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Novel treatments prostate

Makito Miyake, Nobumichi Tanaka, Shunta Hori, Sayuri Ohnishi, Hiroo Takahashi, Tomomi Fujii, Takuya Owari, Kenta Ohnishi, Kota Iida, Yosuke Morizawa, Daisuke Gotoh, Yoshitaka Itami, Yasushi Nakai, Takeshi Inoue, Satoshi Anai, Kazumasa Torimoto, Katsuya Aoki, Kiyohide Fujimoto
BACKGROUND: Normal tissue damage caused by radiotherapy remains the largest dose-limiting factor in radiotherapy for cancer. Therefore, the aim of this study was to investigate the supplementary oral 5-aminolevulinic acid (ALA) to standard radiation therapy as a novel radioprotective approach that would not compromise the antitumor effect of radiation in normal rectal and bladder mucosa in a syngenic prostate cancer (PCa) model. METHODS: To evaluate the radiosensitizing effect of ALA in vitro, clonogenic survival assays were performed in DU145, PC3, and MyC-CaP cell lines...
November 18, 2018: Prostate
Amro Aboukameel, Irfana Muqbil, Erkan Baloglu, William Senapedis, Yosef Landesman, Christian Argueta, Michael Kauffman, Hua Chang, Trinayan Kashyap, Sharon Shacham, Jasper E Neggers, Dirk Daelemans, Elisabeth I Heath, Asfar S Azmi
Emerging studies have shown that the expression of AR splice variants (ARv) lacking ligand-binding domain is associated with castrate-resistant prostate cancer (CRPC) and higher risk of tumor metastasis and recurrence. Nuclear export protein XPO1 regulates the nuclear localization of many proteins including tumor suppressor proteins. Increased XPO1 in prostate cancer is associated with a high Gleason score and bone metastasis. In this study, we found that high expression of AR splice variant 7 (AR-v7) was correlated with increased XPO1 expression...
October 19, 2018: Oncotarget
Elise J Devlin, Hayley S Whitford, Linley A Denson, Andrew E Potter
CONTEXT: Previous research has indicated pre-treatment response expectancies of side effects often predict subsequent toxicity severity. However, this has been largely based on female patients undergoing chemotherapy. OBJECTIVES: We tested whether this association also occurred in a novel cohort; men with prostate cancer undergoing radiotherapy. We investigated these associations throughout treatment (before and after side effects were medically predicted to occur), controlling known and novel variables...
November 14, 2018: Journal of Pain and Symptom Management
Chengfei Liu, Wei Lou, Joy C Yang, Liangren Liu, Cameron M Armstrong, Alan P Lombard, Ruining Zhao, Onika D V Noel, Clifford G Tepper, Hong-Wu Chen, Marc Dall'Era, Christopher P Evans, Allen C Gao
Protein homeostasis (proteostasis) is a potential mechanism that contributes to cancer cell survival and drug resistance. Constitutively active androgen receptor (AR) variants confer anti-androgen resistance in advanced prostate cancer. However, the role of proteostasis involved in next generation anti-androgen resistance and the mechanisms of AR variant regulation are poorly defined. Here we show that the ubiquitin-proteasome-system (UPS) is suppressed in enzalutamide/abiraterone resistant prostate cancer...
November 16, 2018: Nature Communications
Takayuki Arai, Satoko Kojima, Yasutaka Yamada, Sho Sugawara, Mayuko Kato, Kazuto Yamazaki, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
Androgen deprivation therapy is frequently used to treat prostate cancer (PCa) but resistance can occur, a condition known as castration-resistant prostate cancer (CRPC). Thus, novel approaches for identification of CRPC are important for designing effective prostate cancer (PCa) treatments. Analysis of microRNA (miRNA) expression signatures by RNA sequencing showed that both passenger and guide strands of the miR-455 duplex (miR-455-5p and miR-455-3p, respectively) acted as anti-tumor miRNAs in PCa cells. The involvement of miRNA passenger strands in cancer pathogenesis is a novel concept for miRNA functionality...
November 15, 2018: Molecular Oncology
Faisal M Khan
Prostate cancer is the most prevalent form of cancer and second most common form of cancer deaths among men in the United States. Physicians work with patients to make difficult treatment decisions. They are often aided by a multitude of prognostic models to assess risk and predict outcomes. These survival analysis models may analyze features characterizing biomolecular and histomorphic properties of the solid tumor sample. Commonly, multiple samples per patient are analyzed and features are combined in some way to generate a single result, such as by taking the median measurement...
July 2018: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Marzena Wyganowska-Świątkowska, Mateusz Tarnowski, Daniel Murtagh, Ewa Skrzypczak-Jankun, Jerzy Jankun
The mortality rates of cancer patients decreased by ~1.5% per year between 2001 and 2015, although the decrease depends on patient sex, ethnic group and type of malignancy. Cancer remains a significant global health problem, requiring a search for novel treatments. The most common property of malignant tumors is their capacity to invade adjacent tissue and to metastasize, and this cancer aggressiveness is contingent on overexpression of proteolytic enzymes. The components of the plasminogen activation system (PAS) and the metalloproteinase family [mainly matrix metalloproteinases (MMPs)] are overexpressed in malignant tumors, driving the local invasion, metastasis and angiogenesis...
November 7, 2018: International Journal of Molecular Medicine
Ariunbold Natsagdorj, Kouji Izumi, Kaoru Hiratsuka, Kazuaki Machioka, Hiroaki Iwamoto, Renato Naito, Tomoyuki Makino, Suguru Kadomoto, Kazuyoshi Shigehara, Yoshifumi Kadono, Wen-Jye Lin, Aerken Maolake, Atsushi Mizokami
Understanding the mechanism of chemoresistance and disease progression in patients with prostate cancer is important for developing novel treatment strategies. In particular, developing resistance to cabazitaxel is a major challenge in patients with docetaxel- and castration-resistant prostate cancer (CRPC) because cabazitaxel is often administered as a last resort. However, the mechanism by which cabazitaxel resistance develops is still unclear. C-C motif chemokine ligands (CCLs) were shown to contribute to castration resistance of prostate cancer cells via an autocrine mechanism...
November 13, 2018: Cancer Science
Lixia Fan, Zhenglei He, Sarah A Head, Yinghui Zhou, Ting Lu, Xulong Feng, Xueqing Zhang, Meng Zhang, Yongjun Dang, Xinghong Jiang, Minghua Wang
Background/Purpose: Prostate cancer is a major burden on public health and a major cause of morbidity and mortality among men worldwide. Drug combination therapy is known as a powerful tool for the treatment of cancer. The aim of this study is to evaluate the synergistic inhibitory mechanisms of clofoctol and sorafenib in the treatment of prostate cancer. However, the molecular mechanisms of this phenomenon have not been illuminated clearly. In this study, we investigated the anti-tumor effects of clofoctol in combination with sorafenib in vitro and in vivo...
2018: Cancer Management and Research
Marcello Tucci, Clizia Zichi, Consuelo Buttigliero, Francesca Vignani, Giorgio V Scagliotti, Massimo Di Maio
The new-generation hormonal agent enzalutamide has been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC), in both post- and predocetaxel setting, due to the significant improvement in overall survival. More recently, enzalutamide also showed impressive results in the treatment of men with nonmetastatic CRPC. Unfortunately, not all patients with CRPC are responsive to enzalutamide, and even in responders, benefits are limited by the development of drug resistance. Adaptive resistance of metastatic prostate cancer to enzalutamide treatment can be due to the activation of both androgen receptor (AR)-dependent pathways (expression of constitutively active AR splice variants, AR point mutations, gene amplification and overexpression) and mechanisms independent of AR signaling pathway (altered steroidogenesis, upregulation of the glucocorticoid receptor, epithelial-mesenchymal transition, neuroendocrine transformation, autophagy and activation of the immune system)...
2018: OncoTargets and Therapy
Spyridon Skoufias, Mikaël Sturny, Rodrigo Fraga-Silva, Theodore G Papaioannou, Nikolaos Stergiopoulos, Ioannis Adamakis, Constantinos A Constantinides
INTRODUCTION: Many studies have shown that electrostimulation of the cavernosal nerve can induce and maintain penile erection. Based on these discoveries, neurostimulation to activate the erectile response has been considered a potential solution to treat erectile dysfunction (ED). However, despite recognized potential, this technology has not been further developed. The barrier is the complex anatomy of the human cavernous nerve, which challenges the intraoperative identification of the cavernosal nerves for electrode placement...
November 2018: Journal of Sexual Medicine
Ying Chen, Qing Wang, Mi Wang, Ming Li
Prostate cancer (PC) is one of the most common human malignancies, which has been steadily rising among males in many countries. The leucine-rich repeats and immunoglobulin-like domains (LRIG) genes were applied in the prognosis of different types of cancers, including PC. In that case, this study is supposed to investigate the effects of LRIG3 on PC cells. LRIG3 was overexpressed or under-expressed by the rAd and siRNA to determine the effect of LRIG3 on PC and explore the possible mechanism. The mRNA and protein levels of LRIG3 were tested by RT-qPCR and western blot analysis...
November 6, 2018: International Journal of Biological Macromolecules
Justine M Cunningham, Enzo A Barberi, John Miller, Joshua P Kim, Carri K Glide-Hurst
MR-only treatment planning and MR-IGRT leverage MRI's powerful soft tissue contrast for high-precision radiation therapy. However, anthropomorphic MR-compatible phantoms are currently limited. This work describes the development and evaluation of a custom-designed, modular, pelvic end-to-end (PETE) MR-compatible phantom to benchmark MR-only and MR-IGRT workflows. For construction considerations, subject data were assessed for phantom/skeletal geometry and internal organ kinematics to simulate average male pelvis anatomy...
November 8, 2018: Journal of Applied Clinical Medical Physics
Edson Crusca, Luis Guilherme Mansor Basso, Wanessa Fernanda Altei, Reinaldo Marchetto
Antimicrobial peptides have been extensively described as bioactive agents, mainly considering their selective toxicity towards bacteria but not to healthy mammalian cells. In past years, this class of compounds has been classified as an attractive and novel family of anticancer agents. Pantinin peptides isolated from scorpion Pandinus imperator presented antimicrobial activity. In this study, we have explored the in vitro antitumor activity of antimicrobial pantinin peptides against the tumor cell lines MDA-MB-231 (breast adenocarcinoma) and DU - 145 (prostate adenocarcinoma) and healthy fibroblasts HGF - 1...
November 2018: Biochimica et biophysica acta. Biomembranes
Lindsay Dearden, Natalie Shalet, Cristiana Artenie, Andrew Mills, Claire Jackson, Laura Grant, Adam Gater
Clinical studies have demonstrated the benefits of abiraterone acetate + prednisone (AAP) and enzalutamide (ENZ) in significantly improving survival among metastatic castration-resistant prostate cancer (mCRPC) patients. However, evidence regarding patient's real-world experience, particularly with respect to fatigue, treatment satisfaction and health-related quality of life (HRQoL) is limited. Interviews were initially conducted with patients (n = 38) and carers (n = 12) to elicit qualitative data regarding their experiences...
November 8, 2018: European Journal of Cancer Care
Yi Zhi, Xiaojun Wu, Wenhao Shen, Yongquan Wang, Xiaozhou Zhou, Peng He, Jinhong Pan, Zhiwen Chen, Weibing Li, Zhansong Zhou
The aim of the present study was to investigate the activities of novel synthetic epidermal growth factor receptor (EGFR) inhibitors (ZINC05463076, ZINC2102846 and ZINC19901103) against prostate tumors, in vitro models and investigate the potential underlying mechanisms. A panel of prostate tumor cell lines (LNCaP, DU-145, PC-3 and LNCaP-AI cells) were used to evaluate antitumor activity of ZINC05463076, ZINC2102846, and ZINC19901103 in vitro . Cell growth and clonal formation were determined by MTT assay and Soft agar colony formation assay, respectively...
November 2018: Oncology Letters
Ryan L Steinberg, Brett A Johnson, Jeffrey A Cadeddu
Minimally invasive radical prostatectomy has rapidly been adopted as the primary means of surgical intervention for prostate cancer. Intraoperative tissue retraction relies on either gravity (via positioning) or use of additional ports and instrumentation. We report the use of a novel trocar-less magnetic retractor system to aid with tissue retraction. Three patients underwent robotic-assisted radical prostatectomy in the treatment of prostatic adenocarcinoma at a single tertiary care institution. All surgeries utilized the Levita™ Magnetic Surgical System (San Mateo, CA) without the use of a fourth robotic arm...
November 7, 2018: Journal of Robotic Surgery
Marah Hehemann, Shawn Choe, Elizabeth Kalmanek, Daniel Harrington, Samuel I Stupp, Kevin T McVary, Carol A Podlasek
Urinary incontinence affects 40% of elderly men, is common in diabetic patients and in men treated for prostate cancer, with a prevalence of up to 44%. Seventy-two percent of prostatectomy patients develop stress urinary incontinence (SUI) in the first week after surgery and individuals who do not recover within 6 months generally do no regain function without intervention. Incontinence has a profound impact on patient quality of life and a critical unmet need exists to develop novel and less invasive SUI treatments...
November 6, 2018: Scientific Reports
Sounak Roy, Haley D Axelrod, Kenneth C Valkenburg, Sarah Amend, Kenneth J Pienta
Approximately 29 000 men die of prostate cancer (PCa) each year in the United States, and 90% to 100% of them are due to incurable bone metastasis. It is difficult to determine (1) when PCa disseminates in the natural history of the disease; (2) where cancer cell disseminates before becoming overt metastatic lesions; and (3) which tumors are aggressive and which are indolent. Tumor tissue and liquid (blood and bone marrow) biopsies provide important information to answer these questions, but significant limitations exist for immunostaining strategies that assess protein expression in these tissues...
November 2, 2018: Journal of Cellular Biochemistry
O E Kale, O Awodele, A J Akindele
ETHNOPHARMACOLOGICAL RELEVANCE: Novel therapeutic opportunities from medicinal agents continue to arouse scientific interest in recent times. Still, there is a dearth of information as regards experimental evidence generated from medicinal plants that would yield pharmacological agents for the treatment of erectile dysfunction. Acridocarpus Smeathmannii (DC.) Guill. & Perr. Root (ASR) has a long history as an aphrodisiac in African traditional medicine. Thus, this study investigated the reproductive potentials and associated biochemical mechanisms of its hydroethanolic extract (HEASR) in male Wistar rats...
October 31, 2018: Journal of Ethnopharmacology
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