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https://www.readbyqxmd.com/read/27911119/phase-ii-study-of-dasatinib-in-previously-treated-patients-with-advanced-non-small-cell-lung-cancer
#1
Michael J Kelley, Gautam Jha, Debra Shoemaker, James E Herndon, Lin Gu, William T Barry, Jeffrey Crawford, Neal Ready
The Src pathway in activated in about one-third of non-small cell lung cancer (NSCLC) tumors. Dasatinib has Src-inhibitor activity. We examined the activity of dasatinib in 37 patients with advanced, previously treated NSCLC. Among the 29 patients who underwent pre-treatment biopsy for RNA biomarker analysis, 25 were treated with dasatinib 70 mg twice daily. There were no responses. Five patients discontinued treatment due to toxicity. Three patients had minor biopsy-related pneumothoraces. Given the lack of responses, no biomarkers were analyzed...
December 2, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/27910855/l-type-calcium-channels-regulate-filopodia-stability-and-cancer-cell-invasion-downstream-of-integrin-signalling
#2
Guillaume Jacquemet, Habib Baghirov, Maria Georgiadou, Harri Sihto, Emilia Peuhu, Pierre Cettour-Janet, Tao He, Merja Perälä, Pauliina Kronqvist, Heikki Joensuu, Johanna Ivaska
Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis. We further demonstrate that, at filopodia, L-type calcium channels are activated by integrin inside-out signalling, integrin activation and Src...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27906699/reversal-effects-of-local-anesthetics-on-p-glycoprotein-mediated-cancer-multidrug-resistance
#3
Yong Hu, Xiaobing Qin, Haixia Cao, Shaorong Yu, Jifeng Feng
The existence of multidrug resistance (MDR) is the main reason for failure in cancer chemotherapy. The main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). P-gp, a 170 kDa transmembrane phosphorylated glycoprotein encoded by ABCB1 belonging to a member of the ATP-binding cassette (ABC) super-family of the membrane transporters, is also known as the MDR protein. Local anesthetics (LAs) are a major contributor to medical practice. As a cornerstone of analgesia, LAs provides myriad benefits...
November 30, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27905550/deep-sequencing-of-transcriptome-profiling-of-gstm2-knock-down-in-swine-testis-cells
#4
Yuqi Lv, Yi Jin, Yongqiang Zhou, Jianjun Jin, Zhenfa Ma, Zhuqing Ren
Glutathione-S-transferases mu 2 (GSTM2), a kind of important Phase II antioxidant enzyme of eukaryotes, is degraded by nonsense mediated mRNA decay due to a C27T substitution in the fifth exon of pigs. As a reproductive performance-related gene, GSTM2 is involved in embryo implantation, whereas, functional deficiency of GSTM2 induces pre- or post-natal death in piglets potentially. To have some insight into the role of GSTM2 in embryo development, high throughput RNA sequencing is performed using the swine testis cells (ST) with the deletion of GSTM2...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904688/molecular-mechanism-of-prostate-cancer-cell-apoptosis-induced-by-busulfan-via-adjustment-of-androgen-receptor-phosphatization
#5
Jun Liu, Guojun Jiang, Aiping Yang, Guohui Yang, Wenjuan Yang, Yi Fang
OBJECTIVE: To probe killing effect of busulfan to prostate cancer cell without androgen and the influence of androgen receptor phosphatization and analyze its molecular mechanism. METHODS: prostate cancer cell line 22RV1, LAPC4 and LNCaP treated with busulfan under androgen-free condition underwent CCK-8 examination to probe killing ability of the medicine. Flow cytometry was used to check the influence of busulfan on apoptosis rate of prostate cancer cell line LAPC4...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904239/student-and-preceptor-experiences-at-an-inter-professional-student-run-clinic-a-physical-therapy-perspective
#6
Andrea Passmore, Corey Persic, Drew Countryman, Laura Rankine, Meghan Henderson, Tina Hu, Joyce Nyhof-Young, Cheryl Cott
Purpose: Student-run clinics (SRCs) provide a unique opportunity for inter-professional education; they prepare health care students for a collaborative future by enabling them to interact with other such students in a clinical setting focused on inter-professional learning and collaboration. Physical therapy (PT) students are increasingly being included in SRCs; however, most research on student experiences in SRCs has been carried out with medical students. This qualitative study explores the perceived benefits of the PT experience in an SRC through the lens of PT students and their preceptors...
2016: Physiotherapy Canada. Physiothérapie Canada
https://www.readbyqxmd.com/read/27903968/novel-src-abl-tyrosine-kinase-inhibitor-bosutinib-suppresses-neuroblastoma-growth-via-inhibiting-src-abl-signaling
#7
Shayahati Bieerkehazhi, Zhenghu Chen, Yanling Zhao, Yang Yu, Huiyuan Zhang, Sanjeev A Vasudevan, Sarah E Woodfield, Ling Tao, Joanna S Yi, Jodi A Muscal, Jonathan C Pang, Shan Guan, Hong Zhang, Jed G Nuchtern, Hui Li, Huiwu Li, Jianhua Yang
Neuroblastoma (NB) is the most common extracranial solid tumor in children. Aberrant activation of the non-receptor tyrosine kinases Src and c-Abl contributes to the progression of NB. Thus, targeting these kinases could be a promising strategy for NB therapy. In this paper, we report that the potent dual Src/Abl inhibitor bosutinib exerts anti-tumor effects on NB. Bosutinib inhibited NB cell proliferation in a dose-dependent manner and suppressed colony formation ability of NB cells. Mechanistically, bosutinib effectively decreased the activity of Src/Abl and PI3K/AKT/mTOR, MAPK/ERK, and JAK/STAT3 signaling pathways...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903584/src-independent-erk-signaling-through-the-%C3%AE-3-isoform-of-na-k-atpase
#8
Namrata Madan, Yunhui Xu, Qiming Duan, Moumita Banerjee, Isabel Larre, Sandrine V Pierre, Zijian Xie
The Na/K-ATPase α1 polypeptide supports both ion pumping and signaling functions. The Na/K-ATPase α3 polypeptide differs from α1 in both its primary structure and its tissue distribution. Alpha3 expression seems particularly important in neurons, and recent clinical evidence supports a unique role of this isoform in normal brain function. The nature of this specific role of α3 has remained elusive, because the ubiquitous presence of α1 has hindered efforts to characterize α3-specific functions in mammalian cell systems...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27901489/membrane-bound-icam-1-contributes-to-the-onset-of-proinvasive-tumor-stroma-by-controlling-acto-myosin-contractility-in-carcinoma-associated-fibroblasts
#9
Stephanie Bonan, Jean Albrengues, Eloise Grasset, Sanya-Eduarda Kuzet, Nicolas Nottet, Isabelle Bourget, Thomas Bertero, Bernard Mari, Guerrino Meneguzzi, Cedric Gaggioli
Acto-myosin contractility in carcinoma-associated fibroblasts leads to assembly of the tumor extracellular matrix. The pro-inflammatory cytokine LIF governs fibroblast activation in cancer by regulating the myosin light chain 2 activity. So far, however, how LIF mediates cytoskeleton contractility remains unknown. Using phenotypic screening assays based on knock-down of LIF-dependent genes in fibroblasts, we identified the glycoprotein ICAM-1 as a crucial regulator of stroma fibroblast proinvasive matrix remodeling...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900636/cardamonin-represses-proliferation-invasion-and-causes-apoptosis-through-the-modulation-of-signal-transducer-and-activator-of-transcription-3-pathway-in-prostate-cancer
#10
Jingwen Zhang, Sakshi Sikka, Kodappully S Siveen, Jong Hyun Lee, Jae-Young Um, Alan Prem Kumar, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Basappa, Kanchugarakoppal S Rangappa, Gautam Sethi, Kwang Seok Ahn
The pleiotropic transcription factor, signal transducer and activator of transcription 3 (STAT3) is often aberrantly activated in a wide variety of cancers and plays a pivotal role in tumor initiation, promotion and progression. Targeting deregulated STAT3 activation by small molecule inhibitors is generally considered as an important therapeutic strategy. Hence, in the present study, we evaluated the potential of cardamonin (CD), a 2',4'-dihydroxy-6'-methoxychalcone, to modulate STAT3 activation in prostate cancer (PC) cells and found that this chalcone can indeed exhibit significant anticancer effects through negatively regulating STAT3 activation by diverse molecular mechanism(s)...
November 29, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27900042/antitumor-activity-of-7rh-a-discoidin-domain-receptor-1-inhibitor-alone-or-in-combination-with-dasatinib-exhibits-antitumor-effects-in-nasopharyngeal-carcinoma-cells
#11
Qiu-Ping Lu, Wen-Dan Chen, Jie-Ren Peng, Yao-Dong Xu, Qian Cai, Gong-Kan Feng, Ke Ding, Xiao-Feng Zhu, Zhong Guan
Dysregulation of the discoidin domain receptors (DDRs) has been implicated in the development of numerous types of tumors, including head and neck cancer, and nasopharyngeal, breast, ovarian and esophageal carcinomas. Furthermore, agents that inhibit DDR1 activity are hypothesized to be useful for the treatment of nasopharyngeal carcinoma (NPC). The aim of the present study was to evaluate the effect of the DDR1 inhibitory (3-(2-(pyrazolo(1,5-a)pyrimidin-6-yl)-ethynyl)benzamide compound, 7RH, in NPC cells both in vitro and in vivo, and its effect when used in combination with dasatinib, a SRC family kinase (SFK) inhibitor...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899592/an-mrna-specific-trnai-carrier-eif2a-plays-a-pivotal-role-in-cell-proliferation-under-stress-conditions-stress-resistant-translation-of-c-src-mrna-is-mediated-by-eif2a
#12
Oh Sung Kwon, Sihyeon An, Eunah Kim, Jinbae Yu, Ka Young Hong, Jae Seung Lee, Sung Key Jang
c-Src, a non-receptor protein tyrosine kinase, activates NF-κB and STAT3, which in turn triggers the transcription of anti-apoptosis- and cell cycle-related genes. c-Src protein regulates cell proliferation, cell motility and programmed cell death. And the elevated level of activated c-Src protein is related with solid tumor generation. Translation of c-Src mRNA is directed by an IRES element which mediates persistent translation under stress conditions when translation of most mRNAs is inhibited by a phosphorylation of the alpha subunit of eIF2 carrying the initiator tRNA (tRNAi) to 40S ribosomal subunit under normal conditions...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27897110/identification-of-tyrosine-kinase-src-responsible-for-antimicrobial-peptides-production-in-bombyx-mori
#13
Xianyang Li, Xiaoting Hua, Liang Song, Qingyou Xia, Fei Wang
Src is a non-receptor protein tyrosine kinase ubiquitously expressed in animals. It is involved in various cellular processes, including the innate immune response in mammals. However, less is known about the function of insect Src. Here we presented a homologue of Src in silkworm (Bombyx mori), named as BmSrc by phylogenetic analysis, homologous comparison and domain prediction. BmSrc contains the conserved phosphorylation residues and possesses tyrosine kinase activity. The expression pattern of BmSrc mRNA was specific in stages and tissues...
November 29, 2016: Protein and Peptide Letters
https://www.readbyqxmd.com/read/27896837/cd6-and-linker-of-activated-t-cells-are-potential-interaction-partners-for-t-cell-specific-adaptor-protein
#14
Cecilie Dahl Hem, Marianne Ekornhol, Stine Granum, Vibeke Sundvold-Gjerstad, Anne Spurkland
The T cell specific adaptor protein (TSAd) contains several protein interaction domains, and is merging as a modulator of T cell activation. Several interaction partners for the TSAd proline rich region and phosphotyrosines have been identified, including the Src and Tec family kinases Lymphocyte specific protein tyrosine kinase (Lck) and Interleukin 2-Inducible T-cell kinase (Itk). Via its Src homology 2 (SH2) domain, TSAd may thus function as a link between these enzymes and other signaling molecules. However, few binding partners to the TSAd SH2 domain in T cells are hitherto known...
November 29, 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27896567/foxo1-and-lxr%C3%AE-downregulate-the-apolipoprotein-a-i-gene-expression-during-hydrogen-peroxide-induced-oxidative-stress-in-hepg2-cells
#15
Vladimir S Shavva, Alexandra M Bogomolova, Artemy A Nikitin, Ella B Dizhe, Galina N Oleinikova, Ivan A Lapikov, Dmitry A Tanyanskiy, Andrej P Perevozchikov, Sergey V Orlov
Reactive oxygen species damage various cell components including DNA, proteins, and lipids, and these impairments could be a reason for severe human diseases including atherosclerosis. Forkhead box O1 (FOXO1), an important metabolic transcription factor, upregulates antioxidant and proapoptotic genes during oxidative stress. Apolipoprotein A-I (ApoA-I) forms high density lipoprotein (HDL) particles that are responsible for cholesterol transfer from peripheral tissues to liver for removal in bile in vertebrates...
November 28, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27895735/crk-like-adapter-protein-is-overexpressed-in-cervical-carcinoma-facilitates-proliferation-invasion-and-chemoresistance-and-regulates-src-and-akt-signaling
#16
Hong Ji, Bo Li, Shitai Zhang, Zheng He, Yang Zhou, Ling Ouyang
Overexpression of Crk-like (CrkL) adapter protein has been implicated in a number of types of human cancer. However, its involvement in human cervical carcinoma remains unclear. The present study aimed to explore the clinical significance and biological characteristics of CrkL in human cervical carcinoma. CrkL protein expression was examined in tissue samples from 92 cases of cervical carcinoma using immunohistochemistry, and was found to be overexpressed in 48.9% (45/92 cases). CrkL was transfected into HeLa and CaSki cervical carcinoma cell lines and its effects on biological behavior were examined...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895564/neural-systems-underlying-emotional-and-non-emotional-interference-processing-an-ale-meta-analysis-of-functional-neuroimaging-studies
#17
Min Xu, Guiping Xu, Yang Yang
Understanding how the nature of interference might influence the recruitments of the neural systems is considered as the key to understanding cognitive control. Although, interference processing in the emotional domain has recently attracted great interest, the question of whether there are separable neural patterns for emotional and non-emotional interference processing remains open. Here, we performed an activation likelihood estimation meta-analysis of 78 neuroimaging experiments, and examined common and distinct neural systems for emotional and non-emotional interference processing...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27895176/the-syk-nfat-il-2-pathway-in-dendritic-cells-is-required-for-optimal-sterile-immunity-elicited-by-alum-adjuvants
#18
Hanif Javanmard Khameneh, Adrian W S Ho, Roberto Spreafico, Heidi Derks, Hazel Q Y Quek, Alessandra Mortellaro
Despite a long history and extensive usage of insoluble aluminum salts (alum) as vaccine adjuvants, the molecular mechanisms underpinning Ag-specific immunity upon vaccination remain unclear. Dendritic cells (DCs) are crucial initiators of immune responses, but little is known about the molecular pathways used by DCs to sense alum and, in turn, activate T and B cells. In this article, we show that alum adjuvanticity requires IL-2 specifically released by DCs, even when T cell secretion of IL-2 is intact. We demonstrate that alum, as well as other sterile particulates, such as uric acid crystals, induces DCs to produce IL-2 following initiation of actin-mediated phagocytosis that leads to Src and Syk kinase activation, Ca(2+) mobilization, and calcineurin-dependent activation of NFAT, the master transcription factor regulating IL-2 expression...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27894895/molecular-characterization-and-expression-analysis-of-olive-flounder-paralichthys-olivaceus-phospholipase-c-gamma-1-and-gamma-2
#19
Soo Ji Woo, Hyae In Jo, Hyung Ho Lee, Joon Ki Chung
Phospholipase C gamma 1 and gamma 2 (PLCG1 and PLCG2) are influential in modulating Ca(2+) and diacylglycerol, second messengers involved in tyrosine kinase-dependent signaling, including growth factor activation. Here, we used RACE (rapid amplification of cDNA ends) to clone cDNA encoding PLCG1 (PoPLCG1) and PLCG2 (PoPLCG2) in the olive flounder (Paralichthys olivaceus). The respective 1313 and 1249 amino acid sequences share high identity with human PLCG1 and PLCG2, and contain the following domains: pleckstrin homology (PH), EF-hand, catalytic X and Y, Src homology 2 (SH2), Src homology 3 (SH3), and C2...
November 25, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27894086/the-anti-tumor-drug-2-hydroxyoleic-acid-minerval-stimulates-signaling-and-retrograde-transport
#20
Maria L Torgersen, Tove Irene Klokk, Simona Kavaliauskiene, Christian Klose, Kai Simons, Tore Skotland, Kirsten Sandvig
2-hydroxyoleic acid (OHOA, Minerval®) is an example of a substance used for membrane lipid therapy, where the cellular membranes rather than specific proteins constitute the therapeutical target. OHOA is thought to mediate its anti-tumor effect by affecting the biophysical properties of membranes, which leads to altered recruitment and activation of amphitropic proteins, altered cellular signaling, and eventual cell death. Little is known about the initial signaling events upon treatment with OHOA, and whether the altered membrane properties would have any impact on the dynamic intracellular transport system...
November 22, 2016: Oncotarget
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