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https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#1
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29132681/-dna-repair-as-a-therapeutic-target
#2
REVIEW
Lauriane Eberst, Medhi Brahmi, Philippe A Cassier
The transmission of an intact and stable genetic code at each cell division relies on different DNA repair systems. Germline mutations of some of these genes cause cancer predisposition, whereas somatic mutations are frequently found in various cancer types, generating genomic instability. As a consequence, cancer cell becomes more susceptible to additional DNA damage. Pharmacological inhibition of DNA repair pathways exploits this frailty: it triggers more damages than cancer cell can tolerate, finally leading to apoptosis...
November 10, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29117515/metformin-and-epothilone-a-treatment-up-regulate-pro-apoptotic-parp-1-casp-3-and-h2ax-genes-and-decrease-of-akt-kinase-level-to-control-cell-death-of-human-hepatocellular-carcinoma-and-ovary-adenocarcinoma-cells
#3
Aneta Rogalska, Barbara Bukowska, Agnieszka Marczak
High mortality rates in ovarian and liver cancer are largely a result of resistance to currently used chemotherapy. Here, we investigated genotoxic and pro-oxidant effects of metformin (MET) and epothilone A (A) in combination with respect to apoptosis in HepG2 and SKOV-3 cancer cells. Reactive oxygen species (ROS) was studied using 2',7'-dichlorodihydrofluoresein diacetate, and samples were analyzed for the presence and absence of the N-acetylcysteine (NAC). Expression of genes involved in programmed cell death, oxidative and alkylating DNA damage was measured...
November 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29109859/candidate-synthetic-lethality-partners-to-parp-inhibitors-in-the-treatment-of-ovarian-clear-cell-cancer
#4
Naoki Kawahara, Kenji Ogawa, Mika Nagayasu, Mai Kimura, Yoshikazu Sasaki, Hiroshi Kobayashi
Inhibitors of poly(ADP-ribose) polymerase (PARP) are new types of personalized treatment of relapsed platinum-sensitive ovarian cancer harboring BRCA1/2 mutations. Ovarian clear cell cancer (CCC), a subset of ovarian cancer, often appears as low-stage disease with a higher incidence among Japanese. Advanced CCC is highly aggressive with poor patient outcome. The aim of the present study was to determine the potential synthetic lethality gene pairs for PARP inhibitions in patients with CCC through virtual and biological screenings as well as clinical studies...
November 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29104854/chirality-controls-reaction-diffusion-of-nanoparticles-for-inhibiting-cancer-cells
#5
Xuewen Du, Jie Zhou, Jiaqing Wang, Rong Zhou, Bing Xu
Reaction-diffusion (RD) is the most important inherent feature of living organism, but it has yet to be used for developing biofunctional nanoparticles (NPs). Here we show the use of chirality to control the RD of NPs for selectively inhibiting cancer cells. We observe that L-phosphotyrosine (L-pY) decorated NPs (NP@L-pYs) are innocuous to cells, but D-pY decorated ones (NP@D-pYs) selectively inhibit cancer cells. Our study shows that alkaline phosphatases (ALP), presented in the culture and overexpressed on the cancer cells, dephosphorylates NP@L-pYs much faster than NP@D-pYs...
January 2017: ChemNanoMat: Chemistry of Nanomaterials for Energy, Biology and More
https://www.readbyqxmd.com/read/29075510/lipiodol-nanoemulsions-stabilized-with-polyglycerol-polycaprolactone-block-copolymers-for-theranostic-applications
#6
Trang Huyen Le Kim, Hwiseok Jun, Jin Ho Kim, Keunchil Park, Jee Seon Kim, Yoon Sung Nam
BACKGROUND: Polyglycerol is an attractive hydrophilic building block of amphiphilic copolymers for biomedical and pharmaceutical applications due to its biocompatibility, facile chemical modification, and anti-fouling activity. Herein we introduce theranostic nanoemulsions incorporating anti-cancer therapeutic and contrast agents using linear polyglycerol-poly(ε-caprolactone) diblock copolymers (PG-b-PCL). Lipiodol is used as a core oil that dissolves paclitaxel and serves as a contrast agent for computer tomography (CT)...
2017: Biomaterials Research
https://www.readbyqxmd.com/read/29072978/maintenance-poly-adp-ribose-polymerase-inhibitor-therapy-for-ovarian-cancer-precision-oncology-or-one-size-fits-all
#7
Andrew Berchuck, Angeles Alvarez Secord, Haley A Moss, Laura J Havrilesky
No abstract text is available yet for this article.
October 26, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29069866/germline-mutations-in-pancreatic-cancer-and-potential-new-therapeutic-options
#8
REVIEW
Rille Pihlak, Juan W Valle, Mairéad G McNamara
Due to short-lived treatment responses in unresectable disease, pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest cancers. There is availability of new information about germline and sporadic mutations in the deoxyribonucleic acid (DNA) damage repair pathway in PDAC in recent decades and the expectation is that novel targeted therapies will thus be developed. A variety of germline mutations (BRCA2, BRCA1, PALB2, CDKN2A, ATM, TP53 and mismatch repair genes MLH1, MSH2, MSH6) have been reported in these patients with the highest prevalence being BRCA1/2...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29063517/parp-inhibitors-in-the-treatment-of-triple-negative-breast-cancer
#9
REVIEW
Jill J J Geenen, Sabine C Linn, Jos H Beijnen, Jan H M Schellens
Breast cancer is a heterogeneous disease, manifesting in a broad differentiation in phenotypes and morphologic profiles, resulting in variable clinical behavior. Between 10 and 20% of all breast cancers are triple negative. Triple-negative breast cancer (TNBC) lacks the expression of human epidermal growth factor receptor 2 (HER2) and hormone receptors; therefore, to date, chemotherapy remains the backbone of treatment. TNBC tends to be aggressive and has a high histological grade, resulting in a poor 5-year prognosis...
October 23, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29058797/the-fabrication-of-3d-surface-scaffold-of-collagen-poly-l-lactide-co-caprolactone-with-dynamic-liquid-system-and-its-application-in-urinary-incontinence-treatment-as-a-tissue-engineered-sub-urethral-sling-in-vitro-and-in-vivo-study
#10
Kaile Zhang, Nailong Cao, Xuran Guo, Qingsong Zou, Shukui Zhou, Ranxing Yang, Weixin Zhao, Xiumei Mo, Wei Liu, Qiang Fu
AIMS: To fabricate a novel nanoyarn biomaterial via a dynamic liquid electrospinning system, and to simultaneously evaluate whether nanoyarn is capable of being applied as a urinary sling for future clinical transfer. METHODS: Nanoyarn was cultured with adipose-derived stem cells (ADSCs). Cell morphology and function were observed on nanoyarn. Female rats that underwent vagina dilatation (VD) and bilateral ovarian resection (BOR) were used as the urinary incontinence model...
October 23, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29056443/pre-clinical-evaluation-of-a-themosensitive-gel-containing-epothilone-b-and-mtor-hsp90-targeted-agents-in-an-ovarian-tumor-model
#11
Dae Hwan Shin, Glen S Kwon
Despite clinical remission of epithelial ovarian cancer (EOC) after surgical resection and first-line chemotherapy, about 60% of patients will re-develop peritoneal metastasis and about 50% will relapse with chemoresistant disease. Clinical studies suggest that intra-peritoneal (i.p.) chemotherapy effectively treats residual EOC after cyto-reduction by gaining direct access into the peritoneal cavity, enabling elevated drug levels versus intravenous (i.v.) injection. However, chemoresistant disease is still problematic...
October 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29054544/-abnormalities-of-dna-repair-and-gynecological-cancers
#12
REVIEW
Aurélie Auguste, Alexandra Leary
The demonstration of frequent defects in the DNA damage response in high grade ovarian cancer has paved the way for a new therapeutic approach aimed at exploiting this unique vulnerability. The efficacy of poly (ADP) ribose polymerase inhibitors (PARPi) in patients with homologous recombination (HR) DNA repair deficient ovarian cancer (OC) resulting from a BRCA1/2 mutation has provided the proof of concept for synthetic lethality. Thus, olaparib is now approved by the EMA as maintenance therapy after response to a platinum regimen for patients with recurrent, platinum-sensitive, high-grade serous, BRCA1/2-mutated ovarian cancer...
October 17, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29043410/determination-of-the-absolute-oral-bioavailability-of-niraparib-by-simultaneous-administration-of-a-14-c-microtracer-and-therapeutic-dose-in-cancer-patients
#13
L van Andel, H Rosing, Z Zhang, L Hughes, V Kansra, M Sanghvi, M M Tibben, A Gebretensae, J H M Schellens, J H Beijnen
INTRODUCTION: Niraparib (Zejula™) is a poly(ADP-ribose) polymerase inhibitor recently approved by the US Food and Drug Administration for the maintenance treatment of patients with recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The pivotal phase III clinical trial has shown improved progression-free survival in patients receiving niraparib compared with those receiving placebo...
October 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29040190/novel-therapeutics-for-ovarian-cancer-the-11th-biennial-rivkin-center-ovarian-cancer-research-symposium
#14
Neil Johnson, John B Liao
OBJECTIVE: The aim of this study was to summarize developments in novel therapeutics for ovarian cancer presented at the Ovarian Cancer Research Symposium held at the University of Washington. METHODS: A symposium of the leaders in ovarian cancer research was convened to present and discuss current advances and future directions in ovarian cancer research. RESULTS: The fourth session was held on September 13, 2016, and focused on Novel Therapeutics for Ovarian Cancer...
October 17, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29020474/laser-assisted-hair-removal-for-facial-hirsutism-in-women-a-review-of-evidence
#15
Chun-Man Lee
Poly cystic ovarian syndrome (PCOS) has been described as the common diagnosis for hirsutism in women. Facial hirsutism is by far the most distressing symptom of hyperandrogenism in women with PCOS. A statistically significant improvement in psychological well-being has been reported in patients with PCOS allocated for laser-assisted hair removal. The theory of selective photothermolysis has revolutionised laser hair removal in that it is effective and safe, when operated by sufficiently trained and experienced professionals...
October 11, 2017: Journal of Cosmetic and Laser Therapy: Official Publication of the European Society for Laser Dermatology
https://www.readbyqxmd.com/read/28994564/targeted-therapy-for-ovarian-cancer-the-rapidly-evolving-landscape-of-parp-inhibitor-use
#16
Christine Walsh
INTRODUCTION: PARP (poly(ADP-ribose) polymerase) inhibitors are a targeted therapy option for ovarian cancer. The goal of this review was to organize and summarize the clinical trials evaluating PARP inhibitor therapy in ovarian cancer as monotherapy, maintenance therapy after partial or complete remission to therapy or as a part of a combination regimen. EVIDENCE ACQUISITION: PubMed, ClinicalTrials.gov, data from the United States Food and Drug Administration (US FDA) and proceedings from scientific conferences were searched for published and unpublished data pertaining to clinical trials and approvals of PARP inhibitor use in ovarian cancer...
October 9, 2017: Minerva Ginecologica
https://www.readbyqxmd.com/read/28978184/poly-adp-ribose-polymerase-inhibitors-as-radiosensitizers-a-systematic-review-of-pre-clinical-and-clinical-human-studies
#17
REVIEW
Paul Lesueur, François Chevalier, Jean-Baptiste Austry, Waisse Waissi, Hélène Burckel, Georges Noël, Jean-Louis Habrand, Yannick Saintigny, Florence Joly
BACKGROUND: Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28950147/genomic-signatures-as-predictive-biomarkers-of-homologous-recombination-deficiency-in-ovarian-cancer
#18
Adriaan Vanderstichele, Pieter Busschaert, Siel Olbrecht, Diether Lambrechts, Ignace Vergote
DNA repair deficiency is a common hallmark of many cancers and is increasingly recognised as a target for cancer therapeutics. Selecting patients for these treatments requires a functional assessment of multiple redundant DNA repair pathways. With the advent of whole-genome sequencing of cancer genomes, it is increasingly recognised that multiple signatures of mutational and chromosomal alterations can be correlated with specific DNA repair defects. The clinical relevance of this approach is underlined by the use of poly-(ADP-ribose) polymerase inhibitors (PARPi) in homologous recombination (HR) deficient high-grade serous ovarian cancers...
September 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28948407/synthesis-and-inhibitory-effect-of-10-chlorocanthin-6-one-on-ovarian-cancer-ho8910pm-cells
#19
Wenhua Li, Yuwen Chen, Yuwen Sheng, Zeyu Xie, Yaxiong Tang
OBJECTIVE: To synthesize and determine the antitumor activity of 10-chlorocanthin-6-one in ovarian cancer HO8910PM cells. RESULTS: Among the synthesized canthin-6-one analogs, 10-chlorocanthin-6-one was the most cytotoxic (IC50 = 4.9 μM), as demonstrated by a dose-dependent cytotoxicity assay. Moreover, 10-chlorocanthin-6-one induced apoptosis through the activation of poly(ADP-ribose) polymerase and caspase-3 cleavage, upregulation of Bcl-2, and downregulation of Bim, x-linked inhibitor of apoptosis protein (XIAP), and survivin in HO8910PM cells...
September 25, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28925391/ezh2-contributes-to-the-response-to-parp-inhibitors-through-its-parp-mediated-poly-adp-ribosylation-in-breast-cancer
#20
H Yamaguchi, Y Du, K Nakai, M Ding, S-S Chang, J L Hsu, J Yao, Y Wei, L Nie, S Jiao, W-C Chang, C-H Chen, Y Yu, G N Hortobagyi, M-C Hung
Inhibitors against poly (ADP-ribose) polymerase (PARP) are promising targeted agents currently used to treat BRCA-mutant ovarian cancer and are in clinical trials for other cancer types, including BRCA-mutant breast cancer. To enhance the clinical response to PARP inhibitors (PARPis), understanding the mechanisms underlying PARPi sensitivity is urgently needed. Here, we show enhancer of zeste homolog 2 (EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells...
September 18, 2017: Oncogene
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