gupta, Hitesh; Banerjee, Alakananda

2014-01-01

Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function. PMID:25045555

Synchronous presentation of nasopharyngeal and renal cell carcinomas

Directory of Open Access Journals (Sweden)

Cem Boruban

2006-06-01

Full Text Available We report a rare case of synchronous presentation of nasopharyngeal and renal cell carcinomas in a-50-year old male patient with long standing smoking history. The patient was initially presented with a diagnosis of nasopharyngeal carcinoma. During staging process, the abdominal computed tomography detected a right renal solid mass, 6.5 cm in diameter, originating from posterior portion of the right renal cortex. Right radical nephrectomy was performed and pathological examination revealed renal cell carcinoma. Smoking was thought to be a risk factor for both cancers. Systemic evaluation of kidney should not be discarded in patients diagnosed with nasopharyngeal carcinoma living in western countries with a smoking history.

Image-guided radiofrequency ablation of renal cell carcinoma

International Nuclear Information System (INIS)

Boss, Andreas; Clasen, Stephan; Pereira, Philippe L.; Kuczyk, Markus; Schick, Fritz

2007-01-01

The incidence of renal cell carcinoma is rising with the increased number of incidental detection of small tumours. During the past few years, percutaneous imaging-guided radiofrequency ablation has evolved as a minimally invasive treatment of small unresectable renal tumours offering reduced patient morbidity and overall health care costs. In radiofrequency ablation, thermal energy is deposited into a targeted tumour by means of a radiofrequency applicator. In recent studies, radiofrequency ablation was shown to be an effective and safe modality for local destruction of renal cell carcinoma. Radiofrequency applicator navigation can be performed via ultrasound, computed tomography or magnetic resonance guidance; however, ultrasound seems less favourable because of the absence of monitoring capabilities during ablation. On-line monitoring of treatment outcome can only be performed with magnetic resonance imaging giving the possibility of eventual applicator repositioning to ablate visible residual tumour tissue. Long-term follow-up is crucial to assess completeness of tumour ablation. New developments in ablation technology and radiological equipment will further increase the indication field for radiofrequency ablation of renal cell carcinoma. Altogether, radiofrequency ablation seems to be a promising new modality for the minimally invasive treatment of renal cell carcinoma, which was demonstrated to exhibit high short-term effectiveness. (orig.)

Hematopoietic stem cell mobilization therapy accelerates recovery of renal function independent of stem cell contribution

NARCIS (Netherlands)

Stokman, Geurt; Leemans, Jaklien C.; Claessen, Nike; Weening, Jan J.; Florquin, Sandrine

2005-01-01

Acute renal failure and tubular cell loss as a result of ischemia constitute major challenges in renal pathophysiology. Increasing evidence suggests important roles for bone marrow stem cells in the regeneration of renal tissue after injury. This study investigated whether the enhanced availability

Renal Sinus Fat Invasion and Tumoral Thrombosis of the Inferior Vena Cava-Renal Vein: Only Confined to Renal Cell Carcinoma

OpenAIRE

Turker Acar; Mustafa Harman; Serkan Guneyli; Sait Sen; Nevra Elmas

2014-01-01

Epithelioid angiomyolipoma (E-AML), accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS) and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC). In this...

Effect of indomethacin and salt depletion on renal proton MR imaging

International Nuclear Information System (INIS)

Heyman, S.N.; Mammen, M.

1991-01-01

Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti-inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may effect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non-steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion. (orig.)

Diagnosis of renal cell cancer by dynamic MRI

International Nuclear Information System (INIS)

Togami, Izumi; Kitagawa, Takahiro; Katoh, Katsuya

1992-01-01

Dynamic MRI was performed in 15 cases (16 lesions) of renal cell cancer. The enhanced pattern of the tumor was mainly evaluated and findings were compared with these of dynamic CT and renal angiography. Enhanced patterns on dynamic MRI and dynamic CT were similar, but each phase on dynamic MRI tended to be prolonged compared with dynamic CT. Many hypervascular tumors on renal angiography had prominent enhancement in an early phase on dynamic MRI, but there was no prominent enhancement in cases with tumor thrombi in the renal vein or IVC. All hypovascular tumors were enhanced to some degree without exception on dynamic MRI. Dynamic MRI is considered to be useful for the evaluation of the characterization, especially vascularity, of renal cell cancer, but we should pay attention to the differential diagnosis from other tumor in atypical cases because its enhanced patterns are various on dynamic MRI. (author)

Comparison of para-aminophenol cytotoxicity in rat renal epithelial cells and hepatocytes.

Science.gov (United States)

Li, Ying; Bentzley, Catherine M; Tarloff, Joan B

2005-04-01

Several chemicals, including para-aminophenol (PAP), produce kidney damage in the absence of hepatic damage. Selective nephrotoxicity may be related to the ability of the kidney to reabsorb filtered water, thereby raising the intraluminal concentration of toxicants and exposing tubular epithelial cells to higher concentrations than would be present in other tissues. The present experiments tested the hypothesis that hepatocytes and renal epithelial cells exposed to equivalent concentrations of PAP would be equally susceptible to toxicity. Hepatocytes and renal epithelial cells were prepared by collagenase digestion of tissues obtained from female Sprague-Dawley rats. Toxicity was monitored using trypan blue exclusion, oxygen consumption and ATP content. We measured the rate of PAP clearance and formation of PAP-glutathione conjugate by HPLC. We found that renal epithelial cells accumulated trypan blue and showed declines in oxygen consumption and ATP content at significantly lower concentrations of PAP and at earlier time points than hepatocytes. The half-life of PAP in hepatocyte incubations was significantly shorter (0.71+/-0.07 h) than in renal epithelial cell incubations (1.33+/-0.23 h), suggesting that renal epithelial cells were exposed to PAP for longer time periods than hepatocytes. Renal epithelial cells formed significantly less glutathione conjugates of PAP (PAP-SG) than did hepatocytes, consistent with less efficient detoxification of reactive PAP intermediates by renal epithelial cells. Finally, hepatocytes contained significant more reduced glutathione (NPSH) than did renal epithelial cells, possibly explaining the enhanced formation of PAP-SG by this cell population. In conclusion, our data indicates that renal epithelial cells are intrinsically more susceptible to PAP cytotoxicity than are hepatocytes. This enhanced cytotoxicity may be due to longer exposure to PAP and/or reduced detoxification of reactive intermediates due to lower concentrations

Quantification of deep medullary veins at 7 T brain MRI

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Kuijf, Hugo J.; Viergever, Max A.; Vincken, Koen L. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Bouvy, Willem H.; Razoux Schultz, Tom B.; Biessels, Geert Jan [University Medical Center Utrecht, Department of Neurology, Brain Center Rudolf Magnus, Utrecht (Netherlands); Zwanenburg, Jaco J.M. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands)

2016-10-15

Deep medullary veins support the venous drainage of the brain and may display abnormalities in the context of different cerebrovascular diseases. We present and evaluate a method to automatically detect and quantify deep medullary veins at 7 T. Five participants were scanned twice, to assess the robustness and reproducibility of manual and automated vein detection. Additionally, the method was evaluated on 24 participants to demonstrate its application. Deep medullary veins were assessed within an automatically created region-of-interest around the lateral ventricles, defined such that all veins must intersect it. A combination of vesselness, tubular tracking, and hysteresis thresholding located individual veins, which were quantified by counting and computing (3-D) density maps. Visual assessment was time-consuming (2 h/scan), with an intra-/inter-observer agreement on absolute vein count of ICC = 0.76 and 0.60, respectively. The automated vein detection showed excellent inter-scan reproducibility before (ICC = 0.79) and after (ICC = 0.88) visually censoring false positives. It had a positive predictive value of 71.6 %. Imaging at 7 T allows visualization and quantification of deep medullary veins. The presented method offers fast and reliable automated assessment of deep medullary veins. (orig.)

[Case report of rare co-occurrence of renal cell carcinoma and crossed renal dystopia (L-shaped kidney)].

Science.gov (United States)

Bakov, V N; Los, M S

2017-10-01

L-shaped kidney refers to a rare anomaly of the relative kidney positioning. Due to low prevalence, the literature on the co-occurrence of this anomaly with malignancy is lacking. And, if the diagnosis of a renal anomaly does not present difficulties, if a tumor is detected in such a kidney, even MSCT does not always help differentiate a pelvic tumor from a tumor of the renal parenchyma spreading to the pelvicalyceal system. This has important implications for choosing an appropriate surgical strategy. A feature of the presented clinical observation is the co-occurrence of the rare anomaly of kidney position and locally advanced renal cell carcinoma spreading to the renal pelvis. Due to the massive spread of the tumor, an organ-sparing surgery was not feasible. Due to the suspicion of tumor spread to the renal pelvis, the patient underwent nephrureterectomy of the L-shaped kidney. Introduction to renoprival state with transfer to chronic hemodialysis became the only option to maintain homeostasis and extend the patients life. Histological examination revealed clear cell renal cell carcinoma with invasion of the pelvis and renal capsule, with no clear demarcation between the fused kidneys.

Evaluation of morphologically unclassified renal cell carcinoma with electron microscopy and novel renal markers: implications for tumor reclassification.

Science.gov (United States)

Talento, Romualdo; Hewan-Lowe, Karlene; Yin, Ming

2013-02-01

Despite progress in the classification of renal cell carcinomas (RCC), a subset of these carcinomas remains unclassified (RCC-U). Patients with RCC-U usually present at a late stage and have a poor prognosis. Several studies have attempted to extract new classifications of newly recognized renal carcinomas from the group of RCC-U. However, to date, no studies in the literature have attempted to characterize the RCC-U with unrecognizable cell types beyond the morphologic evaluation on H&E-stained sections. The purpose of this study was to evaluate this group of RCC-U using electron microscopy and novel renal markers. Ten cases of such RCC-U were identified for this study. At the ultrastructural level, they did not show typical morphology that resembled any of the well-studied, recognizable subtypes of RCC. However, they did reveal features of renal tubular epithelial differentiation. The histologic, ultrastructural, and immunophenotypic features indicated that these tumors are poorly differentiated renal epithelial tumors, possibly derived from the proximal nephron, with an immunohistochemical profile similar to high-grade clear cell RCC. It is, therefore, proposed that this group of renal carcinomas be renamed "poorly differentiated renal cell carcinoma, not otherwise specified." The current study showed that PAX-8 and carbonic anhydrase IX are reliable markers for this novel group of renal carcinoma, and that electron microscopy is an important adjunct in the evaluation of new and unusual renal entities.

Comparison of mammographic and sonographic findings in typical and atypical medullary carcinomas of the breast

International Nuclear Information System (INIS)

Yilmaz, E.; Lebe, B.; Balci, P.; Sal, S.; Canda, T.

2002-01-01

AIM: The aim of this study was to describe the contribution of mammographic and sonographic findings to the discrimination of typical and atypical histopathologic groups of medullary carcinomas of the breast. MATERIALS AND METHODS: Imaging findings were retrospectively assessed in 33 women with medullary carcinomas (15 typical medullary carcinomas and 18 atypical medullary carcinomas) identified during pre-operative mammography. Twenty-nine of these women also had ultrasound and these findings were reviewed. RESULTS: Mammography showed a well circumscribed mass in 10 of the 15 (67%) typical medullary carcinomas and in four of the 17 (24%) atypical medullary carcinomas (P < 0.02). One small tumour in a woman with atypical medullary carcinoma was missed on mammography and was shown only on sonography. Sonographically, an irregular margin surrounding the whole mass or part of it was seen in three out of 14 (21%) patients with typical medullary carcinoma and in nine out of 15 (60%) patients with atypical medullary carcinomas (P < 0.05). Posterior acoustic shadowing was more often observed in the typical medullary carcinoma group than in atypical medullary carcinoma and the difference was found to be statistically significant (P < 0.05). None of the other mammographic and sonographic findings were sufficiently characteristic to allow for a differentiation between two groups. CONCLUSION: When typical medullary carcinomas were compared with atypical medullary carcinomas according to imaging features, they tended to be well circumscribed masses on both mammography and sonography, and a posterior acoustic shadow was not found on sonography. However, the imaging findings in these two subgroups often resembled each other and histopathology will always be required to confirm the diagnosis. Yilmaz, E. et al. (2002)

Comparison of mammographic and sonographic findings in typical and atypical medullary carcinomas of the breast

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Yilmaz, E.; Lebe, B.; Balci, P.; Sal, S.; Canda, T

2002-07-01

AIM: The aim of this study was to describe the contribution of mammographic and sonographic findings to the discrimination of typical and atypical histopathologic groups of medullary carcinomas of the breast. MATERIALS AND METHODS: Imaging findings were retrospectively assessed in 33 women with medullary carcinomas (15 typical medullary carcinomas and 18 atypical medullary carcinomas) identified during pre-operative mammography. Twenty-nine of these women also had ultrasound and these findings were reviewed. RESULTS: Mammography showed a well circumscribed mass in 10 of the 15 (67%) typical medullary carcinomas and in four of the 17 (24%) atypical medullary carcinomas (P < 0.02). One small tumour in a woman with atypical medullary carcinoma was missed on mammography and was shown only on sonography. Sonographically, an irregular margin surrounding the whole mass or part of it was seen in three out of 14 (21%) patients with typical medullary carcinoma and in nine out of 15 (60%) patients with atypical medullary carcinomas (P < 0.05). Posterior acoustic shadowing was more often observed in the typical medullary carcinoma group than in atypical medullary carcinoma and the difference was found to be statistically significant (P < 0.05). None of the other mammographic and sonographic findings were sufficiently characteristic to allow for a differentiation between two groups. CONCLUSION: When typical medullary carcinomas were compared with atypical medullary carcinomas according to imaging features, they tended to be well circumscribed masses on both mammography and sonography, and a posterior acoustic shadow was not found on sonography. However, the imaging findings in these two subgroups often resembled each other and histopathology will always be required to confirm the diagnosis. Yilmaz, E. et al. (2002)

Clinical study of 12 cases of medullary carcinoma of the breast

International Nuclear Information System (INIS)

Shibuya, Hitoshi; Sasaki, Kenichi; Yamamoto, Masaaki; Higaki, Nagato; Nakamura, Yukio

2006-01-01

Medullary carcinoma of the breast is a rare type breast cancer, and shows peculiar clinical features. In a series of 460 cases of breast cancer operated on at the hospital from 1975 to 2004, twelve (2.6%) cases were diagnosed as medullary carcinoma of the breast by postoperative pathological study. When the specimens from the twelve tumors were reevaluated according to the Ridolfi's subtype classification, six tumors were classified into typical medullary carcinoma (TMC) and the remaining six tumors into atypical medullary carcinoma (AMC). On mammography these tumors were visualized as homogeneously enhancing oval masses without calcification and the boundary was comparatively well-defined. US demonstrated well-defied masses with a heterogeneous, hypoechoic texture and with reinforcement of posterior echoes. The rate of lymph node metastasis was 33.3% in medullary carcinomas which was not significantly different from that of infiltrative ductal carcinomas experienced during the same period. The rate of a positivity of a hormone receptor was 8.3% in medullary carcinomas which was low in predominance in comparison with that of infiltrative ductal carcinomas. The positive rate for a HER2/neu (above2+) by the IHC method was 58%. An average observation period is 11 years, and all patients are alive. (author)

Clinical presentation of renal cell carcinoma

International Nuclear Information System (INIS)

Rehman, R.A.; Ashraf, S.; Jamil, N.

2015-01-01

Most common malignant tumour of the kidney is Renal Cell Carcinoma (RCC) and is known for its unpredictable clinical behaviour. Aetiology and risk factors are not completely understood. Extensive workup is being done in the understanding of the disease, especially to diagnose early and to treat promptly. The objective of this study was to determine the clinical presentation and pathological pattern of RCC. Methods: After approval from ethical committee a retrospective review of records was conducted extending from January 2012 to January 2014 to identify clinical characteristics of renal cell carcinomas. The study included all renal cancer patients presented to Sheikh Zayed Hospital Lahore with in this specified period. The data was retrieved regarding, history, physical examination and necessary investigations such as ultrasonography of abdomen and pelvis and CT scan of abdomen and pelvis. Results: There were total of 50 cases. The male to female ratio was 3:2. Mean age of patients were 52.38 (18-93) years old. Most common clinical presentation was gross haematuria(66%).The mean tumour size was 8.34 (3-24) cm. Tumour histology were clear cell (84%), papillary transitional cell carcinoma (12%) and oncosytoma contributed 4%. Conclusion: We observed that large number of the patients with RCC presented with haematuria and most of them were male. Common pathological type was clear cell carcinoma. (author)

Introduction to European comments on "Medullary Thyroid Cancer

DEFF Research Database (Denmark)

Jarzab, Barbara; Feldt-Rasmussen, Ulla

2013-01-01

Guest Editors of Thyroid Research supplement devoted to medullary thyroid cancer present the history on how the discussion about "Medullary Thyroid Cancer: management guidelines of the American Thyroid Association" was initiated and subsequently widely commented before and during European Thyroid...... Association - Cancer Research Network Meeting in Lisbon. It is explained why it has been decided to publish the manuscripts within the supplement - to document voices from the discussion and popularize them....

Renal cell apoptosis in human lupus nephritis: a histological study

DEFF Research Database (Denmark)

Faurschou, M; Penkowa, Milena; Andersen, C B

2009-01-01

Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...

Imaging Renal Urea Handling in Rats at Millimeter Resolution using Hyperpolarized Magnetic Resonance Relaxometry

DEFF Research Database (Denmark)

Reed, Galen D; von Morze, Cornelius; Verkman, Alan S

2016-01-01

of the renal urea handling process: glomerular filtration and the inner-medullary urea transporter (UT)-A1 and UT-A3 mediated urea concentrating process. Simple motion correction and subspace denoising algorithms are presented to aid in the multi exponential data analysis. Furthermore, a T2-edited, ultra long...

Dragon (Repulsive Guidance Molecule RGMb) Inhibits E-cadherin Expression and Induces Apoptosis in Renal Tubular Epithelial Cells*

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Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y.; Xia, Yin

2013-01-01

Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45–66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo. PMID:24052264

Lateral medullary infarction with ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy.

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Li, Xiaodi; Wang, Yuzhou

2014-04-01

Here, we present a rare case of a lateral medullary infarction with ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy. In this case, we proved Opalski's hypothesis by diffusion tensor tractography that ipsilateral hemiparesis in a medullary infarction is due to the involvement of the decussated corticospinal tract. We found that the clinical triad of ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy, which had been regarded as a variant of medial medullary syndrome, turned out to be caused by lateral lower medullary infarction. Therefore, this clinical triad does not imply the involvement of the anteromedial part of medulla oblongata, when it is hard to distinguish a massive lateral medullary infarction from a hemimedullary infarction merely from MR images. At last, we suggest that hyperreflexia and Babinski's sign may not be indispensable to the diagnosis of Opalski's syndrome and we propose that "hemimedullary infarction with ipsilateral hemiparesis" is intrinsically a variant of lateral medullary infarction.

Medullary carcinoma of the thyroid - an unusual case of hyalinizing ...

African Journals Online (AJOL)

Medullary thyroid carcinoma is a neoplasm occurring in sporadic and familial patterns. A rare variant of medullary thyroid carcinoma shows microscopic features similar to hyalinizing trabecular adenoma of thyroid. Detection of this variant requires a high index of suspicion and immunohistochemical confirmation by ...

Renal abscess in a child with sickle cell anemia

OpenAIRE

Taksande Amar; Vilhekar K

2009-01-01

Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess.

Renal abscess in a child with sickle cell anemia.

Science.gov (United States)

Taksande, Amar M; Vilhekar, K Y

2009-03-01

Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess.

Alteraciones renales en la drepanocitosis Renal disorders in sickle cell disease

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Aramís Núñez-Quintana

2011-06-01

Full Text Available La drepanocitosis está asociada con un amplio espectro de alteraciones renales que tienen su base en la falciformación de los eritrocitos en los vasos de la médula renal, que conduce a fenómenos de isquemia, microinfartos y anomalías de la función tubular. Se producen también alteraciones glomerulares funcionales reversibles de la autorregulación renal (hiperfiltración, que pueden conducir a cambios anatómicos irreversibles con glomeruloesclerosis segmentaria focal. Estas anomalías se expresan tempranamente como microalbuminuria, proteinuria y de forma mas tardía, como síndrome nefrótico e insuficiencia renal crónica. Medidas terapéuticas como el uso de inhibidores de la enzima convertidora de la angiotensina II, de los bloqueadores del receptor de la angiotensina II, asociados o no con la hidroxiurea, pueden prevenir o retardar el daño glomerular. En el presente trabajo se exponen de forma resumida aspectos relacionados con la fisiopatología del daño renal en la drepanocitosis y su tratamiento.Sickle cell disease is associated with a wide range of renal disorders resulting from the falciformation of erythrocytes in vessels of the renal medulla, leading to ischemia, microinfarctions and tubular function abnormalities. Reversible glomerular functional renal self-regulation disorders (hyperfiltration also occur, which may lead to irreversible anatomical changes with focal segmental glomerular sclerosis. These anomalies are expressed at an early stage as microalbuminuria and proteinuria, and at a later stage as nephrotic syndrome and chronic renal failure. Therapeutic measures such as the use of angiotensin-II converting enzyme inhibitors and angiotensin-II receptor blockers, associated or not with hydroxyurea, may either prevent or delay glomerular damage. The paper succinctly presents the physiopathology of renal damage in drepanocytosis and its treatment.

Renal cell carcinoma in childhood

International Nuclear Information System (INIS)

Zanier, J.F.C.; Ramos, C.O.P.; Pereira, A.A.

1990-01-01

The authors present five cases of renal cell carcinoma in children, describing its aspects on excretory urography, ultra-sonography and computerized tomography. The clinical, pathological and radiological features are compared with those of the literature. (author)

Validation and utilization of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinoma and alveolar soft part sarcoma.

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Pradhan, Dinesh; Roy, Somak; Quiroga-Garza, Gabriela; Cieply, Kathleen; Mahaffey, Alyssa L; Bastacky, Sheldon; Dhir, Rajiv; Parwani, Anil V

2015-09-29

Xp11.2 or TFE3 translocation renal cell carcinomas (RCC) and alveolar soft part sarcoma (ASPS) are characterized by chromosome translocations involving the Xp11.2 breakpoint resulting in transcription factor TFE3 gene fusions. The most common translocations documented in TFE3 RCCs are t(X;1) (p11.2;q21) and t(X;17) (p11.2;q25) which leads to fusion of TFE3 gene on Xp11.2 with PRCC or ASPL respectively. TFE3 immunohistochemistry (IHC) has been inconsistent over time due to background staining problems in part related to fixation issues. Karyotyping to detect TFE3 gene rearrangement requires typically unavailable fresh tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) is generally very challenging due to degradation of RNA in archival material. The study objective was to develop and validate a TFE3 break-apart fluorescence in situ hybridization (FISH) assay to confirm Xp11 translocation RCCs and ASPS. Representative sections of formalin-fixed paraffin-embedded tissue blocks were selected in 40 possible cases. Approximately 60 tumor cells were analyzed in the targeted region. The validation of TFE3 FISH was done with 11 negative and two positive cases. Cut off for a positive result was validated as >7.15 % positive nuclei with any pattern of break-apart signals. FISH evaluation was done blinded of the immunohistochemical or karyotype data. Three out of forty cases were positive for the TFE3 break-apart signals by FISH. The negative cases were reported as clear cell RCC with papillary features (10), clear cell RCC with sarcomatoid areas (2), Papillary RCC with clear cell areas (9), Chromophobe RCC (2), RCC, unclassified type (3) and renal medullary carcinoma (1). 3 of the negative cases were consultation cases for renal tumor with unknown histology. Seven negative cases were soft tissue tumor suspicious for ASPS. Our study validates the utility of TFE3 break-apart FISH on formalin-fixed paraffin-embedded tissue sections for diagnosis and confirmation of

Medullary breast carcinoma: anatomo-radiological correlation

International Nuclear Information System (INIS)

Matheus, Valeria Soares; Canella, Ellyete de Oliveira; Djahjah, Maria Celia Resende; Koch, Hilton Augusto; Kestelman, Fabiola Procaci

2008-01-01

To evaluate radiological findings in patients submitted to surgical treatment for medullary breast cancer at Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ, Brazil, correlating them with histological results. A retrospective descriptive study was developed with patients submitted to surgery at INCa, in the period from January 1997 to December 2006, for identifying the presence of medullary breast carcinoma and analyzing radiological findings. Among 21,287 patients diagnosed with carcinoma, 76 (0.357%) had typical medullary breast carcinoma. The age range of these patients was 32-81 years (mean = 59.1 years). Mammography demonstrated lesions in 19 of these patients, 17 (89.5%) of them with masses, and 2 with focal asymmetry. Among the patients with masses, 15 (88.1%) presented with high density and 2 (11.9%) with isodensity. Twelve patients presented sonographic findings, 11 (91.6%) of them with hypoechoic masses, and one with an anechoic mass with areas of cystic degeneration. Nodular mass was the predominant radiological finding (89.5%), 88.1% of them corresponding to masses with high density and circumscribed margins. Despite the radiological characteristics of benignity, a solid, fast growing, highly dense mass with circumscribed margins should be further investigated to confirm the diagnosis. (author)

Medullary breast carcinoma: anatomo-radiological correlation

Energy Technology Data Exchange (ETDEWEB)

Matheus, Valeria Soares; Canella, Ellyete de Oliveira; Djahjah, Maria Celia Resende; Koch, Hilton Augusto [Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ (Brazil); Kestelman, Fabiola Procaci [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ (Brazil)]. E-mail: msavaleria@yahoo.com

2008-11-15

To evaluate radiological findings in patients submitted to surgical treatment for medullary breast cancer at Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ, Brazil, correlating them with histological results. A retrospective descriptive study was developed with patients submitted to surgery at INCa, in the period from January 1997 to December 2006, for identifying the presence of medullary breast carcinoma and analyzing radiological findings. Among 21,287 patients diagnosed with carcinoma, 76 (0.357%) had typical medullary breast carcinoma. The age range of these patients was 32-81 years (mean = 59.1 years). Mammography demonstrated lesions in 19 of these patients, 17 (89.5%) of them with masses, and 2 with focal asymmetry. Among the patients with masses, 15 (88.1%) presented with high density and 2 (11.9%) with isodensity. Twelve patients presented sonographic findings, 11 (91.6%) of them with hypoechoic masses, and one with an anechoic mass with areas of cystic degeneration. Nodular mass was the predominant radiological finding (89.5%), 88.1% of them corresponding to masses with high density and circumscribed margins. Despite the radiological characteristics of benignity, a solid, fast growing, highly dense mass with circumscribed margins should be further investigated to confirm the diagnosis. (author)

Renal abscess in a child with sickle cell anemia

International Nuclear Information System (INIS)

Taksande, Amar M; Vilhekar, KY

2009-01-01

Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess. (author)

Stem cell factor expression after renal ischemia promotes tubular epithelial survival.

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Geurt Stokman

Full Text Available BACKGROUND: Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration of renal tissue. The cytokine stem cell factor (SCF has been shown to protect the tubular epithelium against apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse model for renal ischemia/reperfusion injury, we studied how expression of c-KIT on tubular epithelium and its ligand SCF protect cells against apoptosis. Administration of SCF specific antisense oligonucleotides significantly decreased specific staining of SCF following ischemia. Reduced SCF expression resulted in impaired renal function, increased tubular damage and increased tubular epithelial apoptosis, independent of inflammation. In an in vitro hypoxia model, stimulation of tubular epithelial cells with SCF activated survival signaling and decreased apoptosis. CONCLUSIONS/SIGNIFICANCE: Our data indicate an important role for c-KIT and SCF in mediating tubular epithelial cell survival via an autocrine pathway.

Kidney (Renal Cell) Cancer—Patient Version

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Kidney cancer can develop in adults and children. The main types of kidney cancer are renal cell cancer, transitional cell cancer, and Wilms tumor. Certain inherited conditions increase the risk of kidney cancer. Start here to find information on kidney cancer treatment, research, and statistics.

Magnetic resonance imaging of large chromophobe renal cell carcinomas

International Nuclear Information System (INIS)

Sasaguri, Kohei; Irie, Hiroyuki; Kamochi, Noriyuki; Nakazono, Takahiko; Yamaguchi, Ken; Uozumi, Jiro; Kudo, Sho

2010-01-01

The objective of this study was to clarify the magnetic resonance imaging (MRI) findings of large chromophobe renal cell carcinomas. Five patients diagnosed pathologically with chromophobe renal cell carcinoma are included. MRI findings were retrospectively evaluated for the tumor contour, uniformity and hypointensity of the rim of the tumor on T2-weighted images, ''micro-scopic fat'', enhancement degree and pattern on dynamic study, and necrosis in the tumor, among other findings. The tumor size ranged from 4.8 to 13.7 cm (mean 7.9 cm). The tumor contour was well defined in four patients. All but one tumor showed a hypointensity rim, and all tumors had a heterogeneous appearance on T2-weighted images. ''Microscopic fat'' was detected in one case. All tumors demonstrated low enhancement compared to that of the renal cortex. All tumors showed heterogeneous enhancement on postcontrast images. Necrosis was seen in four. Hemorrhage and renal vein thrombosis was seen in one. Chromophobe renal cell carcinomas of large size tend to have a heterogeneous appearance on post-contrast and T2-weighted images, a well-defined tumor contour with a hypointensity rim on T2-wighted images, and lower enhancement than that of the renal cortex. Tumor necrosis is easily apparent, and ''microscopic fat'' may be observed. (author)

Renal abscess in a child with sickle cell anemia

Directory of Open Access Journals (Sweden)

Taksande Amar

2009-01-01

Full Text Available Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess.

Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

DEFF Research Database (Denmark)

Kyriakopoulos, Christos E; Chittoria, Namita; Choueiri, Toni K

2015-01-01

BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology......% intermediate risk, and 40% vs. 24% poor risk; P system metastases (6...... of second- (P = .018) and third-line (P systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P

Measurement of arterial transit time and renal blood flow using pseudocontinuous ASL MRI with multiple post-labeling delays: Feasibility, reproducibility, and variation.

Science.gov (United States)

Kim, Dong Won; Shim, Woo Hyun; Yoon, Seong Kuk; Oh, Jong Yeong; Kim, Jeong Kon; Jung, Hoesu; Matsuda, Tsuyoshi; Kim, Dongeun

2017-09-01

To evaluate the feasibility, reproducibility, and variation of renal perfusion and arterial transit time (ATT) using pseudocontinuous arterial spin labeling magnetic resonance imaging (PCASL MRI) in healthy volunteers. PCASL MRI at 3T was performed in 25 healthy volunteers on two different occasions. The ATT and ATT-corrected renal blood flow (ATT-cRBF) were calculated at four different post-labeling delay points (0.5, 1.0, 1.5, and 2.0 s) and evaluated for each kidney and subject. The intraclass correlation (ICC) and Bland-Altman plot were used to assess the reproducibility of the PCASL MRI technique. The within-subject coefficient of variance was determined. Results were obtained for 46 kidneys of 23 subjects with a mean age of 38.6 ± 9.8 years and estimated glomerular filtration rate (eGFR) of 89.1 ± 21.2 ml/min/1.73 m 2 . Two subjects failed in the ASL MRI examination. The mean cortical and medullary ATT-cRBF for the subjects were 215 ± 65 and 81 ± 21 ml/min/100 g, respectively, and the mean cortical and medullary ATT were 1141 ± 262 and 1123 ± 245 msec, correspondingly. The ICC for the cortical ATT-cRBF was 0.927 and the within-subject coefficient of variance was 14.4%. The ICCs for the medullary ATT-cRBF and the cortical and medullary ATT were poor. The Bland-Altman plot for cortical RBF showed good agreement between the two measurements. PCASL MRI is a feasible and reproducible method for measuring renal cortical perfusion. In contrast, ATT for the renal cortex and medulla has poor reproducibility and high variation. 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:813-819. © 2017 International Society for Magnetic Resonance in Medicine.

Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ®)—Health Professional Version

Science.gov (United States)

Genetics of Kidney Cancer (Renal Cell) includes the hereditary cancer syndromes von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Get comprehensive information on these syndromes in this clinician summary.

Renal epithelial cells can release ATP by vesicular fusion

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Randi G Bjaelde

2013-09-01

Full Text Available Renal epithelial cells have the ability to release nucleotides as paracrine factors. In the intercalated cells of the collecting duct, ATP is released by connexin30 (cx30, which is selectively expressed in this cell type. However, ATP is released by virtually all renal epithelia and the aim of the present study was to identify possible alternative nucleotide release pathways in a renal epithelial cell model. We used MDCK (type1 cells to screen for various potential ATP release pathways. In these cells, inhibition of the vesicular H+-ATPases (bafilomycin reduced both the spontaneous and hypotonically (80%-induced nucleotide release. Interference with vesicular fusion using N-ethylamide markedly reduced the spontaneous nucleotide release, as did interference with trafficking from the endoplasmic reticulum to the Golgi apparatus (brefeldin A1 and vesicular transport (nocodazole. These findings were substantiated using a siRNA directed against SNAP-23, which significantly reduced spontaneous ATP release. Inhibition of pannexin and connexins did not affect the spontaneous ATP release in this cell type, which consists of ∼90% principal cells. TIRF-microscopy of either fluorescently-labeled ATP (MANT-ATP or quinacrine-loaded vesicles, revealed that spontaneous release of single vesicles could be promoted by either hypoosmolality (50% or ionomycin. This vesicular release decreased the overall cellular fluorescence by 5.8% and 7.6% respectively. In summary, this study supports the notion that spontaneous and induced ATP release can occur via exocytosis in renal epithelial cells.

Role of 188Re(V)DMSA in the diagnosis and therapy of medullary thyroid carcinoma: a pilot study in an animal model

International Nuclear Information System (INIS)

Learoyd, D.L.; Roach, P.J.; Snowdon, G.M.; Dadachova, K.; Moreau, A.M.; Robinson, B.G.

1999-01-01

Full text: 99 Tc m (V)DMSA has been reported to be highly sensitive in the diagnosis of medullary thyroid cancer (MTC). Rhenium-188, a beta emitter, has potential for therapy of MTC. However, initial studies with 188 Re indicate high renal uptake which may interfere with potential therapeutic applications of this radiopharmaceutical. A modified radiolabelling method has been shown to reduced the renal uptake of 188 Re(V)DMSA in control animals. The aims of this study were to determine whether there is uptake of modified 188 Re(V)DMSA in nude mice injected with an MTC cell line and whether there is potential for MTC therapy. Two groups of mice were injected in the left flank (SC) with TT cell line, and in mice showing tumour growth a low-dose (400 kBq) of 188 Re(V)DMSA was injected via a tail vein 8 weeks later. Biodistribution was performed on several mice and several others were given 'therapy' injections (8 MBq) to determine whether tumour shrinkage could be objectively observed. Tracer uptake was highest in bone and kidneys but tumour uptake was relatively low. However, no new tumour growth was seen in any of the mice subsequent to therapy injections and 1 mouse showed complete remission within 5 weeks of injection. Further animal and human studies will need to be performed to determine the potential role of this modified 118 Re(V)DMSA in patients with MTC

Renal sinus fat invasion and tumoral thrombosis of the inferior vena cava-renal vein: only confined to renal cell carcinoma.

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Acar, Turker; Harman, Mustafa; Guneyli, Serkan; Sen, Sait; Elmas, Nevra

2014-01-01

Epithelioid angiomyolipoma (E-AML), accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS) and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC). In this case presentation, we aimed to report cross-sectional imaging findings of two cases diagnosed as E-AML and pathological correlation of these aforementioned masses mimicking RCC.

Microwave treatment of renal cell carcinoma adjacent to renal sinus

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Gao, Yongyan; Liang, Ping; Yu, Xiaoling; Yu, Jie; Cheng, Zhigang; Han, Zhiyu; Duan, Shaobo; Huang, Hui

2016-01-01

Highlights: • This study shows US-guided microwave ablation appears to be a promising method to treat renal cell carcinoma adjacent to renal sinus. • The estimated 1-, 3- and 5-year RCC-related survival were 100%, 93.3% and 93.3%, respectively. • The estimated 1-, 3- and 5-year overall survival were 97.1%, 87.8%, 83.6%, respectively. • For patients with RCC ≤4 cm, initial ablation success was 100% (29/29) and the estimated 5-year disease-free survival were 81.5%. - Abstract: Purpose: To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. Materials and methods: This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1 day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. Results: IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4 cm (100%, 29/29) and RCCs >4 cm (75%, 9/12, p = 0.021). During the median follow-up of 37.6 (range, 3.0–97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4 cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. Conclusion: US-guided percutaneous MWA

Microwave treatment of renal cell carcinoma adjacent to renal sinus

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Gao, Yongyan, E-mail: gaoyongyan7@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Department of Ultrasound, The General Hospital of Chinese People’s Armed Police Forces, 69 Yongding Road, Beijing, 100039 (China); Liang, Ping, E-mail: liangping301@hotmail.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu, Xiaoling, E-mail: 784107477@qq.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu, Jie, E-mail: 1411495161@qq.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Cheng, Zhigang, E-mail: 13691367317@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Han, Zhiyu, E-mail: hanzhiyu122@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Duan, Shaobo, E-mail: Dustin2662@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Huang, Hui, E-mail: 309hh@sina.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China)

2016-11-15

Highlights: • This study shows US-guided microwave ablation appears to be a promising method to treat renal cell carcinoma adjacent to renal sinus. • The estimated 1-, 3- and 5-year RCC-related survival were 100%, 93.3% and 93.3%, respectively. • The estimated 1-, 3- and 5-year overall survival were 97.1%, 87.8%, 83.6%, respectively. • For patients with RCC ≤4 cm, initial ablation success was 100% (29/29) and the estimated 5-year disease-free survival were 81.5%. - Abstract: Purpose: To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. Materials and methods: This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1 day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. Results: IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4 cm (100%, 29/29) and RCCs >4 cm (75%, 9/12, p = 0.021). During the median follow-up of 37.6 (range, 3.0–97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4 cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. Conclusion: US-guided percutaneous MWA

Renal angiographic and computed tomographic evaluation of local extension of renal cell carcinoma

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Masuda, Fujio; Onishi, Tetsuro; Sasaki, Tadamasa; Arai, Yoshikazu; Shoji, Ryo

1981-01-01

In 23 cases of renal cell carcinoma, the degree of local invasion of carcinoma was diagnosed using renal angiography and CT, and compared with the findings obtained by operation or autopsy. Among 5 cases in which the tumor was confined to the renal capsule, accurate diagnosis could be established with renal angiography in 4 cases and with CT in all of 5 cases. Both renal angiography and CT provided correct diagnosis in 7 of 8 cases in which the tumor showed infiltration extending to the perinephric fat. Out of 5 cases with tumor invasion of renal vein or inferior vena cava, diagnosis could be established correctly by renal angiography and CT in 3 cases. Among the remaining 2 cases the diagnosis could be established by renal angiography and CT in one each case. Among 5 cases with metastases to the regional lymph nodes, diagnosis could be established by renal angiography in only 2 cases, while all of 5 cases could be diagnosed by CT. In 3 cases where the tumor invaded an ajacent organ beyond Gerota's fastia, renal angiography could diagnose in none of the 3 cases while with CT all of 3 cases could successfully be diagnosed. The consistency of degree of local invasion as revealed by renal angiography and CT was seen in 15 of 23 cases (65%) for renal agniography and 20 of 23 cases (87%) for CT, indicating superiority of CT in this respect. In particular, CT appears to be more superior to renal angiography for determining whether the tumor confined to Gerota's fastia or it infiltrated over it. Both combined use of renal angiography and CT, the degree of infiltration of tumor could be diagnosed correctly in 22 of 23 cases (96%). (author)

Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival and

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Dmytro Starenki

2015-12-01

Full Text Available BackgroundMedullary thyroid carcinoma (MTC is a neuroendocrine tumor mainly caused by mutations in the rearranged during transfection (RET proto-oncogene. Not all patients with progressive MTC respond to current therapy inhibiting RET, demanding additional therapeutic strategies. We recently demonstrated that disrupting mitochondrial metabolism using a mitochondria-targeted agent or by depleting a mitochondrial chaperone effectively suppressed human MTC cells in culture and in mouse xenografts by inducing apoptosis and RET downregulation. These observations led us to hypothesize that mitochondria are potential therapeutic targets for MTC. This study further tests this hypothesis using1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden]-4-oxothiazolidin-2-ylidenemethyl] pyridinium chloride (MKT-077, a water-soluble rhodocyanine dye analogue, which can selectively accumulate in mitochondria.MethodsThe effects of MKT-077 on cell proliferation, survival, expression of RET and tumor protein 53 (TP53, and mitochondrial activity were determined in the human MTC lines in culture and in mouse xenografts.ResultsMKT-077 induced cell cycle arrest in TT and MZ-CRC-1. Intriguingly, MKT-077 also induced RET downregulation and strong cell death responses in TT cells, but not in MZ-CRC-1 cells. This discrepancy was mainly due to the difference between the capacities of these cell lines to retain MKT-077 in mitochondria. The cytotoxicity of MKT-077 in TT cells was mainly attributed to oxidative stress while being independent of TP53. MKT-077 also effectively suppressed tumor growth of TT xenografts.ConclusionMKT-077 can suppress cell survival of certain MTC subtypes by accumulating in mitochondria and interfering with mitochondrial activity although it can also suppress cell proliferation via other mechanisms. These results consistently support the hypothesis that mitochondrial targeting has therapeutic potential for MTC.

Oncogenic micro-RNAs and Renal Cell Carcinoma

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Cristina eGrange

2014-03-01

Full Text Available Tumor formation is a complex process that occurs in different steps and involves many cell types, including tumor cells, endothelial cells, and inflammatory cells, which interact to promote growth of the tumor mass and metastasization. Epigenetic alterations occurring in transformed cells result in de-regulation of miRNA expression (a class of small non-coding RNA that regulates multiple functions which contributes to tumorigenesis. The specific miRNAs, which have an aberrant expression in tumors, are defined as oncomiRNAs, and may be either over- or under-expressed, but down-regulation is most commonly observed.Renal cell carcinoma is a frequent form of urologic tumor, associated with an alteration of multiple signaling pathways. Many molecules involved in the progression of renal cell carcinomas, such as HIF, VEGF or mTOR, are possible targets of deregulated miRNAs. Within tumor mass, the cancer stem cell population is a fundamental component that promotes tumor growth. The cancer stem cell hypothesis postulates that cancer stem cells have the unique ability to self-renew and to maintain tumor growth and metastasis. Cancer stem cells present in renal cell carcinoma were shown to express the mesenchymal stem cell marker CD105 and to exhibit self-renewal and clonogenic properties, as well as the ability to generate serially transplantable tumors. The phenotype of cancer stem cell has been related to the potential to undergo the epithelial-mesenchymal transition, which has been linked to the expression pattern of tumorigenic miRNAs or down-regulation of anti-tumor miRNAs. In addition, the pattern of circulating miRNAs may allow discrimination between healthy and tumor patients. Therefore, a miRNA signature may be used as a tumor biomarker for cancer diagnosis, as well as to classify the risk of relapse and metastasis, and for a guide for therapy.

Renal cell carcinoma presenting as mandibular metastasis

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Hassan Ahmadnia

2013-01-01

Full Text Available Renal clear cell carcinoma (RCC has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.

Experimental depletion of different renal interstitial cell populations

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Bohman, S.O.; Sundelin, B.; Forsum, U.; Tribukait, B.

1988-01-01

To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells

Renal cell carcinoma and occupational exposure to chemicals in Canada

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Hu, J.; Mao, Y.; White, K. [Health Canada, Ottawa, ON (Canada). Population & Public Health Branch

2002-05-01

This study assesses the effect of occupational exposure to specific chemicals on the risk of renal cell carcinoma in people in Canada. Mailed questionnaires were used to obtain data on 1279 (691 male and 588 female) newly diagnosed, histologically confirmed renal cell carcinoma cases and 5370 population controls in eight Canadian provinces, between 1994 and 1997. Data were collected on socio-economic status, smoking habit, alcohol use, diet, residential and occupational histories, and years of exposure to any of 17 chemicals. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using unconditional logistic regression. The study found an increased risk of renal cell carcinoma in males only, which was associated with occupational exposure to benzene; benzidine; coal tar, soot, pitch, creosote or asphalt; herbicides; mineral, cutting or lubricating oil; mustard gas; pesticides; and vinyl chloride. Very few females were exposed to specific chemicals in this study; further research is needed to clarify the association between occupational exposure to chemicals and renal cell carcinoma in females.

Arterial spin labelling MRI for detecting pseudocapsule defects and predicting renal capsule invasion in renal cell carcinoma.

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Zhang, H; Wu, Y; Xue, W; Zuo, P; Oesingmann, N; Gan, Q; Huang, Z; Wu, M; Hu, F; Kuang, M; Song, B

2017-11-01

To evaluate prospectively the performance of combining morphological and arterial spin labelling (ASL) magnetic resonance imaging (MRI) for detecting pseudocapsule defects in renal cell carcinoma (RCC), and to predict renal capsule invasion confirmed histopathologically. Twenty consecutive patients with suspicious renal tumours underwent MRI. Renal ASL imaging was performed and renal blood flow was measured quantitatively. The diagnostic performance of T2-weighted images alone, and a combination of T2-weighted and ASL images for predicting renal capsule invasion were assessed. Twenty renal lesions were evaluated in 20 patients. All lesions were clear cell RCCs (ccRCCs) confirmed at post-surgical histopathology. Fifteen ccRCCs showed pseudocapsule defects on T2-weighted images, of which 12 cases showed existing blood flow in defect areas on perfusion images. To predict renal capsule invasion, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 71.4%, 86.7%, 100%, respectively, for T2-weighted images alone, and 92.3%, 100%, 100%, 87.5%, respectively, for the combination of T2-weighted and ASL images. ASL images can reflect the perfusion of pseudocapsule defects and as such, the combination of T2-weighted and ASL images produces promising diagnostic accuracy for predicting renal capsule invasion. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Renal Sinus Fat Invasion and Tumoral Thrombosis of the Inferior Vena Cava-Renal Vein: Only Confined to Renal Cell Carcinoma

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Turker Acar

2014-01-01

Full Text Available Epithelioid angiomyolipoma (E-AML, accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC. In this case presentation, we aimed to report cross-sectional imaging findings of two cases diagnosed as E-AML and pathological correlation of these aforementioned masses mimicking RCC.

Renal Tissue Oxygenation in Essential Hypertension and Chronic Kidney Disease

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Menno Pruijm

2013-01-01

Full Text Available Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI, detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD. In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.

Breast Metastasis from Renal Cell Carcinoma: A Case Report

International Nuclear Information System (INIS)

Kim, Seon Jeong; Kim, Ji Young; Jeong, Myeong Ja; Kim, Jae Hyung; Kim, Soung Hee; Kim, Soo Hyun; Jun, Woo Sun; Kim, Hyun Jung; Han, Se Hwan

2010-01-01

Metastatic breast cancer from renal cell carcinoma is extremely rare and has non-specific findings that include a well circumscribed lesion without calcification on mammography and a well circumscribed hypoechoic lesion without posterior acoustic shadowing on sonography. We report a case of metastatic breast cancer from renal cell carcinoma and describe the radiologic findings in a 63-year-old woman who has no history of primary neoplasm

Breast Metastasis from Renal Cell Carcinoma: A Case Report

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Kim, Seon Jeong; Kim, Ji Young; Jeong, Myeong Ja; Kim, Jae Hyung; Kim, Soung Hee; Kim, Soo Hyun; Jun, Woo Sun; Kim, Hyun Jung; Han, Se Hwan [Sanggye Paik Hospital, Seoul (Korea, Republic of)

2010-01-15

Metastatic breast cancer from renal cell carcinoma is extremely rare and has non-specific findings that include a well circumscribed lesion without calcification on mammography and a well circumscribed hypoechoic lesion without posterior acoustic shadowing on sonography. We report a case of metastatic breast cancer from renal cell carcinoma and describe the radiologic findings in a 63-year-old woman who has no history of primary neoplasm.

Longitudinal assessment of mouse renal injury using high-resolution anatomic and magnetization transfer MR imaging.

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Wang, Feng; Jiang, Rosie; Takahashi, Keiko; Gore, John; Harris, Raymond C; Takahashi, Takamune; Quarles, C Chad

2014-11-01

The purpose of this study is to evaluate the utility of high-resolution non-invasive endogenous high-field MRI methods for the longitudinal structural and quantitative assessments of mouse kidney disease using the model of unilateral ureter obstruction (UUO). T1-weighted, T2-weighted and magnetization transfer (MT) imaging protocols were optimized to improve the regional contrast in mouse kidney. Conventional T1 and T2 weighted images were collected in UUO mice on day 0 (~3h), day 1, day 3 and day 6 after injury, on a 7 T small animal MRI system. Cortical and medullary thickness, corticomedullary contrast and Magnetization Transfer Ratio (MTR) were assessed longitudinally. Masson trichrome staining was used to histologically assess changes in tissue microstructure. Over the course of UUO progression there were significant (prenal cortical and medullary atrophy, cortical-medullary differentiation and MTR changes provide an endogenous, non-invasive and quantitative evaluation of renal morphology and tissue composition during UUO progression. Copyright © 2014 Elsevier Inc. All rights reserved.

An unusual cause of acute renal failure in sickle cell disease

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Rockx, Marie-Antoinette; Gibson, Ian W.; Reslerova, Martina

2009-01-01

A young female with sickle cell disease was treated for biopsy-proven IgA nephropathy. Serum creatinine levels resolved to normal range, but a year later, she presented with oedema, hypertension and acute renal failure. A repeat renal biopsy showed acute-on-chronic thrombotic microangiopathy (TMA). We suggest that circulating microparticles could be a pathophysiological link between sickle cell disease and the development of renal TMA. This case emphasizes the importance of a further biopsy for acutely declining renal function, even when a definite diagnosis has been made from a previous biopsy. PMID:25949348

Histones from Dying Renal Cells Aggravate Kidney Injury via TLR2 and TLR4

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Allam, Ramanjaneyulu; Scherbaum, Christina Rebecca; Darisipudi, Murthy Narayana; Mulay, Shrikant R.; Hägele, Holger; Lichtnekert, Julia; Hagemann, Jan Henrik; Rupanagudi, Khader Valli; Ryu, Mi; Schwarzenberger, Claudia; Hohenstein, Bernd; Hugo, Christian; Uhl, Bernd; Reichel, Christoph A.; Krombach, Fritz; Monestier, Marc; Liapis, Helen; Moreth, Kristin; Schaefer, Liliana

2012-01-01

In AKI, dying renal cells release intracellular molecules that stimulate immune cells to secrete proinflammatory cytokines, which trigger leukocyte recruitment and renal inflammation. Whether the release of histones, specifically, from dying cells contributes to the inflammation of AKI is unknown. In this study, we found that dying tubular epithelial cells released histones into the extracellular space, which directly interacted with Toll-like receptor (TLR)-2 (TLR2) and TLR4 to induce MyD88, NF-κB, and mitogen activated protein kinase signaling. Extracellular histones also had directly toxic effects on renal endothelial cells and tubular epithelial cells in vitro. In addition, direct injection of histones into the renal arteries of mice demonstrated that histones induce leukocyte recruitment, microvascular vascular leakage, renal inflammation, and structural features of AKI in a TLR2/TLR4-dependent manner. Antihistone IgG, which neutralizes the immunostimulatory effects of histones, suppressed intrarenal inflammation, neutrophil infiltration, and tubular cell necrosis and improved excretory renal function. In summary, the release of histones from dying cells aggravates AKI via both its direct toxicity to renal cells and its proinflammatory effects. Because the induction of proinflammatory cytokines in dendritic cells requires TLR2 and TLR4, these results support the concept that renal damage triggers an innate immune response, which contributes to the pathogenesis of AKI. PMID:22677551

Methods of Blood Oxygen Level-Dependent Magnetic Resonance Imaging Analysis for Evaluating Renal Oxygenation

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Fen Chen

2018-03-01

Full Text Available Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI has recently been utilized as a noninvasive tool for evaluating renal oxygenation. Several methods have been proposed for analyzing BOLD images. Regional ROI selection is the earliest and most widely used method for BOLD analysis. In the last 20 years, many investigators have used this method to evaluate cortical and medullary oxygenation in patients with ischemic nephropathy, hypertensive nephropathy, diabetic nephropathy, chronic kidney disease (CKD, acute kidney injury and renal allograft rejection. However, clinical trials of BOLD MRI using regional ROI selection revealed that it was difficult to distinguish the renal cortico-medullary zones with this method, and that it was susceptible to observer variability. To overcome these deficiencies, several new methods were proposed for analyzing BOLD images, including the compartmental approach, fractional hypoxia method, concentric objects (CO method and twelve-layer concentric objects (TLCO method. The compartmental approach provides an algorithm to judge whether the pixel belongs to the cortex or medulla. Fractional kidney hypoxia, measured by using BOLD MRI, was negatively correlated with renal blood flow, tissue perfusion and glomerular filtration rate (GFR in patients with atherosclerotic renal artery stenosis. The CO method divides the renal parenchyma into six or twelve layers of thickness in each coronal slice of BOLD images and provides a R2* radial profile curve. The slope of the R2* curve associated positively with eGFR in CKD patients. Indeed, each method invariably has advantages and disadvantages, and there is generally no consensus method so far. Undoubtedly, analytic approaches for BOLD MRI with better reproducibility would assist clinicians in monitoring the degree of kidney hypoxia and thus facilitating timely reversal of tissue hypoxia.

ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from Col4a1 mutations in mice

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Frances E. Jones

2016-02-01

Full Text Available Collagen IV is a major component of basement membranes, and mutations in COL4A1, which encodes collagen IV alpha chain 1, cause a multisystemic disease encompassing cerebrovascular, eye and kidney defects. However, COL4A1 renal disease remains poorly characterized and its pathomolecular mechanisms are unknown. We show that Col4a1 mutations in mice cause hypotension and renal disease, including proteinuria and defects in Bowman's capsule and the glomerular basement membrane, indicating a role for Col4a1 in glomerular filtration. Impaired sodium reabsorption in the loop of Henle and distal nephron despite elevated aldosterone levels indicates that tubular defects contribute to the hypotension, highlighting a novel role for the basement membrane in vascular homeostasis by modulation of the tubular response to aldosterone. Col4a1 mutations also cause diabetes insipidus, whereby the tubular defects lead to polyuria associated with medullary atrophy and a subsequent reduction in the ability to upregulate aquaporin 2 and concentrate urine. Moreover, haematuria, haemorrhage and vascular basement membrane defects confirm an important vascular component. Interestingly, although structural and compositional basement membrane defects occurred in the glomerulus and Bowman's capsule, no tubular basement membrane defects were detected. By contrast, medullary atrophy was associated with chronic ER stress, providing evidence for cell-type-dependent molecular mechanisms of Col4a1 mutations. These data show that both basement membrane defects and ER stress contribute to Col4a1 renal disease, which has important implications for the development of treatment strategies for collagenopathies.

A case report of renal cell carcinoma in a dog

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A.-S. Paşca

2013-10-01

Full Text Available Mix renal carcinoma was noticed during the necropsic examination of a 14 year old mix breed female. Tumours were bilateral and metastasis was noticed in the spleen and myocard. Histological examination evidenced morphological aspects characteristic to the mixt renal carcinoma. Histological aspects described in this individual characterize renal cell carcinoma, also known as renal adenocarcinoma, hypernephroma or, in older literature, Grawitz tumour.

Endothelin-like action of Pausinystalia yohimbe aqueous extract on vascular and renal regional hemodynamics in Sprague Dawley rats.

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Ajayi, A A; Newaz, M; Hercule, H; Saleh, M; Bode, C O; Oyekan, A O

2003-12-01

The bark of the African tree Pausinystalia yohimbe has been used as a food additive with aphrodisiac and penile erection enhancing properties. The effect of an aqueous extract of P. yohimbe (CCD-X) on renal circulation was assessed in order to test the hypothesis that it possesses additional effects on nitric oxide production and/or endothelin-1 (ET-1)-like actions. In vivo studies with CCD-X in Sprague Dawley rats demonstrated a dose-dependent (1-1000 ng/kg) increase in mean blood pressure (p < 0.001) and an increase in medullary blood flow (MBF) (p < 0.001). Both the pressor action and renal medullary vasodilation were blocked by endothelinA (ETA) receptor antagonist BMS182874 and endothelinB (ETB) receptor antagonist BQ788 in combination. L-Nomega-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg) also inhibited the increase in MBF induced by CCD-X. In vitro studies in isolated perfused kidney and in pressurized renal microvessels confirmed the dose-dependent vasoconstrictor action of this extract. ETA receptor antagonist BQ610 and ETB receptor antagonist BQ788 separately and significantly attenuated the renal vasoconstrictor actions of the extract (p < 0.001 ANOVA). These preliminary observations indicate that, in addition to the alpha-adrenergic antagonist actions that characterize yohimbine, CCD-X possesses endothelin-like actions and affects nitric oxide (NO) production in renal circulation. These findings suggest a strong possibility of post-receptor cross-talk between alpha2-adrenoceptors and endothelin, as well as a direct effect of alpha2-adrenoceptors on renal NO production. (c) 2003 Prous Science

The affection of APA microcapsulation on catecholamine and leucine-enkephalin secretion from the bovine adrenal medullary chromaffin cells

International Nuclear Information System (INIS)

Guo Shuilong; Cui Xin; Luo Yun; Xue Yilong

2002-01-01

The affection of alginate-polylysine-alginate (APA) microcapsulation on catecholamine (CA) and leucine-enkephalin (L-EK) secretion from bovine adrenal medullary chromaffin cells was analysed. Encapsulating BCCs with the APA microcapsulation, the secretion of CA and L-EK in encapsulated BCCs was detected by high-performance liquid chromatography-electrochemical assay and radioimmunoassay, respectively. There is little difference between the encapsulated BCCs and the non-encapsulated BCCs in the secretion of epinephrine (E) and noradrenaline (NE) but the secretion of dopamine (DA) and L-EK in several points decline. The studies indicated that APA microcapsulation of BCCs didn't affect the secretion of E and NE, but did the secretion DA and L-EK in forepart

Mutant HABP2 Causes Non-Medullary Thyroid Cancer | Center for Cancer Research

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The thyroid is a butterfly-shaped gland that lies at the base of the throat in front of the windpipe. A member of the endocrine system, the thyroid secretes hormones to regulate heart rate, blood pressure, temperature, and metabolism. Cancer of the thyroid is the most common endocrine cancer and the eighth most common cancer in the U.S. An estimated 63,450 Americans will be diagnosed with thyroid cancer this year. The vast majority is of follicular cell origin, and the remaining cancer originates from parafollicular cells, so called medullary thyroid cancer.

The PPARδ Ligand GW501516 Reduces Growth but Not Apoptosis in Mouse Inner Medullary Collecting Duct Cells

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Jordan Clark

2009-01-01

Full Text Available The collecting duct (CD expresses considerable amounts of PPARδ. While its role is unknown in the CD, in other renal cells it has been shown to regulate both growth and apoptosis. We thus hypothesized that PPARδ reduces apoptotic responses and stimulates cell growth in the mouse CD, and examined the effect of GW501516, a synthetic PPARδ ligand, on these responses in mouse IMCD-K2 cells. High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability. Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels. These results show that a PPARδ ligand inhibits growth but does not affect anisomycin-apoptosis in a mouse IMCD cell line. This could have therapeutic implications for renal diseases associated with increased CD growth responses.

PRIMARY SQUAMOUS CELL CARCINOMA OF RENAL PELVIS ASSOCIATED WITH RENAL CALCULUS AND RECURRENT PYONEPHROSIS

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Hoti Lal

2015-11-01

Full Text Available Primary Squamous Cell Carcinoma in the kidney is a rare malignant neoplasm associated with nephrolithiasis, typically monobacterial pyonephrosis and rarely Xanthogranulomatous pyelonephritis. It is an aggressive disease with a poor prognosis mostly due to lack of presenting clinical features like a palpable mass, gross haematuria and pain. We report a case presenting with renal calculus and pyonephrosis managed initially with percutaneous nephrostomy followed by nephrectomy due to complete loss of renal function. Histopathological evaluation revealed poorly differentiated squamous cell carcinoma which is managed by chemotherapy, although initially beneficial, patients later develop disseminated metastatic disease which holds a poor prognosis.

Molecular features of renal cell carcinoma: early diagnostics and perspectives for therapy

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O. V. Kovaleva

2014-01-01

Full Text Available Kidney cancer (renal cell carcinoma is one of the major problems of modern urological oncology. In Russia renal cell carcinoma accountsfor 4.3 % of all cancers. The global incidence of renal cell carcinoma has increased over the past two decades. Worldwide renal cell carcinoma accounts for 3.6 % of all cancers and is 10th frequent malignancy. For some malignancies, for instance tumours of prostate, there are markers known that allowed improved early diagnostics. Kidney cancer, however, remains to be hard to diagnose and to treat, since the symptoms can be detected on advanced stages of the disease. In Russia 75.4 % of renal cell carcinoma cases detected at the stage of local and locally advanced disease. Though there are various target drugs on the market aimed to treat this disease, the results of renal cell carcinoma treatment did not reach any substantial success. Most of existing target drugs for kidney cancer treatment include inhibitors of a single signalingpathway regulated by VHL1, which expression is lost in the vast majority of renal-cell carcinomas. Till now existing drugs did not reach sufficient efficacy. Therefore, it is highly important to search for new signaling pathways, regulating such cellular processes as proliferation, migration and apoptosis. Further, prognostic markers and therapy targets identified so far are not sufficient and poorly specific. Therefore identification and validation of new markers, and especially new specific targets for the treatment of kindey oncopathologies is highly important and timely task.

A brief symptom index for advanced renal cell carcinoma

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Cella David

2006-09-01

Full Text Available Abstract Background Our objective was to test a brief, symptom index for advanced renal cell carcinoma, a disease affecting over 38,000 Americans each year and often diagnosed in late stages. Methods We conducted secondary data analyses on patient-reported outcomes of 209 metastatic renal cell carcinoma patients participating in a Phase III clinical trial. Patient-reported outcomes, obtained from the FACT-Biological Response Modifier (FACT-BRM scale, were available at baseline, 2, and 8 weeks. We analyzed data from eight FACT-BRM items previously identified by clinical experts to represent the most important symptoms of advanced renal cell carcinoma. Items comprising this index assess nausea, pain, appetite, perceived sickness, fatigue and weakness, with higher scores indicating fewer symptoms. We determined reliability and validity of the index and estimated a minimally important difference. Results The index had excellent internal reliability at all three time points (alphas ≥ 0.83. Baseline scores were able to discriminate patients across Karnofsky performance status, number of metastatic sites, and risk group categories (ps Conclusion The 8-item index of patient-reported symptoms of renal cell carcinoma appears to be a psychometrically sound measure. It is a brief, reliable, and valid measure that can easily be adapted for use in clinical trials and observational studies.

Characterizing the outcomes of metastatic papillary renal cell carcinoma

DEFF Research Database (Denmark)

Connor Wells, John; Donskov, Frede; Fraccon, Anna P

2017-01-01

Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were...... compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer...

Papillary renal cell carcinoma in allograft kidney

International Nuclear Information System (INIS)

Roy, Catherine; El Ghali, Sofiane; Buy, Xavier; Gangi, Afshin; Lindner, Veronique

2005-01-01

Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. Its occurrence in allograft transplanted kidney has not been debated in the literature. We report two pathologically proven cases and discuss the clinical hypothesis for such neoplasms and the aspect on MR images. The paramagnetic effect of the iron associated with an absence of signal coming from calcifications is a plausible explanation for this unusual hypointense appearance on T2-weighted sequence. (orig.)

Laparoscopic bilateral nephroureterectomy and bladder cuff excision for native renal pelvic and ureteral transitional cell carcinoma after renal transplantation.

Directory of Open Access Journals (Sweden)

Chen C

2003-01-01

Full Text Available A 37-years-old female who was suffering from end-stage renal disease for about 6 years received allograft renal transplantation 4 years ago. She has been receiving 50mg of Cyclosporin A orally daily for immuno-suppression since then. Gross haematuria was noted and computerised tomography showed native left renal pelvic and ureteral multi-focal transitional cell carcinoma with severe hydronephrosis. Laparoscopic bilateral nephroureterectomy and bladder cuff excision were performed. In the past, history of previous operation was considered a relative contraindication for laparoscopic surgery. To our knowledge, we present the first case of laparoscopic treatment for native renal pelvic and ureteral transitional cell carcinoma after renal allograft transplantation without a hand-assisted device. This case shows the feasibility of laparoscopic bilateral nephroureterectomy in patients with transplanted kidneys.

Triphasic and epithelioid minimal fat renal angiomyolipoma and clear cell renal cell carcinoma: qualitative and quantitative CEUS characteristics and distinguishing features.

Science.gov (United States)

Lu, Qing; Li, Cui-xian; Huang, Bei-jian; Xue, Li-yun; Wang, Wen-ping

2015-02-01

To determine the contrast-enhanced ultrasonography (CEUS) characteristics of minimal fat renal angiomyolipoma (AML) (triphasic and epithelioid) and compare them to each other and to clear cell renal cell carcinoma (ccRCC) to explore their differential diagnostic clue. Qualitative and quantitative CEUS analyses were retrospectively conducted for epithelioid renal AMLs (EAMLs) (n = 15), triphasic minimal fat AMLs (TAMLs) (n = 25), and ccRCCs (n = 113). Enhancement patterns and features with CEUS were qualitatively evaluated. As for the quantitative parameters, rise times (RT), time to peak (TTP), and tumor-to-cortex enhancement ratio (TOC ratio) were compared among these renal tumor histotypes. No significant differences were detected on conventional ultrasound in the three histotypes of renal tumor. On qualitative CEUS analysis, centripetal enhancement in cortical phase (73.3% in EAMLs, 84.0% in TAMLs vs. 18.6% in ccRCCs, p qualitative and quantitative characteristics made no significant difference between EAMLs and TAMLs. In the differential diagnosis of EAMLs from TAMLs, pseudocapsule sign was valuable (40.0% in EAMLs vs. 0.0% in TAMLs, p 97.34% as the criteria to differentiate ccRCCs and EAMLs from TAMLs, the sensitivity and specificity were 80.0% and 87.5%, respectively. Qualitative and quantitative CEUS analyses are helpful in the differential diagnosis of ccRCCs, EAMLs, and TAMLs.

Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

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Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

2015-01-01

Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

Insulin-like growth factor-1 sustains stem cell mediated renal repair.

NARCIS (Netherlands)

Imberti, B.; Morigi, M.; Tomasoni, S.; Rota, C.; Corna, D.; Longaretti, L.; Rottoli, D.; Valsecchi, F.; Benigni, A.; Wang, J.; Abbate, M.; Zoja, C.; Remuzzi, G.

2007-01-01

In mice with cisplatin-induced acute kidney injury, administration of bone marrow-derived mesenchymal stem cells (MSC) restores renal tubular structure and improves renal function, but the underlying mechanism is unclear. Here, we examined the process of kidney cell repair in co-culture experiments

Hematopoiesis stimulation test by interleukin 1α gene transfer in the Cynomolgus macaque: application to secondary medullary aplasia from an accidental irradiation

International Nuclear Information System (INIS)

De Revel, Th.

2002-12-01

After a description of the context of medullary aplasia (haematological radiobiology, radiation acute syndrome, therapeutic care), and an overview of knowledge about the interleukin-1 and medullary stroma cells, this research thesis aims at investigating therapeutic alternatives for radio-accidental aplasia. More precisely, it aims at defining means to get cytokines which are efficient for haematopoiesis. Interleukin-1 is chosen for its properties and tests are performed on a macaque with two approaches for gene transfer: an ex vivo transfer by retroviral vector enabling an integration in the target cell genome, and an in situ transfer by adeno-viral vector directly applied in the animal osseous medulla

Renal cortical volume measured using automatic contouring software for computed tomography and its relationship with BMI, age and renal function

International Nuclear Information System (INIS)

Muto, Natalia Sayuri; Kamishima, Tamotsu; Harris, Ardene A.; Kato, Fumi; Onodera, Yuya; Terae, Satoshi; Shirato, Hiroki

2011-01-01

Purpose: To evaluate the relationship between renal cortical volume, measured by an automatic contouring software, with body mass index (BMI), age and renal function. Materials and methods: The study was performed in accordance to the institutional guidelines at our hospital. Sixty-four patients (34 men, 30 women), aged 19 to 79 years had their CT scans for diagnosis or follow-up of hepatocellular carcinoma retrospectively examined by a computer workstation using a software that automatically contours the renal cortex and the renal parenchyma. Body mass index and estimated glomerular filtration rate (eGFR) were calculated based on data collected. Statistical analysis was done using the Student t-test, multiple regression analysis, and intraclass correlation coefficient (ICC). Results: The ICC for total renal and renal cortical volumes were 0.98 and 0.99, respectively. Renal volume measurements yielded a mean cortical volume of 105.8 cm 3 ± 28.4 SD, mean total volume of 153 cm 3 ± 39 SD and mean medullary volume of 47.8 cm 3 ± 19.5 SD. The correlation between body weight/height/BMI and both total renal and cortical volumes presented r = 0.6, 0.6 and 0.4, respectively, p < 0.05, while the correlation between renal cortex and age was r = -0.3, p < 0.05. eGFR showed correlation with renal cortical volume r = 0.6, p < 0.05. Conclusion: This study demonstrated that renal cortical volume had a moderate positive relationship with BMI, moderate negative relationship with age, and a strong positive relationship with the renal function, and provided a new method to routinely produce volumetric assessment of the kidney.

Recurrent intramedullary epidermoid cyst of conus medullaris.

LENUS (Irish Health Repository)

Fleming, Christina

2011-01-01

Spinal intramedullary epidermoid cyst is a rare condition. Recurrent epidermoid cyst in the spine cord is known to occur. The authors describe a case of recurrent conus medullaris epidermoid cyst in a 24-year-old female. She initially presented at 7 years of age with bladder disturbance in the form of diurnal enuresis and recurrent urinary tract infection. MRI lumbar spine revealed a 4 cm conus medullaris epidermoid cyst. Since the initial presentation, the cyst had recurred seven times in the same location and she underwent surgical intervention in the form of exploration and debulking. This benign condition, owing to its anatomical location, has posed a surgical and overall management challenge. This occurrence is better managed in a tertiary-care centre requiring multi-disciplinary treatment approach.

Blood oxygenation level dependent (BOLD). Renal imaging. Concepts and applications; Blood Oxygenation Level Dependent (BOLD). Bildgebung der Nieren. Konzepte und Anwendungen

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Nissen, Johanna C.; Haneder, Stefan; Schoenberg, Stefan O.; Michaely, Henrik J. [Heidelberg Univ. Medizinische Fakultaet Mannheim (Germany). Inst. fuer Klinische Radiologie und Nuklearmedizin; Mie, Moritz B.; Zoellner, Frank G. [Heidelberg Univ. Medizinische Fakultaet Mannheim (DE). Inst. fuer Computerunterstuetzte Klinische Medizin (CKM)

2010-07-01

Many renal diseases as well as several pharmacons cause a change in renal blood flow and/or renal oxygenation. The blood oxygenation level dependent (BOLD) imaging takes advantage of local field inhomogeneities and is based on a T2{sup *}-weighted sequence. BOLD is a non-invasive method allowing an estimation of the renal, particularly the medullary oxygenation, and an indirect measurement of blood flow without administration of contrast agents. Thus, effects of different drugs on the kidney and various renal diseases can be controlled and observed. This work will provide an overview of the studies carried out so far and identify ways how BOLD can be used in clinical studies. (orig.)

Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration.

Science.gov (United States)

Muller, Marie; Guillaud-Bataille, Marine; Salleron, Julia; Genestie, Catherine; Deveaux, Sophie; Slama, Abdelhamid; de Paillerets, Brigitte Bressac; Richard, Stéphane; Benusiglio, Patrick R; Ferlicot, Sophie

2018-02-06

Hereditary leiomyomatosis and renal cell carcinoma syndrome is characterized by an increased risk of agressive renal cell carcinoma, often of type 2 papillary histology, and is caused by FH germline mutations. A prominent eosinophilic macronucleolus with a perinucleolar clear halo is distinctive of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma according to the 2012 ISUP and 2016 WHO kidney tumor classification. From an immunohistochemistry perspective, tumors are often FH-negative and S-(2-succino)-cysteine (2SC) positive. We performed a pathology review of 24 renal tumors in 23 FH mutation carriers, and compared them to 12 type 2 papillary renal cell carcinomas from FH wild-type patients. Prominent eosinophilic nucleoli with perinucleolar halos were present in almost all FH-deficient renal cell carcinomas (23/24). Unexpectedly, they were also present in 58% of type 2 papillary renal cell carcinomas from wild-type patients. Renal cell carcinoma in mutation carriers displayed a complex architecture with multiple patterns, typically papillary, tubulopapillary, and tubulocystic, but also sarcomatoid and rhabdoid. Such pattern diversity was not seen in non-carriers. FH/2SC immunohistochemistry was informative as all hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas were either FH- or 2SC+. For FH and 2SC immunohistochemistries taken separately, sensitivity of negative anti-FH immunohistochemistry was 87.5% and specificity was 100%. For positive anti-2SC immunohistochemistry, sensitivity, and specificity were 91.7% and 91.7%, respectively. All FH wild-type renal cell carcinoma were FH-positive, and all but one were 2SC-negative. In conclusion, multiplicity of architectural patterns, rhabdoid/sarcomatoid components and combined FH/2SC staining, but not prominent eosinophilic nucleoli with perinucleolar halos, differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal

Multilocular cystic renal cell carcinoma: imaging and clinical correlation

International Nuclear Information System (INIS)

Xu Yong; Zhang Sheng

2013-01-01

Multilocular cystic renal cell carcinoma (MCRCC) is a subtype of clear cell renal cell carcinoma and has mild clinical symptoms and a favorable prognosis. Accordingly, nephron-sparing surgery is recommended as a therapeutic strategy. If histologic subtype of MCRCC can be predicted preoperatively with an acceptable level of accuracy, it may be important in predicting prognosis and make clinical management. Most MCRCCs show characteristic cross-sectional imaging findings and permit accurate diagnosis before the treatment. Cross -sectional imaging of MCRCC reveals a well -defined multilocular cystic mass with irregularly enhanced thickened septa and without enhanced intracystic solid nodule. It is often classified as Bosniak classification Ⅲ , which is significantly different from that of other renal cystic masses. The clinical, pathologic, and radiologic features of MCRCC were discussed and illustrated in this article. The role of the imaging preoperative evaluation for MCRCC, and management implications were emphasized. (authors)

Neural control of adrenal medullary and cortical blood flow during hemorrhage

International Nuclear Information System (INIS)

Breslow, M.J.; Jordan, D.A.; Thellman, S.T.; Traystman, R.J.

1987-01-01

Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, the authors compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Carbonized microspheres labeled with 153 Gd, 114 In, 113 Sn, 103 Ru, 95 Nb or 46 Se were used. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. They conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension

Renal amyloidosis in a child with sickle cell anemia.

Science.gov (United States)

Simşek, Behçet; Bayazit, Aysun K; Ergin, Melek; Soran, Mustafa; Dursun, Hasan; Kilinc, Yurdanur

2006-06-01

The kidney is frequently affected in patients with sickle cell syndrome, i.e., homozygous and heterozygous patients, with a consequently large spectrum of renal abnormalities that may range from minimal functional changes to chronic renal failure. Here, we present a 13-year-old boy with sickle cell anemia (SCA) (HbSS) who was referred to our unit with nephrotic syndrome. Renal biopsy revealed AA type amyloidosis on the basis of light microscopic findings, indicating Congo red staining and immunohistochemistry. He had neither a family history of familial Mediterranean fever (FMF) nor any complaint of recurrent abdominal pain, arthritis, and fever, but frequent painful vaso-occlusive crises. The patient was found to have no MEFV gene (Mediterranean feVer) mutations either. Painful episodic attacks might provoke recurrent acute inflammation, leading to repeated stimulation of acute phase responses and cause secondary amyloidosis. To our knowledge, this boy is the first case of SCA complicated by renal amyloidosis observed in childhood.

Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

Directory of Open Access Journals (Sweden)

Kenan Ashouri

2015-09-01

Full Text Available Von Hippel-Lindau syndrome (VHLS is a rare hereditary neoplastic disorder caused by mutations in the vhl gene leading to the development of tumors in several organs including the central nervous system, pancreas, kidneys, and reproductive organs. Manifestations of VHLS can present at different ages based on the affected organ and subclass of disease. In the subclasses of VHLS that cause renal disease, renal involvement typically begins closer to the end of the second decade of life and can present in different ways ranging from simple cystic lesions to solid tumors. Mutations in vhl are most often associated with clear cell renal carcinoma, the most common type of renal cancer, and also play a major role in sporadic cases of clear cell renal carcinoma. The recurrent, multifocal nature of this disease presents difficult challenges in the long-term management of patients with VHLS. Optimization of renal function warrants the use of several different approaches common to the management of renal carcinoma such as nephron sparing surgery, enucleation, ablation, and targeted therapies. In VHLS, renal lesions of 3 cm or bigger are considered to have metastatic potential and even small lesions often harbor malignancy. Many of the aspects of management revolve around optimizing both oncologic outcome and long-term renal function. As new surgical strategies and targeted therapies develop, the management of this complex disease evolves.  This review will discuss the key aspects of the current management of VHLS.

Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma

International Nuclear Information System (INIS)

Sun, Shiren; Ning, Xiaoxuan; Liu, Jie; Liu, Lili; Chen, Yu; Han, Shuang; Zhang, Yanqi; Liang, Jie; Wu, Kaichun; Fan, Daiming

2007-01-01

Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of S100, has been identified as a component of a novel ubiquitinylation complex leading to β-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer. However, the roles of CacyBP/SIP in renal cell carcinoma still remain unclear. In the present study, we had analyzed the expression of the CacyBP/SIP protein in human renal cancer cells and clinical tissue samples. The possible roles of CacyBP/SIP in regulating the malignant phenotype of renal cancer cells were also investigated. The results demonstrated that the expression of CacyBP/SIP was markedly down-regulated in renal cell carcinoma tissues and cell lines. Ectopic overexpression of CacyBP/SIP in A498 cells inhibited the proliferation of this cell and delayed cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1 through reducing β-catenin protein. CacyBP/SIP also suppressed colony formation in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that CacyBP/SIP, as a novel down-regulated gene in renal cell carcinoma, suppressed proliferation and tumorigenesis of renal cancer cells

[Renal cell carcinoma producing erythrocytosis due to inappropriate production of erythropoietin].

Science.gov (United States)

Villanueva-Gimeno, M M; Vicario-Bermúdez, J M; Fonseca-López, Ch; Caballero-Castro, J P; Zabala-López, S I; Sánchez-Elipe, M A; González-Gómez, N

2013-01-01

Erythrocytosis, or polycythaemia, is an increase, in absolute terms, of the erythrocyte mass. The most common solid tumour related to this phenomenon is renal cell carcinoma, which can produce erythrocytosis by increasing erythropoietin production. About 30% of symptomatic renal cell carcinomas are diagnosed due to the appearance of a paraneoplastic syndrome. Polycythaemia is one of these. Surgery, (radical or partial nephrectomy), is the treatment of choice in renal cell carcinoma and helps to keep the erythrocytosis situation under control. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Renal hemodynamics and oxygenation in transient renal artery occluded rats evaluated with iron-oxide particles and oxygenation-sensitive imaging

International Nuclear Information System (INIS)

Pedersen, Michael; Aarhus Univ.; Univ. Victor Segalen Bordeaux 2; Laustsen, Christoffer; Perot, Vincent; Grenier, Nicolas; Basseau, Fabrice; Moonen, Chrit

2010-01-01

Mild or severe renal arterial occlusion is a phenomenon occasionally observed in daily clinical practice, potentially leading to renal ischemia and a general impairment of renal function. Secondly, closing the blood flow to the kidneys can also occur during kidney transplantation procedures. However, the exact physiological effects of these conditions on renal blood perfusion as well as the renal oxygen handling are poorly understood. The objectives of this study were therefore to measure the lateral changes of renal blood perfusion in rats subjected to transient unilateral arterial occlusion (RAS), and in addition, to measure the consequences on the intrarenal oxygenation. Experimental studies were performed using sixteen adolescent rats. The left renal artery was exposed through a flank incision and acute RAS for 45 min was achieved by placing a ligature around the renal artery. MRI was performed 3 days after the surgical procedure, where a blood oxygenation sensitive sequence (BOLD MRI) was performed, followed by a perfusion-weighted imaging sequence using a single bolus of the iron-oxide nanoparticle Sinerem. The renal oxygenation of blood was indirectly measured by the BOLD-parameter R2 * , and perfusion measures include relative renal blood flow, relative renal blood volume and mean transit time. Histopathologic changes through the outer stripe of the outer medulla showing typical histopathologic findings of ischemia. This study demonstrated that rats with transient renal arterial stenosis (for 45 min) showed a reduction in intrarenal oxygenation and intrarenal blood flow three days after the surgical procedure. A decreased R2 * was measured within the ipsilateral medulla in parallel with a decreased medullary blood flow, is probably related to a lower reabsorption load within the ipsilateral kidney. MRI may therefore be a promising tool in long-term evaluation of RAS. (orig.)

Renal hemodynamics and oxygenation in transient renal artery occluded rats evaluated with iron-oxide particles and oxygenation-sensitive imaging

Energy Technology Data Exchange (ETDEWEB)

Pedersen, Michael [Aarhus Univ. Hospital (Denmark). MR Research Centre; Aarhus Univ. (Denmark). Inst. of Experimental Clinical Medicine; Univ. Victor Segalen Bordeaux 2 (France). Lab. Imagerie Moleculaire et Fonctionnelle: de la physiologie a la therapie CNRS UMR 5231; Laustsen, Christoffer [Aarhus Univ. Hospital (Denmark). MR Research Centre; Perot, Vincent; Grenier, Nicolas [Hopital Pellegrin, CHU Bordeaux (France). Service d' Imagerie Diagnostique et Therapeutique de l' Adulte; Basseau, Fabrice; Moonen, Chrit [Univ. Victor Segalen Bordeaux 2 (France). Lab. Imagerie Moleculaire et Fonctionnelle: de la physiologie a la therapie CNRS UMR 5231

2010-07-01

Mild or severe renal arterial occlusion is a phenomenon occasionally observed in daily clinical practice, potentially leading to renal ischemia and a general impairment of renal function. Secondly, closing the blood flow to the kidneys can also occur during kidney transplantation procedures. However, the exact physiological effects of these conditions on renal blood perfusion as well as the renal oxygen handling are poorly understood. The objectives of this study were therefore to measure the lateral changes of renal blood perfusion in rats subjected to transient unilateral arterial occlusion (RAS), and in addition, to measure the consequences on the intrarenal oxygenation. Experimental studies were performed using sixteen adolescent rats. The left renal artery was exposed through a flank incision and acute RAS for 45 min was achieved by placing a ligature around the renal artery. MRI was performed 3 days after the surgical procedure, where a blood oxygenation sensitive sequence (BOLD MRI) was performed, followed by a perfusion-weighted imaging sequence using a single bolus of the iron-oxide nanoparticle Sinerem. The renal oxygenation of blood was indirectly measured by the BOLD-parameter R2{sup *}, and perfusion measures include relative renal blood flow, relative renal blood volume and mean transit time. Histopathologic changes through the outer stripe of the outer medulla showing typical histopathologic findings of ischemia. This study demonstrated that rats with transient renal arterial stenosis (for 45 min) showed a reduction in intrarenal oxygenation and intrarenal blood flow three days after the surgical procedure. A decreased R2{sup *} was measured within the ipsilateral medulla in parallel with a decreased medullary blood flow, is probably related to a lower reabsorption load within the ipsilateral kidney. MRI may therefore be a promising tool in long-term evaluation of RAS. (orig.)

Sodium-bicarbonate cotransporter NBCn1 in the kidney medullary thick ascending limb cell line is upregulated under acidic conditions and enhances ammonium transport.

Science.gov (United States)

Lee, Soojung; Lee, Hye Jeong; Yang, Han Soo; Thornell, Ian M; Bevensee, Mark O; Choi, Inyeong

2010-09-01

In this study, we examined the effect of bicarbonate transporters on ammonium/ammonia uptake in the medullary thick ascending limb cell line ST-1. Cells were treated with 1 mm ouabain and 0.2 mM bumetanide to minimize carrier-mediated NH(4)(+) transport, and the intracellular accumulation of (14)C-methylammonium/methylammonia ((14)C-MA) was determined. In CO(2)/HCO(3)(-)-free solution, cells at normal pH briefly accumulated (14)C-MA over 7 min and reached a plateau. In CO(2)/HCO(3)(-) solution, however, cells markedly accumulated (14)C-MA over the experimental period of 30 min. This CO(2)/HCO(3)(-)-dependent accumulation was reduced by the bicarbonate transporter blocker, 4,4-diisothiocyanatostilbene-2,2-disulfonate (DIDS; 0.5 mM). Replacing Cl(-) with gluconate reduced the accumulation, but the reduction was more substantial in the presence of DIDS. Incubation of cells at pH 6.8 (adjusted with NaHCO(3) in 5% CO(2)) for 24 h lowered the mean steady-state intracellular pH to 6.96, significantly lower than 7.28 for control cells. The presence of DIDS reduced (14)C-MA accumulation in control conditions but had no effect after acidic incubation. Immunoblotting showed that NBCn1 was upregulated after acidic incubation and in NH(4)Cl-containing media. The Cl(-)-HCO(3)(-) exchanger AE2 was present, but its expression remained unaffected by acidic incubation. Expressed in Xenopus oocytes, NBCn1 increased carrier-mediated (14)C-MA transport, which was abolished by replacing Na(+). Two-electrode voltage clamp of oocytes exhibited negligible current after NH(4)Cl application. These results suggest that DIDS-sensitive HCO(3)(-) extrusion normally governs NH(4)(+)/NH(3) uptake in the medullary thick ascending limb cells. We propose that, in acidic conditions, DIDS-sensitive HCO(3)(-) extrusion is inactivated, while NBCn1 is upregulated to stimulate NH(4)(+) transport.

Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells.

Science.gov (United States)

Payne, Emily H; Ramalingam, Dhivya; Fox, Donald T; Klotman, Mary E

2018-01-15

Prior studies have found that HIV, through the Vpr protein, promotes genome reduplication (polyploidy) in infection-surviving epithelial cells within renal tissue. However, the temporal progression and molecular regulation through which Vpr promotes polyploidy have remained unclear. Here we define a sequential progression to Vpr-mediated polyploidy in human renal tubule epithelial cells (RTECs). We found that as in many cell types, Vpr first initiates G 2 cell cycle arrest in RTECs. We then identified a previously unreported cascade of Vpr-dependent events that lead to renal cell survival and polyploidy. Specifically, we found that a fraction of G 2 -arrested RTECs reenter the cell cycle. Following this cell cycle reentry, two distinct outcomes occur. Cells that enter complete mitosis undergo mitotic cell death due to extra centrosomes and aberrant division. Conversely, cells that abort mitosis undergo endoreplication to become polyploid. We further show that multiple small-molecule inhibitors of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, including those that target ATR, ATM, and mTOR, indirectly prevent Vpr-mediated polyploidy by preventing G 2 arrest. In contrast, an inhibitor that targets DNA-dependent protein kinase (DNA-PK) specifically blocks the Vpr-mediated transition from G 2 arrest to polyploidy. These findings outline a temporal, molecularly regulated path to polyploidy in HIV-positive renal cells. IMPORTANCE Current cure-focused efforts in HIV research aim to elucidate the mechanisms of long-term persistence of HIV in compartments. The kidney is recognized as one such compartment, since viral DNA and mRNA persist in the renal tissues of HIV-positive patients. Further, renal disease is a long-term comorbidity in the setting of HIV. Thus, understanding the regulation and impact of HIV infection on renal cell biology will provide important insights into this unique HIV compartment. Our work identifies mechanisms that distinguish

Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma

Science.gov (United States)

Denis, Catherine J.; Van Acker, Nathalie; De Schepper, Stefanie; De Bie, Martine; Andries, Luc; Fransen, Erik; Hendriks, Dirk; Kockx, Mark M.

2013-01-01

Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney. PMID:23172796

The multislice CT findings of renal carcinoma associated with XP11.2 translocation/TFE gene fusion and collecting duct carcinoma

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Zhu Qingqiang; Zhu Wenrong; Chen Wenxin; Wu Jingtao [Subei People' s Hospital, Clinical School of Medical Coll., Yangzhou (China)], e-mail: wujingtaodoctor@163.com; Wang Zhongqiu [Dept. of Radiology, East Hospital, Tongji Univ. School of Medicine, Shanghai (China)

2013-04-15

Background: Renal cell carcinoma associated with Xp11.2 translocation and TFE gene fusion (Xp11.2/TFE RCC), and collecting duct carcinoma (CDC) are uncommon subtypes of renal cell carcinomas. Purpose: To investigate the multislice CT (MSCT) characteristics of these two tumor types. Material and Methods Nine patients with Xp11.2/TFE RCC and 10 patients with CDC were studied retrospectively. MSCT was undertaken to investigate differences in tumor characteristics and enhancement patterns. Results: All patients had single tumors centered in the renal medulla. Two patients with each tumor type had lymph node involvement and there was a single case of hepatic metastasis (Xp11.2/TFE RCC). The mean tumor diameter of Xp11.2/TFE RCC tumors was significantly larger than for CDC tumors. Two patients with Xp11.2/TFE RCC had cystic components as did eight patients with CDC (P < 0.05). Calcifications were present in six patients, each with CDC. Clear tumor boundaries were visible in two patients with CDC and in nine with Xp11.2/TFE RCC (P < 0.05). The density of Xp11.2/TFE RCC tumors was greater than that of CDC tumors, normal renal cortex, or medulla on unenhanced CT. Enhancement was higher with Xp11.2/TFE RCC than with CDC tumors during all phases. Xp11.2/TFE RCC enhancement was higher than in the renal medulla during cortical and medullary phase but lower than in normal renal medulla during the delayed phase. CDC tumor enhancement was lower than that for normal renal medulla during all enhanced phases. Conclusion: Both tumor types originated from the renal medulla. Distinguishing features included density on unenhanced CT, enhancement patterns, and capsule signs. Identifying these differences may aid diagnosis.

Chronological alterations of diagnostic imaging of renal cell carcinoma

International Nuclear Information System (INIS)

Arima, Kiminobu; Sugimura, Yoshiki; Yanagawa, Makoto; Tochigi, Hiromi; Kawamura, Juichi

1994-01-01

A review of 156 cases of renal cell carcinoma diagnosed during a 20-year period demonstrated the changes of initial signs/symptoms and imaging modalities for detection and definition. According to the imaging modality used for diagnosing renal cell carcinoma, clinical pictures were chronologically examined over 4 periods: 1973 to 1979 (before CT era), 1980 to 1984 (early CT era), 1985 to 1987 (CT era) and 1988 to 1992 (CT/MRI era). With regards to initial signs or symptoms, the proportion of classical trials has gradually decreased, while that of tumors noted incidentally has increased. As for imaging modalities for detection, the proportion of IVP has gradually decreased and that of CT and US has increased over the periods. With regard to imaging modalities for definition, the proportion of angiography has decreased and that of CT has increased. From chronological changes in clinical pictures and imaging modalities, we suggested a decision tree of imaging modalities for detection and definition of renal cell carcinoma. (author)

Clinical and pathological features of papillary renal cell carcinoma ...

African Journals Online (AJOL)

Introduction and objectives: Papillary renal cell carcinoma (PRCC) accounts for 10–15% of renal tumors in adults. This type of tumor contains more than 75% of tubulo-papillary structures and is divided histologically into two subtypes. The distinction between these two subtypes is essential because of their prognostic value.

Renal cell apoptosis in human lupus nephritis: a histological study

DEFF Research Database (Denmark)

Faurschou, M; Penkowa, Milena; Andersen, C B

2009-01-01

Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...... biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any...... cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis....

The unique organization of filamentous actin in the medullary canal of the medulla oblongata.

Science.gov (United States)

Tan, Bai-Hong; Guo, Chun-Yan; Xiong, Tian-Qing; Chen, Ling-Meng; Li, Yan-Chao

2017-04-01

In the central canal, F-actin is predominantly localized in the apical region, forming a ring-like structure around the circumference of the lumen. However, an exception is found in the medulla oblongata, where the apical F-actin becomes interrupted in the ventral aspect of the canal. To clarify the precise localization of F-actin, the fluorescence signals for F-actin were converted to the peroxidase/DAB reaction products in this study by a phalloidin-based ultrastructural technique, which demonstrated that F-actin is located mainly in the microvilli and terminal webs in the ependymocytes. It is because the ventrally oriented ependymocytes do not possess well-developed microvilli or terminal web that led to a discontinuous labeling of F-actin in the medullary canal. Since spinal motions can change the shape and size of the central canal, we next examined the cytoskeletons in the medullary canal in both rats and monkeys, because these two kinds of animals show different kinematics at the atlanto-occipital articulation. Our results first demonstrated that the apical F-actin in the medullary canal is differently organized in the animals with different head-neck kinemics, which suggests that the mechanic stretching of spinal motions is capable of inducing F-actin reorganization and the subsequent cell-shape changes in the central canal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of indomethacin and salt depletion on renal proton MR imaging; An experimental study in the rat

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Heyman, S.N.; Mammen, M. (Harvard Medical School, Boston, MA (United States). Charles A Dana Research Inst. Beth Israel Hospital, Boston, MA (United States))

1991-11-01

Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti-inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may effect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non-steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion. (orig.).

Cells derived from young bone marrow alleviate renal aging.

Science.gov (United States)

Yang, Hai-Chun; Rossini, Michele; Ma, Li-Jun; Zuo, Yiqin; Ma, Ji; Fogo, Agnes B

2011-11-01

Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.

The effect of renal denervation on kidney oxygenation as determined by BOLD MRI in patients with hypertension

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Vink, E.E.; Boer, A.; Blankestijn, P.J. [University Medical Center Utrecht, Department of Nephrology, P.O. Box 85500, GA, Utrecht (Netherlands); Verloop, W.L.; Voskuil, M. [University Medical Center Utrecht, Department of Cardiology, Utrecht (Netherlands); Spiering, W.; Leiner, T. [University Medical Center Utrecht, Department of Vascular Medicine, Utrecht (Netherlands); Vonken, E.; Hoogduin, J.M. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Bots, M.L. [University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands)

2015-07-15

Renal denervation (RDN) is a promising therapy for resistant hypertension. RDN is assumed to decrease sympathetic activity. Consequently, RDN can potentially increase renal oxygenation. Blood oxygen level-dependent MRI (BOLD-MRI) provides a non-invasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the effect of RDN on renal oxygenation as determined by BOLD-MRI. Patients with resistant hypertension or the inability to follow a stable drug regimen due to unacceptable side effects were included. BOLD-MRI was performed before and 12 months after RDN. Twenty-seven patients were imaged on 3 T and 19 on 1.5 T clinical MRI systems. Fifty-four patients were included, 46 patients (23 men, mean age 57 years) completed the study. Mean 24-h BP changed from 163(±20)/98(±14) mmHg to 154(±22)/92(±13) mmHg (p = 0.001 and p < 0.001). eGFR did not change after RDN [77(±18) vs. 79(±20) mL/min/1.73 m{sup 2}; p = 0.13]. RDN did not affect renal oxygenation [1.5 T: cortical R2*: 12.5(±0.9) vs. 12.5(±0.9), p = 0.94; medullary R2*: 19.6(±1.7) vs. 19.3(1.4), p = 0.40; 3 T: cortical R2*: 18.1(±0.8) vs. 17.8(±1.2), p = 0.47; medullary R2*: 27.4(±1.9) vs. 26.7(±1.8), p = 0.19]. The current study shows that RDN does not lead to changes in renal oxygenation 1 year after RDN as determined by BOLD-MRI. (orig.)

An aggressive merkel cell carcinoma in a patient with chronic renal failure

Directory of Open Access Journals (Sweden)

Sevda Gizlenti

2014-12-01

Full Text Available Merkel cell carcinoma (MCC is a rare cutaneous tumor arising from neuroendocrine cells and Merkel cells. Early diagnosis and treatment is important because of its aggressive course. We here report a 61 years old man with chronic renal failure, 3x5 cm mass on his right leg and inguinal-paraaortic lymph node metastases and resulting in death. MCC in the literature of the AIDS disease, organ transplantation, immunosuppressive therapy areas, and additional malignancies (multiple myeloma, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and melanoma have been reported in patients with increased incidence. Up to date a patient with renal transplantation and Merkel cell carcinoma have been reported in the literature, Merkel cell carcinoma with chronic renal failure have not been reported.

Two-dimensional Fourier analysis of the spongy medullary keratin of structurally coloured feather barbs

Science.gov (United States)

Prum, R. O.; Torres, R.; Williamson, S.; Dyck, J.

1999-01-01

We conducted two-dimensional (2D) discrete Fourier analyses of the spatial variation in refractive index of the spongy medullary keratin from four different colours of structurally coloured feather barbs from three species of bird: the rose-faced lovebird, Agapornis roseicollis (Psittacidae), the budgerigar, Melopsittacus undulatus (Psittacidae), and the Gouldian finch, Poephila guttata (Estrildidae). These results indicate that the spongy medullary keratin is a nanostructured tissue that functions as an array of coherent scatterers. The nanostructure of the medullary keratin is nearly uniform in all directions. The largest Fourier components of spatial variation in refractive index in the tissue are of the appropriate size to produce the observed colours by constructive interference alone. The peaks of the predicted reflectance spectra calculated from the 2D Fourier power spectra are congruent with the reflectance spectra measured by using microspectrophotometry. The alternative physical models for the production of these colours, the Rayleigh and Mie theories, hypothesize that medullary keratin is an incoherent array and that scattered waves are independent in phase. This assumption is falsified by the ring-like Fourier power spectra of these feathers, and the spacing of the scattering air vacuoles in the medullary keratin. Structural colours of avian feather barbs are produced by constructive interference of coherently scattered light waves from the optically heterogeneous matrix of keratin and air in the spongy medullary layer.

MiT family translocation renal cell carcinoma.

Science.gov (United States)

Argani, Pedram

2015-03-01

The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

Renal cells activate the platelet receptor CLEC-2 through podoplanin

Science.gov (United States)

Christou, Charita M.; Pearce, Andrew C.; Watson, Aleksandra A.; Mistry, Anita R.; Pollitt, Alice Y.; Fenton-May, Angharad E.; Johnson, Louise A.; Jackson, David G.; Watson, Steve P.; O'Callaghan, Chris A.

2009-01-01

We have recently shown that the C-type lectin-like receptor, CLEC-2, is expressed on platelets and that it mediates powerful platelet aggregation by the snake venom toxin, rhodocytin. In addition, we have provided indirect evidence for an endogenous ligand for CLEC-2 in renal cells expressing human immunodeficiency virus type 1 (HIV-1). This putative ligand facilitates transmission of HIV through its incorporation into the viral envelope and binding to CLEC-2 on platelets. The aim of this study was to identify the ligand on these cells which binds to CLEC-2 on platelets. Recombinant CLEC-2 exhibits specific binding to 293T cells in which the HIV can be grown. Further, 293T cells activate both platelets and CLEC-2-transfected DT-40 B cells. The transmembrane protein podoplanin was identified on 293T cells and demonstrated to mediate both binding of 293T cells to CLEC-2 and 293T cell activation of CLEC-2-transfected DT-40 B cells. Podoplanin is expressed on renal cells (podocytes). Further, a direct interaction between CLEC-2 and podoplanin was confirmed using surface plasmon resonance and was shown to be independent of glycosylation of CLEC-2. The interaction has an affinity of 24.5 ± 3.7μM. The present study identifies podoplanin as a ligand for CLEC-2 on renal cells. PMID:18215137

Dynamic magnetic resonance imaging in the assessment of chronic medical nephropathies with impaired renal function

International Nuclear Information System (INIS)

Dalla-Palma, L.; Pozzi-Mucelli, R.S.; Cova, M.; Meduri, S.; Panzetta, G.; Galli, G.

2000-01-01

We examined the value of dynamic magnetic resonance imaging (MRI) in chronic renal disease with renal insufficiency. In 33 consecutive patients (21 vascular nephropathy, 12 glomerular nephropathy) MRI was performed using a 1.5-T unit and a body coil, with SE T1-weighted (TR/TE = 600/19 ms) and dynamic TFFE T1-weighted sequences (TR/TE = 12/5 ms, flip angle = 25 ) after manual bolus injection (via a cubital vein) of 0.1 mmol/kg Gd-DTPA-BMA. Morphological evaluation was performed in unblinded fashion by three radiologists, evaluating renal size, cortical thickness, and corticomedullary differentiation. Functional analysis was performed by one reviewer. Time-signal intensity curves, peak intensity value (P), time to peak intensity (T), and the P/T ratio were obtained at the cortex, medulla, and pyelocaliceal system of each kidney. The relationship of these parameters to serum creatinine and with creatinine clearance was investigated. A good correlation between morphological features of the kidneys and serum creatinine values was found. Morphological findings could not distinguish between vascular and glomerular nephropathies. A statistically significant correlation (P <0.01) between cortical P, cortical P/T, medullary P, and serum creatinine and creatinine clearance was found. A significant correlation (P <0.01) was also found between cortical T, medullary P/T, T of the excretory system, and creatinine clearance. The cortical T value was significantly higher (P <0.01) in vascular nephropathy than in glomerular nephropathy. Thus in patients with chronic renal failure dynamic MRI shows both morphological and functional changes. Morphological changes are correlated with the degree of renal insufficiency and not with the type of nephropathy; the functional changes seem to differ in vascular from glomerular nephropathies. (orig.)

Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection.

Science.gov (United States)

Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

2015-11-03

Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules including chemokine receptor type 5 (CXCR5), inducible T cell co-stimulator (ICOS), programmed death-1 (PD-1), ICOSL, PDL-1 and interleukin-21 (IL-21), of peripheral blood were comparatively measured in 42 primary renal allograft recipients within 1-3 years after transplantation. Among them, 24 patients had definite chronic rejection, while other 18 patients had normal renal function. Tfh-cell ratio was significantly increased with PD-1 down-regulation in the patients with chronic renal allograft rejection, while B cells and the alloimmune-regulating molecules studied did not show any appreciable change in parallel. The patients with chronic renal allograft rejection have a characteristic increase in circulating Tfh cells with a decrease in PD-1 expression. These pathological changes may be a therapeutic target for the treatment of chronic renal allograft rejection and can be useful as a clinical index for monitoring conditions of renal transplant.

Renal venous thrombosis in an infant with predisposing thrombotic factors: color Doppler ultrasound and MR evaluation

Energy Technology Data Exchange (ETDEWEB)

Argyropoulou, Maria I.; Papadopoulou, Frederica; Nikolopoulos, Pangiotis [Department of Radiology, Medical School, University of Ioannina, 45110, Ioannina (Greece); Giapros, Vassilios I.; Drougia, Aikaterini A.; Andronikou, Styliani [Neonatology Clinic, Medical School, University of Ioannina, 45110, Ioannina (Greece); Vartholomatos, Georgios A. [Department of Haematology, Medical School, University of Ioannina, 45110, Ioannina (Greece)

2003-08-01

We report a case of a neonate with hereditary thrombophilia presenting with renal venous thrombosis (RVT). Early color Doppler findings of RVT were lacking venous flow, and the arterial diastolic flow was reversed. This very high-resistance arterial flow is for the first time described in neonatal RVT. Magnetic resonance imaging showed low signal intensity of the renal pyramids on T1- and T2-weighted images, suggesting acute hemorrhage. After intravenous contrast injection, persistent cortical enhancement was observed along with lack of medullary enhancement. Despite the progressive reestablishment of some venous drainage, the kidney showed atrophy and loss of function. (orig.)

Renal venous thrombosis in an infant with predisposing thrombotic factors: color Doppler ultrasound and MR evaluation

International Nuclear Information System (INIS)

Argyropoulou, Maria I.; Papadopoulou, Frederica; Nikolopoulos, Pangiotis; Giapros, Vassilios I.; Drougia, Aikaterini A.; Andronikou, Styliani; Vartholomatos, Georgios A.

2003-01-01

We report a case of a neonate with hereditary thrombophilia presenting with renal venous thrombosis (RVT). Early color Doppler findings of RVT were lacking venous flow, and the arterial diastolic flow was reversed. This very high-resistance arterial flow is for the first time described in neonatal RVT. Magnetic resonance imaging showed low signal intensity of the renal pyramids on T1- and T2-weighted images, suggesting acute hemorrhage. After intravenous contrast injection, persistent cortical enhancement was observed along with lack of medullary enhancement. Despite the progressive reestablishment of some venous drainage, the kidney showed atrophy and loss of function. (orig.)

Direct Reprogramming of Human Bone Marrow Stromal Cells into Functional Renal Cells Using Cell-free Extracts

Directory of Open Access Journals (Sweden)

Evangelia Papadimou

2015-04-01

Full Text Available The application of cell-based therapies in regenerative medicine is gaining recognition. Here, we show that human bone marrow stromal cells (BMSCs, also known as bone-marrow-derived mesenchymal cells, can be reprogrammed into renal proximal tubular-like epithelial cells using cell-free extracts. Streptolysin-O-permeabilized BMSCs exposed to HK2-cell extracts underwent morphological changes—formation of “domes” and tubule-like structures—and acquired epithelial functional properties such as transepithelial-resistance, albumin-binding, and uptake and specific markers E-cadherin and aquaporin-1. Transmission electron microscopy revealed the presence of brush border microvilli and tight intercellular contacts. RNA sequencing showed tubular epithelial transcript abundance and revealed the upregulation of components of the EGFR pathway. Reprogrammed BMSCs integrated into self-forming kidney tissue and formed tubular structures. Reprogrammed BMSCs infused in immunodeficient mice with cisplatin-induced acute kidney injury engrafted into proximal tubuli, reduced renal injury and improved function. Thus, reprogrammed BMSCs are a promising cell resource for future cell therapy.

Renal cortical and medullary blood flow responses to altered NO-availability in humans

DEFF Research Database (Denmark)

Damkjaer, Mads; Vafaee, Manoucher; Møller, Michael Lehd

2010-01-01

The objective was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned and regional renal blood flow determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were performed...... of one voxel were eliminated stepwise from the external surface of the VOI ('voxel peeling'), and the blood flow subsequently determined in each new, reduced VOI. Blood flow in the shrinking volumes of interest (VOIs) decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood...... flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ±0.17 ml·(g·min)(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ±0.18 ml·(g·min)(-1) (p...

Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database.

Science.gov (United States)

Favazza, Laura; Chitale, Dhananjay A; Barod, Ravi; Rogers, Craig G; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam; Gupta, Nilesh S; Williamson, Sean R

2017-11-01

Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.

Neurobrucellosis presenting as an intra-medullary spinal cord abscess

Directory of Open Access Journals (Sweden)

Patil Chidanand S

2005-09-01

Full Text Available Abstract Background Of the diverse presentation of neurobrucellosis, intra-medullary spinal cord abscess is extremely rare. Only four other cases have been reported so far. We present a case of spinal cord intra-medullary abscess due to Brucella melitensis. Case presentation A forty-year-old female presented with progressive weakness of both lower limb with urinary incontinence of 6 months duration. She was febrile. Neurological examination revealed flaccid areflexic paraplegia with T10 below sensory impairment including perianal region. An intramedullary mass was diagnosed on Magnetic Resonance Image (MRI scan extending from T12 to L2. At surgery, a large abscess was encountered at the conus medullaris, from which Brucella melitensis was grown on culture. She was started on streptomycin and doxycycline for 1 month, followed by rifampicin and doxycycline for 1 month. At 2-year follow-up, she had recovered only partially and continued to have impaired bladder function. Conclusion Neurobrucellosis, if not treated early, can result in severe neurological morbidity and sequale, which may be irreversible. Hence it is important to consider the possibility of neurobrucellosis in endemic region and treat aggressively.

A 9 years boy with MEN-2B variant of medullary thyroid carcinoma.

Science.gov (United States)

Sattar, M A; Hadi, H I; Ekramuddoula, F M; Hasanuzzaman, S M

2013-04-01

To highlight a rare disease like multiple endocrine neoplasia (MEN)-2B variant of medullary thyroid carcinoma and to optimize the management option in such cases, we present a nine year old boy with thyroid swelling, cervical lymphadenopathy and thick lips. His calcitonin level was raised. Investigation's results of the boy were as following fine needle aspiration cytology (FNAC) was medullary carcinoma of thyroid, preoperative calcitonin was >2000pg/ml, post operative histopathological report was medullary carcinoma. Total thyroidectomy with aggressive initial neck surgery may reduce the recurrence and increase better prognosis and survival rate. Calcitonin is used as diagnostic and follow-up marker.

Radionuclide bone scanning of medullary chondrosarcoma

International Nuclear Information System (INIS)

Hudson, T.M.; Chew, F.S.; Manaster, B.J.

1982-01-01

Technetium-99m methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan intake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the ''extended pattern of uptake'' beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogenous uptake on the scan

Radionuclide bone scanning of medullary chondrosarcoma

International Nuclear Information System (INIS)

Hudson, T.M.; Chew, F.S.; Manaster, B.J.

1982-01-01

/sup 99m/Tc methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan uptake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the extended pattern of uptake beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogeneous uptake on the scan

mTOR inhibitors in the treatment of advanced renal cell carcinoma

International Nuclear Information System (INIS)

Barilla, R.; Sycova-Mila, Z.

2009-01-01

Renal Cell Carcinoma (RCC) accounts for approximately 4 % of all malignancies. Much is known about the pathogenesis of RCC because of studies examining its close relationship with dysfunction of the Von Hippel-Lindau gene (VHL) and hypoxia inducible factor (HIF). Mammalian target of rapamycin (mTOR) regulates nutritional needs, cell growth, and angiogenesisi in cells by down regulating or up regulating a variety of proteins including HIF. Until 2005, only a single agent high dose interleukin 2 was approved by Food and Drug Administration (FDA) for treatment of advanced renal cell carcinoma. More recently thanks to better knowledge in the field of molecular biology new treatment options appeared. Sunitinib and bevacizumab are currently considered to be treatment of first choice for patients in good and intermediate prognostic group and sorafenib is preferred second line treatment in the same patient population pretreated with cytokines after disease progression. Temsirolimus and everolimus, rapamycin analouges, have recently been tested in III trials in first and second line treatment in patients with advanced metastatic clear cell renal cell carcinoma. (author)

Cardiac Metastasis in Renal Cell Carcinoma

African Journals Online (AJOL)

abp

2015-10-21

Oct 21, 2015 ... Metastatic disease of the heart is over twenty times more common than primary heart tumors [1]. They are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Cardiac involvement in renal cell carcinoma (RCC) commonly arises from direct ...

Regulatory mechanism of ulinastatin on autophagy of macrophages and renal tubular epithelial cells

Directory of Open Access Journals (Sweden)

Wu Ming

2018-04-01

Full Text Available Kidney ischemia and hypoxia can cause renal cell apoptosis and activation of inflammatory cells, which lead to the release of inflammatory factors and ultimately result in the damage of kidney tissue and the whole body. Renal tubular cell and macrophage autophagy can reduce the production of reactive oxygen species (ROS, thereby reducing the activation of inflammatory cytoplasm and its key effector protein, caspase-1, which reduces the expression of IL-1β and IL-18 and other inflammatory factors. Ulinastatin (UTI, as a glycoprotein drug, inhibits the activity of multiple proteases and reduces myocardial damage caused by ischemia-reperfusion by upregulating autophagy. However, it can be raised by macrophage autophagy, reduce the production of ROS, and ultimately reduce the expression of inflammatory mediators, thereby reducing renal cell injury, promote renal function recovery is not clear. In this study, a series of cell experiments have shown that ulinastatin is reduced by regulating the autophagy of renal tubular epithelial cells and macrophages to reduce the production of reactive oxygen species and inflammatory factors (TNF-α, IL-1β and IL-1, and then, increase the activity of the cells under the sugar oxygen deprivation model. The simultaneous use of cellular autophagy agonists Rapamycin (RAPA and ulinastatin has a synergistic effect on the production of reactive oxygen species and the expression of inflammatory factors.

Mitochondria-Targeted Nitroxide, Mito-CP, Suppresses Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo

Science.gov (United States)

Starenki, Dmytro

2013-01-01

Context: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the RET proto-oncogene. For MTC therapy, the U.S. Food and Drug Administration recently approved vandetanib and cabozantinib, multikinase inhibitors targeting RET and other tyrosine kinase receptors of vascular endothelial growth factor, epidermal growth factor, or hepatocyte growth factor. Nevertheless, not all patients with the progressive MTC respond to these drugs, requiring the development of additional therapeutic modalities that have distinct activity. Objective: We aimed to evaluate mitochondria-targeted carboxy-proxyl (Mito-CP), a mitochondria-targeted redox-sensitive agent, for its tumor-suppressive efficacy against MTC. Design: In vitro cultures of 2 human MTC cell lines, TT and MZ-CRC-1, and TT xenografts in mice were treated with Mito-CP in comparison with vandetanib. The effects on cell survival/death, RET expression, mitochondrial integrity, and oxidative stress were determined. Results: Contrary to vandetanib, Mito-CP induced RET downregulation and strong cytotoxic effects in both cell lines in vitro, including caspase-dependent apoptosis. These effects were accompanied by mitochondrial membrane depolarization, decreased oxygen consumption, and increased oxidative stress in cells. Intriguingly, Mito-CP–induced cell death, but not RET downregulation, was partially inhibited by the reactive oxygen species scavenger, N-acetyl-cysteine, indicating that Mito-CP mediates tumor-suppressive effects via redox-dependent as well as redox-independent mechanisms. Orally administered Mito-CP effectively suppressed TT xenografts in mice, with an efficacy comparable to vandetanib and relatively low toxicity to animals. Conclusion: Our results suggest that Mito-CP can effectively suppress MTC cell growth/survival via a mechanism distinct from vandetanib effects. Mitochondrial targeting may be a potential strategy for MTC therapy. PMID:23509102

Concurrent Multilocular Cystic Renal Cell Carcinoma and Leiomyoma in the Same Kidney: Previously Unreported Association

Directory of Open Access Journals (Sweden)

Min Su Cheong

2010-07-01

Full Text Available We present an unusual case of concurrent occurrence of a multilocular cystic renal cell carcinoma and a leiomyoma in the same kidney of a patient with no evident clinical symptoms. A 38-year-old man was found incidentally to have a cystic right renal mass on computed tomography. Laparoscopic radical nephrectomy was performed under a preoperative diagnosis of cystic renal cell carcinoma. Histology revealed a multilocular cystic renal cell carcinoma and a leiomyoma. This is the first report of this kind of presentation.

T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma-Implications for Adoptive Cell Therapy

DEFF Research Database (Denmark)

Andersen, Rikke; Westergaard, Marie Christine Wulff; Kjeldsen, Julie Westerlin

2018-01-01

In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC...

Cell-metal interactions: A comparison of natural uranium to other common metals in renal cells and bone osteoblasts

International Nuclear Information System (INIS)

Milgram, S.; Carriere, M.; Thiebault, C.; Berger, P.; Khodja, H.; Gouget, B.

2007-01-01

Uranium acute intoxication has been documented to induce nephrotoxicity. Kidneys are the main target organs after short term exposures to high concentrations of the toxic, while chronic exposures lead to its accumulation in the skeleton. In this paper, chemical toxicity of uranium is investigated for rat osteoblastic bone cells and compared to results previously obtained on renal cells. We show that bone cells are less sensitive to uranium than renal cells. The influence of the chemical form on U cytotoxicity is demonstrated. For both cell types, a comparison of uranium toxicity with other metals or metalloids toxicities (Mn, Ni, Co, Cu, Zn, Se and Cd) permits classification of Cd, Zn, Se IV and Cu as the most toxic and Ni, Se VI , Mn and U as the least toxic. Chemical toxicity of natural uranium proves to be far less than that of cadmium. To try to explain the differences in sensitivities observed between metals and different cell types, cellular accumulations in cell monolayers are quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), function of time or function of dose: lethal doses which simulate acute intoxications and sub-lethal doses which are more realistic with regard to environmentally metals concentrations. In addition to being more resistant, bone cells accumulated much more uranium than did renal cells. Moreover, for both cell models, Mn, U-citrate and U-bicarbonate are strongly accumulated whereas Cu, Zn and Ni are weakly accumulated. On the other hand, a strong difference in Cd behaviour between the two cell types is shown: whereas Cd is very weakly accumulated in bone cells, it is very strongly accumulated in renal cells. Finally, elemental distribution of the toxics is determined on a cellular scale using nuclear microprobe analysis. For both renal and osteoblastic cells, uranium was accumulated in as intracellular precipitates similar to those observed previously by SEM/EDS

Cell-metal interactions: A comparison of natural uranium to other common metals in renal cells and bone osteoblasts

Energy Technology Data Exchange (ETDEWEB)

Milgram, S. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Carriere, M. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Thiebault, C. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Berger, P. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Khodja, H. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Gouget, B. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France)]. E-mail: barbara.gouget@cea.fr

2007-07-15

Uranium acute intoxication has been documented to induce nephrotoxicity. Kidneys are the main target organs after short term exposures to high concentrations of the toxic, while chronic exposures lead to its accumulation in the skeleton. In this paper, chemical toxicity of uranium is investigated for rat osteoblastic bone cells and compared to results previously obtained on renal cells. We show that bone cells are less sensitive to uranium than renal cells. The influence of the chemical form on U cytotoxicity is demonstrated. For both cell types, a comparison of uranium toxicity with other metals or metalloids toxicities (Mn, Ni, Co, Cu, Zn, Se and Cd) permits classification of Cd, Zn, Se{sup IV} and Cu as the most toxic and Ni, Se{sup VI}, Mn and U as the least toxic. Chemical toxicity of natural uranium proves to be far less than that of cadmium. To try to explain the differences in sensitivities observed between metals and different cell types, cellular accumulations in cell monolayers are quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), function of time or function of dose: lethal doses which simulate acute intoxications and sub-lethal doses which are more realistic with regard to environmentally metals concentrations. In addition to being more resistant, bone cells accumulated much more uranium than did renal cells. Moreover, for both cell models, Mn, U-citrate and U-bicarbonate are strongly accumulated whereas Cu, Zn and Ni are weakly accumulated. On the other hand, a strong difference in Cd behaviour between the two cell types is shown: whereas Cd is very weakly accumulated in bone cells, it is very strongly accumulated in renal cells. Finally, elemental distribution of the toxics is determined on a cellular scale using nuclear microprobe analysis. For both renal and osteoblastic cells, uranium was accumulated in as intracellular precipitates similar to those observed previously by SEM/EDS.

Is thyroidectomy necessary in RET mutations carriers of the familial medullary thyroid carcinoma syndrome?

DEFF Research Database (Denmark)

Hansen, H S; Torring, H; Godballe, C

2000-01-01

BACKGROUND: The results and consequences of genetic testing in a family with familial medullary thyroid carcinoma (FMTC) are described. METHODS: In the screening of relatives, serum calcitonin is replaced by RET mutation analysis that was performed in families suspected of hereditary medullary th...

Medullary neurons in the core white matter of the olfactory bulb: a new cell type.

Science.gov (United States)

Paredes, Raúl G; Larriva-Sahd, Jorge

2010-02-01

The structure of a new cell type, termed the medullary neuron (MN) because of its intimate association with the rostral migratory stream (RMS) in the bulbar core, is described in the adult rat olfactory bulb. The MN is a triangular or polygonal interneuron whose soma lies between the cellular clusters of the RMS or, less frequently, among the neuron progenitors therein. MNs are easily distinguished from adjacent cells by their large size and differentiated structure. Two MN subtypes have been categorized by the Golgi technique: spiny pyramidal neurons and aspiny neurons. Both MN subtypes bear a large dendritic field impinged upon by axons in the core bulbar white matter. A set of collaterals from the adjacent axons appears to terminate on the MN dendrites. The MN axon passes in close apposition to adjacent neuron progenitors in the RMS. MNs are immunoreactive with antisera raised against gamma-aminobutyric acid and glutamate decarboxylase 65/67. Electron-microscopic observations confirm that MNs correspond to fully differentiated, mature neurons. MNs seem to be highly conserved among macrosmatic species as they occur in Nissl-stained brain sections from mouse, guinea pig, and hedgehog. Although the functional role of MNs remains to be determined, we suggest that MNs represent a cellular interface between endogenous olfactory activity and the differentiation of new neurons generated during adulthood.

Differential regulation of renal cyclooxygenase mRNA by dietary salt intake

DEFF Research Database (Denmark)

Jensen, B L; Kurtz, A

1997-01-01

RNA correlated directly with salt intake. We conclude that dietary salt intake influences renal cyclooxygenase mRNAs zone-specifically with opposite responses between cortex and medulla. Cortical COX II-mediated prostaglandin formation is probably important in low salt states whereas medullary COX I......Experiments were done to investigate the influence of dietary salt intake on renal cyclooxygenase (COX) I and II mRNA levels. To this end rats were fed either a low NaCl diet (LS; 0.02% NaCl wt/wt) or a high NaCl diet (HS diet; 4% NaCl wt/wt) for 5, 10 and 20 days. After 10 days Na excretion...... differed 760-fold, plasma renin activity and renin mRNA were increased eight- and threefold in LS compared to HS animals. Total renal COX I mRNA decreased 50% following the LS diet and did not change after the HS diet. Conversely, COX II mRNA declined after HS intake and transiently increased after salt...

VAC Therapy Direct to the Medullary Cavity for Chronic Tibial Osteomyelitis.

Science.gov (United States)

Miyamura, Satoshi; Tsuji, Shigeyoshi; Iwai, Takao; Hamada, Masayuki

2016-06-01

Vacuum-assisted wound closure (VAC) is useful for difficult wound beds, although sites where bleeding or infection is expected are usually regarded as problematic for this therapy. This report outlines the treatment of chronic tibial osteomyelitis (Cierny- Mader type III) due to mixed infection with Nocardia spp and Bacteroi- des fragilis by postoperative VAC therapy direct to the medullary cavity, followed by wound coverage with a gastrocnemius myocutaneous skin flap. A 64-year-old man developed chronic left tibial os- teomyelitis after a work injury. The nonviable tissues were debrided, including a sequestrum. Nocardia spp and B. fragilis were isolated from surgical bone specimens, and chronic tibial osteomyelitis due to mixed infection was diagnosed. Postoperatively, VAC therapy was performed directly to the open medullary cavity of the tibia and sub- sequently covered the residual soft tissue defect with a gastrocnemius myocutaneous flap. The authors could not find any English literature on VAC therapy direct to the medullary cavity combined with transplantation of a myocutaneous flap for osteomyelitis. Nocardia spp can cause a variety of infections, among which osteomyelitis occupies a relatively small percentage. This case raises the possibil- ity of treating chronic tibial osteomyelitis caused by mixed infection with Nocardia spp and B. fragilis by applying postoperative VAC ther- apy directly to the medullary cavity and covering the residual wound with a gastrocnemius myocutaneous flap.

Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS).

Science.gov (United States)

Johnston, Kimberly A; Westover, Angela J; Rojas-Pena, Alvaro; Buffington, Deborah A; Pino, Christopher J; Smith, Peter L; Humes, H David

2017-11-01

Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in end-stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 × 10 8 renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cell-treated sheep retained neutrophil oxidative activity better than sham-treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Preparation of positional renal slices for study of cell-specific toxicity.

Science.gov (United States)

Ruegg, C E; Gandolfi, A J; Nagle, R B; Krumdieck, C L; Brendel, K

1987-04-01

To reduce structural complexity, rabbit kidneys were sliced perpendicular to their cortical-papillary axis to isolate four distinct cell groupings. This positional orientation allows identification of each renal cell type based on its location within the slice. A mechanical slicer was used to make several precision-cut slices rapidly from an oriented cylindrical core of renal tissue, with minimal tissue trauma. Slices were then submerged under a gently circulating oxygenated media in a fritted glass support system that maintains viability (intracellular K+/DNA ratio) and structural integrity (histology) for at least 30 h. A high dose of mercuric chloride (10(-3) M) was used to demonstrate the structural and biochemical changes of intoxicated slices. This method provides a controlled subchronic in vitro system for the study of the individual cell types involved in cell-specific renal toxicities and may also be a useful tool for addressing other pharmacological and physiological research questions.

Microwave treatment of renal cell carcinoma adjacent to renal sinus.

Science.gov (United States)

Gao, Yongyan; Liang, Ping; Yu, Xiaoling; Yu, Jie; Cheng, Zhigang; Han, Zhiyu; Duan, Shaobo; Huang, Hui

2016-11-01

To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4cm (100%, 29/29) and RCCs >4cm (75%, 9/12, p=0.021). During the median follow-up of 37.6 (range, 3.0-97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. US-guided percutaneous MWA appears to be a promising method for RCCs adjacent to renal sinus, especially for tumors ≤4cm. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Heavy metals toxicity after acute exposure of cultured renal cells. Intracellular accumulation and repartition

International Nuclear Information System (INIS)

Khodja, Hicham; Carriere, Marie; Avoscan, Laure; Gouget, Barbara

2005-01-01

Lead (Pb), cadmium (Cd) and uranium (U) present no known biological function but are toxic in various concentration ranges. Pb and Cd lead generally to nephrotoxicity consisting in proximal renal tubular dysfunction and accumulation while U has been reported to induce chemical kidney toxicity, functional and histological damages being as well mainly observed in proximal tubule cells. This work address the question of Cd, Pb, and U cytotoxicity, intracellular accumulation and repartition after acute intoxication of renal proximal tubule epithelial cells. After cells exposure to different concentrations of metals for various times, morphological changes were observed and intracellular concentrations and distributions of toxic metals were specified by PIXE coupled to RBS. Cell viability, measured by biochemical tests, was used as toxicity indicator. A direct correlation between cytotoxicity and intracellular accumulation in renal epithelial cells have been established. Finally, intracellular Pb and U localizations were detected while Cd was found to be uniformly distributed in renal cells. (author)

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

Directory of Open Access Journals (Sweden)

Tokiko Ishida

Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

Successful intraosseous infusion in the critically ill patient does not require a medullary cavity.

LENUS (Irish Health Repository)

McCarthy, Gerard

2012-02-03

OBJECTIVES: To demonstrate that successful intraosseous infusion in critically ill patients does not require bone that contains a medullary cavity. DESIGN: Infusion of methyl green dye via standard intraosseous needles into bones without medullary cavity-in this case calcaneus and radial styloid-in cadaveric specimens. SETTING: University department of anatomy. PARTICIPANTS: Two adult cadaveric specimens. MAIN OUTCOME MEASURES: Observation of methyl green dye in peripheral veins of the limb in which the intraosseous infusion was performed. RESULTS: Methyl green dye was observed in peripheral veins of the chosen limb in five out of eight intraosseous infusions into bones without medullary cavity-calcaneus and radial styloid. CONCLUSIONS: Successful intraosseous infusion does not always require injection into a bone with a medullary cavity. Practitioners attempting intraosseous access on critically ill patients in the emergency department or prehospital setting need not restrict themselves to such bones. Calcaneus and radial styloid are both an acceptable alternative to traditional recommended sites.

P2Y2 receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb

Directory of Open Access Journals (Sweden)

Rita Delgado Marques

2013-10-01

Full Text Available Local purinergic signals modulate renal tubular transport. Acute activation of renal epithelial P2 receptors causes inhibition of epithelial transport and thus, should favor increased water and salt excretion by the kidney. So far only a few studies have addressed the effects of extracellular nucleotides on ion transport in the thick ascending limb. In the medullary thick ascending limb (mTAL, basolateral P2X receptors markedly (~25% inhibit NaCl absorption. Although this segment does express both apical and basolateral P2Y2 receptors, acute activation of the basolateral P2Y2 receptors had no apparent effect on transepithelial ion transport. Here we studied, if the absence of the P2Y2 receptor causes chronic alterations in mTAL NaCl absorption by comparing basal and AVP-stimulated transepithelial transport rates. We used perfused mouse mTALs to electrically measure NaCl absorption in juvenile (35 days male mice. Using microelectrodes, we determined the transepithelial voltage (Vte and the transepithelial resistance (Rte and thus, transepithelial NaCl absorption (equivalent short circuit current, I’sc.We find that mTALs from adult wild type (WT mice have significantly lower NaCl absorption rates when compared to mTALs from juvenile WT mice. This could be attributed to significantly higher Rte values in mTALs from adult WT mice. This pattern was not observed in mTALs from P2Y2 receptor knockout (KO mice. In addition, adult P2Y2 receptor KO mTALs have significantly lower Vte values compared to the juvenile. No difference in absolute I´sc was observed when comparing mTALs from WT and KO mice. AVP stimulated the mTALs to similar increases of NaCl absorption irrespective of the absence of the P2Y2 receptor. No difference was observed in the medullary expression level of NKCC2 in between the genotypes.These data indicate that the lack of P2Y2 receptors does not cause substantial differences in resting and AVP-stimulated NaCl absorption in

Long-term response to nivolumab and acute renal failure in a patient with metastatic papillary renal-cell carcinoma and a PD-L1 tumor expression increased with sunitinib therapy: A case report.

Directory of Open Access Journals (Sweden)

Juan Ruiz-Bañobre

2016-11-01

Full Text Available Introduction: Papillary renal-cell carcinoma, which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programmed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus, but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal-cell carcinoma. Case report: We describe a case of a young man diagnosed with papillary renal-cell carcinoma that achieved a durable response to nivolumab despite a temporary suspension of the treatment due to a renal function side effect. To our knowledge, it is the first renal failure secondary to nivolumab in a metastatic renal-cell carcinoma patient.Concluding Remarks: Nivolumab is a promising drug in patients with metastatic papillary renal-cell carcinoma and long-term responses can be achieved. In case of acute renal failure secondary to this treatment, temporary therapy suspension and a low dose of systemic corticosteroids can recover renal function without a negative impact on treatment efficacy.

Percutaneous and laparoscopic assisted cryoablation of small renal cell carcinomas

DEFF Research Database (Denmark)

Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Borre, Michael

Aim: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation. Materials and methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made...... Medical® was used. Treatment was considered successful when tumors gradually shrunk and showed no sign of contrast enhancement, assessed by CT or MRI. Results: Mean patient age and tumor size was 65 yr [17 - 83] and 26 mm [10 - 62], respectively [min-max]. Treatment modalities consisted of percutaneous...

Metastatic Renal Cell Carcinoma to Jejunum: An Unusual Case Presentation

Directory of Open Access Journals (Sweden)

Igor Medic

2017-07-01

Full Text Available The small intestine is a very uncommon and peculiar site for metastasis from renal cell carcinoma (RCC. We present a clinical presentation of insidious and unusual development of a jejunal metastasis while having stable disease in a remainder of metastatic sites, in a patient undergoing immunotherapy with nivolumab. Due to the extreme rarity of metastatic renal cell carcinoma to the lumen of the small bowel, it is easy to overlook and misdiagnose symptoms of this pathologic entity, particularly when the remainder of metastatic disease responds well to ongoing therapy.

Magnetic resonance imaging in the staging of renal cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Kishi, Hiroichi; Umeda, Takashi; Niijima, Tadao; Yashiro, Naobumi; Kawabe, Kazuki

1987-07-01

Eighteen patients with renal neoplasm underwent magnetic resonance imaging (MRI) using a 1.5 Tesla superconducting magnetic system and spin echo images were obtained by quick scan technique under holding breath. MR images were interpreted independently of the computerized tomography (CT) findings. The preoperative stagings of the 18 renal carcinomas, as judged by MRI, were compared with those obtained at laparotomy. The anatomic staging was correctly performed by MRI in 13 patients (72 %). In the patients who had intrarenal small tumor with normal renal contour, MRI demonstrated a solid mass clearly distinguishable from surrounding renal parenchyma using the paramagnetic contrast agent (gadolinium-DTPA). When compared with results of evaluation by CT in staging, MRI appeared to have several advantages in determination of whole mass; the detection of tumor thrombus into renal vein and inferior vena cava; and the evaluation of direct tumor invasion of adjacent organs. MRI should play an important role in the staging of renal cell carcinoma.

Magnetic resonance imaging in the staging of renal cell carcinoma

International Nuclear Information System (INIS)

Kishi, Hiroichi; Umeda, Takashi; Niijima, Tadao; Yashiro, Naobumi; Kawabe, Kazuki

1987-01-01

Eighteen patients with renal neoplasm underwent magnetic resonance imaging (MRI) using a 1.5 Tesla superconducting magnetic system and spin echo images were obtained by quick scan technique under holding breath. MR images were interpreted independently of the computerized tomography (CT) findings. The preoperative stagings of the 18 renal carcinomas, as judged by MRI, were compared with those obtained at laparotomy. The anatomic staging was correctly performed by MRI in 13 patients (72 %). In the patients who had intrarenal small tumor with normal renal contour, MRI demonstrated a solid mass clearly distinguishable from surrounding renal parenchyma using the paramagnetic contrast agent (gadolinium-DTPA). When compared with results of evaluation by CT in staging, MRI appeared to have several advantages in determination of whole mass; the detection of tumor thrombus into renal vein and inferior vena cava; and the evaluation of direct tumor invasion of adjacent organs. MRI should play an important role in the staging of renal cell carcinoma. (author)

Neural regulation of the kidney function in rats with cisplatin induced renal failure

Science.gov (United States)

Goulding, Niamh E.; Johns, Edward J.

2015-01-01

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

[Knockdown of ATG5 enhances the sensitivity of human renal carcinoma cells to sunitinib].

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Li, Peng; Han, Qi; Tang, Ming; Zhang, Keqin

2017-03-01

Objective To investigate the expression levels of autophagy-related gene 5 (ATG5) and microtubule-associated protein 1 light chain 3 (LC3) and their effects on sunitinib resistance in human renal carcinoma cells. Methods After clinic-pathologic feature and survival analysis, 99 renal clear cell carcinoma tissues with different histological grades were used to detect the expression of ATG5 and LC3 by immunohistochemistry. Renal carcinoma cell line A-498 was infected with lentivirus-mediated ATG5 shRNA. Western blot analysis was performed to confirm the efficiency of ATG5 knockdown. Proliferation rate of A-498 cells in control group and ATG5 low expression group was determined by flow cytometry. Finally, the survival rate was detected by MTT assay after A-498 cells were treated with different concentrations of sunitinib. Results The expression levels of ATG5 and LC3 in renal clear cell carcinoma tissues were significantly higher than those in para-tumor tissues. The expression levels of ATG5 and LC3 were associated with classification, histological grade, TNM stage and survival rate, rather than gender, age, location, tumor size. Compared with the control group, the protein expressions of ATG5 and LC3 significantly decreased in A-498 cells with ATG5 low expression. The cell proliferation rate in ATG5 downregulation group was lower than that in the control group. Compared with control group, the survival rate in ATG5 low expression group were significantly reduced in a dose-dependent manner after sunitinib treatment. Conclusion Autophagy is active in renal clear cell carcinoma, and the drug sensitivity to sunitinib in renal cancer cells can be enhanced by the downregulation of ATG5.

Not all renal stem cell niches are the same: anatomy of an evolution

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Clara Gerosa

2016-08-01

Full Text Available The renal stem cell niche represents the most important structure of the developing kidney, responsible for nephrogenesis. Recently, some Authors have reported, at ultrastructural level, a previously unknown complexity of the architecture of renal stem cell niche in experimental models. This study was aimed at studying, at histological level, the anatomy of renal stem cell niches in the human fetal kidney. To this end, ten fetal kidneys, whose gestational ages ranged from 11 up to 24 weeks, were studied. H&E-stained sections were observed at high power. The study of the anatomy of renal stem cell niches in the human kidney revealed a previously unreported complexity: some niches appeared as a roundish arrangement of mesenchymal cells; others showed the initial phases of induction by ureteric buds; in other niches the process of mesenchymal epithelial transition was more evident; finally, in other stem cell niches the first signs of nephron origin were detectable. These findings suggest the existence of niches with different anatomy in the same kidney, indicating different stages of evolution even in adjacent niches. All stem cell niches were in strict contact with the capsular cells, suggesting a major role of the renal capsule in nephrogenesis. Finally, our study confirms the existence of a strict contact between the bud tip cells and the surrounding mesenchyme in the human developing kidney, giving a morphological support to the theory of intercellular channels allowing the passage of transcription factors from the epithelial to the mesenchymal stem/progenitors cells.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

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Christopher J. Ricketts

2018-04-01

Full Text Available Summary: Renal cell carcinoma (RCC is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD ChRCC that associated with extremely poor survival. : Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes. Keywords: clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, CDKN2A, DNA hypermethylation, immune signature, chromatin remodeling, TCGA, PanCanAtlas

Role of pressure in angiotensin II-induced renal injury: chronic servo-control of renal perfusion pressure in rats.

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Mori, Takefumi; Cowley, Allen W

2004-04-01

Renal perfusion pressure was servo-controlled chronically in rats to quantify the relative contribution of elevated arterial pressure versus angiotensin II (Ang II) on the induction of renal injury in Ang II-induced hypertension. Sprague-Dawley rats fed a 4% salt diet were administered Ang II for 14 days (25 ng/kg per minute IV; saline only for sham rats), and the renal perfusion pressure to the left kidney was continuously servo-controlled to maintain a normal pressure in that kidney throughout the period of hypertension. An aortic occluder was implanted around the aorta between the two renal arteries and carotid and femoral arterial pressure were measured continuously throughout the experiment to determine uncontrolled and controlled renal perfusion pressure, respectively. Renal perfusion pressure of uncontrolled, controlled, and sham kidneys over the period of Ang II or saline infusion averaged 152.6+/-7.0, 117.4+/-3.5, and 110.7+/-2.2 mm Hg, respectively. The high-pressure uncontrolled kidneys exhibited tubular necrosis and interstitial fibrosis, especially prominent in the outer medullary region. Regional glomerular sclerosis and interlobular artery injury were also pronounced. Controlled kidneys were significantly protected from interlobular artery injury, juxtamedullary glomeruli injury, tubular necrosis, and interstitial fibrosis as determined by comparing the level of injury. Glomerular injury was not prevented in the outer cortex. Transforming growth factor (TGF)-beta and active NF-kappaB proteins determined by immunohistochemistry were colocalized in the uncontrolled kidney in regions of interstitial fibrosis. We conclude that the preferential juxtamedullary injury found in Ang II hypertension is largely induced by pressure and is probably mediated through the TGF-beta and NF-kappaB pathway.

Resveratrol promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism.

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Li, Jianchang; Qiu, Mingning; Chen, Lieqian; Liu, Lei; Tan, Guobin; Liu, Jianjun

2017-02-01

The aim of the present study was to investigate the effect of resveratrol on renal carcinoma cells and explore possible renin-angiotensin system-associated mechanisms. Subsequent to resveratrol treatment, the cell viability, apoptosis rate, cytotoxicity levels, caspase 3/7 activity and the levels of angiotensin II (AngII), AngII type 1 receptor (AT1R), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were evaluated in renal carcinoma cells. The effects of AngII, AT1R, VEGF and COX-2 on resveratrol-induced cell growth inhibition and apoptosis were also examined. The results indicated that resveratrol treatment may suppress growth, induce apoptosis, and decrease AngII, AT1R, VEGF and COX-2 levels in renal carcinoma ACHN and A498 cells. In addition, resveratrol-induced cell growth suppression and apoptosis were reversed when co-culturing with AT1R or VEGF. Thus, resveratrol may suppress renal carcinoma cell proliferation and induce apoptosis via an AT1R/VEGF pathway.

Renal type a intercalated cells contain albumin in organelles with aldosterone-regulated abundance.

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Thomas Buus Jensen

Full Text Available Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1, late endosomes/lysosomes (cathepsin D or recycling endosomes (Rab11. Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells.

The effects of renal transplantation on circulating dendritic cells

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D.A. Hesselink (Dennis); L.M.B. Vaessen (Leonard); W.C.J. Hop (Wim); W. Schoordijk-Verschoor (Wenda); J.N.M. IJzermans (Jan); C.C. Baan (Carla); W. Weimar (Willem)

2005-01-01

textabstractThe effects of immunosuppressive agents on T cell function have been well characterized but virtually nothing is known about the effects of renal transplantation on human dendritic cells (DCs). With the use of flow cytometry, we studied the kinetics of myeloid and plasmacytoid DCs in

Application of modified R.E.N.A.L. nephrometry score system in evaluating the retroperitoneal partial nephrectomy for T1 renal cell carcinoma.

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Wang, Qinzhang; Qian, Biao; Li, Qiang; Ni, Zhao; Li, Yinglong; Wang, Xinmin

2015-01-01

This study aims to investigate the application of the modified R.E.N.A.L. nephrometry score system in evaluating the operation difficulty of retroperitoneal partial nephrectomy in T1 renal cell carcinoma patients. A total of 52 patients with T1 renal cell carcinoma were enrolled. They all had retroperitoneal partial nephrectomy. Their clinical data was retrospectively analyzed. R.E.N.A.L. nephrometry score system was modified based on the features of retroperitoneal partial nephrectomy. The specificity, sensitivity and Youden index were compared between R.E.N.A.L. nephrometry score system and the modified R.E.N.A.L. nephrometry score system. The effect of the modified R.E.N.A.L. nephrometry score system on perioperative outcomes was analyzed. Three degrees of operation difficulty were defined by the modified R.E.N.A.L. nephrometry score system, which included the low, medium and high degree of operation difficulty. The specificity, sensitivity and Youden index of the modified R.E.N.A.L. nephrometry score system were better than those of the original R.E.N.A.L. nephrometry score system. Compared with low degree of operation difficulty, patients with medium and high degree of operation difficulty had significantly higher levels of operative time, warm ischemia time, and intraoperative blood loss (P system has a good effect in evaluating the operation difficulty of retroperitoneal partial nephrectomy.

Wnt Signaling in Renal Cell Carcinoma

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Qi Xu

2016-06-01

Full Text Available Renal cell carcinoma (RCC accounts for 90% of all kidney cancers. Due to poor diagnosis, high resistance to the systemic therapies and the fact that most RCC cases occur sporadically, current research switched its focus on studying the molecular mechanisms underlying RCC. The aim is the discovery of new effective and less toxic anti-cancer drugs and novel diagnostic markers. Besides the PI3K/Akt/mTOR, HGF/Met and VHL/hypoxia cellular signaling pathways, the involvement of the Wnt/β-catenin pathway in RCC is commonly studied. Wnt signaling and its targeted genes are known to actively participate in different biological processes during embryonic development and renal cancer. Recently, studies have shown that targeting this pathway by alternating/inhibiting its intracellular signal transduction can reduce cancer cells viability and inhibit their growth. The targets and drugs identified show promising potential to serve as novel RCC therapeutics and prognostic markers. This review aims to summarize the current status quo regarding recent research on RCC focusing on the involvement of the Wnt/β-catenin pathway and how its understanding could facilitate the identification of potential therapeutic targets, new drugs and diagnostic biomarkers.

IgG4-related tubulointerstitial nephritis with plasma cell-rich renal arteritis.

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Sharma, Shree G; Vlase, Horia L; D'Agati, Vivette D

2013-04-01

Immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis is a newly recognized clinicopathologic entity that may occur as an isolated renal lesion or as part of a multisystem disorder. It is characterized by plasma cell-rich interstitial nephritis with abundant IgG4-positive plasma cells and IgG-dominant tubulointerstitial immune deposits. We report the first case of IgG4-related tubulointerstitial nephritis with multifocal plasma cell-rich renal arteritis presenting as acute kidney injury in a 72-year-old man. Seven weeks of prednisone therapy led to nearly complete recovery of kidney function. This case enlarges the morphologic spectrum of this disorder and emphasizes the need to distinguish it from other causes of renal vasculitis. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Cell therapy in renal and cardiovascular disease Terapia celular en enfermedades renales y cardiovasculares

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Juan Manuel Senior Sánchez

2006-01-01

Full Text Available Although there have been important advances in the field of molecular biology, the mechanisms responsible for nephrogenesis and the factors that modulate the process of development, proliferation, growth, and maturation during fetal and adult life have not been thoroughly explained. Animals, including mammals, share the intrinsic ability to regenerate tissues and organs as an important biological defense mechanism. In the case of the kidney, after tissue damage secondary to injury, anatomical and functional recovery of integrity is achieved, accompanied by the activation of a complex, poorly understood process, leading to the replacement of damaged tubular cells by functional ones that reorganize tubular architecture. This regeneration and repair process is produced by somatic, exogenous, adult stem cells, and probably by intrinsic renal stem cells, that are responsible for maintaining renal homeostasis Aunque se han logrado grandes avances en el campo de la biología molecular, todavía no se han esclarecido completamente los mecanismos responsables de la organogénesis y los factores que modulan el proceso de desarrollo, proliferación, crecimiento y maduración celulares durante la vida fetal y adulta. Los animales comparten la capacidad de regenerar tejidos y órganos, como un mecanismo biológico importante de defensa. En el caso del riñón, luego del daño tisular secundario a una noxa, se produce recuperación anatómica y funcional de la integridad, acompañada por la activación de un proceso sofisticado, mal comprendido, que lleva al reemplazo de las células tubulares dañadas por otras funcionalmente normales que reorganizan la arquitectura tubular. Este fenómeno de recambio se produce gracias a la presencia de células madre adultas somáticas exógenas, responsables del proceso de mantenimiento de la homeostasis renal, y posiblemente por células renales intrínsecas.

Metallothionein gene expression in renal cell carcinoma

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Deeksha Pal

2014-01-01

Full Text Available Introduction: Metallothioneins (MTs are a group of low-molecular weight, cysteine-rich proteins. In general, MT is known to modulate three fundamental processes: (1 the release of gaseous mediators such as hydroxyl radical or nitric oxide, (2 apoptosis and (3 the binding and exchange of heavy metals such as zinc, cadmium or copper. Previous studies have shown a positive correlation between the expression of MT with invasion, metastasis and poor prognosis in various cancers. Most of the previous studies primarily used immunohistochemistry to analyze localization of MT in renal cell carcinoma (RCC. No information is available on the gene expression of MT2A isoform in different types and grades of RCC. Materials and Methods: In the present study, total RNA was isolated from 38 histopathologically confirmed cases of RCC of different types and grades. Corresponding adjacent normal renal parenchyma was taken as control. Real-time polymerase chain reaction (RT PCR analysis was done for the MT2A gene expression using b-actin as an internal control. All statistical calculations were performed using SPSS software. Results: The MT2A gene expression was found to be significantly increased (P < 0.01 in clear cell RCC in comparison with the adjacent normal renal parenchyma. The expression of MT2A was two to three-fold higher in sarcomatoid RCC, whereas there was no change in papillary and collecting duct RCC. MT2A gene expression was significantly higher in lower grade (grades I and II, P < 0.05, while no change was observed in high-grade tumor (grade III and IV in comparison to adjacent normal renal tissue. Conclusion: The first report of the expression of MT2A in different types and grades of RCC and also these data further support the role of MT2A in tumorigenesis.

Combined effect of angioinfarction with immunotherapy in patients with stage IV renal cell carcinoma

International Nuclear Information System (INIS)

Oh, Joo Hyeong; Yoon, Yup; Jeong, Yu Mee; Ko, Young Tae; Chang, Sung Goo

1994-01-01

To assess the combined effectiveness of angioinfarction and immunotherapy for improving survival in patients with stage IV renal cell carcinoma. During the past 3 years, 13 patients of stage IV renal cell carcinoma were treated with angioinfarction and immunotherapy. Angioinfarction was performed on these 13 patients using absolute ethanol and occlusive balloon catheter. After angioinfarction, Interferon alpha was used for immunotherapy. For our analysis, 12 control patients of stage IV renal cell carcinoma without treatment were included in the study. Survival has been calculated according to the Kaplan and Meier method. The 1 year survival rate and median survival time in patients treated with angioinfarction and immunotherapy, were 46% and 13 months and in patients without treatment, 16% and 4 months, respectively. The combined treatment of angioinfarction and immunotherapy is of considerable value for improving survival in patients with stage IV renal cell carcinoma

Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma.

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Riss, Joseph; Khanna, Chand; Koo, Seongjoon; Chandramouli, Gadisetti V R; Yang, Howard H; Hu, Ying; Kleiner, David E; Rosenwald, Andreas; Schaefer, Carl F; Ben-Sasson, Shmuel A; Yang, Liming; Powell, John; Kane, David W; Star, Robert A; Aprelikova, Olga; Bauer, Kristin; Vasselli, James R; Maranchie, Jodi K; Kohn, Kurt W; Buetow, Ken H; Linehan, W Marston; Weinstein, John N; Lee, Maxwell P; Klausner, Richard D; Barrett, J Carl

2006-07-15

Cancers have been described as wounds that do not heal, suggesting that the two share common features. By comparing microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), we asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority (77%) of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.e., changed in opposite directions). The orchestrated processes of regeneration, involving cell proliferation and immune response, were reflected in the concordant genes. The discordant gene signature revealed processes (e.g., morphogenesis and glycolysis) and pathways (e.g., hypoxia-inducible factor and insulin-like growth factor-I) that reflect the intrinsic pathologic nature of RCC. This is the first study that compares gene expression patterns in RCC and RRR. It does so, in particular, with relation to the hypothesis that RCC resembles the wound healing processes seen in RRR. However, careful attention to the genes that are regulated in the discordant direction provides new insights into the critical differences between renal carcinogenesis and wound healing. The observations reported here provide a conceptual framework for further efforts to understand the biology and to develop more effective diagnostic biomarkers and therapeutic strategies for renal tumors and renal ischemia.

Evaluation of renal function with dynamic MRI-T2-weighted gradient echo technique

International Nuclear Information System (INIS)

Kato, Katsuya

1995-01-01

To evaluate the usefulness of dynamic MRI of kidneys in healthy volunteers and patients with different 24-hour creatinine clearance (Ccr) levels, a dynamic study that employed the T2 weighted gradient echo technique (FLASH: TR/TE=34/25 msec, flip angle= 20 degrees) with single images during breathhold was performed on 10 healthy volunteers and 35 patients, all examined for the Ccr and suspected of having renal parenchymal disease after a phantom study. T1-weighted and dynamic MR imagings were obtained with a 1.5T imager. I analyzed the time-intensity curve of renal cortex and medulla, and defined a cortex decreased ratio (CDR) and medulla decreased ratio (MDR) in comparison with the Ccr. The cortico-medullary difference ratio (CMDR) of T1WI was also compared with the Ccr. The parameters of the T2 dynamic MRI study (CDR, MDR) better correlated with the Ccr than CMDR. Renal function can be quantitatively evaluated with the T2 dynamic MRI and there is a possibility that we can qualitatively evaluate the renal dysfunction and estimate its cause. (author)

Suture Granuloma Mimicking Renal Cell Carcinoma: Magnetic Resonance Imaging (MRI and Pathologic Correlation

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İbrahim İlker Öz

2014-11-01

Full Text Available Solid renal masses are generally distinguished with contrast enhancement and intratumoral fatty foci by radiological examinations. The present of enhancement is most important criteria for diagnosis of malignant lesions. Generally, a contrast enhanced solid mass in kidney is accepted as a neoplasm. Foreign body granuloma is an extraordinary cause of enhanced solid renal mass. This case of a renal suture granuloma demonstrated peripheral enhanced exophytic renal mass mimic renal cell carcinoma, and underwent surgery. At the solid renal mass with different radiological features, biopsy is an option to determining the necessity of surgery as well as the surgical approach.

Radiofrequency ablation of renal cell carcinoma under CT guidance. Present and Future status

International Nuclear Information System (INIS)

Nasu, Yasutomo; Kobayashi, Yasuyuki; Uematsu, Katsutoshi; Saika, Takashi; Kumon, Hiromi; Gohara, Hideo; Mimura, Hidefumi; Kanazawa, Susumu

2011-01-01

At Okayama University, radiofrequency ablation (RFA) of renal cell carcinoma was performed in May 2002 as the initial case in Japan. In 2004, it was regarded as an advanced medical technique by the Japanese authority. Since then, RFA has been actively performed for renal cell carcinoma not only at the primary site but also at the metastatic site, including the lung and bone. The clinical outcome has been compatible with other institutes and no serious adverse events have occurred. From the view paint of fusing technical innovation with medical safety, this treatment is a potent therapeutic option for renal cell carcinoma. In the era of laparoscopic surgery, RFA is indicated for cases with von Hippel-Lindau disease (VHL), recurrence after partial nephrectomy, a single kidney and intolerance to general anesthesia, due to its technical advantage in that RFA can be repeated. In this review, the current clinical outcome is reported and future prospects are discussed as to whether it can be the safest and most concrete treatment for renal cell carcinoma in the 21 st century. (author)

Evaluation of resectability of renal cell carcinoma by computed tomography

International Nuclear Information System (INIS)

Hiramatsu, Yoshihiro; Matsumoto, Kunihiko; Tatezawa, Takashi; Kikuchi, Yoichi; Akisada, Masahiro; Kitagawa, Ryuichi

1982-01-01

Renal cell carcinoma is one of the unique neoplasm which is characterized by disappearing of the metastatic tumors after removal of the primary lesion. Angiography has been performed to evaluate the resectability of the primary tumor by nephrectomy in the past. With the use of computed tomography, detailed evaluation of the retroperitoneal structures is now possible. We have evaluated the resectability of renal cell tumor by computed tomography and compared the results with the angiographic findings and operative findings. Computed tomography is very accurate in determining the extent of the tumor especially in evaluation of tumor and the Gerota's fascia, which is essential to determine the resectability of the tumor. Informations about lymph node metastasis and invasion to the renal veins or inferior vena cava are also obtained.FIn most of the cases, angiography can be spared if computed tomography is properly performed. (author)

Imaging features of renal complications after crizotinib treatment for non–small-cell lung cancer: a case report

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Wan Ying Chan, MBBS

2016-09-01

Full Text Available Crizotinib has been approved for the treatment of advanced ALK-positive non–small cell lung cancer. Its use is associated with the development of complex renal cysts. However, there is limited literature regarding imaging features of renal cystic disease during crizotinib therapy and its complications or progression. Here, we describe a case of a patient with ALK-positive advanced non–small cell lung cancer who developed complex renal cyst during crizotinib treatment. The renal cyst is complicated by infection and abscess formation. Subsequent renal biopsy, antibiotics treatment, and open drainage of loculated renal abscess showed no malignant cells and contributed to the diagnosis. The imaging features should be recognized as renal cystic disease of crizotinib treatment and not to be mistaken as new metastasis and disease progression.

Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas

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Kostianets Olga

2012-11-01

Full Text Available Abstract Background On the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer. Methods Semi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples. Results All 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors. Conclusions This pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy. Virtual slides The virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892

Choroid plexus metastasis of renal-cell carcinoma. A case report

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Shigemori, Minoru; Shimamoto, Houtetsu; Noguchi, Shinji; Yoshitake, Yasuhiro; Sugita, Yasuo; Kuramoto, Shinken

1987-10-01

A rare case of the choroid plexus metastasis of renal-cell carcinoma is reported. A 58-year-old man was admitted on March 3, 1982, with complaints of mild headache and a transient attack of muscle weakness of the left upper extremity. He had undergone a left nephrectomy because of renal-cell carcinoma 2 years before this admission. A CT scan revealed a small mass in the right lateral ventricle that was markedly enhanced by the contrast medium. A carotid angiogram was normal, but a left vertebral angiogram showed a round tumor stain in the distal portion of the right posterior choroidal artery. To determine the nature of the tumor, it was successfully removed via the right frontal transventricular approach. The immediate recovery from the operation was uneventful, but the patient became semicomatose 6 hours later because of a large subdural hematoma over the left hemisphere. An emergency operation for clot removal and external decompression failed to improve the patient's status, and he died on the 3rd postoperative day. An histological examination of the tumor determined the diagnosis of clear-cell-type renal-cell carcinoma. The CT demonstration of choroid plexus metastasis is quite rare. To our knowledge, only two cases have been described.

Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

International Nuclear Information System (INIS)

Mellas, J.; Hammerman, M.R.

1986-01-01

We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na + -H + exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using [ 14 C]-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 γ phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular [Na + ] > intracellular [Na + ], was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na + -H + exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells

Renal Replacement Therapy in End-Stage Sickle Cell Nephropathy: Presentation of Two Cases and Literature Review

International Nuclear Information System (INIS)

Al-Mueilo, Samir H.

2005-01-01

Chronic renal failure develops in 4-18% of patients with sickle cell anemia. Hemodialysis and kidney transplant are viable options in the management of end-stage renal disease in patients with sickle cell diseases (SCD). Information on kidney disease among Saudi patients with SCD is non-existing. In this report, the clinical course of two adult males with end-stage sickle cell nephropathy from Eastern Saudi Arabia is described. Literature on renal replacement therapy in sickle cell anemia (SCA) is discussed. (author)

Renal morphology of Bradypus torquatus

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Pedro Kastein Faria da Cunha Bianchi

2012-11-01

Full Text Available Among the Xenarthras, sloths present a hydric ingestion restricted to water from leaves, fruits, and vegetables. As a first approach to verify whether these animals have some morphophysiological difference which could justify or compensate this low hydric ingestion, the renal anatomy of these animals was investigated, particularly that of maned sloth (Bradypus torquatus. Kidneys from these animals were macroscopically analyzed, through light microscopy and scanning electron microscopy. The Bradypus torquatus kidneys are bean-shaped paired organs, located dorso-cranially to the pelvic girdle, between the peritoneum and the posterior abdominal wall. The use of histological techniques allowed us to identify, in the cortical region, the renal corpuscles and tubules, and, in the medullary region, a significant amount of interstitial tissue with a collecting duct. The results of this study showed that, although Bradypus torquatus doesn’t drink water directly, its kidneys doesn’t differ from that of most mammals, presenting the same anatomical structure, suggesting that these animals fully reach their hydric needs, basically by consuming leaves, fruits, and sprouts. Nevertheless, in order to confirm this hypothesis, studies on the effectiveness of water reabsorption, such as the renin-angiotensin-aldosterone system, must be carried out.

Ischiogluteal bursitis mimicking soft-tissue metastasis from a renal cell carcinoma

International Nuclear Information System (INIS)

Voelk, M.; Gmeinwieser, J.; Manke, C.; Strotzer, M.; Hanika, H.

1998-01-01

We report a case of ischiogluteal bursitis mimicking a soft-tissue metastasis from a renal cell carcinoma. A 66-year-old woman suffered from pain over the left buttock 6 months after she was operated on for renal cell carcinoma of the left kidney. CT of the abdomen and pelvis revealed a tumor-like lesion adjacent to the left os ischii, which was suspected to be a soft-tissue metastasis. Percutaneous biopsy revealed no evidence of malignancy, but the histopathological diagnosis of chronic bursitis. (orig.)

Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

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Wu, Cheng Tien [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Weng, Te I. [Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Chen, Li Ping [Department of Dentistry, Chang Gang Memorial Hospital, Chang Gang University, Taoyuan, Taiwan (China); Chiang, Chih Kang [Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Liu, Shing Hwa, E-mail: shinghwaliu@ntu.edu.tw [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China)

2013-01-01

Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

The role of renal aquaporin 2 in the alleviation of dehydration associated with diabetic polyuria in KKAy mice.

Science.gov (United States)

Satake, Masako; Ikarashi, Nobutomo; Ichikawa, Yuhei; Maniwa, Ayaka; Toda, Takahiro; Ito, Kiyomi; Ochiai, Wataru; Sugiyama, Kiyoshi

2010-10-09

Polyuria is a symptom that appears in association with diabetes mellitus. Because sustained polyuria causes serious dehydration, it is believed that the body has a compensating mechanism to alleviate dehydration. In the present study, the role of renal aquaporin 2 (AQP2) in the compensating mechanism was investigated in KKAy mice, a type 2 diabetes model. The renal AQP2 expression levels in KKAy mice aged between 5 and 24 weeks were determined using Western blotting. The hypothalamic vasopressin mRNA expression levels also were measured by real-time RT-PCR. Insulin was subcutaneously administered to 11-week-old KKAy mice twice a day for 7 days. After insulin treatment, the renal AQP2 protein expression and the hypothalamic vasopressin mRNA expression were measured. The urinary volumes of 5- and 12-week-old KKAy mice were 1.5 ± 0.3 mL and 9.5 ± 1.2 mL, respectively. The inner medullary AQP2 protein expression of 12-week-old KKAy mice was approximately 2.5-fold higher than that of 5-week-old KKAy mice. The hypothalamic vasopressin mRNA expression of 12-week-old KKAy mice was approximately twice that of 5-week-old KKAy mice. Insulin treatment in KKAy mice resulted in a significant reduction in the plasma glucose level, urinary volume, and inner medullary AQP2 protein and hypothalamic vasopressin mRNA expression. The present study demonstrated that AQP2 is a renal functional molecule of vasopressin that controls urinary volume and that AQP2 in the kidney increases to alleviate dehydration due to type 2 diabetes with polyuria. Copyright © 2010 Elsevier Inc. All rights reserved.

Gonadal vein tumor thrombosis due to renal cell carcinoma

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Hamidreza Haghighatkhah

2015-01-01

Full Text Available Renal cell carcinoma (RCC had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC

Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.

Science.gov (United States)

Hitomi, Hirofumi; Kasahara, Tomoko; Katagiri, Naoko; Hoshina, Azusa; Mae, Shin-Ichi; Kotaka, Maki; Toyohara, Takafumi; Rahman, Asadur; Nakano, Daisuke; Niwa, Akira; Saito, Megumu K; Nakahata, Tatsutoshi; Nishiyama, Akira; Osafune, Kenji

2017-09-27

The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzyme inhibitors, and insulin-like growth factor 1. The EPO protein secreted from hiPSC-derived EPO-producing (hiPSC-EPO) cells induced the erythropoietic differentiation of human umbilical cord blood progenitor cells in vitro. Furthermore, transplantation of hiPSC-EPO cells into mice with CKD induced by adenine treatment improved renal anemia. Thus, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and may be useful as a therapeutic strategy for treating renal anemia. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Iodine quantification to distinguish clear cell from papillary renal cell carcinoma at dual-energy multidetector CT: a multireader diagnostic performance study.

Science.gov (United States)

Mileto, Achille; Marin, Daniele; Alfaro-Cordoba, Marcela; Ramirez-Giraldo, Juan Carlos; Eusemann, Christian D; Scribano, Emanuele; Blandino, Alfredo; Mazziotti, Silvio; Ascenti, Giorgio

2014-12-01

To investigate whether dual-energy multidetector row computed tomographic (CT) imaging with iodine quantification is able to distinguish between clear cell and papillary renal cell carcinoma ( RCC renal cell carcinoma ) subtypes. In this retrospective, HIPAA-compliant, institutional review board-approved study, 88 patients (57 men, 31 women) with diagnosis of either clear cell or papillary RCC renal cell carcinoma at pathologic analysis, who underwent contrast material-enhanced dual-energy nephrographic phase study between December 2007 and June 2013, were included. Five readers, blinded to pathologic diagnosis, independently evaluated all cases by determining the lesion iodine concentration on color-coded iodine maps. The receiving operating characteristic curve analysis was adopted to estimate the optimal threshold for discriminating between clear cell and papillary RCC renal cell carcinoma , and results were validated by using a leave-one-out cross-validation. Interobserver agreement was assessed by using an intraclass correlation coefficient. The correlation between tumor iodine concentration and tumor grade was investigated. A tumor iodine concentration of 0.9 mg/mL represented the optimal threshold to discriminate between clear cell and papillary RCC renal cell carcinoma , and it yielded the following: sensitivity, 98.2% (987 of 1005 [95% confidence interval: 97.7%, 98.7%]); specificity, 86.3% (272 of 315 [95% confidence interval: 85.0%, 87.7%]); positive predictive value, 95.8% (987 of 1030 [95% confidence interval: 95.0%, 96.6%]); negative predictive value, 93.7% (272 of 290 [95% confidence interval: 92.8%, 94.7%]); overall accuracy of 95.3% (1259 of 1320 [95% confidence interval: 94.6%, 96.2%]), with an area under the curve of 0.923 (95% confidence interval: 0.913, 0.933). An excellent agreement was found among the five readers in measured tumor iodine concentration (intraclass correlation coefficient, 0.9990 [95% confidence interval: 0. 9987, 0.9993). A

Vitamin E Intake and Risk of Renal Cell Carcinoma: A Meta-Analysis of 7 Case-Control Studies.

Science.gov (United States)

Shang, Yonggang; Yi, Shanhong; Cui, Dong; Han, Guangwei; Liu, Chengcheng

2015-07-01

Vitamin E intake may reduce the risk of renal cell carcinoma, but the results were inconsistent. Hence, we conducted a meta-analysis to assess the association between dietary vitamin E intake and the risk of renal cell carcinoma. We searched PubMed to identify the relevant case-control studies up to June 2014. Reference lists of retrieved articles were also reviewed. Odds ratios and corresponding 95% confidence intervals were used to estimate the association between dietary vitamin E intake and the risk of renal cell carcinoma. We identified 7 case-control studies regarding dietary vitamin E intake and risk of renal cell carcinoma, involving 5789 cases and 14866 controls. The odds ratio of renal cell carcinoma for the highest compared with the lowest dietary vitamin E intake was 0.75 (95% confidence interval: 0.59-0.91), and heterogeneity was observed across studies. The association between dietary vitamin E intake and the risk of renal cell carcinoma was not significantly differed by gender, but this association were inconsistent in the North American and European populations. Our study provided a evidence that there was a significant inverse association of dietary vitamin E intake with risk of renal cell carcinoma. However, this finding was based on the case-control studies, more well-designed cohort studies are needed. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Cutaneous metastasis of bilateral renal cell carcinoma.

Science.gov (United States)

Abbasi, Fariba; Alizadeh, Mansur; Noroozinia, Farahnaz; Moradi, Amin

2013-01-01

Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of metastasis. However, metastasis from RCC to the skin is much less common. It is virtually a sign of poor prognosis. We represent a 42 years old man with bilateral RCC of clear cell type followed by metastasis to the scalp one month later. In this case the relatively young age of the patient, bilaterality of RCC and occurance of skin metastasis in the absence of recurrent kidney tumour are interesting.

The entire miR-200 seed family is strongly deregulated in clear cell renal cell cancer compared to the proximal tubular epithelial cells of the kidney

NARCIS (Netherlands)

Duns, Gerben; van den Berg, Anke; van Dijk, Marcory C. R. F.; van Duivenbode, Inge; Giezen, Cor; Kluiver, Joost; van Goor, Harry; Hofstra, Robert M. W.; van den Berg, Eva; Kok, Klaas

Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart: the renal proximal tubular epithelial cells (PTECs). The aim of this study was to

Computed tomography findings of pancreatic metastases from renal cell carcinoma

International Nuclear Information System (INIS)

Prando, Adilson

2008-01-01

Objective: To present computed tomography findings observed in four patients submitted to radical nephrectomy for renal cell carcinoma who developed pancreatic metastases afterwards. Materials and methods: The four patients underwent radical nephrectomy for stage Tz1 (n=2) and stage T3a (n=2) renal cell carcinoma. The mean interval between nephrectomy and detection of pancreatic metastases was eight years. Two asymptomatic patients presented with solitary pancreatic metastases (confined to the pancreas). Two symptomatic patients presented with single and multiple pancreatic metastases, both with tumor recurrence in the contralateral kidney. Results: Computed tomography studies demonstrated pancreatic metastases as solitary (n=2), single (n=1) or multiple (n=1) hypervascular lesions. Partial pancreatectomy was performed in two patients with solitary pancreatic metastases and both are free of disease at four and two years after surgery. Conclusion: Pancreatic metastases from renal cell carcinoma are rare and can occur many years after the primary tumor presentation. Multiple pancreatic metastases and pancreatic metastases associated with tumor recurrence in the contralateral kidney are uncommon. Usually, on computed tomography images pancreatic metastases are visualized as solitary hypervascular lesions, simulating isletcell tumors. Surgical management should be considered for patients with solitary pancreatic lesions. (author)

Computed tomography findings of pancreatic metastases from renal cell carcinoma

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Prando, Adilson [Hospital Vera Cruz, Campinas, SP (Brazil). Dept. of Radiology and Imaging Diagnosis]. E-mail: adilson.prando@gmail.com

2008-07-15

Objective: To present computed tomography findings observed in four patients submitted to radical nephrectomy for renal cell carcinoma who developed pancreatic metastases afterwards. Materials and methods: The four patients underwent radical nephrectomy for stage Tz1 (n=2) and stage T3a (n=2) renal cell carcinoma. The mean interval between nephrectomy and detection of pancreatic metastases was eight years. Two asymptomatic patients presented with solitary pancreatic metastases (confined to the pancreas). Two symptomatic patients presented with single and multiple pancreatic metastases, both with tumor recurrence in the contralateral kidney. Results: Computed tomography studies demonstrated pancreatic metastases as solitary (n=2), single (n=1) or multiple (n=1) hypervascular lesions. Partial pancreatectomy was performed in two patients with solitary pancreatic metastases and both are free of disease at four and two years after surgery. Conclusion: Pancreatic metastases from renal cell carcinoma are rare and can occur many years after the primary tumor presentation. Multiple pancreatic metastases and pancreatic metastases associated with tumor recurrence in the contralateral kidney are uncommon. Usually, on computed tomography images pancreatic metastases are visualized as solitary hypervascular lesions, simulating isletcell tumors. Surgical management should be considered for patients with solitary pancreatic lesions. (author)

Different Cytokine and Chemokine Expression Patterns in Malignant Compared to Those in Nonmalignant Renal Cells

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Nadine Gelbrich

2017-01-01

Full Text Available Objective. Cytokines and chemokines are widely involved in cancer cell progression and thus represent promising candidate factors for new biomarkers. Methods. Four renal cell cancer (RCC cell lines (Caki-1, 786-O, RCC4, and A498 and a nonmalignant renal cell line (RC-124 were examined with respect to their proliferation. The cytokine and chemokine expression pattern was examined by a DNA array (Human Cytokines & Chemokines RT2 Profiler PCR Array; Qiagen, Hilden, Germany, and expression profiles were compared. Results. Caki-1 and 786-O cells exhibited significantly increased proliferation rates, whereas RCC4 and A498 cells demonstrated attenuated proliferation, compared to nonmalignant RC-124 cells. Expression analysis revealed 52 cytokines and chemokines primarily involved in proliferation and inflammation and differentially expressed not only in malignant and nonmalignant renal cells but also in the four RCC cell lines. Conclusion. This is the first study examining the expression of 84 cytokines and chemokines in four RCC cell lines compared to that in a nonmalignant renal cell line. VEGFA, NODAL, and BMP6 correlated with RCC cell line proliferation and, thus, may represent putative clinical biomarkers for RCC progression as well as for RCC diagnosis and prognosis.

Diagnostic value of multidetector computed tomography for renal sinus fat invasion in renal cell carcinoma patients

International Nuclear Information System (INIS)

Kim, Cherry; Choi, Hyuck Jae; Cho, Kyoung-Sik

2014-01-01

Objective: Although renal sinus fat invasion has prognostic significance in patients with renal cell carcinomas (RCCs), there are no previous studies about the value of multidetector computed tomography (MDCT) about this issue in the current literature. Materials and methods: A total of 863 consecutive patients (renal sinus fat invasion in 110 patients (12.7%)) from single institutions with surgically-confirmed renal cell carcinoma who underwent MDCT between 2010 and 2012 were included in this study. The area under the curves (AUCs) of the receiver operating characteristic (ROC) analysis was used to compare diagnostic performance. Reference standard was pathologic examination. Weighted κ statistics were used to measure the level of interobserver agreement. Multivariate logistic regression model was used to find the predictors for renal sinus fat invasion. Image analysis was first performed with axial-only CT images. A second analysis was then performed with both axial and coronal CT images. A qualitative analysis was then conducted by two reviewers who reached consensus regarding tumor size, decreased perfusion, tumor margin, vessel displacement, and lymph node metastasis. The reference standard was pathologic evaluation. Results: The AUCs of the ROC analysis were 0.881 and 0.922 for axial-only images and 0.889 and 0.902 for combined images in both readers. The AUC of tumor size was 0.884, a similar value to that of the reviewers. In multivariate analysis, tumor size, a linear-nodular or nodular type of fat infiltration, and an irregular tumor margin were independent predicting factors for perinephric fat invasion. Conclusion: MDCT shows relatively high diagnostic performance in detecting perinephric fat invasion of RCC but suffers from a relatively low PPV related to low prevalence of renal sinus fat invasion. Applying tumor size alone we could get similar diagnostic performance to those of radiologists. Tumor size, fat infiltration with a nodular appearance, and

First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

DEFF Research Database (Denmark)

Ruiz-Morales, Jose Manuel; Swierkowski, Marcin; Wells, J Connor

2016-01-01

BACKGROUND: Sunitinib (SU) and pazopanib (PZ) are standards of care for first-line treatment of metastatic renal cell carcinoma (mRCC). However, how the efficacy of these drugs translates into effectiveness on a population-based level is unknown. PATIENTS AND METHODS: We used the International mR...

Ischiogluteal bursitis mimicking soft-tissue metastasis from a renal cell carcinoma

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Voelk, M.; Gmeinwieser, J.; Manke, C.; Strotzer, M. [Department of Radiology, University Hospital, Regensburg (Germany); Hanika, H. [Department of Urology, St. Josef Hospital, Regensburg (Germany)

1998-09-01

We report a case of ischiogluteal bursitis mimicking a soft-tissue metastasis from a renal cell carcinoma. A 66-year-old woman suffered from pain over the left buttock 6 months after she was operated on for renal cell carcinoma of the left kidney. CT of the abdomen and pelvis revealed a tumor-like lesion adjacent to the left os ischii, which was suspected to be a soft-tissue metastasis. Percutaneous biopsy revealed no evidence of malignancy, but the histopathological diagnosis of chronic bursitis. (orig.) With 2 figs., 8 refs.

Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data

International Nuclear Information System (INIS)

Lenburg, Marc E; Liou, Louis S; Gerry, Norman P; Frampton, Garrett M; Cohen, Herbert T; Christman, Michael F

2003-01-01

Renal cell carcinoma is a common malignancy that often presents as a metastatic-disease for which there are no effective treatments. To gain insights into the mechanism of renal cell carcinogenesis, a number of genome-wide expression profiling studies have been performed. Surprisingly, there is very poor agreement among these studies as to which genes are differentially regulated. To better understand this lack of agreement we profiled renal cell tumor gene expression using genome-wide microarrays (45,000 probe sets) and compare our analysis to previous microarray studies. We hybridized total RNA isolated from renal cell tumors and adjacent normal tissue to Affymetrix U133A and U133B arrays. We removed samples with technical defects and removed probesets that failed to exhibit sequence-specific hybridization in any of the samples. We detected differential gene expression in the resulting dataset with parametric methods and identified keywords that are overrepresented in the differentially expressed genes with the Fisher-exact test. We identify 1,234 genes that are more than three-fold changed in renal tumors by t-test, 800 of which have not been previously reported to be altered in renal cell tumors. Of the only 37 genes that have been identified as being differentially expressed in three or more of five previous microarray studies of renal tumor gene expression, our analysis finds 33 of these genes (89%). A key to the sensitivity and power of our analysis is filtering out defective samples and genes that are not reliably detected. The widespread use of sample-wise voting schemes for detecting differential expression that do not control for false positives likely account for the poor overlap among previous studies. Among the many genes we identified using parametric methods that were not previously reported as being differentially expressed in renal cell tumors are several oncogenes and tumor suppressor genes that likely play important roles in renal cell

Effect of dietary protein restriction on renal ammonia metabolism

Science.gov (United States)

Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Guo, Hui; Verlander, Jill W.

2015-01-01

Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction. PMID:25925252

High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

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Daisuke Ogawa

2011-01-01

Full Text Available Metallothionein (MT is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2 are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy.

Incidental renal neoplasms

DEFF Research Database (Denmark)

Rabjerg, Maj; Mikkelsen, Minne Nedergaard; Walter, Steen

2014-01-01

On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive...... series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients...

Epidemiology, molecular epidemiology, and risk factors for renal cell carcinoma

Directory of Open Access Journals (Sweden)

Chiara Paglino

2011-12-01

Full Text Available Despite only accounting for approximately 2% of all new primary cancer cases, renal cell carcinoma (RCC incidence has dramatically increased over time. Incidence rates vary greatly according to geographic areas, so that it is extremely likely that exogenous risk factors could play an important role in the development of this cancer. Several risk factors have been linked with RCC, including cigarette smoking, obesity, hypertension (and antihypertensive drugs, chronic kidney diseases (also dialysis and transplantation, as well as the use of certain analgesics. Furthermore, although RCC has not generally been considered an occupational cancer, several types of occupationally-derived exposures have been implicated in its pathogenesis. These include exposure to asbestos, chlorinated solvents, gasoline, diesel exhaust fumes, polycyclic aromatic hydrocarbons, printing inks and dyes, cadmium and lead. Finally, families with a predisposition to the development of renal neoplasms were identified and the genes involved discovered and characterized. Therefore, there are now four well-characterized, genetically determined syndromes associated with an increased incidence of kidney tumors, i.e., Von Hippel Lindau (VHL, Hereditary Papillary Renal Carcinoma (HPRC, Birt-Hogg-Dubé Syndrome (BHD, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC. This review will address present knowledge about the epidemiology, molecular epidemiology and risk factors of RCC.

Cell-type-specific activation of mitogen-activated protein kinases in PAN-induced progressive renal disease in rats

International Nuclear Information System (INIS)

Park, Sang-Joon; Jeong, Kyu-Shik

2004-01-01

We examined the time-course activation and the cell-type specific role of MAP kinases in puromycin aminonucleoside (PAN)-induced renal disease. The maximal activation of c-Jun-NH 2 -terminal kinase (JNK), extracellular signal regulated kinase (ERK), and p38 MAP kinase was detected on Days 52, 38, and 38 after PAN-treatment, respectively. p-JNK was localized in mesangial and proximal tubular cells at the early renal injury. It was expressed, therefore, in the inflammatory cells of tubulointerstitial lesions. While, p-ERK was markedly increased in the glomerular regions and macrophages p-p38 was observed in glomerular endothelial cells, tubular cells, and some inflammatory cells. The results show that the activation of MAP kinases in the early renal injury by PAN-treatment involves cellular changes such as cell proliferation or apoptosis in renal native cells. The activation of MAP kinases in infiltrated inflammatory cells and fibrotic cells plays an important role in destructive events such as glomerulosclerosis and tubulointerstitial fibrosis

Stem cells and their role in renal ischaemia reperfusion injury.

Science.gov (United States)

Bagul, Atul; Frost, Jodie H; Drage, Martin

2013-01-01

Ischaemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI). IRI is an underlying multifactorial pathophysiological process which affects the outcome in both native and transplanted patients. The high morbidity and mortality associated with IRI/AKI and disappointing results from current available clinical therapeutic approaches prompt further research. Stem cells (SC) are undifferentiated cells that can undergo both renewal and differentiation into one or more cell types which can possibly ameliorate IRI. To carry out a detailed literature analysis and construct a comprehensive literature review addressing the role of SC in AKI secondary to IRI. Evidence favouring the role of SC in renal IRI and evidence showing no benefits of SC in renal IRI are the two main aspects to be studied. The search strategy was based on an extensive search addressing MESH terms and free text terms. The majority of studies in the field of renal IRI and stem cell therapy show substantial benefits. Studies were mostly conducted in small animal models, thus underscoring the need for further pre-clinical studies in larger animal models, and results should be taken with caution. SC therapy may be promising though controversy exists in the exact mechanism. Thorough scientific exploration is required to assess mechanism, safety profile, reproducibility and methods to monitor administered SC. Copyright © 2012 S. Karger AG, Basel.

Erythrocytosis caused by giant chromophobe renal cell carcinoma: a case report indicating a 9-year misdiagnosis of polycythemia vera.

Science.gov (United States)

Guo, Renbo; Liang, Yiran; Yan, Lei; Xu, Zhonghua; Ren, Juchao

2017-09-06

Erythrocytosis, a rare paraneoplastic syndrome, generally occurs in patients with clear cell renal cell carcinoma and has never been reported in patients with chromophobe renal cell carcinoma. We report a case of a young man suffering from a giant (22-cm) mass on his left kidney. Because of a history of polycythemia vera, the patient had been treated for the condition for 9 years. Radical nephrectomy was successfully performed, and the postoperative pathologic examination confirmed a diagnosis of chromophobe renal cell carcinoma. Unexpectedly, the symptom of erythrocytosis disappeared after the surgery. Further examination and analysis were performed, and we finally attributed his erythrocytosis to chromophobe renal cell carcinoma. Chromophobe renal cell carcinoma could cause erythrocytosis, but the clear-cut mechanism needs further research. Secondary erythrocytosis such as those related with renal tumors should be taken into consideration during the diagnosis of polycythemia vera.

The radiologist's role in the management of papillary renal cell carcinoma.

Science.gov (United States)

Corral de la Calle, M Á; Encinas de la Iglesia, J; Martín López, M R; Fernández Pérez, G C; Águeda Del Bas, D S

Papillary carcinoma is the second most common renal cell carcinoma. It has a better prognosis than the more frequent clear cell carcinoma, although this does not hold true for advanced cases, because no specific treatment exists. It presents as a circumscribed peripheral tumor (small and homogeneously solid or larger and cystic/hemorrhagic) or as an infiltrating lesion that invades the veins, which has a worse prognosis. Due to their low vascular density, papillary renal cell carcinomas enhance less than other renal tumors, and this facilitates their characterization. On computed tomography, they might not enhance conclusively, and in these cases they are impossible to distinguish from hyperattenuating cysts. Contrast-enhanced ultrasonography and magnetic resonance imaging are more sensitive for detecting vascularization. Other characteristics include a specific vascular pattern, hypointensity on T2-weighted images, restricted water diffusion, and increased signal intensity in opposed phase images. We discuss the genetic, histologic, clinical, and radiological aspects of these tumors in which radiologists play a fundamental role in management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Tubulocystic renal cell carcinoma: a new radiological entity

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Cornelis, F.; Grenier, N. [Pellegrin Hospital, Department of Radiology, Bordeaux (France); Helenon, O.; Correas, J.M. [Necker Hospital, Department of Radiology, Paris (France); Lemaitre, L. [Claude Huriez Hospital, Department of Radiology, Lille (France); Andre, M. [La-Conception Hospital, Department of Radiology, Marseille (France); Meuwly, J.Y. [Centre Hospitalier Universitaire Vaudois, Department of Radiology, Lausanne (Switzerland); Sengel, C. [Grenoble Hospital, Department of Radiology, Grenoble (France); Derchi, L. [Universita di Genova, Radiologia - DICMI, Genova (Italy); Yacoub, M. [Pellegrin Hospital, Department of Pathology, Bordeaux (France); Verkarre, V. [Necker Hospital, Department of Pathology, Paris (France)

2016-04-15

Tubulocystic renal cell carcinoma (TC-RCC) is a recently identified renal malignancy. While approximately 100 cases of TC-RCC have been reported in the pathology literature, imaging features have not yet been clearly described. The purpose of this review is to describe the main radiologic features of this rare sub-type of RCC on ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective HIPAA-compliant review of pathology and imaging databases. Using a combination of sonographic and CT/MRI features, diagnosis of TC-RCC appeared to be strongly suggested in many cases. (orig.)

A Unique Presentation of an Undiagnosed Renal Cell Carcinoma

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Georgios Kravvas

2014-01-01

Full Text Available We describe a 58-year-old lady who presented initially to her general practitioner with a palpable warty urethral nodule. She was subsequently referred to the urology department for further investigations. She underwent flexible cystoscopy and imaging, followed by rigid cystoscopy and excision of the nodule. Histological analysis was consistent with renal cell carcinoma (RCC. CT imaging confirmed the presence of an invading metastatic left renal cell carcinoma with bilateral metastatic deposits to the lungs and adrenal glands. The patient was enlisted on the Panther Trial and received a course of Pazopanib before undergoing radical nephrectomy. Two years later she is still alive with metastases remaining reduced in size and numbers. During this study we have performed a literature review of similar cases with this unusual presentation of RCC.

Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

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Alcendor, Donald J

2017-07-15

Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.

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Smeets, Bart; Angelotti, Maria Lucia; Rizzo, Paola; Dijkman, Henry; Lazzeri, Elena; Mooren, Fieke; Ballerini, Lara; Parente, Eliana; Sagrinati, Costanza; Mazzinghi, Benedetta; Ronconi, Elisa; Becherucci, Francesca; Benigni, Ariela; Steenbergen, Eric; Lasagni, Laura; Remuzzi, Giuseppe; Wetzels, Jack; Romagnani, Paola

2009-12-01

Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase-PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations: CD133(+)CD24(+)podocalyxin (PDX)(-)nestin(-) renal progenitors, CD133(+)CD24(+)PDX(+)nestin(+) transitional cells, and CD133(-)CD24(-)PDX(+)nestin(+) differentiated podocytes. In addition, TGF-beta induced CD133(+)CD24(+) progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.

Large cell non-Hodgkin's lymphoma masquerading as renal carcinoma with inferior vena cava thrombosis: a case report

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Weissman Alan

2011-06-01

Full Text Available Abstract Introduction Many cancers are associated with inferior vena cava (IVC obstruction, but very few cancers have the ability to propagate within the lumen of the renal vein or the IVC. Renal cell carcinoma is the most common of these cancers. Renal cancer with IVC extension has a high rate of recurrence and a low five year survival rate. Case presentation A 62-year-old Caucasian woman previously in good health developed the sudden onset of severe reflux symptoms and right-sided abdominal pain that radiated around the right flank. A subsequent ultrasound and CT scan revealed a right upper pole renal mass with invasion of the right adrenal gland, liver, left renal vein and IVC. This appeared to be consistent with stage III renal cancer with IVC extension. Metastatic nodules were believed to be present in the right pericardial region; the superficial anterior abdominal wall; the left perirenal, abdominal and pelvic regions; and the left adrenal gland. The pattern of these metastases, as well as the invasion of the liver by the tumor, was thought to be atypical of renal cancer. A needle biopsy of a superficial abdominal wall mass revealed a surprising finding: The malignant cells were diagnostic of large-cell, B-cell non-Hodgkin's lymphoma. The lymphoma responded dramatically to systemic chemotherapy, which avoided the need for nephrectomy. Conclusion Lymphomas only rarely progress via intraluminal vascular extension. We have been able to identify only one other case report of renal lymphoma with renal vein and IVC extension. While renal cancer would have been treated with radical nephrectomy and tumor embolectomy, large-cell B-cell lymphomas are treated primarily with chemotherapy, and nephrectomy would have been detrimental. It is important to remember that, rarely, other types of cancer arise from the kidney which are not derived from the renal tubular epithelium. These may be suspected if an atypical pattern of metastases or unusual

Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

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Choueiri, Toni K; Escudier, Bernard; Powles, Thomas

2015-01-01

BACKGROUND: Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to an...

Unusual Upper Gastrointestinal Bleeding due to Late Metastasis from Renal Cell Carcinoma: A Case Report

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Wen-Tsan Chang

2004-03-01

Full Text Available A case of recurrent massive upper gastrointestinal bleeding originating from metastatic renal cell carcinoma is reported. A 63-year-old woman underwent right nephrectomy 9 years previously and experienced no recurrence during follow-up. A gradually enlarging ulcerative tumor over the bulb of the duodenum and four subsequent episodes of massive bleeding from this tumor occurred between June 2001 and March 2002. The patient underwent surgery in April 2002 for intractable bleeding from the tumor. Renal cell carcinoma metastasis to the duodenum was confirmed from the surgical specimen. Upper gastrointestinal bleeding due to malignancy is very rare and the duodenum is the least frequently involved site. Furthermore, a solitary late renal cell carcinoma metastasis 9 years after a nephrectomy is extremely uncommon. This case suggests that life-long follow-up of renal cell carcinoma patients is necessary, owing to unpredictable behavior and the possibility of long disease-free intervals. In nephrectomized patients suffering from gastrointestinal bleeding, complete evaluation, especially endoscopic examination, is indicated. The possibility of late recurrent renal cell carcinoma metastasis to the gastrointestinal tract should be kept in mind, although it is rare. If the patient is fit for surgery, metastatectomy is the first choice of treatment.

Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc

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Liu, Yongchao; Yin, Bingde; Zhang, Changcun; Zhou, Libin [Department of Urology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China); Fan, Jie, E-mail: jief67@sina.com [Department of Urology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China)

2012-01-06

Highlights: Black-Right-Pointing-Pointer This study is the first to test the let-7a/c-myc loop in renal cell carcinoma cell lines. Black-Right-Pointing-Pointer Let-7a down-regulated c-myc in three renal cell carcinoma cell lines. Black-Right-Pointing-Pointer c-myc target genes were down-regulated because of the let-7a-mediated down-regulation of c-myc. Black-Right-Pointing-Pointer The let-7a/c-myc loop has a significant function in renal cell carcinoma cell lines. -- Abstract: Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.

Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

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Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

2017-11-30

Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

RENAL CRYOABLATION

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A. V. Govorov

2012-01-01

Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

Understanding familial and non-familial renal cell cancer

NARCIS (Netherlands)

Bodmer, Daniëlle; van den Hurk, Wilhelmina; van Groningen, Jan J. M.; Eleveld, Marc J.; Martens, Gerard J. M.; Weterman, Marian A. J.; van Kessel, Ad Geurts

2002-01-01

Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

Understanding familial and non-familial renal cell cancer.

NARCIS (Netherlands)

Bodmer, D.; Hurk, W.H. van den; Groningen, J.J.M. van; Eleveld, M.J.; Martens, G.J.M.; Weterman, M.A.J.; Geurts van Kessel, A.H.M.

2002-01-01

Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

Renal cell carcinoma: an atypical case containing fat

International Nuclear Information System (INIS)

Saez Castan, J.; Perez Paya, F.; Ramon Sanchez, J.; Rausell Felix, M.; Alpera Tenza, M.; Orti Tarazona, C.

1995-01-01

An atypical form of presentation of renal cell carcinoma is reported. The lesion contained fat collections, an exceptional findings in these neoplasms. We describe the intravenous urography, ultrasound and CT images, as well as the preoperative follow-up using CT, performed 11 months after the first study. 11 refs

Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.

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Xia, Yin; Babitt, Jodie L; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Samad, Tarek A; Brenner, Gary J; Anderson, Jennifer L; Hong, Charles C; Schneyer, Alan L; Brown, Dennis; Lin, Herbert Y

2010-04-01

The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.

Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro

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Morizane, Ryuji [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Monkawa, Toshiaki, E-mail: monkawa@sc.itc.keio.ac.jp [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Itoh, Hiroshi [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan)

2009-12-25

Embryonic stem (ES) cells which have the unlimited proliferative capacity and extensive differentiation potency can be an attractive source for kidney regeneration therapies. Recent breakthroughs in the generation of induced pluripotent stem (iPS) cells have provided with another potential source for the artificially-generated kidney. The purpose of this study is to know how to differentiate mouse ES and iPS cells into renal lineage. We used iPS cells from mouse fibroblasts by transfection of four transcription factors, namely Oct4, Sox2, c-Myc and Klf4. Real-time PCR showed that renal lineage markers were expressed in both ES and iPS cells after the induction of differentiation. It also showed that a tubular specific marker, KSP progressively increased to day 18, although the differentiation of iPS cells was slower than ES cells. The results indicated that renal lineage cells can be differentiated from both murine ES and iPS cells. Several inducing factors were tested whether they influenced on cell differentiation. In ES cells, both of GDNF and BMP7 enhanced the differentiation to metanephric mesenchyme, and Activin enhanced the differentiation of ES cells to tubular cells. Activin also enhanced the differentiation of iPS cells to tubular cells, although the enhancement was lower than in ES cells. ES and iPS cells have a potential to differentiate to renal lineage cells, and they will be an attractive resource of kidney regeneration therapy. This differentiation is enhanced by Activin in both ES and iPS cells.

Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

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Nobuhiko Satoh

2015-01-01

Full Text Available A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2 and stimulates sodium-bicarbonate cotransporter (NBCe1, resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC and epithelial sodium channel (ENaC activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1 mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK. Moreover, sodium-proton exchanger 3 (NHE3 in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.

Renal cell carcinoma: histological classification and correlation with imaging findings

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Muglia, Valdair F., E-mail: fmuglia@fmrp.usp.br [Universidade de Sao Paulo (CCIFM/FMRP/USP), Ribeirao Preto, SP (Brazil). Centro de Ciencias das Imagens e Fisica Medica. Faculdade de Medicina; Prando, Adilson [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Hospital Vera Cruz, Campinas, SP (Brazil). Dept. de Imaginologia

2015-05-15

Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes. (author)

Wallenberg's lateral medullary syndrome: diffusion-weighted imaging findings

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Kitis, O.; Calli, C.; Yunten, N.; Kocaman, A.; Sirin, H. [Ege Univ., Izmir (Turkey). Dept. of Radiology

2004-02-01

To investigate the efficacy of diffusion-weighted imaging in patients with Wallenberg's lateral medullary syndrome. Thirteen patients with Wallenberg's lateral medullary syndrome were examined with conventional and echoplanar diffusion-weighted magnetic resonance (MR) imaging in a 1.5 T magnetic resonance unit. MR examinations were obtained in the acute or subacute stage of clinical syndrome, and diffusion-weighted imaging (DWI) was considered to be positive for infarction when an increase in signal was seen on b = 1000 s/mm2 images in the posterolateral medullary localization. DWIs were positive in 12 patients in the acute or subacute stages of this clinical syndrome. A false-negative result was obtained in only one patient examined within the first day, 10 h after onset of the symptoms. In the visual evaluation of the DWI, the contrast between normal and infarcted brainstem area was better in the high b-value images than in the apparent diffusion coefficient map images. DWI is a valuable technique for examining patients presenting with the signs and symptoms of Wallenberg's syndrome and high b-value images can provide complementary data to T2-weighted images. However, because most of our case group were in either the acute or subacute stage, true sensitivity of the method in the hyperacute stage of the syndrome remains unclear.

Ketamine inhibits 45Ca influx and catecholamine secretion by inhibiting 22Na influx in cultured bovine adrenal medullary cells

International Nuclear Information System (INIS)

Takara, Hiroshi; Wada, Akihiko; Arita, Masahide; Izumi, Futoshi; Sumikawa, Koji

1986-01-01

The effects of ketamine, an intravenous anesthetic, on 22 Na influx, 45 Ca influx and catecholamine secretion were investigated in cultured bovine adrenal medullary cells. Ketamine inhibited carbachol-induced 45 Ca influx and catecholamine secretion in a concentration-dependent manner with a similar potency. Ketamine also reduced veratridine-induced 45 Ca influx and catecholamine secretion. The influx of 22 Na caused by carbachol or by veratridine was suppressed by ketamine with a concentration-inhibition curve similar to that of 45 Ca influx and catecholamine secretion. Inhibition by ketamine of the carbachol-induced influx of 22 Na, 45 Ca and secretion of catecholamines was not reversed by the increased concentrations of carbachol. These observations indicate that ketamine, at clinical concentrations, can inhibit nicotinic receptor-associated ionic channels and that the inhibition of Na influx via the receptor-associated ionic channels is responsible for the inhibition of carbachol-induced Ca influx and catecholamine secretion. (Auth.)

Ciglitazone induces caspase-independent apoptosis via p38-dependent AIF nuclear translocation in renal epithelial cells

International Nuclear Information System (INIS)

Kwon, Chae Hwa; Yoon, Chang Soo; Kim, Yong Keun

2008-01-01

Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been reported to induce apoptosis in a variety of cell types including renal proximal epithelial cells. However, the underlying mechanism of cell death induced by PPARγ agonists has not been clearly defined in renal proximal tubular cells. This study was therefore undertaken to determine the mechanism by which ciglitazone, a synthetic PPARγ agonist, induces apoptosis in opossum kidney (OK) cells, an established renal epithelial cell line. Ciglitazone treatment induced apoptotic cell death in a dose- and time-dependent manner. Ciglitazone caused a transient activation of ERK and sustained activation of p38 MAP kinase. Ciglitazone-mediated cell death was attenuated by the p38 inhibitor SB203580 and transfection of dominant-negative form of p38, but not by the MEK inhibitor U0126, indicating that p38 MAP kinase activation is involved in the ciglitazone-induced cell death. Although ciglitazone-induced caspase-3 activation, the ciglitazone-mediated cell death was not affected by the caspase-3 inhibitor DEVD-CHO. Ciglitazone-induced mitochondrial membrane depolarization and apoptosis-inducing factor (AIF) nuclear translocation and these effects were prevented by the p38 inhibitor. These results suggest that ciglitazone induces caspase-independent apoptosis through p38 MAP kinase-dependent AIF nuclear translocation in OK renal epithelial cells

Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

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Daniel Y.C. Heng

2011-12-01

Full Text Available The treatment of metastatic renal cell carcinoma (RCC has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Many retrospective studies on the use of all three of these targeted therapies in patients with non-clear cell histology have demonstrated response rates ranging from 3.7%–16%. Although response rates may not be as high compared to patients with clear cell histologies, targeted therapy does provide a clinically meaningful response.

Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy.

Science.gov (United States)

Ravaud, Alain; Motzer, Robert J; Pandha, Hardev S; George, Daniel J; Pantuck, Allan J; Patel, Anup; Chang, Yen-Hwa; Escudier, Bernard; Donskov, Frede; Magheli, Ahmed; Carteni, Giacomo; Laguerre, Brigitte; Tomczak, Piotr; Breza, Jan; Gerletti, Paola; Lechuga, Mariajose; Lin, Xun; Martini, Jean-Francois; Ramaswamy, Krishnan; Casey, Michelle; Staehler, Michael; Patard, Jean-Jacques

2016-12-08

Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects. Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC Clinical

Second messenger production in avian medullary nephron segments in response to peptide hormones.

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Goldstein, D L; Reddy, V; Plaga, K

1999-03-01

We examined the sites of peptide hormone activation within medullary nephron segments of the house sparrow (Passer domesticus) kidney by measuring rates of hormone-induced generation of cyclic nucleotide second messenger. Thin descending limbs, thick ascending limbs, and collecting ducts had baseline activity of adenylyl cyclase that resulted in cAMP accumulation of 207 +/- 56, 147 +/- 31, and 151 +/- 41 fmol. mm-1. 30 min-1, respectively. In all segments, this activity increased 10- to 20-fold in response to forskolin. Activity of adenylyl cyclase in the thin descending limb was stimulated approximately twofold by parathyroid hormone (PTH) but not by any of the other hormones tested [arginine vasotocin (AVT), glucagon, atrial natriuretic peptide (ANP), or isoproterenol, each at 10(-6) M]. Thick ascending limb was stimulated two- to threefold by both AVT and PTH; however, glucagon and isoproterenol had no effect, and ANP stimulated neither cAMP nor cGMP accumulation. Adenylyl cyclase activity in the collecting duct was stimulated fourfold by AVT but not by the other hormones; likewise, ANP did not stimulate cGMP accumulation in this segment. These data support a tubular action of AVT and PTH in the avian renal medulla.

Insulin-like growth factor-1 signaling in renal cell carcinoma

International Nuclear Information System (INIS)

Tracz, Adam F.; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M.

2016-01-01

Renal cell carcinoma (RCC) incidence is highest in highly developed countries and it is the seventh most common neoplasm diagnosed. RCC management include nephrectomy and targeted therapies. Type 1 insulin-like growth factor (IGF-1) pathway plays an important role in cell proliferation and apoptosis resistance. IGF-1 and insulin share overlapping downstream signaling pathways in normal and cancer cells. IGF-1 receptor (IGF1R) stimulation may promote malignant transformation promoting cell proliferation, dedifferentiation and inhibiting apoptosis. Clear cell renal cell carcinoma (ccRCC) patients with IGF1R overexpression have 70 % increased risk of death compared to patients who had tumors without IGF1R expression. IGF1R signaling deregulation may results in p53, WT, BRCA1, VHL loss of function. RCC cells with high expression of IGF1R are more resistant to chemotherapy than cells with low expression. Silencing of IGF1R increase the chemosensitivity of ccRCC cells and the effect is greater in VHL mutated cells. Understanding the role of IGF-1 signaling pathway in RCC may result in development of new targeted therapeutic interventions. First preclinical attempts with anti-IGF-1R monoclonal antibodies or fragment antigen-binding (Fab) fragments alone or in combination with an mTOR inhibitor were shown to inhibit in vitro growth and reduced the number of colonies formed by of RCC cells

Comparative effects of mesenchymal stem cell therapy in distinct stages of chronic renal failure.

Science.gov (United States)

Caldas, Heloisa Cristina; de Paula Couto, Thaís Amarante Peres; Fernandes, Ida Maria Maximina; Baptista, Maria Alice Sperto Ferreira; Kawasaki-Oyama, Rosa Sayoko; Goloni-Bertollo, Eny Maria; Braile, Domingo Marcolino; Abbud-Filho, Mario

2015-10-01

The therapeutic potential of adult stem cells in the treatment of chronic diseases is becoming increasingly evident. In the present study, we sought to assess whether treatment with mesenchymal stem cells (MSCs) efficiently retards progression of chronic renal failure (CRF) when administered to experimental models of less severe CRF. We used two renal mass reduction models to simulate different stages of CRF (5/6 or 2/3 mass renal reduction). Renal functional parameters measured were serum creatinine (SCr), creatinine clearance (CCr), rate of decline in CCr (RCCr), and 24-h proteinuria (PT24h). We also evaluated renal morphology by histology and immunohistochemistry. MSCs were obtained from bone marrow aspirates and injected into the renal parenchyma of the remnant kidneys of both groups of rats with CRF (MSC5/6 or MSC2/3). Animals from groups MSC5/6 and CRF2/3 seemed to benefit from MSC therapy because they showed significantly reduction in SCr and PT24h, increase in CCr and slowed the RCCr after 90 days. Treatment reduced glomerulosclerosis but significant improvement did occur in the tubulointerstitial compartment with much less fibrosis and atrophy. MSC therapy reduced inflammation by decreasing macrophage accumulation proliferative activity (PCNA-positive cells) and fibrosis (α-SM-actin). Comparisons of renal functional and morphological parameters responses between the two groups showed that rats MSC2/3 were more responsive to MSC therapy than MSC5/6. This study showed that MSC therapy is efficient to retard CRF progression and might be more effective when administered during less severe stages of CRF.

Lactate dehydrogenase as a biomarker for early renal damage in patients with sickle cell disease

Directory of Open Access Journals (Sweden)

Mohammad S Alzahri

2015-01-01

Full Text Available Among many complications of sickle cell disease, renal failure is the main contributor to early mortality. It is present in up to 21% of patients with sickle cell disease. Although screening for microalbuminuria and proteinuria is the current acceptable practice to detect and follow renal damage in patients with sickle cell disease, there is a crucial need for other, more sensitive biomarkers. This becomes especially true knowing that those biomarkers start to appear only after more than 60% of the kidney function is lost. The primary purpose of this study is to determine whether lactate dehydrogenase (LDH correlates with other, direct and indirect bio-markers of renal insufficiency in patients with sickle cell disease and, therefore, could be used as a biomarker for early renal damage in patients with sickle cell disease. Fifty-five patients with an established diagnosis of sickle cell disease were recruited to in the study. Blood samples were taken and 24-h urine collection samples were collected. Using Statcrunch, a data analysis tool available on the web, we studied the correlation between LDH and other biomarkers of kidney function as well as the distribution and relationship between the variables. Regression analysis showed a significant negative correlation between serum LDH and creatinine clearance, R (correlation coefficient = -0.44, P = 0.0008. This correlation was more significant at younger age. This study shows that in sickle cell patients LDH correlates with creatinine clearance and, therefore, LDH could serve as a biomarker to predict renal insufficiency in those patients.

Salubrious effect of C-phycocyanin against oxalate-mediated renal cell injury.

Science.gov (United States)

Farooq, Shukkur Muhammed; Asokan, Devarajan; Sakthivel, Ramasamy; Kalaiselvi, Periandavan; Varalakshmi, Palaninathan

2004-10-01

C-phycocyanin, a biliprotein pigment found in some blue green algae (Spirulina platensis) with nutritional and medicinal properties, was investigated for its efficacy on sodium oxalate-induced nephrotoxicity in experimentally induced urolithic rats. Male Wistar rats were divided into four groups. Hyperoxaluria was induced in two of these groups by intraperitoneal infusion of sodium oxalate (70 mg/kg), and a pretreatment of phycocyanin (100 mg/kg) as a single oral dosage was given to one of these groups by 1 h prior to sodium oxalate infusion challenges. The study also encompasses an untreated control group and a phycocyanin-alone treated drug control group. The extent of lipid peroxidation (LPO) was evaluated in terms of renal concentrations of MDA, conjugated diene and hydroperoxides. The following assay was performed in the renal tissue (a) antioxidant enzymes such as superoxide dismutase (SOD) and catalase, (b) glutathione metabolizing enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glucose 6-phosphate dehydrogenase (G6PD), (c) the low molecular weight antioxidants (GSH, vitamins E and C) and protein carbonyl content. The increased concentrations of MDA, conjugated diene and hydroperoxide (index of the lipid peroxidation) were controlled (P antioxidants were appreciably increased (P antioxidants. It was noticed that the activities of antioxidant enzymes and glutathione metabolizing enzymes were considerably stabilized in rats pretreated with phycocyanin. We suggest that phycocyanin protects the integrity of the renal cell by stabilizing the free radical mediated LPO and protein carbonyl, as well as low molecular weight antioxidants and antioxidant enzymes in renal cells. Thus, the present analysis reveals that the antioxidant nature of C-phycocyanin protects the renal cell against oxalate-induced injury and may be a nephroprotective agent.

Renal cell carcinoma: new insights and challenges for a clinician scientist.

Science.gov (United States)

Shingarev, Roman; Jaimes, Edgar A

2017-08-01

There is a growing recognition of the complex interplay between renal cell cancer (RCC), kidney function, mechanical reduction of nephron mass, and systemic agents targeting the cancer. Earlier detection of RCC and rising life expectancy of cancer survivors places a greater emphasis on preservation of renal function after cancer resection and during systemic therapy. Unique adverse effects associated with RCC drugs not only help reveal cancer pathophysiology but also expand our knowledge of normal cell signaling and metabolism. In this review, we outline our current understanding of RCC biology and treatment, their bidirectional relationship with kidney function, and unmet research needs in this field. Copyright © 2017 the American Physiological Society.

Renal cell carcinoma: incidental detection and pathological staging.

Science.gov (United States)

Siow, W Y; Yip, S K; Ng, L G; Tan, P H; Cheng, W S; Foo, K T

2000-10-01

In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.

Lateral medullary infarction with cardiovascular autonomic dysfunction: an unusual presentation with review of the literature.

Science.gov (United States)

Huynh, Tridu R; Decker, Barbara; Fries, Timothy J; Tunguturi, Ajay

2018-01-24

We report an unusual case of lateral medullary infarction presenting with orthostatic hypotension with pre-syncope without vertigo or Horner's syndrome. Case report with review of the literature. A 67-year-old man presented with pre-syncope and ataxia without vertigo. Initial brain CT and MRI were normal. Neurological evaluation revealed right-beating nystagmus with left gaze, vertical binocular diplopia, right upper-extremity dysmetria, truncal ataxia with right axial lateropulsion, and right-facial and lower extremity hypoesthesia. Bedside blood pressure measurements disclosed orthostatic hypotension. He had normal sinus rhythm on telemetry and normal ejection fraction on echocardiogram. A repeat brain MRI disclosed an acute right dorsolateral medullary infarct. Autonomic testing showed reduced heart rate variability during paced deep breathing, attenuated late phase II and phase IV overshoot on Valsalva maneuver, and a fall of 25 mmHg of blood pressure at the end of a 10-min head-up tilt with no significant change in heart rate. These results were consistent with impaired sympathetic and parasympathetic cardiovascular reflexes. He was discharged to acute rehabilitation a week later with residual right dysmetria and ataxia. Lateral medullary infarctions are usually reported as partial presentations of classical lateral medullary syndrome with accompanying unusual symptoms ranging from trigeminal neuralgias to hiccups. Pre-syncope from orthostatic hypotension is a rare presentation. In the first 3-4 days, absence of early DWI MRI findings is possible in small, dorsolateral medullary infarcts with sensory disturbances. Physicians should be aware of this presentation, as early diagnosis and optimal therapy are associated with good prognosis.

Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection

OpenAIRE

Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

2015-01-01

Background Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. Methods The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules inc...

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

NARCIS (Netherlands)

Ricketts, Christopher J.; De Cubas, Aguirre A.; Fan, Huihui; Smith, Christof C.; Lang, Martin; Reznik, Ed; Bowlby, Reanne; Gibb, Ewan A.; Akbani, Rehan; Beroukhim, Rameen; Bottaro, Donald P.; Choueiri, Toni K.; Gibbs, Richard A.; Godwin, Andrew K.; Haake, Scott; Hakimi, A. Ari; Henske, Elizabeth P.; Hsieh, James J.; Ho, Thai H.; Kanchi, Rupa S.; Krishnan, Bhavani; Kwaitkowski, David J.; Lui, Wembin; Merino, Maria J.; Mills, Gordon B.; Myers, Jerome; Nickerson, Michael L.; Reuter, Victor E.; Schmidt, Laura S.; Shelley, Carl Simon; Shen, Hui; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Vincent, Benjamin G.; Vocke, Cathy D.; Wheeler, David A.; Yang, Lixing; Kim, William T.; Robertson, A. Gordon; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Gonzalez, Ana Maria Angulo; Behrens, Carmen; Bondaruk, Jolanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, onathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Pinero, Edna M.Mora; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz; Spellman, Paul T.; Rathmell, W. Kimryn; Linehan, W. Marston

2018-01-01

Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC,

Alveolar architecture of clear cell renal carcinomas (≤5.0 cm) show high attenuation on dynamic CT scanning

International Nuclear Information System (INIS)

Fujimoto, Hiroyuki; Wakao, Fumihiko; Moriyama, Noriyuki; Tobisu, Kenichi; Kakizoe, Tadao; Sakamoto, Michiie

1999-01-01

To establish the correlation between tumor appearance on CT and tumor histology in renal cell carcinomas. The density and attenuation patterns of 96 renal cell carcinomas, each ≤5 cm in greatest diameter, were studied by non-enhanced CT and early and late after bolus injection of contrast medium using dynamic CT. The density and attenuation patterns and pathological maps of each tumor were individually correlated. High attenuated areas were present in 72 of the 96 tumors on early enhanced dynamic CT scanning. All 72 high attenuated areas were of the clear cell renal cell carcinoma and had alveolar architecture. The remaining 24 tumors that did not demonstrate high attenuated foci on early enhanced scanning included three clear cell, nine granular cell, six papillary, five chromophobe and one collecting duct type. With respect to tumor architecture, all clear cell tumors of alveolar architecture demonstrated high attenuation on early enhanced scanning. Clear cell renal cell carcinomas of alveolar architecture show high attenuation on early enhanced dynamic CT scanning. A larger number of patients are indispensable to obtaining clear results. However, these findings seem to be an important clue to the diagnosis of renal cell carcinomas as having an alveolar structure. (author)

Use of the gamma probe and of 99mTc-DMSA (V) in the identification of the neck recurrence of medullary carcinoma thyroid

International Nuclear Information System (INIS)

Melo, Rosana Leite de; Kowalski, Luiz P.; Ubrich, Fabio F.; Lima, Eduardo N. Pereira; Torres, Ivone C.G.

2003-01-01

Medullary carcinoma of the thyroid, a malignant neoplasm of para follicular C cells, represent about 5-10% of thyroid tumors. The symptoms are related to local invasion and hormonal secretion. The clinical course is variable, from indolent cases to extremely aggressive. Many radionuclide imaging have been described to locate metastasis of medullary cancer. Tl-201 and Tc-99m (V)DMS A showed to be useful in the evaluation o persistent elevated serum calcitonin levels. On the other hand, the use of the 131 I-Mibg, that is the isotope more used, has not been demonstrating efficiency in identifying metastasis. Our objective is to report a case of a patient with medullary thyroid carcinoma in which the follow-up use DMS A(V) demonstrated a recurrence no identified for other methods. A 34-year-old man had a diagnosis of medullary thyroid carcinoma and has submitted a total thyroidectomy and neck lymph node dissection. He presented elevated serum calcitonin levels and DMS A(V) scintigraphy demonstrated focal area of pathologic uptake at the medline of the neck, but the surgical exploration was negative. He persisted with high calcitonin levels and it was used a new DMS A(V). On this occasion he was submitted to the radio-guided surgery that located the recurrence and it was confirmed with anatomo-pathologic exam. This case allowed to demonstrate that the use of radionuclide associated to the gamma-probe is promising, allowing a precise surgical approach. (author)

Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial

DEFF Research Database (Denmark)

Berntsen, Annika; Trepiakas, Redas; Wenandy, Lynn

2008-01-01

Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...... with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype......, and low-dose IL-2 was administered concomitantly. Tumor response, immune response, and serum IL-6 and YKL-40 were measured during treatment. Vaccine generation was successful in all patients and no serious adverse events were observed. None of the patients had an objective response but 13/27 patients...

Mathematical Model of Ammonia Handling in the Rat Renal Medulla

Science.gov (United States)

Noiret, Lorette; Baigent, Stephen; Jalan, Rajiv; Thomas, S. Randall

2015-01-01

The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and NH4+, and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts. PMID:26280830

Evaluation of Renal Blood Flow and Oxygenation in CKD Using Magnetic Resonance Imaging.

Science.gov (United States)

Khatir, Dinah S; Pedersen, Michael; Jespersen, Bente; Buus, Niels H

2015-09-01

Animal studies suggest that progression of chronic kidney disease (CKD) is related to renal hypoxia. With renal blood supply determining oxygen delivery and sodium absorption being the main contributor to oxygen consumption, we describe the relationship between renal oxygenation, renal artery blood flow, and sodium absorption in patients with CKD and healthy controls. Cross-sectional study. 62 stable patients with CKD stages 3 to 4 (mean age, 61±13 [SD] years) and 24 age- and sex-matched controls. CKD versus control status. Renal artery blood flow, tissue oxygenation (relative changes in deoxyhemoglobin concentration of the renal medulla [MR2*] and cortex [CR2*]), and sodium absorption. Renal artery blood flow was determined by phase-contrast magnetic resonance imaging (MRI); MR2* and CR2* were determined by blood oxygen level-dependent MRI. Ultrafiltered and reabsorbed sodium were determined from measured glomerular filtration rate (mGFR) and 24-hour urine collections. mGFR in patients was 37% that of controls (36±15 vs 97±23 mL/min/1.73 m(2); P renal artery blood flow was 72% that of controls (319 vs 443 mL/min; P renal artery blood flow or sodium absorption. Increasing arterial blood oxygen tension by breathing 100% oxygen had very small effects on CR2*, but reduced MR2* in both groups. Only renal artery blood flow was determined and thus regional perfusion could not be related to CR2* or MR2*. In CKD, reductions of mGFR and reabsorbed sodium are more than double that of renal artery blood flow, whereas cortical and medullary oxygenation are within the range of healthy persons. Reduction in glomerular filtration fraction may prevent renal hypoxia in CKD. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Directory of Open Access Journals (Sweden)

Ding F

2014-09-01

Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

Does injection of metanephric mesenchymal cells improve renal function in rats?

Directory of Open Access Journals (Sweden)

Yu-qing Jiao

2011-01-01

Full Text Available Chronic kidney disease (CKD is a massive global health-care problem. Cell therapy offers a potential treatment for CKD. The aim of this study was to investigate whether the administration of a population of stem cells could be used to treat adriamycin (ADR-induced glomerulopathy in rats, a form of CKD. We intravenously transplanted metanephric mesenchymal cells (MMCs into rats treated with ADR. We also induced MMC differentiation in vitro using a medium derived from serum and homogenates of ADR-induced glomerulopathy rats. We detected the induction of an early epithelial phenotype (cytokeratin-18 expression and a proximal tubule phenotype (vitamin D receptor expression in vitro, and MMC-derived epithelial cells corresponding to the proximal tubule and glomeruli in vivo. Transplantation of MMCs after induction of glomerulopathy significantly increased the creatinine clearance rate (Ccr, a marker for glomerular filtration rate, but had no significant effect on other parameters (24-hour urinary protein excretion, serum albumin, total cholesterol. In addition, there was no significant difference in blood urea nitrogen or serum creatinine levels in rats with and without ADR administration. Our results indicate that MMCs might survive, engraft and differentiate into renal epithelia in vivo when transplanted into ADR-treated rats. However, further studies are needed to determine whether MMC transplantation improves renal function and causes renal repair in this model.

Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

DEFF Research Database (Denmark)

Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff

2015-01-01

stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

Metastasis Targeted Therapies in Renal Cell Cancer

OpenAIRE

K. Fehmi Narter; Bora Özveren

2018-01-01

Metastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improvi...

Frequency of Cushing's syndrome due to ACTH-secreting adrenal medullary lesions: a retrospective study over 10 years from a single center.

Science.gov (United States)

Falhammar, Henrik; Calissendorff, Jan; Höybye, Charlotte

2017-01-01

Cushing's syndrome due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions has occasionally been described. We retrospectively reviewed all 164 cases of Cushing's syndrome and 77 cases of pheochromocytomas during 10 years. Of all cases with Cushing's syndrome, only two cases (1.2 %) were due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions (one case of pheochromocytoma and one case of adrenal medullary hyperplasia). Of all pheochromocytomas only the above-mentioned case (1.3 %) also gave rise to an ectopic adrenocorticotropic hormone syndrome. The clinical presentation of adrenocorticotropic hormone-secreting pheochromocytoma and adrenal medullary hyperplasia can be anything from mild to dramatic. These are rare conditions important to bear in mind in the workup of a patient with Cushing's syndrome or with pheochromocytoma. The identification of ectopic adrenocorticotropic hormone secretion from adrenal medullary lesions can be life-saving.

Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Twite, Nicolas [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Andrei, Graciela [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Kummert, Caroline [ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Donner, Catherine [Department of Obstetrics and Gynecology, Erasme Hospital, Route de Lennik 808, 1070 Brussels (Belgium); Perez-Morga, David [Laboratory of Molecular Parasitology, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies (Belgium); De Vos, Rita [Pathology Department, U.Z. Leuven, Minderbroedersstraat 12, Leuven (Belgium); Snoeck, Robert, E-mail: Robert.Snoeck@Rega.kuleuven.be [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Marchant, Arnaud, E-mail: arnaud.marchant@ulb.ac.be [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium)

2014-07-15

Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

NARCIS (Netherlands)

Davis, Caleb F; Ricketts, Christopher J; Wang, Min; Yang, Lixing; Cherniack, Andrew D; Shen, Hui; Buhay, Christian; Kang, Hyojin; Kim, Sang Cheol; Fahey, Catherine C; Hacker, Kathryn E; Bhanot, Gyan; Gordenin, Dmitry A; Chu, Andy; Gunaratne, Preethi H; Biehl, Michael; Seth, Sahil; Kaipparettu, Benny A; Bristow, Christopher A; Donehower, Lawrence A; Wallen, Eric M; Smith, Angela B; Tickoo, Satish K; Tamboli, Pheroze; Reuter, Victor; Schmidt, Laura S; Hsieh, James J; Choueiri, Toni K; Hakimi, A Ari; Chin, Lynda; Meyerson, Matthew; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A Gordon; Laird, Peter W; Henske, Elizabeth P; Kwiatkowski, David J; Park, Peter J; Morgan, Margaret; Shuch, Brian; Muzny, Donna; Wheeler, David A; Linehan, W Marston; Gibbs, Richard A; Rathmell, W Kimryn; Creighton, Chad J

2014-01-01

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared

Recovery of Dysphagia in Lateral Medullary Stroke

OpenAIRE

Gupta, Hitesh; Banerjee, Alakananda

2014-01-01

Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia...

Hydronephrosis in the Wnt5a-ablated kidney is caused by an abnormal ureter-bladder connection.

Science.gov (United States)

Yun, Kangsun; Perantoni, Alan O

The Wnt5a null mouse is a complex developmental model which, among its several posterior-localized axis defects, exhibits multiple kidney phenotypes, including duplex kidney and loss of the medullary zone. We previously reported that ablation of Wnt5a in nascent mesoderm causes duplex kidney formation as a result of aberrant development of the nephric duct and abnormal extension of intermediate mesoderm. However, these mice also display a loss of the medullary region late in gestation. We have now genetically isolated duplex kidney formation from the medullary defect by specifically targeting the progenitors for both the ureteric bud and metanephric mesenchyme. The conditional mutants fail to form a normal renal medulla but no longer exhibit duplex kidney formation. Approximately 1/3 of the mutants develop hydronephrosis in the kidneys either uni- or bilaterally when using Dll1Cre. The abnormal kidney phenotype becomes prominent at E16.5, which approximates the time when urine production begins in the mouse embryonic kidney, and is associated with a dramatic increase in apoptosis only in mutant kidneys with hydronephrosis. Methylene blue dye injection and histologic examination reveal that aberrant cell death likely results from urine toxicity due to an abnormal ureter-bladder connection. This study shows that Wnt5a is not required for development of the renal medulla and that loss of the renal medullary region in the Wnt5a-deleted kidney is caused by an abnormal ureter-bladder connection. Published by Elsevier B.V.

The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma

Energy Technology Data Exchange (ETDEWEB)

Doerr, U.; Bihl, H. (Katharinenhospital, Stuttgart (Germany). Dept. of Nuclear Medicine); Frank-Raue, K.; Raue, F. (Heidelberg Univ. (Germany). Dept. of Internal Medicine); Sautter-Bihl, M.L.; Buhr, H.J. (Staedt. Klinikum, Karlsruhe (Germany). Dept. of Radiooncology and Nuclear Medicine); Guzman, G. (Katherinenhospital, Stuttgart (Germany). Dept. of Nuclear Medicine Inst. de Neurocirugia, Investigationes Cerebrales ' Dr Asenjo' Santiago (Chile). Dept. de Medicina Nuclear)

1993-06-01

In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with [sup 111]In-pentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group. (Author).

The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma

International Nuclear Information System (INIS)

Doerr, U.; Bihl, H.; Frank-Raue, K.; Raue, F.; Sautter-Bihl, M.L.; Buhr, H.J.; Guzman, G.; Inst. de Neurocirugia, Investigationes Cerebrales 'Dr Asenjo' Santiago

1993-01-01

In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with 111 In-pentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group. (Author)

Cell kinetics of differentiation of Na+-dependent hexose transport in a cultured renal epithelial cell line

International Nuclear Information System (INIS)

Cook, J.S.; Weiss, E.R.

1985-01-01

Fully differentiated cells of the renal proximal tubule have the capability of taking up hexoses across their apical borders by transport coupled to the Na + -electrochemical gradient. This property is also found in postconfluent cultures of the cloned cell line LLC-PK 1 , a morphologically polarized line of renal cells. Postconfluent cells develop the Na + -dependent capacity to transport hexoses at their apical surface. This function is not observable during the growth phase of the cultures. To analyze the developmental process at the cellular level a method has been derived to separate transporting cells, expressing the differentiated function, from nontransporting cells. The method is based on the swelling of the cells accompanying the uptake of the nonmetabolizable glucose analog alpha methylglucoside. The swollen cells have a lower buoyant density than the undifferentiated cells and may be separated from them on density gradients. Analysis of the distribution of cells on such gradients shows that after the cells reach confluence the undifferentiated subpopulation is recruited onto the differentiation pathway with a rate constant of 0.2 per day, that 5 to 7 days are required for a cell to traverse this pathway to the fully differentiated state, and that once the maximum uptake capacity is achieved the cells do not develop further

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

Science.gov (United States)

Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

A case of renal cell carcinoma and angiomyolipoma in an ...

African Journals Online (AJOL)

Abstract. We describe a case of renal cell carcinoma in the right kidney together with an angiomyolipoma in the left kidney, encountered in an adolescent girl at Potchefstroom Provincial Hospital, North West Province, South Africa.

Urinary acidification and urinary excretion of calcium and citrate in women with bilateral medullary sponge kidney

DEFF Research Database (Denmark)

Osther, P J; Mathiasen, Helle; Hansen, A B

1994-01-01

Urinary acidification ability, acid-base status and urinary excretion of calcium and citrate were evaluated in 10 women with bilateral medullary sponge kidney (MSK) and in 10 healthy women. Patients with MSK had higher fasting urine pH compared to normal controls (p ... in the mechanism of hypercalciuria and hypocitraturia in patients with medullary sponge kidney.(ABSTRACT TRUNCATED AT 250 WORDS)...

Intensity ratio curve analysis of small renal masses on T2-weighted magnetic resonance imaging: Differentiation of fat-poor angiomyolipoma from renal cell carcinoma.

Science.gov (United States)

Moriyama, Shingo; Yoshida, Soichiro; Tanaka, Hajime; Tanaka, Hiroshi; Yokoyama, Minato; Ishioka, Junichiro; Matsuoka, Yoh; Saito, Kazutaka; Kihara, Kazunori; Fujii, Yasuhisa

2018-03-25

To assess the diagnostic ability of a pixel intensity-based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat-poor angiomyolipoma from renal cell carcinoma. T2-weighted images from 121 solid small renal masses (ratio curve was plotted using intensity ratios, which were ratios of signal intensities of tumor pixels (each pixel along a linear region of interest drawn across the renal tumor on T2-weighted image) to the signal intensity of a normal renal cortex. The diagnostic ability of the intensity ratio curve analysis was evaluated. The tumors were classified into three types: intensity ratio fat-poor angiomyolipoma (n = 19) with no pseudocapsule, iso-low intensity and no heterogeneity; intensity ratio clear cell renal cell carcinoma (n = 76) with a pseudocapsule, iso-high intensity and heterogeneity; and other type of intensity ratio (n = 26), including tumors that did not fall into the above two categories. The sensitivity/specificity/accuracy of the intensity ratio curve analysis in diagnosing fat-poor angiomyolipoma was 93%/94%/94%, respectively. When the intensity ratio curve analysis was applied only to the tumor with undetermined radiological diagnosis, the sensitivity for diagnosing fat-poor angiomyolipoma compared with subjective reading alone significantly improved (93% vs 50%; P = 0.014). Our novel semiquantitative model for combined assessment of key features of fat-poor angiomyolipoma, including low intensity, homogeneity and absence of a pseudocapsule on T2-weighted image, might make diagnosis of fat-poor angiomyolipoma more accurate. © 2018 The Japanese Urological Association.

Influence of Bisphosphonate Treatment on Medullary Macrophages and Osteoclasts: An Experimental Study

Directory of Open Access Journals (Sweden)

Natalia Daniela Escudero

2012-01-01

Full Text Available Nitrogen-containing bisphosphonates are widely used for treating diverse bone pathologies. They are anticatabolic drugs that act on osteoclasts inhibiting bone resorption. It remains unknown whether the mechanism of action is by decreasing osteoclast number, impairing osteoclast function, or whether they continue to effectively inhibit bone resorption despite the increase in osteoclast number. There is increasing evidence that bisphosphonates also act on bone marrow cells like macrophages and monocytes. The present work sought to evaluate the dynamics of preosteoclast fusion and possible changes in medullary macrophage number in bisphosphonate-treated animals. Healthy female Wistar rats received olpadronate, alendronate, or vehicle during 5 weeks, and 5-bromo-2-deoxyuridine (BrdU on day 7, 28, or 34 of the experiment. Histomorphometric studies were performed to study femurs and evaluate: number of nuclei per osteoclast (N.Nu/Oc; number of BrdU-positive nuclei (N.Nu BrdU+/Oc; percentage of BrdU-positive nuclei per osteoclast (%Nu.BrdU+/Oc; medullary macrophage number (mac/mm2 and correlation between N.Nu/Oc and mac/mm2. Results showed bisphosphonate-treated animals exhibited increased N.Nu/Oc, caused by an increase in preosteoclast fusion rate and evidenced by higher N.Nu BrdU+/Oc, and significantly decreased mac/mm2. Considering the common origin of osteoclasts and macrophages, the increased demand for precursors of the osteoclast lineage may occur at the expense of macrophage lineage precursors.

Biochemical markers in the follow-up of medullary thyroid cancer

NARCIS (Netherlands)

de Groot, Jan Willem B.; Kema, Ido P.; Breukelman, Henk; van der Veer, Eveline; Wiggers, Theo; Plukker, John T. M.; Wolffenbuttel, Bruce H. R.; Links, Thera P.

2006-01-01

Medullary thyroid cancer (MTC) shares biochemical features with other neuroendocrine tumors but the particular characteristics are largely unexplored. We investigated the biochemical neuroendocrine profile of MTC and whether specific markers could be useful in follow-up. In addition to the standard

Can bone marrow differentiate into renal cells?

Science.gov (United States)

Imai, Enyu; Ito, Takahito

2002-10-01

A considerable plasticity of adult stem cells has been confirmed in a wide variety of tissues. In particular, the pluripotency of bone marrow-derived stem cells may influence the regeneration of injured tissues and may provide novel avenues in regenerative medicine. Bone marrow contains at least hematopoietic and mesenchymal stem cells, and both can differentiate into a wide range of differentiated cells. Side population (SP) cells, which are originally defined in bone marrow cells by high efflux of DNA-binding dye, seem to be a new class of multipotent stem cells. Irrespective of the approach used to obtain stem cells, the fates of marrow-derived cells following bone marrow transplantation can be traced by labeling donor cells with green fluorescence protein or by identifying donor Y chromosome in female recipients. So far, bone marrow-derived cells have been reported to differentiate into renal cells, including mesangial cells, endothelial cells, podocytes, and tubular cells in the kidney, although controversy exists. Further studies are required to address this issue. Cell therapy will be promising when we learn to control stem cells such as bone marrow-derived stem cells, embryonic stem cells, and resident stem cells in the kidney. Identification of factors that support stem cells or promote their differentiation should provide a relevant step towards cell therapy.

Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

International Nuclear Information System (INIS)

Heck, Julia E.; Moore, Lee E.; Lee, Yuan-Chin A.; McKay, James D.; Hung, Rayjean J.; Karami, Sara; Gaborieau, Valérie; Szeszenia-Dabrowska, Neonila; Zaridze, David G.; Mukeriya, Anush; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Kollárová, Helena; Bencko, Vladimir; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Boffetta, Paolo

2012-01-01

Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

Energy Technology Data Exchange (ETDEWEB)

Heck, Julia E. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); Moore, Lee E. [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Lee, Yuan-Chin A. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); McKay, James D. [International Agency for Research on Cancer, Lyon (France); Hung, Rayjean J. [Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON (Canada); Karami, Sara [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Gaborieau, Valérie [International Agency for Research on Cancer, Lyon (France); Szeszenia-Dabrowska, Neonila [Department of Epidemiology, Institute of Occupational Medicine, Lodz (Poland); Zaridze, David G. [Cancer Research Centre, Institute of Carcinogenesis, Moscow (Russian Federation); Mukeriya, Anush [Cancer Research Centre, Department of Epidemiology, Moscow (Russian Federation); Mates, Dana [Institute of Public Health, Bucharest (Romania); Foretova, Lenka [Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno (Czech Republic); Janout, Vladimir; Kollárová, Helena [Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc (Czech Republic); Bencko, Vladimir [First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University in Prague, Prague, Czech Republic (Czech Republic); Rothman, Nathaniel [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Brennan, Paul [International Agency for Research on Cancer, Lyon (France); Chow, Wong-Ho [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Boffetta, Paolo, E-mail: paolo.boffetta@mssm.edu [International Prevention Research Institute, Lyon (France); Tisch Cancer Institute, Mt. Sinai School of Medicine, New York, NY (United States)

2012-02-20

Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.

NARCIS (Netherlands)

Smeets, B.; Angelotti, M.L.; Rizzo, P.; Dijkman, H.; Lazzeri, E.; Mooren, F.; Ballerini, L.; Parente, E.; Sagrinati, C.; Mazzinghi, B.; Ronconi, E.; Becherucci, F.; Benigni, A.; Steenbergen, E.; Lasagni, L.; Remuzzi, G.; Wetzels, J.F.M.; Romagnani, P.

2009-01-01

Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner

βENaC acts as a mechanosensor in renal vascular smooth muscle cells that contributes to renal myogenic blood flow regulation, protection from renal injury and hypertension.

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Drummond, Heather A; Stec, David E

2015-06-01

Pressure-induced constriction (also known as the "myogenic response") is an important mechanodependent response in small renal arteries and arterioles. The response is initiated by vascular smooth muscle cell (VSMC) stretch due to an increase in intraluminal pressure and leads to vasoconstriction. The myogenic response has two important roles as a mechanism of local blood flow autoregulation and protection against systemic blood pressure-induced microvascular damage. However, the molecular mechanisms underlying initiation of myogenic response are unresolved. Although several molecules have been considered initiators of the response, our laboratory has focused on the role of degenerin proteins because of their strong evolutionary link to mechanosensing in the nematode. Our laboratory has addressed the hypothesis that certain degenerin proteins act as mechanosensors in VSMCs. This article discusses the importance of a specific degenerin protein, β Epithelial Na + Channel (βENaC), in pressure-induced vasoconstriction, renal blood flow and susceptibility to renal injury. We propose that loss of the renal myogenic constrictor response delays the correction of renal blood flow that occurs with fluctuations in systemic pressure, which allows pressure swings to be transmitted to the microvasculature, thus increasing the susceptibility to renal injury and hypertension. The role of βENaC in myogenic regulation is independent of tubular βENaC and thus represents a non-tubular role for βENaC in renal-cardiovascular homeostasis.

Clinical Relevance of Gene Copy Number Variation in Metastatic Clear Cell Renal Cell Carcinoma.

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Nouhaud, François-Xavier; Blanchard, France; Sesboue, Richard; Flaman, Jean-Michel; Sabourin, Jean-Christophe; Pfister, Christian; Di Fiore, Frédéric

2018-02-23

Gene copy number variations (CNVs) have been reported to be frequent in renal cell carcinoma (RCC), with potential prognostic value for some. However, their clinical utility, especially to guide treatment of metastatic disease remains to be established. Our objectives were to assess CNVs on a panel of selected genes and determine their clinical relevance in patients who underwent treatment of metastatic RCC. The genetic assessment was performed on frozen tissue samples of clear cell metastatic RCC using quantitative multiplex polymerase chain reaction of short fluorescent fragment method to detect CNVs on a panel of 14 genes of interest. The comparison of the electropherogram obtained from both tumor and normal renal adjacent tissue allowed for CNV identification. The clinical, biologic, and survival characteristics were assessed for their associations with the most frequent CNVs. Fifty patients with clear cell metastatic RCC were included. The CNV rate was 21.4%. The loss of CDKN2A and PLG was associated with a higher tumor stage (P relevance, especially those located on CDKN2A, PLG, and ALDOB, in a homogeneous cohort of patients with clear cell metastatic RCC. Copyright © 2018 Elsevier Inc. All rights reserved.

Microsatellite instability in medullary carcinoma of the colon

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Mario Martinotti

2017-03-01

Full Text Available Medullary carcinoma (MC of the large intestine is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and an intraepithelial lymphocytic infiltrate. MC can be associated to a defective mechanism for DNA mismatch repair, caused by the so-called microsatellite instability (MSI. We present the case of a 44 years old Caucasian woman, who referred to the Emergency Room with symptoms mimicking an acute appendicitis. Computed tomography and colonoscopy demonstrated an ulcerated and stenotic lesion of the caecum without signs of metastasis and peritoneal carcinosis. Patient underwent a laparoscopic right colectomy. The final pathologic findings provided the diagnosis of medullary carcinoma with MSI. Patient then underwent adjuvant chemotherapy according to the FOLFOX- 4 protocol (association of 5-Fluorouracil, Leucovorin, and Oxaliplatin for twelve cycles. At two-years follow-up, patient is disease free. MC in association with MSI is a non-frequent tumor of the colon characterized by a better prognosis compared to other types of poorly differentiated adenocarcinoma. In the observed case, 24 months after the surgical operation, the patient is in good health and there is no evidence of metastasis or relapse.

[Current role of color Doppler ultrasound in acute renal failure].

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Bertolotto, M; Quaia, E; Rimondini, A; Lubin, E; Pozzi Mucelli, R

2001-01-01

Acute Renal Failure (ARF) is characterized by a rapid decline of the glomerular filtration rate, due to hypotension (prerenal ARF), obstruction of the urinary tract (post-renal ARF) or renal parenchymal disease (renal ARF). The differential diagnosis among different causes of ARF is based on anamnesis, clinical symptoms and laboratory data. Usually ultrasound (US) is the only imaging examination performed in these patients, because it is safe and readily available. In patients with ARF gray scale US is usually performed to rule out obstruction since it is highly sensitive to recognize hydronephrosis. Patients with renal ARF have no specific changes in renal morphology. The size of the kidneys is usually normal or increased, with smooth margins. Detection of small kidneys suggests underlying chronic renal pathology and worse prognosis. Echogenicity and parenchymal thickness are usually normal, but in some cases there are hyperechogenic kidneys, increased parenchymal thickness and increased cortico-medullary differentiation. Evaluation of renal vasculature with pulsed Doppler US is useful in the differential diagnosis between prerenal ARF and acute tubular necrosis (ATN), and in the diagnosis of renal obstruction. Latest generation US apparatus allow color Doppler and power Doppler evaluation of renal vasculature up to the interlobular vessels. A significant, but non specific, reduction in renal perfusion is usually appreciable in the patients with ARF. There are renal pathologic conditions presenting with ARF in which color Doppler US provides more specific morphologic and functional information. In particular, color Doppler US often provides direct or indirect signs which can lead to the right diagnosis in old patients with chronic renal insufficiency complicated with ARF, in patients with acute pyelonephritis, hepatic disease, vasculitis, thrombotic microangiopathies, and in patients with acute thrombosis of the renal artery and vein. Contrast enhanced US is

Leiomyosarcoma of the renal pelvis

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Dhamne Sagar

2009-10-01

Full Text Available Leiomyosarcomas are rare malignant tumors of the kidney. They may arise from the renal capsule, renal vein, renal pelvic musculature or renal parenchyma. Renal pelvis is an uncommon site of occurrence, with around 10 cases reported in the literature so far. Here we present a 60-year-old male who presented with increased urinary frequency, lower limb weakness, anorexia and weight loss. Imaging showed a right renal mass. A renal cell carcinoma was suspected clinically. A right nephrectomy was performed, which showed a large circumscribed mass in the hilar region. Histology revealed a tumor mass arising from the renal pelvis. The tumor was composed of spindle cells arranged in fascicles. Immunohistochemistry showed tumor cells to be positive for smooth muscle actin (SMA and desmin (Des and negative for cytokeratin (CK, HMB 45, CD117 (C-kit, and CD34. That confirmed the diagnosis of leiomyosarcoma.

Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

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Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

2012-05-01

Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

In vivo imaging of cellular proliferation in renal cell carcinoma using 18F-fluorothymidine PET

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Wong, Peter K.; Lee, Sze Ting; Murone, Carmel; Eng, John; Lawrentschuk, Nathan; Berlangieri, Salvatore University; Pathmaraj, Kunthi; O’Keefe, Graeme J.; Sachinidis, John; Byrne, Amanda J.; Bolton, Damien M.; Davis, Ian D.; Scott, Andrew M.

2014-01-01

The ability to measure cellular proliferation non-invasively in renal cell carcinoma may allow prediction of tumour aggressiveness and response to therapy. The aim of this study was to evaluate the uptake of 18F-fluorothymidine (FLT) PET in renal cell carcinoma (RCC), and to compare this to 18F-fluorodeoxyglucose (FDG), and to an immunohistochemical measure of cellular proliferation (Ki-67). Twenty seven patients (16 male, 11 females; age 42-77) with newly diagnosed renal cell carcinoma suitable for resection were prospectively enrolled. All patients had preoperative FLT and FDG PET scans. Visual identification of tumour using FLT PET compared to normal kidney was facilitated by the use of a pre-operative contrast enhanced CT scan. After surgery tumour was taken for histologic analysis and immunohistochemical staining by Ki-67. The SUVmax (maximum standardized uptake value) mean±SD for FLT in tumour was 2.59±1.27, compared to normal kidney (2.47±0.34). The mean SUVmax for FDG in tumour was similar to FLT (2.60±1.08). There was a significant correlation between FLT uptake and the immunohistochemical marker Ki-67 (r=0.72, P<0.0001) in RCC. Ki-67 proliferative index was mean ± SD of 13.3%±9.2 (range 2.2% - 36.3%). There is detectable uptake of FLT in primary renal cell carcinoma, which correlates with cellular proliferation as assessed by Ki-67 labelling index. This finding has relevance to the use of FLT PET in molecular imaging studies of renal cell carcinoma biology

Isolated Late Metastasis of a Renal Cell Cancer Treated by Radical Distal Pancreatectomy

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J. P. Barras

1996-01-01

Full Text Available A 53–year-old man underwent right nephrectomy for a locally advanced renal cell carcinoma with concomitant resection of a solitary metastasis in the right lung. Ten years later, he presented with haematochezia caused by a tumour in the tail of pancreas, invading the transverse colon and the greater curvature of the stomach. The tumour was radically resected, and histological examination revealed a solitary metastasis of the previous renal cell carcinoma. This case illustrates a rare indication for pancreatic resection because of pancreatic metastasis.

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

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Marcelo Zerati

2013-07-01

Full Text Available Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC is evolving, and Carbonic Anhydrase type IX (CA-IX has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1 overall survival, and 2 with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion. Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS, TNM stage, tumor size (TS, Fuhrman nuclear grade (FNG, microvascular invasion (MVI, peri-renal fat invasion (PFI. We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years. The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790; T stage (p = 0.179; tumor size (p = 0.143; grouped Fuhrman nuclear grade (p = 0.598; microvascular invasion (p = 0.685, and peri-renal fat invasion (p = 0.104. Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.