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EGFR as a stable marker of prostate cancer dissemination to bones.

Paulina Nastały, Sara Stoupiec, Marta Popęda, Julia Smentoch, Thorsten Schlomm, Colm Morrissey, Anna Joanna Żaczek, Burkhard Beyer, Pierre Tennstedt, Markus Graefen, Elke Eltze, Paolo Maiuri, Axel Semjonow, Klaus Pantel, Burkhard Brandt, Natalia Bednarz-Knoll,

BACKGROUND:Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men. Although 5-year survival in patients with localised disease reaches nearly 100%, metastatic disease still remains incurable. Therefore, there is a need for markers indicating metastatic dissemination. METHODS:EGFR overexpression (EGFRover) was tracked in 1039 primary tumours, circulating tumour cells ... Read more >>

Br. J. Cancer (British journal of cancer)
[2020, :]

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Targeting RET Kinase in Neuroendocrine Prostate Cancer.

Halena R VanDeusen, Johnny R Ramroop, Katherine L Morel, Song Yi Bae, Anjali V Sheahan, Zoi Sychev, Nathan A Lau, Larry C Cheng, Victor M Tan, Zhen Li, Ashley Petersen, John K Lee, Jung Wook Park, Rendong Yang, Justin H Hwang, Ilsa Coleman, Owen N Witte, Colm Morrissey, Eva Corey, Peter S Nelson, Leigh Ellis, Justin M Drake,

The increased treatment of metastatic castration-resistant prostate cancer (mCRPC) with second-generation antiandrogen therapies (ADT) has coincided with a greater incidence of lethal, aggressive variant prostate cancer (AVPC) tumors that have lost dependence on androgen receptor (AR) signaling. These AR-independent tumors may also transdifferentiate to express neuroendocrine lineage markers and are ... Read more >>

Mol. Cancer Res. (Molecular cancer research : MCR)
[2020, 18(8):1176-1188]

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SAT-114 Loss of DHEA-Targeting SULT2b1b Sulfotransferase Exacerbates Aggressive Traits of Prostate Cancer.

Chung Seog Song, Sulgi Park, Shoulei Jiang, Pawel Osmulski, Brett T Marck, Alvin M Matsumoto, Colm Morrissey, Maria E Gaczynska, Elahe A Mostaghel, Bandana Chatterjee,

AbstractThe prostate-expressed sulfotransferase SULT2B1b (SULT2B) regulates intracrine androgen homeostasis by mediating 3β-sulfation of DHEA, thus reducing the precursor pool in the androgen biosynthesis pathway. We explored how loss of SULT2B might influence prostate cancer progression. Results show that SULT2B ablation in castration-resistant prostate cancer (CRPC) cells, generated by stable RNA ... Read more >>

J Endocr Soc (Journal of the Endocrine Society)
[2020, 4(Suppl 1):]

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Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress.

Michael D Nyquist, Alexandra Corella, Ilsa Coleman, Navonil De Sarkar, Arja Kaipainen, Gavin Ha, Roman Gulati, Lisa Ang, Payel Chatterjee, Jared Lucas, Colin Pritchard, Gail Risbridger, John Isaacs, Bruce Montgomery, Colm Morrissey, Eva Corey, Peter S Nelson,

Prostate cancers (PCs) with loss of the potent tumor suppressors TP53 and RB1 exhibit poor outcomes. TP53 and RB1 also influence cell plasticity and are frequently lost in PCs with neuroendocrine (NE) differentiation. Therapeutic strategies that address these aggressive variant PCs are urgently needed. Using deep genomic profiling of 410 ... Read more >>

Cell Rep (Cell reports)
[2020, 31(8):107669]

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Alternative splicing of LSD1+8a in neuroendocrine prostate cancer is mediated by SRRM4.

Daniel J Coleman, David A Sampson, Archana Sehrawat, Anbarasu Kumaraswamy, Duanchen Sun, Yuzhuo Wang, Jacob Schwartzman, Joshua Urrutia, Ahn R Lee, Ilsa M Coleman, Peter S Nelson, Xuesen Dong, Colm Morrissey, Eva Corey, Zheng Xia, Joel A Yates, Joshi J Alumkal,

Neuroendocrine prostate cancer (NEPC) is the most virulent form of prostate cancer. Importantly, our recent work examining metastatic biopsy samples demonstrates NEPC is increasing in frequency. In contrast to prostate adenocarcinomas that express a luminal gene expression program, NEPC tumors express a neuronal gene expression program. Despite this distinction, the ... Read more >>

Neoplasia (Neoplasia (New York, N.Y.))
[2020, 22(6):253-262]

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Correction: Activation of MAPK Signaling by CXCR7 Leads to Enzalutamide Resistance in Prostate Cancer.

Shangze Li, Ka-Wing Fong, Galina Gritsina, Ali Zhang, Jonathan C Zhao, Jung Kim, Adam Sharp, Wei Yuan, Caterina Aversa, Ximing J Yang, Peter S Nelson, Felix Y Feng, Arul M Chinnaiyan, Johann S de Bono, Colm Morrissey, Matthew B Rettig, Jindan Yu,

Cancer Res. (Cancer research)
[2020, 80(10):2072]

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Neutrophils are mediators of metastatic prostate cancer progression in bone.

Diane L Costanzo-Garvey, Tyler Keeley, Adam J Case, Gabrielle F Watson, Massar Alsamraae, Yangsheng Yu, Kaihong Su, Cortney E Heim, Tammy Kielian, Colm Morrissey, Jeremy S Frieling, Leah M Cook,

Bone metastatic prostate cancer (BM-PCa) significantly reduces overall patient survival and is currently incurable. Current standard immunotherapy showed promising results for PCa patients with metastatic, but less advanced, disease (i.e., fewer than 20 bone lesions) suggesting that PCa growth in bone contributes to response to immunotherapy. We found that: (1) ... Read more >>

Cancer Immunol. Immunother. (Cancer immunology, immunotherapy : CII)
[2020, 69(6):1113-1130]

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Inhibitory Interplay of SULT2B1b Sulfotransferase with AKR1C3 Aldo-keto Reductase in Prostate Cancer.

Sulgi Park, Chung-Seog Song, Chun-Lin Lin, Shoulei Jiang, Pawel A Osmulski, Chiou-Miin Wang, Brett T Marck, Alvin M Matsumoto, Colm Morrissey, Maria E Gaczynska, Yidong Chen, Elahe A Mostaghel, Bandana Chatterjee,

SULT2B1b (SULT2B) is a prostate-expressed hydroxysteroid sulfotransferase, which may regulate intracrine androgen homeostasis by mediating 3β-sulfation of dehydroepiandrosterone (DHEA), the precursor for 5α-dihydrotestosterone (DHT) biosynthesis. The aldo-keto reductase (AKR)1C3 regulates androgen receptor (AR) activity in castration-resistant prostate cancer (CRPC) by promoting tumor tissue androgen biosynthesis from adrenal DHEA and also ... Read more >>

Endocrinology (Endocrinology)
[2020, 161(2):]

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Diverse AR Gene Rearrangements Mediate Resistance to Androgen Receptor Inhibitors in Metastatic Prostate Cancer.

Yingming Li, Rendong Yang, Christine M Henzler, Yeung Ho, Courtney Passow, Benjamin Auch, Suzanne Carreira, Daniel Nava Rodrigues, Claudia Bertan, Tae Hyun Hwang, David A Quigley, Ha X Dang, Colm Morrissey, Michael Fraser, Stephen R Plymate, Christopher A Maher, Felix Y Feng, Johann S de Bono, Scott M Dehm,

PURPOSE:Prostate cancer is the second leading cause of male cancer deaths. Castration-resistant prostate cancer (CRPC) is a lethal stage of the disease that emerges when endocrine therapies are no longer effective at suppressing activity of the androgen receptor (AR) transcription factor. The purpose of this study was to identify genomic ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(8):1965-1976]

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Differential Expression of Glucose Transporters and Hexokinases in Prostate Cancer with a Neuroendocrine Gene Signature: A Mechanistic Perspective for 18F-FDG Imaging of PSMA-Suppressed Tumors.

Martin K Bakht, Jessica M Lovnicki, Janice Tubman, Keith F Stringer, Jonathan Chiaramonte, Michael R Reynolds, Iulian Derecichei, Rosa-Maria Ferraiuolo, Bre-Anne Fifield, Dorota Lubanska, So Won Oh, Gi Jeong Cheon, Cheol Kwak, Chang Wook Jeong, Keon Wook Kang, John F Trant, Colm Morrissey, Ilsa M Coleman, Yuzhuo Wang, Hojjat Ahmadzadehfar, Xuesen Dong, Lisa A Porter,

Although the incidence of de novo neuroendocrine prostate cancer (PC) is rare, recent data suggest that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine hallmarks and androgen receptor (AR) suppression in PC. Previous clinical reports indicate that PCs with a phenotype similar to neuroendocrine ... Read more >>

J. Nucl. Med. (Journal of nuclear medicine : official publication, Society of Nuclear Medicine)
[2020, 61(6):904-910]

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Identification of Therapeutic Vulnerabilities in Small-cell Neuroendocrine Prostate Cancer.

Alexandra N Corella, Ma Victoria Andrea Cabiliza Ordonio, Ilsa Coleman, Jared M Lucas, Arja Kaipainen, Holly M Nguyen, Daniel Sondheim, Lisha G Brown, Lawrence D True, John K Lee, David MacPherson, Paul Nghiem, Roman Gulati, Colm Morrissey, Eva Corey, Peter S Nelson,

PURPOSE:Small-cell neuroendocrine prostate cancer (SCNPC) exhibits an aggressive clinical course and incidence rates seem to be increasing following resistance to potent androgen receptor (AR) antagonists. Currently, treatment options are limited and few model systems are available to identify new approaches for treatment. We sought to evaluate commonalities between SCNPC and ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(7):1667-1677]

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COMMD3:BMI1 Fusion and COMMD3 Protein Regulate C-MYC Transcription: Novel Therapeutic Target for Metastatic Prostate Cancer.

Syed Umbreen, Mudassir Meraj Banday, Anmbreen Jamroze, Adrian P Mansini, Arsheed A Ganaie, Marina G Ferrari, Raihana Maqbool, Firdous H Beigh, Paari Murugan, Colm Morrissey, Eva Corey, Badrinath R Konety, Mohammad Saleem,

Gene rearrangement is reported to be associated to the aggressive phenotype and poor prognosis in prostate cancer. We identified a gene fusion between a transcription repressor (BMI1) and transcriptional factor (COMMD3) in human prostate cancer. We show that COMMD3:BMI1 fusion expression is significantly increased in prostate cancer disease in an ... Read more >>

Mol. Cancer Ther. (Molecular cancer therapeutics)
[2019, 18(11):2111-2123]

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Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer.

Mark P Labrecque, Ilsa M Coleman, Lisha G Brown, Lawrence D True, Lori Kollath, Bryce Lakely, Holly M Nguyen, Yu C Yang, Rui M Gil da Costa, Arja Kaipainen, Roger Coleman, Celestia S Higano, Evan Y Yu, Heather H Cheng, Elahe A Mostaghel, Bruce Montgomery, Michael T Schweizer, Andrew C Hsieh, Daniel W Lin, Eva Corey, Peter S Nelson, Colm Morrissey,

Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with diverse drivers of disease progression and mechanisms of therapeutic resistance. We conducted deep phenotypic characterization of CRPC metastases and patient-derived xenograft (PDX) lines using whole genome RNA sequencing, gene set enrichment analysis and immunohistochemistry. Our analyses revealed five mCRPC phenotypes ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2019, 129(10):4492-4505]

Cited: 4 times

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The androgen receptor regulates a druggable translational regulon in advanced prostate cancer.

Yuzhen Liu, Jessie L Horn, Kalyan Banda, Asha Z Goodman, Yiting Lim, Sujata Jana, Sonali Arora, Alexandre A Germanos, Lexiaochuan Wen, William R Hardin, Yu C Yang, Ilsa M Coleman, Robin G Tharakan, Elise Y Cai, Takuma Uo, Smitha P S Pillai, Eva Corey, Colm Morrissey, Yu Chen, Brett S Carver, Stephen R Plymate, Slobodan Beronja, Peter S Nelson, Andrew C Hsieh,

The androgen receptor (AR) is a driver of cellular differentiation and prostate cancer development. An extensive body of work has linked these normal and aberrant cellular processes to mRNA transcription; however, the extent to which AR regulates posttranscriptional gene regulation remains unknown. Here, we demonstrate that AR uses the translation ... Read more >>

Sci Transl Med (Science translational medicine)
[2019, 11(503):]

Cited: 1 time

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Distinct expression patterns of SULT2B1b in human prostate epithelium.

Jiang Yang, Meaghan M Broman, Paula O Cooper, Nadia A Lanman, Douglas W Strand, Colm Morrissey, Timothy L Ratliff,

BACKGROUND:SULT2B1b (sulfotransferase family cytosolic 2B member 1b) catalyzes the sulfate conjugation of substrates such as cholesterol and oxysterols. Our laboratory has previously shown that SULT2B1b inhibition modulates androgen receptor signaling and induces apoptosis in prostate cancer cells. However, the functions of SULT2B1b in the prostate remain poorly understood. METHODS:We characterized ... Read more >>

Prostate (The Prostate)
[2019, 79(11):1256-1266]

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Publisher Correction: The long tail of oncogenic drivers in prostate cancer.

Joshua Armenia, Stephanie A M Wankowicz, David Liu, Jianjiong Gao, Ritika Kundra, Ed Reznik, Walid K Chatila, Debyani Chakravarty, G Celine Han, Ilsa Coleman, Bruce Montgomery, Colin Pritchard, Colm Morrissey, Christopher E Barbieri, Himisha Beltran, Andrea Sboner, Zafeiris Zafeiriou, Susana Miranda, Craig M Bielski, Alexander V Penson, Charlotte Tolonen, Franklin W Huang, Dan Robinson, Yi Mi Wu, Robert Lonigro, Levi A Garraway, Francesca Demichelis, Philip W Kantoff, Mary-Ellen Taplin, Wassim Abida, Barry S Taylor, Howard I Scher, Peter S Nelson, Johann S de Bono, Mark A Rubin, Charles L Sawyers, Arul M Chinnaiyan, , Nikolaus Schultz, Eliezer M Van Allen,

An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Read more >>

Nat. Genet. (Nature genetics)
[2019, 51(7):1194]

Cited: 2 times

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Targeting RET Kinase in Neuroendocrine Prostate Cancer

Halena VanDeusen, Johnny Ramroop, Katherine Morel, Anjali Sheahan, Zoi Sychev, Nathan Lau, Larry Cheng, Victor Tan, Zhen Li, Ashley Petersen, John Lee, Jung Wook Park, Rendong Yang, Ilsa Coleman, Owen Witte, Colm Morrissey, Eva Corey, Peter Nelson, Leigh Ellis, Justin Drake,

Abstract Increased treatment of metastatic castration resistant prostate cancer (mCRPC) with second-generation anti-androgen therapies (ADT) has coincided with a greater incidence of lethal, aggressive variant prostate cancer (AVPC) tumors that have lost androgen receptor (AR) signaling. AVPC tumors may also express neuroendocrine markers, termed neuroendocrine prostate cancer (NEPC). Recent evidence ... Read more >>

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Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer.

Giorgia Zadra, Caroline F Ribeiro, Paolo Chetta, Yeung Ho, Stefano Cacciatore, Xueliang Gao, Sudeepa Syamala, Clyde Bango, Cornelia Photopoulos, Ying Huang, Svitlana Tyekucheva, Debora C Bastos, Jeremy Tchaicha, Brian Lawney, Takuma Uo, Laura D'Anello, Alfredo Csibi, Radha Kalekar, Benjamin Larimer, Leigh Ellis, Lisa M Butler, Colm Morrissey, Karen McGovern, Vito J Palombella, Jeffery L Kutok, Umar Mahmood, Silvano Bosari, Julian Adams, Stephane Peluso, Scott M Dehm, Stephen R Plymate, Massimo Loda,

A hallmark of prostate cancer progression is dysregulation of lipid metabolism via overexpression of fatty acid synthase (FASN), a key enzyme in de novo fatty acid synthesis. Metastatic castration-resistant prostate cancer (mCRPC) develops resistance to inhibitors of androgen receptor (AR) signaling through a variety of mechanisms, including the emergence of ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2019, 116(2):631-640]

Cited: 21 times

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ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis.

Mirja Rotinen, Sungyong You, Julie Yang, Simon G Coetzee, Mariana Reis-Sobreiro, Wen-Chin Huang, Fangjin Huang, Xinlei Pan, Alberto Yáñez, Dennis J Hazelett, Chia-Yi Chu, Kenneth Steadman, Colm M Morrissey, Peter S Nelson, Eva Corey, Leland W K Chung, Stephen J Freedland, Dolores Di Vizio, Isla P Garraway, Ramachandran Murali, Beatrice S Knudsen, Michael R Freeman,

Treatment of prostate cancer (PC) by androgen suppression promotes the emergence of aggressive variants that are androgen receptor (AR) independent. Here we identify the transcription factor ONECUT2 (OC2) as a master regulator of AR networks in metastatic castration-resistant prostate cancer (mCRPC). OC2 acts as a survival factor in mCRPC models, ... Read more >>

Nat. Med. (Nature medicine)
[2018, 24(12):1887-1898]

Cited: 16 times

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ALDH1-positive intratumoral stromal cells indicate differentiated epithelial-like phenotype and good prognosis in prostate cancer.

Paulina Nastały, Martyna Filipska, Colm Morrissey, Elke Eltze, Axel Semjonow, Burkhard Brandt, Klaus Pantel, Natalia Bednarz-Knoll,

Aldehyde dehydrogenase 1 (ALDH1) characterizes tumor-initiating cells in solid tumors; however, little is known about its expression in intratumoral stromal cells. Herein, we aimed to dissect its potential dual relevance in prostate cancer (PCa). ALDH1 expression was evaluated immunohistochemically in tumor and stromal cells in primary PCa and metastases. It ... Read more >>

Transl Res (Translational research : the journal of laboratory and clinical medicine)
[2019, 203:49-56]

Cited: 1 time

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Contribution of Adrenal Glands to Intratumor Androgens and Growth of Castration-Resistant Prostate Cancer.

Elahe A Mostaghel, Ailin Zhang, Susana Hernandez, Brett T Marck, Xiaotun Zhang, Daniel Tamae, Heather E Biehl, Maria Tretiakova, Jon Bartlett, John Burns, Ruth Dumpit, Lisa Ang, Alvin M Matsumoto, Trevor M Penning, Steven P Balk, Colm Morrissey, Eva Corey, Lawrence D True, Peter S Nelson,

PURPOSE:Tumor androgens in castration-resistant prostate cancer (CRPC) reflect de novo intratumoral synthesis or adrenal androgens. We used C.B.-17 SCID mice in which we observed adrenal CYP17A activity to isolate the impact of adrenal steroids on CRPC tumors in vivo. EXPERIMENTAL DESIGN:We evaluated tumor growth and androgens in LuCaP35CR and LuCaP96CR ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2019, 25(1):426-439]

Cited: 3 times

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BMI1 Drives Metastasis of Prostate Cancer in Caucasian and African-American Men and Is A Potential Therapeutic Target: Hypothesis Tested in Race-specific Models.

Arsheed A Ganaie, Firdous H Beigh, Matteo Astone, Marina G Ferrari, Raihana Maqbool, Syed Umbreen, Aijaz S Parray, Hifzur R Siddique, Tabish Hussain, Paari Murugan, Colm Morrissey, Shahriar Koochekpour, Yibin Deng, Badrinath R Konety, Luke H Hoeppner, Mohammad Saleem,

PURPOSE:Metastasis is the major cause of mortality in prostate cancer patients. Factors such as genetic makeup and race play critical role in the outcome of therapies. This study was conducted to investigate the relevance of BMI1 in metastatic prostate cancer disease in Caucasian and African-Americans. EXPERIMENTAL DESIGN:We employed race-specific prostate ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2018, 24(24):6421-6432]

Cited: 1 time

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The long tail of oncogenic drivers in prostate cancer.

Joshua Armenia, Stephanie A M Wankowicz, David Liu, Jianjiong Gao, Ritika Kundra, Ed Reznik, Walid K Chatila, Debyani Chakravarty, G Celine Han, Ilsa Coleman, Bruce Montgomery, Colin Pritchard, Colm Morrissey, Christopher E Barbieri, Himisha Beltran, Andrea Sboner, Zafeiris Zafeiriou, Susana Miranda, Craig M Bielski, Alexander V Penson, Charlotte Tolonen, Franklin W Huang, Dan Robinson, Yi Mi Wu, Robert Lonigro, Levi A Garraway, Francesca Demichelis, Philip W Kantoff, Mary-Ellen Taplin, Wassim Abida, Barry S Taylor, Howard I Scher, Peter S Nelson, Johann S de Bono, Mark A Rubin, Charles L Sawyers, Arul M Chinnaiyan, , Nikolaus Schultz, Eliezer M Van Allen,

Comprehensive genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate ... Read more >>

Nat. Genet. (Nature genetics)
[2018, 50(5):645-651]

Cited: 102 times

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ALDH1-positive intratumoral stromal cells indicate epithelial differentiation and good prognosis in prostate cancer

Paulina Nastały, Martyna Filipska, Colm Morrissey, Elke Eltze, Axel Semjonow, Burkhard Brandt, Klaus Pantel, Natalia Bednarz-Knoll,

Abstract Aldehyde dehydrogenase 1 (ALDH1) characterizes tumor-initiating cells in solid tumors, however little is known about its expression in intratumoral stromal cells. Herein, we aimed to dissect its potential dual relevance in prostate cancer (PCa). ALDH1 expression was evaluated immunohistochemically in tumor and stromal cells in primary PCa and metastasis. ... Read more >>

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Plasma Fatty Acids as Surrogate for Prostate Levels.

Jeannette M Schenk, Xiaoling Song, Colm Morrissey, Robert L Vessella, Daniel W Lin, Marian L Neuhouser,

Inconsistent results from epidemiologic studies of circulating fatty acids and prostate cancer risk may be partly due to use of blood concentrations as surrogate biomarkers of prostate tissue concentrations. To determine whether blood concentrations reflect prostate tissue fatty acid profiles, we evaluated associations between phospholipid fatty acid (PLFA) profiles measured ... Read more >>

Nutr Cancer (Nutrition and cancer)
[2018, 70(1):45-50]

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