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Novel treatments prostate

Eu Chang Hwang, Jae Hung Jung, Michael Borofsky, Myung Ha Kim, Philipp Dahm
BACKGROUND: New, minimally invasive surgeries have emerged as alternatives to transurethral resection of the prostate (TURP) for the management of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Aquablation is a novel, minimally invasive, water-based therapy, combining image guidance and robotics for the removal of prostatic tissue. OBJECTIVES: To assess the effects of Aquablation for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia...
February 13, 2019: Cochrane Database of Systematic Reviews
Mizuho Ishikawa, Mitsuhiko Osaki, Makoto Yamagishi, Kunishige Onuma, Hisao Ito, Futoshi Okada, Hideya Endo
Extensive studies on metastasis-associated proteins, S100A4 and MTA1, have been carried out for over two decades, but correlation of both proteins remains obscure. Here we show evidence for the correlation in angiogenesis. First, silencing of each protein by siRNA-mediated knockdown in mouse endothelial MSS31 cells resulted in the inhibition of tube formation. Unexpectedly, the knockdown of MTA1 affected not only its own expression but also the expression of S100A4, whereas silencing of S100A4 did not affect the MTA1 expression...
February 11, 2019: Oncogene
Sahar Kandil, Kok Yung Lee, Laurie Davies, Sebastiano A Rizzo, D Alwyn Dart, Andrew D Westwell
Deshydroxy propioanilides were synthesised by Michael addition reaction between substituted thiophenols onto four different phenylacrylamide derivatives to give twenty-three novel deshydroxy bicalutamide derivatives lacking the central hydroxyl group. The antiproliferative activities of these compounds were evaluated against human prostate cancer cell lines and thirteen compounds showed better inhibitory activities (IC50  = 2.67-13.19 μM) compared to bicalutamide (IC50  = 20.44 μM) in LNCaP. Remarkably, novel double branched bicalutamide analogues (27 and 28) were isolated as major by-products and found to have the best activity across three human prostate cancer cell lines (LNCaP, VCaP and PC3)...
February 2, 2019: European Journal of Medicinal Chemistry
Martina Pagliuca, Carlo Buonerba, Karim Fizazi, Giuseppe Di Lorenzo
Prostate cancer (PC) is a major health issue in developed countries, with, on the one hand, men suffering from sequelae related to unnecessary treatment of non-lethal PC, and, on the other hand, still dying because of advanced PC that progresses to castration-resistant disease. Systemic treatment is the mainstay of therapy of castration-resistant PC (CRPC). To date, a multitude of systemic agents have been tested and many of these have failed to provide a clinically meaningful benefit in CRPC, while others have been approved by the US Food and Drug Administration and/or the European Medicines Agency, including antiandrogen hormonal drugs (abiraterone, enzalutamide, apalutamide), chemotherapy (docetaxel and cabazitaxel), immunotherapy (Sipuleucel-T), and radiopharmaceutical (Radium-223) agents...
February 11, 2019: Drugs
A C Hepburn, R E Steele, R Veeratterapillay, L Wilson, E E Kounatidou, A Barnard, P Berry, J R Cassidy, M Moad, A El-Sherif, L Gaughan, I G Mills, C N Robson, R Heer
Stem cell characteristics have been associated with treatment resistance and poor prognosis across many cancer types. The ability to induce and regulate the pathways that sustain these characteristic hallmarks of lethal cancers in a novel in vitro model would greatly enhance our understanding of cancer progression and treatment resistance. In this work, we present such a model, based simply on applying standard pluripotency/embryonic stem cell media alone. Core pluripotency stem cell master regulators (OCT4, SOX2 and NANOG) along with epithelial-mesenchymal transition (EMT) markers (Snail, Slug, vimentin and N-cadherin) were induced in human prostate, breast, lung, bladder, colorectal, and renal cancer cells...
February 11, 2019: Oncogene
Varadha Balaji Venkadakrishnan, Adam D DePriest, Sangeeta Kumari, Dhirodatta Senapati, Salma Ben-Salem, Yixue Su, Giridhar Mudduluru, Qiang Hu, Eduardo Cortes, Elena Pop, James L Mohler, Gissou Azabdaftari, Kristopher Attwood, Rajal B Shah, Christina Jamieson, Scott M Dehm, Cristina Magi-Galluzzi, Eric Klein, Nima Sharifi, Song Liu, Hannelore V Heemers
Sustained reliance on androgen receptor (AR) after failure of AR-targeting androgen deprivation therapy (ADT) prevents effective treatment of castration-recurrent (CR) prostate cancer (CaP). Interfering with the molecular machinery by which AR drives CaP progression may be an alternative therapeutic strategy but its feasibility remains to be tested. Here, we explore targeting the mechanism by which AR, via RhoA, conveys androgen-responsiveness to serum response factor (SRF), which controls aggressive CaP behavior and is maintained in CR-CaP...
February 11, 2019: Oncogene
John Esther, Benjamin L Maughan, Neysi Anderson, Neeraj Agarwal, Andrew W Hahn
Nonmetastatic castration-resistant prostate cancer (nmCRPC) comprises a relatively narrow niche of advanced prostate cancer, but the treatment landscape for men with nmCRPC has drastically changed over the past year. Prior to the SPARTAN and PROSPER trials, men with nmCRPC were commonly treated with first-generation androgen receptor antagonists, such as bicalutamide or flutamide, or with estrogens or ketoconazole, none of which were associated with any proven survival benefit. The SPARTAN trial evaluated apalutamide versus placebo for men with nmCRPC and found that apalutamide significantly improved metastasis-free survival (MFS), the primary endpoint of this trial...
February 11, 2019: Current Treatment Options in Oncology
C Duarte, A Jimeno, E R Kessler
Prostate cancer is one of the most common cancers in the United States, with an estimated incidence of 164,690 cases, accounting for 9.5% of all new cancer diagnoses. The mainstay of therapy for metastatic prostate cancer involves suppressing testosterone production through androgen deprivation therapy. However, nearly all patients on androgen deprivation therapy will develop resistance to hormone therapy. An improved understanding of the biology of castration resistance has allowed for the development of novel inhibitors of the androgen axis...
January 2019: Drugs of Today
Hideaki Miyake, Yuto Matsushita, Hiromitsu Watanabe, Keita Tamura, Daisuke Motoyama, Toshiki Ito, Takayuki Sugiyama, Atsushi Otsuka
BACKGROUND: To compare the prognostic outcomes between first-generation antiandrogen (FGA) and novel androgen-receptor-axis-targeted agent (ARATA) as first-line therapy in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). METHODS: This study retrospectively included a total of 103 consecutive nmCRPC patients consisting of 47 (45.6%) and 56 (54.4%) who received FGA (bicalutamide or flutamide) and ARATA (abiraterone acetate or enzalutamide), respectively, as the first-line agent after the failure of primary androgen deprivation therapy (ADT)...
February 9, 2019: International Journal of Clinical Oncology
Seyed Nooreddin Faraji, Foroogh Nejatollahi, Ali-Mohammad Tamaddon, Mozafar Mohammadi, Ali Reza Aminsharifi
Isolation of specific single chain antibodies (scFvs) against key epitopes of cancer markers are applied for cancer immunotherapy and diagnosis. In this study following the prediction of the 3D structure of the DSP part of Dentin sialophosphoprotein (DSPP), the epitope was chosen using in silico programs. Panning process was applied to isolate specific human scFv against the epitope. PCR and DNA fingerprinting differentiated the specific clones, which were evaluated by phage ELISA. Following DNA sequencing, the 3D structure of isolated scFv was modeled and Docked on DSP...
February 6, 2019: International Immunopharmacology
Vibha Singh, Praveen Kumar Jaiswal, Ishita Ghosh, Hari K Koul, Xiuping Yu, Arrigo De Benedetti
Standard therapy for advanced Prostate Cancer (PCa) consists of anti-androgens, which provide respite from disease progression, but ultimately fail resulting in the incurable phase of the disease: mCRPC. Targeting PCa cells before their progression to mCRPC would greatly improve the outcome. Combination therapy targeting the DNA Damage Response (DDR) has been limited by general toxicity, and a goal of clinical trials is how to target the DDR more specifically. We now show that androgen deprivation therapy (ADT) of LNCaP cells results in increased expression of TLK1B, a key kinase upstream of NEK1 and ATR and mediating the DDR that typically results in a temporary cell cycle arrest of androgen responsive PCa cells...
February 9, 2019: International Journal of Cancer. Journal International du Cancer
Nerella Sridhar Goud, S Mahammad Ghouse, Jatoth Vishnu, Jakkula Pranay, Ravi Alvala, Venu Talla, Insaf A Qureshi, Mallika Alvala
BACKGROUND: Human Galectin-1, protein of lectin family showing affinity towards β-galactosides has emerged as critical regulator of tumor progression and metastasis, by modulating diverse biological events including homotypic cell aggregation, migration, apoptosis, angiogenesis and immune escape. Therefore, galectin-1 inhibitors might represent novel therapeutic agents for cancer. METHODS: A new series of heterocyclic imines linked coumarin-thiazole hybrids (6a-6r) has been synthesized and evaluated for their cytotoxic potential against a panel of six human cancer cell lines namely, lung (A549), prostate (DU-145), breast (MCF-7 & MDA-MB-231), colon (HCT-15 & HT-29) using MTT assay...
February 7, 2019: Anti-cancer Agents in Medicinal Chemistry
Andrea Fratter, Vera Mason, Marzia Pellizzato, Stefano Valier, Arrigo Francesco Giuseppe Cicero, Erik Tedesco, Elisa Meneghetti, Federico Benetti
The class of lipophilic compounds coming from vegetal source represents a perspective in the adjuvant treatment of several human diseases, despite their poor bioavailability in humans. These compounds are generally soluble in fats and poorly soluble in water. The major reason for the poor bioavailability of lipophilic natural compounds after oral uptake in humans is related to their reduced solubility in enteric water-based fluids, leading to an ineffective contact with absorbing epithelium. The main goal to ensure efficacy of such compounds is then creating technological conditions to deliver them into the first enteric tract as hydro-dispersible forms to maximize epithelial absorption...
February 4, 2019: International Journal of Molecular Sciences
H Fan, Y-S Zhang
OBJECTIVE: microRNAs (miRNAs) were regarded as critical participators for human cancers progression including prostate cancer (PCa) and have the potential to be used as treatment targets for cancers. Herein, we validated a tumor-suppressive miRNA, miR-490-3p, which may suppress PCa progression. Histone deacetylase 2 (HDAC2) is a protein that aberrantly expressed in several cancers. However, the role of HDAC2 in the progression of PCa has not been fully elucidated. MATERIALS AND METHODS: Expression of miR-490-3p and HDAC2 in PCa was investigated...
January 2019: European Review for Medical and Pharmacological Sciences
F-B Zhang, Y Du, Y Tian, Z-G Ji, P-Q Yang
OBJECTIVE: The aim of this study was to investigate the inhibitory role of microRNA-1299 (miR-1299) in prostate cancer, and to explore the possible underlying mechanism. PATIENTS AND METHODS: The expression of miR-1299 in 35 PCa tissues and para-carcinoma tissues, as well as PCa cell lines (PC-3) and prostatic epithelial cell line (RWPE-1), was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, we explored the possible targets of miR-1299 by searching online databases...
January 2019: European Review for Medical and Pharmacological Sciences
Feng Zhou, Shuai Gao, Dong Han, Wanting Han, Sujun Chen, Susan Patalano, Jill A Macoska, Housheng Hansen He, Changmeng Cai
The aberrant activation of the ERG oncogenic pathway due to the TMPRSS2-ERG gene fusion is the major event that contributes to prostate cancer (PCa) development. However, the critical downstream effectors that can be therapeutically targeted remain to be identified. In this study, we have found that the expression of the α1 and β1 subunits of soluble guanylyl cyclase (sGC) was directly and specifically regulated by ERG in vitro and in vivo and was significantly associated with TMPRSS2-ERG fusion in clinical PCa cohorts...
February 4, 2019: Oncogene
Stefanus C Maree, Ngoc Hoang Luong, Ernst S Kooreman, Niek van Wieringen, Arjan Bel, Karel A Hinnen, Henrike Westerveld, Bradley R Pieters, Peter A N Bosman, Tanja Alderliesten
PURPOSE: Bi-objective treatment planning for high-dose-rate prostate brachytherapy is a novel treatment planning method with two separate objectives that represent target coverage and organ-at-risk sparing. In this study, we investigated the feasibility and plan quality of this method by means of a retrospective observer study. METHODS AND MATERIALS: Current planning sessions were recorded to configure a bi-objective optimization model and to assess its applicability to our clinical practice...
February 1, 2019: Brachytherapy
Rihan El Bezawy, Stella Tinelli, Monica Tortoreto, Valentina Doldi, Valentina Zuco, Marco Folini, Claudio Stucchi, Tiziana Rancati, Riccardo Valdagni, Paolo Gandellini, Nadia Zaffaroni
BACKGROUND: Radiotherapy is one of the main treatment options for non-metastatic prostate cancer (PCa). Although treatment technical optimization has greatly improved local tumor control, a considerable fraction of patients still experience relapse due to the development of resistance. Radioresistance is a complex and still poorly understood phenomenon involving the deregulation of a variety of signaling pathways as a consequence of several genetic and epigenetic abnormalities. In this context, cumulative evidence supports a functional role of microRNAs in affecting radioresistance, suggesting the modulation of their expression as a novel radiosensitizing approach...
February 4, 2019: Journal of Experimental & Clinical Cancer Research: CR
Yijie Cheng, Yanfang Cao, Awais Ullah Ihsan, Farhan Ullah Khan, Xue Li, Dianyou Xie, Xingxing Cui, Wenlu Wang, Ziwei Liu, Cunyu Li, Khalil Ali Ahmad, Kiganda Raymond Sembatya, Reyaj Mikrani, Xiaohui Zhou
The exact etiology and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still unknown, as a result, available therapeutic options for patients are far from satisfactory. Therefore, there is a need to develop a valid therapeutic approach that can ameliorate the manifestations of CP/CPPS. Fifty male C57BL/6 mice were randomly divided into five groups of ten mice each. All groups except naïve were subcutaneously injected with 0.2 ml of T2 plus complete Freund adjuvant (CFA) on day 0 and 14 to generate valid CP/CPPS model...
February 4, 2019: Inflammation
Leonidas Apostolidis, Cathleen Nientiedt, Eva Caroline Winkler, Anne Katrin Berger, Clemens Kratochwil, Annette Kaiser, Anne-Sophie Becker, Dirk Jäger, Markus Hohenfellner, Clemens Hüttenbrink, Sascha Pahernik, Florian A Distler, Carsten Grüllich
Background: Neuroendocrine carcinomas of the prostate (NEPCs) are rare tumors with poor prognosis. While platinum and etoposide-based chemotherapy regimens (PE) are commonly applied in first-line for advanced disease, evidence for second-line therapy and beyond is very limited. Methods: Retrospective analysis of all patients with NEPCs including mixed differentiation with adenocarcinoma component and well differentiated neuroendocrine tumors (NETs, carcinoids) at two high-volume oncological centers between 12/2000 and 11/2017...
January 1, 2019: Oncotarget
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