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Circulating tumor cells in prostate cancer

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https://www.readbyqxmd.com/read/28295408/circulating-tumor-cells-as-a-marker-for-progression-free-survival-in-metastatic-castration-na%C3%A3-ve-prostate-cancer
#1
Andreas Josefsson, Anna Linder, Despina Flondell Site, Giacomo Canesin, Anna Stiehm, Aseem Anand, Anders Bjartell, Jan-Erik Damber, Karin Welén
BACKGROUND: Analysis of circulating tumor cells (CTC) is a promising prognostic marker in castration-resistant prostate cancer (CRPC). The aim of this study was to investigate CTC detection and phenotyping as prognostic biomarkers for response to primary androgen deprivation therapy (ADT) of metastatic prostate cancer (PC). METHODS: PC patients presenting with a prostate specific antigen (PSA) >80 ng/ml and/or metastatic disease, intended for ADT were enrolled in the study...
March 10, 2017: Prostate
https://www.readbyqxmd.com/read/28292326/immune-mediators-in-the-tumor-microenvironment-of-prostate-cancer
#2
REVIEW
Jinlu Dai, Yi Lu, Hernan Roca, Jill M Keller, Jian Zhang, Laurie K McCauley, Evan T Keller
Prostate cancer tissue is composed of both cancer cells and host cells. The milieu of host components that compose the tumor is termed the tumor microenvironment (TME). Host cells can be those derived from the tissue in which the tumor originates (e.g., fibroblasts and endothelial cells) or those recruited, through chemotactic or other factors, to the tumor (e.g., circulating immune cells). Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor...
March 14, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28267564/development-of-17%C3%AE-hydroxysteroid-dehydrogenase-type-3-as-a-target-in-hormone-dependent-prostate-cancer-therapy
#3
REVIEW
Xiaohui Ning, Yan Yang, Hong Deng, Qihao Zhang, Yadong Huang, Zhijian Su, Yongmei Fu, Qi Xiang, Shu Zhang
17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is expressed almost exclusively in the testes and specifically converts the weak androgenic androstenedione to active testosterone (T) in the presence of NADPH. Additionally, studies have demonstrated that 17β-HSD3 is over-expressed in hormone-dependent prostate cancer. T, which interacts with the androgen receptor (AR), eventually stimulates the growth of prostate cancer cells. Defects in T synthesis or action impair the development of the male phenotype during embryogenesis and cause the autosomal recessive disorder male pseudohermaphroditism...
March 4, 2017: Steroids
https://www.readbyqxmd.com/read/28259476/treatment-outcomes-and-tumor-loss-of-heterozygosity-in-germline-dna-repair-deficient-prostate-cancer
#4
Matti Annala, Werner J Struss, Evan W Warner, Kevin Beja, Gillian Vandekerkhove, Amanda Wong, Daniel Khalaf, Irma-Liisa Seppälä, Alan So, Gregory Lo, Rahul Aggarwal, Eric J Small, Matti Nykter, Martin E Gleave, Kim N Chi, Alexander W Wyatt
BACKGROUND: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to androgen receptor (AR)-directed therapy. OBJECTIVE: To determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies and to establish whether biallelic DNA repair gene loss is detectable in matched circulating tumor DNA (ctDNA)...
March 1, 2017: European Urology
https://www.readbyqxmd.com/read/28240870/a-multifunctional-envelope-type-sirna-delivery-nanoparticle-platform-for-prostate-cancer-therapy
#5
Xiaoding Xu, Jun Wu, Yanlan Liu, Phei Er Saw, Wei Tao, Mikyung Yu, Harshal R Zope, Michelle Si, Amanda Victorious, Jonathan Rasmussen, Dana Ayyash, Omid C Farokhzad, Jinjun Shi
With the capability of specific silencing of target gene expression, RNA interference (RNAi) technology is emerging as a promising therapeutic modality for the treatment of cancer and other diseases. One key challenge for the clinical applications of RNAi is the safe and effective delivery of RNAi agents such as small interfering RNA (siRNA) to a particular non-liver diseased tissue (e.g., tumor) and cell type with sufficient cytosolic transport. In this work, we proposed a multifunctional envelope-type nanoparticle (NP) platform for prostate cancer (PCa)-specific in vivo siRNA delivery...
February 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28238187/circulating-tumor-cells-clinical-validity-and-utility
#6
REVIEW
Luc Cabel, Charlotte Proudhon, Hugo Gortais, Delphine Loirat, Florence Coussy, Jean-Yves Pierga, François-Clément Bidard
Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs...
February 25, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28228136/circulating-tumor-cells-capture-disease-evolution-in-advanced-prostate-cancer
#7
Justin Lack, Marc Gillard, Maggie Cam, Gladell P Paner, David J VanderWeele
BACKGROUND: Genetic analysis of advanced cancer is limited by availability of representative tissue. Biopsies of prostate cancer metastasized to bone are invasive with low quantity of tumor tissue. The prostate cancer genome is dynamic, however, with temporal heterogeneity requiring repeated evaluation as the disease evolves. Circulating tumor cells (CTCs) offer an alternative, "liquid biopsy", though single CTC sequencing efforts are laborious with high failure rates. METHODS: We performed exome sequencing of matched treatment-naïve tumor tissue, castrate resistant tumor tissue, and pooled CTC samples, and compared mutations identified in each...
February 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28212371/circulating-tumor-cells-in-prostate-cancer-beyond-enumeration
#8
Jie-Fu Chen, Yi-Tsung Lu, Shirley Cheng, Hsian-Rong Tseng, Robert A Figlin, Edwin M Posadas
Circulating tumor cells (CTCs) are a population of rare cancer cells that have detached from the primary tumor and/or metastatic lesions and entered the peripheral circulation. Enumeration of CTCs has demonstrated value as a prognostic biomarker, and newer studies have pointed to information beyond enumeration that is of critical importance in prostate cancer. Technologic advances that permit examination of the morphology, function, and molecular content of CTCs have made it possible to measure these factors as part of liquid biopsy...
January 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28202510/myc-mediates-large-oncosome-induced-fibroblast-reprogramming-in-prostate-cancer
#9
Valentina R Minciacchi, Cristiana Spinelli, Mariana Reis-Sobreiro, Lorenzo Cavallini, Sungyong You, Mandana Zandian, Xiaohong Li, Paola Chiarugi, Rosalyn M Adam, Edwin M Posadas, Giuseppe Viglietto, Michael R Freeman, Emanuele Cocucci, Neil A Bhowmick, Dolores Di Vizio
Communication between cancer cells and the tumor microenvironment results in the modulation of complex signaling networks that facilitate tumor progression. Here we describe a new mechanism of intercellular communication originating from large oncosomes (LO), which are cancer cell-derived, atypically large (1-10 μm) extracellular vesicles (EV). We demonstrate that, in the context of prostate cancer, LO harbor sustained AKT1 kinase activity, nominating them as active signaling platforms. Active AKT1 was detected in circulating EV from the plasma of metastatic prostate cancer patients and was LO specific...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202223/filtration-based-enrichment-of-circulating-tumor-cells-from-all-prostate-cancer-risk-groups
#10
Julius Adebayo Awe, Jeff Saranchuk, Darrel Drachenberg, Sabine Mai
OBJECTIVE: To combine circulating tumor cell (CTC) isolation by filtration and immunohistochemistry to investigate the presence of CTCs in low, intermediate, and high-risk prostate cancer (PCa). CTCs isolated from these risk groups stained positive for both cytokeratin and androgen receptors, but negative for CD45. PATIENTS AND METHODS: Blood samples from 41 biopsy confirmed patients with PCa at different clinical stages such as low, intermediate, and high risk were analyzed...
February 12, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28183253/optimal-management-of-prostate-cancer-based-on-its-natural-clinical-history
#11
Gaetano Facchini, Francesco Perri, Gabriella Misso, Carmine D Aniello, Giuseppina Della Vittoria Scarpati, Sabrina Rossetti, Chiara Della Pepa, Salvatore Pisconti, Gerhard Unteregger, Alessia Cossu, Michele Caraglia, Massimiliano Berretta, Carla Cavaliere
Prostate cancer is the most common malignancy in males and, despite a marked improvement in diagnostic techniques, a not small percentage of prostate tumours is still diagnosed in advanced stage. It is now clear that prostate cancer passes through distinct phases during its natural history, starting from an initial phase, in which the disease has a locoregional extent, until a very late phase when it becomes refractory to hormone therapy. It is important to distinguish between local disease, in which tumor may be considered localized in the gland and a systemic disease characterized by high tumor burden and/or dissemination of circulating tumour cells...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28178640/a-phase-i-ii-study-of-the-investigational-drug-alisertib-in-combination-with-abiraterone-and-prednisone-for-patients-with-metastatic-castration-resistant-prostate-cancer-progressing-on-abiraterone
#12
Jianqing Lin, Sheel A Patel, Ashwin R Sama, Jean H Hoffman-Censits, Brooke Kennedy, Deborah Kilpatrick, Zhong Ye, Hushan Yang, Zhaomei Mu, Benjamin Leiby, Nancy Lewis, Massimo Cristofanilli, William Kevin Kelly
LESSONS LEARNED: Patients with metastatic castration-resistant prostate cancer did not tolerate the combination of alisertib with abiraterone and prednisone.There was no clear signal indicating that adding alisertib might be beneficial for those patients progressing on abiraterone. BACKGROUND: We hypothesized that Aurora A kinase (AK) contributes to castrate resistance in prostate cancer (PCa) and that inhibiting AK with alisertib can resensitize PCa cells to androgen receptor (AR) inhibitor abiraterone...
November 2016: Oncologist
https://www.readbyqxmd.com/read/28166262/l1-retrotransposon-expression-in-circulating-tumor-cells
#13
Ioannis Papasotiriou, Katerina Pantopikou, Panagiotis Apostolou
Long interspersed nuclear element 1 (LINE-1 or L1) belongs to the non-long terminal repeat (non-LTR) retrotransposon family, which has been implicated in carcinogenesis and disease progression. Circulating tumor cells (CTCs) are also known to be involved in cancer progression. The present study aimed to compare the L1 expression between circulating tumor cells and non-cancerous samples. Blood samples were collected from 10 healthy individuals and 22 patients with different types of cancer. The whole blood cells were isolated using enrichment protocols and the DNA and RNA were extracted...
2017: PloS One
https://www.readbyqxmd.com/read/28153390/nucleolin-staining-may-aid-in-the-identification-of-circulating-prostate-cancer-cells
#14
Heather J Chalfin, James E Verdone, Emma E van der Toom, Stephanie Glavaris, Michael A Gorin, Kenneth J Pienta
INTRODUCTION: Circulating tumor cells (CTCs) have great potential as circulating biomarkers for solid malignancies. Currently available assays for CTC detection rely on epithelial markers with somewhat limited sensitivity and specificity. We found that the staining pattern of nucleolin, a common nucleolar protein in proliferative cells, separates CTCs from white blood cells (WBCs) in men with metastatic prostate cancer. PATIENTS AND METHODS: Whole peripheral blood from 3 men with metastatic prostate cancer was processed with the AccuCyte CTC system (RareCyte, Seattle, WA)...
January 4, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28116598/enterolactone-glucuronide-and-%C3%AE-glucuronidase-in-antibody-directed-enzyme-prodrug-therapy-for-targeted-prostate-cancer-cell-treatment
#15
Yunyun Di, Shaoping Ji, Philipp Wolf, Ed S Krol, Jane Alcorn
Evidence from preclinical and animal studies demonstrated an anticancer effect of flaxseed lignans, particularly enterolactone (ENL), against prostate cancer. However, extensive first-pass metabolism following oral lignan consumption results in their systemic availability primarily as glucuronic acid conjugates (ENL-Gluc) and their modest in vivo effects. To overcome the unfavorable pharmacokinetics and improve their effectiveness in prostate cancer, antibody-directed enzyme prodrug therapy (ADEPT) might offer a novel strategy to allow for restricted activation of ENL from circulating ENL-Gluc within the tumor environment...
January 23, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28068321/analysis-of-dna-methylation-in-single-circulating-tumor-cells
#16
C F Pixberg, K Raba, F Müller, B Behrens, E Honisch, D Niederacher, H Neubauer, T Fehm, W Goering, W A Schulz, P Flohr, G Boysen, M Lambros, J S De Bono, W T Knoefel, C Sproll, N H Stoecklein, R P L Neves
Direct analysis of circulating tumor cells (CTCs) can inform on molecular mechanisms underlying systemic spread. Here we investigated promoter methylation of three genes regulating epithelial-to-mesenchymal transition (EMT), a key mechanism enabling epithelial tumor cells to disseminate and metastasize. For this, we developed a single-cell protocol based on agarose-embedded bisulfite treatment, which allows investigating DNA methylation of multiple loci via a multiplex PCR (multiplexed-scAEBS). We established our assay for the simultaneous analysis of three EMT-associated genes miR-200c/141, miR-200b/a/429 and CDH1 in single cells...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28064442/tumor-derived-spheroids-relevance-to-cancer-stem-cells-and-clinical-applications
#17
REVIEW
Tatsuya Ishiguro, Hirokazu Ohata, Ai Sato, Kaoru Yamawaki, Takayuki Enomoto, Koji Okamoto
Recently, many types of in vitro three-dimensional (3D) culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3D culture methods aim to preserve the biological characteristics of original tumors better than conventional two-dimensional (2D) monolayer cultures, and include tumor-derived organoids, tumor-derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28032524/classifying-circulating-tumor-cells-to-monitor-cancer-progression
#18
Panagiota Economopoulou, Vassilis Georgoulias, Athanasios Kotsakis
The term 'liquid biopsy' refers to molecular analysis of a tumor's genetic features based on circulating genetic material in the peripheral blood derived from circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and circulating miRNAs, and has emerged as a minimally invasive tool in early cancer diagnosis and disease monitoring. CTCs are believed to originate from the primary tumor and obtain genetic heterogeneity during evolution. Areas covered: The presence of CTCs has been associated with poor clinical outcome in patients with metastatic breast cancer, lung cancer, colorectal cancer and prostate cancer...
February 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28018216/targeting-the-sr-b1-receptor-as-a-gateway-for-cancer-therapy-and-imaging
#19
REVIEW
Linda K Mooberry, Nirupama A Sabnis, Marlyn Panchoo, Bhavani Nagarajan, Andras G Lacko
Malignant tumors display remarkable heterogeneity to the extent that even at the same tissue site different types of cells with varying genetic background may be found. In contrast, a relatively consistent marker the scavenger receptor type B1 (SR-B1) has been found to be consistently overexpressed by most tumor cells. Scavenger Receptor Class B Type I (SR-BI) is a high density lipoprotein (HDL) receptor that facilitates the uptake of cholesterol esters from circulating lipoproteins. Additional findings suggest a critical role for SR-BI in cholesterol metabolism, signaling, motility, and proliferation of cancer cells and thus a potential major impact in carcinogenesis and metastasis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28009470/proportion-of-circulating-tumor-cell-clusters-increases-during-cancer-metastasis
#20
Yuanzhen Suo, Chengying Xie, Xi Zhu, Zhichao Fan, Zhangru Yang, Hao He, Xunbin Wei
Circulating tumor cell (CTC) clusters are found among CTCs and show significantly greater potential for an important role in cancer metastasis than single CTCs, which have been traditionally believed as the majority of CTCs. The accurate proportion and dynamics of CTC clusters remain unclear due to the fact that CTCs in blood flow are very difficult to detect in vivo and in vitro. CTC clusters are even more difficult to be distinguished from CTCs without perturbation by state-of-the-art detection methods. Here, we demonstrate that by using in vivo flow cytometry (IVFC), we can reliably measure the proportion and dynamics of CTC clusters in two murine tumor models...
March 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
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