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metastatic prostate cancer

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
Elena Incerti, Paola Mapelli, Luigi Gianolli, Maria Picchio
The detection of neoplastic lymph nodal involvement in prostate cancer (PCa) patients has relevant therapeutic and prognostic significance, both in the clinical settings of primary staging and restaging. Lymph nodal dissection (LND) currently represents the gold standard for evaluating the presence of lymph nodal involvement. However, this procedure is invasive, associated with morbidity, and may fail in detecting all potential lymph nodal metastatic regions. Currently the criteria for lymph nodal detection using conventional imaging techniques mainly rely on morphological assessment with unsatisfactory diagnostic accuracy...
October 17, 2016: World Journal of Urology
Jeffrey J Tosoian, Michael A Gorin, Steven P Rowe, Darian Andreas, Zsolt Szabo, Kenneth J Pienta, Martin G Pomper, Tamara L Lotan, Ashley E Ross
No abstract text is available yet for this article.
September 19, 2016: Clinical Genitourinary Cancer
Michael Rehman, Sreeharsha Gurrapu, Gabriella Cagnoni, Lorena Capparuccia, Luca Tamagnone
The secreted semaphorin Sema3E controls cell migration and invasiveness in cancer cells. Sema3E-receptor, PlexinD1, is frequently upregulated in melanoma, breast, colon, ovarian and prostate cancers; however, the mechanisms underlying PlexinD1 upregulation and the downstream events elicited in tumor cells are still unclear. Here we show that the canonical RBPjk-dependent Notch signaling cascade controls PlexinD1 expression in primary endothelial and cancer cells. Transcriptional activation was studied by quantitative PCR and promoter activity reporter assays...
2016: PloS One
Tapas Das, Ajit Shinto, Koramadai Karuppuswamy Kamaleshwaran, Sharmila Banerjee
Radiochemical studies and biological evaluation in animal models have shown superior radiochemical properties and better clearance pattern for Lu-DOTMP compared with Lu-EDTMP, an agent recently proven to be efficacious and safe for metastatic bone pain palliation. This prompted us to initiate the clinical evaluation of Lu-DOTMP. The images represent the whole-body scans of a prostate cancer patient (man, 67 years) with skeletal metastases recorded after administering 3.7 GBq (100 mCi) of Lu-DOTMP.
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
Elena Castro, Joaquin Mateo, David Olmos, Johann S de Bono
Several genomic studies have identified DNA repair gene defects in prostate cancer in the last 5 years. The mechanisms by which these DNA repair defects promote carcinogenesis and tumor progression in the prostate have not been fully elucidated, but their presence in at least 20-25% of metastatic castration-resistant prostate cancers (CRPCs) provides an opportunity for a therapeutic strategy that turns a tumor strength into its weakness and may lead to arguably the first molecularly stratified treatment for this disease...
September 2016: Cancer Journal
Min Yuen Teo, Michael J Morris
Prostate-specific membrane antigen (PSMA) is highly expressed on both benign and malignant prostatic tissue. Prostate-specific membrane antigen-directed therapy is conceptually promising, with a potential to additionally serve as a theranostic model in management of advanced prostate cancer. To date, various approaches have been devised and tested, including radiolabeled PSMA antibodies and inhibitor and antibody-drug conjugates. However, development and progress have faced challenges in determining the optimal combination of payload, PSMA-binding moiety, and linker technology...
September 2016: Cancer Journal
Oliver Sartor
Radiopharmaceuticals used in the treatment of castrate-resistant prostate cancer are reviewed herein with an emphasis on sequential and combination therapies. Four bone-seeking radiopharmaceuticals had been approved in the United States. Three of these are β-emitters (phosphorus-32, strontium-89, samarium-153-ethylenediaminetetramethylene-phosphonic acid) that are approved for palliative purposes. One α-emitter (radium-223 [Ra]) is approved for prolongation of survival in bone metastatic castrate-resistant prostate cancer...
September 2016: Cancer Journal
Michael W Drazer, Walter M Stadler
Most men with metastatic prostate cancer who are treated with androgen deprivation therapy will eventually develop castration-resistant disease. In this review, we examine the molecular mechanisms that constitute castration resistance and how these processes may be exploited using testosterone-based therapies. We detail how the utilization of superphysiologic doses of testosterone at regular intervals, followed by a rapid clearance of testosterone through continued chemical castration, also known as bipolar androgen therapy, offers an especially promising therapeutic approach...
September 2016: Cancer Journal
Zachery R Reichert, Maha Hussain
The development of metastatic castration-resistant prostate cancer (mCRPC) signals the terminal disease phase. The preceding hormone-dependent disease setting is effectively managed with androgen deprivation therapy. This foundation of treatment has a high rate of biochemical and clinical response and meaningful clinical benefit but is finite in duration as most cancers will progress to castration resistance. Historically, treatment for mCRPC entailed androgen receptor (AR) inhibitors (nilutamide, flutamide, bicalutamide), nonspecific steroidal biosynthesis inhibitors (ketoconazole, itraconazole), steroids (prednisone, diethylstilbesterol, dexamethasone), or palliative chemotherapy (mitoxantrone, estramustine), but none of these strategies impacted survival...
September 2016: Cancer Journal
Christos E Kyriakopoulos, Glenn Liu
Ever since the critical role of androgen deprivation therapy for the treatment of metastatic prostate cancer was established, several trials aimed to show an improved outcome with the early introduction of chemotherapy in metastatic disease. Until recently, all these trials-including the GETUG-AFU 15 trial-failed to confirm an improvement in survival. The recently published CHAARTED and STAMPEDE trials showed a striking benefit and changed the standard of care for patients with newly diagnosed metastatic prostate cancer...
September 2016: Cancer Journal
Daniel P Petrylak
No abstract text is available yet for this article.
September 2016: Cancer Journal
Daniel C Danila, Aliaksandra Samoila, Chintan Patel, Nicole Schreiber, Amrita Herkal, Aseem Anand, Diogo Bastos, Glenn Heller, Martin Fleisher, Howard I Scher
Circulating tumor cell (CTC) number measured with the CellSearch assay is prognostic for survival in metastatic castration-resistant prostate cancer before and after therapy. Using a standard operating protocol for sample collection, processing, and analysis, we compared detection rates of CellSearch performed using US Food and Drug Administration-cleared methodology with a second positive selection assay, AdnaTest, and a nonselection polymerase chain reaction (PCR)-based (direct detection PCR [DDPCR]) assay in 55 blood samples from 47 men with progressive metastatic castration-resistant prostate cancer...
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
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
Sanjoy Kumar Sureka, Ruchir Maheshwari, Shalini Agnihotri, Nilay Mitash, Shamim Ahmad, Anil Mandhani
BACKGROUND & OBJECTIVES: There is lack of data on natural history and progression of prostate cancer (PC) which have implications in the management of the disease. We undertook this retrospective study to analyze factors predicting progression of metastatic PC to castration-resistant prostate cancer (CRPC) in Indian men. METHODS: Complete records of 223 of the 489 patients with metastatic PC were obtained from computerized data based system in a tertiary care hospital in north India between January 2000 to June 2012...
May 2016: Indian Journal of Medical Research
T Bach-Gansmo, C Nanni, P T Nieh, L Zanoni, T V Bogsrud, H Sletten, K Korsan, J Kieboom, F Tade, O Odewole, A Chau, P Ward, M M Goodman, S Fanti, D M Schuster, F Willoch
PURPOSE: Sensitive detection of cancer foci in men experiencing biochemical recurrence following initial treatment of prostate cancer is of great clinical significance, with possible impact on subsequent treatment choice. We describe a multi-site experience of the efficacy and safety of the positron emission tomography/computer tomography agent fluciclovine ((18)F) following biochemical recurrence. MATERIALS AND METHODS: A total of 596 patients underwent fluciclovine ((18)F) positron emission tomography/computer tomography scanning at 4 clinical sites...
October 13, 2016: Journal of Urology
Yuan-Chin Tsai, Wei-Yu Chen, Man Kit Siu, Hong-Yuan Tsai, Juan Juan Yin, Jiaoti Huang, Yen-Nien Liu
It has been suggested that ETV6 serves as a tumor suppressor; however, its molecular regulation and cellular functions remain unclear. We used prostate cancer as a model system and demonstrated a molecular mechanism in which ETV6 can be regulated by epidermal growth factor receptor (EGFR) signaling through microRNA-96 (miR-96)-mediated downregulation. In addition, EGFR acts as a transcriptional coactivator that binds to the promoter of primary miR-96 and transcriptionally regulates miR-96 levels. We analyzed two sets of clinical prostate cancer samples, confirmed association patterns that were consistent with the EGFR-miR-96-ETV6 signaling model and demonstrated that the reduced ETV6 levels were associated with malignant prostate cancer...
October 13, 2016: Cancer Letters
Che-Kai Tsao, John Sfakianos, Bobby Liaw, Kiev Gimpel-Tetra, Margaret Kemeny, Linda Bulone, Mohammad Shahin, William Kyu Oh, Matthew David Galsky
LESSONS LEARNED: The safety and activity findings of abiraterone acetate plus prednisone treatment in black men with mCRPC were similar to results from previously conducted studies with largely white populations.Poor trial accrual continues to be a challenge in black men with mCRPC and further efforts are needed to address such underrepresentation. BACKGROUND: Self-identified black men have higher incidence and mortality from prostate cancer in the United States compared with white men but are dramatically underrepresented in clinical trials exploring novel therapies for metastatic castration-resistant prostate cancer (mCRPC)...
October 14, 2016: Oncologist
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