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B1 Prostate Cancer

Rachana Patel, Janis Fleming, Ernest Mui, Carolyn Loveridge, Peter Repiscak, Arnaud Blomme, Victoria Harle, Mark Salji, Imran Ahmad, Katy Teo, Freddie C Hamdy, Ann Hedley, Niels van den Broek, Gillian Mackay, Joanne Edwards, Owen J Sansom, Hing Y Leung
Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of treatment-resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre-clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self-sufficient form of CRPC Mechanistically, HER2-IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1-mediated cholesterol uptake in SPRY2-deficient tumours...
March 14, 2018: EMBO Molecular Medicine
Zhixiong Dong, Yang Yang, Shuxia Liu, Jun Lu, Baiqu Huang, Yu Zhang
HDAC inhibitors (HDACis) have been demonstrated with profound antiproliferative activities in various tumor types. Previously, we screened several polyoxometalate HDACis based on our p21 luciferase promoter system and demonstrated that such HDACis have antitumor activity. Here, we further investigate the antitumor mechanism of PAC-320, a compound among the polyoxometalates, in human prostate cancer. We demonstrate that PAC-320 is a broad-spectrum HDACi and could inhibit growth of prostate cancer cells in vitro and in vivo...
January 2, 2018: Oncotarget
James W Peacock, Ario Takeuchi, Norihiro Hayashi, Liangliang Liu, Kevin J Tam, Nader Al Nakouzi, Nastaran Khazamipour, Tabitha Tombe, Takashi Dejima, Kevin Ck Lee, Masaki Shiota, Daksh Thaper, Wilson Cw Lee, Daniel Hf Hui, Hidetoshi Kuruma, Larissa Ivanova, Parvin Yenki, Ivy Zf Jiao, Shahram Khosravi, Alice L-F Mui, Ladan Fazli, Amina Zoubeidi, Mads Daugaard, Martin E Gleave, Christopher J Ong
Growth factor receptor tyrosine kinase (RTK) pathway activation is a key mechanism for mediating cancer growth, survival, and treatment resistance. Cognate ligands play crucial roles in autocrine or paracrine stimulation of these RTK pathways. Here, we show SEMA3C drives activation of multiple RTKs including EGFR, ErbB2, and MET in a cognate ligand-independent manner via Plexin B1. SEMA3C expression levels increase in castration-resistant prostate cancer (CRPC), where it functions to promote cancer cell growth and resistance to androgen receptor pathway inhibition...
January 18, 2018: EMBO Molecular Medicine
M E Gasparian, M L Bychkov, A V Yagolovich, M P Kirpichnikov, D A Dolgikh
Cytokine TRAIL selectively induces apoptosis in vitro and in vivo in tumor cells without affecting normal cells, but its therapeutic application is limited, since many primary tumors are insensitive to TRAIL. To improve the efficiency of TRAIL, we have previously developed TRAIL mutant variant DR5-B, which binds the apoptosis-inducing death receptor DR5 as efficiently as wild type TRAIL, but shows almost no affinity to other receptors. In this study, we investigated the effect of the chemotherapeutic agent cisplatin on the cytotoxicity of TRAIL variants in 12 tumor cell lines of various origin...
November 2017: Doklady. Biochemistry and Biophysics
Jin Zeng, Wei Liu, Yi-Zeng Fan, Da-Lin He, Lei Li
Rationale: Docetaxel-mediated chemotherapy is the first-line standard approach and has been determined to show a survival advantage for metastatic castration-resistant prostate cancer (mCRPC) patients. However, a substantial proportion of patients eventually becomes refractory due to drug resistance. The detailed mechanisms remain unclear. We have previously reported that Prostate Leucine Zipper (PrLZ), a specific oncogene of prostate cancer (PCa), promotes PCa cell growth at the castration-resistant stage, thus suggesting a vital role of PrLZ in the progression of CRPC...
2018: Theranostics
Biyan Zhang, Yun Lai, Yufeng Li, Nan Shu, Zheng Wang, Yanping Wang, Yunsen Li, Zijun Chen
Isoliquiritigenin is a natural chalcone derived from Glycyrrhiza, which has been reported to have anti-tumor activity in recent years. Here, we investigate the anticancer efficacy and associated mechanisms of isoliquiritigenin in human prostate cancer PC-3 and 22RV1 cells. Isoliquiritigenin (25-50μM) inhibited cell proliferation, induced cell apoptosis, and caused G2/M cell cycle arrest in vitro. This agent also repressed the growth of PC-3 xenograft tumors in vivo with the results of hematoxylin/eosin staining and immunohistochemistry staining showing differences between isoliquiritigenin-treated groups and control group...
December 22, 2017: European Journal of Pharmacology
Peipei Xu, Xiaotian Xia, Zhili Yang, Yuan Tian, Jianzhong Di, Minggao Guo
Tectonic family member 1 (TCTN1) is one of the tectonic family members, and a regulator of the hedgehog signaling pathway, which has been studied in various cancer types, including prostate and pancreatic cancer. However, its function in thyroid cancer has not been well documented. Therefore, the present study investigated the function of TCTN1 in thyroid cancer using a loss-of-function assay. Lentivirus-mediated RNA interference was applied to downregulate TCTN1 in the thyroid cancer cell lines, CAL62 and 8305C...
October 2017: Experimental and Therapeutic Medicine
DeAnna Henderson, Danielle Frieson, Jeffrey Zuber, Solomon S Solomon
BACKGROUND: Metformin (MF), a diabetic drug, has antineoplastic activity as adjuvant therapy for breast cancer and prostate cancer. MF is thought to work via inhibition of mammalian target of rapamycin and activation of p53 and liver kinase B1 via adenosine 5'-monophosphate-activated protein kinase. We investigated survival, recurrences and metastasis in patients with type 2 diabetes mellitus (DM2) along with colorectal cancer (CC) or lung cancer (LC) taking MF using the electronic medical record in Memphis Veterans Affairs Medical Center (colon, n = 202; lung, n = 180)...
September 2017: American Journal of the Medical Sciences
Long Fan, Qingyi Zhu, Li Liu, Cuicui Zhu, Haojie Huang, Shan Lu, Ping Liu
Androgen receptor (AR) is a key transcription factor playing a critical role in prostate cancer (PCa) initiation and progression. However, the molecular mechanisms of AR action in prostate cancer are not very clear. CXCL13, known as B cell attracting chemokine1 (BCA-1), is a member of CXC chemokine family and relevant to cancer metastasis. This study shows that CXCL13 is an androgen-responsive gene and involved in AR-induced PCa cell migration and invasion. In clinical specimens, expression of CXCL13 in PCa tissues is markedly higher than that in adjacent normal tissues...
August 8, 2017: Oncotarget
Chen Gao, Yinglu Zhou, Zhongling Jiang, Yuan Zhao, Dongjun Zhang, Xia Cong, Rongfeng Cao, Huatao Li, Wenru Tian
Scutellaria altissima L. is a common traditional Chinese medicine used to treat inflammation in some countries. Scutellarin, an active major flavone glycoside isolated from the traditional Chinese medicine Scutellaria altissima L., has been shown to offer various beneficial biochemical effects on cerebrovascular diseases and inflammation. However, the antiproliferative effects of Scutellarin in prostate cancer and the underlying mechanism are not fully elucidated. In the present study, we aimed to ascertain whether Scutellarin inhibits cancer cell growth and to further explore the molecular mechanism...
September 2017: Oncology Reports
Kaylin M McMahon, Michael P Plebanek, C Shad Thaxton
Efficient systemic administration of therapeutic short interfering RNA (siRNA) is challenging. High-density lipoproteins (HDL) are natural in vivo RNA delivery vehicles. Specifically, native HDLs: 1) Load single-stranded RNA; 2) Are anionic, which requires charge reconciliation between the RNA and HDL, and 3) Actively target scavenger receptor type B-1 (SR-B1) to deliver RNA. Emphasizing these particular parameters, we employed templated lipoprotein particles (TLP), mimics of spherical HDLs, and self-assembled them with single-stranded complements of, presumably, any highly unmodified siRNA duplex pair after formulation with a cationic lipid...
November 15, 2016: Advanced Functional Materials
Long Fan, Qingyi Zhu, Li Liu, Cuicui Zhu, Haojie Huang, Shan Lu, Ping Liu
Androgen receptor (AR) is a key transcription factor playing a critical role in prostate cancer (PCa) initiation and progression. However, the molecular mechanisms of AR action in prostate cancer are not very clear. CXCL13, known as B cell attracting chemokine1 (BCA-1), is a member of CXC chemokine family and relevant to cancer metastasis. This study shows that CXCL13 is an androgen-responsive gene and involved in AR-induced PCa cell migration and invasion. In clinical specimens, expression of CXCL13 in PCa tissues is markedly higher than that in adjacent normal tissues...
June 7, 2017: Oncotarget
Nassim Tayari, Isabell K Steinseifer, Kirsten M Selnæs, Tone F Bathen, Marnix C Maas, Arend Heerschap
OBJECTIVES: Inclusion of 3-dimensional H magnetic resonance spectroscopic imaging (3D-H-MRSI) in routine multiparametric MRI of the prostate requires good quality spectra and easy interpretable metabolite maps of the whole organ obtained without endorectal coil in clinically feasible acquisition times. We evaluated if a semi-LASER pulse sequence with gradient offset independent adiabaticity refocusing pulses (GOIA-sLASER) for volume selection can meet these requirements. MATERIALS AND METHODS: Thirteen patients with suspicion of prostate cancer and 1 patient known to have prostate cancer were examined at 3 T with a multichannel body-receive coil...
June 19, 2017: Investigative Radiology
Siddiq Pasha Shaik, M V P S Vishnuvardhan, Faria Sultana, A V Subba Rao, Chandrakant Bagul, Debanjan Bhattacharjee, Jeevak Sopanrao Kapure, Nishant Jain, Ahmed Kamal
1,2,3-Triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates (5a-v) were designed, synthesized and evaluated for their cytotoxic potency against some human cancer cell lines like DU-145 (prostate), HeLa (cervical), MCF-7 (breast) HepG2 (liver) and A549 (lung). Preliminary results revealed that some of these conjugates like 5f and 5k exhibited significant antiproliferative effect against human breast cancer cells (MCF-7) with IC50 values of 0.60 and 0.78µM respectively. Flow cytometric analysis of the cell cycle demonstrated an increase in the percentage of cells in the G2 /M phase which was further authenticated by elevation of cyclin B1 protein levels...
July 1, 2017: Bioorganic & Medicinal Chemistry
Jian-Zhong Lin, Zeng-Jun Wang, Wei De, Ming Zheng, Wei-Zhang Xu, Hong-Fei Wu, Alex Armstrong, Jia-Geng Zhu
Resistance to docetaxel is a major clinical problem in advanced prostate cancer. The overexpression of AXL receptor tyrosine kinase (AXL) has been correlated with chemotherapeutic drug resistance. However, the role of AXL expression in docetaxel resistance in prostate cancer is yet unclear. In this study, we demonstrate that AXL is overexpressed and activated independent of Gas6 in docetaxel-resistant prostate cancer cells (PC3-DR and DU145-DR). Moreover, we show that forced overexpression of AXL in PC3 and DU145 cells is sufficient to induce resistance to docetaxel in these cell lines...
June 20, 2017: Oncotarget
Xuan Zhang, Jing Zhao, Xiangyang Gao, Dongsheng Pei, Chao Gao
As microtubules have a vital function in the cell cycle, oncologists have developed microtubule inhibitors capable of preventing uncontrolled cell division, as in the case of cancer. The anthelmintic drug albendazole (ABZ) has been demonstrated to inhibit hepatocellular, ovarian and prostate cancer cells via microtubule targeting. However, its activity against human gastric cancer (GC) cells has remained to be determined. In the present study, ABZ was used to treat GC cells (MKN-45, SGC-7901 and MKN-28). A a CCK-8 cell proliferation assay was performed to assess the effects of ABZ on cell viability and cell cycle changes were assessed using flow cytometry...
February 2017: Experimental and Therapeutic Medicine
Tae-Hyun Kim, Joo-Man Park, Mi-Young Kim, Yong-Ho Ahn
The incidence of prostate cancer (PC) is growing rapidly throughout the world, in probable association with the adoption of western style diets. Thus, understanding the molecular pathways triggering the development of PC is crucial for both its prevention and treatment. Here, we investigated the role of the metabolism-associated protein, CREB3L4, in the proliferation of PC cells. CREB3L4 was upregulated by the synthetic androgen, R1881, in LNCaP PC cells (an androgen-dependent cell line). Knockdown of CREB3L4 resulted in decreased androgen-dependent PC cell growth...
March 24, 2017: Scientific Reports
Fang Zhang, Jun-Jun Shi, Kiran Thakur, Fei Hu, Jian-Guo Zhang, Zhao-Jun Wei
In this study, four homo/heterogenous polysaccharides (HBSS, CHSS, DASS, and CASS) extracted from peony seed dreg with respective molecular weights of 3467, 4677, 229, and 56 kDa were evaluated for anti-cancerous attributes in prostate cancer cells (Pc-3), colon cancer cells (HCT-116), human breast cancer cells (MCF-7), cervical cancer (Hela cells) and human embryonic kidney 293 (HEK 293) cells as control. Among them, CASS and DASS extracted by alkali, consisted of 34.43% Gal, 26.39% Ara, 21.80% Glc and 35...
2017: Frontiers in Pharmacology
Santosh Kumar Singh, Saswati Banerjee, Edward P Acosta, James W Lillard, Rajesh Singh
Resveratrol (RES) is the most effective natural products used for the treatment of a variety of cancers. In this study, we tested the effect of RES in enhancing the efficacy of docetaxel (DTX) treatment in prostate cancer (PCa) cells. The C4-2B and DU-145 cell lines were treated with RES, DTX and combination followed by evaluating the apoptosis and cell cycle progression. The combined drug treatment up-regulates the pro-apoptotic genes (BAX, BID, and BAK), cleaved PARP and down regulates the anti-apoptotic genes (MCL-1, BCL-2, BCL-XL) promoting apoptosis...
March 7, 2017: Oncotarget
Qingping Liu, Xiaoli Ji, Zehe Ge, Haipeng Diao, Xiuli Chang, Lihua Wang, Qing Wu
Connexins (Cxs), the subunits of gap junction channels, are involved in many physiological processes. Aberrant control of Cxs and gap junction intercellular communication may contribute to many diseases, including the promotion of cancer. Cd exposure is associated with increased risk of human prostate cancer and benign prostatic hyperplasia. The roles of Cxs in the effects of Cd on the prostate have, however, not been reported previously. In this study, the human prostate epithelial cell line RWPE-1 was exposed to Cd...
February 8, 2017: Journal of Applied Toxicology: JAT
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