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Sabina Signoretti, MD


Researcher

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Researcher

  • Associate Pathologist
  • Professor of Pathology, Harvard Medical School

Contact Information

  • Office Phone Number617-525-7437

Bio

Dr. Signoretti received her MD from the University of Rome, Italy, where she trained in pathology. She completed a research fellowship in molecular pathology with Dr. Loda at Beth Israel Deaconess Medical Center. In 1999, she joined the faculty of DFCI and Brigham and Women's Hospital, where she is an Independent Investigator involved in both basic and translational research of genitourinary cancer. In addition, she serves as director of the DF/HCC Tissue Microarrays and Imaging (TMI) Core. She also directs the Tissue Acquisition, Pathology, and Clinical Data Core of the Dana-Farber/Harvard Cancer Center Renal Cancer SPORE/Program.

Research

Molecular mechanisms underlying the development Genitourinary Cancers

Research #1: Role of p63 in development and renewal of the prostate epithelium

Unraveling the mechanisms regulating the development and renewal of normal tissues is not only one of the main goals of developmental biology but also an essential step for the elucidation of the mechanisms underlying the development of pathological processes, namely cancer. Although epithelial stem cells have been identified in the skin and intestine, the way the prostate and epithelium are formed and maintained remains unclear. The basal cell marker p63 is selectively expressed in the basal cells of several epithelia, including the prostate. My research group has previously demonstrated that p63-deficient (p63-/-) mice present defects in prostate buds indicating that p63-positive cells are required for normal prostate development  (Signoretti et al., Am J Pathol 2000). We have more recently performed in vivo studies and found that ΔNp63-positive cells of the urogenital sinus generate all epithelial lineages of the prostate, indicating that these cells represent the stem/progenitor cells of this epithelium during development. We also observed ΔNp63 expression in caudal gut endoderm and the contribution of ΔNp63-positive cells to the stem/progenitor compartment of adult colorectal epithelium. Because p63 is a master regulator of stratified epithelial development, this finding provides a unique developmental insight into the cell of origin of squamous cell metaplasia and squamous cell carcinoma of the colon (Signoretti et al, Proc Natl Acad Sci U S A 2005; Pignon et al, Proc Natl Acad Sci U S A 2013). My current research aims at further defining stem cells and differentiation programs in the adult prostate epithelium. Specifically, we are performing genetic lineage tracing experiments to directly follow the fate of p63-positive cells in the adult prostate in vivo. The secondary goal of this endeavor is to identify molecular mechanisms mediating p63 function during both development and tumorogenesis. We have shown that prostate basal cells predominantly express the ΔNp63α isosform and that ΔNp63α is required for cell survival. Importantly, we have also demonstrated that Fatty Acid Synthase (FASN) is a functionally relevant target of p63 and is required for mediating its pro-survival effects (Sabbisetti, PLoS ONE, 2009). Our results establish a novel functional link between this p53 family member and lipid metabolism and suggest that maintenance of fatty acid synthesis is a key mechanism through which p63 acts as a pro-survival molecule in both development and cancer.

Research #2: Molecular Analysis Of Renal Cell Carcinoma

Clear cell renal cell carcinoma (cRCC) represents the most common and fatal form of renal cancer and accounts for 70-80% of cases. In patients with advanced disease, response rates to traditional chemotherapy and radiotherapy are, unfortunately, very low. The introduction of cytokine-based immunotherapy with interferon-α or interleukin-2 for patients with metastatic disease has shown survival improvements, but the treatment is often not well tolerated and only a limited subset of patients experience clinically meaningful benefit. Recently, tyrosine kinase inhibitors (TKIs) that target the VHL pathway have shown clear activity in metastatic cRCC and have received approval by the FDA. However, not all the patients treated with these targeted therapies experience a substantial clinical benefit and almost all of them eventually progress. Therefore, more effective treatments for cRCC are warranted. High-throughput genetic studies represent a unique opportunity to identify the tumor suppressor genes (TSGs) and oncogenes,  upon which genetic subtypes of cRCC depend. In collaboration with Drs. Kaelin and Beroukhim at DFCI and the Broad Institute, we have performed integrated analysis of SNP array data describing chromosomal aberrations with matched gene expression data to identify candidate genes targeted by these aberrations in cRCC (Beroukhim et al, Cancer Res, 2009). We continue to carry out this work as part of the NCI-sponsored TCGA effort. Results from these studies will shed light on the molecular mechanisms underlying kidney cancer development and might eventually lead to more effective targeted therapies for this disease.



Development of a histopathology informatics pipeline for classification and prediction of clinical outcome in subtypes of renal cell carcinoma. Clin Cancer Res. 2021 Mar 15.
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Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma. Cancer Cell. 2021 Mar 10.
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Progressive immune dysfunction with advancing disease stage in renal cell carcinoma. Cancer Cell. 2021 Mar 09.
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Summary From the First Kidney Cancer Research Summit, September 12-13, 2019: A Focus on Translational Research. J Natl Cancer Inst. 2021 Mar 01; 113(3):234-243.
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Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma. Nat Commun. 2021 02 05; 12(1):808.
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ACE2 abrogates tumor resistance to VEGFR inhibitors suggesting angiotensin-(1-7) as a therapy for clear cell renal cell carcinoma. Sci Transl Med. 2021 Jan 20; 13(577).
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KIR3DL3 Is an Inhibitory Receptor for HHLA2 that Mediates an Alternative Immunoinhibitory Pathway to PD1. Cancer Immunol Res. 2021 Feb; 9(2):156-169.
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Expression of T-Cell Exhaustion Molecules and Human Endogenous Retroviruses as Predictive Biomarkers for Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma. Clin Cancer Res. 2021 Mar 01; 27(5):1371-1380.
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Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma. J Immunother Cancer. 2020 11; 8(2).
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Author Correction: A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Nat Genet. 2020 Oct; 52(10):1132.
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Efficacy and Safety of Nivolumab Plus Ipilimumab versus Sunitinib in First-line Treatment of Patients with Advanced Sarcomatoid Renal Cell Carcinoma. Clin Cancer Res. 2021 Jan 01; 27(1):78-86.
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Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma: The SAVOIR Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 08 01; 6(8):1247-1255.
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Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma. Nat Med. 2020 06; 26(6):909-918.
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Mammalian SWI/SNF Complex Genomic Alterations and Immune Checkpoint Blockade in Solid Tumors. Cancer Immunol Res. 2020 08; 8(8):1075-1084.
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A model combining clinical and genomic factors to predict response to PD-1/PD-L1 blockade in advanced urothelial carcinoma. Br J Cancer. 2020 02; 122(4):555-563.
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The KDM5A/RBP2 histone demethylase represses NOTCH signaling to sustain neuroendocrine differentiation and promote small cell lung cancer tumorigenesis. Genes Dev. 2019 12 01; 33(23-24):1718-1738.
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Results of a Multicenter Phase II Study of Atezolizumab and Bevacizumab for Patients With Metastatic Renal Cell Carcinoma With Variant Histology and/or Sarcomatoid Features. J Clin Oncol. 2020 01 01; 38(1):63-70.
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Mutations and Response to Rapalogs in Patients with Metastatic Renal Cell Carcinoma. Mol Cancer Ther. 2020 02; 19(2):690-696.
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HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species. Sci Signal. 2019 10 01; 12(601).
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Metabolomic adaptations and correlates of survival to immune checkpoint blockade. Nat Commun. 2019 09 25; 10(1):4346.
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PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: Analysis of the Randomized Clinical Trials METEOR and CABOSUN. Clin Cancer Res. 2019 10 15; 25(20):6080-6088.
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Editor's Note: The Efficacy of the Novel Dual PI3-Kinase/mTOR Inhibitor NVP-BEZ235 Compared with Rapamycin in Renal Cell Carcinoma. Clin Cancer Res. 2019 Jul 01; 25(13):4194.
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Corrigendum: Loss of LDAH associated with prostate cancer and hearing loss. Hum Mol Genet. 2019 05 15; 28(10):1753-1754.
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The future of perioperative therapy in advanced renal cell carcinoma: how can we PROSPER? Future Oncol. 2019 May; 15(15):1683-1695.
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A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis. Nat Commun. 2019 04 08; 10(1):1617.
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Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate. Science. 2019 03 15; 363(6432):1217-1222.
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irRECIST for the Evaluation of Candidate Biomarkers of Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma: Analysis of a Phase II Prospective Clinical Trial. Clin Cancer Res. 2019 04 01; 25(7):2174-2184.
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Loss of LDAH associated with prostate cancer and hearing loss. Hum Mol Genet. 2018 12 15; 27(24):4194-4203.
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Cells Lacking the RB1 Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival. Cancer Discov. 2019 02; 9(2):230-247.
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Renal Cell Carcinoma in the Era of Precision Medicine: From Molecular Pathology to Tissue-Based Biomarkers. J Clin Oncol. 2018 Oct 29; JCO2018792259.
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Mechanisms of acquired resistance to rapalogs in metastatic renal cell carcinoma. PLoS Genet. 2018 09; 14(9):e1007679.
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Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. Nat Genet. 2018 09; 50(9):1271-1281.
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The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. Cell Rep. 2018 Jun 19; 23(12):3698.
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The Clinical Activity of PD-1/PD-L1 Inhibitors in Metastatic Non-Clear Cell Renal Cell Carcinoma. Cancer Immunol Res. 2018 07; 6(7):758-765.
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Comprehensive Genomic Profiling of Metastatic Tumors in a Phase 2 Biomarker Study of Everolimus in Advanced Renal Cell Carcinoma. Clin Genitourin Cancer. 2018 10; 16(5):341-348.
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Targeted genomic landscape of metastases compared to primary tumours in clear cell metastatic renal cell carcinoma. Br J Cancer. 2018 05; 118(9):1238-1242.
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The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. Cell Rep. 2018 04 03; 23(1):313-326.e5.
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Autochthonous tumors driven by Rb1 loss have an ongoing requirement for the RBP2 histone demethylase. Proc Natl Acad Sci U S A. 2018 04 17; 115(16):E3741-E3748.
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A Non-integrating Lentiviral Approach Overcomes Cas9-Induced Immune Rejection to Establish an Immunocompetent Metastatic Renal Cancer Model. Mol Ther Methods Clin Dev. 2018 Jun 15; 9:203-210.
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An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer. Nat Genet. 2018 02; 50(2):206-218.
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Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms. Nat Med. 2018 02; 24(2):165-175.
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Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018 Feb 16; 359(6377):801-806.
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Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression. Oncotarget. 2017 Nov 28; 8(61):103428-103436.
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In Reply. Oncologist. 2017 12; 22(12):1561.
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Transforming the Perioperative Treatment Paradigm in Non-Metastatic RCC-A Possible Path Forward. Kidney Cancer. 2017 Jul 26; 1(1):31-40.
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HIF activation causes synthetic lethality between the VHL tumor suppressor and the EZH1 histone methyltransferase. Sci Transl Med. 2017 07 12; 9(398).
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Differential Expression of PD-L1 in High Grade T1 vs Muscle Invasive Bladder Carcinoma and its Prognostic Implications. J Urol. 2017 10; 198(4):817-823.
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p63+ ureteric bud tip cells are progenitors of intercalated cells. JCI Insight. 2017 May 04; 2(9).
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Evolution of Circulating Tumor DNA Profile from First-line to Subsequent Therapy in Metastatic Renal Cell Carcinoma. Eur Urol. 2017 10; 72(4):557-564.
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Renal cell carcinoma. Nat Rev Dis Primers. 2017 Mar 09; 3:17009.
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Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity. Cancer Discov. 2017 07; 7(7):750-765.
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Molecular Subtypes Improve Prognostic Value of International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Model. Oncologist. 2017 03; 22(3):286-292.
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Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Michaelson MD, McKay RR, Werner L, Atkins MB, Van Allen EM, Olivier KM, Song J, Signoretti S, McDermott DF, Choueiri TK.Cancer. 2015 Oct 1;121(19):3435-43. [Epub 2015 Jun 8]. doi: 10.1002/cncr.29503. Urol Oncol. 2017 03; 35(3):117-118.
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Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer. J Clin Invest. 2016 11 01; 126(11):4387.
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Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations. J Clin Oncol. 2016 Oct 20; 34(30):3655-3663.
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FCGR Polymorphisms Influence Response to IL2 in Metastatic Renal Cell Carcinoma. Clin Cancer Res. 2017 May 01; 23(9):2159-2168.
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Killer immunoglobulin-like receptor (KIR) and KIR-ligand genotype do not correlate with clinical outcome of renal cell carcinoma patients receiving high-dose IL2. Cancer Immunol Immunother. 2016 12; 65(12):1523-1532.
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On-target efficacy of a HIF-2a antagonist in preclinical kidney cancer models. Nature. 2016 11 03; 539(7627):107-111.
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pVHL suppresses kinase activity of Akt in a proline-hydroxylation-dependent manner. Science. 2016 08 26; 353(6302):929-32.
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Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol. 2016 08 22; 17(1):174.
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Whole Exome Sequencing Identifies TSC1/TSC2 Biallelic Loss as the Primary and Sufficient Driver Event for Renal Angiomyolipoma Development. PLoS Genet. 2016 08; 12(8):e1006242.
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Inhibition of ALK1 signaling with dalantercept combined with VEGFR TKI leads to tumor stasis in renal cell carcinoma. Oncotarget. 2016 Jul 05; 7(27):41857-41869.
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Whole-Exome Sequencing in Two Extreme Phenotypes of Response to VEGF-Targeted Therapies in Patients With Metastatic Clear Cell Renal Cell Carcinoma. J Natl Compr Canc Netw. 2016 07; 14(7):820-4.
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Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine. Cell. 2016 Jun 30; 166(1):126-39.
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Correlation of Apobec Mrna Expression with overall Survival and pd-l1 Expression in Urothelial Carcinoma. Sci Rep. 2016 06 10; 6:27702.
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Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model. Oncotarget. 2016 Jun 07; 7(23):34341-55.
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Landscape of tumor-infiltrating T cell repertoire of human cancers. Nat Genet. 2016 07; 48(7):725-32.
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Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation. Oncotarget. 2016 May 24; 7(21):29901-15.
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A phase 1 study of buparlisib and bevacizumab in patients with metastatic renal cell carcinoma progressing on vascular endothelial growth factor-targeted therapies. Cancer. 2016 Aug 01; 122(15):2389-98.
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Pharmacogenomic Markers of Targeted Therapy Toxicity in Patients with Metastatic Renal Cell Carcinoma. Eur Urol Focus. 2016 Dec 15; 2(6):633-639.
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Intratumor Heterogeneity of Perfusion and Diffusion in Clear-Cell Renal Cell Carcinoma: Correlation With Tumor Cellularity. Clin Genitourin Cancer. 2016 12; 14(6):e585-e594.
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Phase 2 Study of Bevacizumab and Temsirolimus After VEGFR TKI in Metastatic Renal Cell Carcinoma. Clin Genitourin Cancer. 2016 08; 14(4):304-313.e6.
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Mutations in TSC1, TSC2, and MTOR Are Associated with Response to Rapalogs in Patients with Metastatic Renal Cell Carcinoma. Clin Cancer Res. 2016 05 15; 22(10):2445-2452.
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Corrigendum: Essential roles of PI(3)K-p110ß in cell growth, metabolism and tumorigenesis. Nature. 2016 05 12; 533(7602):278.
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Young investigator challenge: Application of cytologic techniques to circulating tumor cell specimens: Detecting activation of the oncogenic transcription factor STAT3. Cancer Cytopathol. 2015 Dec; 123(12):696-706.
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Adult Renal Cell Carcinoma: A Review of Established Entities from Morphology to Molecular Genetics. Surg Pathol Clin. 2015 Dec; 8(4):587-621.
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PD-L1 Antibodies to Its Cytoplasmic Domain Most Clearly Delineate Cell Membranes in Immunohistochemical Staining of Tumor Cells. Cancer Immunol Res. 2015 Dec; 3(12):1308-15.
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Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma. N Engl J Med. 2016 Jan 14; 374(2):135-45.
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Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discov. 2015 Nov; 5(11):1164-1177.
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Tumor Vascularity in Renal Masses: Correlation of Arterial Spin-Labeled and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Assessments. Clin Genitourin Cancer. 2016 Feb; 14(1):e25-36.
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Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo. Mol Cancer. 2015 Jun 11; 14:119.
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Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Cancer. 2015 Oct 01; 121(19):3435-43.
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Cell kinetic studies fail to identify sequentially proliferating progenitors as the major source of epithelial renewal in the adult murine prostate. PLoS One. 2015; 10(5):e0128489.
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Differential Expression of PD-L1 between Primary and Metastatic Sites in Clear-Cell Renal Cell Carcinoma. Cancer Immunol Res. 2015 Oct; 3(10):1158-64.
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Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory biomarker study. J Immunother Cancer. 2015; 3:3.
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Suppression of CHK1 by ETS Family Members Promotes DNA Damage Response Bypass and Tumorigenesis. Cancer Discov. 2015 May; 5(5):550-63.
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Immunohistochemical staining for BRAF V600E supports the diagnosis of metanephric adenoma. Histopathology. 2015 May; 66(6):901-4.
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Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann Oncol. 2015 Apr; 26(4):812-817.
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Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer. Clin Cancer Res. 2015 Apr 15; 21(8):1925-1934.
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Correlation of PD-L1 tumor expression and treatment outcomes in patients with renal cell carcinoma receiving sunitinib or pazopanib: results from COMPARZ, a randomized controlled trial. Clin Cancer Res. 2015 Mar 01; 21(5):1071-7.
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Genomic investigation of etiologic heterogeneity: methodologic challenges. BMC Med Res Methodol. 2014 Dec 22; 14:138.
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?Np63 (p40) expression in prostatic adenocarcinoma with diffuse p63 positivity. Hum Pathol. 2015 Mar; 46(3):384-9.
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The high-dose aldesleukin "select" trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2015 Feb 01; 21(3):561-8.
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PD-L1 expression in nonclear-cell renal cell carcinoma. Ann Oncol. 2014 Nov; 25(11):2178-2184.
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RNA-seq reveals aurora kinase-driven mTOR pathway activation in patients with sarcomatoid metastatic renal cell carcinoma. Mol Cancer Res. 2015 Jan; 13(1):130-7.
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A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol Med. 2014; 6(10):1357.
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Phosphorylation of ETS1 by Src family kinases prevents its recognition by the COP1 tumor suppressor. Cancer Cell. 2014 Aug 11; 26(2):222-34.
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Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov. 2014 Oct; 4(10):1140-53.
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Identification of ALK gene alterations in urothelial carcinoma. PLoS One. 2014; 9(8):e103325.
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D-cyclins repress apoptosis in hematopoietic cells by controlling death receptor Fas and its ligand FasL. Dev Cell. 2014 Aug 11; 30(3):255-67.
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Vulnerabilities of PTEN-TP53-deficient prostate cancers to compound PARP-PI3K inhibition. Cancer Discov. 2014 Aug; 4(8):896-904.
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Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. J Clin Oncol. 2014 Jun 20; 32(18):1889-94.
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MET as a target in papillary renal cell carcinoma. Clin Cancer Res. 2014 Jul 01; 20(13):3361-3.
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Targeting lactate dehydrogenase--a inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells. Cell Metab. 2014 May 06; 19(5):795-809.
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Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib. Cancer Discov. 2014 May; 4(5):546-53.
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Poor prognosis and advanced clinicopathological features of clear cell renal cell carcinoma (ccRCC) are associated with cytoplasmic subcellular localisation of Hypoxia inducible factor-2a. Eur J Cancer. 2014 May; 50(8):1531-40.
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A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol Med. 2014 04; 6(4):519-38.
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Integrative analysis of 1q23.3 copy-number gain in metastatic urothelial carcinoma. Clin Cancer Res. 2014 Apr 01; 20(7):1873-83.
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GRK3 is essential for metastatic cells and promotes prostate tumor progression. Proc Natl Acad Sci U S A. 2014 Jan 28; 111(4):1521-6.
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SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer. Cancer Cell. 2013 Dec 09; 24(6):738-50.
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Depletion of a putatively druggable class of phosphatidylinositol kinases inhibits growth of p53-null tumors. Cell. 2013 Nov 07; 155(4):844-57.
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The role of aberrant VHL/HIF pathway elements in predicting clinical outcome to pazopanib therapy in patients with metastatic clear-cell renal cell carcinoma. Clin Cancer Res. 2013 Sep 15; 19(18):5218-26.
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Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013 Jul 04; 499(7456):43-9.
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Zbtb7a suppresses prostate cancer through repression of a Sox9-dependent pathway for cellular senescence bypass and tumor invasion. Nat Genet. 2013 Jul; 45(7):739-746.
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A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Nat Genet. 2013 Jul; 45(7):747-55.
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p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia. Proc Natl Acad Sci U S A. 2013 May 14; 110(20):8105-10.
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Animal models of human prostate cancer: the consensus report of the New York meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee. Cancer Res. 2013 May 01; 73(9):2718-36.
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Investigating the association of cytoplasmic and nuclear HIF-2 expression with cancer specific survival (CSS) in clear cell renal cell carcinoma. J Clin Oncol. 2013 Feb 20; 31(6_suppl):387.
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A phase II multicenter study of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) chemotherapy with pegfilgrastim support in patients (pts) muscle-invasive urothelial cancer (MIUC): Safety, pathologic, radiologic, and molecular correlates. J Clin Oncol. 2013 Feb 20; 31(6_suppl):278.
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Relationship of ERCC1 genotype variant with mRNA expression and ERCC1 protein levels in advanced urothelial carcinoma (UC). J Clin Oncol. 2013 Feb 20; 31(6_suppl):260.
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Inhibition of tumor growth in a VEGFR TKI-resistant model of renal cell carcinoma using dalantercept combined with sunitinib. J Clin Oncol. 2013 Feb 20; 31(6_suppl):370.
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Identification of CDCP1 as a hypoxia-inducible factor 2a (HIF-2a) target gene that is associated with survival in clear cell renal cell carcinoma patients. Proc Natl Acad Sci U S A. 2013 Feb 26; 110(9):3483-8.
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Renal-cell carcinoma: a step closer to a new classification. Lancet Oncol. 2013 Feb; 14(2):105-7.
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Cox-2 inhibition enhances the activity of sunitinib in human renal cell carcinoma xenografts. Br J Cancer. 2013 Feb 05; 108(2):319-26.
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Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention. Cancer Discov. 2013 Jan; 3(1):44-51.
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Single nucleotide polymorphisms and risk of recurrence of renal-cell carcinoma: a cohort study. Lancet Oncol. 2013 Jan; 14(1):81-7.
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Carbonic anhydrase IX as a potential biomarker of efficacy in metastatic clear-cell renal cell carcinoma patients receiving sorafenib or placebo: analysis from the treatment approaches in renal cancer global evaluation trial (TARGET). Urol Oncol. 2013 Nov; 31(8):1788-93.
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The requirement for cyclin D function in tumor maintenance. Cancer Cell. 2012 Oct 16; 22(4):438-51.
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Identification of luminal breast cancers that establish a tumor-supportive macroenvironment defined by proangiogenic platelets and bone marrow-derived cells. Cancer Discov. 2012 Dec; 2(12):1150-65.
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BRAF mutations in metanephric adenoma of the kidney. Eur Urol. 2012 Nov; 62(5):917-22.
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The glomuvenous malformation protein Glomulin binds Rbx1 and regulates cullin RING ligase-mediated turnover of Fbw7. Mol Cell. 2012 Apr 13; 46(1):67-78.
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Assessment of a cell-line-derived HIF1a gene signature in tumor tissue from a metastatic renal cell carcinoma (RCC) trial of pazopanib. J Clin Oncol. 2012 Feb 10; 30(5_suppl):408.
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Association of DNA repair factors with overall survival in advanced urothelial carcinoma treated with platinum-based chemotherapy. J Clin Oncol. 2012 Feb 10; 30(5_suppl):291.
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Carbonic anhydrase IX (CAIX) as a potential biomarker of efficacy in metastatic clear-cell renal cell carcinoma (mccRCC) in patients (pts) receiving sorafenib: Analysis of a randomized controlled trial (TARGET). J Clin Oncol. 2012 Feb 10; 30(5_suppl):352.
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High dose intermittent sorafenib shows improved efficacy over conventional continuous dose in renal cell carcinoma. J Transl Med. 2011 Dec 21; 9:220.
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Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion. Nat Genet. 2011 Sep 04; 43(10):964-968.
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Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. Proc Natl Acad Sci U S A. 2011 Aug 16; 108(33):13379-86.
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Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumours in patients. J Pathol. 2011 Oct; 225(2):212-21.
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Genetic and functional studies implicate HIF1a as a 14q kidney cancer suppressor gene. Cancer Discov. 2011 Aug; 1(3):222-35.
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Do genetic polymorphisms predict risk of recurrence in patients with localized renal cell carcinoma? Results from a cohort study. J Clin Oncol. 2011 May 20; 29(15_suppl):4506.
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Identification of a novel urothelial carcinoma (UC) biomarker of lethality. J Clin Oncol. 2011 May 20; 29(15_suppl):4569.
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Identification of ALK gene alterations in urothelial carcinoma (UC). J Clin Oncol. 2011 May 20; 29(15_suppl):4568.
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Resistance of renal cell carcinoma to sorafenib is mediated by potentially reversible gene expression. PLoS One. 2011 Apr 29; 6(4):e19144.
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Transgenic expression of polyomavirus middle T antigen in the mouse prostate gives rise to carcinoma. J Virol. 2011 Jun; 85(11):5581-92.
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RET protein expression in papillary renal cell carcinoma. Urol Oncol. 2012 Nov-Dec; 30(6):900-5.
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Pml represses tumour progression through inhibition of mTOR. EMBO Mol Med. 2011 May; 3(5):249-57.
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SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression. Nature. 2011 Feb 10; 470(7333):269-73.
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Radiofrequency ablation combined with liposomal quercetin to increase tumour destruction by modulation of heat shock protein production in a small animal model. Int J Hyperthermia. 2011; 27(6):527-38.
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Carbonic anhydrase IX expression in renal neoplasms: correlation with tumor type and grade. Am J Clin Pathol. 2010 Dec; 134(6):873-9.
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FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis. Cancer Cell. 2010 Nov 16; 18(5):472-84.
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Do liposomal apoptotic enhancers increase tumor coagulation and end-point survival in percutaneous radiofrequency ablation of tumors in a rat tumor model? Radiology. 2010 Dec; 257(3):685-96.
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Loss of hypoxia-inducible factor prolyl hydroxylase activity in cardiomyocytes phenocopies ischemic cardiomyopathy. Circulation. 2010 Sep 07; 122(10):1004-16.
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Renal cancer resistance to antiangiogenic therapy is delayed by restoration of angiostatic signaling. . 2010 Oct; 9(10):2793-802.
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The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma. Clin Cancer Res. 2010 Jul 15; 16(14):3628-38.
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A constitutively activated form of the p110beta isoform of PI3-kinase induces prostatic intraepithelial neoplasia in mice. Proc Natl Acad Sci U S A. 2010 Jun 15; 107(24):11002-7.
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Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy. BJU Int. 2010 Sep; 106(6):772-8.
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The landscape of somatic copy-number alteration across human cancers. Nature. 2010 Feb 18; 463(7283):899-905.
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Liposomal doxorubicin increases radiofrequency ablation-induced tumor destruction by increasing cellular oxidative and nitrative stress and accelerating apoptotic pathways. Radiology. 2010 Apr; 255(1):62-74.
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Risk of bilateral renal cell cancer. J Clin Oncol. 2009 Aug 10; 27(23):3737-41.
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p63 promotes cell survival through fatty acid synthase. PLoS One. 2009 Jun 11; 4(6):e5877.
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Reciprocal effects of STAT5 and STAT3 in breast cancer. Mol Cancer Res. 2009 Jun; 7(6):966-76.
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Patterns of gene expression and copy-number alterations in von-hippel lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer Res. 2009 Jun 01; 69(11):4674-81.
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Does arterial spin-labeling MR imaging-measured tumor perfusion correlate with renal cell cancer response to antiangiogenic therapy in a mouse model? Radiology. 2009 Jun; 251(3):731-42.
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Prognostic and predictive values of carbonic anhydrase IX (CAIX) and pathologic features in patients with metastatic clear cell renal cell carcinoma receiving targeted therapy. J Clin Oncol. 2009 May 20; 27(15_suppl):e16067.
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Innovations and challenges in renal cancer: summary statement from the Third Cambridge Conference. Cancer. 2009 May 15; 115(10 Suppl):2247-51.
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Treatment selection for patients with metastatic renal cell carcinoma. Cancer. 2009 May 15; 115(10 Suppl):2327-33.
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Tissue biomarkers in renal cell carcinoma: issues and solutions. Cancer. 2009 May 15; 115(10 Suppl):2290-7.
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Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer. J Natl Cancer Inst. 2009 Apr 01; 101(7):519-32.
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LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer. . 2009 Mar; 8(3):626-35.
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A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression. Cancer Cell. 2008 Aug 12; 14(2):146-55.
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Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy. AJR Am J Roentgenol. 2008 Jul; 191(1):133-9.
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Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature. 2008 Aug 07; 454(7205):776-9.
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Tissue-based research in kidney cancer: current challenges and future directions. Clin Cancer Res. 2008 Jun 15; 14(12):3699-705.
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Carbonic anhydrase IX as a predictive biomarker of response to kidney cancer therapy. BJU Int. 2008 Jun; 101 Suppl 4:31-5.
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Carbonic anhydrase IX (CA IX) and pathologic features as predictors of outcome in patients (pts) with metastatic renal cell carcinoma (mRCC) receiving VEGF-targeted therapy. J Clin Oncol. 2008 May 20; 26(15_suppl):16042.
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Array-based comparative genomic hybridization (CGH) identifies chromosomal imbalances between Interleukin-2 complete and non-responders. J Clin Oncol. 2008 May 20; 26(15_suppl):5043.
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The association between overexpression of skp2 and the risk of recurrence following prostatectomy. J Clin Oncol. 2008 May 20; 26(15_suppl):11052.
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p63 in prostate biology and pathology. J Cell Biochem. 2008 Apr 01; 103(5):1354-68.
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VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol. 2008 Mar; 10(3):361-9.
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Potential histologic and molecular predictors of response to temsirolimus in patients with advanced renal cell carcinoma. Clin Genitourin Cancer. 2007 Sep; 5(6):379-85.
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Combination of radiofrequency ablation with antiangiogenic therapy for tumor ablation efficacy: study in mice. Radiology. 2007 Aug; 244(2):464-70.
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High-throughput oncogene mutation profiling in human cancer. Nat Genet. 2007 Mar; 39(3):347-51.
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The role of mammalian target of rapamycin inhibitors in the treatment of advanced renal cancer. Clin Cancer Res. 2007 Jan 15; 13(2 Pt 2):758s-763s.
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Cytokeratin15-positive basal epithelial cells targeted in graft-versus-host disease express a constitutive antiapoptotic phenotype. J Invest Dermatol. 2007 Jan; 127(1):106-15.
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A working group classification of focal prostate atrophy lesions. Am J Surg Pathol. 2006 Oct; 30(10):1281-91.
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Androgen-dependent regulation of Her-2/neu in prostate cancer cells. J Clin Oncol. 2006 Jun 20; 24(18_suppl):10099.
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Androgen-dependent regulation of Her-2/neu in prostate cancer cells. Cancer Res. 2006 Jun 01; 66(11):5723-8.
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Improved tumor destruction with arsenic trioxide and radiofrequency ablation in three animal models. Radiology. 2006 Jul; 240(1):82-9.
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Prostate stem cells: from development to cancer. Semin Cancer Biol. 2007 Jun; 17(3):219-24.
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Defining cell lineages in the prostate epithelium. . 2006 Jan; 5(2):138-41.
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Traumatic brain edema in diffuse and focal injury: cellular or vasogenic? Acta Neurochir Suppl. 2006; 96:24-9.
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p63 regulates commitment to the prostate cell lineage. Proc Natl Acad Sci U S A. 2005 Aug 09; 102(32):11355-60.
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Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide 3-kinase. Proc Natl Acad Sci U S A. 2005 Jul 19; 102(29):10238-43.
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Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res. 2005 May 15; 11(10):3714-21.
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Combination radiofrequency ablation with intratumoral liposomal doxorubicin: effect on drug accumulation and coagulation in multiple tissues and tumor types in animals. Radiology. 2005 May; 235(2):469-77.
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Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res. 2005 Apr 15; 65(8):3044-8.
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Reduced tumor growth with combined radiofrequency ablation and radiation therapy in a rat breast tumor model. Radiology. 2005 Apr; 235(1):81-8.
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Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells. Cancer Res. 2004 Dec 15; 64(24):8867-75.
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Hypoxia regulation of the cell cycle in malignant melanoma: putative role for the cyclin-dependent kinase inhibitor p27. J Cutan Pathol. 2004 Aug; 31(7):477-82.
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Carbonic Anhydrase IX (CAIX) expression predicts for renal cell cancer (RCC) patient response and survival to IL-2 therapy. J Clin Oncol. 2004 Jul 15; 22(14_suppl):4512.
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The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell. 2004 Mar; 5(3):253-61.
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Intermediate basal cells of the prostate: in vitro and in vivo characterization. Prostate. 2003 May 15; 55(3):206-18.
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Gene transcript quantitation by real-time RT-PCR in cells selected by immunohistochemistry-laser capture microdissection. Diagn Mol Pathol. 2002 Dec; 11(4):187-92.
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Diagnostic utility of immunohistochemical staining for p63, a sensitive marker of prostatic basal cells. Mod Pathol. 2002 Dec; 15(12):1302-8.
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Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature. 2002 Sep 12; 419(6903):162-7.
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Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer. J Clin Invest. 2002 Sep; 110(5):633-41.
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Stabilization of beta-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia. Oncogene. 2002 Jun 13; 21(26):4099-107.
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Growth factor requirements and basal phenotype of an immortalized mammary epithelial cell line. Cancer Res. 2002 Jan 01; 62(1):89-98.
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Obligate roles for p16(Ink4a) and p19(Arf)-p53 in the suppression of murine pancreatic neoplasia. Mol Cell Biol. 2002 Jan; 22(2):635-43.
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Application of chemical shift imaging for measurement of NAA in head injured patients. Acta Neurochir Suppl. 2002; 81:373-5.
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Estrogen receptor beta in prostate cancer: brake pedal or accelerator? Am J Pathol. 2001 Jul; 159(1):13-6.
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Androgen-driven prostate epithelial cell proliferation and differentiation in vivo involve the regulation of p27. Mol Endocrinol. 2001 May; 15(5):765-82.
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Transition from in situ to invasive testicular germ cell neoplasia is associated with the loss of p21 and gain of mdm-2 expression. Mod Pathol. 2001 May; 14(5):437-42.
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Primary effusion lymphoma in HIV-infected patients with multicentric Castleman's disease. J Pathol. 2001 Feb; 193(2):200-9.
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BCR/ABL regulates expression of the cyclin-dependent kinase inhibitor p27Kip1 through the phosphatidylinositol 3-Kinase/AKT pathway. J Biol Chem. 2000 Dec 15; 275(50):39223-30.
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Her-2-neu expression and progression toward androgen independence in human prostate cancer. J Natl Cancer Inst. 2000 Dec 06; 92(23):1918-25.
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Forkhead transcription factors are critical effectors of cell death and cell cycle arrest downstream of PTEN. Mol Cell Biol. 2000 Dec; 20(23):8969-82.
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p63 is a prostate basal cell marker and is required for prostate development. Am J Pathol. 2000 Dec; 157(6):1769-75.
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Role of the Cdc25A phosphatase in human breast cancer. J Clin Invest. 2000 Sep; 106(6):753-61.
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Detection of TCR-gamma gene rearrangements in early mycosis fungoides by non-radioactive PCR-SSCP. J Cutan Pathol. 2000 May; 27(5):228-34.
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Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues. Cancer Res. 2000 Apr 15; 60(8):2095-100.
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Distinguishing between cellular and vasogenic edema in head injured patients with focal lesions using magnetic resonance imaging. Acta Neurochir Suppl. 2000; 76:349-51.
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Clonality of cutaneous B-cell infiltrates determined by microdissection and immunoglobulin gene rearrangement. Diagn Mol Pathol. 1999 Dec; 8(4):176-82.
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Detection of concurrent/recurrent non-Hodgkin's lymphoma in effusions by PCR. Hum Pathol. 1999 Nov; 30(11):1361-6.
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The surgical treatment of pituitary adenomas in the eighth decade. Surg Neurol. 1999 Mar; 51(3):261-6; discussion 266-7.
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Melanocytic nevi of palms and soles: a histological study according to the plane of section. Am J Surg Pathol. 1999 Mar; 23(3):283-7.
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Detection of clonal T-cell receptor gamma gene rearrangements in paraffin-embedded tissue by polymerase chain reaction and nonradioactive single-strand conformational polymorphism analysis. Am J Pathol. 1999 Jan; 154(1):67-75.
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Loss or altered subcellular localization of p27 in Barrett's associated adenocarcinoma. Cancer Res. 1998 Apr 15; 58(8):1730-5.
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Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous B-cell lymphoma. Am J Surg Pathol. 1997 Nov; 21(11):1307-15.
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Neutrophilic figurate erythema of infancy. Am J Dermatopathol. 1997 Aug; 19(4):403-6.
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Papular clear cell hyperplasia of the eccrine duct in a diabetic. Br J Dermatol. 1996 Jul; 135(1):139-43.
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Safety and efficacy of in vivo gene transfer into the porcine heart with replication-deficient, recombinant adenovirus vectors. Gene Ther. 1996 Feb; 3(2):145-53.
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