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neuroendocrine prostate cancer

Manish K Thakur, Lance Heilbrun, Kimberlee Dobson, Julie Boerner, Karri Stark, Jing Li, Daryn Smith, Elisabeth Heath, Joseph Fontana, Ulka Vaishampayan
BACKGROUND: Pasireotide (SOM230; Novartis Inc, Basel, Switzerland) is a multitargeted somatostatin receptor analogue likely to treat the neuroendocrine, and docetaxel resistant components within metastatic castrate-resistant prostate cancer (mCRPC). This phase I trial tested the combination of pasireotide, docetaxel, and prednisone in pretreated mCRPC. PATIENTS AND METHODS: Chemotherapy naive mCRPC patients received docetaxel 75 mg/m2 intravenously every 21 days and pasireotide intramuscularly every 28 days at escalating dose levels of 40, 60, and 80 mg...
February 13, 2018: Clinical Genitourinary Cancer
Yan Qiao, Tingting Yang, Yong Gan, Wenzhen Li, Chao Wang, Yanhong Gong, Zuxun Lu
BACKGROUND: Epidemiological studies have clarified the potential associations between regular aspirin use and cancers. However, it remains controversial on whether aspirin use decreases the risk of cancers risks. Therefore, we conducted an updated meta-analysis to assess the associations between aspirin use and cancers. METHODS: The PubMed, Embase, and Web of Science databases were systematically searched up to March 2017 to identify relevant studies. Relative risks (RRs) with 95% confidence intervals (CIs) were used to assess the strength of associations...
March 13, 2018: BMC Cancer
David P Labbé, Myles Brown
Prostate cancer development involves corruption of the normal prostate transcriptional network, following deregulated expression or mutation of key transcription factors. Here, we provide an overview of the transcription factors that are important in normal prostate homeostasis (NKX3-1, p63, androgen receptor [AR]), primary prostate cancer (ETS family members, c-MYC), castration-resistant prostate cancer (AR, FOXA1), and AR-independent castration-resistant neuroendocrine prostate cancer (RB1, p53, N-MYC). We use functional (in vitro and in vivo) as well as clinical data to discuss evidence that unveils their roles in the initiation and progression of prostate cancer, with an emphasis on results of chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq)...
March 12, 2018: Cold Spring Harbor Perspectives in Medicine
Xinpei Ci, Jun Hao, Xin Dong, Stephen Y C Choi, Hui Xue, Rebecca Wu, Sifeng Qu, Peter W Gout, Fang Zhang, Anne M Haegert, Ladan Fazil, Francesco Crea, Christopher J Ong, Amina Zoubedi, Housheng H He, Martin E Gleave, Colin C Collins, Dong Lin, Yuzhuo Wang
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer (PCa) arising mostly from adenocarcinoma via NE transdifferentiation following androgen deprivation therapy. Mechanisms contributing to both NEPC development and its aggressiveness remain elusive. In light of the fact that hyperchromatic nuclei are a distinguishing histopathological feature of NEPC, we utilized transcriptomic analyses of our patient-derived xenograft (PDX) models, multiple clinical cohorts, and genetically engineered mouse models to identify 36 heterochromatin-related genes that are significantly enriched in NEPC...
February 27, 2018: Cancer Research
Brandon A Mahal, David D Yang, Natalie Q Wang, Mohammed Alshalalfa, Elai Davicioni, Voleak Choeurng, Edward M Schaeffer, Ashley E Ross, Daniel E Spratt, Robert B Den, Neil E Martin, Kent W Mouw, Peter F Orio, Toni K Choueiri, Mary-Ellen Taplin, Quoc-Dien Trinh, Felix Y Feng, Paul L Nguyen
BACKGROUND: The consequences of low prostate-specific antigen (PSA) in high-grade (Gleason 8-10) prostate cancer are unknown. OBJECTIVE: To evaluate the clinical implications and genomic features of low-PSA, high-grade disease. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective study of clinical data for 494 793 patients from the National Cancer Data Base and 136 113 patients from the Surveillance, Epidemiology, and End Results program with cT1-4N0M0 prostate cancer (median follow-up 48...
February 22, 2018: European Urology
Girish Kumar Parida, Sarthak Tripathy, Shreya Datta Gupta, Abhinav Singhal, Rakesh Kumar, Chandrasekhar Bal, Shamim Ahmed Shamim
Ga-PSMA PET/CT is the upcoming imaging modality for staging, restaging and response assessment of prostate cancer. However, due to neuroendocrine differentiation in some of patients with prostate cancer, they express somatostatin receptors instead of prostate specific membrane antigen. This can be exploited and other modalities like Ga-DOTANOC PET/CT and F-FDG PET/CT should be used in such cases for guiding management. We hereby discuss a similar case of 67-year-old man of adenocarcinoma prostate with neuroendocrine differentiation, which shows the potential pitfall of Ga-PSMA PET/CT imaging and benefit of Ga-DOTANOC PET/CT and F-FDG PET/CT in such cases...
February 23, 2018: Clinical Nuclear Medicine
James R Ballinger
Although use of the term "theranostic" is relatively recent, the concept goes back to the earliest days of nuclear medicine, with the use of radioiodine for diagnosis and therapy of benign and malignant thyroid disease being arguably the most successful molecular radiotherapy in history. A diagnostic scan with123 I-,124 I-, or a low activity of131 I-iodide is followed by therapy with high activity131 I-iodide. Similarly, adrenergic tumours such as phaeochromocytoma and neuroblastoma can be imaged with123 I-metaiodobenzylguanidine (MIBG) and treated with131 I-MIBG...
February 23, 2018: British Journal of Radiology
Alastair H Davies, Himisha Beltran, Amina Zoubeidi
The success of next-generation androgen receptor (AR) pathway inhibitors, such as abiraterone acetate and enzalutamide, in treating prostate cancer has been hampered by the emergence of drug resistance. This acquired drug resistance is driven, in part, by the ability of prostate cancer cells to change their phenotype to adopt AR-independent pathways for growth and survival. Around one-quarter of resistant prostate tumours comprise cells that have undergone cellular reprogramming to become AR-independent and to acquire a continuum of neuroendocrine characteristics...
February 20, 2018: Nature Reviews. Urology
Younghun Jung, Frank C Cackowski, Kenji Yumoto, Ann Decker, Jingcheng Wang, Jinkoo Kim, Eunsohl Lee, Yugang Wang, Jae-Seung Chung, Amy M Gursky, Paul H Krebsbach, Kenneth J Pienta, Todd M Morgan, Russell S Taichman
There is evidence that cancer stem-like cells (CSC) and neuroendocrine (NE) behavior play critical roles in the pathogenesis and clinical course of metastatic castration-resistant prostate cancer (m-CRPC). However, there is limiting mechanistic understanding of how CSC and NE phenotypes impact the development of m-CRPC, which could improve opportunities to identify useful biomarkers and therapeutics. In this study, we explored the role of the intracellular chemokine CXCL12γ in CSC induction and NE differentiation and its impact on m-CRPC...
February 5, 2018: Cancer Research
Lin Ruan, Lei Wang, Xiaosong Wang, Ming He, Xiaoguang Yao
The epigenetic factor SIRT1 can promote prostate cancer progression, but it is unclear whether SIRT1 contributes to neuroendocrine differentiation. In this study, we showed that androgen deprivation can induce reactive oxygen species production and that reactive oxygen species, in turn, activate SIRT1 expression. The increased SIRT1 expression induces neuroendocrine differentiation of prostate cancer cells by activating the Akt pathway. In addition, the interaction between Akt and SIRT1 is independent of N-Myc and can drive the development of neuroendocrine prostate cancer when N-Myc is blocked...
January 5, 2018: Oncotarget
Shusuke Akamatsu, Takahiro Inoue, Osamu Ogawa, Martin E Gleave
Treatment-related neuroendocrine prostate cancer is a lethal form of prostate cancer that emerges in the later stages of castration-resistant prostate cancer treatment. Treatment-related neuroendocrine prostate cancer transdifferentiates from adenocarcinoma as an adaptive response to androgen receptor pathway inhibition. The incidence of treatment-related neuroendocrine prostate cancer has been rising due to the increasing use of potent androgen receptor pathway inhibitors. Typically, treatment-related neuroendocrine prostate cancer is characterized by either low or absent androgen receptor expression, small cell carcinoma morphology and expression of neuroendocrine markers...
February 3, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
Anjali V Sheahan, Leigh Ellis
Prostate cancer initiation, development and progression is driven by androgen receptor (AR) signaling. Androgen deprivation therapy is the primary treatment for patients that present with locally advanced or metastatic disease. However, androgen deprivation therapy is not curative, and patients will progress to castrate-resistant disease (CRPC). Although most patient's progress to CRPC via restoration of AR signaling (CRPC-Ad), approximately a quarter of patients will progress via mechanisms independent of AR signaling...
January 26, 2018: Urologic Oncology
Xiaomeng Li, Gene Moon, Sook Shin, Bin Zhang, Ralf Janknecht
The E26 transformation-specific (ETS) variant 2 (ETV2) protein, also designated as ETS-related 71, is a member of the ETS transcription factor family and is essential for blood and vascular development in the embryo. The role of ETV2 in cancer has not yet been investigated. In the present study, the expression of ETV2 mRNA was identified in a variety of tumor types, including prostate carcinoma. In addition, ETV2 gene amplification was identified in several types of cancer, suggesting that ETV2 plays an oncogenic role in tumorigenesis...
January 26, 2018: Molecular Medicine Reports
Alessandro Antonelli, Carlotta Palumbo, Alessandro Veccia, Salvatore Grisanti, Luca Triggiani, Stefania Zamboni, Maria Furlan, Claudio Simeone, Stefano Magrini, Alfredo Berruti
INTRODUCTION: Androgen-deprivation therapy (ADT) administered in neoadjuvant setting before radical prostatectomy (RP) represents an ideal in vivo human model to test the efficacy of hormonal treatments in prostate cancer (PCa). This review summarizes the findings from published studies specifically focused on the biological effects of ADT assessed on specimens from RP. The aim is to provide a base of knowledge that might be used to design future studies on neoadjuvant therapy for PCa...
February 1, 2018: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
Athar Haroon, Asim Afaq, Soujanya Nuthakki, Alex Freeman, Lorenzo Biassoni, Stefano Fanti, Mohsen Beheshti, Hikmat Jan, Sobhan Vinjamuri, Mark Emberton, Jamshed Bomanji
The objective of this study was to highlight the role of multimodality imaging and present the differential diagnosis of abnormal tracer accumulation in the prostate and periprostatic tissue. Our departments have performed molecular imaging of the prostate utilizing PET-CT and PET-MRI with a range of biomarkers including F-FDG, radiolabelled choline, Ga-DOTATATE PET-CT and Ga-PSMA images. We retrospectively reviewed the varying appearances of the prostate gland in different diseases and incidental findings in periprostatic region...
March 2018: Nuclear Medicine Communications
Matthew G Oser, Pasi A Janne
Small cell neuroendocrine cancers often originate in the lung, but can also arise in the bladder or prostate. Phenotypically, small cell carcinoma of the bladder (SCCB) shares many similarities with small cell lung cancer (SCLC). It is unknown whether SCCB and SCLC share common genetic driver mutations.
January 26, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hossein Jadvar, Xiaoyuan Chen, Weibo Cai, Umar Mahmood
The fundamental foundation for precision medicine is accurate and specific targeting of cancer cells. Advances in the understanding of cancer biology, developments in diagnostic technologies, and expansion of therapeutic options have all contributed to the concept of personalized cancer care. Theranostics is the systematic integration of targeted diagnostics and therapeutics. The theranostic platform includes an imaging component that "sees" the lesions followed by administration of the companion therapy agent that "treats" the same lesions...
February 2018: Radiology
Cornelia Nitipir, Dana Niculae, Cristina Orlov, Maria Alexandra Barbu, Bogdan Popescu, Ana Maria Popa, Anca Mihaela Stoian Pantea, Adina Elena Stanciu, Bianca Galateanu, Octav Ginghina, Georgios Z Papadakis, Boris N Izotov, Demetrios A Spandidos, Aristides M Tsatsakis, Carolina Negrei
Unstable isotopes and their capacity to emit ionizing radiation have been employed in clinical practice not only for diagnostic, but also for therapeutic purposes, with significant contribution in several fields of medicine and primarily in the management of oncologic patients. Their efficacy is associated with their ability to provide the targeted delivery of ionizing radiation for a determined duration. These compounds can be used for curative or palliative treatment, as well as for a diagnostic-therapeutic (theranostic) approach...
December 2017: Oncology Letters
Chee Wai Chua, Nusrat J Epsi, Eva Y Leung, Shouhong Xuan, Ming Lei, Bo I Li, Sarah K Bergren, Hanina Hibshoosh, Antonina Mitrofanova, Michael M Shen
Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor that functions in prostate regeneration. Using genetically-engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation in vivo...
January 15, 2018: ELife
Samson W Fine
Neuroendocrine (NE) differentiation in tumors of the prostate or in the setting of prostate cancer (PCa) is rare. A survey of these lesions is presented, including usual PCa with focal NE marker-positive cells, Paneth cell-like change, prostatic 'carcinoid', high-grade NE carcinoma, as well as other tumors that do not fit neatly into these categories. The most significant clinical and pathologic features, emerging molecular evidence and the importance of differentiating NE tumors involving the prostate from secondary involvement are highlighted...
January 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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