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Hormone sensitive prostate cancer

Jillian S Weissenrieder, Jacqueline E Reilly, Jeffrey D Neighbors, Raymond J Hohl
BACKGROUND: Following androgen deprivation for the treatment of advanced adenocarcinoma of the prostate, tumors can progress to neuroendocrine prostate cancer (NEPC). This transdifferentiation process is poorly understood, but trafficking of transcriptional factors and/or cytoskeletal rearrangements may be involved. We observed the role of geranylgeranylation in this process by treatment with digeranyl bisphosphonate (DGBP), a selective inhibitor of geranylgeranyl pyrophosphate synthase which blocks the prenylation of small GTPases such as Rho and Rab family proteins, including Cdc42 and Rac1...
August 14, 2018: Prostate
Lai Xu, Russell K Pachynski
PURPOSE OF REVIEW: Androgen deprivation therapy (ADT) has been the standard-of-care (SOC) for metastatic hormone-sensitive prostate cancer (mHSPC) since the middle of the twentieth century. Recently, several practice-changing trials have added new therapy options for these patients. Here we review these studies and discuss guidelines on treatment decision-making. RECENT FINDINGS: A trio of studies (GETUG-AFU15, STAMPEDE, CHAARTED) combining docetaxel chemotherapy with ADT all showed clinical benefit of the addition...
August 13, 2018: Current Urology Reports
Isil Ezgi Eryilmaz, Gamze Guney Eskiler, Unal Egeli, Beste Yurdacan, Gulsah Cecener, Berrin Tunca
The aim of the current study was first to investigate cytotoxic activity of usnic acid (UA) on hormone-dependent breast and prostate cancer, and normal cells. Cells were treated with increasing concentrations (25 to 150 µM) of UA for 48 hours and cell viability, quantitative and morphological analysis of cell death, and cell cycle analysis were performed. UA was shown to have selective cytotoxicity on hormone-dependent cancer cells with the IC50 levels of 71.4 and 77.5 µM for MCF7 and LNCaP cells, respectively...
August 13, 2018: Journal of Biochemical and Molecular Toxicology
Charlotte Fenioux, Christophe Louvet, Emilie Charton, Francois Rozet, Stanislas Ropert, Dominique Prapotnich, Eric Barret, Rafael Sanchez-Salas, Annick Mombet, Nathalie Cathala, Marie-Liesse Joulia, Jean-Luc Molitor, Julie Henriques, Franck Bonnetain, Xavier Cathelineau, Mostefa Bennamoun
OBJECTIVE: To evaluate the effects of switching from Prednisone (P) to Dexamethasone (D) at asymptomatic PSA progression in mCRPC patients treated with Abiraterone-acetate (AA). MATERIAL AND METHODS: Among 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic mCRPC patients, progressing biochemically on AA+P 10mg/d, were included. A corticosteroid-switch to AA+D 0.5mg/d at PSA increase was administered until radiological and/or clinical progression...
August 11, 2018: BJU International
Omar Abdel-Rahman, Winson Y Cheung
BACKGROUND: Local treatment of metastatic prostate cancer and its impact on future disease course requires further assessment. We sought to evaluate the impact of prior local treatment to the prostate on the outcomes of hormone-sensitive prostate cancer (HSPC) patients recruited in the CHAARTED study. PATIENTS AND METHODS: We performed a retrospective analysis of the prospectively collected data among patients with metastatic HSPC in the CHAARTED study, a phase 3 multicenter study conducted between 2006 and 2014...
July 21, 2018: Clinical Genitourinary Cancer
Mauro Carrara, Eleonora Massari, Alessandro Cicchetti, Tommaso Giandini, Barbara Avuzzi, Federica Palorini, Claudio Stucchi, Giovanni Fellin, Pietro Gabriele, Vittorio Vavassori, Claudio Degli Esposti, Cesare Cozzarini, Emanuele Pignoli, Claudio Fiorino, Tiziana Rancati, Riccardo Valdagni
OBJECTIVES: To apply artificial neural network (ANN) classification methods for the prediction of late fecal incontinence (LFI) following high-dose prostate cancer radiotherapy (RT) and to develop a "ready to use" graphical-tool. MATERIAL & METHODS: 598 men recruited in two national multicentre trials were analyzed. Information was recorded on comorbidity, previous abdominal surgery, use of drugs and dose distribution. Fecal incontinence was prospectively evaluated through self-reported questionnaires...
August 6, 2018: International Journal of Radiation Oncology, Biology, Physics
Charles C Vu, Kevin G Blas, Thomas B Lanni, Gary S Gustafson, Daniel J Krauss
PURPOSE: The recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer. METHODS AND MATERIALS: A multistate Markov model was created to model a patient with intermediate-high risk prostate cancer...
July 31, 2018: Brachytherapy
Ciro Franzese, Paolo Andrea Zucali, Lucia Di Brina, Giuseppe D'Agostino, Pierina Navarria, Davide Franceschini, Armando Santoro, Marta Scorsetti
BACKGROUND: Diagnoses of oligometastatic prostate cancer (PC) increased in the recent years thanks to the advancement in imaging and more effective systemic therapies. Here we evaluate the efficacy of Stereotactic Body Radiation Therapy (SBRT) in oligorecurrent and oligoprogressive PC. METHODS: We included patients with a maximum of five metastases diagnosed in a maximum of two target organs. Concomitant treatment with hormonal therapies or chemotherapies was allowed...
August 2, 2018: Cancer Medicine
Oliver Sartor, Deepali Sharma
223 Radium (223 Ra) is the first alpha-emitting therapy proven effective in human cancer. Prospective randomized trials indicate that 223 Ra, which concentrates after intravenous injection in areas of osteoblastic metastatic disease, can prolong survival in bone-dominant castrate resistant prostate cancer patients. Though radium isotopic therapy is conceptually critical to demonstrate that alpha emitters can be safe and effective, 223 Ra has inherent limitations given its restriction to bone metastatic disease...
June 2018: Translational Andrology and Urology
Tyler Etheridge, Jinning Liou, Tracy M Downs, E Jason Abel, Kyle A Richards, David F Jarrard
Recent work suggests the selective Cox-2 inhibitor celecoxib delays progression to androgen independence in hormone sensitive prostate cancer (HSPC) through inhibition of the androgen receptor (AR) and ErbB signaling. However, human studies examining its effect on delaying disease progression while on hormone therapy are limited. This study explores the effect of celecoxib use on PC survival in VA patients undergoing androgen deprivation therapy (ADT) for advanced PC. We retrospectively examined the association between celecoxib use (defined as duration of medication use ≥180 days) in men with PC being treated with ADT in national VA databases...
2018: American Journal of Clinical and Experimental Urology
Aditya Prakash Sharma, Ravimohan S Mavuduru, Girdhar Singh Bora, Sudheer K Devana, Shrawan K Singh, Arup K Mandal
With the emergence of recent landmark trials, the treatment for hormone-sensitive metastatic prostate cancer (hsMPC) is changing from androgen deprivation therapy (ADT) alone to combination therapy. Both, docetaxel chemotherapy and abiraterone in addition to ADT have been extensively studied in well-conducted randomized controlled trials and were shown to improve outcomes. However, this paradigm shift in the treatment has also raised some queries. This mini review reflects upon the four landmark trials and tries to provide some perspective about the decision-making process for the patients with hsMPC...
July 2018: Indian Journal of Urology: IJU: Journal of the Urological Society of India
K Miller
No abstract text is available yet for this article.
August 2018: Der Urologe. Ausg. A
Jumpei Asakawa, Taro Iguchi, Satoshi Tamada, Sayaka Yasuda, Noriko Ninomiya, Minoru Kato, Takeshi Yamasaki, Tetusji Ohmachi, Tatsuya Nakatani
Background: The aim of our retrospective study was to evaluate the 5-year survival and time to castration resistant prostate cancer in patients with hormone sensitive prostate cancer treated with the gonadotropin releasing hormone antagonist, degarelix. Another aim was to evaluate the effects of changing the treatment from degarelix to a gonadotropin releasing hormone agonist after achieving stable disease control, on the clinical and oncological outcomes. Results: Our analysis was based on the data of 108 patients with prostate cancer who were treated with degarelix...
2018: Basic and Clinical Andrology
Hongtuan Zhang, Zhenpeng Lian, Guangyu Sun, Ranlu Liu, Yong Xu
To gain a comprehensive understanding of whether ABCC5 can regulate prostate cancer (PCa) progression, we performed microarray data analyses and identified that ABCC5 was drastically increased in primary PCa relative to normal samples, metastatic PCa relative to primary PCa, and castration-resistant PCa relative to hormone naïve PCa, respectively. Multivariate Cox regression analysis suggested that ABCC5 overexpression in PCa was an independent prognostic factor for both poor biochemical recurrence-free and overall survival...
2018: OncoTargets and Therapy
Kurt Miller, Günther G Steger, Daniela Niepel, Diana Lüftner
BACKGROUND: Patients with prostate cancer are at risk of impaired bone health. Prostate cancer has a propensity to metastasize to bone, after which patients are at risk of skeletal-related events (SREs). These complications are associated with increased mortality, substantial pain, and reduced quality of life. Patients are also at risk of bone loss due to androgen deprivation therapy (ADT), which can be compounded in elderly patients with reduced bone density. It is essential, therefore, that aspects of bone health and therapies able to prevent the occurrence of SREs are considered throughout the clinical course of prostate cancer...
July 9, 2018: Prostate Cancer and Prostatic Diseases
Elena V Ivanets, Anton N Yurchenko, Olga F Smetanina, Anton B Rasin, Olesya I Zhuravleva, Mikhail V Pivkin, Roman S Popov, Gunhild von Amsberg, Shamil Sh Afiyatullov, Sergey A Dyshlovoy
Four new indole-diterpene alkaloids asperindoles A⁻D ( 1 ⁻ 4 ) and the known p -terphenyl derivative 3″-hydroxyterphenyllin ( 5 ) were isolated from the marine-derived strain of the fungus Aspergillus sp., associated with an unidentified colonial ascidian. The structures of 1 ⁻ 5 were established by 2D NMR and HRESIMS data. The absolute configurations of all stereocenters of 1 ⁻ 4 were determined by the combination of ROESY data, coupling constants analysis, and biogenetic considerations. Asperindoles C and D contain a 2-hydroxyisobutyric acid (2-HIBA) residue, rarely found in natural compounds...
July 9, 2018: Marine Drugs
Ximena Leighton, Alakesh Bera, Ofer Eidelman, Michael Eklund, Narayanan Puthillathu, Harvey B Pollard, Meera Srivastava
BACKGROUND/AIM: Our studies showed that ANXA7 is a novel tumor suppressor gene that is lost in various aggressive forms of prostate cancer. However, little is known about the role of ANXA7 in the anticancer drug treatment towards different cancers. MATERIALS AND METHODS: The expression of ANXA7 was measured in the 60 cancer cell lines of the NCI-60 ADS project and correlated with the enhanced sensitivity to over 30,000 natural and synthetic compounds. RESULTS: Eucalyptol showed a high positive correlation with ANXA7 expression and castration-resistant prostate cancer cell death occurred very effectively in response to the combination of eucalyptol and overexpressed wt-ANXA7 than either agent alone...
July 2018: Anticancer Research
Rodney F Minchin, Neville J Butcher
BACKGROUND: Arylamine N-acetyltransferase 1 (NAT1) is a drug metabolizing enzyme that has been associated with cancer cell proliferation in vitro and with survival in vivo. NAT1 expression has been associated with the estrogen receptor and it has been proposed as a prognostic marker for estrogen receptor positive cancers. However, little is known about the distribution of NAT1 mRNA across an entire patient population or its effects on outcomes. To address this, gene expression data from breast cancer patient cohorts were investigated to identify sub-populations based on the level of NAT1 expression...
July 3, 2018: BMC Genomics
Matteo Giulietti, Matteo Santoni, Alessia Cimadamore, Francesco Carrozza, Francesco Piva, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli, Nicola Battelli, Rodolfo Montironi
Tumor microenvironment constitutes a complex network in which tumor cells communicate among them and with stromal and immune cells. It has been shown that cancer cells are able to exchange genetic materials through small extracellular vesicles (EVs), a heterogeneous group of vesicles with different size and shape, cargo content, and function. The importance to investigate populations of circulating EVs would be of great importance as prostate cancer (PCa) biomarkers. In several neoplasms as well as in PCa, nanometer-sized EVs of endosomal origin are implicated in supporting tumor growth and metastatic spread by both altering local stroma cells and creating a protumor environment that favors the formation of pre-metastatic niches...
2018: Frontiers in Oncology
Pasquale Rescigno, David Lorente, David Dolling, Roberta Ferraldeschi, Daniel Nava Rodrigues, Ruth Riisnaes, Susana Miranda, Diletta Bianchini, Zafeiris Zafeiriou, Spyridon Sideris, Ana Ferreira, Ines Figueiredo, Semini Sumanasuriya, Joaquin Mateo, Raquel Perez-Lopez, Adam Sharp, Nina Tunariu, Johann S de Bono
Background: Loss of PTEN is a common genomic aberration in castration-resistant prostate cancer (CRPC) and is frequently concurrent with ERG rearrangements, causing resistance to next-generation hormonal treatment (NGHT) including abiraterone. The relationship between PTEN loss and docetaxel sensitivity remains uncertain. Objective: To study the antitumor activity of docetaxel in metastatic CRPC in relation to PTEN and ERG aberrations. Design setting and participants: Single-centre, retrospective analysis of PTEN loss and ERG expression using a previously described immunohistochemistry (IHC) binary classification system...
May 2018: European urology oncology
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