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Locally advanced prostate cancer

H Kumon, Y Ariyoshi, K Sasaki, T Sadahira, M Araki, S Ebara, H Yanai, M Watanabe, Y Nasu
As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kattan's nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection...
October 21, 2016: Cancer Gene Therapy
Annabelle South, Wendy R Parulekar, Matthew R Sydes, Bingshu E Chen, Mahesh K Parmar, Noel Clarke, Padraig Warde, Malcolm Mason
BACKGROUND: Recent trials have shown that the addition of external beam radiotherapy (EBRT) to androgen deprivation therapy (ADT) improves survival among men with locally advanced prostate cancer. OBJECTIVE: To examine the potential impact of these trials on changes in clinical practice and life-years saved. DESIGN SETTING AND PARTICIPANTS: A model was developed to examine the impact of changes in clinical practice in the UK. A survey of clinicians who treat men with prostate cancer in the UK and Canada was performed...
August 2016: European Urology Focus
Sirong Chen, Shing Kee Cheung, Ka-Nin Wong, Kwok Kee Wong, Chi-Lai Ho
A bedridden 90-year-old man with fever and elevated prostate-specific antigen (PSA) (49 ng/mL) was referred for differentiation between infection and tumor. F-FDG PET/CT was negative for infection, but Ga-PSMA PET/CT showed multiple lesions in prostate gland with infiltration to bladder wall and seminal vesicle, consistent with locally advanced prostate cancer. The lesion with the highest Ga-PSMA uptake was strongly avid for Ga-DOTATOC, suggesting neuroendocrine tumor differentiation. After hormonal therapy, PSA normalized, but chromogranin-A increased (from 251 to 398 ng/mL), inferring progression of neuroendocrine tumor differentiation...
October 18, 2016: Clinical Nuclear Medicine
Duncan C Gilbert, Trinh Duong, Howard G Kynaston, Abdulla A Alhasso, Fay H Cafferty, Stuart D Rosen, Subramanian Kanaga-Sundaram, Sanjay Dixit, Marc Laniado, Sanjeev Madaan, Gerald Collins, Alvan Pope, Andrew Welland, Matthew Nankivell, Richard Wassersug, Mahesh Kb Parmar, Ruth E Langley, Paul D Abel
OBJECTIVES: To compare quality of life (QoL) outcomes at 6 months between men with advanced prostate cancer (PCa) receiving either transdermal oestradiol (tE2) or LHRH agonists (LHRHa) for androgen deprivation therapy (ADT). PATIENTS AND METHODS: Men with locally advanced or metastatic PCa participating in an ongoing randomised, multi-centre UK trial comparing tE2 versus LHRHa for ADT were enrolled into a QoL sub-study. tE2 was delivered via 3 or 4 transcutaneous patches containing 100mcg of oestradiol/24 hours...
October 18, 2016: BJU International
Cavit Ceylan, Senol Tonyali, Ibrahim Keles
This study aimed to determine the effect of surgical margin positivity on biochemical recurrence (BCR) in patients with locally advanced prostate cancer (PCa) who underwent radical retropubic prostatectomy (RRP). The medical records of all patients with locally advanced PCa that underwent RRP were retrospectively reviewed. Patient demographics, digital rectal examination findings, prostate biopsy Gleason score, prostate volume, pre- and post-treatment prostate-specific antigen (PSA) levels, definitive pathology Gleason score, surgical margin status, seminal vesicle invasion, perineural invasion, absence or presence of BCR, and the time to BCR were analyzed...
October 2016: Kaohsiung Journal of Medical Sciences
David T Hoang, Kenneth A Iczkowski, Deepak Kilari, William See, Marja T Nevalainen
Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways...
October 10, 2016: Oncotarget
M H Jazayeri, H Amani, A A Pourfatollah, A Avan, G A Ferns, H Pazoki-Toroudi
Prostate-specific antigen (PSA) is used to screen for prostate disease, although it has several limitations in its application as an organ-specific or cancer-specific marker. Furthermore, a highly specific/sensitive and/or label-free identification of PSA still remains a challenge in the diagnosis of prostate anomalies. We aimed to develop a gold nanoparticle (GNP)-conjugated anti-PSA antibody-based localized surface plasmon resonance (LSPR) as a novel approach to detect prostatic disease. A total of 25 nm colloidal gold particles were prepared followed by conjugation with anti-PSA pAb (GNPs-PSA pAb)...
October 14, 2016: Cancer Gene Therapy
L Steentjes, S Siesling, F J Drummond, J G van Manen, L Sharp, A Gavin
We identified patient and disease characteristics associated with (1) "current" physical side-effects of any severity; and (2) "severe" physical side-effects "ever" experienced by 3,348 (54%) prostate cancer (PCa) survivors in Ireland diagnosed 2-18 years previously. Postal questionnaires collected symptoms at diagnosis, post-biopsy complications, comorbidities, primary treatments and physical side-effects post-treatment (urinary incontinence, erectile dysfunction, libido loss, bowel problems, breast changes, hot flushes, and fatigue, "ever" and "current" at time of questionnaire completion)...
October 10, 2016: European Journal of Cancer Care
Jeffrey J Tosoian, Michael A Gorin, Ashley E Ross, Kenneth J Pienta, Phuoc T Tran, Edward M Schaeffer
The oligometastatic state has been proposed as an intermediate stage of cancer spread between localized disease and widespread metastases. With improvements in diagnostic modalities such as functional imaging, oligometastatic prostate cancer is being diagnosed with greater frequency than ever before. Furthermore, the paradigm for treatment of advanced prostate cancers is shifting toward a more aggressive approach. Many questions surround the understanding of the process and consequences of oligometastasis, meaning that the contemporary literature offers a wide variety of definitions of oligometastatic prostate cancer...
October 11, 2016: Nature Reviews. Urology
J Ai, L E Pascal, L Wei, Y Zang, Y Zhou, X Yu, Y Gong, S Nakajima, J B Nelson, A S Levine, L Lan, Z Wang
Androgens are known to protect prostate cancer cells from DNA damage. Recent studies showed regulation of DNA repair genes by androgen receptor signaling in prostate cancers. ELL-associated factor 2 (EAF2) is an androgen-regulated tumor suppressor and its intracellular localization can be modulated by ultraviolet light, suggesting a potential role for EAF2 in androgen regulation of DNA repair in prostate cancer cells. Here we show that knockdown of EAF2 or its homolog EAF1 sensitized prostate cancer cells to DNA damage and the sensitization did not require p53...
October 10, 2016: Oncogene
Bhumika Wadhwa, Rashmi Dumbre
Prostate (CaP) cancer is the second-leading cause of cancer-related mortality in men in Western societies. Androgen receptor (AR) signaling is a critical survival pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease. Although a majority of patients initially respond to ADT, most will eventually develop castrate resistance. The recent discovery that AR signaling persists during systemic castration via intratumoral production of androgens led to the development of novel anti-androgen therapies...
October 6, 2016: Chemico-biological Interactions
Thomas J Johnston, Greg L Shaw, Alastair D Lamb, Deepak Parashar, David Greenberg, Tengbin Xiong, Alison L Edwards, Vincent Gnanapragasam, Peter Holding, Phillipa Herbert, Michael Davis, Elizabeth Mizielinsk, J Athene Lane, Jon Oxley, Mary Robinson, Malcolm Mason, John Staffurth, Prasad Bollina, James Catto, Andrew Doble, Alan Doherty, David Gillatt, Roger Kockelbergh, Howard Kynaston, Steve Prescott, Alan Paul, Philip Powell, Derek Rosario, Edward Rowe, Jenny L Donovan, Freddie C Hamdy, David E Neal
BACKGROUND: Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. OBJECTIVE: To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. DESIGN, SETTING, AND PARTICIPANTS: Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN...
October 6, 2016: European Urology
Stian Knappskog, Beryl Leirvaag, Liv B Gansmo, Pål Romundstad, Kristian Hveem, Lars Vatten, Per E Lønning
BACKGROUND: While germline CHEK2 mutations have been linked to a moderately elevated cancer risk, to date, a limited number of such mutations have been identified. Recently, we reported a germline nonsense mutation (C283T; R95*), introducing an early stop-codon, in two Norwegian patients diagnosed with locally advanced breast cancer. Both patients were resistant to anthracycline therapy, resembling what has been observed for TP53 mutations. METHODS: In the present study, we screened a large population based sample, including 3748 non-cancer individuals and 7081 incident cancer cases (breast cancer, n = 1717; prostate cancer n = 2501, lung cancer n = 1331 and colorectal cancer n = 1532), for the distribution of CHEK2 R95*...
2016: Hereditary Cancer in Clinical Practice
Zoran Campara, Dejan Simic, Predrag Aleksic, Aleksandar Spasic, Snjezana Milicevic
INTRODUCTION: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease...
July 27, 2016: Medical Archives
Florence Huguet, David Goldstein, Pascal Hammel
No abstract text is available yet for this article.
October 4, 2016: JAMA: the Journal of the American Medical Association
Ashish Jani, David P Horowitz
No abstract text is available yet for this article.
October 4, 2016: JAMA: the Journal of the American Medical Association
Adam T Szafran, Cliff Stephan, Michael Bolt, Maureen G Mancini, Marco Marcelli, Michael A Mancini
BACKGROUND: AR-V7 is an androgen receptor (AR) splice variant that lacks the ligand-binding domain and is isolated from prostate cancer cell lines. Increased expression of AR-V7 is associated with the transition from hormone-sensitive prostate cancer to more advanced castration-resistant prostate cancer (CRPC). Due to the loss of the ligand-binding domain, AR-V7 is not responsive to traditional AR-targeted therapies, and the mechanisms that regulate AR-V7 are still incompletely understood...
October 4, 2016: Prostate
Liyong Xing, Zhifei Liu, Gang Deng, Huan Wang, Yanfeng Zhu, Peng Shi, Bingyue Huo, Yindong Li
PURPOSE: Xanthogranulomatous prostatitis (XP) is a rare form of nonspecific granulomatous prostatitis that can clinically mimic high-grade prostatic carcinoma. It is difficult to diagnose it definitely in clinical settings. METHODS: We report a case of XP with prostate-rectal fistula and review the relevant literatures. RESULT: A 75-year-old man presented with rectal bleeding when he urinated. A locally advanced carcinoma of prostate was suspected initially following the physical, imaging, and hematologic examinations...
2016: Research and Reports in Urology
T Uo, H Dvinge, C C Sprenger, R K Bradley, P S Nelson, S R Plymate
The presence of intact ligand-binding domain (LBD) ensures the strict androgen-dependent regulation of androgen receptor (AR): binding of androgen induces structural reorganization of LBD resulting in release of AR from HSP90, suppression of nuclear export which otherwise dominates over import and nuclear translocation of AR as a transcription factor. Thus, loss or defects of the LBD abolish constraint from un-liganded LBD as exemplified by constitutively active AR variants (AR-Vs), which are associated with emerging resistance mechanism to anti-AR therapy in castration-resistant prostate cancer (mCRPC)...
October 3, 2016: Oncogene
Tanya Stoyanova, Mireille Riedinger, Shu Lin, Claire M Faltermeier, Bryan A Smith, Kelvin X Zhang, Catherine C Going, Andrew S Goldstein, John K Lee, Justin M Drake, Meghan A Rice, En-Chi Hsu, Behdokht Nowroozizadeh, Brandon Castor, Sandra Y Orellana, Steven M Blum, Donghui Cheng, Kenneth J Pienta, Robert E Reiter, Sharon J Pitteri, Jiaoti Huang, Owen N Witte
Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered in early disease to promote the development of prostate adenocarcinoma...
September 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
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