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neuroendocrine prostate cancer

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https://www.readbyqxmd.com/read/28734980/histone-demethylase-phf8-regulates-hypoxia-signaling-through-hif1%C3%AE-and-h3k4me3
#1
Peterson Kariuki Maina, Peng Shao, Xiongfei Jia, Qi Liu, Shaikamjad Umesalma, Maximo Marin, Donald Long, Samantha Concepción-Román, Hank Heng Qi
Hypoxia through transcription factor HIF1α plays a critical role in cancer development. In prostate cancer, HIF1α interplays with androgen receptor (AR) to contribute to the progression of this disease to its lethal form-castration-resistant prostate cancer (CRPC). Hypoxia upregulates several epigenetic factors including histone demethylase KDM3A which is a critical co-factor of HIF1α. However, how histone demethylases regulate hypoxia signaling is not fully understood. Here, we report that histone demethylase PHF8 plays an essential role in hypoxia signaling...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28684411/the-path-of-most-resistance-transdifferentiation-underlies-exceptional-nonresponses-to-androgen-receptor-pathway-inhibition-in-prostate-cancer
#2
Seema Sinha, Peter S Nelson
In this issue of Cancer Discovery, Zou and colleagues describe a mechanism involving cellular transdifferentiation that promotes exceptional resistance to antiandrogen therapy in prostate cancer. A background of coinactivation of Trp53 and Pten increased the frequency of the transdifferentiated neuroendocrine phenotype. These findings have implications for developing approaches to repress cellular plasticity and overcome treatment resistance. Cancer Discov; 7(7); 673-4. ©2017 AACRSee related article by Zou et al...
July 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28678785/dependency-of-a-therapy-resistant-state-of-cancer-cells-on-a-lipid-peroxidase-pathway
#3
Vasanthi S Viswanathan, Matthew J Ryan, Harshil D Dhruv, Shubhroz Gill, Ossia M Eichhoff, Brinton Seashore-Ludlow, Samuel D Kaffenberger, John K Eaton, Kenichi Shimada, Andrew J Aguirre, Srinivas R Viswanathan, Shrikanta Chattopadhyay, Pablo Tamayo, Wan Seok Yang, Matthew G Rees, Sixun Chen, Zarko V Boskovic, Sarah Javaid, Cherrie Huang, Xiaoyun Wu, Yuen-Yi Tseng, Elisabeth M Roider, Dong Gao, James M Cleary, Brian M Wolpin, Jill P Mesirov, Daniel A Haber, Jeffrey A Engelman, Jesse S Boehm, Joanne D Kotz, Cindy S Hon, Yu Chen, William C Hahn, Mitchell P Levesque, John G Doench, Michael E Berens, Alykhan F Shamji, Paul A Clemons, Brent R Stockwell, Stuart L Schreiber
Plasticity of the cell state has been proposed to drive resistance to multiple classes of cancer therapies, thereby limiting their effectiveness. A high-mesenchymal cell state observed in human tumours and cancer cell lines has been associated with resistance to multiple treatment modalities across diverse cancer lineages, but the mechanistic underpinning for this state has remained incompletely understood. Here we molecularly characterize this therapy-resistant high-mesenchymal cell state in human cancer cell lines and organoids and show that it depends on a druggable lipid-peroxidase pathway that protects against ferroptosis, a non-apoptotic form of cell death induced by the build-up of toxic lipid peroxides...
July 27, 2017: Nature
https://www.readbyqxmd.com/read/28676692/copy-number-alteration-of-neuropeptides-and-receptors-in-multiple-cancers
#4
Min Zhao, Tianfang Wang, Qi Liu, Scott Cummins
Neuropeptides are peptide hormones used as chemical signals by the neuroendocrine system to communicate between cells. Recently, neuropeptides have been recognized for their ability to act as potent cellular growth factors on many cell types, including cancer cells. However, the molecular mechanism for how this occurs is unknown. To clarify the relationship between neuropeptides and cancer, we manually curated a total of 127 human neuropeptide genes by integrating information from the literature, homologous sequences, and database searches...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673439/-neuroendocrine-prostate-cancer-natural-history-molecular-features-therapeutic-management-and-future-directions
#5
Luca Campedel, Myriam Kossaï, Paul Blanc-Durand, Morgan Rouprêt, Thomas Seisen, Eva Compérat, Jean-Philippe Spano, Gabriel Malouf
Neuroendocrine prostate cancer is a rare malignancy with a an adverse prognostic. Histologically, It can be pure (small cells or large cells neuroendocrine carcinoma) or mixed with a adenocarcinoma component. Rarely diagnosed de novo, neuroendocrine prostate cancer is generally associated with advanced stage disease resistant to castration. As such, this histological subtype could represent an aggressive evolution of prostatic adenocarcinoma, through the epithelio-neuroendocrine transdifferentiation mechanism (phenomenon of lineage plasticity)...
June 30, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28642484/mir-100-5p-inhibition-induces-apoptosis-in-dormant-prostate-cancer-cells-and-prevents-the-emergence-of-castration-resistant-prostate-cancer
#6
Noushin Nabavi, Nur Ridzwan Nur Saidy, Erik Venalainen, Anne Haegert, Abhijit Parolia, Hui Xue, Yuwei Wang, Rebecca Wu, Xin Dong, Colin Collins, Francesco Crea, Yuzhuo Wang
Carcinoma of the prostate is the most common cancer in men. Treatment of aggressive prostate cancer involves a regiment of radical prostectomy, radiation therapy, chemotherapy and hormonal therapy. Despite significant improvements in the last decade, the treatment of prostate cancer remains unsatisfactory, because a significant fraction of prostate cancers develop resistance to multiple treatments and become incurable. This prompts an urgent need to investigate the molecular mechanisms underlying the evolution of therapy-induced resistance of prostate cancer either in the form of castration-resistant prostate cancer (CRPC) or transdifferentiated neuroendocrine prostate cancer (NEPC)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638669/external-beam-radiation-and-brachytherapy-for-prostate-cancer-is-it-a-possible-trigger-of-large-cell-neuroendocrine-carcinoma-of-the-urinary-bladder
#7
Ali Zakaria, Bayan Al Share, Sri Kollepara, Cynthia Vakhariya
Neuroendocrine tumors commonly involve the respiratory and gastrointestinal systems. Primary genitourinary neuroendocrine tumors are rare, accounting for less than 1% of all bladder carcinomas. Four histopathologic subtypes have been described. Among those, large cell neuroendocrine carcinoma (LCNEC) is the least common, is more aggressive, and generally presents in an advanced stage with poor prognosis compared to transitional cell bladder carcinoma. There is no standardized treatment regimen because of the rarity of the disease...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28631533/u-can-a-prospective-longitudinal-collection-of-biomaterials-and-clinical-information-from-adult-cancer-patients-in-sweden
#8
Bengt Glimelius, Beatrice Melin, Gunilla Enblad, Irina Alafuzoff, Anna Beskow, Håkan Ahlström, Anna Bill-Axelson, Helgi Birgisson, Ove Björ, Per-Henrik Edqvist, Tony Hansson, Thomas Helleday, Per Hellman, Kerstin Henriksson, Göran Hesselager, Magnus Hultdin, Michael Häggman, Martin Höglund, Håkan Jonsson, Chatarina Larsson, Henrik Lindman, Ingrid Ljuslinder, Stephanie Mindus, Peter Nygren, Fredrik Pontén, Katrine Riklund, Richard Rosenquist, Fredrik Sandin, Jochen M Schwenk, Roger Stenling, Karin Stålberg, Peter Stålberg, Christer Sundström, Camilla Thellenberg Karlsson, Bengt Westermark, Anders Bergh, Lena Claesson-Welsh, Richard Palmqvist, Tobias Sjöblom
BACKGROUND: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population...
June 20, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28623637/pure-small-cell-recurrent-prostate-cancer-developing-syndrome-of-inappropriate-antidiuretic-hormone-secretion
#9
Giorgia Peverelli, Paolo Grassi
PURPOSE: Pure small cell neuroendocrine carcinoma of the prostate is a rare entity characterized by a poor prognosis due to early metastatic spread as well as resistance to treatment. Considering its increasing occurrence, clinicians should be aware of its aggressive behavior, the relevance of an early diagnosis, and proper management. METHODS: A 71-year-old man treated with brachytherapy for localized low-risk prostate cancer developed widespread disease 7 years later with a prostate-specific antigen-negative neuroendocrine small cell phenotype...
June 14, 2017: Tumori
https://www.readbyqxmd.com/read/28621319/foxa2-is-a-sensitive-and-specific-marker-for-small-cell-neuroendocrine-carcinoma-of-the-prostate
#10
Jung Wook Park, John K Lee, Owen N Witte, Jiaoti Huang
The median survival of patients with small cell neuroendocrine carcinoma is significantly shorter than that of patients with classic acinar-type adenocarcinoma. Small cell neuroendocrine carcinoma is traditionally diagnosed based on histologic features because expression of current immunohistochemical markers is inconsistent. This is a challenging diagnosis even for expert pathologists and particularly so for pathologists who do not specialize in prostate cancer. New biomarkers to aid in the diagnosis of small cell neuroendocrine carcinoma are therefore urgently needed...
June 16, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28620903/emerging-categories-of-disease-in-advanced-prostate-cancer-and-their-therapeutic-implications
#11
REVIEW
Rahul R Aggarwal, Felix Y Feng, Eric J Small
The treatment of advanced prostate cancer has changed significantly in the last decade, as a result of the introduction of multiple new systemic therapies that have had a positive impact on treatment outcomes. The increasing number of therapies, along with new insights into the biological underpinnings of prostate cancer, have led to a growing appreciation for the heterogeneity of the disease and an awareness of emerging subcategories that have direct therapeutic implications for the practicing clinician. In the metastatic hormone-naive setting, the extent of metastatic disease visible on scans can serve as a useful measure to guide treatment decisions; the addition of docetaxel chemotherapy to hormonal therapy has significant benefit in patients whose scans show more extensive disease...
June 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28604629/androgen-receptor-dependent-and-independent-mechanisms-involved-in-prostate-cancer-therapy-resistance
#12
REVIEW
Daniel J Crona, Young E Whang
Despite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamide, has improved survival of metastatic CRPC (mCRPC) patients. However, a significant proportion of patients presents with primary resistance to these agents, and in the remainder, secondary resistance will invariably develop, which makes mCRPC the lethal form of the disease...
June 12, 2017: Cancers
https://www.readbyqxmd.com/read/28602980/suppression-of-akt1-%C3%AE-catenin-pathway-in-advanced-prostate-cancer-promotes-tgf%C3%AE-1-mediated-epithelial-to-mesenchymal-transition-and-metastasis
#13
Fei Gao, Abdulrahman Alwhaibi, Harika Sabbineni, Arti Verma, Wael Eldahshan, Payaningal R Somanath
Akt1 is essential for the oncogenic transformation and tumor growth in various cancers. However, the precise role of Akt1 in advanced cancers is conflicting. Using a neuroendocrine TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, we first show that the genetic ablation or pharmacological inhibition of Akt1 in mice blunts oncogenic transformation and prostate cancer (PCa) growth. Intriguingly, triciribine (TCBN)-mediated Akt inhibition in 25-week old, tumor-bearing TRAMP mice and Akt1 gene silencing in aggressive PCa cells enhanced epithelial to mesenchymal transition (EMT) and promoted metastasis to the lungs...
June 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28561699/personalizing-therapy-for-metastatic-prostate-cancer-the-role-of-solid-and-liquid-tumor-biopsies
#14
Terence W Friedlander, Colin C Pritchard, Himisha Beltran
Although biopsies of metastatic prostate cancer are rarely undertaken in the clinical setting, there is increasing interest in developing personalized approaches to therapy by taking into account the genetic and phenotypic changes in an individual tumor. Indeed, analysis of metastatic prostate tumors can predict sensitivity to agents that inhibit DNA repair and resistance to novel hormonal agents, such as abiraterone and enzalutamide, and identify phenotypic changes, such as neuroendocrine differentiation, that have important clinical implications...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28533641/image-findings-of-a-rare-case-of-neuroendocrine-tumor-metastatic-to-orbital-extraocular-muscle-in-gallium-68-dotanoc-positron-emission-tomography-computed-tomography-and-therapy-with-lutetium-177-dotatate
#15
Koramadai Karuppusamy Kamaleshwaran, Jephy Joseph, Indra Upadhya, Ajit Sugunan Shinto
Metastatic tumor is one of several etiologies of space-occupying masses in the orbit that accounts for 1-13% of all orbital masses. In the adult patient population, breast cancer is the most common tumor to metastasize to the orbit, followed by metastasis from the lung, prostate, and gastrointestinal tract. Carcinoid tumors are rare neuroendocrine neoplasms derived from enterochromaffin cells, which are found primarily in the gastrointestinal tract and bronchial tree. Liver metastases are the classic presentation of distant disease...
April 2017: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/28522124/-prostate-cancer-histoseminar-update-of-the-2016-who-classification%C3%A2-%C3%A2-case-n-o-6-castration-resistant-prostate-cancer-with-partial-neuroendocrin-differenciation
#16
https://www.readbyqxmd.com/read/28506524/contemporary-incidence-and-cancer-control-outcomes-of-primary-neuroendocrine-prostate-cancer-a-seer-database-analysis
#17
Emanuele Zaffuto, Raisa Pompe, Marc Zanaty, Helen Davis Bondarenko, Sami-Ramzi Leyh-Bannurah, Marco Moschini, Paolo Dell'Oglio, Giorgio Gandaglia, Nicola Fossati, Armando Stabile, Kevin C Zorn, Francesco Montorsi, Alberto Briganti, Pierre I Karakiewicz
INTRODUCTION: Neuroendocrine carcinoma of the prostate (NEPC) is a rare entity. We aimed at providing contemporary data on incidence and survival figures of de-novo NEPC. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database, we identified 309 individuals with de-novo NEPC diagnosed between 2004 and 2013. We evaluated age-adjusted incidence rates over the study. Kaplan-Meier analyses assessed overall survival (OS) after stratification according to histologic subtype, metastatic status, and treatment...
April 13, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28489892/exposure-to-maternal-obesogenic-diet-worsens-some-but-not-all-pre-cancer-phenotypes-in-a-murine-genetic-model-of-prostate-cancer
#18
Theresa Okeyo-Owuor, Emily Benesh, Scott Bibbey, Michaela Reid, Jacques Halabi, Siobhan Sutcliffe, Kelle Moley
Prostate cancer research has been predominantly focused on adult exposures and risk factors. However, because the prostate develops during gestation and early life, exposure to external factors, such as obesity, during development could affect the prostate cancer progression in adults. Our previous work demonstrated that exposure to a high fat/high sugar (HF/HS) diet during gestation and until weaning stimulated prostate hyperplasia and altered the Pten/Akt pathway in adult mice fed a normal diet after weaning...
2017: PloS One
https://www.readbyqxmd.com/read/28482433/-clinical-characteristics-of-13-neuroendocrine-prostate-cancer-patients
#19
W H Zhang, T G Si, X L Yang, B Yang, C F Liu, H P Yu, W G Xing, Z Guo
Objective: To explore the radiological, pathological features and clinical characteristics of neuroendocrine prostate cancer patients(NEPC). Methods: The clinical characteristics and pathology data of 13 neuroendocrine prostate cancer patients treated in the Affiliated Hospital of Tianjin Medical University from January 2004 to January 2015 were analyzed retrospectively. Results: Of all 13 patients, three cases were primally diagnosed small cell cancer, and 10 cases were translated to neuroendocrine type from adenocarcinoma after endocrine therapy...
May 9, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28473655/lipid-catabolism-inhibition-sensitizes-prostate-cancer-cells-to-antiandrogen-blockade
#20
Thomas W Flaig, Maren Salzmann-Sullivan, Lih-Jen Su, Zhiyong Zhang, Molishree Joshi, Miguel A Gijón, Jihye Kim, John J Arcaroli, Adrie Van Bokhoven, M Scott Lucia, Francisco G La Rosa, Isabel R Schlaepfer
Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. We have found that deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid oxidation to fuel PCa growth. Using immunohistochemistry we have found that the CPT1A isoform is abundant in PCa compared to benign tissue (n=39, p<0...
April 21, 2017: Oncotarget
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