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Daurkin I.,University of Florida | Eruslanov E.,University of Florida | Stoffs T.,University of Florida | Perrin G.Q.,University of Florida | And 6 more authors.
Cancer Research | Year: 2011

Renal cell carcinoma (RCC), the most common human kidney cancer, is frequently infiltrated with tumor-associated macrophages (TAM) that can promote malignant progression. Here, we show that TAMs isolated from human RCC produce substantial amounts of the proinflammatory chemokine CCL2 and immunosuppressive cytokine IL-10, in addition to enhanced eicosanoid production via an activated 15-lipoxygenase-2 (15-LOX2) pathway. TAMs isolated from RCC tumors had a high 15-LOX2 expression and secreted substantial amounts of 15(S)- hydroxyeicosatetraenoic acid, its major bioactive lipid product. Inhibition of lipoxygenase activity significantly reduced production of CCL2 and IL-10 by RCC TAMs. In addition, TAMs isolated from RCC were capable of inducing in T lymphocytes, the pivotal T regulatory cell transcription factor forkhead box P3 (FOXP3), and the inhibitory cytotoxic T-lymphocyte antigen 4 (CTLA-4) coreceptor. However, this TAM-mediated induction of FOXP3 and CTLA-4 in T cells was independent of lipoxygenase and could not be reversed by inhibiting lipoxygenase activity. Collectively, our results show that TAMs, often present in RCCs, display enhanced 15-LOX2 activity that contributes to RCC-related inflammation, immunosuppression, and malignant progression. Furthermore, we show that TAMs mediate the development of immune tolerance through both 15-LOX2-dependent and 15-LOX2-independent pathways. We propose that manipulating LOX-dependent arachidonic acid metabolism in the tumor microenvironment could offer new strategies to block cancer-related inflammation and immune escape in patients with RCC. ©2011 AACR.

Beilan J.A.,Urologic | Beilan J.A.,University of Central Florida | Lawton A.,Orlando Health Anderson Cancer Center Orlando | Hajdenberg J.,Anderson Cancer Center Orlando | And 2 more authors.
BMC Urology | Year: 2013

Background: Pheochromocytoma (paraganglioma) of the urinary bladder is a rare tumor. Herein we sought to review the contemporary literature on pheochromocytomas of the urinary bladder in order to further illustrate the presentation, treatment options and outcomes of patients diagnosed with these tumors. Methods. A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database and using the search terms "paraganglioma, pheochromocytoma, bladder." This search resulted in the identification of 186 articles published between January 1980 and April 2012 of which 80 articles were ultimately included in our analysis. Results: Pheochromocytomas usually occurred in young adult Caucasians (mean age, 43.3 years; range,11-84 years). According to the literature, the most common symptoms and signs of pheochromocytomas of the urinary bladder were hypertension, headache, and hematuria. Of the 77 cases that commented on catecholamine production, 65 patients had biochemically functional tumors. Approximately 20% of patients were treated by transurethral resection alone, 70% by partial cystectomy and 10% by radical cystectomy. The 75 patients with follow-up information had a mean follow-up of 35 months. At the time of last follow-up, 15 (14.2%) had disease recurrence, 10 (9.4%) had metastasis, and 65 (61.3%) were alive. Conclusions: Pheochromocytomas of the urinary bladder tend to be functional and occur mostly in young adult Caucasians. Patients with localized tumors have an extremely favorable prognosis and may be managed by less aggressive modalities, whereas patients with metastatic disease have a significant reduction in survival rates despite aggressive treatment. © 2013 Beilan et al.; licensee BioMed Central Ltd.

Bakhru A.,University of Michigan | Bakhru A.,Anderson Cancer Center Orlando
Journal of Gynecologic Oncology | Year: 2012

Objective: Deep venous thrombosis and pulmonary embolism are common in patients with epithelial ovarian cancer, resulting in high costs associated with diagnosis and treatment. I aimed to identify subtypes of epithelial ovarian cancer that pose greater and lesser venous thromboembolism (VTE) risk. Methods: I assessed the outcomes of 641 patients with epithelial ovarian, fallopian tube, and primary peritoneal cancer over a ten-year period. All inpatient, outpatient, and pathology records were reviewed. The rates at which people were evaluated for and diagnosed with venous thromboembolism were assessed. Results: Of the 641 cases, 30.0% underwent an imaging test to evaluate for deep venous thrombosis (DVT) and 21.7% underwent testing for pulmonary embolism (PE). A 10.8% of all subjects were diagnosed with DVT and 7.2% were diagnosed with PE. Borderline tumors and mucinous showed a strikingly low rate of both DVT and PE. Clear cell and high-grade undifferentiated adenocarcinomas were the most likely to result in VTE. In a multivariate model, pathologic subtype was not only a significant predictor of VTE, but was the single best predictor of VTE. Conclusion: Clear cell and undifferentiated pathology in epithelial ovarian carcinomas is associated with a higher VTE risk. The underlying reason for this may related to differences in tumor biology. By identifying low and high risk groups, I may both better conserve medical resources and design more effective thromboprophylaxis for my patients. © 2013. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

El-Khoueiry A.B.,University of Southern California | Rankin C.,Statistical Center | Siegel A.B.,Columbia University | Iqbal S.,University of Southern California | And 5 more authors.
British Journal of Cancer | Year: 2014

Background:Gallbladder cancers and cholangiocarcinomas make up a heterogenous group of tumours with a poor prognosis in advanced stages. On the basis of evidence of dysregulation of the epidermal growth factor receptor, vascular endothelial growth factor and mitogen-activated protein kinase pathways in biliary cancers, we performed a phase 2 trial of sorafenib and erlotinib in patients with advanced biliary cancers.Methods:Eligible patients were previously untreated in the advanced setting with adequate hepatic and bone marrow function. Sorafenib and erlotinib were administered continuously at 400 mg BID and 100 mg daily, respectively.Results:Thirty-four eligible patients were recruited. The study was terminated after the first stage of accrual owing to failure to meet the predetermined number of patients who were alive and progression free at 4 months. There were two unconfirmed partial responses (6%, 95% CI: 1-20%), with a median progression-free survival of 2 months (95% CI: 2-3), and median overall survival of 6 months (95% CI: 3-8 months). Grade 3 and 4 adverse events included hypertension, AST/ALT increase, bilirubin increase, diarrhoea, hypokalaemia, hypophosphatemia and rash.Conclusions:Despite compelling preclinical rationale, the combination of sorafenib and erlotinib does not have promising clinical activity in an unselected population of patients with biliary cancers. Improved patient selection based on tumour biology and molecular markers is critical for future evaluation of targeted therapies in this disease. © 2014 Cancer Research UK.

Huh W.W.,University of Houston | Holsinger F.C.,University of Houston | Levy A.,Anderson Cancer Center Orlando | Palla F.S.L.,University of Houston | Anderson P.M.,University of Houston
Head and Neck | Year: 2012

Background. Pediatric jaw osteosarcoma is uncommon, and data are scarce regarding clinical presentation, prognostic factors, and outcome. Methods. A single-institution medical record review from 1983 to 2008 for 12 patients age ≤21 years was undertaken for this study. Results. Median diagnosis age was 16.3 years (range, 6.3-21.9). Nine patients had mandible tumors. Osteoblastic subtype was most common (4 patients). Most tumors were large (ie, T2; n = 8) and high-grade (n = 8). Treatment characteristics were varied. Median follow-up was 27.1 months (range, 8-252 months). Five patients had tumor necrosis <80% after chemotherapy. No deaths were observed. Conclusion. Jaw osteosarcoma outcome is better compared to extremity osteosarcoma, but further study is required regarding clinical prognostic factors. © 2011 Wiley Periodicals, Inc.

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