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https://www.readbyqxmd.com/read/29340285/quantitative-bone-scan-lesion-area-as-an-early-surrogate-outcome-measure-indicative-of-overall-survival-in-metastatic-prostate-cancer
#1
Matthew S Brown, Grace Hyun J Kim, Gregory H Chu, Bharath Ramakrishna, Martin Allen-Auerbach, Cheryce P Fischer, Benjamin Levine, Pawan K Gupta, Christiaan W Schiepers, Jonathan G Goldin
A clinical validation of the bone scan lesion area (BSLA) as a quantitative imaging biomarker was performed in metastatic castration-resistant prostate cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71 placebo) from a clinical trial involving a different drug from the initial biomarker development. BSLA computation involved automated image normalization, lesion segmentation, and summation of the total area of segmented lesions on bone scan AP and PA views as a measure of tumor burden...
January 2018: Journal of Medical Imaging
https://www.readbyqxmd.com/read/29340160/stereotactic-body-radiation-therapy-for-the-treatment-of-oligoprogression-on-androgen-receptor-targeted-therapy-in-castration-resistant-prostate-cancer
#2
Thu-Cuc Nguyen, Ravneet Bajwa, Shahla Bari, Azka Ali, William Paul Skelton, Roland-Austin Federico, Rohit Bishnoi, Justin W Wray, Robert A Zlotecki, Long H Dang, Jameel Muzaffar
Castration-resistant prostate cancer is an incurable disease. To date, six agents-abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223 and sipuleucel-T- have shown clinical efficacy in phase III clinical trials, leading to their FDA approval. Patients are typically sequenced through most or all of these agents, and then eventually succumb to their disease. Development of new treatments remains an unmet need. We report a case of a patient who progressed on enzalutamide with a single enlarging metastatic lesion, was treated with ablative stereotactic body radiation therapy while maintaining the same systemic treatment, who then had durable complete remission...
January 2018: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29340049/pharmacological-treatment-with-inhibitors-of-nuclear-export-enhances-the-antitumor-activity-of-docetaxel-in-human-prostate-cancer
#3
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Francesco Marampon, Roberta Sferra, Simona Pompili, Leda Assunta Biordi, Roberto Iorio, Vincenzo Flati, Christian Argueta, Yosef Landesman, Michael Kauffman, Sharon Shacham, Claudio Festuccia
Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340039/integrative-molecular-network-analysis-identifies-emergent-enzalutamide-resistance-mechanisms-in-prostate-cancer
#4
Carly J King, Josha Woodward, Jacob Schwartzman, Daniel J Coleman, Robert Lisac, Nicholas J Wang, Kathryn Van Hook, Lina Gao, Joshua Urrutia, Mark A Dane, Laura M Heiser, Joshi J Alumkal
Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors harbor countless genomic aberrations that control many hallmarks of cancer. While some specific mutations in CRPC may be actionable, many others are not. We hypothesized that genomic aberrations in cancer may operate in concert to promote drug resistance and tumor progression, and that organization of these genomic aberrations into therapeutically targetable pathways may improve our ability to treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant CRPC, we performed transcriptional and copy number profiling studies using paired enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339807/overexpression-of-%C3%AE-1-6-fucosyltransferase-in-the-development-of-castration-resistant-prostate-cancer-cells
#5
Naseruddin Höti, Shuang Yang, Yingwei Hu, Punit Shah, Michael C Haffner, Hui Zhang
Glycosylation is recognized as one of the most common modifications on proteins. Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer. While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer...
January 16, 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29339090/patched-1-expression-correlates-with-biochemical-relapse-in-high-risk-prostate-cancer-patients
#6
Annelies Gonnissen, Sofie Isebaert, Christiaan Perneel, Chad M McKee, Filip Van Utterbeeck, Evelyne Lerut, Clare Verrill, Richard J Bryant, Steven Joniau, Ruth J Muschel, Karin Haustermans
There is an unmet clinical need for adequate biomarkers to aid risk stratification and management of prostate cancer (PCa) patients. Even within the high-risk PCa category not all patients will invariably have a poor prognosis, and improved stratification of this heterogeneous group is needed. In this context, components of the hedgehog (Hh) pathway may have promise as biomarkers, as the available evidence suggests increased Hh pathway activity may confer a poorer outcome in advanced and castrate-resistant PCa...
January 12, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29339044/the-cardiovascular-toxicity-of-abiraterone-and-enzalutamide-in-prostate-cancer
#7
Roberto Iacovelli, Chiara Ciccarese, Emilio Bria, Mario Romano, Emanuela Fantinel, Davide Bimbatti, Alessandro Muraglia, Antonio Benito Porcaro, Salvatore Siracusano, Matteo Brunelli, Renzo Mazzarotto, Walter Artibani, Giampaolo Tortora
INTRODUCTION: The cardiovascular toxicity related to abiraterone and enzalutamide has been previously studied by our group. In this analysis, we aim to update our previous findings related to abiraterone and enzalutamide, including the new available evidence, both in castration-resistant and hormone-sensitive prostate cancer. PATIENTS AND METHODS: Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29336978/metastatic-burden-in-newly-diagnosed-hormone-naive-metastatic-prostate-cancer-comparing-definitions-of-chaarted-and-latitude-trial
#8
Sarah Buelens, Filip Poelaert, Bert Dhondt, Valérie Fonteyne, Pieter De Visschere, Piet Ost, Sofie Verbeke, Geert Villeirs, Kathia De Man, Sylvie Rottey, Karel Decaestecker, Nicolaas Lumen
OBJECTIVES: No uniformity exists in the definition of metastatic burden in metastatic hormone-naive prostate cancer (mHNPC) across clinical trials making their comparison challenging. We explored definition agreement and prognostic significance of bulky mHNPC according to the CHAARTED and LATITUDE trial. MATERIALS AND METHODS: Since 2014, 95 patients with newly diagnosed mHNPC were prospectively registered. For this study, they were categorized as having high-volume (HVD) vs...
January 11, 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29334610/phase-ii-study-of-dovitinib-in-patients-with-castration-resistant-prostate-cancer-kcsg-gu11-05
#9
Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park
Purpose: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). Materials and Methods: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500mg/day (5-days-on/2-days-off schedule)...
January 2, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29334357/differential-requirements-of-androgen-receptor-in-luminal-progenitors-during-prostate-regeneration-and-tumor-initiation
#10
Chee Wai Chua, Nusrat J Epsi, Eva Y Leung, Shouhong Xuan, Ming Lei, Bo I Li, Sarah K Bergren, Hanina Hibshoosh, Antonina Mitrofanova, Michael M Shen
Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor that functions in prostate regeneration. Using genetically-engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation in vivo...
January 15, 2018: ELife
https://www.readbyqxmd.com/read/29333925/androgen-receptor-independent-prostate-cancer-an-emerging-clinical-entity
#11
Ilyas Sahin, Anthony E Mega, Benedito A Carneiro
Androgen deprivation therapy remains the backbone of prostate cancer treatment given its pivotal role in the pathogenesis of prostate cancer. The growing knowledge of androgen receptor-independent (i.e. AR-null) prostate cancer cells, however, might advance the treatment paradigm of prostate cancer particularly in castration resistance stage by targeting these pathways. Here, we examined the results of two recent studies, published in Cancer Cell by Bluemn and Shukla et al., and possible clinical impact of these studies in the near future in castration resistance prostate cancer...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333469/utility-of-f-18-fdg-pet-ct-for-detection-of-bone-marrow-metastases-in-prostate-cancer-patients-treated-with-radium-223
#12
Kaoru Maruyama, Keita Utsunomia, Takahiro Nakamoto, Shigenari Kawakita, Takashi Murota, Noboru Tanigawa
A 76-year-old man with symptomatic bone metastases from castration-resistant prostate cancer underwent Radium-223-dichloride (Ra-223) therapy. Before Ra-223 therapy, he had normal peripheral blood cell counts. Ra-223 therapy relieved his shoulder and low back pain. The elevation of the serum prostate-specific antigen (PSA), doubling every month during Ra-223 therapy, suggested a PSA flare or relapse. Some lesions showed decrease and some lesions showed increase on Tc-99m hydroxymethylene diphosphonate bone scintigraphy at two weeks after the third injection of Ra-223 therapy...
2018: Asia Oceania Journal of Nuclear Medicine & Biology
https://www.readbyqxmd.com/read/29332354/inhibition-of-telomerase-potentiates-enzalutamide-efficiency-of-androgen-sensitive-human-prostate-cancer-cells
#13
Karaca Kaan Gecgel, Mustafa Muduroglu, Suat Erdogan
PURPOSE: Androgen deprivation therapy (ADT) is one of the main strategies to treat prostate cancer (PCa) at various stages of its development. Androgen receptor (AR) antagonists such as enzalutamide are mainstay treatments for castration-sensitive prostate cancer. Though, a majority of patients initially respond to ADT, most will eventually progress to castrate-resistant, due to the development of different mutations on the AR. PCa cells express high telomerase activity, and there is a correlation between the total activity of telomerase and the Gleason score...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331381/clinical-outcomes-of-first-line-abiraterone-acetate-or-enzalutamide-for-metastatic-castration-resistant-prostate-cancer-after-androgen-deprivation-therapy%C3%A2-docetaxel-or-adt-alone-for-metastatic-hormone-sensitive-prostate-cancer
#14
Edoardo Francini, Steven Yip, Shubidito Ahmed, Haocheng Li, Luke Ardolino, Carolyn P Evan, Marina Kaymakcalan, Grace K Shaw, Philip W Kantoff, Mary-Ellen Taplin, Nimira S Alimohamed, Anthony M Joshua, Daniel Y C Heng, Christopher J Sweeney
BACKGROUND: The CHAARTED (ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) and STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trials showed that the addition of docetaxel (D) to androgen deprivation therapy (ADT) prolonged longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of upfront D on subsequent therapies is still unexplored. As abiraterone acetate (AA) and enzalutamide (E) are the most commonly used first-line treatment for metastatic castration-resistant prostate cancer (mCRPC), we aimed to assess whether they maintained their efficacy after ADT+D versus ADT alone...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29330943/epigenetic-markers-in-circulating-cell-free-dna-as-prognostic-markers-for-survival-of-castration-resistant-prostate-cancer-patients
#15
Rianne J Hendriks, Siebren Dijkstra, Frank P Smit, Johan Vandersmissen, Hendrik Van de Voorde, Peter F A Mulders, Inge M van Oort, Wim Van Criekinge, Jack A Schalken
BACKGROUND: Noninvasive biomarkers to guide personalized treatment for castration-resistant prostate cancer (CRPC) are needed. In this study, we analyzed hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA concentrations and levels of the epigenetic markers and to assess the value of these biomarkers for prognosis. METHODS: In this prospective study, patients were included before starting new treatment after developing CRPC...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29330929/adipocytes-affect-castration-resistant-prostate-cancer-cells-to-develop-the-resistance-to-cytotoxic-action-of-nk-cells-with-alterations-of-pd-l1-nkg2d-ligand-levels-in-tumor-cells
#16
Lijun Xu, Mingjing Shen, Xiaodong Chen, Rongying Zhu, Dong-Rong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown. We investigated the adipocyte role in controlling the susceptibility of castration-resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29327946/posttranscriptional-regulation-of-human-antigen-r-by-mir-133b-enhances-docetaxel-cytotoxicity-through-the-inhibition-of-atp-binding-cassette-subfamily-g-member-2-in-prostate-cancer-cells
#17
Hui Liu, Xiaolong Song, Junqing Hou, Zhenhua Zhao, Junkai Chang
Docetaxel (DTX)-based chemotherapy is a first-line therapy in patients with castration-resistant prostate cancer. However, development of DTX resistance remains a challenge in cancer treatment. miRNAs have been shown to be involved in drug resistance in tumors. Nevertheless, little is known about the function and detailed molecular mechanism of miR-133b in DTX resistance of prostate cancer cells. The current study showed that miR-133b was downregulated, while human antigen R (HuR) was upregulated in prostate cancer cells...
January 12, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29326358/targeted-alpha-therapy-of-mcrpc-with-225actinium-psma-617-swimmer-plot-analysis-suggests-efficacy-regarding-duration-of-tumor-control
#18
Clemens Kratochwil, Frank Bruchertseifer, Hendrik Rathke, Markus Hohenfellner, Frederik L Giesel, Uwe Haberkorn, Alfred Morgenstern
The aim of this evaluation is to identify first indicators regarding the efficacy of 225Ac-PSMA-617 therapy in a retrospectively analyzed group of patients. Methods: Forty patients with metastatic castration-resistant prostate cancer were selected for treatment with 3 cycles of 100 kBq/kgBW 225Ac-PSMA-617 in 2 months intervals. Prostate-specific antigen (PSA) and blood cell count were measured every 4 weeks. Prostate-specific membrane antigen (PSMA)-PET/CT or PSMA-SPECT/CT were used for baseline staging and imaging follow-up at month six...
January 11, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29324927/hematopoiesis-is-prognostic-for-toxicity-and-survival-of-223radium-treatment-in-patients-with-metastatic-castration-resistant-prostate-cancer
#19
A Leisser, M Nejabat, M Hartenbach, H Duan, S F Shariat, G Kramer, M Krainer, M Hacker, A R Haug
OBJECTIVE: We evaluated the impact of pre-therapeutic hematopoiesis on survival, hematotoxicity (HT) and number of 223Radium (223Ra) treatments in patients with metastatic castration-resistant prostate cancer. SUBJECTS AND METHOD: Hemoglobin-levels (Hb), the number of platelets (Plts), leukocytes (Leuk), and survival data were collected in 56 patients treated with 223Ra. Pre-therapeutic hematopoiesis as well as adverse events during and after therapy were scored (grade 0-4) according to the CTCAE recommendations...
September 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/29323792/the-retinamide-vnlg-152-inhibits-ar-ar-v7-and-mnk-eif4esignaling-pathways-to-suppress-emt-and-castration-resistant-prostate-cancer-xenograft-growth
#20
Vidya P Ramamurthy, Senthilmurugan Ramalingam, Lalji K Gediya, Vincent C O Njar
VNLG-152, a lead novel retinamide (NR) shown to suppress growth and progression in genetically diverse PCa cells via inhibition of AR signaling and eIF4E translational machinery. Herein, we report therapeutic effects of VNLG-152 on castration resistant prostate cancer (CRPC) growth and metastatic phenotype in CRPC tumor xenograft model. Administration of VNLG-152 significantly and dose-dependently suppressed the growth of aggressive CWR22Rv1 tumors by 63.4% and 76.3% respectively (P = 0.001), vs. vehicle with no host toxicity...
January 11, 2018: FEBS Journal
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