Chikako Funasaka, Yusuke Kanemasa, Akihiko Kageyama, Tatsu Shimoyama, Yasushi Omuro
Standard regimens for extrapulmonary neuroendocrine carcinomas(EPNEC)are not established. Treatment used for small cell lung cancer is also used for EPNECs. Amrubicin(AMR) monotherapy is used as salvage therapy for small cell lung cancer, but its efficacy in EPNEC is not clear. The aim of this study was to estimate the efficacy of AMR monotherapy in EPNEC. We retrospectively investigated patients with EPNEC who received first-line platinum-based chemotherapy between April 2007 and March 2019. The time to treatment failure(TTF)and the efficacy and toxicity was analyzed in the patients who received AMR monotherapy...
August 2020: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Abrar Samiea, Jeff S J Yoon, Christopher J Ong, Amina Zoubeidi, Thomas C Chamberlain, Alice L-F Mui
Interleukin-10 (IL10) is best studied for its inhibitory action on immune cells and ability to suppress an antitumour immune response. But IL10 also exerts direct effects on nonimmune cells such as prostate cancer epithelial cells. Elevated serum levels of IL10 observed in prostate and other cancer patients are associated with poor prognosis. After first-line androgen-deprivation therapy, prostate cancer patients are treated with androgen receptor antagonists such as enzalutamide to inhibit androgen-dependent prostate cancer cell growth...
2020: Prostate Cancer
Swethan Alagaratnam, Marilena Loizidou, Shi- Yu Yang, Barry Fuller, Bala Ramesh
PURPOSE: IGF-1Ec is an isoform of Insulin-like growth factor 1 (IGF-1) and has recently been identified to be overexpressed in cancers including prostate and neuroendocrine tumours. The aim of this paper is to investigate the expression of IGF-1Ec in colorectal cancer and polyps compared to normal colon tissues and its association with recurrent disease using semi-quantitative immunohistochemistry. METHODS: Immunohistochemistry for IGF-1Ec expression was performed for colorectal cancer, colorectal polyps and normal colonic tissues...
August 8, 2020: Journal of Cancer Research and Clinical Oncology
Ritika Tiwari, Nishat Manzar, Bushra Ateeq
Despite the current advances in the treatment for prostate cancer, the patients often develop resistance to the conventional therapeutic interventions. Therapy-induced drug resistance and tumor progression have been associated with cellular plasticity acquired due to reprogramming at the molecular and phenotypic levels. The plasticity of the tumor cells is mainly governed by two factors: cell-intrinsic and cell-extrinsic. The cell-intrinsic factors involve alteration in the genetic or epigenetic regulators, while cell-extrinsic factors include microenvironmental cues and drug-induced selective pressure...
2020: Frontiers in Molecular Biosciences
Helen Saxby, Christos Mikropoulos, Stergios Boussios
Serum biomarkers are molecules produced by normal and abnormal cells. Prostate specific antigen (PSA) is an example of a serum biomarker used widely in the diagnosis and prognostication of prostate cancer. PSA has its limitations as it is organ- but not cancer-specific. The aim of this review is to summarize the current published data on the potential prognostic and predictive biomarkers in metastatic prostate cancer (mPC) that can be used in conjunction with PSA. These biomarkers include microRNAs, androgen receptor variants, bone metabolism, neuroendocrine and metabolite biomarkers, and could guide treatment selection and sequence in an era where we strive to personalized therapy...
July 31, 2020: Diagnostics
Mathilde Cancel, Claire Castellier, Celine Debiais-Delpech, Thomas Charles, François Rozet, Nathalie Rioux-Leclercq, Romain Mathieu, Françoise Beltjens, Luc Cormier, Franck Bruyère, Gaëlle Fromont
OBJECTIVES: To determine whether small cell neuroendocrine prostate cancers (NEPCa) emerging after anti-androgen treatments are different from the rarest cases diagnosed de novo, and to identify effective predictive markers. MATERIAL AND METHODS: The expression of neuroendocrine markers, androgen receptor (AR) and androgen-regulated genes, as well as markers of aggressiveness, were analyzed by immunohistochemistry on a tissue microarray containing samples of 30 sNEPCa, either pure or admixed with conventional PCa, and including 14 cases diagnosed de novo and 16 cases subsequent to prior androgen deprivation...
July 29, 2020: Urologic Oncology
Valerio Farfariello, Natalia Prevarskaya, Dimitra Gkika
In the last three decades, a growing number of studies have implicated ion channels in all essential processes of prostate carcinogenesis, including cell proliferation, apoptosis, migration, and angiogenesis. The changes in the expression of individual ion channels show a specific profile, making these proteins promising clinical biomarkers that may enable better molecular subtyping of the disease and lead to more rapid and accurate clinical decision-making. Expression profiles and channel function are mainly based on the tumoral tissue itself, in this case, the epithelial cancer cell population...
August 1, 2020: Reviews of Physiology, Biochemistry and Pharmacology
Murat Tuncel, Meltem Çağlar Tuncalı, Tuğçe Telli, Mustafa Erman
Prostate cancer (Pca) is the most common cancer and the second leading cause of death among men. Although conventional bone scans and abdominal CT are preferred in most of the guidelines and clinical trials, PET/CT has already started to become the inevitable part of Pca management because of its higher sensitivity and specificity. Radiotracers used for PET imaging show different molecular aspects of the disease process. Although Ga-prostate-specific membrane antigen offers the highest sensitivity and specificity, other PET radiotracers such as F-FDG and Ga-DOTATATE still have a role in patients with prostate-specific membrane antigen-negative diseases such as Pca with neuroendocrine differentiation...
October 2020: Clinical Nuclear Medicine
Jagpreet S Nanda, Wisam N Awadallah, Sarah E Kohrt, Petra Popovics, Justin M M Cates, Janni Mirosevich, Peter E Clark, Giovanna A Giannico, Magdalena M Grabowska
BACKGROUND: Most prostate cancers express androgen receptor (AR), and our previous studies have focused on identifying transcription factors that modify AR function. We have shown that nuclear factor I/B (NFIB) regulates AR activity in androgen-dependent prostate cancer cells in vitro. However, the status of NFIB in prostate cancer was unknown. METHODS: We immunostained a tissue microarray including normal, hyperplastic, prostatic intraepithelial neoplasia, primary prostatic adenocarcinoma, and castration-resistant prostate cancer tissue samples for NFIB, AR, and synaptophysin, a marker of neuroendocrine differentiation...
July 21, 2020: Prostate
Jordan S Shafran, Naser Jafari, Allison N Casey, Balázs Győrffy, Gerald V Denis
BACKGROUND: Androgen deprivation therapies for the hormone-dependent stages of prostate cancer have become so effective that new forms of chemoresistant tumors are emerging in clinical practice, and require new targeted therapies in the metastatic setting. Yet there are important gaps in our understanding of the relevant transcriptional networks driving this process. Progression from localized to metastatic castration resistant prostate cancer (mCRPC) occurs as a result of accumulated resistance mechanisms that develop upon sustained androgen receptor (AR) suppression...
July 21, 2020: Prostate Cancer and Prostatic Diseases
Katharina Kessel, Robert Seifert, Matthias Weckesser, Wolfgang Roll, Verena Humberg, Katrin Schlack, Martin Bögemann, Christof Bernemann, Kambiz Rahbar
Rationale: Lu-177-PSMA-617 radioligand therapy (RLT) is currently under approval for treatment of metastatic castration resistant prostate cancer (mCRPC) patients with late stage disease. However, previous studies demonstrated both heterogeneity of prostate specific membrane antigen (PSMA) expression, as well as response to PSMA treatment among mCRPC patients. Thus, there is an unmet need for identifying predictive parametres prior or under PSMA-RLT treatment. We therefore aimed to correlate several clinical and molecular parameters with response to PSMA treatment in a cohort of mCRPC patients undergoing PSMA RLT followed by a detailed analysis of promising candidates...
2020: Theranostics
F J Valentín Bravo, M A Saornil Álvarez, C García Álvarez, E García Lagarto, R López Castro
A 68 year-old male was referred for assessment of an amelanotic lesion in the right eye (RE) that was associated with a gradual loss of visual acuity (VA), of 2 months onset, as the main symptom. It was noted in his medical history, that 6 years ago, he had prostate cancer treated with prostatectomy, lymphadenectomy, and coadjuvant local radiotherapy (RT). He was asymptomatic until 6 months ago, when a metastasis was discovered in the left femur, which was treated with radiotherapy. There were no findings of interest in the left eye (LE)...
July 16, 2020: Archivos de la Sociedad Española de Oftalmología
Younghun Jung, Jin Koo Kim, Eunsohl Lee, Frank C Cackowski, Ann M Decker, Paul H Krebsbach, Russell S Taichman
BACKGROUND: Epithelial stem cells (ESCs) demonstrate a capacity to maintain normal tissues homeostasis and ESCs with a deregulated behavior can contribute to cancer development. The ability to reprogram normal tissue epithelial cells into prostate or mammary stem-like cells holds great promise to help understand cell of origin and lineage plasticity in prostate and breast cancers in addition to understanding normal gland development. We previously showed that an intracellular chemokine, CXCL12γ induced cancer stem cells and neuroendocrine characteristics in both prostate and breast adenocarcinoma cell lines...
July 13, 2020: Prostate
Harsimar Kaur, Iryna Samarska, Jiayun Lu, Farzana Faisal, Benjamin L Maughan, Sanjana Murali, Kaushal Asrani, Mohamed Alshalalfa, Emmanuel S Antonarakis, Jonathan I Epstein, Corinne E Joshu, Edward M Schaeffer, Juan Miguel Mosquera, Tamara L Lotan
BACKGROUND: Small cell neuroendocrine (NE) carcinomas of the prostate classically lose androgen receptor (AR) expression, may harbor loss of the RB1, TP53, and PTEN tumor suppressor genes, and are associated with a poor prognosis. However usual-type adenocarcinomas may also contain areas of NE differentiation, and in this context the molecular features and biological significance are less certain. METHODS: We examined the molecular phenotype and oncologic outcomes of primary prostate adenocarcinomas with ≥5% NE differentiation (≥5% chromogranin A-positive NE cells in any given tumor spot on tissue microarray) using three independent study sets: a set of tumors with paneth cell-like NE differentiation (n = 26), a retrospective case-cohort of intermediate- and high-risk patients enriched for adverse outcomes (n = 267), and primary tumors from a retrospective series of men with eventual castration-resistant metastatic prostate cancer (CRPC) treated with abiraterone or enzalutamide (n = 55)...
July 10, 2020: Prostate
Jessica M Lovnicki, Yu Gan, Tingting Feng, Yinan Li, Ning Xie, Chia-Hao Ho, Ahn R Lee, Xufeng Chen, Lucia Nappi, Bo Han, Ladan Fazli, Jiaoti Huang, Martin Gleave, Xuesen Dong
Therapy-induced neuroendocrine prostate cancer (t-NEPC) is a highly aggressive subtype of prostate cancer with poor patient survival. Emerging evidence indicates that t-NEPC can develop when prostate adenocarcinoma cells acquire cancer stem-like cell signaling in the presence of androgen receptor inhibition, followed by re-differentiation toward neuroendocrine lineage and subsequent t-NEPC progression. Whether the stem-like signaling is controlled by the core pluripotency stem cell genes (e.g., LIN28 and SOX2) remains unknown...
July 7, 2020: Journal of Clinical Investigation
Daniel H Kwon, Li Zhang, David A Quigley, Adam Foye, William S Chen, Christopher K Wong, Felix Y Feng, Adina Bailey, Jiaoti Huang, Joshua M Stuart, Verena Friedl, Alana S Weinstein, Tomasz M Beer, Joshi J Alumkal, Matthew Rettig, Martin Gleave, Primo N Lara, George V Thomas, Patricia Li, Austin Lui, Eric J Small, Rahul R Aggarwal
OBJECTIVES: The net oncogenic effect of β2-adrenergic receptor ADRB2, whose downstream elements induce neuroendocrine differentiation and whose expression is regulated by EZH2, is unclear. ADRB2 expression and associated clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) are unknown. METHODS AND MATERIALS: This was a retrospective analysis of a multi-center, prospectively enrolled cohort of mCRPC patients. Metastatic biopsies were obtained at progression, and specimens underwent laser capture microdissection and RNA-seq...
July 2, 2020: Urologic Oncology
Zhi Wang, Laura E Pascal, Uma R Chandran, Srilakshmi Chaparala, Shidong Lv, Hui Ding, Lin Qi, Zhou Wang
Background: Elongation factor for RNA polymerase II 2 (ELL2) was reported as a putative tumor suppressor in the prostate. ELL2 is frequently down-regulated in prostatic adenocarcinoma specimens, and loss of ELL2 induced murine prostatic intraepithelial neoplasia and enhanced AR-positive prostate cancer cell proliferation. However, the ELL2 gene appears to be amplified in AR-negative neuroendocrine prostate tumors, suggesting a potential oncogenic role for ELL2 in AR-negative prostate cancer cells...
2020: Cancer Management and Research
Zuzana Kahounová, Ján Remšík, Radek Fedr, Jan Bouchal, Alena Mičková, Eva Slabáková, Lucia Binó, Aleš Hampl, Karel Souček
Deciphering the properties of adult stem cells is crucial for understanding of their role in healthy tissue and in cancer progression as well. Both stem cells and cancer stem cells have shown association with epithelial-to-mesenchymal transition (EMT) in various tissue types. Aiming to investigate the epithelial and mesenchymal phenotypic traits in adult mouse prostate, we sorted subpopulations of basal prostate stem cells (mPSCs) and assessed the expression levels of EMT regulators and markers with custom-designed gene expression array...
May 12, 2020: Stem Cell Research
Shervin Tabrizi, Mohammed Alshalalfa, Brandon A Mahal, Elai Davicioni, Yang Liu, Kent W Mouw, Felix Feng, Paul L Nguyen, Vinayak Muralidhar
INTRODUCTION: Recent work using prostate cancer mouse models implicated doublecortin (DCX)-expressing neural progenitor cells in prostate adenocarcinoma, reporting a strong association between DCX expression and histologic grade and clinical outcome. We sought to evaluate the relationship between DCX expression and these variables in human prostate cancer. METHODS AND MATERIALS: DCX expression was measured in transcriptome-wide microarray data from 18,501 patients with localized prostate cancer and 290 patients with metastatic castration-resistant prostate cancer (mCRPC), and compared across disease states, histologic grades, and clinical outcomes...
June 22, 2020: International Journal of Radiation Oncology, Biology, Physics
Ranulf Crooke, Christine Haseler, Tobias Haseler, Jack Collins, Andrew Crockett
Non-communicable diseases are a leading cause of death and levels are rising. Lifestyle changes, including physical activity, have benefits in all-cause mortality, cardiovascular and metabolic disease, respiratory conditions and cognitive and mental health. In some cancers, particularly colon, prostate and breast, physical activity improves quality of life and outcomes before, during and after treatment. Sedentary time is an independent risk factor with adverse effects in hospitalised patients. Mechanisms include anti-inflammatory effects and augmentation of physiological and neuroendocrine responses to stressors...
June 2020: Journal of the Royal College of Physicians of Edinburgh
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