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Parp inhibitors prostate

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https://www.readbyqxmd.com/read/28069876/targeting-plk1-to-enhance-efficacy-of-olaparib-in-castration-resistant-prostate-cancer
#1
Xiaoqi Liu, Jie Li, Ruixin Wang, Yifan Kong, Meaghan M Broman, Colin Carlock, Long Chen, Zhiguo Li, Elia Farah, Timothy L Ratliff
Olaparib is a FDA-approved PARP inhibitor (PARPi) that has shown promise as a synthetic lethal treatment approach for BRCA-mutant castration-resistant prostate cancer (CRPC) in clinical use. However, emerging data has also shown that even BRCA-mutant cells may be resistant to PARPi. The mechanistic basis for these drug resistances is poorly understood. Polo-like kinase 1 (Plk1), a critical regulator of many cell cycle events, is significantly elevated upon castration of mice carrying xenograft prostate tumors...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28046739/su-f-j-225-histology-study-of-mr-guided-pulsed-focused-ultrasound-on-treatment-of-prostate-cancer-in-vivo
#2
L Chen, D Cvetkovic, X Chen, B Wang, R Gupta, C Ma
PURPOSE: Our previous study demonstrated significant tumor growth delay in the mice treated with pulsed high intensity focused ultrasound (pHIFU). The purpose of this study is to understand the cell killing mechanisms of pHIFU. METHODS: Prostate cancer cells (LNCaP), were grown orthotopically in 17 nude mice. Tumor-bearing mice were treated using pHIFU with an acoustic power of 25W, pulse width 100msec and 300 pulses in one sonication under MR guidance. Mutiple sonications were used to cover the whole tumor volume...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/27994514/the-correlation-between-parp1-and-brca1-in-ar-positive-triple-negative-breast-cancer
#3
Jiayan Luo, Juan Jin, Fang Yang, Zijia Sun, Wenwen Zhang, Yaqin Shi, Jing Xu, Xiaoxiang Guan
Triple-negative breast cancer (TNBC) lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression and thus cannot benefit from conventional hormonal or anti-HER2 targeted therapies. Anti-androgen therapy has shown a certain effect on androgen receptor (AR) positive TNBC. The emerging researches have proved that poly (ADP-ribose) polymerase (PARP) inhibitor is effective in BRCA1-deficient breast cancers. We demonstrated that combination of AR antagonist (bicalutamide) and PARP inhibitor (ABT-888) could inhibit cell viability and induce cell apoptosis significantly whatever in vitro or in vivo setting in AR-positive TNBC...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27956098/identification-of-natural-allosteric-inhibitor-for-akt1-protein-through-computational-approaches-and-in-vitro-evaluation
#4
T Pragna Lakshmi, Amit Kumar, Veena Vijaykumar, Sakthivel Natarajan, Ramadas Krishna
Akt, a serine/threonine protein kinase, is often hyper activated in breast and prostate cancers, but with poor prognosis. Allosteric inhibitors regulate aberrant kinase activity by stabilizing the protein in inactive conformation. Several natural compounds have been reported as inhibitors for kinases. In this study, to identify potential natural allosteric inhibitor for Akt1, we generated a seven-point pharmacophore model and screened it through natural compound library. Quercetin-7-O-β-d-glucopyranoside or Q7G was found to be the best among selected molecules based on its hydrogen bond occupancy with key allosteric residues, persistent polar contacts and salt bridges that stabilize Akt1 in inactive conformation and minimum binding free energy during molecular dynamics simulation...
December 9, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27915154/lipopolysaccharides-stimulated-macrophage-products-enhance-withaferin-a-induced-apoptosis-via-activation-of-caspases-and-inhibition-of-nf-%C3%AE%C2%BAb-pathway-in-human-cancer-cells
#5
Liang Piao, Zhao Canguo, Lu Wenjie, Cheng Xiaoli, Shi Wenli, Lu Li
Macrophages, as a major cellular component in tumor microenvironment, play an important role in tumor progression. However, their roles in modulation of cytotoxic chemotherapy are still not fully understood. Here, we investigated the influence of Lipoplysaccharides (LPS)-stimulated macrophage products (LSMP) on Withaferin A (WA), a natural compound that derived from the medicinal plant Withania somnifera, as an antitumor agent in human breast cancer cells MDA-MB-231 and prostate cancer cells PC-3. Our results revealed that LSMP may enhance WA-induced apoptosis in both cell lines, the underlying mechanisms of which are closely associated with activation of caspase-8, -9 and -3, cleavage of poly ADP-ribose polymerase (PARP), as well as specifically inhibiting the translocation of nuclear factor-κB (NF-κB) and down-regulation of anti-apoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and inhibitor of apoptosis protein (cIAP1/2)...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27849335/mycotoxin-verrucarin-a-inhibits-proliferation-and-induces-apoptosis-in-prostate-cancer-cells-by-inhibiting-prosurvival-akt-nf-kb-mtor-signaling
#6
Yongbo Liu, Xiaohua Gao, Dorrah Deeb, Yiguan Zhang, Jiajiu Shaw, Frederick A Valeriote, Subhash C Gautam
Trichothecenes are powerful mycotoxins that inhibit protein synthesis and induce ribotoxic stress response in mammalian cells. Verrucarin A (VC-A) is a Type D macrocyclic mycotoxin which inhibits cell proliferation and induces apoptosis in cancer cells. However, the antitumor activity of VC-A for prostate cancer cells has not been investigated. The objective of the present study was to determine the anticancer activity and its mechanism of action in hormone-responsive (LNCaP) and hormone-refractory (PC-3) carcinoma of the prostate (CaP) cell lines...
November 2016: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/27822685/sequencing-treatment-for-castration-resistant-prostate-cancer
#7
REVIEW
Catherine E Handy, Emmanuel S Antonarakis
Prostate cancer is the most common non-cutaneous cancer diagnosed in men and the second leading cause of male cancer deaths in the USA. While most cases are diagnosed in early stages, some will present as or progress to metastatic disease and eventually castration-resistant prostate cancer (mCRPC) which has a mortality rate exceeding 50 %. There are currently six approved systemic life-prolonging therapies for use in mCRPC, yet little data to guide sequencing. Clinical factors, including the presence or absence of symptoms and the presence or absence of visceral metastases, should help determine the best therapeutic choice at each treatment node...
December 2016: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/27755556/muscadine-grape-skin-extract-induces-an-unfolded-protein-response-mediated-autophagy-in-prostate-cancer-cells-a-tmt-based-quantitative-proteomic-analysis
#8
Liza J Burton, Mariela Rivera, Ohuod Hawsawi, Jin Zou, Tamaro Hudson, Guangdi Wang, Qiang Zhang, Luis Cubano, Nawal Boukli, Valerie Odero-Marah
Muscadine grape skin extract (MSKE) is derived from muscadine grape (Vitis rotundifolia), a common red grape used to produce red wine. Endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR) that serves as a survival mechanism to relieve ER stress and restore ER homeostasis. However, when persistent, ER stress can alter the cytoprotective functions of the UPR to promote autophagy and cell death. Although MSKE has been documented to induce apoptosis, it has not been linked to ER stress/UPR/autophagy...
2016: PloS One
https://www.readbyqxmd.com/read/27753448/the-molecular-underpinnings-of-prostate-cancer-impacts-on-management-and-pathology-practice
#9
REVIEW
Daniel Nava Rodrigues, Gunther Boysen, Semini Sumanasuriya, George Seed, Angelo M De Marzo, Johann de Bono
Prostate cancer (PCa) is a clinically heterogeneous disease and current treatment strategies are based largely on anatomical and pathological parameters. In the recent past, several DNA sequencing studies of primary and advanced PCa have revealed recurrent patterns of genomic aberrations that expose mechanisms of resistance to available therapies and potential new drug targets. Suppression of androgen receptor (AR) signalling is the cornerstone of advanced prostate cancer treatment. Genomic aberrations of the androgen receptor or alternative splicing of its mRNA are increasingly recognised as biomarkers of resistance to AR-targeted therapies such as abiraterone or enzalutamide...
January 2017: Journal of Pathology
https://www.readbyqxmd.com/read/27749330/targeting-dna-repair-the-role-of-parp-inhibition-in-the-treatment-of-castration-resistant-prostate-cancer
#10
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
https://www.readbyqxmd.com/read/27727003/non-nad-like-poly-adp-ribose-polymerase-1-inhibitors-effectively-eliminate-cancer-in-vivo
#11
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...
November 2016: EBioMedicine
https://www.readbyqxmd.com/read/27686597/parp-inhibitors-and-stratified-treatment-of-prostate-cancer
#12
Anita Lavery, Clare Gilson, Simon Chowdhury
No abstract text is available yet for this article.
October 17, 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27675112/nanoformulation-of-the-parp-inhibitor-olaparib-enables-radiosensitization-of-a-radiation-resistant-prostate-cancer-model
#13
P Baldwin, A L Van De Ven, N Seitzer, S Clohessy, R A Cormack, M Makrigiorgos, P P Pandolfi, S Sridhar
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27665838/contemporary-molecular-tests-for-prognosis-and-treatment-guidance-for-castration-resistant-prostate-cancer
#14
Carlo Buonerba, Giuseppe Di Lorenzo, Guru Sonpavde
Currently, clinical factors related to the malignancy and patient-related factors such as performance status and comorbidities are employed to select agents to treat metastatic castration resistant prostate cancer (mCRPC). Areas covered: This paper covers emerging molecular panels that may be used in the clinic as prognostic or predictive biomarkers to treat mCRPC. Expert commentary: The expression of androgen receptor variant (AR-V)-7 in circulating tumor cells appears especially promising to select patients for taxane chemotherapy versus androgen inhibitors, abiraterone and enzalutamide...
October 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/27600766/evaluation-of-the-radiosensitizing-potency-of-chemotherapeutic-agents-in-prostate-cancer-cells
#15
Colin Rae, Robert J Mairs
PURPOSE: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. Although ionizing radiation is used to treat localized and metastatic prostate cancer, the most efficient use of radiotherapy is yet to be defined. Our purpose was to determine in vitro the potential benefit to be gained by combining radiation treatment with cytotoxic drugs. MATERIALS AND METHODS: Inhibitors of DNA repair and heat shock protein 90 and an inducer of oxidative stress were evaluated in combination with X-radiation for their capacity to reduce clonogenic survival and delay the growth of multicellular tumor spheroids...
October 3, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27596623/loss-of-chd1-causes-dna-repair-defects-and-enhances-prostate-cancer-therapeutic-responsiveness
#16
Vijayalakshmi Kari, Wael Yassin Mansour, Sanjay Kumar Raul, Simon J Baumgart, Andreas Mund, Marian Grade, Hüseyin Sirma, Ronald Simon, Hans Will, Matthias Dobbelstein, Ekkehard Dikomey, Steven A Johnsen
The CHD1 gene, encoding the chromo-domain helicase DNA-binding protein-1, is one of the most frequently deleted genes in prostate cancer. Here, we examined the role of CHD1 in DNA double-strand break (DSB) repair in prostate cancer cells. We show that CHD1 is required for the recruitment of CtIP to chromatin and subsequent end resection during DNA DSB repair. Our data support a role for CHD1 in opening the chromatin around the DSB to facilitate the recruitment of homologous recombination (HR) proteins. Consequently, depletion of CHD1 specifically affects HR-mediated DNA repair but not non-homologous end joining...
November 2016: EMBO Reports
https://www.readbyqxmd.com/read/27590317/dna-repair-in-prostate-cancer-biology-and-clinical-implications
#17
REVIEW
Joaquin Mateo, Gunther Boysen, Christopher E Barbieri, Helen E Bryant, Elena Castro, Pete S Nelson, David Olmos, Colin C Pritchard, Mark A Rubin, Johann S de Bono
CONTEXT: For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA damage repair pathway are common in PC, particularly in late-stage disease, and may be relevant for treatment stratification. OBJECTIVE: To review current knowledge on the prevalence and clinical significance of aberrations in DNA repair genes in PC, particularly in metastatic disease...
August 31, 2016: European Urology
https://www.readbyqxmd.com/read/27428646/parp-inhibitors-in-clinical-use-induce-genomic-instability-in-normal-human-cells
#18
Shuhei Ito, Conleth G Murphy, Ekaterina Doubrovina, Maria Jasin, Mary Ellen Moynahan
Poly(ADP-ribose) polymerases (PARPs) are the first proteins involved in cellular DNA repair pathways to be targeted by specific inhibitors for clinical benefit. Tumors harboring genetic defects in homologous recombination (HR), a DNA double-strand break (DSB) repair pathway, are hypersensitive to PARP inhibitors (PARPi). Early phase clinical trials with PARPi have been promising in patients with advanced BRCA1 or BRCA2-associated breast, ovary and prostate cancer and have led to limited approval for treatment of BRCA-deficient ovary cancer...
2016: PloS One
https://www.readbyqxmd.com/read/27426307/combined-inhibition-of-pi3k-and-parp-is-effective-in-the-treatment-of-ovarian-cancer-cells-with-wild-type-pik3ca-genes
#19
Dong Wang, Chengbo Li, Yuan Zhang, Min Wang, Nan Jiang, Lin Xiang, Ting Li, Thomas M Roberts, Jean J Zhao, Hailing Cheng, Pixu Liu
OBJECTIVE: Combined inhibition of PI3K and PARP has been shown to be effective in the treatment of preclinical models of breast cancer and prostate cancer independent of BRCA or PIK3CA mutational status. However, the knowledge about this combination treatment in ovarian cancer is limited. The aim of this study was to evaluate the therapeutic effect of PI3K inhibitor BKM120 and PARP inhibitor Olaparib on ovarian cancer cell lines bearing wild-type PIK3CA genes. METHODS: We exposed three wild-type PIK3CA ovarian cancer cell lines to a PI3K inhibitor BKM120 and/or a PARP inhibitor Olaparib...
September 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27351942/norcantharidin-induces-apoptosis-in-human-prostate-cancer-cells-through-both-intrinsic-and-extrinsic-pathways
#20
Pei-Yu Yang, Dan-Ning Hu, Ying-Hsien Kao, I-Ching Lin, Chih-Yuan Chou, Yang-Chang Wu
BACKGROUND: Norcantharidin, a modified pure compound from blister beetles, was previously demonstrated to induce apoptosis of cancer cells. This study investigated its anti-cancer activity in prostate cancer cells and the mechanisms involved. METHODS: Two human prostate cancer cell lines, 22Rv1 and Du145, were treated with norcantharidin at concentrations ranging from 3 to 30μg/ml. Cytotoxic effect of norcantharidin was determined by use of the 3-(4,5-dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay...
October 2016: Pharmacological Reports: PR
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