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https://www.readbyqxmd.com/read/28427756/human-tissue-kallikreins-blood-levels-and-response-to-radiotherapy-in-intermediate-risk-prostate-cancer
#1
Nicola J Nasser, John Thoms, Antoninus Soosaipillai, Melania Pintilie, Ri Wang, Eleftherios P Diamandis, Robert G Bristow
OBJECTIVES: Kallikreins are serine proteases over expressed in many malignancies. In this study, we measure changes in serum kallikrein (KLKs) levels during intensity-modulated radiotherapy (IMRT) in prostate cancer patients, and find potential correlations between serum kallikrein level and normal tissues toxicity during radiation. METHODS: Forty-nine patients with prostate cancer were recruited as follows: group 1, definitive standard fractionation IMRT (78Gy in 39 fractions, n=15); group 2, definitive hypofractionated IMRT (60Gy in 20 fractions, n=15); and group 3, IMRT postprostatectomy (66Gy in 33 fractions, n=19)...
April 17, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28427152/radioligand-therapy-of-metastatic-prostate-cancer-using-177lu-psma-617-after-radiation-exposure-to-223ra-dichloride
#2
Hojjat Ahmadzadehfar, Stefanie Zimbelmann, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Florian C Gaertner, Xiao Wei, Stefan Hauser, Markus Essler
Radioligand therapy with 177Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with 223Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of 177Lu-PSMA-617 after exposure to more cycles of 223Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with 223Ra...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425472/label-free-single-cell-separation-and-imaging-of-cancer-cells-using-an-integrated-microfluidic-system
#3
Maria Antfolk, Soo Hyeon Kim, Saori Koizumi, Teruo Fujii, Thomas Laurell
The incidence of cancer is increasing worldwide and metastatic disease, through the spread of circulating tumor cells (CTCs), is responsible for the majority of the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical information supporting therapeutic decision making, and improved methods for CTC enumeration are asked for. Microfluidics has been extensively used for this purpose but most methods require several post-separation processing steps including concentration of the sample before analysis...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28415742/androgen-receptor-amplification-is-concordant-between-circulating-tumor-cells-and-biopsies-from-men-undergoing-treatment-for-metastatic-castration-resistant-prostate-cancer
#4
Jennifer Podolak, Kristi Eilers, Timothy Newby, Rachel Slottke, Erin Tucker, Susan B Olson, Hui-Wen Lue, Jack Youngren, Rahul Aggarwal, Eric J Small, Julie N Graff, Joshi J Alumkal, Tomasz M Beer, George V Thomas
Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH)...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28384066/clinical-significance-of-androgen-receptor-splice-variant-7-mrna-detection-in-circulating-tumor-cells-of-men-with-metastatic-castration-resistant-prostate-cancer-treated-with-first-and-second-line-abiraterone-and-enzalutamide
#5
Emmanuel S Antonarakis, Changxue Lu, Brandon Luber, Hao Wang, Yan Chen, Yezi Zhu, John L Silberstein, Maritza N Taylor, Benjamin L Maughan, Samuel R Denmeade, Kenneth J Pienta, Channing J Paller, Michael A Carducci, Mario A Eisenberger, Jun Luo
Purpose We reported previously that the detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumor cells (CTCs) correlated with poor outcomes from the use of abiraterone and enzalutamide in patients with castration-resistant prostate cancer (CRPC). Here, we expanded our cohort size to better characterize the prognostic significance of AR-V7 in this setting. Methods We prospectively enrolled 202 patients with CRPC starting abiraterone or enzalutamide and investigated the prognostic value of CTC detection (+ v -) and AR-V7 detection (+ v -) using a CTC-based AR-V7 mRNA assay...
April 6, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28337529/the-impact-of-repeated-cycles-of-radioligand-therapy-using-177-lu-lu-psma-617-on-renal-function-in-patients-with-hormone-refractory-metastatic-prostate-cancer
#6
Anna Yordanova, Anja Becker, Elisabeth Eppard, Stefan Kürpig, Christian Fisang, Georg Feldmann, Markus Essler, Hojjat Ahmadzadehfar
BACKGROUND: [(177)Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring. METHODS: Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [(177)Lu]Lu-PSMA-617 were investigated...
March 23, 2017: European Journal of Nuclear Medicine and Molecular Imaging
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
#7
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/28238187/circulating-tumor-cells-clinical-validity-and-utility
#8
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
#9
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/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/28181495/expression-of-%C3%AE-globin-by-cancer-cells-promotes-cell-survival-during-blood-borne-dissemination
#11
Yu Zheng, David T Miyamoto, Ben S Wittner, James P Sullivan, Nicola Aceto, Nicole Vincent Jordan, Min Yu, Nezihi Murat Karabacak, Valentine Comaills, Robert Morris, Rushil Desai, Niyati Desai, Erin Emmons, John D Milner, Richard J Lee, Chin-Lee Wu, Lecia V Sequist, Wilhelm Haas, David T Ting, Mehmet Toner, Sridhar Ramaswamy, Shyamala Maheswaran, Daniel A Haber
Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4...
February 9, 2017: Nature Communications
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/28153390/nucleolin-staining-may-aid-in-the-identification-of-circulating-prostate-cancer-cells
#13
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/28152506/detection-fidelity-of-ar-mutations-in-plasma-derived-cell-free-dna
#14
Alexa Goldstein, Patricia Valda Toro, Justin Lee, John L Silberstein, Mary Nakazawa, Ian Waters, Karen Cravero, David Chu, Rory L Cochran, Minsoo Kim, Daniel Shinn, Samantha Torquato, Robert M Hughes, Aparna Pallavajjala, Michael A Carducci, Channing J Paller, Samuel R Denmeade, Bruce Kressel, Bruce J Trock, Mario A Eisenberger, Emmanuel S Antonarakis, Ben H Park, Paula J Hurley
Somatic genetic alterations including copy number and point mutations in the androgen receptor (AR) are associated with resistance to therapies targeting the androgen/AR axis in patients with metastatic castration resistant prostate cancer (mCRPC). Due to limitations associated with biopsying metastatic lesions, plasma derived cell-free DNA (cfDNA) is increasingly being used as substrate for genetic testing. AR mutations detected by deep next generation sequencing (NGS) of cfDNA from patients with mCRPC have been reported at allelic fractions ranging from over 25% to below 1%...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28009470/proportion-of-circulating-tumor-cell-clusters-increases-during-cancer-metastasis
#15
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
https://www.readbyqxmd.com/read/28000772/improved-detection-of-circulating-tumor-cells-in-non-metastatic-high-risk-prostate-cancer-patients
#16
Andra Kuske, Tobias M Gorges, Pierre Tennstedt, Anne-Kathrin Tiebel, Raisa Pompe, Felix Preißer, Sandra Prues, Martine Mazel, Athina Markou, Evi Lianidou, Sven Peine, Catherine Alix-Panabières, Sabine Riethdorf, Burkhard Beyer, Thorsten Schlomm, Klaus Pantel
The relevance of blood-based assays to monitor minimal residual disease (MRD) in non-metastatic prostate cancer (PCa) remains unclear. Proving that clinically relevant circulating tumor cells (CTCs) can be detected with available technologies could address this. This study aimed to improve CTC detection in non-metastatic PCa patients by combining three independent CTC assays: the CellSearch system, an in vivo CellCollector and the EPISPOT. Peripheral blood samples from high-risk PCa patients were screened for CTCs before and three months after radical prostatectomy (RP)...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27956006/dynamics-of-three-dimensional-telomere-profiles-of-circulating-tumor-cells-in-patients-with-high-risk-prostate-cancer-who-are-undergoing-androgen-deprivation-and-radiation-therapies
#17
Landon Wark, Thomas Klonisch, Julius Awe, Cecile LeClerc, Brandon Dyck, Harvey Quon, Sabine Mai
INTRODUCTION: Accurate assessment and monitoring of the therapeutic efficacy of locally advanced prostate cancer remains a major clinical challenge. Contrary to prostate biopsies, circulating tumor cells (CTCs) are a cellular source repeatedly obtainable by blood sampling and could serve as a surrogate marker for treatment efficacy. In this study, we used size-based filtration to isolate and enumerate CTCs from the blood of 20 patients with high-risk (any one of cT3, Gleason 8-10, or prostate-specific antigen>20ng/ml), nonmetastatic, and treatment-naive prostate cancer before and after androgen deprivation therapy (ADT) and radiation therapy (RT)...
March 2017: Urologic Oncology
https://www.readbyqxmd.com/read/27936891/comparison-of-different-contouring-definitions-of-the-rectum-as-organ-at-risk-oar-and-dose-volume-parameters-predicting-rectal-inflammation-in-radiotherapy-of-prostate-cancer-which-definition-to-use
#18
COMPARATIVE STUDY
Mirko Nitsche, Werner Brannath, Matthias Brückner, Dirk Wagner, Alexander Kaltenborn, Nils Temme, Robert M Hermann
OBJECTIVE: The objective of this retrospective planning study was to find a contouring definition for the rectum as an organ at risk (OAR) in curative three-dimensional external beam radiotherapy (EBRT) for prostate cancer (PCa) with a predictive correlation between the dose-volume histogram (DVH) and rectal toxicity. METHODS: In a pre-study, the planning CT scans of 23 patients with PCa receiving definitive EBRT were analyzed. The rectum was contoured according to 13 different definitions, and the dose distribution was correlated with the respective rectal volumes by generating DVH curves...
February 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/27928807/prognostic-value-of-circulating-tumor-cells-in-castration-resistant-prostate-cancer-a-meta-analysis
#19
Yuxiao Zheng, Cheng Zhang, Jie Wu, Gong Cheng, Haiwei Yang, Lixin Hua, Zengjun Wang
PURPOSE: The prognostic value of circulating tumor cells (CTC) detected in castration-resistant prostate cancer(CRPC) is currently under debate. The aim of our meta-analysis was to evaluate the prognostic effect of CTC andto elucidate whether the detection of CTC in the peripheral blood (PB) of patients diagnosed with CRPC can beused as an independent prognostic factor for survival. MATERIALS AND METHODS: The Pubmed, Science Citation Index, Cochrane Database, Embase Cell Research databaseand the references in relevant studies were systematically searched...
December 8, 2016: Urology Journal
https://www.readbyqxmd.com/read/27916908/epidermal-growth-factor-receptor-status-in-circulating-tumor-cells-as-a-predictive-biomarker-of-sensitivity-in-castration-resistant-prostate-cancer-patients-treated-with-docetaxel-chemotherapy
#20
Takatsugu Okegawa, Naoshi Itaya, Hidehiko Hara, Mitsuhiro Tambo, Kikuo Nutahara
OBJECTIVE: We examined whether epidermal growth factor receptor (EGFR) expression in circulating tumor cells (CTCs) can be used to predict survival in a population of bone-metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel chemotherapy. METHODS: All patients with mCRPC who had experienced treatment failure with androgen-deprivation therapy and had received docetaxel chemotherapy were eligible. CTCs and EGFR expression in CTCs were enumerated with the CellSearch System in whole blood...
November 30, 2016: International Journal of Molecular Sciences
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