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https://www.readbyqxmd.com/read/29156837/meta-analysis-of-efficacy-and-adverse-events-of-erlotinib-based-targeted-therapies-for-advanced-metastatic-non-small-cell-lung-cancer
#1
Fei Li, Shu-Hua Zhang, Li-Min Pang
A network meta-analysis evaluating efficacy and adverse events of eight erlotinib-based therapies (erlotinib+placebo, erlotinib+tivantinib, erlotinib+celecoxib, erlotinib+onartuzumab, erlotinib+sunitinib, erlotinib+entinostat, erlotinib+sorafenib, and erlotinib+bevacizumab) for advanced/metastatic non-small-cell lung cancer (NSCLC) was performed. PubMed and Cochrane Library were reviewed, and ten randomized controlled trials were identified in which patients receiving at least one erlotinib-based therapy. Efficacy outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), and adverse outcomes were evaluated...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156828/the-%C3%AE-glucan-from-lentinus-edodes-suppresses-cell-proliferation-and-promotes-apoptosis-in-estrogen-receptor-positive-breast-cancers
#2
Hui Xu, Siwei Zou, Xiaojuan Xu
Breast cancer is now the most common cancer in worldwide women, and novel interventions are needed to overcome the resistance occurring in the estrogen-targeted endocrine therapy. Herein, we demonstrate that the β-glucan from Lentinus edodes (LNT) exhibited a profound inhibition ratio of ∼53% against estrogen receptor positive (ER+) MCF-7 tumor growth in nude mice similar to the positive control of cisplatin. Immunohistochemistry images showed that LNT evidently suppressed cell proliferation and promoted apoptosis in MCF-7 tumor tissues...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156817/near-infrared-photothermal-therapy-using-anti-egfr-gold-nanorod-conjugates-for-triple-negative-breast-cancer
#3
Meihua Zhang, Hoe Suk Kim, Tiefeng Jin, Jisu Woo, Yin Ji Piao, Woo Kyung Moon
Current EGFR-targeted therapy for triple negative breast cancer (TNBC) has produced disappointing results. A rational therapeutic strategy to improve EGFR-targeted treatment for TNBC is therefore needed. In this study we evaluated the feasibility of treating TNBC using photoacoustic imaging (PAI)-guided near-infrared photothermal therapy (NIR-PTT) with anti-EGFR-conjugated gold nanorods (anti-EGFR-GN). NIR-PTT combined with anti-EGFR-GN exerted synergistic anti-proliferative and apoptotic actions through upregulation of HSP70 and cleaved caspase-3, downregulation of Ki-67 and EGFR, and inhibition of several intracellular signaling molecules (mTOR, AKT, ERK1/2 and FAK)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156788/modulation-of-hif-1%C3%AE-and-stat3-signaling-contributes-to-anti-angiogenic-effect-of-yc-1-in-mice-with-liver-fibrosis
#4
Tzung-Yan Lee, Yann-Lii Leu, Chorng-Kai Wen
Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The aim of the study was to evaluate the mechanisms of HIF-1α inhibitor, YC-1, during bile duct ligation (BDL)-induced liver fibrosis in mice. Liver fibrosis was induced in mice, and YC-1 was then given intraperitoneally (50 mg/kg) once daily following 5 days. Liver injuries mice that were treated with YC-1 showed improved inflammatory response and diminished angiogenesis and hepatic fibrosis. YC-1 treatment inhibited liver neutrophil infiltration, while a decreased in TNF-α signaling as well as macrophage aggregation...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156785/in-silico-and-in-vitro-identification-of-inhibitory-activities-of-sorafenib-on-histone-deacetylases-in-hepatocellular-carcinoma-cells
#5
Tsang-Pai Liu, Yi-Han Hong, Pei-Ming Yang
Although sorafenib has been approved for treating hepatocellular carcinoma (HCC), clinical results are not satisfactory. Polypharmacology (one drug with multiple molecular targets) is viewed as an attractive strategy for identifying novel mechanisms of a drug and then rationally designing more-effective next-generation therapeutic agents. In this study, a polypharmacological study of sorafenib was performed by mining the next-generation Connectivity Map (CMap) database, CLUE (https://clue.io/). We found that sorafenib may act as a histone deacetylase (HDAC) inhibitor based on similar gene expression profiles...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156780/baicalein-inhibits-progression-of-osteosarcoma-cells-through-inactivation-of-the-wnt-%C3%AE-catenin-signaling-pathway
#6
Guo Dai, Di Zheng, Qianliang Wang, Jian Yang, Gaiwei Liu, Qi Song, Xiangran Sun, Chunjie Tao, Qingzhu Hu, Tian Gao, Ling Yu, Weichun Guo
Osteosarcoma is a very common type of malignant bone tumor in children and young adults and aberrant activation of Wnt/β-catenin signaling pathway has been discovered in osteosarcoma. The traditional Chinese medicine baicalein was proved to have anti-proliferative and anti-metastatic properties in osteosarcoma, but the mechanism remained poorly understood. In the present study, we assessed the effects of baicalein on osteosarcoma and detected the potential molecular mechanism. We found that baicalein significantly suppressed the proliferation of osteosarcoma cells in a concentration- and time-dependent manner...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156766/isobaric-tags-for-relative-and-absolute-quantification-based-proteomic-analysis-of-testis-biopsies-in-rhesus-monkeys-treated-with-transient-scrotal-hyperthermia
#7
Meng Rao, Sha Ma, Shifu Hu, Hui Lei, Yanqing Wu, Yanfei Zhou, Wei Xia, Changhong Zhu
This study aimed to examine the cellular and molecular events that occur in rhesus monkey testes after scrotal hyperthermia. Eight male adult rhesus monkeys were subjected to scrotal hyperthermia at 43°C for 30 min daily for 6 consecutive days. Sperm concentration, reproductive hormones, and testis histology were examined before hyperthermia (day 0), and at 8, 15, 30, 45, 60, 75, and 90 days after the initiation of hyperthermia. iTRAQ-based proteomic analysis was conducted on testicular tissues collected on days 0, 8, and 60 to identify differentially expressed proteins at the early and recovery stages of testicular damage...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156719/the-micrornas-mir-200b-3p-and-mir-429-5p-target-the-limk1-cfl1-pathway-to-inhibit-growth-and-motility-of-breast-cancer-cells
#8
Dengfeng Li, Hong Wang, Hongming Song, Hui Xu, Bingkun Zhao, Chenyang Wu, Jiashu Hu, Tianqi Wu, Dan Xie, Junyong Zhao, Qiang Shen, Lin Fang
Triple-negative breast cancer (TNBC) has the worst prognosis of all subtypes of breast cancer (BC), with limited options for conventional therapy and no targeted therapies. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. In this study, we aimed to determine whether two members of the miR-200 family, miR-200b-3p and miR-429-5p, are involved in BC cell proliferation and motility and to elucidate their target genes and pathways. We performed a meta-analysis that reveals down-regulated expression of miR-200b-3p and miR-429-5p in BC tissues and cell lines, consistent with a lower expression of miR-200b-3p and miR-429-5p in MDA-MB-231 and HCC1937 cells than in MCF-7 and MCF-10 cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156714/investigation-of-factors-affecting-the-efficacy-of-3c23k-a-human-monoclonal-antibody-targeting-misiir
#9
Sarah E Gill, Qing Zhang, Gary L Keeney, William A Cliby, S John Weroha
MISIIR is a potential target for ovarian cancer (OC) therapy due to its tissue-specific pattern of expression. 3C23K is a novel therapeutic monoclonal anti-MISIIR antibody designed to recruit effector cells and promote cell death through ADCC (antibody dependent cell-mediated cytotoxicity). Our objective was to determine the tolerability and efficacy of 3C23K in OC patient-derived xenografts (PDX) and to identify factors affecting efficacy. Quantitative RT-PCR, immunohistochemistry (IHC), and flow cytometry were used to categorize MISIIR expression in established PDX models derived from primary OC patients...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156680/vemurafenib-resistance-via-de-novo-rbm-genes-mutations-and-chromosome-5-aberrations-is-overcome-by-combined-therapy-with-palbociclib-in-thyroid-carcinoma-with-braf-v600e
#10
Zeus A Antonello, Nancy Hsu, Manoj Bhasin, Giovanni Roti, Mukta Joshi, Paul Van Hummelen, Emily Ye, Agnes S Lo, S Ananth Karumanchi, Christine R Bryke, Carmelo Nucera
Purpose: Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAF(V600E) represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAF(WT/V600E)-positive PTC patient-derived cells with P16(-/-) (CDKN2A(-/-))...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156556/cdx2-stimulates-the-proliferation-of-porcine-intestinal-epithelial-cells-by-activating-the-mtorc1-and-wnt-%C3%AE-catenin-signaling-pathways
#11
Hong-Bo Fan, Zhen-Ya Zhai, Xiang-Guang Li, Chun-Qi Gao, Hui-Chao Yan, Zhe-Sheng Chen, Xiu-Qi Wang
Caudal type homeobox 2 (CDX2) is expressed in intestinal epithelial cells and plays a role in gut development and homeostasis by regulating cell proliferation. However, whether CDX2 cooperates with the mammalian target of rapamycin complex 1 (mTORC1) and Wnt/β-catenin signaling pathways to stimulate cell proliferation remains unknown. The objective of this study was to investigate the effect of CDX2 on the proliferation of porcine jejunum epithelial cells (IPEC-J2) and the correlation between CDX2, the mTORC1 and Wnt/β-catenin signaling pathways...
November 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156531/heated-naringin-mitigate-the-genotoxicity-effect-of-mitomycin-c-in-balb-c-mice-through-enhancing-the-antioxidant-status
#12
Mouna Maatouk, Nadia Mustapha, Imen Mokdad-Bzeouich, Hind Chaaban, Irina Ioannou, Kamel Ghedira, Mohamed Ghoul, Leila Chekir-Ghedira
A major problem with cancer chemotherapy is its severe toxic effects on non-target tissues. Assessment of natural products for their protective effect against anticancer drugs induced toxicity is gaining importance in cancer biology. The aim of the present study was to evaluate the effect of native and thermal treated naringin on the protective effect against mitomycin C (MMC) induced genotoxicity. The genotoxicity in liver kidney and brain cells isolated from Balb/C mice were evaluated by performing the comet assay...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156148/cm-101-type-i-collagen-targeted-mr-imaging-probe-for-detection-of-liver-fibrosis
#13
Christian T Farrar, Eric M Gale, Richard Kennan, Ian Ramsay, Ricard Masia, Gunisha Arora, Kailyn Looby, Lan Wei, Jayashree Kalpathy-Cramer, Michelle M Bunzel, Chunlian Zhang, Yonghua Zhu, Taro E Akiyama, Michael Klimas, Shirly Pinto, Himashinie Diyabalanage, Kenneth K Tanabe, Valerie Humblet, Bryan C Fuchs, Peter Caravan
Purpose To evaluate the biodistribution, metabolism, and pharmacokinetics of a new type I collagen-targeted magnetic resonance (MR) probe, CM-101, and to assess its ability to help quantify liver fibrosis in animal models. Materials and Methods Biodistribution, pharmacokinetics, and stability of CM-101 in rats were measured with mass spectrometry. Bile duct-ligated (BDL) and sham-treated rats were imaged 19 days after the procedure by using a 1.5-T clinical MR imaging unit. Mice were treated with carbon tetrachloride (CCl4) or with vehicle two times a week for 10 weeks and were imaged with a 7...
November 20, 2017: Radiology
https://www.readbyqxmd.com/read/29156043/tenofovir-alafenamide-fumarate-a-new-tenofovir-prodrug-for-the-treatment-of-chronic-hepatitis-b-infection
#14
Maria Buti, Mar Riveiro-Barciela, Rafael Esteban
Tenofovir alafenamide fumarate (TAF), a new prodrug of tenofovir and a potential successor of tenofovir disoproxil fumarate (TDF), has been approved in the United States and Europe for treating adolescents and adults with chronic hepatitis B infection. TAF is formulated to deliver the active metabolite to target cells more efficiently than TDF at lower doses, thereby reducing systemic exposure to tenofovir. In patients with chronic hepatitis B, TAF appears to be as effective as TDF, with lower bone and renal toxicity...
November 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#15
Fernando J Bustos, Estibaliz Ampuero, Nur Jury, Rodrigo Aguilar, Fahimeh Falahi, Jorge Toledo, Juan Ahumada, Jaclyn Lata, Paula Cubillos, Berta Henríquez, Miguel V Guerra, Jimmy Stehberg, Rachael L Neve, Nibaldo C Inestrosa, Ursula Wyneken, Marco Fuenzalida, Steffen Härtel, Miguel Sena-Esteves, Lorena Varela-Nallar, Marianne G Rots, Martin Montecino, Brigitte van Zundert
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9)...
November 16, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29155703/modeling-amyloid-%C3%AE-42-toxicity-and-neurodegeneration-in-adult-zebrafish-brain
#16
Prabesh Bhattarai, Alvin Kuriakose Thomas, Mehmet Ilyas Cosacak, Christos Papadimitriou, Violeta Mashkaryan, Yixin Zhang, Caghan Kizil
Alzheimer's disease (AD) is a debilitating neurodegenerative disease in which accumulation of toxic amyloid-β42 (Aβ42) peptides leads to synaptic degeneration, inflammation, neuronal death, and learning deficits. Humans cannot regenerate lost neurons in the case of AD in part due to impaired proliferative capacity of the neural stem/progenitor cells (NSPCs) and reduced neurogenesis. Therefore, efficient regenerative therapies should also enhance the proliferation and neurogenic capacity of NSPCs. Zebrafish (Danio rerio) is a regenerative organism, and we can learn the basic molecular programs with which we could design therapeutic approaches to tackle AD...
October 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155624/functional-and-targeted-lymph-node-imaging-in-prostate-cancer-current-status-and-future-challenges
#17
Harriet C Thoeny, Sebastiano Barbieri, Johannes M Froehlich, Baris Turkbey, Peter L Choyke
Patients with prostate cancer who have regional lymph node (LN) metastases face an increased risk of death from disease and are therefore treated aggressively. Surgical LN dissection is the established method of staging regional nodes; however, this invasive technique carries substantial morbidities and a noninvasive imaging method is needed to reduce or eliminate the need for extended pelvic LN dissections (ePLND). Conventional computed tomography and magnetic resonance (MR) imaging have proven insensitive and nonspecific because both use nodal size criteria, which is notoriously inaccurate...
December 2017: Radiology
https://www.readbyqxmd.com/read/29155590/semisynthesis-and-biological-evaluation-of-xanthone-amphiphilics-as-selective-highly-potent-antifungal-agents-to-combat-fungal-resistance
#18
Shuimu Lin, Wan Ling Wendy Sin, Jun-Jie Koh, Fanghui Lim, Lin Wang, Derong Cao, Roger W Beuerman, Li Ren, Shouping Liu
New efficient antifungal agents are urgently needed to treat drug-resistant fungal infections. Here, we designed and synthesized a series of cationic xanthone amphiphilics as antifungal agents from natural α-mangostin to combat fungal resistance. The attachment of cationic residues on the xanthone scaffold of α-mangostin resulted in interesting antifungal agents with a novel mode of action. Two lead compounds (1 and 2) showed potent antifungal activity against a wide range of fungal pathogens, including drug-resistant C...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29155449/baicalein-inhibits-acinar-to-ductal-metaplasia-of-pancreatic-acinal-cell-ar42j-via-improving-the-inflammatory-microenvironment
#19
Wei-Ling Pu, Ying-Ying Luo, Ru-Yu Bai, Ao-Wei Guo, Kun Zhou, Yun-Sha Zhang, Lin Miao, Curzio Rüegg, Micheal O Hottiger, Xiu-Mei Gao, Li-Kang Sun
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29155426/cd22-targeted-car-t-cells-induce-remission-in-b-all-that-is-naive-or-resistant-to-cd19-targeted-car-immunotherapy
#20
Terry J Fry, Nirali N Shah, Rimas J Orentas, Maryalice Stetler-Stevenson, Constance M Yuan, Sneha Ramakrishna, Pamela Wolters, Staci Martin, Cindy Delbrook, Bonnie Yates, Haneen Shalabi, Thomas J Fountaine, Jack F Shern, Robbie G Majzner, David F Stroncek, Marianna Sabatino, Yang Feng, Dimiter S Dimitrov, Ling Zhang, Sang Nguyen, Haiying Qin, Boro Dropulic, Daniel W Lee, Crystal L Mackall
Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent effects in relapsed and/or refractory pre-B cell acute lymphoblastic leukemia (B-ALL), but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed in most cases of B-ALL and is usually retained following CD19 loss. We report results from a phase 1 trial testing a new CD22-targeted CAR (CD22-CAR) in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy...
November 20, 2017: Nature Medicine
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