Fabio Quaglia, Shiv Ram Krishn, George G Daaboul, Srawasti Sarker, Raffaella Pippa, Josep Domingo-Domenech, Gaurav Kumar, Paolo Fortina, Peter McCue, William K Kelly, Himisha Beltran, Qin Liu, Lucia R Languino
The ability of small extracellular vesicles (sEVs) to reprogram cancer cells is well established. However, the specific sEV components able to mediate aberrant effects in cancer cells have not been characterized. Integrins are major players in mediating sEV functions. We have previously reported that the αVβ3 integrin is detected in sEVs of prostate cancer (PrCa) cells and transferred into recipient cells. Here, we investigate whether sEVs from αVβ3-expressing cells affect tumour growth differently than sEVs from control cells that do not express αVβ3...
May 24, 2020: Journal of Extracellular Vesicles
Siroos Mirzaei, Fairoz Mohammed, Shahin Zandieh
The successful use of theranostic twins in neuroendocrine tumors (NET) was the pioneering approach to radionuclide therapy in other tumor types. 64Cu/18F PSMA for molecular imaging with PET-CT and peptide radioligand therapy (PRLT) with 177Lu labeled PSMA inhibitors are the next theranostic twins in nuclear medicine. 68Ga/ 64Cu/18F PSMA PET-CT detects metastatic prostate cancer with high diagnostic sensitivity and specificity and can be used to select patients for PRLT and evaluate therapy response. Radionuclide therapy with 177Lu-PSMA inhibitors has been shown to be effective in the treatment of metastatic CRPC...
September 8, 2020: Current Radiopharmaceuticals
Ruidong Chen, Xin Liang, Mollianne M Murray, Ellen Karasik, Jenny J Han, Ming Zhu, Barbara A Foster, Daniel E Frigo, Guocan Wang
BACKGROUND: The TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model remains one of the most widely used transgenic mouse models of prostate cancer. This is due to its ability to recapitulate with ~100% penetrance multiple aspects of the human disease such as prostatic intraepithelial neoplasia lesions, invasive carcinoma, progression to castration-resistant prostate cancer including aggressive neuroendocrine prostate cancer and metastasis. Despite its popularity, the use of TRAMP mice is limited/slowed by the inability to distinguish the zygosity of the TRAMP transgene...
September 7, 2020: Prostate Cancer and Prostatic Diseases
Madonna R Peter, Misha Bilenky, Ruth Isserlin, Gary D Bader, Shu Yi Shen, Daniel D De Carvalho, Aaron R Hansen, Pingzhao Hu, Neil E Fleshner, Anthony M Joshua, Martin Hirst, Bharati Bapat
Aim: We examined methylation changes in cell-free DNA (cfDNA) in metastatic castration-resistant prostate cancer (mCRPC) during treatment. Patients & methods: Genome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. Results: Alterations in methylation states of genes previously implicated in prostate cancer progression were observed and patients that maintained methylation changes throughout therapy tended to have a longer time to clinical progression...
September 1, 2020: Epigenomics
S Koukouraki, N Kapsoritakis, O Bourogianni
The global COVID-19 health and economic crisis has forced people to adopt challenging rules of social distancing and self-isolation. Health care staff has been advised to change working routines to keep themselves and their patients safe. Radionuclide therapy has had an increasing role in clinical practice. Most therapeutic radionuclide procedures have applications in oncology. Cancer patients are an especially fragile and vulnerable population with higher risk due to co morbidities and immunosuppression. COVID-19 is another risk that must be considered in treatment planning...
May 2020: Hellenic Journal of Nuclear Medicine
S Koukouraki, N Kapsoritakis, O Bourogianni
The global COVID-19 health and economic crisis has forced people to adopt challenging rules of social distancing and self-isolation. Health care staff has been advised to change working routines to keep themselves and their patients safe. Radionuclide therapy has had an increasing role in clinical practice. Most therapeutic radionuclide procedures have applications in oncology. Cancer patients are an especially fragile and vulnerable population with higher risk due to co morbidities and immunosuppression. COVID-19 is another risk that must be considered in treatment planning...
May 2020: Hellenic Journal of Nuclear Medicine
F Mosele, J Remon, J Mateo, C B Westphalen, F Barlesi, M P Lolkema, N Normanno, A Scarpa, M Robson, F Meric-Bernstam, N Wagle, A Stenzinger, J Bonastre, A Bayle, S Michiels, I Bièche, E Rouleau, S Jezdic, J-Y Douillard, J Reis-Filho, R Dienstmann, F André
Next-generation sequencing (NGS) allows sequencing a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about their use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous NSCLC, prostate cancers, ovarian cancers and cholangiocarcinoma...
July 28, 2020: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Yinhang Wu, Yongsheng Gao, Xue Dou, Jinbo Yue
A 63-year-old man with a significantly high prostate-specific antigen level was diagnosed via pathology to have advanced prostate adenocarcinoma due to multiple lung metastases. He was then treated with androgen deprivation therapy (ADT) comprising bicalutamide and goserelin. Only after 6 months of stable disease, the cancer progressed and the drug was changed to abiraterone; however, no significant therapeutic effect was observed and the disease was considered as castration-resistant prostate cancer. The histopathologic analysis of the biopsied metastatic lymph node confirmed small-cell neuroendocrine carcinoma, and genetic testing revealed BRCA1 germ-line mutation...
2020: OncoTargets and Therapy
Gang Li, Mao-Lin Tian, Yun-Tao Bing, Chun-Hui Yuan, Dian-Rong Xiu
OBJECTIVE: The aim of the study was to investigate the impact of a previous nonpancreatic malignancy on the survival outcomes in patients with a stage IV pancreatic neuroendocrine tumor (PanNET). METHODS: The Surveillance, Epidemiology, and End Results database was reviewed, and patients diagnosed with a stage IV PanNET between 2004 and 2015 were selected. Patients were divided into 2 groups according to the presence or absence of a previous nonpancreatic malignancy...
September 2020: Pancreas
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...
July 17, 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
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