The Experts below are selected from a list of 186 Experts worldwide ranked by ideXlab platform
Hanna E. Abboud - One of the best experts on this subject based on the ideXlab platform.
-
Novel Mechanism of Regulation of the DNA repair enzyme OGG1 in Tuberin- deficient
2016Co-Authors: Nahed Sadek, Hanna E. Abboud, Sherry Abboudwerner, Samy L. HabibAbstract:D ow nloaded from Tuberin (encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in Tumour Kidney of TSC patients. The purpose of this study was to elucidate the mechanisms by which tuberin regulates OGG1. The partial deficiency in tuberin expression that occurs in the renal proximal tubular cells and Kidney cortex of the Eker rat is associated with decreased AP4 and OGG1 expression. A complete deficiency in tuberin is associated with loss of AP4 and OGG1 expression in Kidney Tumour from Eker rats and the accumulation of significant levels of 8-oxodG. Knockdown of tuberin expression in human renal epithelial cells (HEK293) with siRNA also resulted in a marked decrease in the expression of AP4 and OGG1. In contrast, overexpression of tuberin in HEK293 cells increased the expression of AP4 and OGG1 proteins. Downregulation of AP4 expressio
-
Novel mechanism of regulation of the DNA repair enzyme OGG1 in tuberin-deficient cells
Carcinogenesis, 2010Co-Authors: Samy L. Habib, Nahed Sadek, Besant K. Bhandari, Sherry L. Abboud-werner, Hanna E. AbboudAbstract:Tuberin (protein encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease in the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in Tumour Kidney of tuberous sclerosis complex (TSC) patients. The purpose of this study was to elucidate the mechanisms by which tuberin regulates OGG1. The partial deficiency in tuberin expression that occurs in the renal proximal tubular cells and Kidney cortex of the Eker rat is associated with decreased activator protein 4 (AP4) and OGG1 expression. A complete deficiency in tuberin is associated with loss of AP4 and OGG1 expression in Kidney Tumour from Eker rats and the accumulation of significant levels of 8-oxo-deoxyguanosine. Knockdown of tuberin expression in human renal epithelial cells (HEK293) with small interfering RNA (siRNA) also resulted in a marked decrease in the expression of AP4 and OGG1. In contrast, overexpression of tuberin in HEK293 cells increased the expression of AP4 and OGG1 proteins. Downregulation of AP4 expression using siRNA resulted in a significant decrease in the protein expression of OGG1. Immunoprecipitation studies show that AP4 is associated with tuberin in cells. Gel shift analysis and chromatin immunoprecipitation identified the transcription factor AP4 as a positive regulator of the OGG1 promoter. AP4 DNA-binding activity is significantly reduced in Tsc2−/− as compared with Tsc2+/+ cells. Transcriptional activity of the OGG1 promoter is also decreased in tuberin-null cells compared with wild-type cells. These data indicate a novel role for tuberin in the regulation of OGG1 through the transcription factor AP4. This regulation may be important in the pathogenesis of Kidney Tumours in patients with TSC disease.
Samy L. Habib - One of the best experts on this subject based on the ideXlab platform.
-
Novel Mechanism of Regulation of the DNA repair enzyme OGG1 in Tuberin- deficient
2016Co-Authors: Nahed Sadek, Hanna E. Abboud, Sherry Abboudwerner, Samy L. HabibAbstract:D ow nloaded from Tuberin (encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in Tumour Kidney of TSC patients. The purpose of this study was to elucidate the mechanisms by which tuberin regulates OGG1. The partial deficiency in tuberin expression that occurs in the renal proximal tubular cells and Kidney cortex of the Eker rat is associated with decreased AP4 and OGG1 expression. A complete deficiency in tuberin is associated with loss of AP4 and OGG1 expression in Kidney Tumour from Eker rats and the accumulation of significant levels of 8-oxodG. Knockdown of tuberin expression in human renal epithelial cells (HEK293) with siRNA also resulted in a marked decrease in the expression of AP4 and OGG1. In contrast, overexpression of tuberin in HEK293 cells increased the expression of AP4 and OGG1 proteins. Downregulation of AP4 expressio
-
Novel mechanism of regulation of the DNA repair enzyme OGG1 in tuberin-deficient cells
Carcinogenesis, 2010Co-Authors: Samy L. Habib, Nahed Sadek, Besant K. Bhandari, Sherry L. Abboud-werner, Hanna E. AbboudAbstract:Tuberin (protein encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease in the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in Tumour Kidney of tuberous sclerosis complex (TSC) patients. The purpose of this study was to elucidate the mechanisms by which tuberin regulates OGG1. The partial deficiency in tuberin expression that occurs in the renal proximal tubular cells and Kidney cortex of the Eker rat is associated with decreased activator protein 4 (AP4) and OGG1 expression. A complete deficiency in tuberin is associated with loss of AP4 and OGG1 expression in Kidney Tumour from Eker rats and the accumulation of significant levels of 8-oxo-deoxyguanosine. Knockdown of tuberin expression in human renal epithelial cells (HEK293) with small interfering RNA (siRNA) also resulted in a marked decrease in the expression of AP4 and OGG1. In contrast, overexpression of tuberin in HEK293 cells increased the expression of AP4 and OGG1 proteins. Downregulation of AP4 expression using siRNA resulted in a significant decrease in the protein expression of OGG1. Immunoprecipitation studies show that AP4 is associated with tuberin in cells. Gel shift analysis and chromatin immunoprecipitation identified the transcription factor AP4 as a positive regulator of the OGG1 promoter. AP4 DNA-binding activity is significantly reduced in Tsc2−/− as compared with Tsc2+/+ cells. Transcriptional activity of the OGG1 promoter is also decreased in tuberin-null cells compared with wild-type cells. These data indicate a novel role for tuberin in the regulation of OGG1 through the transcription factor AP4. This regulation may be important in the pathogenesis of Kidney Tumours in patients with TSC disease.
M Stockle - One of the best experts on this subject based on the ideXlab platform.
-
assessing the impact of ischaemia time during partial nephrectomy
European Urology, 2009Co-Authors: F Becker, Hendrik Van Poppel, Oliver W Hakenberg, Christian G Stief, Inderbir S Gill, Giorgio Guazzoni, Francesco Montorsi, Paul Russo, M StockleAbstract:Abstract Context The impact of applying renal ischaemia during nephron-sparing surgery to avoid renal damage in the treated Kidney has gained importance in different surgical techniques. Objective The main objective of the present study is to point out the limit of renal ischaemia times for warm and cold ischaemia approaches. Important results of research on renal ischaemia and different surgical techniques as well as results of clinical studies concerning renal function after renal ischaemia in partial nephrectomy are highlighted. Evidence acquisition A Medline literature research was performed, combining queries on the keywords nephron-sparing surgery, partial nephrectomy , and ischemia . Links to related articles and cross-reading of citations in related articles were surveyed, as were reviews, letters to editors, and information collected from urologic textbooks. The references formed the basis of this review article, with selection and deletion based on the relevance and importance of the content. In a final step, interactive peer review by the expert panel of coauthors completed the review. Evidence synthesis Renal ischaemia research showed an increasing renal damage proportional to ischemic time. Current clinical data support safe ischaemia times, within 20min of warm ischaemia and up to 2h of cold ischaemia, to minimise renal ischemic damage. To date, no ischaemia dose-response curve or algorithm is available to predict the risk of acute Kidney injury and chronic Kidney disease in patients undergoing intraoperative ischaemia. In general, there seems to be a higher risk for comorbidity caused by renal damage in patients suffering from Kidney Tumour. Conclusions If ischaemia is required, the Tumour should be removed within 20min of warm ischaemia, regardless of surgical approach. Efforts should be made to start immediately with cold ischaemia, if the feasibility within this span of time seems to be jeopardised. Thus, cold ischaemia times up to 2h can be tolerated by the Kidney, depending on the individual method. Nevertheless, cold ischaemia with ice slush should be kept as short as possible—at best within 35min. In ischemic nephron-sparing surgery, one of the surgeon's main aims should be to avoid loss of renal function. Only after optimal preoperative appraisal and planning can the best postoperative outcomes for renal function be achieved.
-
nephrectomy work bench surgery and autotransplantation a case of a solitary left Kidney with an extensive centrally located renal cell carcinoma and a Tumour thrombus entering the vena cava
European Urology, 2007Co-Authors: Helene Kemmer, Stefan Siemer, M StockleAbstract:Abstract Objectives In patients with imperative indication, organ preserving Kidney Tumour surgery is state of the art. We present our management of an extensive centrally located renal cell carcinoma. Methods The patient was suffering from a 8×6×6cm centrally located Tumour in the solitary left Kidney which infiltrated the lower pole of the Kidney, the hilum and built a large Tumour thrombus entering the vena cava inferior. We performed a radical nephrectomy with cavotomy, Tumour trombectomy and Tumour resection in cold ischemia at the work bench (R0). Results Total ischemic time took 4 h, warm ischemic time 60 min. The pathological Tumour stage was pT3b, pN0, R0. During 17 mo of aftercare, the patient was free of metastatic disease and without complaints (serum creatinine actually 1.6 mg/dl). Conclusions Hemodialysis reduces the quality of life for 30–40%, the mean mortality rate on hemodialysis is 13% per patient year. To prevend patients from hemodialysis, nephrectomy, work bench surgery and autotransplantation, even in large centrally located Tumours and multimorbid patients should be considered to maintain quality and to extend expectancy of life.
Hendrik Van Poppel - One of the best experts on this subject based on the ideXlab platform.
-
assessing the impact of ischaemia time during partial nephrectomy
European Urology, 2009Co-Authors: F Becker, Hendrik Van Poppel, Oliver W Hakenberg, Christian G Stief, Inderbir S Gill, Giorgio Guazzoni, Francesco Montorsi, Paul Russo, M StockleAbstract:Abstract Context The impact of applying renal ischaemia during nephron-sparing surgery to avoid renal damage in the treated Kidney has gained importance in different surgical techniques. Objective The main objective of the present study is to point out the limit of renal ischaemia times for warm and cold ischaemia approaches. Important results of research on renal ischaemia and different surgical techniques as well as results of clinical studies concerning renal function after renal ischaemia in partial nephrectomy are highlighted. Evidence acquisition A Medline literature research was performed, combining queries on the keywords nephron-sparing surgery, partial nephrectomy , and ischemia . Links to related articles and cross-reading of citations in related articles were surveyed, as were reviews, letters to editors, and information collected from urologic textbooks. The references formed the basis of this review article, with selection and deletion based on the relevance and importance of the content. In a final step, interactive peer review by the expert panel of coauthors completed the review. Evidence synthesis Renal ischaemia research showed an increasing renal damage proportional to ischemic time. Current clinical data support safe ischaemia times, within 20min of warm ischaemia and up to 2h of cold ischaemia, to minimise renal ischemic damage. To date, no ischaemia dose-response curve or algorithm is available to predict the risk of acute Kidney injury and chronic Kidney disease in patients undergoing intraoperative ischaemia. In general, there seems to be a higher risk for comorbidity caused by renal damage in patients suffering from Kidney Tumour. Conclusions If ischaemia is required, the Tumour should be removed within 20min of warm ischaemia, regardless of surgical approach. Efforts should be made to start immediately with cold ischaemia, if the feasibility within this span of time seems to be jeopardised. Thus, cold ischaemia times up to 2h can be tolerated by the Kidney, depending on the individual method. Nevertheless, cold ischaemia with ice slush should be kept as short as possible—at best within 35min. In ischemic nephron-sparing surgery, one of the surgeon's main aims should be to avoid loss of renal function. Only after optimal preoperative appraisal and planning can the best postoperative outcomes for renal function be achieved.
-
what does the urologist expect from the pathologist and what can the pathologists give in reporting on adult Kidney Tumour specimens
European Urology, 2007Co-Authors: Ziya Kirkali, Ferran Algaba, Marina Scarpelli, Isabel Trias, Francesco Paolo Selvaggi, Hendrik Van PoppelAbstract:Abstract Objective To identify the parameters required by the urologist to determine the prognosis and the treatment of renal cancer in adults, and to establish the potential therapeutic targets of the new treatments that started to show clinical efficacy. Methods A literature search of the last 10 yr was done, paying specific attention to TNM 2002 (UICC staging) and Fuhrman's grading. Also, the main genetic characteristics of the different subtypes (according to the WHO 2004 classification) with potential therapeutic implications have been compiled. Results After the review of the literature, the opinion of the joint meeting including urologists and pathologists is that some aspects of the TNM 2002 classification must be refined. Criteria for nuclear grading should be different for the subtypes of renal cell carcinoma, and the WHO 2004 histological classification is clinically useful. Conclusions In the workshop held in Palermo, common opinion was achieved on a number of points. The TNM 2002 classification is useful, but some adjustments should be made, particularly as referred to the Tumour size cut-off, assessment of the invasion of the renal sinus fat tissue, and invasion of the ipsilateral adrenal gland. The Fuhrman's grading system is useful in clear cell renal cell carcinoma (RCC), and probably also in papillary RCC, but a redefinition for chromophobe RCC is needed. Finally, the determination of certain markers, such as VEGF and HIF, could constitute good target markers for the new therapies, but they remain under investigation.
Nahed Sadek - One of the best experts on this subject based on the ideXlab platform.
-
Novel Mechanism of Regulation of the DNA repair enzyme OGG1 in Tuberin- deficient
2016Co-Authors: Nahed Sadek, Hanna E. Abboud, Sherry Abboudwerner, Samy L. HabibAbstract:D ow nloaded from Tuberin (encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in Tumour Kidney of TSC patients. The purpose of this study was to elucidate the mechanisms by which tuberin regulates OGG1. The partial deficiency in tuberin expression that occurs in the renal proximal tubular cells and Kidney cortex of the Eker rat is associated with decreased AP4 and OGG1 expression. A complete deficiency in tuberin is associated with loss of AP4 and OGG1 expression in Kidney Tumour from Eker rats and the accumulation of significant levels of 8-oxodG. Knockdown of tuberin expression in human renal epithelial cells (HEK293) with siRNA also resulted in a marked decrease in the expression of AP4 and OGG1. In contrast, overexpression of tuberin in HEK293 cells increased the expression of AP4 and OGG1 proteins. Downregulation of AP4 expressio
-
Novel mechanism of regulation of the DNA repair enzyme OGG1 in tuberin-deficient cells
Carcinogenesis, 2010Co-Authors: Samy L. Habib, Nahed Sadek, Besant K. Bhandari, Sherry L. Abboud-werner, Hanna E. AbboudAbstract:Tuberin (protein encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease in the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in Tumour Kidney of tuberous sclerosis complex (TSC) patients. The purpose of this study was to elucidate the mechanisms by which tuberin regulates OGG1. The partial deficiency in tuberin expression that occurs in the renal proximal tubular cells and Kidney cortex of the Eker rat is associated with decreased activator protein 4 (AP4) and OGG1 expression. A complete deficiency in tuberin is associated with loss of AP4 and OGG1 expression in Kidney Tumour from Eker rats and the accumulation of significant levels of 8-oxo-deoxyguanosine. Knockdown of tuberin expression in human renal epithelial cells (HEK293) with small interfering RNA (siRNA) also resulted in a marked decrease in the expression of AP4 and OGG1. In contrast, overexpression of tuberin in HEK293 cells increased the expression of AP4 and OGG1 proteins. Downregulation of AP4 expression using siRNA resulted in a significant decrease in the protein expression of OGG1. Immunoprecipitation studies show that AP4 is associated with tuberin in cells. Gel shift analysis and chromatin immunoprecipitation identified the transcription factor AP4 as a positive regulator of the OGG1 promoter. AP4 DNA-binding activity is significantly reduced in Tsc2−/− as compared with Tsc2+/+ cells. Transcriptional activity of the OGG1 promoter is also decreased in tuberin-null cells compared with wild-type cells. These data indicate a novel role for tuberin in the regulation of OGG1 through the transcription factor AP4. This regulation may be important in the pathogenesis of Kidney Tumours in patients with TSC disease.
