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prostate cancer progression

Benjamin Kearns, Abdullah Pandor, Matt Stevenson, Jean Hamilton, Duncan Chambers, Mark Clowes, John Graham, M Satish Kumar
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana(®), Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
October 22, 2016: PharmacoEconomics
Weidan Na, Qing Liu, Bowen Sui, Tianyu Hu, Xingguang Su
A novel and effective fluorescence strategy was developed for sensitive and selective detection of acid phosphatase (ACP). A förster resonance energy transfer (FRET) biosensor was established by attaching nile red (NR) to graphene quantum dots (GQDs) via lecithin/β-Cyclodextrin (lecithin/β-CD) complex as the linker. The introduction of lecithin/β-CD would brought GQDs-NR pair close enough through both electrostatic interaction and hydrophobic interaction, thereby making the FRET occur and thus resulting in the fluorescence quenching of GQDs (donor) and meanwhile the fluorescence enhancement of NR (acceptor)...
December 1, 2016: Talanta
Meng-Bo Hu, Hua Xu, Ji-Meng Hu, Wen-Hui Zhu, Tian Yang, Qiang Ding
Leptin and adiponectin signaling was associated with development and progression of various cancers. The present study aimed to clarify the role of genetic variants in leptin, adiponectin and their receptors in prostate cancer. After comprehensive search and manuscript scanning, a total of 49 genetic variants were enrolled and examined for their relations to cancer risk and aggressiveness. In the meta-analysis, LEP rs7799039 (allele contrast: OR 1.133, 95%CI 1.024-1.254), ADIPOQ rs2241766 (allele contrast: OR 1...
October 19, 2016: Oncotarget
Stefano Salciccia, Alessandro Gentilucci, Susanna Cattarino, Alessandro Sciarra
On the basis of the trials available, are we ready to consider GnRH antagonists better than agonists? Is there a population of patients who may benefit from antagonists more than agonists?We specifically focused our analysis on the significance of oncological results obtained in phase III trials directly comparing Degarelix with GnRH agonists. Oncological results were evaluated only in 1 trial (CS21) with some subanalysis and they were not the primary endpoints of the study. The follow-up duration was 364 days, and therefore, the number of events (all causes deaths and prostate cancer (PC), Prostate Specific Antigen (PSA), Hazard ratio (HR)-related deaths) was very low in both groups and this aspect strongly reduces the significance of overall survival evaluation...
October 15, 2016: Urologia
Pavel Damborský, Katarzyna M Koczula, Andrea Gallotta, Jaroslav Katrlík
Lateral flow assays (LFAs) enable the simple and rapid detection and quantification of analytes and is popular for point-of-care (PoC), point-of-use and outdoor testing applications. LFAs typically depend on antibody or nucleic acid based recognition. We present the innovative concept of a LFA using lectins in the role of the biorecognition element. Lectins are a special kind of glycan-binding protein and the lectin-based LFA herein described was developed for the determination of the glycosylation of free prostate specific antigen (PSA)...
October 21, 2016: Analyst
Sundhar Ramalingam, Adva Eisenberg, Wen Chi Foo, Jennifer Freedman, Andrew J Armstrong, Larry G Moss, Michael R Harrison
Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome...
October 21, 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
David Jarrard, Badrinath Konety, Wei Huang, Tracy Downs, Jill Kolesar, Kyung Mann Kim, Tom Havighurst, Joel Slaton, Margaret G House, Howard L Parnes, Howard H Bailey
INTRODUCTION AND OBJECTIVES: Prostate cancer (PCa) represents an important target for chemoprevention given its prolonged natural history and high prevalence. Epidemiologic and laboratory data suggest that vitamin D and genistein (soy isoflavone) may decrease PCa progression. The effect of vitamin D on prostate epithelial cell proliferation and differentiation is well documented and genistein may augment this affect through inhibition of the CYP24 enzyme, which is responsible for intracellular vitamin D metabolism...
2016: American Journal of Clinical and Experimental Urology
Nada Lallous, Eric Leblanc, Ravi Sn Munuganti, Mohamed D H Hassona, Nader Al Nakouzi, Shannon Awrey, Helene Morin, Mani Roshan-Moniri, Kriti Singh, Sam Lawn, Takeshi Yamazaki, Hans H Adomat, Christophe Andre, Mads Daugaard, Robert N Young, Emma S Tomlinson Guns, Paul S Rennie, Artem Cherkasov
The development of new anti-androgens such as enzalutamide or androgen synthesis inhibitors like abiraterone have improved patient outcomes in the treatment of advanced prostate cancer (PCa). However, due to the development of drug resistance and tumor cell survival, the majority of these patients progress to the refractory state of castration-resistant prostate cancer (CRPC). Thus, newer therapeutic agents and a better understanding of their mode of action are needed for treating these CRPC patients. We demonstrated previously that targeting the Binding Function 3 (BF3) pocket of the androgen receptor (AR) has great potential for treating patients with CRPC...
October 7, 2016: Molecular Cancer Therapeutics
Matthew I Milowsky, Matthew D Galsky, Michael J Morris, Daniel J Crona, Daniel J George, Robert Dreicer, Kin Tse, Jesika Petruck, Iain J Webb, Neil H Bander, David M Nanus, Howard I Scher
BACKGROUND: This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer. PATIENTS AND METHODS: A total of 62 patients received MLN2704 at ascending doses on 4 schedules: weekly (60, 84, 118, and 165mg/m(2); 12 patients); every 2 weeks (120, 168, 236, and 330mg/m(2); 15 patients); every 3 weeks (330 and 426mg/m(2); 18 patients); and on days 1 and 15 of a 6-week schedule (6-week cycle, 330mg/m(2); 17 patients)...
October 17, 2016: Urologic Oncology
Lori E Lowes, David Goodale, Ying Xia, Carl Postenka, Matthew M Piaseczny, Freeman Paczkowski, Alison L Allan
Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of ≥5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch® system, the "gold standard" clinical platform. However, ~35% of metastatic PCa patients assessed by CellSearch® have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis...
October 15, 2016: Oncotarget
Peter Hammarsten, Tove Dahl Scherdin, Christina Hägglöf, Pernilla Andersson, Pernilla Wikström, Pär Stattin, Lars Egevad, Torvald Granfors, Anders Bergh
In the present study we have investigated whether Caveolin-1 expression in non-malignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients managed by watchful waiting. Caveolin-1 was measured in prostate tissues obtained through transurethral resection of the prostate from 395 patients diagnosed with prostate cancer. The majority of the patients (n = 298) were followed by watchful waiting after diagnosis. Tissue microarrays constructed from malignant and non-malignant prostate tissue were stained with an antibody against Caveolin-1...
2016: PloS One
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
Silvana Giacinti, Paolo Carlini, Michela Roberto, Maria Bassanelli, Lidia Strigari, Francesco Pavese, Anna M Aschelter, Alessandra Felici, Maurizio Valeriani, Francesco Cognetti, Paolo Marchetti
Abiraterone acetate (AA) demonstrated its efficacy in the treatment of patients with metastatic castration resistance prostate cancer (mCRPC) in predocetaxel and postdocetaxel setting. However, we learn from pivotal studies that forms of primary and acquired resistance to this drug exist. Patient selection becomes so crucial to optimize treatment results. Potential predictive biomarkers have been identified but are not yet validated. In this scenario, clinical features and disease characteristics may still be of value in selecting patients for different treatments...
October 19, 2016: Anti-cancer Drugs
Eugenio Zoni, Gabri van der Pluijm
The skeleton represents a common site of metastases for osteotropic cancers such as prostate and breast tumors and novel therapeutic targets and new markers for the monitoring of bone lesions are urgently needed. The formation of bone metastases is a complex process that starts at the level of the confined tumor and that is characterized by a dynamic crosstalk between the primary cancer and the future metastatic site, the bone. Factors released by the primary tumor contribute to prepare a fertile "soil", where a "pre-metastatic niche" is established prior to future colonization by cancer cells...
September 2016: Journal of Bone Oncology
Meng Wu, Lishann Ingram, Ezequiel J Tolosa, Renzo E Vera, Qianjin Li, Sungjin Kim, Yongjie Ma, Demetri D Spyropoulos, Zanna Beharry, Jiaoti Huang, Martin E Fernandez-Zapico, Houjian Cai
Although the differentiation of oncogenically transformed basal progenitor cells is one of the key steps in prostate tumorigenesis, the mechanisms mediating this cellular process are still largely unknown. Here we demonstrated that an expanded p63+ and CK5+ basal/progenitor cell population, induced by the concomitant activation of oncogenic Kras(G12D) and androgen receptor (AR) signaling, underwent cell differentiation in vivo. The differentiation process led to suppression of the p63 expressing cells with a decreased number of CK5+ basal cells, but an increase of CK8+ luminal tumorigenic cells, and revealed a hierarchal lineage pattern consisting of p63+/CK5+ progenitor, CK5+/CK8+ transitional progenitor, and CK8+ differentiated luminal cells...
October 19, 2016: Journal of Biological Chemistry
Shuai Gao, Yanfei Gao, Housheng Hansen He, Dong Han, Wanting Han, Amy Avery, Jill A Macoska, Xiaming Liu, Sen Chen, Fen Ma, Shaoyong Chen, Steven P Balk, Changmeng Cai
Although well characterized as a transcriptional activator that drives prostate cancer (PCa) growth, androgen receptor (AR) can function as a transcriptional repressor, and high-level androgens can suppress PCa proliferation. The molecular basis for this repression activity remains to be determined. Genes required for DNA replication are highly enriched among androgen-repressed genes, and AR is recruited to the majority of these genes, where it rapidly represses their transcription. This activity is enhanced in PCa cells expressing high AR levels and is mediated by recruitment of hypophosphorylated retinoblastoma protein (Rb)...
October 18, 2016: Cell Reports
Mandi M Hopkins, Kathryn E Meier
The effects of fatty acids on cancer cells have been studied for decades. The roles of dietary long-chain n-3 polyunsaturated fatty acids, and of microbiome-generated short-chain butyric acid, have been of particular interest over the years. However, the roles of free fatty acid receptors (FFARs) in mediating effects of fatty acids in tumor cells have only recently been examined. In reviewing the literature, the data obtained to date indicate that the long-chain FFARs (FFA1 and FFA4) play different roles than the short-chain FFARs (FFA2 and FFA3)...
October 19, 2016: Handbook of Experimental Pharmacology
Zheng Zhang, Bo Jin, Yaqiong Jin, Shengquan Huang, Xiaohua Niu, Zebin Mao, Dianqi Xin
Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex...
October 15, 2016: Experimental Cell Research
Ruo-Kai Lin, Yuh-Feng Lin, Ming-Jen Hsu, Chang-Lin Hsieh, Chen-Yu Wang, Chih-Chiang Huang, Wei-Jan Huang
Some hydroxamate compounds induce cancer cell death by intracellular reactive oxygen species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited higher activity than original lovastatin. Of these compounds, compound 3c had the most potent activity. Test of cytotoxicity in a panel of human cancer cell lines indicated compound 3c had activities superior to cisplatin in prostate cancer PC-3 cells and breast cancer T47D cells...
October 6, 2016: Bioorganic & Medicinal Chemistry Letters
Yoko Yamada, Nobuaki Matsubara, Ken-Ichi Tabata, Takefumi Satoh, Naoto Kamiya, Hiroyoshi Suzuki, Takashi Kawahara, Hiroji Uemura, Akihiro Yano, Satoru Kawakami
BACKGROUND: Both abiraterone acetate (AA) and enzalutamide are promising agents for patients with pre- and post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC). Several retrospective analysis suggested clinical cross-resistance between these agents in patients previously treated with docetaxel. However, data on the antitumor activity of AA as a second androgen receptor-targeting new agent after the failure of enzalutamide in chemotherapy-naive mCRPC patients is unavailable...
October 18, 2016: BMC Research Notes
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