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17 results on '"Ramnarine, Varune Rohan"'

1. Supplementary Figure 2 from NKX3.1 Haploinsufficiency Is Prognostic for Prostate Cancer Relapse following Surgery or Image-Guided Radiotherapy

Author

Locke, Jennifer A., primary, Zafarana, Gaetano, primary, Ishkanian, Adrian S., primary, Milosevic, Michael, primary, Thoms, John, primary, Have, Cherry L., primary, Malloff, Chad A., primary, Lam, Wan L., primary, Squire, Jeremy A., primary, Pintilie, Melania, primary, Sykes, Jenna, primary, Ramnarine, Varune Rohan, primary, Meng, Alice, primary, Ahmed, Omer, primary, Jurisica, Igor, primary, van der Kwast, Theo, primary, and Bristow, Robert G., primary

Published
2023
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2. Supplementary Figure Legends 1-2, Tables 1-6 from NKX3.1 Haploinsufficiency Is Prognostic for Prostate Cancer Relapse following Surgery or Image-Guided Radiotherapy

Author

Locke, Jennifer A., primary, Zafarana, Gaetano, primary, Ishkanian, Adrian S., primary, Milosevic, Michael, primary, Thoms, John, primary, Have, Cherry L., primary, Malloff, Chad A., primary, Lam, Wan L., primary, Squire, Jeremy A., primary, Pintilie, Melania, primary, Sykes, Jenna, primary, Ramnarine, Varune Rohan, primary, Meng, Alice, primary, Ahmed, Omer, primary, Jurisica, Igor, primary, van der Kwast, Theo, primary, and Bristow, Robert G., primary

Published
2023
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3. Supplementary Figure 1 from NKX3.1 Haploinsufficiency Is Prognostic for Prostate Cancer Relapse following Surgery or Image-Guided Radiotherapy

Author

Locke, Jennifer A., primary, Zafarana, Gaetano, primary, Ishkanian, Adrian S., primary, Milosevic, Michael, primary, Thoms, John, primary, Have, Cherry L., primary, Malloff, Chad A., primary, Lam, Wan L., primary, Squire, Jeremy A., primary, Pintilie, Melania, primary, Sykes, Jenna, primary, Ramnarine, Varune Rohan, primary, Meng, Alice, primary, Ahmed, Omer, primary, Jurisica, Igor, primary, van der Kwast, Theo, primary, and Bristow, Robert G., primary

Published
2023
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6. Protease nexin 1 inhibits Hedgehog signaling in prostate adenocarcinoma

Author

McKee, Chad M., Xu, Danmei, Cao, Yunhong, Kabraji, Sheheryar, Allen, Danny, Kersemans, Veerle, Beech, John, Smart, Sean, Hamdy, Freddie, Ishkanian, Adrian, Sykes, Jenna, Pintile, Melania, Milosevic, Michael, Kwast, Theodorus van der, Zafarana, Gaetano, Ramnarine, Varune Rohan, Jurisica, Igor, Mallof, Chad, Lam, Wan, Bristow, Robert G., and Muschel, Ruth J.

Subjects
Prostate cancer -- Diagnosis -- Care and treatment, Proteases -- Properties, Adenocarcinoma -- Diagnosis -- Care and treatment, Hedgehog proteins -- Properties, Cellular signal transduction -- Genetic aspects, Health care industry
Abstract

Prostate adenocarcinoma (CaP) patients are classified into low-, intermediate-, and high-risk groups that reflect relative survival categories. While there are accepted treatment regimens for low- and high-risk patients, intermediate-risk patients pose a clinical dilemma, as treatment outcomes are highly variable for these individuals. A better understanding of the factors that regulate the progression of CaP is required to delineate risk. For example, aberrant activation of the Hedgehog (Hh) pathway is implicated in CaP progression. Here, we identify the serine protease inhibitor protease nexin 1 (PN1) as a negative regulator of Hh signaling in prostate. Using human CaP cell lines and a mouse xenograft model of CaP, we demonstrate that PN1 regulates Hh signaling by decreasing protein levels of the Hh ligand Sonic (SHH) and its downstream effectors. Further-more, we show that SHH expression enhanced tumor growth while overexpression of PN1 inhibited tumor growth and angiogenesis in mice. Finally, using comparative genome hybridization, we found that genetic alterations in Hh pathway genes correlated with worse clinical outcomes in intermediate-risk CaP patients, indicating the importance of this pathway in CaP., Introduction Prostate adenocarcinoma (CaP) is the second leading cause of male cancer death in the Western world (1). Various risk groups (low, intermediate, high, and metastatic) that reflect relative survival [...]

Published
2012
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7. Transient SOX9 expression facilitates resistance to androgen-targeted therapy in prostate cancer

Author

Nouri, Mannan, Massah, Shabnam, Caradec, Josselin, Lubik, Amy A., Li, Na, Truong, Sarah, Lee, Ahn R., Fazli, Ladan, Ramnarine, Varune Rohan, Lovnicki, Jessica M, Moore, Jackson, Wang, Mike, Foo, Jane, Gleave, Martin E, Hollier, Brett G, Nelson, Colleen C, Collins, Colin C, Dong, Xuesen, Buttyan, Ralph, Nouri, Mannan, Massah, Shabnam, Caradec, Josselin, Lubik, Amy A., Li, Na, Truong, Sarah, Lee, Ahn R., Fazli, Ladan, Ramnarine, Varune Rohan, Lovnicki, Jessica M, Moore, Jackson, Wang, Mike, Foo, Jane, Gleave, Martin E, Hollier, Brett G, Nelson, Colleen C, Collins, Colin C, Dong, Xuesen, and Buttyan, Ralph

Abstract

Purpose: Patients with metastatic prostate cancer are increasingly presenting with treatment-resistant, androgen receptor-negative/ low (AR /Low) tumors, with or without neuroendocrine characteristics, in processes attributed to tumor cell plasticity. This plasticity has been modeled by Rb1/p53 knockdown/knockout and is accompanied by overexpression of the pluripotency factor, Sox2. Here, we explore the role of the developmental transcription factor Sox9 in the process of prostate cancer therapy response and tumor progression. Experimental Design: Unique prostate cancer cell models that capture AR. / Low stem cell-like intermediates were analyzed for features of plasticity and the functional role of Sox9. Human prostate cancer xenografts and tissue microarrays were evaluated for temporal alterations in Sox9 expression. The role of NF-kB pathway activity in Sox9 overexpression was explored. Results: Prostate cancer stem cell-like intermediates have reduced Rb1 and p53 protein expression and overexpress Sox2 as well as Sox9. Sox9 was required for spheroid growth, and overexpression increased invasiveness and neural features of prostate cancer cells. Sox9 was transiently upregulated in castration-induced progression of prostate cancer xenografts and was specifically overexpressed in neoadjuvant hormone therapy (NHT)-treated patient tumors. High Sox9 expression in NHT-treated patients predicts biochemical recurrence. Finally, we link Sox9 induction to NF-kB dimer activation in prostate cancer cells. Conclusions: Developmentally reprogrammed prostate cancer cell models recapitulate features of clinically advanced prostate tumors, including downregulated Rb1/p53 and overexpression of Sox2 with Sox9. Sox9 is a marker of a transitional state that identifies prostate cancer cells under the stress of therapeutic assault and facilitates progression to therapy resistance. Its expression may index the relative activity of the NF-kB pathway.

Published
2020

10. The long non-coding RNA landscape of neuroendocrine prostate cancer and its clinical implications, biological dysregulation, and functional impact

Author

Ramnarine, Varune Rohan

Abstract

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (CRPC). It can develop de novo from prostate neuroendocrine cells, yet primarily is a treatment-induced phenotype arising from transdifferentiated prostate adenocarcinoma (AD) cells (NEtD). Currently there is an unmet clinical need for predictive biomarkers, therapeutic targets, and more reliable diagnostics. In this dissertation we use the first-in-field patient-derived xenograft model of NEtD, six in vitro CRPC/NEPC models, and ~30,000 PCa patient samples, including 344 NEPC or molecular analogous NEPC samples. We implement a state-of-the-art next-generation sequence analysis pipeline, capable of detecting transcripts at low expression levels to build a comprehensive lncRNA catalog (~N=40,000). Our xenograft model enabled identification of transcriptional changes during NEtD. Our in vitro models were used for functionalization and our patient samples were used to determine clinical relevancy and/or to test for patient survival. In Chapter I, we review lncRNA research in PCa over the last 30 years. We include known genomic structures, mechanisms of actions, roles in PCa progression, and their use in disease management. In Chapter II, we identify a 122-lncRNA signature capable of robustly classifying NEPC from AD, 25 with predictive ability to classify metastatic patients, and 2 (SSTR5-AS1 and LINC00514) capable of stratifying patients more probable to develop metastasis following androgen deprivation therapy (ADT). In Chapter III, we identify two NEPC molecular subtypes driven by lncRNAs FENDRR and GAS5. They also have a predictive ability to stratify ADT patients by clinical outcome. In Chapter IV, we investigate our top candidate NEPC lncRNA H19. We identify the active isoform, determine it is conserved, a dozen associated PCa risk single nucleotide polymorphisms (SNPs) nearby, and NEPC-related TFBS (MYC/MAX) embedded within. H19 was highly sensitive and relatively specific for NEPC. Functionally, we identified associations to invasion, proliferation, the NEPC phenotype, and physical interactions with EZH2. Most importantly H19 is predictive for ADT-patient outcome. Collectively, this thesis constitutes a step forward in understanding the complexity of the transcriptome for NEPC and the NEtD process. The results here will advance our knowledge of clinically relevant lncRNAs involved in cancer progression and treatment resistance.

Published
2019
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12. The long noncoding RNA landscape of neuroendocrine prostate cancer and its clinical implications

Author

Ramnarine, Varune Rohan, primary, Alshalalfa, Mohammed, additional, Mo, Fan, additional, Nabavi, Noushin, additional, Erho, Nicholas, additional, Takhar, Mandeep, additional, Shukin, Robert, additional, Brahmbhatt, Sonal, additional, Gawronski, Alexander, additional, Kobelev, Maxim, additional, Nouri, Mannan, additional, Lin, Dong, additional, Tsai, Harrison, additional, Lotan, Tamara L, additional, Karnes, R Jefferey, additional, Rubin, Mark A, additional, Zoubeidi, Amina, additional, Gleave, Martin E, additional, Sahinalp, Cenk, additional, Wyatt, Alexander W, additional, Volik, Stanislav V, additional, Beltran, Himisha, additional, Davicioni, Elai, additional, Wang, Yuzhuo, additional, and Collins, Colin C, additional

Published
2018
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13. Stromal Gene Expression is Predictive for Metastatic Primary Prostate Cancer

Author

Mo, Fan, primary, Lin, Dong, additional, Takhar, Mandeep, additional, Ramnarine, Varune Rohan, additional, Dong, Xin, additional, Bell, Robert H., additional, Volik, Stanislav V., additional, Wang, Kendric, additional, Xue, Hui, additional, Wang, Yuwei, additional, Haegert, Anne, additional, Anderson, Shawn, additional, Brahmbhatt, Sonal, additional, Erho, Nicholas, additional, Wang, Xinya, additional, Gout, Peter W., additional, Morris, James, additional, Karnes, R. Jeffrey, additional, Den, Robert B., additional, Klein, Eric A., additional, Schaeffer, Edward M., additional, Ross, Ashley, additional, Ren, Shancheng, additional, Sahinalp, S. Cenk, additional, Li, Yingrui, additional, Xu, Xun, additional, Wang, Jun, additional, Wang, Jian, additional, Gleave, Martin E., additional, Davicioni, Elai, additional, Sun, Yinghao, additional, Wang, Yuzhuo, additional, and Collins, Colin C., additional

Published
2018
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14. The long non-coding RNA PCGEM1 is regulated by androgen receptor activity in vivo

Author

Parolia, Abhijit, primary, Crea, Francesco, additional, Xue, Hui, additional, Wang, Yuwei, additional, Mo, Fan, additional, Ramnarine, Varune Rohan, additional, Liu, Hui Hsuan, additional, Lin, Dong, additional, Saidy, Nur Ridzwan Nur, additional, Clermont, Pier-Luc, additional, Cheng, Hongwei, additional, Collins, Colin, additional, Wang, Yuzhuo, additional, and Helgason, Cheryl D, additional

Published
2015
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15. Using NBN to predict biochemical relapse following image-guided radiotherapy (IGRT) for intermediate-risk prostate cancer (IR-PCa).

Author

Berlin, Alejandro, primary, Lalonde, Emilie, additional, Zafarana, Gaetano, additional, Sykes, Jenna, additional, Ramnarine, Varune Rohan, additional, Lam, Wan, additional, Meng, Alice, additional, Milosevic, Michael, additional, van der Kwast, Theodorus, additional, Boutros, Paul C, additional, and Bristow, Robert Glen, additional

Published
2014
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16. NKX3.1 Haploinsufficiency Is Prognostic for Prostate Cancer Relapse following Surgery or Image-Guided Radiotherapy

Author

Locke, Jennifer A., primary, Zafarana, Gaetano, additional, Ishkanian, Adrian S., additional, Milosevic, Michael, additional, Thoms, John, additional, Have, Cherry L., additional, Malloff, Chad A., additional, Lam, Wan L., additional, Squire, Jeremy A., additional, Pintilie, Melania, additional, Sykes, Jenna, additional, Ramnarine, Varune Rohan, additional, Meng, Alice, additional, Ahmed, Omer, additional, Jurisica, Igor, additional, van der Kwast, Theo, additional, and Bristow, Robert G., additional

Published
2012
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17. Allelic loss of the loci containing the androgen synthesis gene, StAR , is prognostic for relapse in intermediate-risk prostate cancer

Author

Locke, Jennifer A., primary, Zafarana, Gaetano, additional, Malloff, Chad A., additional, Lam, Wan L., additional, Sykes, Jenna, additional, Pintilie, Melania, additional, Ramnarine, Varune Rohan, additional, Meng, Alice, additional, Ahmed, Omer, additional, Jurisica, Igor, additional, Guns, Emma Tomlinson, additional, van der Kwast, Theo, additional, Milosevic, Michael, additional, and Bristow, Robert G., additional

Published
2011
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