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https://www.readbyqxmd.com/read/29780364/antibacterial-efficacy-of-polysaccharide-capped-silver-nanoparticles-is-not-compromised-by-acrab-tolc-efflux-pump
#1
Mitali Mishra, Satish Kumar, Rakesh K Majhi, Luna Goswami, Chandan Goswami, Harapriya Mohapatra
Antibacterial therapy is of paramount importance in treatment of several acute and chronic infectious diseases caused by pathogens. Over the years extensive use and misuse of antimicrobial agents has led to emergence of multidrug resistant (MDR) and extensive drug resistant (XDR) pathogens. This drastic escalation in resistant phenotype has limited the efficacy of available therapeutic options. Thus, the need of the hour is to look for alternative therapeutic approaches to mitigate healthcare concerns caused due to MDR bacterial infections...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29777599/immense-random-colocalization-revealed-by-automated-high-content-image-cytometry-seriously-questions-fish-as-gold-standard-for-detecting-eml4-alk-fusion
#2
Gábor Smuk, Tamás Tornóczky, László Pajor, Ilse Chudoba, Béla Kajtár, Veronika Sárosi, Gábor Pajor
EML4-ALK gene fusion (inv2(p21p23)) of non-small cell lung cancer (NSCLC) predisposes to tyrosine kinase inhibitor treatment. One of the gold standard diagnostics is the dual color (DC) break-apart (BA) FISH technique, however, the unusual closeness of the involved genes has been suggested to raise likelihood of random co-localization (RCL) of signals. Although this is suspected to decrease sensitivity (often to as low as 40-70%), the exact level and effect of RCL has not been revealed thus far. Signal distances were analyzed to the 0...
May 19, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/29773553/intratumoral-androgen-levels-are-linked-to-tmprss2-erg-fusion-in-prostate-cancer
#3
Matias Knuuttila, Arfa Mehmood, Jenni Mäki-Jouppila, Henrik Ryberg, Pekka Taimen, Juha Knaapila, Otto Ettala, Peter J Bostrom, Claes Ohlsson, Mikko S Venäläinen, Asta Laiho, Laura L Elo, Petra Sipilä, Sari Makela, Matti Poutanen
Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral DHT concentrations were significantly higher in the cancerous tissues compared to benign prostate (p<0...
May 17, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29766299/molecularly-defined-diffuse-leptomeningeal-glioneuronal-tumor-dlgnt-comprises-two-subgroups-with-distinct-clinical-and-genetic-features
#4
Maximilian Y Deng, Martin Sill, Jason Chiang, Jens Schittenhelm, Martin Ebinger, Martin U Schuhmann, Camelia-Maria Monoranu, Till Milde, Andrea Wittmann, Christian Hartmann, Clemens Sommer, Werner Paulus, Jutta Gärtner, Wolfgang Brück, Thomas Rüdiger, Alfred Leipold, Zane Jaunmuktane, Sebastian Brandner, Felice Giangaspero, Paolo Nozza, Jaume Mora, Andres Morales la Madrid, Ofelia Cruz Martinez, Jordan R Hansford, Torsten Pietsch, Anna Tietze, Pablo Hernáiz-Driever, Iris Stoler, David Capper, Andrey Korshunov, David W Ellison, Andreas von Deimling, Stefan M Pfister, Felix Sahm, David T W Jones
Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of > 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs...
May 15, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29764594/-research-progress-of-kras-mutation-in-non-small-cell-lung-cancer
#5
Lei Liu, Suju Wei
Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all patients with lung cancer, the majority of patients with lung cancer at the time of diagnosis is in the advanced stage. The development of target therapy based on has changed the mode of treatment in patients with advanced NSCLC. In NSCLC, epidermal growth factor receptor mutation (EGFR) fusion with echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) has been shown to be a powerful biomarker...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29764505/xenograft-tumors-derived-from-malignant-pleural-effusion-of-the-patients-with-non-small-cell-lung-cancer-as-models-to-explore-drug-resistance
#6
Yunhua Xu, Feifei Zhang, Xiaoqing Pan, Guan Wang, Lei Zhu, Jie Zhang, Danyi Wen, Shun Lu
BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively...
May 9, 2018: Cancer communications
https://www.readbyqxmd.com/read/29764494/precision-medicine-becomes-reality-tumor-type-agnostic-therapy
#7
REVIEW
Li Yan, Wei Zhang
Precision medicine just witnessed two breakthroughs in oncology in 2017. Pembrolizumab (Keytruda), Merck's anti-programmed cell death-1 (PD-1) monoclonal antibody (mAb), received accelerated approval in May 2017 by the US Food and Drug Administration for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR). Shortly after, nivolumab (Opdivo), Bristol-Myers Squibb's anti-PD-1 mAb, gained an accelerated approval in August 2017 for adult and pediatric patients with MSI-H or dMMR metastatic colorectal cancer that has progressed after standard chemotherapy...
March 31, 2018: Cancer communications
https://www.readbyqxmd.com/read/29763685/autophagy-plays-a-pro-survival-role-against-methamphetamine-induced-apoptosis-in-h9c2-cells
#8
Chao Zhao, Yong Mei, Xufeng Chen, Lei Jiang, Yunfei Jiang, Xu Song, Hang Xiao, Jun Wang, Jingsong Zhang
Methamphetamine (METH) is a commonly abused psychostimulant that can induce severe neurotoxicity. Cardiovascular injury caused by METH has recently gained increasing attention; however, the underlying mechanisms remain unclear. As autophagy has been shown to be associated with cell injury, the association between autophagy and METH-mediated cell apoptosis was investigated in the present study. METH treatment significantly increased the expression of two key autophagy proteins, i.e., Beclin-1 and LC3-II, in the cardiomyocyte cell line H9C2...
May 12, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29762727/development-of-targeted-therapy-and-immunotherapy-for-treatment-of-small-cell-lung-cancer
#9
Motonobu Saito, Kouya Shiraishi, Akiteru Goto, Hiroyuki Suzuki, Takashi Kohno, Koji Kono
Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC...
May 14, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29760553/a-favorable-outcome-of-advanced-dermatofibrosarcoma-protuberans-under-treatment-with-sunitinib-after-imatinib-failure
#10
Wei Xiao, Yi Que, Ruiqing Peng, Ya Ding, Jingjing Zhao, Xizhi Wen, Desheng Weng, Xiaoshi Zhang, Yuanxiang Guan, Xing Zhang
While traditional cytotoxic agents play a limited role in advanced dermatofibrosarcoma protuberans (DFSP), the treatment of sunitinib for patients with advanced DFSP after imatinib failure is not well defined. The objective of this case report was to analyze the relationship between molecular mechanisms and clinical outcomes of sunitinib treatment in patients with advanced DFSP after imatinib failure. In this case report, a 37-year-old man suffered from advanced DFSP progression after surgical operation, microwave ablation, and chemotherapy...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29759975/restoring-the-switch-for-cancer-cell-death-targeting-the-apoptosis-signaling-pathway
#11
REVIEW
Clement Chung
PURPOSE: The relevance of apoptosis to cancer development and pharmacologic agents that target this pathway in selected malignancies are described. SUMMARY: Apoptosis is a tightly regulated biological process mediated by both proapoptotic (i.e., prodeath) and antiapoptotic (i.e., prosurvival) proteins. While apoptosis represents a well-established effector mechanism induced by conventional chemotherapy in many malignancies, the development of apoptosis-based targeted therapy is relatively new...
May 14, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29754163/inhibition-of-autophagy-potentiated-the-anti-tumor-effects-of-vegf-and-cd47-bispecific-therapy-in-glioblastoma
#12
Xuyao Zhang, Shaofei Wang, Yanyang Nan, Jiajun Fan, Wei Chen, Jingyun Luan, Yichen Wang, Yanxu Liang, Song Li, Wenzhi Tian, Dianwen Ju
Glioblastoma, characterized by extensive microvascular proliferation and invasive tumor growth, is one of the most common and lethal malignancies in adults. Benefits of the conventional anti-angiogenic therapy were only observed in a subset of patients and limited by diverse relapse mechanism. Fortunately, recent advances in cancer immunotherapy have offered new hope for patients with glioblastoma. Herein, we reported a novel dual-targeting therapy for glioblastoma through simultaneous blockade of VEGF and CD47 signaling...
May 12, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29752549/promising-new-agents-for-colorectal-cancer
#13
REVIEW
Satya Das, Kristen K Ciombor, Sigurdis Haraldsdottir, Richard M Goldberg
Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility...
May 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29748581/leptin-increases-mitochondrial-opa1-via-gsk3-mediated-oma1-ubiquitination-to-enhance-therapeutic-effects-of-mesenchymal-stem-cell-transplantation
#14
Fan Yang, Rongrong Wu, Zhi Jiang, Jinghai Chen, Jinliang Nan, Sheng'an Su, Na Zhang, Chen Wang, Jing Zhao, Cheng Ni, Yingchao Wang, Wangxing Hu, Zhiru Zeng, Keyang Zhu, Xianbao Liu, Xinyang Hu, Wei Zhu, Hong Yu, Jinyu Huang, Jian'an Wang
Accumulating evidence revealed that mesenchymal stem cells (MSCs) confer cardioprotection against myocardial infarction (MI). However, the poor survival and engraftment rate of the transplanted cells limited their therapeutic efficacy in the heart. The enhanced leptin production associated with hypoxia preconditioning contributed to the improved MSCs survival. Mitochondrial integrity determines the cellular fate. Thus, we aimed to investigate whether leptin can enhance mitochondrial integrity of human MSCs (hMSCs) to protect against various stress...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29747393/anti-rsv-peptide-loaded-liposomes-for-the-inhibition-of-respiratory-syncytial-virus
#15
Sameer Joshi, Atul A Chaudhari, Vida Dennis, Daniel J Kirby, Yvonne Perrie, Shree Ram Singh
Although respiratory syncytial virus (RSV) is one of the leading causes of acute respiratory tract infection in infants and adults, effective treatment options remain limited. To circumvent this issue, there is a novel approach, namely, the development of multifunctional liposomes for the delivery of anti RSV-peptides. While most of the peptides that are used for loading with the particulate delivery systems are the penetrating peptides, an alternative approach is the development of liposome-peptide systems, which are loaded with an RSV fusion peptide (RF-482), which has been designed to inhibit the RSV fusion and block infection...
May 9, 2018: Bioengineering
https://www.readbyqxmd.com/read/29745064/molecular-basis-of-benzimidazole-inhibitors-to-hepatitis-c-virus-envelope-glycoprotein
#16
Reaz Uddin, Kevin M Downard
The molecular basis for the inhibitory action of a benzimidazole inhibitor compound to hepatitis C virus (HCV) E1 envelope protein was examined computationally. Structures for the wild type E1 protein and 7 mutants were modelled using an ab initio protein structure prediction algorithm, and these models were docked with the benzimidazole inhibitor. Top ranked conformers for each docked structure were examined in the context of the putative function of the inhibitor that blocks fusion of the envelope protein to the host cells...
May 9, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29743550/inhibitor-of-apoptosis-proteins-are-required-for-effective-fusion-of-autophagosomes-with-lysosomes
#17
Sylwia Gradzka, Oliver S Thomas, Oliver Kretz, Aladin Haimovici, Lazaros Vasilikos, Wendy Wei-Lynn Wong, Georg Häcker, Ian E Gentle
Inhibitor of Apoptosis Proteins act as E3 ubiquitin ligases to regulate NF-κB signalling from multiple pattern recognition receptors including NOD2, as well as TNF Receptor Superfamily members. Loss of XIAP in humans causes X-linked Lymphoproliferative disease type 2 (XLP-2) and is often associated with Crohn's disease. Crohn's disease is also caused by mutations in the gene encoding NOD2 but the mechanisms behind Crohn's disease development in XIAP and NOD2 deficient-patients are still unknown. Numerous other mutations causing Crohn's Disease occur in genes controlling various aspects of autophagy, suggesting a strong involvement of autophagy in preventing Crohn's disease...
May 9, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29743355/a-novel-gp41-binding-adnectin-with-potent-anti-hiv-activity-is-highly-synergistic-when-linked-to-a-cd4-binding-adnectin
#18
David Wensel, Yongnian Sun, Jonathan Davis, Zhufang Li, Sharon Zhang, Thomas McDonagh, David Fabrizio, Mark Cockett, Mark Krystal
The N17 region of gp41 in HIV-1 is the most conserved region in gp160. mRNA selection technologies were used to identify an Adnectin that binds to this region and inhibits gp41-induced membrane fusion. Additional selection conditions were used to optimize the Adnectin to greater potency (5.4 ± 2.6 nM) to HIV-1 and improved binding affinity to a N17-containing helical trimer (0.8 ± 0.4 nM). Resistance to this Adnectin mapped to a single Glu to Arg change within the N17 coding region. The optimized Adnectin (6200_A08) exhibited high potency and broad spectrum against 123 envelope proteins and multiple clinical isolate viruses, although certain envelope proteins did exhibit reduced susceptibility against 6200_A08 alone...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29742155/the-hsv-1-mechanisms-of-cell-to-cell-spread-and-fusion-are-critically-dependent-on-host-ptp1b
#19
Jillian C Carmichael, Hiroki Yokota, Rebecca C Craven, Anthony Schmitt, John W Wills
All herpesviruses have mechanisms for passing through cell junctions, which exclude neutralizing antibodies and offer a clear path to neighboring, uninfected cells. In the case of herpes simplex virus type 1 (HSV-1), direct cell-to-cell transmission takes place between epithelial cells and sensory neurons, where latency is established. The spreading mechanism is poorly understood, but mutations in four different HSV-1 genes can dysregulate it, causing neighboring cells to fuse to produce syncytia. Because the host proteins involved are largely unknown (other than the virus entry receptor), we were intrigued by an earlier discovery that cells infected with wild-type HSV-1 will form syncytia when treated with salubrinal...
May 9, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29739041/1%C3%AE-25-oh-2-vitamin-d3-inhibits-c2c12-cell-differentiation-by-activating-c-src-and-erk1-2
#20
Zhonghua Wang, Aijun Jiang, Jingwei Mei, Xinyan Zhang
BACKGROUND: The steroid hormone 1α,25(OH)2-vitamin D3 (1,25-D3) induced some biological responses through activation of MAPK cascades in various cell types. It seems that 1,25-D3 plays different roles at different stages of proliferating, differentiating, and differentiated C2C12 cells. We wanted to detect the effect of 1,25-D3 on myogenic differentiation and the role of ERK1/2 in differentiating stage induced by 2% horse serum with 1,25-D3. METHODS: In this study, cells were induced to differentiate with 2% horse serum until the 7th day (with addition of 1,25-D3 every two days)...
May 1, 2018: Clinical Laboratory
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