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Small cell prostate cancer

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
Shankar Vamadevan, Ken Le, Chuong Bui, Robert Mansberg
A 68-year-old man with treated prostate cancer 3 years earlier and small cleaved B-cell follicular lymphoma diagnosed 1 year prior and monitored clinically with no active intervention ("watch and wait" approach) was referred for Ga-prostate-specific membrane antigen (PSMA) PET/CT with rising prostate-specific antigen level. PET/CT demonstrated diffuse PSMA uptake in the prostate (SUVmax 3.6) and multiple PSMA-avid nonenlarged lymph nodes. Moderate PSMA uptake (SUVmax 4.7) was also noted in an enlarged right inguinal lymph node (SUVmax 4...
October 5, 2016: Clinical Nuclear Medicine
Daniel H Hovelson, Scott A Tomlins
Molecular biomarkers play little role in the current treatment of metastatic castration-resistant prostate cancer (CRPC). The advent of next-generation sequencing (NGS) has enabled the comprehensive molecular characterization of the genomic and transcriptomic landscape of both untreated primary prostate cancer and CRPC. Recent studies demonstrating the feasibility of interinstitution studies obtaining and NGS profiling of metastatic biopsies, targeted NGS approaches applicable to routine formalin-fixed, paraffin-embedded specimens, and NGS approaches applicable to circulating DNA and circulating tumor cells portend near-term adoption of NGS approaches in the management and treatment of CRPC...
September 2016: Cancer Journal
Li Qi, Zhong Lu, Yong-Hong Sun, Hai-Tao Song, Wei-Kang Xu
Prostate carcinoma is a devastating disease which is characterized by insidious early symptoms, rapid progression and a poor prognosis. Tripartite motif-containing protein 16 (TRIM16) was identified as an estrogen- and antiestrogen-regulated gene in epithelial cells stably expressing estrogen receptors. The protein encoded by this gene contains two B-box domains and a coiled-coiled region that are characteristic of the B-box zinc finger protein family. Proteins belonging to this family have been reported to be involved in a variety of biological processes including cell growth, differentiation and pathogenesis...
October 17, 2016: International Journal of Molecular Medicine
Sarah A Altınoğlu, Ming Wang, Kathleen Q Li, Yuyang Li, Qiaobing Xu
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor, mutated or inactive in a large percentage of human cancers. Restoring PTEN activity in cancer cells through gene therapy has shown to inhibit cell growth and induce apoptosis, particularly in cells with a PTEN deficiency. Gene therapy, however, comes with some inherent risks such as triggering an immune response and permanent off target effects. Nanoparticle assisted protein delivery could mitigate these liabilities while maintaining therapeutic integrity...
October 17, 2016: Biomaterials Science
Sankar N Maity, Mark A Titus, Revekka Gyftaki, Guanglin Wu, Jing-Fang Lu, S Ramachandran, Elsa M Li-Ning-Tapia, Christopher J Logothetis, John C Araujo, Eleni Efstathiou
Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a validated treatment target for the treatment of metastatic castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) inhibits both 17α-hydroxylase (hydroxylase) and 17,20-lyase (lyase) reactions catalyzed by CYP17A1 and thus depletes androgen biosynthesis. However, coadministration of prednisone is required to suppress the mineralocorticoid excess and cortisol depletion that result from hydroxylase inhibition. VT-464, a nonsteroidal small molecule, selectively inhibits CYP17A1 lyase and therefore does not require prednisone supplementation...
October 17, 2016: Scientific Reports
Jin-Hua He, Bao-Xia Li, Ze-Ping Han, Mao-Xian Zou, Li Wang, Yu-Bing Lv, Jia-Bin Zhou, Ming-Rong Cao, Yu-Guang Li, Jing-Zhi Zhang
Rapidly accumulated evidence has shown that long non-coding RNA (lncRNAs) disregulation is involved in human tumorigenesis in many cancers, including prostate cancer (PCa). LncRNAs can regulate essential pathways that contribute to tumor initiation and progression with tissue specificity, which suggests that lncRNAs could be valuable biomarkers and therapeutic targets. Prostate cancer antigen 3 (PCA3), also known as differential display code 3 (DD3), is one such lncRNA that maps to chromosome 9q21-22. PCA3 expression is highly specific to PCa...
October 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Oleksandr N Kryvenko, Sean R Williamson, Kiril Trpkov, Nilesh S Gupta, Daniel Athanazio, Martin K Selig, Paul Taylor Smith, Cristina Magi-Galluzzi, Merce Jorda
Small cell-like change (SCLC) is a rare prostate lesion which has been described in only two previous studies (total of eight cases). Its relation to possible neuroendocrine differentiation remained unclear. We evaluated 11 SCLC cases with immunohistochemistry and electron microscopy. SCLC was characterized by crowded hyperchromatic small nuclei with scant cytoplasm, rosette-like structures, finely granular chromatin with indistinct nucleoli, and lack of mitoses, apoptoses, and necroses. In nine cases, SCLC was admixed with high-grade cancer, and in two cases, it represented a separate intraductal process, spatially remote from a low-volume Gleason score 6 (grade group 1) cancer...
October 14, 2016: Virchows Archiv: An International Journal of Pathology
Colin Thomas, Yingbiao Ji, Niraj Lodhi, Elena Kotova, Aaron Dan Pinnola, Konstantin Golovine, Peter Makhov, Kate Pechenkina, Vladimir Kolenko, Alexei V Tulin
The clinical potential of PARP-1 inhibitors has been recognized >10years ago, prompting intensive research on their pharmacological application in several branches of medicine, particularly in oncology. However, natural or acquired resistance of tumors to known PARP-1 inhibitors poses a serious problem for their clinical implementation. Present study aims to reignite clinical interest to PARP-1 inhibitors by introducing a new method of identifying highly potent inhibitors and presenting the largest known collection of structurally diverse inhibitors...
October 4, 2016: EBioMedicine
Manuel Gunkel, Inn Chung, Stefan Wörz, Katharina I Deeg, Ronald Simon, Guido Sauter, David T W Jones, Andrey Korshunov, Karl Rohr, Holger Erfle, Karsten Rippe
The microscopic analysis of telomere features provides a wealth of information on the mechanism by which tumor cells maintain their unlimited proliferative potential. Accordingly, the analysis of telomeres in tissue sections of patient tumor samples can be exploited to obtain diagnostic information and to define tumor subgroups. In many instances, however, analysis of the image data is conducted by manual inspection of 2D images at relatively low resolution for only a small part of the sample. As the telomere feature signal distribution is frequently heterogeneous, this approach is prone to a biased selection of the information present in the image and lacks subcellular details...
October 7, 2016: Methods: a Companion to Methods in Enzymology
Rahul Mannan, Tejinder Singh Bhasin, Mridu Manjari, Gagandeep Singh, Puneet Kaur Bhatia, Sonam Sharma
BACKGROUND: Prostate carcinoma is the second leading cause of cancer-related deaths in males worldwide. The burden is expected to grow 1.7 million new cases and 499,000 new deaths by 2030. In developing countries such as India, prostate carcinoma will show an increase by 140% in the next few years. Although the diagnosis of prostate carcinoma can usually be made on histological features, now a days many immunohistochemical (IHC) markers are used to distinguish it from benign mimickers as well as in predicting prognosis and treatment...
October 2016: Indian Journal of Pathology & Microbiology
Stine Krogh Steffensen, Hans Albert Pedersen, Khem B Adhikari, Bente Birgitte Laursen, Elena-Claudia Jensen, Søren Høyer, Michael Borre, Helene Holm Pedersen, Mette Borre, David Edwards, Inge S Fomsgaard
Rye bread contains high amounts of benzoxazinoids and in vitro studies have shown suppressive effects of selected benzoxazinoids on prostate cancer cells. Thus research into benzoxazinoids as possible suppressors of prostate cancer is demanded. A pilot study was performed in which ten prostate cancer patients received a rye-enriched diet one week prior to prostatectomy. Plasma and urine samples were collected pre- and post-intervention. Ten prostate biopsies were obtained from each patient and histologically evaluated...
October 10, 2016: Journal of Agricultural and Food Chemistry
Hesham Fathy Hassan Hassan, Ahmed Mohamed Mansour, Amira Morad Hussein Abo-Youssef, Bakheet E M Elsadek, Basim Anwar Shehata Messiha
Currently, the outcomes of conventional chemotherapeutic approaches are unsatisfactory. Clinical application of nanoparticles seems promising. We aim to evaluate the possible antitumor activity of zinc oxide nanoparticles (ZnONPs) as a chemotherapeutic approach in in vitro and in vivo experimental models. An in vitro study was performed on three different cell lines, namely human hepatocellular carcinoma (HEPG2), human prostate cancer (PC3), and none-small cell lung cancer (A549) cell lines. An in vivo study using diethylnitrosamine (DENA)-induced HCC in adult male Wistar rats was conducted to investigate the potential antitumor activity of ZnONPs in HCC and the possible underlying mechanisms...
October 8, 2016: Clinical and Experimental Pharmacology & Physiology
Daniela Alves, Maria Eufémia Calmeiro, Rosa Silva, Hugo Coelho
A 70-year-old man with a history of prostate cancer, previously submitted to surgical castration and trans-urethral resection of the prostate, was admitted to Accident and Emergency department. He had been suffering from osteoarticular and abdominal pain, and recent weight loss. An abdominal and a pelvic CT showed multiple hepatic metastases and a pelvic mass, but his prostate-specific antigen values were low (0.26 n/mL). A biopsy of a hepatic metastasis and of the pelvic mass revealed a small-cell neuroendocrine prostate cancer, a rare and aggressive androgen-independent form of prostate cancer with a poor prognosis...
October 5, 2016: BMJ Case Reports
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
S Vijaya Laxmi, P Anil, G Rajitha, Asha Jyothi Rao, Peter A Crooks, B Rajitha
In the search of efficient anticancer agents, here, new 5-(4-alkylbenzyledene)thiazolidine-2,4-dione derivatives (5a-g) have been successfully synthesized and characterized and are evaluated for anticancer and antimicrobial activities using DNA cleavage studies. In vitro studies on anticancer activity of compound 5d (NSC: 768619/1) was done against the full panel of 60 human tumor cell lines. The five-level dose activity results revealed that, the compound 5d was active against all the cell lines, it has shown potential activity against leukemia SR (GI50: 2...
October 2016: Journal of Chemical Biology
Steven P Rowe, Alexander Drzezga, Bernd Neumaier, Markus Dietlein, Michael A Gorin, Michael R Zalutsky, Martin G Pomper
Radiohalogenated agents are often the first line of pursuit in the development of new radiopharmaceuticals-whether antibodies, peptides, or small molecules-because of their ease of synthesis, lack of substantial steric perturbation of the original affinity agent (in some cases, providing enhanced affinity), and capacity to be transformed into therapeutics (in some cases, with a mere switch of an isotope). They often provide proof of a principle before optimization for pharmacokinetics or generation of radiometallated agents, when the latter are necessary...
October 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Neeta Pandit-Taskar, Darren R Veach, Josef J Fox, Howard I Scher, Michael J Morris, Steven M Larson
Castration-resistant prostate cancer (CRPC) is the lethal form of prostate cancer, and more than 26,000 men will die from this disease in 2016. The pathophysiology of CRPC is clearly multifactorial, but most often, androgen receptor (AR) upregulation is associated with its earliest beginnings and the AR increase is part of the multimolecular complex including downstream effector proteins linked to AR (AR-axis) responsible for rapid proliferation and malignant features of the malignant cell. In both animal models and patients, glycolysis (Warburg effect) is also an early manifestation of CRPC transformation...
October 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Daniel Ching, Matthew Brown, Cindy Forrest, Dickon Hayne
INTRODUCTION: Pure small cell prostate cancer (SCPC) cases are very rare. Acute zonal occult outer retinopathy (AZOOR) has been described as a non-neoplastic retinopathy. We report the first case of pure SCPC preceded by AZOOR in the literature. CASE REPORT: A 59year old gentleman presented with an obstructed infected urinary system. He had a diagnosis of AZOOR 6 months ago that was investigated with full body imaging without any suspicious findings. However, the most recent CT findings demonstrated extensive disease dissemination...
September 22, 2016: International Journal of Surgery Case Reports
Xiao X Wei, Stephen Chan, Serena Kwek, Jera Lewis, Vinh Dao, Li Zhang, Matthew R Cooperberg, Charles J Ryan, Amy M Lin, Terence W Friedlander, Brian Rini, Christopher Kane, Jeffry P Simko, Peter R Carroll, Eric J Small, Lawrence Fong
Granulocytic-macrophage colony-stimulating factor (GM-CSF) is used as an adjuvant in cancer vaccine trials and has the potential to enhance antitumor efficacy with immunotherapy; however, its immunologic effects are not fully understood. Here, we report results from a phase I study of neoadjuvant GM-CSF in patients with localized prostate cancer undergoing radical prostatectomy. Patients received subcutaneous injections of GM-CSF (250 μg/m(2)/day) daily for 2 weeks (cohort 1; n = 6), 3 weeks (cohort 2; n = 6), or 4 weeks (cohort 3; n = 6)...
September 29, 2016: Cancer Immunology Research
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