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https://www.readbyqxmd.com/read/28938699/change-from-lung-adenocarcinoma-to-small-cell-lung-cancer-as-a-mechanism-of-resistance-to-afatinib
#1
Paolo Manca, Marco Russano, Francesco Pantano, Giuseppe Tonini, Daniele Santini
We report the case of a patient affected by advanced EGFR mutation-positive lung who experienced resistance to therapy during treatment with Afatinib through the occurrence of a switch of tumor histotype to small cell lung cancer (SCLC) with features of a G3 neuroendocrine carcinoma. Unexpectedly, the switch to SCLC histotype occurred in the only site not responsive to afatinib and subsequently the most responsive to chemotherapy. Our case shows that occurrence of switch to SCLC is a possible mechanism of resistance during treatment with Afatinib...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938647/long-non-coding-rna-malat1-for-promoting-metastasis-and-proliferation-by-acting-as-a-cerna-of-mir-144-3p-in-osteosarcoma-cells
#2
Yong Wang, Yueyang Zhang, Tao Yang, Wei Zhao, Ningning Wang, Pengcheng Li, Xiandong Zeng, Weiguo Zhang
Long non-coding RNAs (lncRNAs) are involved in various biological processes and diseases including osteosarcoma. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overly expressed in osteosarcoma. But the function and mechanism it works on in osteosarcoma proliferation and metastasis mediated by Rho associated coiled-coil containing protein kinase 1 (ROCK1) and Rho associated coiled-coil containing protein kinase 2 (ROCK2) remain unclear. In the present study, an elevated MALAT1 was found in osteosarcoma tissues and cell lines, and the elevated MALAT1 was correlated with a poor prognosis in osteosarcoma patients...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938614/phenformin-enhances-the-therapeutic-effect-of-selumetinib-in-kras-mutant-non-small-cell-lung-cancer-irrespective-of-lkb1-status
#3
Jun Zhang, Sreenivas Nannapaneni, Dongsheng Wang, Fakeng Liu, Xu Wang, Rui Jin, Xiuju Liu, Mohammad Aminur Rahman, Xianghong Peng, Guoqing Qian, Zhuo G Chen, Kwok-Kin Wong, Fadlo R Khuri, Wei Zhou, Dong M Shin
MEK inhibition is potentially valuable in targeting KRAS-mutant non-small cell lung cancer (NSCLC). Here, we analyzed whether concomitant LKB1 mutation alters sensitivity to the MEK inhibitor selumetinib, and whether the metabolism drug phenformin can enhance the therapeutic effect of selumetinib in isogenic cell lines with different LKB1 status. Isogenic pairs of KRAS-mutant NSCLC cell lines A549, H460 and H157, each with wild-type and null LKB1, as well as genetically engineered mouse-derived cell lines 634 (kras(G12D/wt)/p53(-/-)/lkb1(wt/wt)) and t2 (kras(G12D/wt)/p53(-/-)/lkb1(-/-)) were used in vitro to analyze the activities of selumetinib, phenformin and their combination...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938599/a-pathways-based-prediction-model-for-classifying-breast-cancer-subtypes
#4
Tong Wu, Yunfeng Wang, Ronghui Jiang, Xinliang Lu, Jiawei Tian
Breast cancer is highly heterogeneous and is classified into four subtypes characterized by specific biological traits, treatment responses, and clinical prognoses. We performed a systemic analysis of 698 breast cancer patient samples from The Cancer Genome Atlas project database. We identified 136 breast cancer genes differentially expressed among the four subtypes. Based on unsupervised clustering analysis, these 136 core genes efficiently categorized breast cancer patients into the appropriate subtypes. Functional enrichment based on Kyoto Encyclopedia of Genes and Genomes analysis identified six functional pathways regulated by these genes: JAK-STAT signaling, basal cell carcinoma, inflammatory mediator regulation of TRP channels, non-small cell lung cancer, glutamatergic synapse, and amyotrophic lateral sclerosis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938595/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#5
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938544/sialyllactose-suppresses-angiogenesis-by-inhibiting-vegfr-2-activation-and-tumor-progression
#6
Tae-Wook Chung, Eun-Young Kim, Seok-Jo Kim, Hee-Jung Choi, Se Bok Jang, Keuk-Jun Kim, Sun-Hyung Ha, Fukushi Abekura, Choong-Hwan Kwak, Cheorl-Ho Kim, Ki-Tae Ha
The oligosaccharides in human milk have various biological functions. However, the molecular mechanism(s) underlying the anti-angiogenic action of sialylated human milk oligosaccharides (HMOs) are still unclear. Here, we show that siallylactose (SL) found in human milk can inhibit the activation of vascular endothelial growth factor (VEGF)-mediated VEGF receptor-2 (VEGFR-2) by binding to its VEGF binding site (second and third IgG-like domains), thus blocking downstream signal activation. SL also inhibits growth of VEGF-stimulated endothelial cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938524/microrna-384-represses-the-growth-and-invasion-of-non-small-cell-lung-cancer-by-targeting-astrocyte-elevated-gene-1-wnt-signaling
#7
Na Fan, Jin Zhang, Chuantao Cheng, Xinwu Zhang, Jie Feng, Ranran Kong
Dysregulation of microRNA (miRNA) expression is a critical event in the development and progression of non-small-cell lung cancer (NSCLC). miR-384 has been identified as a novel cancer-related miRNA in numerous cancers, but little is known about its role and functional mechanism in NSCLC. In this study, we found that miR-384 was significantly downregulated in NSCLC tissues and cell lines. The overexpression of miR-384 repressed the growth and invasion of NSCLC cells, whereas its suppression showed the opposite effect...
September 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28938479/pulmonary-function-and-sleep-breathing-two-new-targets-for-type-2-diabetes-care
#8
Albert Lecube, Rafael Simó, Maria Pallayova, Naresh M Punjabi, Carolina López-Cano, Cecilia Turino, Cristina Hernández, Ferran Barbé
Population based studies showing the negative impact of type 2 diabetes (T2D) on lung function are overviewed. Among the well-recognized pathophysiological mechanisms, the metabolic pathways related to insulin resistance, low-grade chronic inflammation, leptin resistance, microvascular damage, and autonomic neuropathy are emphasized. Histopathological changes are exposed, and findings reported from experimental models are clearly differentiated from those described in humans. The accelerated decline in pulmonary function that appears in patients with cystic fibrosis with related abnormalities of glucose tolerance and diabetes is considered as an example to further investigate the relationship between T2D and the lung...
September 4, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28937686/serine-392-phosphorylation-modulates-p53-mitochondrial-translocation-and-transcription-independent-apoptosis
#9
Cédric Castrogiovanni, Béranger Waterschoot, Olivier De Backer, Patrick Dumont
The tumor suppressor p53 is a key regulator of apoptosis induced by various cellular stresses. p53 can induce apoptosis by two mechanisms. First, p53 acts as a transcription factor inducing and repressing pro-apoptotic and anti-apoptotic targets genes, respectively. Second, p53 is able to translocate to the mitochondria, where it interacts with BCL-2 family members to induce membrane permeabilization and cytochrome c release. p53 transcriptional activity is regulated by a set of post-translational modifications that have been well documented...
September 22, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28937318/the-crosstalk-between-p38-and-akt-signaling-pathways-orchestrates-emt-by-regulating-satb2-expression-in-nsclc-cells
#10
Hakan Kucuksayan, Hakan Akca
Epithelial-mesenchymal transition is a crucial event for metastasis and could be mediated by several pathways such as phosphoinositide 3-kinase/Akt, mitogen-activated protein kinases, as well as many epigenetic regulators. Special AT-rich sequence-binding protein 2 is an epigenetic regulator involved in epithelial-mesenchymal transition and osteoblastic differentiation. It has been reported that the crosstalk between several pathways is responsible for the regulation of epithelial-mesenchymal transition in cancer cells...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28937231/pulmonary-surfactant-and-bacterial-lipopolysaccharide-the-interaction-and-its-functional-consequences
#11
M Kolomaznik, Z Nova, A Calkovska
The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local inflammation and systemic toxicity. LPS affects alveolar type II (ATII) cells and pulmonary surfactant and although surfactant molecule has the effective protective mechanisms, excessive amount of LPS interacts with surfactant film and leads to its inactivation...
September 22, 2017: Physiological Research
https://www.readbyqxmd.com/read/28936967/-effect-of-sedation-on-respiratory-function-of-patients-undergoing-mechanical-ventilation
#12
Jie Yang, Yan Kang
Sedation and analgesia for ventilated patients is an important treatment in intensive care unit (ICU). Patients receiving mechanical ventilation therapy comfortably and safely can improve patient-ventilator synchrony, reduce ventilation-related lung injury (VILI), improve compliance, decrease oxygen consumption and stress, prevent accidents, and reduce the incidence of complications and mortality in critical patients. Although sedation may protect lung function, it also has a greater impact on respiratory function...
September 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28936884/mir-218-suppresses-epithelial-to-mesenchymal-transition-by-targeting-robo1-and-ecop-in-lung-adenocarcinoma-cells
#13
Ying-Jie Li, Wen Zhang, Hui Xia, Bao-Shi Zhang, Ping Chen, Yun-Long Zhao, Jie Li
AIM: Although, miR-218 has been implicated in epithelial-to-mesenchymal transition process, the detailed mechanisms of miR-218 involvement in epithelial-to-mesenchymal transition in human lung adenocarcinoma cell are still unclear. MATERIALS & METHODS: miR-218 function assays and its target gene analysis were performed. RESULTS: miR-218 suppresses human lung adenocarcinoma cell migration and invasion and inhibits its target gene, Ecop and Robo1 expression, which subsequently suppresses NF-κB activity and its downstream targets...
September 22, 2017: Future Oncology
https://www.readbyqxmd.com/read/28936850/-protective-effects-of-schizonepeta-volatile-oil-on-endotoxin-poisoning-induced-by-lipopolysaccharide-in-mice
#14
Tao-Qun Wen, Wen-Tao Sang, Feng Xu, Feng Wang, Nan Zeng
In order to study the protective effects of Schizonepeta volatile oil (Sto)on endotoxin poisoning mice, and the relatively content of each chemical osubstance in Schizonepeta volatile oil was measured using GC-MS. The mare C57BL/6J mice were randomly divided into five groups including the normal group, model group, dexamethasone group (5 mg•kg⁻¹), and Sto (0.226 and 0.452 g•kg⁻¹, respectively) groups. The dexamethasone group was given the drugs once time by intraperitoneal injection on the 5th day, while the other mice were given drugs by oral administration once a day for 5 days...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28936773/intranasal-delivery-of-duox2-dna-using-cationic-polymer-can-prevent-acute-influenza-a-viral-infection-in-vivo-lung
#15
Bong Jik Kim, Sung Woo Cho, Yung Jin Jeon, Sujin An, Ara Jo, Jae Hyun Lim, Dong-Young Kim, Tae-Bin Won, Doo Hee Han, Chae-Seo Rhee, Hyun Jik Kim
We studied the contribution of Duox2 in mucosal host defense against influenza A virus (IAV) infection in in vivo lung. We found that Duox2 was required for the induction of type I and III interferon (IFN)s and transient Duox2 overexpression using cationic polymer polyethyleneimine (PEI) leads to suppression of IAV infection in in vivo lung. Twenty mice (C57BL/6J) were anesthetized and challenged by intranasal administration of 213 pfu/30 μl of IAV (WS/33/H1N1), and IAV-infected mice were euthanized at 1, 3, 5, 7, 10, 14 days post infection (dpi)...
September 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28936698/recommendations-for-mechanical-ventilation-of-critically-ill-children-from-the-paediatric-mechanical-ventilation-consensus-conference-pemvecc
#16
Martin C J Kneyber, Daniele de Luca, Edoardo Calderini, Pierre-Henri Jarreau, Etienne Javouhey, Jesus Lopez-Herce, Jürg Hammer, Duncan Macrae, Dick G Markhorst, Alberto Medina, Marti Pons-Odena, Fabrizio Racca, Gerhard Wolf, Paolo Biban, Joe Brierley, Peter C Rimensberger
PURPOSE: Much of the common practice in paediatric mechanical ventilation is based on personal experiences and what paediatric critical care practitioners have adopted from adult and neonatal experience. This presents a barrier to planning and interpretation of clinical trials on the use of specific and targeted interventions. We aim to establish a European consensus guideline on mechanical ventilation of critically children. METHODS: The European Society for Paediatric and Neonatal Intensive Care initiated a consensus conference of international European experts in paediatric mechanical ventilation to provide recommendations using the Research and Development/University of California, Los Angeles, appropriateness method...
September 22, 2017: Intensive Care Medicine
https://www.readbyqxmd.com/read/28936695/early-application-of-airway-pressure-release-ventilation-may-reduce-the-duration-of-mechanical-ventilation-in-acute-respiratory-distress-syndrome
#17
Yongfang Zhou, Xiaodong Jin, Yinxia Lv, Peng Wang, Yunqing Yang, Guopeng Liang, Bo Wang, Yan Kang
PURPOSE: Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV)...
September 22, 2017: Intensive Care Medicine
https://www.readbyqxmd.com/read/28936464/innate-immune-responses-to-cryptococcus
#18
Lena J Heung
Cryptococcus species are encapsulated fungi found in the environment that predominantly cause disease in immunocompromised hosts after inhalation into the lungs. Even with contemporary antifungal regimens, patients with cryptococcosis continue to have high morbidity and mortality rates. The development of more effective therapies may depend on our understanding of the cellular and molecular mechanisms by which the host promotes sterilizing immunity against the fungus. This review will highlight our current knowledge of how Cryptococcus, primarily the species C...
September 2017: Journal of Fungi (Basel, Switzerland)
https://www.readbyqxmd.com/read/28935869/deoxyribonuclease-1-reduces-pathogenic-effects-of-cigarette-smoke-exposure-in-the-lung
#19
Paul T King, Roleen Sharma, Kim M O'Sullivan, Judy Callaghan, Lovisa Dousha, Belinda Thomas, Saleela Ruwanpura, Steven Lim, Michael W Farmer, Barton R Jennings, Michaela Finsterbusch, Gavin Brooks, Stavros Selemidis, Gary P Anderson, Stephen R Holdsworth, Philip G Bardin
Our aim was to investigate if deoxyribonuclease (DNase) 1 is a potential therapeutic agent to reduce pathogenic effects of cigarette smoke exposure in the lung. Cigarette smoke causes protease imbalance with excess production of proteases, which is a key process in the pathogenesis of emphysema. The mechanisms responsible for this effect are not well-defined. Our studies demonstrate both in vitro and in vivo that cigarette smoke significantly increases the expression of neutrophil and macrophage extracellular traps with coexpression of the pathogenic proteases, neutrophil elastase and matrix metalloproteinases 9 and 12...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935813/asxl3-is-a-novel-pluripotency-factor-in-human-respiratory-epithelial-cells-and-a-potential-therapeutic-target-in-small-cell-lung-cancer
#20
Vivek Shukla, Mahadev Rao, Hongen Zhang, Jeanette Beers, Darawalee Wangsa, Danny Wangsa, Floryne O Buishand, Yonghong Wang, Zhiya Yu, Holly Stevenson, Emily Reardon, Kaitlin C McLoughlin, Andrew Kaufman, Eden Payabyab, Julie A Hong, Mary Zhang, Sean R Davis, Daniel C Edelman, Guokai Chen, Markku Miettinen, Nicholas Restfo, Thomas Ried, Paul S Meltzer, David S Schrump
In this study, we generated induced pluripotent stem cells (iPSC) from normal human small airway epithelial cells (SAEC) to investigate epigenetic mechanisms of stemness and pluripotency in lung cancers. We documented key hallmarks of reprogramming in lung iPSC (Lu-iPSC) that coincided with modulation of more than 15,000 genes relative to parental SAEC. Of particular novelty, we identified the PRC2-associated protein, ASXL3 which was markedly upregulated in Lu-iPSC and small cell lung cancer (SCLC) lines and clinical specimens...
September 21, 2017: Cancer Research
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