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https://www.readbyqxmd.com/read/28212536/targeting-the-stress-oncoprotein-ledgf-p75-to-sensitize-chemoresistant-prostate-cancer-cells-to-taxanes
#1
Leslimar Ríos-Colón, Christina K Cajigas-Du Ross, Anamika Basu, Catherine Elix, Ivana Alicea-Polanco, Tino W Sanchez, Vinodh Radhakrishnan, Chien-Shing Chen, Carlos A Casiano
Prostate cancer (PCa) is associated with chronic prostate inflammation resulting in activation of stress and pro-survival pathways that contribute to disease progression and chemoresistance. The stress oncoprotein lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, promotes cellular survival against environmental stressors, including oxidative stress, radiation, and cytotoxic drugs. Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212321/therapeutic-approaches-targeting-myc-driven-prostate-cancer
#2
REVIEW
Richard J Rebello, Richard B Pearson, Ross D Hannan, Luc Furic
The transcript encoding the proto-oncogene MYC is commonly overexpressed in prostate cancer (PC). MYC protein abundance is also increased in the majority of cases of advanced and metastatic castrate-resistant PC (mCRPC). Accordingly, the MYC-directed transcriptional program directly contributes to PC by upregulating the expression of a number of pro-tumorigenic factors involved in cell growth and proliferation. A key cellular process downstream of MYC activity is the regulation of ribosome biogenesis which sustains tumor growth...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28208664/the-role-of-the-neutrophil-to-lymphocyte-ratio-for-survival-outcomes-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-abiraterone
#3
Martin Boegemann, Katrin Schlack, Stefan Thomes, Julie Steinestel, Kambiz Rahbar, Axel Semjonow, Andres Jan Schrader, Martin Aringer, Laura-Maria Krabbe
The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR) and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR <5 and 17 with NLR >5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months) (HR: 1...
February 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208520/re-activation-of-notch1-synergizes-with-multiple-pathways-in-promoting-castration-resistant-prostate-cancer
#4
Anthony Atala
No abstract text is available yet for this article.
March 2017: Journal of Urology
https://www.readbyqxmd.com/read/28208518/re-genomic-alterations-in-cell-free-dna-and-enzalutamide-resistance-in-castration-resistant-prostate-cancer
#5
Samir S Taneja
No abstract text is available yet for this article.
March 2017: Journal of Urology
https://www.readbyqxmd.com/read/28207202/the-polar-warhead-of-a-trim24-bromodomain-inhibitor-rearranges-a-water-mediated-interaction-network
#6
Jiuyang Liu, Fudong Li, Hongyu Bao, Yiyang Jiang, Shuya Zhang, Rongsheng Ma, Jia Gao, Jihui Wu, Ke Ruan
Tripartite motif-containing protein 24 (TRIM24) is closely correlated with multiple cancers, and a recent study demonstrated that the bromodomain of TRIM24 is essential for the proliferation of lethal castration-resistant prostate cancer. Here, we identify three new inhibitors of the TRIM24 bromodomain using NMR fragment-based screening. The crystal structures of two new inhibitors in complex with the TRIM24 bromodomain reveal that the water-bridged interaction network is conserved in the same fashion as those for known benzoimidazolone inhibitors...
February 16, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28205582/aurora-a-regulates-expression-of-ar-v7-in-models-of-castrate-resistant-prostate-cancer
#7
Dominic Jones, Martin Noble, Steve R Wedge, Craig N Robson, Luke Gaughan
Androgen receptor variants (AR-Vs) provide a mechanism of therapy evasion in castrate-resistant prostate cancer (CRPC), yet mechanisms of regulation remain largely unknown. Here we investigate the role of Aurora A kinase on AR-Vs in models of CRPC and show depletion of Aurora A reduces AR-V target gene expression. Importantly, knockdown of Aurora A reconfigures splicing of AR pre-mRNA to discriminately down-regulate synthesis of AR-V transcripts, including AR-V7, without effecting full-length AR mRNA; and as a consequence, AR-V-driven proliferation and survival of CRPC cells is markedly reduced...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203770/phase-ii-study-of-cabazitaxel-with-or-without-abiraterone-acetate-and-prednisone-in-patients-with-metastatic-castrate-resistant-prostate-cancer-after-prior-docetaxel-and-abiraterone-acetate
#8
E R Kessler, D Gao, T W Flaig, K Breaker, M Wold, M Wacker, E T Lam
No abstract text is available yet for this article.
February 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28197629/rab27a-rab27b-and-vps36-are-downregulated-in-advanced-prostate-cancer-and-show-functional-relevance-in-prostate-cancer-cells
#9
Thomas Stefan Worst, Yannic Meyer, Maria Gottschalt, Cleo-Aron Weis, Jost von Hardenberg, Christine Frank, Annette Steidler, Maurice Stephan Michel, Philipp Erben
Paracrine and long-range signaling via extracellular vesicles, such as exosomes and microvesicles, is deemed crucial for tumorigenesis, invasion and spread of solid tumors. The ESCRT machinery (endosomal sorting complexes required for transport) and Rab-proteins act as key players in vesicular trafficking and secretion. Yet, their role in prostate cancer (PCa) is unknown. Therefore, this study aimed to elucidate the relevance of these components in PCa. In silico reanalysis of genes with known involvement in vesicular trafficking and secretion in an existing microarray dataset revealed low expression of RAB27A, RAB27B and VPS36 to be predictive for reduced BCR-free survival in patients with localized PCa (p=0...
February 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28195088/serotonin-receptor-4-5-hydroxytryptamine-receptor-type-4-regulates-expression-of-estrogen-receptor-beta-and-cell-migration-in-hormone-naive-prostate-cancer
#10
Yasuhiro Nakamura, Kazue Ise, Yuto Yamazaki, Fumiyoshi Fujishima, Keely M McNamara, Hironobu Sasano
BACKGROUND: Estrogens are considered to potentially play some roles in the development and progression of prostate cancer through estrogen receptor beta (ERβ). However, additional factors which could influence the clinical outcome of the patients through modulating these steroid signalings have also been proposed. Among these, increased expression of serotonin receptor especially that of 5-hydroxytryptamine receptor Type 4 (5-HTR4) has been recently proposed to be involved in autocrine/paracrine mechanisms of castration-resistant prostate cancer, but the presence and clinical significance of 5-HTR4 in hormone-naive prostate cancer (HNPC) and its interaction with hormonal signaling pathways have remained virtually unknown...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28192399/c-met-mir-130b-axis-as-novel-mechanism-and-biomarker-for-castration-resistance-state-acquisition
#11
A Cannistraci, G Federici, A Addario, A L Di Pace, L Grassi, G Muto, D Collura, M Signore, L De Salvo, S Sentinelli, G Simone, M Costantini, S Nanni, A Farsetti, V Coppola, R De Maria, D Bonci
Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28188090/independent-association-between-time-to-prostate-specific-antigen-psa-nadir-and-psa-progression-free-survival-in-patients-with-docetaxel-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer-receiving-abiraterone-acetate-but-not-enzalutamide
#12
Hideaki Miyake, Takuto Hara, Keita Tamura, Takayuki Sugiyama, Hiroshi Furuse, Seiichiro Ozono, Masato Fujisawa
PURPOSE: The objective of this study was to compare the prognostic effect of time to prostate-specific antigen (PSA) nadir (TTPN) after treatment with abiraterone acetate (AA) and enzalutamide (Enz) in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer (mCRPC). METHODS: This study included a total of 297 consecutive patients with mCRPC, of whom 125 and 172 received AA and Enz, respectively, without previous treatment with docetaxel and subsequently achieved any degree of PSA reduction after the administration of either agent...
February 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28188049/gene-polymorphism-related-individual-and-interracial-differences-in-the-outcomes-of-androgen-deprivation-therapy-for-prostate-cancer
#13
REVIEW
Naohiro Fujimoto, Masaki Shiota, Ikko Tomisaki, Akinori Minato
Among patients with prostate cancer, the prognosis after androgen deprivation therapy differs significantly among individuals and among races; however, the reasons underlying these differences are poorly understood. Several single nucleotide polymorphisms in genes associated with prostate cancer progression or castration resistance might serve as the host factor that influences prognosis and, thus, accounts for these individual and racial gaps in treatment outcomes. Accordingly, single nucleotide polymorphisms associated with treatment outcomes could be used as predictive and/or prognostic biomarkers for patient stratification and to identify personalized treatment and follow-up protocols...
January 18, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28186973/upregulation-of-fam84b-during-prostate-cancer-progression
#14
Nicholas Wong, Yan Gu, Anil Kapoor, Xiaozeng Lin, Diane Ojo, Fengxiang Wei, Judy Yan, Jason de Melo, Pierre Major, Geoffrey Wood, Tariq Aziz, Jean-Claude Cutz, Michael Bonert, Arthur J Patterson, Damu Tang
Although the FAM84B gene lies within chromosome 8q24, a locus frequently altered in prostate cancer (PC), its alteration during prostate tumorigenesis has not been well studied. We report here FAM84B upregulation in DU145 cell-derived prostate cancer stem-like cells (PCSLCs) and DU145 cell-produced lung metastases compared to subcutaneous xenograft tumors. FAM84B protein was detected in bone metastases and primary PCs. Nanostring examination of 7 pairs of tumor adjacent normal and PC tissues revealed elevations in FAM84B mRNA levels in all carcinomas...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185938/folate-targeted-nanoparticle-delivery-of-androgen-receptor-shrna-enhances-the-sensitivity-of-hormone-independent-prostate-cancer-to-radiotherapy
#15
Xinjun Zhang, Nianli Liu, ZhiYing Shao, Hui Qiu, Hong Yao, JiaYin Ji, Jianshe Wang, Wenchao Lu, Ronald C Chen, Longzhen Zhang
Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa). PCa patients typically receive androgen deprivation therapy; nonetheless, these patients eventually develop castration and radiation resistance. We hypothesized that we could further improve radiotherapeutic efficacy of hormone-independent PCa (HIPC) by silencing AR. In this study, nanoparticle (NP) AR-shRNA was formulated using folate-targeted H1 nanopolymer. We demonstrated that NP AR-shRNA enhances PCa radiosensitivity as indicated by the inhibition of cell growth, increased apoptosis, and increased cell cycle arrest in AR-dependent HIPC in vitro...
February 6, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28185462/-options-of-chemotherapy-in-the-treatment-of-prostate-cancer
#16
I Richter, J Dvořák, J Bartoš
BACKGROUND: Prostate cancer is one of the most common malignancies in men. Chemotherapy has an important role in the management of prostate cancer, especially for the treatment of castrate resistant prostate cancer (mCRPC). According to recently published studies, chemotherapy can also be used to treat advanced hormone sensitive disease. AIM: The aim of this report is to review the currently available options for chemotherapy of prostate cancer. RESULTS: Docetaxel is a chemotherapeutic agent used for standard treatment of mCRPC as 1st line therapy...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28183253/optimal-management-of-prostate-cancer-based-on-its-natural-clinical-history
#17
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/28181296/molecular-dynamics-studies-on-the-enzalutamide-resistance-mechanisms-induced-by-androgen-receptor-mutations
#18
Hongli Liu, Lingyan Wang, Jiaqi Tian, Jiazhong Li, Huanxiang Liu
The second-generation antiandrogen enzalutamide, targeting androgen receptor (AR), was approved to treat castration resistant prostate cancer (CRPC) in 2012. Its resistance was observed when it was in the clinical research stage. AR mutation is the main factor of enzalutamide resistance. AR F876L and F876L_T877A mutations were reported to switch enzalutamide from AR antagonist to agonist, but W741C cannot. There are various mutations in the ligand binding domain of androgen receptor (AR LBD), such as L701H, W741L, H874Y, T877A and M895T, if these mutations can lead to drug resistance problem or not is not known...
February 9, 2017: Journal of Cellular Biochemistry
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
#19
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/28178391/amino-terminal-enhancer-of-split-gene-aes-encodes-a-tumor-and-metastasis-suppressor-of-prostate-cancer
#20
Yoshiyuki Okada, Masahiro Sonoshita, Fumihiko Kakizaki, Naoki Aoyama, Yoshiro Itatani, Masayuki Uegaki, Hiromasa Sakamoto, Takashi Kobayashi, Takahiro Inoue, Tomomi Kamba, Akira Suzuki, Osamu Ogawa, M Mark Taketo
Major cause of cancer death is its metastasis to the vital organs. Few effective therapies are available for metastatic castration-resistant prostate cancer (PCa), and progressive metastatic lesions such as lymph nodes and bones cause mortality. We recently identified AES as a metastasis suppressor for colon cancer. Here, we have studied the roles of AES in PCa progression. We analyzed the relationship between AES expression and PCa stages of progression by immunohistochemistry of human needle biopsy samples...
February 8, 2017: Cancer Science
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