27 results on '"Pantuck, Allan J."'
Search Results
2. Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma.
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Kroeger, Nils, Klatte, Tobias, Chamie, Karim, Rao, P. Nagesh, Birkhäuser, Frédéric D., Sonn, Geoffrey A., Riss, Joseph, Kabbinavar, Fairooz F., Belldegrun, Arie S., and Pantuck, Allan J.
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RENAL cell carcinoma ,CHROMOSOMES ,TUMOR suppressor genes ,CANCER ,TUMORS - Abstract
BACKGROUND: The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau ( VHL) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia-inducible factor 1α ( HIF-1α) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1α gene) in clear cell renal cell carcinoma (ccRCC). METHODS: In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL +3p/+14q (VHL wild type [VHL-WT]), VHL +3p/−14q (VHL-WT plus HIF2α [WT/H2]), −3p/+14q (HIF1α and HIF2α [H1H2]), and −3p/−14q (HIF2α [H2]). RESULTS: Among patients who had loss of 3p, tumors with −3p/−14q (H2) alterations were larger ( P = .002), had higher grade ( P = .002) and stage ( P = .001), and more often were metastatic ( P = .029) than tumors that retained 14q (H1H2). All patients who had tumors with −3p/−14q (H2) had worse cancer-specific survival ( P = .014), and patients who had localized disease ( P = .012) and primary T1 (pT1) tumors ( P = .008) had worse recurrence-free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence-free survival (hazard ratio, 11.19; 95% confidence interval, 1.91-65.63) and cancer-specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09-82.16). The current investigation was limited by its retrospective design, single-center experience, and a lack of confirmatory protein analyses. CONCLUSIONS: Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1α gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1α functions as an important tumor suppressor gene in ccRCC. Cancer 2013. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]
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- 2013
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3. Gain of chromosome 8q is associated with metastases and poor survival of patients with clear cell renal cell carcinoma.
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Klatte, Tobias, Kroeger, Nils, Rampersaud, Edward N., Birkhäuser, Frédéric D., Logan, Joshua E., Sonn, Geoffrey, Riss, Joseph, Rao, P. Nagesh, Kabbinavar, Fairooz F., Belldegrun, Arie S., and Pantuck, Allan J.
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CHROMOSOMES ,METASTASIS ,RENAL cell carcinoma ,KARYOTYPES ,CYTOGENETICS ,MITOGEN-activated protein kinases ,PATIENTS - Abstract
BACKGROUND: The aim of this study was to evaluate the prevalence of chromosome 8q gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings with tumor phenotype and disease-specific survival (DSS). METHODS: The tumor karyotypes of 336 consecutive patients with CCRCC were prospectively evaluated with classical cytogenetic analysis. Chromosome 8q status was correlated with clinicopathological variables, and its impact on DSS was evaluated. RESULTS: Gain of 8q occurred in 28 tumors (8.3%). Gain of 8q was associated with a higher risk of regional lymph node (21.4% vs 6.2%, P = .011) and distant metastases (50.0% vs 24.4%, P = .006), and greater tumor sizes ( P = .030). Patients with gain of 8q had a 3.22-fold increased risk of death from CCRCC ( P < .001). In multivariable analysis, gain of 8q was identified as an independent prognostic factor (hazard ratio, 2.37; P = .006). The concordance index of a multivariable base model increased significantly following inclusion of 8q gain ( P = .0015). CONCLUSIONS: Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an increased risk of metastases and death from CCRCC. Because the proto-oncogene c-MYC is among the list of candidate genes located on 8q, our data suggest that these tumors may have unique pathways activated, which are associated with an aggressive tumor phenotype. If confirmed, defining tumors with gain of 8q may assist in identifying patients who would benefit for specific c-MYC inhibitors or agents that target the MAPK/ERK (mitogen-activated protein kinase) pathway. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]
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- 2012
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4. Impact of pathological tumour characteristics in patients with sarcomatoid renal cell carcinoma.
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Shuch, Brian, Bratslavsky, Gennady, Shih, Joanna, Vourganti, Srinivas, Finley, David, Castor, Brandon, Treat, Eric, Linehan, W. Marston, Pantuck, Allan J., Said, Jonathan W., and Belldegrun, Arie S.
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TUMORS ,SARCOMA ,RENAL cell carcinoma ,COHORT analysis ,PROGNOSIS ,PATIENTS - Abstract
Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Sarcomatoid renal cell carcinoma can occur in the setting of all histological subtypes of kidney cancer. These tumours are very aggressive and many patients present with disseminated disease. Long-term survival is poor and the durable responses to systemic therapy are infrequent. Our large cohort analyses the influence of pathological tumour characteristics in determining prognosis for patients with sarcomatoid renal cell carcinoma undergoing surgical resection. This series helps define the prognostic influence of histological subtype, type of sarcomatoid morphology, the percentage necrosis and sarcomatoid features, and the presence of microvascular invasion. OBJECTIVES To examine the influence of pathological tumour characteristics on survival to aid prognostication and clinical trial design., Patients with sarcomatoid renal cell carcinoma (sRCC) are known to have poor prognosis and response to systemic therapy., PATIENTS AND METHODS A single-centre database was reviewed to identify all patients with sRCC., Clinical variables and pathological information, including histology, necrosis, percentage of sarcomatoid features (PSF) and microvascular invasion (MVI), were recorded and correlated to outcome., RESULTS Analyses of 104 patients with sRCC found that the median (range) size of tumours was 9.5 cm (2.5-30), 65% of patients had areas of clear cell histology, and 69.2% had metastatic disease at presentation., The PSF did not influence tumour size, stage, necrosis, MVI, nodes or metastasis., A total of 85 patients (81.7%) died during the follow-up period with a median (95% confidence interval [CI]) survival of 5.9 months (4.7-8.9)., In the overall cohort, Eastern Cooperative Group performance status (ECOGPS), tumour size and metastatic disease were independent predictors of poor survival. MVI, PSF and percentage necrosis were strongly associated with outcome but were not independent predictors of outcome., A multivariate risk model was established that incorporated six covariates (tumour size, MVI, ECOGPS, PSF, necrosis, and metastatic disease) to produce a predictive tool., CONCLUSIONS Both patients with localized and metastatic sRCC have very poor survival outcomes., Pathological features MVI, PSF and necrosis are important predictors of survival and could be used in a prognostic model while grade and histology do not influence prognosis., A prognostic model, if validated, could aid in patient counselling and/or clinical trial design. [ABSTRACT FROM AUTHOR]
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- 2012
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5. Smoking negatively impacts renal cell carcinoma overall and cancer-specific survival.
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Kroeger, Nils, Klatte, Tobias, Birkhäuser, Frédéric D., Rampersaud, Edward N., Seligson, David B., Zomorodian, Nazy, Kabbinavar, Fairooz F., Belldegrun, Arie S., and Pantuck, Allan J.
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HEALTH ,SMOKING ,RENAL cell carcinoma ,CANCER patients ,IMMUNOHISTOCHEMISTRY ,CIGARETTE smokers - Abstract
BACKGROUND: Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the impact of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC. METHODS: Eight hundred-two patients (457 nonsmokers and 345 smokers) who had up to 232 months of follow-up were compared for differences in their clinicopathologic features and survival outcomes. Immunohistochemical differences in p53 expression were correlated with smoking status. RESULTS: Smokers presented more commonly with pulmonary comorbidities ( P < .0001) and cardiac comorbidities ( P = .014) and with a worse performance status ( P = .031) than nonsmokers. Smoking was associated significantly with tumor multifocality ( P = .022), higher pathologic tumor classification ( P = .037), an increased risk of bulky lymph node metastases ( P = .031), and the presence of distant metastases ( P < .0001), especially lung metastases ( P < .0001). Both overall survival (OS) (62.37 months vs 43.64 months; P = .001) and cancer-specific survival (CSS) (87.43 months vs 56.57 months; P = .005) were significantly worse in patients who smoked. The number of pack-years was retained as an independent predictor of CSS and OS in patients with nonmetastatic disease. Mean expression levels of p53 were significantly higher in current smokers compared with former smokers and nonsmokers ( P = .012). CONCLUSIONS: In patients with RCC, a history of smoking was associated with worse pathologic features and survival outcomes and with an increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in patients with RCC who have a history of smoking is indicated. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]
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- 2012
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6. Quality of pathological reporting for renal cell cancer: implications for systemic therapy, prognostication and surveillance.
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Shuch, Brian, Pantuck, Allan J., Pouliot, Frederic, Finley, David S., Said, Jonathan W., Belldegrun, Arie S., and Saigal, Chris
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RENAL cell carcinoma , *NECROSIS - Abstract
OBJECTIVE • To evaluate whether current nephrectomy pathology reports are sufficient to allow clinicians to use prognostic nomograms, tailor surveillance, enroll patients into adjuvant trials and select systemic therapy for renal cell carcinoma (RCC). PATIENTS AND METHODS • Nephrectomy pathology reports were obtained from the LA County Tumor Registry. Key reporting elements identified by the College of American Pathology (CAP) and utilized in RCC prognostic models were abstracted. Hospital type was coded as community, teaching or cancer centre. • Reporting quality was assessed across hospital type and year. RESULTS • A total of 317 of 344 sampled reports (92.2%) met the inclusion criteria. Tumour size and margin status were commonly reported. Some 90.2% and 84.2% of reports provided data on histology and Fuhrman grade. Tumour classification was omitted in 27.8%. • Microvascular invasion and necrosis were infrequently reported (44.5% and 25.6%, respectively). Only 59.9% of reports met CAP guidelines for tumour classification, margin, size, histology and grade. • Two prognostic nomograms (Stage, Size, Grade and Necrosis system and Kattan) could rarely be utilized (15.8% and 12.3%, respectively), whereas the UCLA Integrated Staging System could be used frequently (65.6%). There were discrepancies satisfying CAP guidelines between community, teaching and cancer centre hospitals, with 54.7%, 70.5% and 75% of reports meeting CAP criteria ( P = 0.0102). CONCLUSIONS • Current RCC pathology reporting fails to satisfy CAP guidelines, does not permit the use of prognostic systems, and may hinder enrollment into adjuvant trials and the selection of systemic therapy. Important reporting discrepancies exist between hospital types, with cancer centres performing best. • Quality improvement initiatives to encourage consistent, comprehensive and clinically relevant pathology reports would improve the quality of RCC patient care. [ABSTRACT FROM AUTHOR]
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- 2011
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7. Cardiopulmonary bypass and renal cell carcinoma with level IV tumour thrombus: can deep hypothermic circulatory arrest limit perioperative mortality?
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Shuch, Brian, Crispen, Paul L., Leibovich, Bradley C., LaRochelle, Jeff C., Pouliot, Frederic, Pantuck, Allan J., Liu, Weiqing, Crepel, Maxime, Schuckman, Anne, Rigaud, Jerome, Bouchot, Oliver, Patard, Jean-Jacques, Skinner, Donald, Belldegrun, Arie S., and Blute, Michael L.
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RENAL cell carcinoma ,TUMORS ,CARDIOPULMONARY bypass ,SURGERY ,MORTALITY ,REGRESSION analysis - Abstract
OBJECTIVE • To review experience with nephrectomy/thrombectomy for a renal cell carcimoma (RCC) with a level IV tumour thrombus and to evaluate the benefit of deep hypothermic circulatory arrest (DHCA) with cardiopulmonary bypass (CPBP). PATIENTS AND METHODS • A multi-institutional retrospective database was created to assess the outcomes of surgery for RCC and associated level IV tumour thrombus from 1983 to 2007. Patients were identified based on radiographic records/operative findings. • Only cases using CPBP were analysed. Clinicopathological and operative characteristics including use of DHCA were recorded. • Overall survival (OS) for all patients and by use of DHCA was assessed. Comparisons of clinical and operative characteristics by use of DHCA were performed. • A Cox regression model determined predictors of perioperative/in-hospital mortality. RESULTS • In all, 63 patients underwent resection with CPBP; overall perioperative mortality was 22.2%. • There were no significant differences in clinicopathological characteristics, operative duration, estimated blood loss, transfusions, and hospital stay by use of DHCA. • Perioperative mortality rate was lower in patients undergoing DHCA (8.3% vs 37.5%, P = 0.006). • The median OS was longer for the patients undergoing DHCA (15.8 vs 7.7 months); however, this failed to reach statistical significance ( P = 0.357). • On multivariate analysis, age of > 60 years (hazard ratio [HR] 6.7, 95% confidence interval [CI] 1.5-31.1, P = 0.015) and the use of DHCA (HR 0.13, 95% CI 0.036-0.51, P = 0.003) were independent predictors of perioperative mortality. CONCLUSIONS • Radical nephrectomy and level IV tumour thrombectomy is associated with significant mortality. • The use of DHCA does not appear to adversely affect operative characteristics and may limit perioperative mortality. • Further prospective studies should be performed to confirm the benefit of DHCA. [ABSTRACT FROM AUTHOR]
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- 2011
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8. Chromosome 9p Deletions Identify an Aggressive Phenotype of Clear Cell Renal Cell Carcinoma.
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Rochelle, Jeffrey La, Klatte, Tobias, Dastane, Aditi, Rao, Nagesh, Seligson, David, Said, Jonathan, Shuch, Brian, Zomorodian, Nazy, Kabbinavar, Fairooz, Belldegrun, Arie, and Pantuck, Allan J.
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CHROMOSOME abnormalities ,RENAL cell carcinoma ,SURVIVAL analysis (Biometry) ,FLUORESCENCE in situ hybridization ,CYTOGENETICS ,CANCER research - Abstract
The article offers information on a study which determined whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicted worse disease-specific survival (DSS) and recurrence-free survival (RFS). The study also investigated the possible association between the deletion and aggressive behavior in small renal masses. Methods used include fluorescence in situ hybridization and cytogenetics. A discussion on the research findings is detailed. The benefits of preoperative identification of patients with 9p deletions are mentioned.
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- 2010
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9. Histologic Evaluation of Metastases in Renal Cell Carcinoma With Sarcomatoid Transformation and Its Implications for Systemic Therapy.
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Shuch, Brian, Said, Jonathan, LaRochelle, Jeffrey C., Ying Zhou, Gang Li, Kiatte, Tobias, Pouliot, Frederic, Kabbinavar, Fairooz F., Belidegrun, Arie S., and Pantuck, Allan J.
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RENAL cell carcinoma ,TUMOR growth ,METASTASIS ,SARCOMA ,HISTOLOGY - Abstract
The article presents a study which investigates the histologic appearance and pattern of the spread of primary tumors with sarcomatoid characteristics in renal cells. It mentions that the study utilizes patients with sarcomatoid histology who are admitted at the University of California, Los Angeles from 1989-2007. Results of the nephrectomy show that the sarcomatoid features are oftentimes observed in the metastases with a solitary pattern that supports the subclone hypothesis.
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- 2010
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10. Carbonic Anhydrase IX in Bladder Cancer: A Diagnostic, Prognostic, and Therapeutic Molecular Marker.
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Kiatte, Tobias, Seligson, David B., Jian Yu Rao, Hong Yu, de Martino, Michela, Kawaoka, Kelly, Wong, Steven G., Belidegrun, Arie S., and Pantuck, Allan J.
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CARBONIC anhydrase ,BLADDER cancer ,IMMUNOHISTOCHEMISTRY ,IMMUNOGLOBULINS ,DISEASE relapse ,PROTEIN microarrays - Abstract
The article presents a study which aims to evaluate the role of carbonic anhydrase IX (CAIX) in urothelial carcinoma of the bladder. It states that the condition may affect about 69,000 Americans in 2008 and 14,000 will die of the disease. Researchers performed immunohistorical staining using antibody, MN-75 and constructed tissue microarray. The study found out that CAIX is seen as a strong predictor of recurrence, progression and overall survival of bladder cancer patients.
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- 2009
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11. Prognostic variables to predict cancer-related death in incidental renal tumours.
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Bensalah, Karim, Pantuck, Allan J., Crepel, Maxime, Verhoest, Grégory, Méjean, Arnaud, Valéri, Antoine, Ficarra, Vincenzo, Pfister, Christian, Ferrière, Jean-Marie, Souli, Michel, Cindolo, Luca, De La Taille, Alexandre, Tostain, Jacques, Chautard, Denis, Schips, Luigi, Zigeuner, Richard, Abbou, Claude C., Lobel, Bernard, Salomon, Laurent, and Lechevallier, Eric
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RENAL cell carcinoma , *KIDNEY diseases , *PATHOLOGY , *METASTASIS , *CANCER patients - Abstract
OBJECTIVE To identify, in a large multicentre series of incidental renal tumours, the key factors that could predict cancer-related deaths, as such tumours have a better outcome than symptomatic tumours and selected patients are increasingly being included in watchful-waiting protocols. PATIENTS AND METHODS Data from 3912 patients were extracted from three international kidney-cancer databases. Age, gender, Eastern Cooperative Oncology Group (ECOG) performance status (PS), Tumour-Node-Metastasis (TNM) stage, tumour size, Fuhrman grade, and final pathology were recorded. Benign tumours and malignant lesions with incomplete information were excluded from final analysis. RESULTS The mean (sd) age of the patients was 60.6 (12.2) years and the mean tumour size 5.5 (3.5) cm. Most tumours were malignant (90.2%) and of low stage (T1-T2, 71.7%) and low grade (G1-G2, 72.4%). There were nodal and distant metastases in 5.7% and 13% of the patients. In all, 525 (14.4%) patients died from cancer; in this group, tumours were >4 cm in 88.2% and had nodal or distant metastases in 20.2% and 49.3%, respectively. Multivariable analysis showed that tumour size >4 cm, ECOG PS ≥1, TNM stage and Fuhrman grade were independent predictors of cancer-related death. CONCLUSION A significant proportion of incidental renal tumours can lead to the death of the patient. Standard prognostic variables for renal cell carcinoma appear to remain valid for this subset of patients. A watchful-waiting strategy should not be recommended if the tumour diameter is >4 cm, if biopsy confirms high-grade tumours, or if there is an impaired ECOG PS, or computed tomography findings suggest the presence of advanced T stage. [ABSTRACT FROM AUTHOR]
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- 2008
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12. Cancer-specific Survival Outcomes Among Patients Treated During the Cytokine Era of Kidney Cancer (1989-2005): A Benchmark for Emerging Targeted Cancer Therapies.
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Belldegrun, Arie S., Kiatte, Tobias, Shuch, Brian, LaRochelle, Jeffrey C., Miller, David C., Said, Jonathan W., Riggs, Stephen B., Zomorodian, Nazy, Kabbinavar, Fairooz F., deKernion, Jean B., and Pantuck, Allan J.
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RENAL cell carcinoma ,IMMUNOTHERAPY ,RENAL cancer ,CYTOKINES ,ADJUVANT treatment of cancer ,SURGICAL excision ,PATIENTS - Abstract
The article discusses a study which investigates the cancer-specific survival outcomes among patients with renal cell carcinoma (RCC) who were treated during the cytokine era from 1989-2005. It reveals that most patients with localized RCC have improved with surgery alone, however, effective adjuvant therapy is required for patients who were at high risk for recurrence. Moreover, less toxic treatments should be at least effective like surgical resection and immunotherapy for advanced disease.
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- 2008
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13. Brain Metastasis From Renal Cell Carcinoma: Presentation, Recurrence, and Survival.
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Shuch, Brian, La Rochelle, Jeff C., Klatte, Tobias, Riggs, Stephen B., Weiqing Liu, Kabbinavar, Fairooz F., Pantuck, Allan J., and Belidegrun, Arie S.
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RENAL cell carcinoma ,CANCER patients ,METASTASIS ,CENTRAL nervous system ,DISEASE relapse - Abstract
The article presents a study that aims to assist in the creation of management guidelines on central nervous system (CNS) surveillance or treatment of patients with renal cell carcinoma brain metastases (RCCBM). It was found that patients with metastatic RCC should be examined with CNS screening to identify smaller and asymptomatic lesions, which maybe amenable to less invasive treatment. Findings show that patients with a solitary BM are less likely to develop CNS recurrence.
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- 2008
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14. Performance Status and Cytoreductive Nephrectomy: Redefining Management in Patients With Poor Performance.
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Shuch, Brian, La Rochelle, Jeff C., Wu, Jon, Kiatte, Tobias, Riggs, Stephen B., Kabbinavar, Fairooz, Belldegrun, Arie S., and Pantuck, Allan J.
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RENAL cancer ,KIDNEY surgery ,CANCER patients ,BONE metastasis ,ONCOLOGY ,STATISTICAL correlation - Abstract
The article focuses on the study of Eastern Cooperative Oncology Group (ECOG) on the effect of cytoreductive nephrectomy (CN) on the performance status (PS) or well-being of patients with kidney cancer. It notes that the outcome of the review of the demography and medical accounts of 418 patients who had CN from 1989 to 2006 were correlated to ECOG PS. Younger patients were noted to have higher tumor classification and generally shows anemia and bone metastases (BM).
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- 2008
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15. Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm.
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Shuch, Brian, Riggs, Stephen B., LaRochelle, Jeff C., Kabbinavar, Fairooz F., Avakian, Raffi, Pantuck, Allan J., Patard, Jean-Jacques, and Belldegrun, Arie S.
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RENAL cell carcinoma ,TUMORS ,THERAPEUTICS ,CANCER treatment ,CANCER patients - Abstract
OBJECTIVE To evaluate our early experience with neoadjuvant therapy (sunitinib or sorafenib) in advanced renal cell carcinoma (RCC), to explore the effect on both tumour biology and potential for downstaging advanced tumours, as systemic therapy for RCC has historically resulted in little if any primary tumour response, but recent experience with targeted therapy suggests otherwise. PATIENTS AND METHODS The preliminary experience with neoadjuvant therapy for the surgical management of RCC was reviewed at two large referral centres. Several unique patients were identified who had a novel response to systemic therapy that altered the surgical strategy. RESULTS Four patients who had targeted therapy before surgery are described and in whom there were effects on tumour biology not seen previously with chemotherapy and cytokine therapy. The selected patients who had neoadjuvant targeted therapy had shrinkage of a tumour thrombus in the inferior vena cava, nodal involvement, renal fossa recurrence and tumour within a solitary kidney. CONCLUSIONS The introduction of new molecular agents has revolutionized the treatment of patients with metastatic RCC. Responses to targeted therapy within the primary tumour, tumour thrombus, renal fossa recurrence, and lymph node metastases are novel findings not seen during treatment with immunotherapeutic-based strategies. This might be a signal for urological surgeons to re-evaluate the paradigm for the surgical management of advanced RCC. Potential applications are presented to encourage further investigations with targeted therapy in the neoadjuvant setting. [ABSTRACT FROM AUTHOR]
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- 2008
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16. Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma.
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Patard, Jean-Jacques, Fergelot, Patricia, Karakiewicz, Pierre I., Klatte, Tobias, Trinh, Quoc-Dien, Rioux-Leclercq, Nathalie, Said, Jonathan W., Belldegrun, Arie S., and Pantuck, Allan J.
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- 2008
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17. The role of carbonic anhydrase IX as a molecular marker for transitional cell carcinoma of the bladder.
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Klatte, Tobias, Belldegrun, Arie S., and Pantuck, Allan J.
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CARBONIC anhydrase ,ZINC enzymes ,CANCER - Abstract
The article features the research conducted by Tobias Klatte and colleagues on the significance of carbonic anhydrase IX as a molecular marker in Los Angeles, California. Result shows carbonic anhydrase IX (CAIX) is a bladder cancer-specific antigen that is not expressed in normal urothelial tissue but is expressed in 70-90% of transitional cell carcinoma (TCC). It reveals that the expression is usually heterogeneous with a maximum staining seen on the luminal surfaces of the papillae.
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- 2008
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18. Cytoreductive Nephron-Sparing Surgery Does Not Appear to Undermine Disease-Specific Survival in Patients With Metastatic Renal Cell Carcinoma.
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Hutterer, Georg C., Patard, Jean-Jacques, Colombel, Marc, Belldegrun, Arie S., Pfister, Christian, Guille, Francois, Artibani, Walter, Montorsi, Francesco, Pantuck, Allan J., and Karakiewicz, Pierre I.
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CANCER patients ,RENAL cell carcinoma ,KIDNEY surgery ,METASTASIS ,RENAL cancer - Abstract
The article focuses on a study which investigated the role of nephron sparing surgery (NSS) in the survival of patients with metastatic renal cell carcinoma (RCC). The study compared NSS and radical nephrectomy (RN) in both unmatched and matched trials. It concluded that survival of patients with RCC will not be influenced by NSS administration.
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- 2007
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19. Unclassified renal cell carcinoma: an analysis of 85 cases.
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Karakiewicz, Pierre I., Hutterer, Georg C., Trinh, Quoc-Dien, Pantuck, Allan J., Klatte, Tobias, Lam, John S., Guille, Francois, de La Taille, Alexandre, Novara, Giacomo, Tostain, Jacques, Cindolo, Luca, Ficarra, Vincenzo, Schips, Luigi, Zigeuner, Richard, Mulders, Peter F., Chautard, Denis, Lechevallier, Eric, Valeri, Antoine, Descotes, Jean-Luc, and Lang, Herve
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RENAL cell carcinoma ,KIDNEY surgery ,CANCER patients ,TUMORS ,MORTALITY ,CANCER invasiveness ,MULTIVARIATE analysis - Abstract
OBJECTIVES To compare cancer-specific mortality in patients with unclassified renal cell carcinoma (URCC) vs clear cell RCC (CRCC) after nephrectomy, as URCC is a rare but very aggressive histological subtype. PATIENTS AND METHODS Eighty-five patients with URCC and 4322 with CRCC were identified within 6530 patients treated with either radical or partial nephrectomy at 18 institutions. Of 85 patients with URCC, 55 were matched with 166 of 4322 for grade, tumour size, and Tumour, Node and Metastasis stages. Kaplan-Meier and life-table analyses were used to address RCC-specific survival. Subsequently, multivariate Cox regression analyses were used to test for differences in RCC-specific survival in unmatched samples. RESULTS Of patients with URCC, 80% had Fuhrman grades III or IV, vs 37.8% for CRCC. Moreover, 36.5% of patients with URCC had pathologically confirmed nodal metastases, vs 8.6% with CRCC. Finally, 54.1% of patients with URCC had distant metastases at the time of nephrectomy, vs 16.8% with CRCC. Despite these differences in the overall analyses, after matching for tumour characteristics, the URCC-specific mortality rate was 1.6 times higher ( P = 0.04) in matched analyses and 1.7 times higher ( P = 0.001) in multivariate analyses. CONCLUSIONS These findings indicate that URCC presents with a higher stage and grade, and even after controlling for the stage and grade differences, predisposes patients to 1.6–1.7 times the mortality of CRCC. [ABSTRACT FROM AUTHOR]
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- 2007
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20. Prognostic relevance of the mTOR pathway in renal cell carcinoma: implications for molecular patient selection for targeted therapy.
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Pantuck, Allan J., Seligson, David B., Klatte, Tobias, Hung Yu, Leppert, John T., Moore, Laurence, O'Toole, Timothy, Gibbons, Jay, Belldegrun, Arie S., Figlin, Robert A., and Yu, Hong
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MEDICAL research , *RAPAMYCIN , *IMMUNOSUPPRESSIVE agents , *MACROLIDE antibiotics , *CANCER treatment , *RENAL cell carcinoma , *IMMUNOHISTOCHEMISTRY , *PROTEIN metabolism , *CELLULAR signal transduction , *COMPARATIVE studies , *IMMUNOENZYME technique , *KIDNEY tumors , *RESEARCH methodology , *MEDICAL cooperation , *PHOSPHATASES , *PHOSPHORYLATION , *PHOSPHOTRANSFERASES , *PROGNOSIS , *PROTEIN kinases , *PROTEINS , *RESEARCH , *SURVIVAL , *TRANSFERASES , *TUMOR classification , *EVALUATION research , *PAPILLARY carcinoma , *TISSUE arrays , *SIGNAL peptides - Abstract
Background: The mammalian target of rapamycin (mTOR) pathway is up-regulated in many human cancers, and agents targeting the mTOR pathway are in various stages of clinical development. The goal of the study was to evaluate the potential and limitations of targeting the mTOR pathway in renal cell carcinoma (RCC).Methods: Immunohistochemical analysis using antibodies against pAkt, PTEN, p27, and pS6 was performed on a tissue microarray constructed from paraffin-embedded specimens from 375 patients treated by nephrectomy for RCC. The expression was associated with pathological parameters and survival.Results: The mTOR pathway was more significantly altered in clear-cell RCC, high-grade tumors, and tumors with poor prognostic features. PS6 and PTEN showed the strongest associations with pathological parameters. Survival tree analysis regarding expression of cytoplasmic pAkt, nuclear pAkt, PTEN, cytoplasmic p27, and pS6 identified staining percentages of 40%, 10%, 75%, 7%, and 70%, respectively, as ideal cutoff values for stratification, with corresponding P-values of .03, .001, .02, .005, and <.0001, respectively. Interestingly, high nuclear pAkt expression was associated with a favorable prognosis, whereas high cytoplasmic pAkt expression was associated with a poor prognosis. In multivariate Cox regression analysis, ECOG PS, T classification, N classification, M classification, cytoplasmic Akt, nuclear pAkt, PTEN, and pS6 were independent prognostic factors of DSS.Conclusions: Components of the mTOR pathway are significantly associated with pathological features and survival. Not all RCC tumor types seem to be equally amenable to mTOR targeted therapy. PTEN, pAkt, p27, and pS6 may serve as surrogate parameters for patient selection and predicting prognosis. Patients with a highly activated mTOR pathway should benefit most from this therapy. External validation of our results is recommended. [ABSTRACT FROM AUTHOR]- Published
- 2007
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21. The role of molecular markers in the staging of renal cell carcinoma.
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Leppert, John T., Pantuck, Allan J., Figlin, Robert A., and Belldegrun, Arie S.
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MEDICAL research , *RENAL cell carcinoma , *PROGNOSIS , *HUMAN molecular genetics , *GENE expression , *PROTEINS , *BIOMARKERS - Abstract
The article presents medical research into the role of human molecular gene/protein expression markers in the staging and prognosis of renal cell carcinoma (RCC). An example of a molecular marker is carbonic anhydrase IX (CAIX). Future directions in molecular staging include predicting the response to targeted treatments and predicting the response to immunotherapy.
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- 2007
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22. Prognostic relevance of capsular involvement and collecting system invasion in stage I and II renal cell carcinoma.
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Klatte, Tobias, Chung, JinSoo, Leppert, John T., Lam, John S., Pantuck, Allan J., Figlin, Robert A., and Belldegrun, Arie S.
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RENAL cell carcinoma ,RENAL cancer ,CANCER ,DATABASES ,CANCER patients - Abstract
OBJECTIVE To define the prognostic relevance of capsular involvement (invasion with no penetration) and collecting-system invasion in patients with stage I (pT1N0M0) and stage II (pT2N0M0) renal cell carcinoma (RCC), by evaluating the outcome of patients treated with nephrectomy. PATIENTS AND METHODS In all, 519 patients from a kidney cancer database treated with nephrectomy for stage I and II RCC between 1985 and 2005 were assessed retrospectively. The primary endpoint was recurrence-free survival time. The prognostic relevance of capsular involvement and collecting-system invasion were examined using univariate and multivariate survival analysis. RESULTS Capsular involvement and collecting-system invasion were evident in 112 (21.6%) and 39 (7.5%) patients, respectively. Capsular involvement was associated with higher Fuhrman grades and larger tumours. The incidence of collecting-system invasion was higher in patients with microvascular invasion. The median follow-up was 49 months. In univariate analysis, patients with capsular involvement and collecting-system invasion had a worse prognosis than patients without ( P = 0.007 and <0.001, respectively). In multivariate analysis, capsular involvement (hazard ratio 1.84, P = 0.036) and collecting-system invasion (3.78, P < 0.001) were independent prognostic factors of recurrence-free survival. Interestingly, there was no survival difference between patients with capsular involvement in stage I/II and patients with invasion of perinephric tissue (pT3aN0M0). CONCLUSIONS These findings suggest that capsular involvement and collecting-system invasion are poor prognostic findings in stage I and II RCC. They should both be considered when planning the follow-up. A revised pT3a stage including patients with capsular involvement could improve its prognostic validity. [ABSTRACT FROM AUTHOR]
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- 2007
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23. Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score.
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Lam, John S., Seligson, David B., Hong Yu, Ali Li, Eeva, Mervi, Pantuck, Allan J., Gang Zeng, Horvath, Steve, and Belldegrun, Arie S.
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ENDONUCLEASES ,GENE expression ,PROSTATE cancer ,DNA microarrays ,CANCER cells ,IMMUNOHISTOCHEMISTRY - Abstract
OBJECTIVE To investigate the expression and potential clinical usefulness of structure-specific flap endonuclease 1 (FEN-1) in human primary prostate cancer using tissue microarray technology, as FEN-1 was recently identified to be overexpressed in CL1.1, the most aggressive clone generated from the hormone-refractory prostate cancer cell line CL1. MATERIALS AND METHODS Immunohistochemistry was performed on tissue microarrays constructed from paraffin-embedded specimens of primary prostate cancer from 246 patients who had had a radical prostatectomy. Prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal prostate epithelium were represented on the array. FEN-1 nuclear expression was scored based on the percentage of target cells staining positively, and correlated with Gleason score, preoperative prostate-specific antigen (PSA) level and pathological stage. The time to PSA recurrence was also analysed. RESULTS The mean expression of FEN-1 was significantly higher in cancer (36.7%) than in normal (13.2%), BPH (4.5%) and PIN (15.4%) specimens ( P < 0.001). FEN-1 expression was significantly correlated with Gleason score (ó = 0.23, P = 0.002). A higher preoperative serum PSA level ( P = 0.015), Gleason score ≥ 7 ( P < 0.001), seminal vesicle invasion ( P < 0.001) and capsular involvement ( P = 0.004) were associated with PSA recurrence, whereas FEN-1 expression was not. In a multivariate analysis, only Gleason score ≥ 7 ( P < 0.001), seminal vesicle invasion ( P = 0.005) and capsular involvement ( P = 0.009) were retained as independent predictors for PSA recurrence. CONCLUSIONS FEN-1 is overexpressed in prostate cancer compared with matched normal prostate, and its expression increases with tumour dedifferentiation, as shown by increasing Gleason score. These results suggest that FEN-1 might be a potential marker for selecting patients at high risk, and a potential target for prostate cancer diagnosis and therapy. [ABSTRACT FROM AUTHOR]
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- 2006
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24. Carbonic anhydrase IX and the future of molecular markers in renal cell carcinoma.
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Leppert, John T., Lam, John S., Pantuck, Allan J., Figlin, Robert A., and Belldegrun, Arie S.
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CARBONIC anhydrase ,RENAL cell carcinoma ,VASCULAR endothelial growth factors ,CANCER patients ,RENAL cancer ,GROWTH factors - Abstract
The use of carbonic anhydrase IX as a promising molecular marker in RCC is described by authors from Los Angeles, who discuss the promise that molecular markers hold to improve diagnosis, staging, treatment surveillance and survival of patients with RCC. There is a whole range of new treatments being introduced in the management of metastatic renal cancer. The use of VEOF-targeted therapy has particular importance, especially as it has a strong genetically linked rationale for its potential success in this area. Authors from the USA show that substantial clinical activity has been reported in initial clinical trials. In prostate cancer, drugs targeting microtubules, such as taxanes, have already been introduced clinically, and their success has received widespread attention. A new group of drugs, the epothilones, have similar but not identical binding properties to microtubules, and authors from the USA describe how they have shown activity in hormone-refractory prostate cancer, and are moving to phase III testing. [ABSTRACT FROM AUTHOR]
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- 2005
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25. Dominant B cell epitope from NY-ESO-1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker.
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Zeng, Gang, Aldridge, Michael E., Wang, Yu, Pantuck, Allan J., Wang, Allen Y., Liu, Yue-xiang, Han, Yan, Yuan, Yan-hua, Robbins, Paul F., Dubinett, Steven M., deKernion, Jean B., and Belldegrun, Arie S.
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- 2005
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26. Gene and immune therapy for renal cell carcinoma.
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Pantuck, Allan J, Zisman, Amnon, and Belldegrun, Arie
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GENE therapy , *RENAL cell carcinoma , *CYTOKINES , *IMMUNOTHERAPY , *CANCER vaccines - Abstract
Abstract Conventional therapy for metastatic renal cell carcinoma is associated with a poor response rate and few patients are long-term survivors. The occurrence of spontaneous regression and the prolonged latency period between primary tumor removal and the appearance of metastases in some patients suggest the existence of important host immune responses to autologous tumor cells. With the advent of molecular gene transfer techniques and increased knowledge of the basic pathways of immune activation, the field of cancer immunotherapy has finally begun to develop novel and effective approaches for harnessing the immune system as a therapeutic agent. Current immunotherapy and gene therapy strategies, including methods of cytokine delivery and tumor-cell-based vaccines, are presented. [ABSTRACT FROM AUTHOR]
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- 2001
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27. Signet Ring Cell Carcinoma of the Prostate: Case Report and Review of the Literature.
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Han, Ken-ryu, Pantuck, Allan J., Lobby, Nancy J., and Marmar, Joel L.
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PROSTATE cancer , *MUCINS , *ANTIGENS , *ADENOCARCINOMA - Abstract
Presents a case report on signet ring cell carcinoma of the prostate. Medical accounts of an 82-year-old man diagnosed with prostate cancer; Defining caracteristic of signet ring cell carcinoma of the prostate; Diagnostic method used in signet ring cell carcinoma of the prostate; Symptoms of signet ring cell carcinoma of the prostate; Criteria for the diagnosis of mucinous carcinoma.
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- 1999
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