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https://www.readbyqxmd.com/read/28211448/cx-5461-is-a-dna-g-quadruplex-stabilizer-with-selective-lethality-in-brca1-2-deficient-tumours
#1
Hong Xu, Marco Di Antonio, Steven McKinney, Veena Mathew, Brandon Ho, Nigel J O'Neil, Nancy Dos Santos, Jennifer Silvester, Vivien Wei, Jessica Garcia, Farhia Kabeer, Daniel Lai, Priscilla Soriano, Judit Banáth, Derek S Chiu, Damian Yap, Daniel D Le, Frank B Ye, Anni Zhang, Kelsie Thu, John Soong, Shu-Chuan Lin, Angela Hsin Chin Tsai, Tomo Osako, Teresa Algara, Darren N Saunders, Jason Wong, Jian Xian, Marcel B Bally, James D Brenton, Grant W Brown, Sohrab P Shah, David Cescon, Tak W Mak, Carlos Caldas, Peter C Stirling, Phil Hieter, Shankar Balasubramanian, Samuel Aparicio
G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition. Exposure to CX-5461, and its related drug CX-3543, blocks replication forks and induces ssDNA gaps or breaks...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28209745/platinum-fluoropyrimidine-and-paclitaxel-based-chemotherapy-in-the-treatment-of-advanced-anal-cancer-patients
#2
Francesco Sclafani, Federica Morano, David Cunningham, Chiara Baratelli, Eleftheria Kalaitzaki, David Watkins, Naureen Starling, Ian Chau, Sheela Rao
BACKGROUND: Although treatment of localized anal cancer (AC) is well established, very little evidence is available to inform the management of advanced tumors, and the prognosis of these patients remains poor. We have analyzed treatment pathways and outcomes of a single-institution series of advanced AC patients in order to provide insight into the management of this rare condition. MATERIALS AND METHODS: Inclusion criteria included epidermoid histology, inoperable locally recurrent or metastatic disease, and availability of full medical records...
February 16, 2017: Oncologist
https://www.readbyqxmd.com/read/28203301/progress-with-palbociclib-in-breast-cancer-latest-evidence-and-clinical-considerations
#3
REVIEW
Andrea Rocca, Alessio Schirone, Roberta Maltoni, Sara Bravaccini, Lorenzo Cecconetto, Alberto Farolfi, Giuseppe Bronte, Daniele Andreis
Deregulation of the cell cycle is a hallmark of cancer, and research on cell cycle control has allowed identification of potential targets for anticancer treatment. Palbociclib is a selective inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6), which are involved, with their coregulatory partners cyclin D, in the G1-S transition. Inhibition of this step halts cell cycle progression in cells in which the involved pathway, including the retinoblastoma protein (Rb) and the E2F family of transcription factors, is functioning, although having been deregulated...
February 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28195818/notch1-overexpression-correlates-to-improved-survival-in-cancer-of-the-oropharynx
#4
Azeem S Kaka, Nicholas B Nowacki, Bhavna Kumar, Songzhu Zhao, Matthew O Old, Amit Agrawal, Enver Ozer, Ricardo L Carrau, David E Schuller, Pawan Kumar, Theodoros N Teknos
Objectives The Notch1 signaling pathway has recently been shown to be highly dysregulated in head and neck squamous cell carcinoma, but the value of Notch1 as a predictive biomarker is yet to be elucidated in oropharyngeal squamous cell carcinoma (OPSCC). The objective of this study is to evaluate Notch1 expression in surgical OPSCC specimens and determine clinicopathologic correlates. Study Design Case series with planned data collection. Setting Tertiary academic medical center. Subjects and Methods Surgical specimens from 181 patients with OPSCC were collected to create a tissue microarray (TMA)...
February 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28195036/gsk-3%C3%AE-inhibition-induced-neuroprotection-regeneration-and-functional-recovery-after-intracerebral-hemorrhagic-stroke
#5
Yingying Zhao, Zheng Zachory Wei, James Ya Zhang, Yongbo Zhang, Soonmi Won, Jinmei Sun, Shan Ping Yu, Jimei Li, Ling Wei
Hemorrhagic stroke is a devastating disease that lacks effective therapies. In the present investigation, we tested 6-bromoindirubin-3'-oxime (BIO) as a selective glycogen synthase kinase-3β (GSK-3β) inhibitor in a mouse model of intracerebral hemorrhage (ICH). ICH was induced by injection of collagenase IV into the striatum of 8 to 10-week old C57BL/6 mice. BIO (8 µg/kg, i.p.) was administered following either an acute delivery (0 - 2 hr delay) or a prolonged regimen (every 48 hrs starting at 3 days postICH)...
February 14, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28194813/microrna-191-acts-as-a-tumor-promoter-by-modulating-the-tet1-p53-pathway-in-intrahepatic-cholangiocarcinoma
#6
Hao Li, Zun-Qiang Zhou, Zhang-Ru Yang, Da-Nian Tong, Jiao Guan, Bao-Jie Shi, Jia Nie, Xian-Ting Ding, Bin Li, Guang-Wen Zhou, Zheng-Yun Zhang
: Current treatment of intrahepatic cholangiocarcinoma (ICC) remains ineffective because knowledge of ICC carcinogenesis is unclear. Increasing evidence suggests that microRNAs (miRNAs), including miRNA-191, play an important role in tumorigenesis, but expression and biological functions of miRNA-191 in ICC remain to be established. This study aimed to investigate the functions and underlying mechanisms of miRNA-191 in ICC. ICC miRNA profiles were generated in 5 pairs of ICC and matched to normal bile duct tissues by next-generation sequencing technology; ICC miRNA profiles were verified in 18 pairs of ICC tissues and normal bile duct tissues by quantitative reverse transcription PCR (qRT-PCR)...
February 14, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28194409/a-variant-in-cox-2-gene-is-associated-with-left-main-coronary-artery-disease-and-clinical-outcomes-of-coronary-artery-bypass-grafting
#7
Hanning Liu, Zhengxi Xu, Cheng Sun, Dachuan Gu, Xiao Teng, Yan Zhao, Zhe Zheng
As a particular severe phenotype of coronary artery disease (CAD), left main coronary artery disease (LMCAD) is heritable. Genetic variants related to prostaglandin metabolism are associated with LMCAD. Cyclooxygenase-2 (COX-2), a key synthase in prostaglandin pathways, displays high density in atherosclerotic lesions and promotes early atherosclerosis in CAD progression. We hypothesized that genetic variants in COX-2 gene contribute to LMCAD phenotype susceptibility compared to more peripheral coronary artery disease (MPCAD)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28193742/delays-and-pathways-to-final-tuberculosis-diagnosis-in-patients-from-a-referral-hospital-in-urban-china
#8
Leonardo Martinez, Lin Xu, Cheng Chen, Juliet N Sekandi, Yongzhong Zhu, Changsheng Zhang, Christopher C Whalen, Limei Zhu
China is among the countries with the largest epidemic of drug susceptible and resistant tuberculosis globally. We investigated the locations tuberculosis patients visited before being diagnosed, total diagnostic delay, and risk factors associated with total delay from a large tuberculosis referral hospital in Nanjing, China. We conducted a retrospective cohort study among tuberculosis patients who initiated anti-tuberculosis treatment within 3 months prior to the study date. Patient information regarding time and locations visited while seeking care for tuberculosis-related symptoms was collected through face-to-face interviews...
February 13, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28193461/gill-structural-integrity-changes-in-fish-deficient-or-excessive-in-dietary-isoleucine-towards-the-modulation-of-tight-junction-protein-inflammation-apoptosis-and-antioxidant-defense-via-nf-%C3%AE%C2%BAb-tor-and-nrf2-signaling-pathways
#9
Lin Feng, Lu Gan, Wei-Dan Jiang, Pei Wu, Yang Liu, Jun Jiang, Ling Tang, Sheng-Yao Kuang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study firstly aimed to test the impact of dietary isoleucine (Ile) on tight junction protein, inflammation, apoptosis, antioxidant defense and related signaling molecule gene expression in the gill of fish. Young grass carp (Ctenopharyngodon idella) (weighing 256.8 ± 3.5 g) were fed six diets containing graded levels of Ile, namely, 3.8, 6.6, 9.3, 12.5, 15.2 and 18.5 g/kg diet for 8 weeks. The results firstly revealed that Ile deficiency down-regulated the mRNA expressions of claudin-3, claudin-b, claudin-c, occludin and zonula occludens-1 (ZO-1) and up-regulated the mRNA expression of claudin-12, which led to the intercellular structure damage of fish gill...
February 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28191270/a-close-look-at-the-structure-of-the-tio2-aptes-interface-in-hybrid-nanomaterials-and-its-degradation-pathway-an-experimental-and-theoretical-study
#10
Daniela Meroni, Leonardo Lo Presti, Giovanni Di Liberto, Michele Ceotto, Robert G Acres, Kevin C Prince, Roberto Bellani, Guido Soliveri, Silvia Ardizzone
The surface functionalization of TiO2-based materials with alkylsilanes is attractive in several cutting-edge applications, such as photovoltaics, sensors, and nanocarriers for the controlled release of bioactive molecules. (3-Aminopropyl)triethoxysilane (APTES) is able to self-assemble to form monolayers on TiO2 surfaces, but its adsorption geometry and solar-induced photodegradation pathways are not well understood. We here employ advanced experimental (XPS, NEXAFS, AFM, HR-TEM, and FT-IR) and theoretical (plane-wave DFT) tools to investigate the preferential interaction mode of APTES on anatase TiO2...
January 12, 2017: Journal of Physical Chemistry. C, Nanomaterials and Interfaces
https://www.readbyqxmd.com/read/28185146/mr-imaging-features-associated-with-distant-metastasis-free-survival-of-patients-with-invasive-breast-cancer-a-case-control-study
#11
Sung Eun Song, Sung Ui Shin, Hyeong-Gon Moon, Han Suk Ryu, Kwangsoo Kim, Woo Kyung Moon
PURPOSE: Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer...
February 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28183787/prognostic-significance-of-diffuse-sclerosing-variant-papillary-thyroid-carcinoma-a-systematic-review-and-meta-analysis
#12
Huy Gia Vuong, Tetsuo Kondo, Thong Quang Pham, Naoki Oishi, Kunio Mochizuki, Tadao Nakazawa, Lewis Hassell, Ryohei Katoh
OBJECTIVE: Diffuse sclerosing variant papillary thyroid carcinoma (DSVPTC) is an uncommon variant of papillary thyroid carcinoma (PTC). The biological behaviors and prognostic outcomes of this variant, however, are still controversial. The aim of this systematic review and meta-analysis is to investigate the prognostic significance and outcomes of DSVPTCs in comparison with classical PTCs (cPTCs). METHODS: An electronic search was performed in five libraries: PubMed, Scopus, ISI, World Health Organization Global Health Library (WHO GHL) and Virtual Health Library (VHL) in June 2016...
April 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28183331/phase-ii-randomized-placebo-controlled-study-of-dovitinib-in-combination-with-fulvestrant-in-postmenopausal-patients-with-hr-her2-breast-cancer-that-had-progressed-during-or-after-prior-endocrine-therapy
#13
Antonino Musolino, Mario Campone, Patrick Neven, Neelima Denduluri, Carlos H Barrios, Javier Cortes, Kimberly Blackwell, Hatem Soliman, Zsuzsanna Kahan, Hervé Bonnefoi, Matthew Squires, Yong Zhang, Stephanie Deudon, Michael M Shi, Fabrice André
BACKGROUND: Overexpression of fibroblast growth factor receptor 1 (FGFR1), found in ≤8% of hormone receptor-positive (HR(+)), human epidermal growth factor receptor 2-negative (HER2(-)) breast cancer cases, is correlated with decreased overall survival and resistance to endocrine therapy (ET). Dovitinib, a potent FGFR inhibitor, has demonstrated antitumor activity in heavily pretreated patients with FGFR pathway-amplified breast cancer. METHODS: In this randomized, placebo-controlled phase II trial, we evaluated whether the addition of dovitinib to fulvestrant would improve outcomes in postmenopausal patients with HR(+), HER2(-) advanced breast cancer that had progressed during or after prior ET...
February 10, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28179491/increases-in-plasma-tryptophan-are-inversely-associated-with-incident-cardiovascular-disease-in-the-prevenci%C3%A3-n-con-dieta-mediterr%C3%A3-nea-predimed-study
#14
Edward Yu, Miguel Ruiz-Canela, Marta Guasch-Ferré, Yan Zheng, Estefania Toledo, Clary B Clish, Jordi Salas-Salvadó, Liming Liang, Dong D Wang, Dolores Corella, Montse Fitó, Enrique Gómez-Gracia, José Lapetra, Ramón Estruch, Emilio Ros, Montserrat Cofán, Fernando Arós, Dora Romaguera, Lluis Serra-Majem, Jose V Sorlí, Frank B Hu, Miguel A Martinez-Gonzalez
Background: During development of cardiovascular disease (CVD), interferon-γ-mediated inflammation accelerates degradation of tryptophan into downstream metabolites. A Mediterranean diet (MedDiet) consisting of a high intake of extra-virgin olive oil (EVOO), nuts, fruits, vegetables, and cereals has been demonstrated to lower the risk of CVD. The longitudinal relation between tryptophan and its downstream metabolites and CVD in the context of a MedDiet is unstudied.Objective: We sought to investigate the relation between metabolites in the tryptophan-kynurenine pathway and CVD in the context of a MedDiet pattern...
February 8, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28178517/meiotic-knockdown-and-complementation-reveals-essential-role-of-rad51-in-mouse-spermatogenesis
#15
Jieqiong Dai, Oleg Voloshin, Svetlana Potapova, R Daniel Camerini-Otero
Meiotic homologous recombination (HR) is important for proper chromosomal segregation during gametogenesis and facilitates evolutionary adaptation via genomic reshuffling. In most eukaryotes, HR is mediated by two recombinases, the ubiquitous RAD51 and the meiosis-specific DMC1. The role of RAD51 in mammalian meiosis is unclear and study of its function is limited due to embryonic lethality of RAD51 knockouts. Here, we developed an in vivo meiotic knockdown and protein complementation system to study RAD51 during mouse spermatogenesis...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28177150/commentary-the-skeleton-is-a-storehouse-of-mineral-that-is-plundered-during-lactation-and-fully-replenished-afterwards
#16
Christopher S Kovacs
During lactation, mammals resorb mineral from the maternal skeleton to provide calcium to milk. Rodents lose 25-35% of skeletal ash weight, ash calcium content, and bone mineral content by DXA, and have compromised material properties of bone, as assessed by crushing vertebrae and 3-pt bend tests of femora or tibiae. The strength, stiffness, and toughness of vertebrae, femora, and tibiae are reduced by as much as 60%. The effects of lactation are not uniform throughout the skeleton, but instead resorption is much more marked in the trabecular-rich spine than in the appendicular skeleton or whole body...
February 8, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28176781/rad52-competes-with-ku70-ku86-for-binding-to-s-region-dsb-ends-to-modulate-antibody-class-switch-dna-recombination
#17
Hong Zan, Connie Tat, Zhifang Qiu, Julia R Taylor, Justin A Guerrero, Tian Shen, Paolo Casali
Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted for recombination, as effected by Ku70/Ku86-mediated NHEJ. Ku-deficient B cells, however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S-S junctions. As microhomology-mediated end-joining requires annealing of single-strand DNA ends, we addressed the contribution of single-strand annealing factors HR Rad52 and translesion DNA polymerase θ to CSR...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28173624/evidence-for-the-role-of-histaminergic-pathways-in-neuroprotective-mechanism-of-ischemic-postconditioning-in-mice
#18
Indresh Kaur, Amit Kumar, Amteshwar S Jaggi, Nirmal Singh
The present study has been designed to investigate the possible role of histaminergic pathway in neuroprotective mechanism of ischemic postconditioning (iPoCo). Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 hr was employed to produce I/R induced cerebral injury in NIH mice. iPoCo involving three episodes of carotid artery occlusion and reperfusion of 10 sec each, was instituted immediately after BCAO just before prolonged reperfusion. Cerebral infarct size was measured using triphenyltetrazolium chloride staining...
February 7, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28169367/development-of-a-novel-simulation-reactor-for-chronic-exposure-to-atmospheric-particulate-matter
#19
Jianhuai Ye, Sepehr Salehi, Michelle L North, Anjelica M Portelli, Chung-Wai Chow, Arthur W H Chan
Epidemiological studies have shown that air pollution is associated with the morbidity and mortality from cardiopulmonary diseases. Currently, limited experimental models are available to evaluate the physiological and cellular pathways activated by chronic multi-pollutant exposures. This manuscript describes an atmospheric simulation reactor (ASR) that was developed to investigate the health effects of air pollutants by permitting controlled chronic in vivo exposure of mice to combined particulate and gaseous pollutants...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28160779/mir-3156-3p-is-downregulated-in-hpv-positive-cervical-cancer-and-performs-as-a-tumor-suppressive-mirna
#20
Yu-Fang Xia, Gui-Hua Pei, Ning Wang, Yan-Ci Che, Feng-Sheng Yu, Fu-Fen Yin, Hai-Xia Liu, Bing Luo, Yan-Kui Wang
BACKGROUND: Cervical cancer (CC) is the second most common cancer in females in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (HR-HPV), and HR-HPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. microRNAs (miRNAs) may be associated with CC pathogenesis. Researches have indicated that human papillomavirus (HPV) may regulate cellular miRNA expression through viral E6 and E7...
February 4, 2017: Virology Journal
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