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https://www.readbyqxmd.com/read/28930680/systematic-kinase-inhibitor-profiling-identifies-cdk9-as-a-synthetic-lethal-target-in-nut-midline-carcinoma
#1
Johannes Brägelmann, Marcel A Dammert, Felix Dietlein, Johannes M Heuckmann, Axel Choidas, Stefanie Böhm, André Richters, Debjit Basu, Verena Tischler, Carina Lorenz, Peter Habenberger, Zhizhou Fang, Sandra Ortiz-Cuaran, Frauke Leenders, Jan Eickhoff, Uwe Koch, Matthäus Getlik, Martin Termathe, Muhammad Sallouh, Zoltán Greff, Zoltán Varga, Hyatt Balke-Want, Christopher A French, Martin Peifer, H Christian Reinhardt, László Örfi, György Kéri, Sascha Ansén, Lukas C Heukamp, Reinhard Büttner, Daniel Rauh, Bert M Klebl, Roman K Thomas, Martin L Sos
Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) and depend on CDK9 and Cyclin-T1 expression. We show that CDK9i leads to robust induction of apoptosis and of markers of DNA damage response in NMC cells. While both CDK9i and bromodomain inhibition over time result in reduced Myc protein expression, only bromodomain inhibition induces cell differentiation and a p21-induced cell-cycle arrest in these cells...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28928993/what-drives-embryo-development-chromosomal-normality-or-mitochondria
#2
A Bayram, I Elkhatib, A Arnanz, A Linan, F Ruiz, B Lawrenz, H M Fatemi
OBJECTIVE: To report the arrest of euploid embryos with high mtDNA content. DESIGN: A report of 2 cases. SETTING: Private fertility clinic. PATIENTS: 2 patients, 45 and 40 years old undergoing IVF treatment. INTERVENTIONS: Mature oocytes were collected and vitrified from two ovarian stimulations. Postthaw, survived mature oocytes underwent fertilization by intracytoplasmic sperm injection (ICSI)...
2017: Case Reports in Genetics
https://www.readbyqxmd.com/read/28928866/ct-721-a-potent-bcr-abl-inhibitor-exhibits-excellent-in-vitro-and-in-vivo-efficacy-in-the-treatment-of-chronic-myeloid-leukemia
#3
Yinghui Sun, Na Zhao, Huan Wang, Qiong Wu, Yunqi Han, Qichao Liu, Mangang Wu, Yuliang Liu, Fansheng Kong, He Wang, Ying Sun, Deguang Sun, Lutao Jing, Guojing Tang, Yuandong Hu, Dengming Xiao, Hong Luo, Yongxin Han, Yong Peng
Kinase inhibitors that target Bcr-Abl are highly effective in the treatment of chronic myeloid leukemia (CML). However, these inhibitors are often invalidated due to the drug resistance. Therefore, the discovery and development of novel Bcr-Abl inhibitors is required to overwhelm the drug resistance in the treatment of CML resistant to the currently used first-line Bcr-Abl inhibitors. Herein we have described a newly developed Bcr-Abl inhibitor CT-721, which displayed potent inhibitory effects on wild-type and T315I mutant Bcr-Abl...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928816/analysis-of-long-non-coding-rna-expression-profiles-in-clear-cell-renal-cell-carcinoma
#4
Fei Yan Yang, Yan Wang, Jian Guo Wu, Shao Li Song, Gang Huang, Wei Min Xi, Li Ling Tan, Jian Wang, Qing Cao
To investigate the expression patterns of long non-coding RNAs (lncRNAs) in clear cell renal cell carcinoma (ccRCC) and in metastatic renal cell carcinoma (RCC), the present study downloaded three human exon arrays available from the public Gene Expression Omnibus. The probes of the human exon arrays were re-annotated and the probes uniquely mapping to lncRNAs were retained at the gene level. Following the analysis of GSE53757 and GSE46699, which contained paired ccRCC cancer and normal adjacent tissue samples, 32 differentially expressed lncRNAs (adjusted P<0...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928575/referrral-systems-development-and-survey-of-perioperative-and-critical-care-referral-to-anesthetists
#5
P L Narendra, Harihar V Hegde, Maroof Ahmad Khan, Dayanand G Talikoti, Samson Nallamilli
INTRODUCTION: Anesthetists come in contact with more than two-third of hospital patients. Timely referral to anesthetists is vital in perioperative and remote site settings. Delayed referrals, improper referrals, and referrals at inappropriate levels can result in inadequate preparation, perioperative complications, and poor outcome. METHODS: The self administered paper survey to delegates attending anesthesia conferences. Questions were asked on how high-risk, emergency surgical cases remote site and critical care patients were referred to anesthetists and presence of rapid response teams...
July 2017: Anesthesia, Essays and Researches
https://www.readbyqxmd.com/read/28928088/20-s-ginsenoside-rh2-suppresses-proliferation-and-migration-of-hepatocellular-carcinoma-cells-by-targeting-ezh2-to-regulate-cdkn2a-2b-gene-cluster-transcription
#6
Qi Li, Bai Li, Chengya Dong, Yajie Wang, Qi Li
20(S)-Ginsenoside Rh2 (20(S)-GRh2) exerts important pharmacological effects with regard to the control of human hepatocellular carcinoma (HCC). EZH2 is a potent histone methyltransferase of H3K27me(3), which has been determined as an oncogene in many malignancies. The CDKN2A-2B gene cluster encodes three important tumor suppressors, P14, P15 and P16. In this study, the anticancer effect and molecular mechanism of 20(S)-GRh2 on HCC was investigated. Treatment of HCC cells with 20(S)-GRh2 inhibited cell proliferation, migration and induced cell cycle arrest at the G0/G1 phase, and inhibited tumor growth in vivo...
September 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28927789/anticancer-efficacy-of-p-dodecylaminophenol-against-high-risk-and-refractory-neuroblastoma-cells-in-vitro-and-in-vivo
#7
Noriko Takahashi, Shunpei Koyama, Shinya Hasegawa, Masahiro Yamasaki, Masahiko Imai
Neuroblastoma is an aggressive and drug-resistant refractory cancer. The human high-risk neuroblastoma cell line, SK-N-AS (non-amplified N-myc) is derived from stromal cells and it is resistant to treatment with retinoic acid (1, RA), which is a chemotherapeutic agent used to induce neuronal cellular differentiation of neuroblastomas. We have developed p-dodecylaminophenol (3, p-DDAP), based on N-(4-hydroxyphenyl)retinamide (2, 4-HPR), a synthetic amide of 1, since 1 and 2 are associated with the side-effect of nyctalopia...
September 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28927114/microrna-383-5p-acts-as-a-prognostic-marker-and-inhibitor-of-cell-proliferation-in-lung-adenocarcinoma-by-cancerous-inhibitor-of-protein-phosphatase-2a
#8
Shasha Zhao, Xinyuan Gao, Shuzhi Zang, Yunxia Li, Xianjun Feng, Xiaomei Yuan
Lung cancer is the leading cause of cancer-associated mortality worldwide. MicroRNAs (miRNAs/miRs) serve a role in the occurrence and development of lung cancer. The aim of the present study was to analyze the expression and function of the proliferation-associated miR-383-5p in lung adenocarcinoma (LAC). Samples of human LAC and matched adjacent normal lung tissues were surgically removed, and miR-383-5p expression and the pathological characteristics of lung adenocarcinoma were investigated. The present study revealed that miR-383-5p expression level was significantly decreased in LAC tissues and its expression levels were markedly associated with tumor size and differentiation...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927075/tumor-initiating-cells-contribute-to-radiation-resistance-in-primary-human-renal-clear-cell-carcinomas-by-activating-the-dna-damage-checkpoint-response
#9
Bo Li, Yong-Ju Gao, Xin-Yu Wu, Jing Cui, Ye Long, Jun-Ling Xu, De-Gang Ding
The use of radiotherapy in patients with clear cell renal carcinoma (ccRCC) is predominantly limited to palliation of metastases or control of local growth, because ccRCC cells readily develop radioresistance. The mechanisms underlying ccRCC resistance remain elusive. The present study demonstrated that ccRCC cells that survive fractionated radiation treatment display tumor-initiating cell (TIC) characteristics, such as high self-renewal and tumorigenic capacities, and overexpress stemness genes. ccRCC cells that survived fractionated radiation exhibited increased activation of the DNA damage checkpoint response and G2/M phase arrest compared with sham-irradiated cells...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926713/phase-separation-kinetics-of-dynamically-self-assembling-nanoparticles-with-toggled-interactions
#10
Zachary M Sherman, Helen Rosenthal, James W Swan
Ordered materials passively self-assembled from dispersions of nanoparticles with steady interactions are subject to thermodynamic constraints on their phase separation kinetics forcing a tradeoff between throughput and quality. Dynamically self-assembling dispersions whose interactions vary in a controlled way with time do not have these constraints and can rapidly form ordered structures while avoiding kinetic arrest. These out-of-equilibrium processes cannot be understood in terms of equilibrium thermodynamics or kinetic models derived from equilibrium thermodynamics, so new theories must be developed before dynamic self-assembly can be used to reliably fabricate nanomaterials...
September 19, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28926101/the-metabolic-cross-talk-between-epithelial-cancer-cells-and-stromal-fibroblasts-in-ovarian-cancer-progression-autophagy-plays-a-role
#11
REVIEW
Chanitra Thuwajit, Alessandra Ferraresi, Rossella Titone, Peti Thuwajit, Ciro Isidoro
Cancer and stromal cells, which include (cancer-associated) fibroblasts, adipocytes, and immune cells, constitute a mixed cellular ecosystem that dynamically influences the behavior of each component, creating conditions that ultimately favor the emergence of malignant clones. Ovarian cancer cells release cytokines that recruit and activate stromal fibroblasts and immune cells, so perpetuating a state of inflammation in the stroma that hampers the immune response and facilitates cancer survival and propagation...
September 19, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28925550/contemporary-concepts-in-carious-tissue-removal-a-review
#12
REVIEW
Falk Schwendicke
OBJECTIVES: Based on a changed understanding of the disease caries and its pathogenesis, strategies for carious tissue removal have changed, too. This review aims to summarize these changes and to provide clinical recommendations. OVERVIEW: Removing all carious dentin from a cavity is not needed any longer to manage caries or the carious lesion. Instead, the carious lesion should be treated in a way allowing to arrest its activity, while preserving sound tooth tissue and pulp vitality...
September 19, 2017: Journal of Esthetic and Restorative Dentistry
https://www.readbyqxmd.com/read/28925526/sub1-has-photoreceptor-dependent-and-independent-functions-in-sexual-development-and-secondary-metabolism-in-trichoderma-reesei
#13
Hoda Bazafkan, Sabrina Beier, Eva Stappler, Stefan Böhmdorfer, Josua T Oberlerchner, Michael Sulyok, Monika Schmoll
Light dependent processes are involved in the regulation of growth, development and enzyme production in Trichoderma reesei. The photoreceptors BLR1, BLR2 and ENV1 exert crucial functions in these processes. We analyzed the involvement of the transcription factor SUB1 in sexual development as well as secondary metabolism and its position in the light signaling cascade. SUB1 influences growth and in contrast to its homologue in N. crassa, SUB1 is not essential for fruiting body formation and male fertility in T...
September 19, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28925395/small-molecules-targeted-to-the-microtubule-hec1-interaction-inhibit-cancer-cell-growth-through-microtubule-stabilization
#14
M Ferrara, G Sessa, M Fiore, F Bernard, I A Asteriti, E Cundari, G Colotti, S Ferla, M Desideri, S Buglioni, D Trisciuoglio, D Del Bufalo, A Brancale, F Degrassi
Highly expressed in cancer protein 1 (Hec1) is a subunit of the kinetochore (KT)-associated Ndc80 complex, which ensures proper segregation of sister chromatids at mitosis by mediating the interaction between KTs and microtubules (MTs). HEC1 mRNA and protein are highly expressed in many malignancies as part of a signature of chromosome instability. These properties render Hec1 a promising molecular target for developing therapeutic drugs that exert their anticancer activities by producing massive chromosome aneuploidy...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28924465/brain-dead-donation-rate-in-month-of-ramadan-and-the-other-months-2005-2014
#15
M Aghighi, M Mahdavi-Mazdeh, M Saberi Isfeedvajani, S A Tavakoli, N Tirgar, A Heidary Rouchi
Regardless of the level of development, religion and beliefs have crucial impact on people's attitude towards organ donation. Although organ donation in Islam is obviously appraised, mainly due to lack of an appropriate infrastructure, post-mortem donation rate in Islamic countries is not comparable to successful settings. We conducted this study to assess the extent of contribution of factors that reduce the level of effectiveness, and also to determine the impact of altruistic feelings in the month of Ramadan on family refusal as the leading modifiable contributor to organ donation rate...
2017: International Journal of Organ Transplantation Medicine
https://www.readbyqxmd.com/read/28924110/bloody-bronchial-cast-formation-due-to-alveolar-hemorrhage-associated-with-h1n1-influenza-infection
#16
Yohei Okada, Asami Okada, Hiromichi Narumiya, Ryoji Iiduka, Kanade Katsura
A previously healthy 55-year-old man with H1N1 influenza A presented with severe respiratory failure and cardiac arrest. Following the return of spontaneous circulation, venovenous extracorporeal membrane oxygenation was required to maintain oxygenation. On day 2, bronchoscopy revealed a bloody bronchial cast obstructing the right main bronchus. A pathological examination revealed that it was composed of intrabronchial and intra-alveolar hemorrhagic tissue. Unfortunately, the patient died due to severe brain ischemia; a subsequent autopsy revealed marked alveolar hemorrhage...
September 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28923513/a-dioxin-like-compound-induces-hyperplasia-and-branching-morphogenesis-in-mouse-mammary-gland-through-alterations-in-tgf-%C3%AE-1-and-aryl-hydrocarbon-receptor-signaling
#17
Miret Noelia, Rico-Leo Eva, Pontillo Carolina, Zotta Elsa, Fernández-Salguero Pedro, Randi Andrea
Hexachlorobenzene (HCB) is a widespread environmental pollutant and a dioxin-like compound that binds weakly to the aryl hydrocarbon receptor (AhR). Because AhR and transforming growth factor β1 (TGF-β1) converge to regulate common signaling pathways, alterations in this crosstalk might contribute to developing preneoplastic lesions. The aim of this study was to evaluate HCB action on TGF-β1 and AhR signaling in mouse mammary gland, through AhR+/+ and AhR-/- models. Results showed a differential effect in mouse mammary epithelial cells (NMuMG), depending on the dose: 0...
September 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28923397/the-two-novel-dll4-targeting-antibody-drug-conjugates-mvm03-and-mgd03-show-potent-anti-tumour-activity-in-breast-cancer-xenograft-models
#18
Shijing Wang, Rihong Zhou, Fumou Sun, Renjie Li, Min Wang, Min Wu
The anti-human Delta-like 4 (DLL4) monoclonal antibody MMGZ01 has a high affinity to hrDLL4 and arrests the DLL4-mediated human umbilical vein endothelial cell (HUVEC) phenotype, promotes immature vessels, and effectively reduces breast cancer cell growth in vivo. To develop a much more effective therapy, we conjugated MMGZ01 with two small-molecule cytotoxic agents, i.e., monomethyl auristatin E (MMAE) and doxorubicin (DOX), with different linkers to generate antibody-drug conjugates (ADCs), i.e., MMGZ01-vc-MMAE (named MvM03) and MMGZ01-GMBS-DOX (named MGD03), that are more potent therapeutic agents than naked antibody therapeutic agents...
September 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28922548/lncrna-plac2-down-regulates-rpl36-expression-and-blocks-cell-cycle-progression-in-glioma-through-a-mechanism-involving-stat1
#19
Yan-Wei Hu, Chun-Min Kang, Jing-Jing Zhao, Ying Nie, Lei Zheng, Hai-Xia Li, Xin Li, Qian Wang, Yu-Rong Qiu
Current glioma therapies allow in situ delivery of cytotoxic drugs to the tumour; however, gliomas show early recurrence due to their highly proliferative character. Long non-coding (lnc)RNAs play critical roles in tumorigenesis by controlling cell proliferation and cycling. However, the mechanism of action of lncRNAs in glioma development remains unclear. Here, we report that the lncRNA PLAC2 induces cell cycle arrest by targeting ribosomal protein (RP)L36 in glioma. RPL36 promoted cell proliferation and G1/S cell cycle progression...
September 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28920564/intentional-overdose-of-the-novel-anti-epileptic-drug-eslicarbazepine-presenting-with-recurrent-seizures-and-ventricular-dysrhythmias
#20
Jesse Thompson, James D Powell, Daniel H Ovakim
Eslicarbazepine is a novel anti-epileptic agent indicated for the treatment of partial-onset seizures. We present the case of an 18 year old female that presented to the Emergency Department four hours after a reported intentional ingestion of an estimated 5600 mg of eslicarbazepine. Although initially hemodynamically stable and neurologically normal, shortly after arrival she developed confusion, rigidity and clonus, followed by recurrent seizures, hypoxemia and cardiac arrest which responded to cardiopulmonary resuscitation and wide complex tachycardia requiring defibrillation...
September 18, 2017: CJEM
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