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https://www.readbyqxmd.com/read/28819699/cudc-907-a-dual-hdac-and-pi3k-inhibitor-reverses-platinum-drug-resistance
#1
Kenneth K W To, Li-Wu Fu
Platinum (Pt)-based anticancer drugs are the mainstay of treatment for solid cancers. However, resistance to Pt drugs develops rapidly, which can be caused by overexpression of multidrug resistance transporters and activation of DNA repair. CUDC-907 is a potent molecular targeted anticancer agent, rationally designed to simultaneously inhibit histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K). We investigated the potentiation effect of CUDC-907 on Pt drugs in resistant cancer cells. ABCC2 stably-transfected HEK293 cells and two pairs of parental and Pt-resistant cancer cell lines were used to test for the circumvention of resistance by CUDC-907...
August 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28819400/rapid-breast-cancer-disease-progression-following-cyclin-dependent-kinase-4-and-6-inhibitor-discontinuation
#2
Sami I Bashour, Iman Doostan, Khandan Keyomarsi, Vicente Valero, Naoto T Ueno, Powel H Brown, Jennifer K Litton, Kimberly B Koenig, Meghan Karuturi, Sausan Abouharb, Debasish Tripathy, Stacy L Moulder-Thompson, Nuhad K Ibrahim
Background: CDK 4 and 6 inhibitors (CDK4/6i), which arrest unregulated cancer cell proliferation, show clinical efficacy in breast cancer. Unexpectedly, a patient treated on a CDK4/6i-based trial, as first-line therapy in metastatic breast cancer, developed rapid disease progression following discontinuation of study drug while receiving standard second-line therapy off trial. We thus sought to expand this observation within a population of patients treated similarly at The University of Texas MD Anderson Cancer Center...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819390/fluorofenidone-inhibits-the-proliferation-of-lung-adenocarcinoma-cells
#3
Zheng-Hao Deng, Jie Meng, Juan Tang, Gao-Yun Hu, Li-Jian Tao
Background: Lung carcinoma is the leading cause of malignant tumor related mortality in China in recent decades, and the development of new and effective therapies for patients with advanced lung carcinoma is needed. We recently found that fluorofenidone (FD), a newly developed pyridine compound, reduced the activation of Stat3 (Signal transducer and activator of transcription 3) in fibroblasts. Stat3 plays a crucial role in the development of lung cancer and may represent a new therapeutic target. In this study, we examined the effect of FD on human lung adenocarcinoma cells in vivo and in vitro...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819136/the-possible-molecular-mechanisms-of-bisphenol-a-action-on-porcine-early-embryonic-development
#4
Jing Guo, Ming-Hui Zhao, Kyung-Tae Shin, Ying-Jie Niu, Yong-Dae Ahn, Nam-Hyung Kim, Xiang-Shun Cui
Bisphenol A (BPA) is an environmental contaminant widely used in the plastic industry. BPA has been demonstrated to be an endocrine disruptor and has an adverse effect on the embryonic development of mammals. However, the mechanism of action of BPA is limited. In this study, we investigated the role and mechanism of BPA in porcine embryonic development. First, the parthenotes were treated with different concentrations of BPA. We found that blastocyst formation was impaired and the parthenotes were arrested at the 4-cell stage after treatment with 100 μm BPA...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818995/maternal-dcaf2-is-crucial-for-maintenance-of-genome-stability-during-the-first-cell-cycle-in-mice
#5
Yi-Wen Xu, Lan-Rui Cao, Min Wang, Ying Xu, Xin Wu, Junping Liu, Chao Tong, Heng-Yu Fan
Precise regulation of DNA replication and genome integrity is crucial for gametogenesis and early embryogenesis. Cullin ring-finger ubiquitin ligase 4 (CRL4) has multiple functions in the maintenance of germ cell survival, oocyte meiotic maturation, and maternal-zygotic transition in mammals. DDB1-cullin 4-associated factor-2 (DCAF2, also known as DTL or CDT2) is an evolutionarily conserved substrate receptor of CRL4. To determine whether DCAF2 is a key CRL4 substrate adaptor in mammalian oocytes, we generated a novel mouse strain that carries a Dcaf2 allele flanked by LoxP sequences, and specifically deleted Dcaf2 in oocytes...
August 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28818030/vitamin-e-%C3%AE-tocopherol-exhibits-antitumour-activity-on-oral-squamous-carcinoma-cells-orl-48
#6
Rahayu Zulkapli, Fathilah Abdul Razak, Rosnah Binti Zain
Cancers involving the oral cavity, head, and neck regions are often treated with cisplatin. In cancer therapy, the main target is to eliminate unwanted cancerous cells. However, reports on the nonselective nature of this drug have raised few concerns. Incorrect nutritional habits and lifestyle practices have been directly linked to cancer incidence. Nutrients with antioxidant activity inhibit cancer cells development, destroying them through oxidative stress and apoptosis. α-tocopherol, the potent antioxidant form of vitamin E is a known scavenger of free radicals...
September 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28816773/synergistic-antitumor-effect-of-3-bromopyruvate-and-5-fluorouracil-against-human-colorectal-cancer-through-cell-cycle-arrest-and-induction-of-apoptosis
#7
Dianlong Chong, Linyan Ma, Fang Liu, Zhirui Zhang, Surong Zhao, Qiang Huo, Pei Zhang, Hailun Zheng, Hao Liu
3-Bromopyruvic acid (3-BP) is a well-known inhibitor of energy metabolism. It has been proposed as an anticancer agent as well as a chemosensitizer for use in combination with anticancer drugs. 5-Fluorouracil (5-FU) is the first-line chemotherapeutic agent for colorectal cancer; however, most patients develop resistance to 5-FU through various mechanisms. The aim of this study was to investigate whether 3-BP has a synergistic antitumor effect with 5-FU on human colorectal cancer cells. In our study, combined 3-BP and 5-FU treatment upregulated p53 and p21, whereas cyclin-dependent kinase CDK4 and CDK2 were downregulated, which led to G0/G1 phase arrest...
September 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28815320/inhibitory-growth-evaluation-and-apoptosis-induction-in-mcf-7-cancer-cells-by-new-5-aryl-2-butylthio-1-3-4-oxadiazole-derivatives
#8
Rashmin Khanam, Kamal Ahmad, Iram I Hejazi, Ibrar A Siddique, Vikash Kumar, Abdul Roouf Bhat, Amir Azam, Fareeda Athar
BACKGROUND: Cancer has become one of the global health issues and it is the life-threatening disease characterized by unrestrained growth of cells. Despite various advances being adopted by chemotherapeutic management, the use of the current anticancer drugs such as Doxorubicin, Asparginase, Methotrexate, Vincristine remains limited due to high toxicity, side effects and developing drug resistance. Apoptosis is a crucial cellular process and improper regulation of apoptotic signaling pathways may lead to cancer formation...
August 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28814798/genetic-polymorphisms-of-lncrna-p53-regulatory-network-genes-are-associated-with-concurrent-chemoradiotherapy-toxicities-and-efficacy-in-nasopharyngeal-carcinoma-patients
#9
Youhong Wang, Zhen Guo, Yu Zhao, Yi Jin, Liang An, Bin Wu, Zhaoqian Liu, Xiaoping Chen, Xiang Chen, Honghao Zhou, Hui Wang, Wei Zhang
The relevance of the transcription factor p53 in cancer is inarguable, and numerous lncRNAs are involved in the p53 regulatory network as either regulators or effectors, triggering a transcriptional response that causes either cell arrest or apoptosis following DNA damage in a p53-dependent manner. Despite the fact that the therapeutic response is improved in NPC, heterogeneity among people remains with regard to the susceptibility of adverse effects and the efficacy of treatments. Therefore, we analysed eight potentially functional SNPs of five genes in the lncRNA-p53 regulatory network in a discovery cohort of 505 NPC patients...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813171/anti-edar-agonist-antibody-therapy-resolves-palate-defects-in-pax9-mice
#10
S Jia, J Zhou, Y Wee, M L Mikkola, P Schneider, R N D'Souza
To date, surgical interventions are the only means by which craniofacial anomalies can be corrected so that function, esthetics, and the sense of well-being are restored in affected individuals. Unfortunately, for patients with cleft palate-one of the most common of congenital birth defects-treatment following surgery is prolonged over a lifetime and often involves multidisciplinary regimens. Hence, there is a need to understand the molecular pathways that control palatogenesis and to translate such information for the development of noninvasive therapies that can either prevent or correct cleft palates in humans...
August 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28812428/microvascular-perfusion-in-cardiac-arrest-a-review-of-microcirculatory-imaging-studies
#11
Petra Krupičková, Zuzana Mormanová, Tomáš Bouček, Tomáš Belza, Jana Šmalcová, Jan Bělohlávek
Cardiac arrest represents a leading cause of mortality and morbidity in developed countries. Extracorporeal cardiopulmonary resuscitation (ECPR) increases the chances for a beneficial outcome in victims of refractory cardiac arrest. However, ECPR and post-cardiac arrest care are affected by high mortality rates due to multi-organ failure syndrome, which is closely related to microcirculatory disorders. Therefore, microcirculation represents a key target for therapeutic interventions in post-cardiac arrest patients...
August 1, 2017: Perfusion
https://www.readbyqxmd.com/read/28812241/plasma-glycoproteomic-study-of-therapeutic-hypothermia-reveals-novel-markers-predicting-neurologic-outcome-post-cardiac-arrest
#12
Wenjun Deng, Jing Cao, Lei Chen, David McMullin, James L Januzzi, Ferdinando S Buonanno, Eng H Lo, MingMing Ning
Therapeutic hypothermia (TH) is a neuroprotective treatment post-cardiac arrest but is grossly underutilized. After TH induction, traditional biomarkers and parameters can no long predict clinical outcome due to a lack of understanding of hypothermic response. Innovative approaches to better understand the clinical effect of TH will help to prognosticate outcome and expand beneficial population. Protein glycosylation is an important extracellular post-translational modification, regulating various extracellular signaling pathways...
August 15, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28811507/global-mapping-of-mirna-target-interactions-in-cattle-bos-taurus
#13
Troels K H Scheel, Michael J Moore, Joseph M Luna, Eiko Nishiuchi, John Fak, Robert B Darnell, Charles M Rice
With roles in development, cell proliferation and disease, micro-RNA (miRNA) biology is of great importance and a potential therapeutic target. Here we used cross-linking immunoprecipitation (CLIP) and ligation of miRNA-target chimeras on the Argonaute (AGO) protein to globally map miRNA interactions in the cow. The interactome is the deepest reported to date. miRNA targeting principles are consistent with observations in other species, but with expanded pairing rules. Experimental mapping robustly predicted functional miR-17 regulatory sites...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810931/a-comprehensive-regional-clinical-and-educational-ecpr-protocol-decreases-time-to-ecmo-in-patients-with-refractory-out-of-hospital-cardiac-arrest
#14
Brian Grunau, Sarah Carrier, Jamil Bashir, William Dick, Luke Harris, Robert Boone, Dan Kalla, Frank Scheuermeyer, Brian Twaites, Ron Straight, James Abel, Ken McDonald, Ruth MacRedmond, David Agulnik, Joe Finkler, Jeanne MacLeod, Jim Christenson, Anson Cheung
OBJECTIVE: Extracorporeal membrane oxygenation within CPR (ECPR) may improve survival for refractory out-of-hospital cardiac arrest (OHCA). We developed a prehospital, emergency department (ED), and hospital-based clinical and educational protocol to improve the key variable of time-to-ECPR (TTE). METHODS: In a single urban health region we involved key prehospital, clinical, and administrative stakeholders over a 2-year period, to develop a regional ECPR program with destination to a single urban tertiary care hospital...
August 16, 2017: CJEM
https://www.readbyqxmd.com/read/28808400/induction-of-apoptosis-and-cell-cycle-arrest-by-flavokawain-c-on-ht-29-human-colon-adenocarcinoma-via-enhancement-of-reactive-oxygen-species-generation-upregulation-of-p21-p27-and-gadd153-and-inactivation-of-inhibitor-of-apoptosis-proteins
#15
Chung-Weng Phang, Saiful Anuar Karsani, Sri Nurestri Abd Malek
Chalcones have been shown to exhibit anti-cancer properties by targeting multiple molecular pathways. It was, therefore, of interest to investigate flavokawain C (FKC), a naturally occurring chalcone, which can be isolated from Kava (Piper methysticum Forst) root extract. The aim of this study was to investigate the inhibitory effect of FKC on the growth of HT-29 cells and its underlying mechanism of action. Cell viability of HT-29 cells was assessed by Sulforhodamine B assay after FKC treatment. Induction of apoptosis was examined by established morphological and biochemical assays...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808378/rutamarin-an-active-constituent-from-ruta-angustifolia-pers-induced-apoptotic-cell-death-in-the-ht29-colon-adenocarcinoma-cell-line
#16
Shafinah Ahmad Suhaimi, Sok Lai Hong, Sri Nurestri Abdul Malek
BACKGROUND: Ruta angustifolia Pers. is a perennial herb that is cultivated worldwide, including Southeast Asia, for the treatment of various diseases as traditional medicine. OBJECTIVE: The purpose of the study was to identify an active principle of R. angustifolia and to investigate its effect on the HT29 cell death. MATERIALS AND METHODS: The methanol and fractionated extracts (hexane, chloroform, ethyl acetate, and water) of R. angustifolia Pers...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28807995/regulation-of-the-cell-cycle-and-inflammatory-arthritis-by-the-transcription-cofactor-lbh-gene
#17
Shinji Matsuda, Deepa Hammaker, Katharyn Topolewski, Karoline J Briegel, David L Boyle, Steven Dowdy, Wei Wang, Gary S Firestein
Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) display unique aggressive behavior, invading the articular cartilage and promoting inflammation. Using an integrative analysis of RA risk alleles, the transcriptome and methylome in RA FLS, we recently identified the limb bud and heart development (LBH) gene as a key dysregulated gene in RA and other autoimmune diseases. Although some evidence suggests that LBH could modulate the cell cycle, the precise mechanism is unknown and its impact on inflammation in vivo has not been defined...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28807898/hypothalamic-sonic-hedgehog-is-required-for-cell-specification-and-proliferation-of-lhx3-lhx4-pituitary-embryonic-precursors
#18
G Carreno, J Apps, E J Lodge, L Panousopoulos, S Haston, J M Gonzalez-Meljem, H Hahn, C L Andoniadou, J P Martinez-Barbera
Sonic hedgehog (SHH) is an essential morphogenetic signal dictating cell fate decisions in several developing organs in mammals. In vitro data suggest that SHH is required to specify LHX3+/LHX4+ Rathke's pouch (RP) progenitor identity. However, in vivo studies have failed to reveal such a function, supporting instead, a critical role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3+/LHX4+ RP identity in mouse embryos...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28807853/aqueous-extract-from-pecan-nut-carya-illinoinensis-wangenh-c-koch-shell-show-activity-against-breast-cancer-cell-line-mcf-7-and-ehrlich-ascites-tumor-in-balb-c-mice
#19
Josiane Hilbig, Priscila de Britto Policarpi, Valdelúcia Maria Alves de Souza Grinevicius, Nádia Sandrine Ramos Santos Mota, Rozangela Curi Pedrosa, Jane Mara Block
ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, use of teas are common for the treatment of many health disorders. Shell extracts of pecan nut (Carya illinoinensis) are popularly taken as tea to prevent diverse pathologies due to their phytochemical composition presenting significant amounts of phenolic substances. AIM OF THE STUDY: Phenolic compounds from pecan nut shell extract have been associated with diverse biological effects but the effect on tumor cells has not been reported yet...
August 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28807782/modulating-protein-protein-interactions-of-the-mitotic-polo-like-kinases-to-target-mutant-kras
#20
Ana J Narvaez, Suzan Ber, Alex Crooks, Amy Emery, Bryn Hardwick, Estrella Guarino Almeida, David J Huggins, David Perera, Meredith Roberts-Thomson, Roberta Azzarelli, Fiona E Hood, Ian A Prior, David W Walker, Richard Boyce, Robert G Boyle, Samuel P Barker, Christopher J Torrance, Grahame J McKenzie, Ashok R Venkitaraman
Mutations activating KRAS underlie many forms of cancer, but are refractory to therapeutic targeting. Here, we develop Poloppin, an inhibitor of protein-protein interactions via the Polo-box domain (PBD) of the mitotic Polo-like kinases (PLKs), in monotherapeutic and combination strategies to target mutant KRAS. Poloppin engages its targets in biochemical and cellular assays, triggering mitotic arrest with defective chromosome congression. Poloppin kills cells expressing mutant KRAS, selectively enhancing death in mitosis...
July 27, 2017: Cell Chemical Biology
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