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https://www.readbyqxmd.com/read/29351412/expression-of-ctgf-ccn2-in-response-to-lpa-is-stimulated-by-fibrotic-extracellular-matrix-via-the-integrin-fak-axis
#1
Camilo Riquelme-Guzman, Osvaldo Contreras, Enrique Brandan
Fibrosis is a common feature of several chronic diseases, and is characterized by exacerbated accumulation of extracellular matrix (ECM). Understanding the cellular and molecular mechanisms involved in the development of this condition is crucial for designing efficient treatments for those pathologies. Connective tissue growth factor (CTGF/CCN2) is a pleiotropic protein with strong pro-fibrotic activity. In this report, we present experimental evidence showing that ECM stimulates the synthesis of CTGF in response to lysophosphatidic acid (LPA)...
December 27, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29340070/a-novel-orally-available-syk-src-jak2-inhibitor-sklb-850-showed-potent-anti-tumor-activities-in-b-cell-lymphoma-bcl-models
#2
Nannan Zhang, Guo Zhang, Ning Liu, Wanting Lin, Sen Ji, Mingwu Zheng, Kai Chen, Xiao Liang, Guobo Li, Yu Ma, Jun Zhu, Ting Niu, Lin-Li Li, Jiong Li, Yu-Quan Wei, Sheng-Yong Yang
B cell lymphoma (BCL) is the most frequently diagnosed type of non-Hodgkin lymphoma (NHL), and accounts for about 4% of all cancers in the USA. Kinases spleen tyrosine kinase (Syk), Src, and Janus kinase 2 (JAK2) have been thought as potential targets for the treatment of BCL. We have recently developed a multikinase inhibitor, SKLB-850, which potently inhibits Syk, Src, and JAK2. The aim of this study is to investigate the anti-BCL activities and mechanisms of action of SKLB-850 both in vitro and in vivo. Our results showed that SKLB-850 significantly inhibited BCL cell proliferation, and induced apoptosis of BCL cells...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339086/the-il-6-stat3-pathway-regulates-adhesion-molecules-and-cytoskeleton-of-endothelial-cells-in-thromboangiitis-obliterans
#3
Zheng Wei, Wenjing Jiang, Hengzhen Wang, Hali Li, Bo Tang, Bing Liu, Hongchi Jiang, Xueying Sun
Thromboangiitis obliterans (TAO) (also known as Buerger's disease) is an inflammatory vascular disease that predominantly affects small- and medium-sized blood vessels of extremities. Endothelial cells play critical roles in the initiation and progression of this disease, but the underlying mechanisms remain unclear. In the present study, we demonstrate that patients with TAO had significantly higher levels of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in their plasmas, and the involved arterial tissues expressed higher levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3), ICAM-1 and VCAM-1...
January 12, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29334266/hyaluronic-acid-modified-daunorubicin-plus-honokiol-cationic-liposomes-for-the-treatment-of-breast-cancer-along-with-the-elimination-vasculogenic-mimicry-channels
#4
Rui-Jun Ju, Lan Cheng, Xiao Qiu, Shuang Liu, Xiao-Li Song, Xiao-Ming Peng, Teng Wang, Cui-Qing Li, Xue-Tao Li
BACKGROUND: Breast cancer is an alarming global public health problem and a main cause of cancer-related death in women. Systemic chemotherapy is the most widely used treatment for breast cancer. However, current chemotherapy treatments are far from desirable due to poor targeting specificity, severe side effects, and vasculogenic mimicry (VM). PURPOSE: Hyaluronic acid (HA) modified daunorubicin plus honokiol cationic liposomes were prepared and characterized for treatment of breast cancer by eliminating VM...
January 15, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29333095/cinnamomum-cassia-extracts-suppress-human-lung-cancer-cells-invasion-by-reducing-u-pa-mmp-expression-through-the-fak-to-erk-pathways
#5
Hsing-Chen Wu, Chi-Ting Horng, You-Li Lee, Pei-Ni Chen, Chin-Yin Lin, Chen-Yu Liao, Yih-Shou Hsieh, Shu-Chen Chu
Cinnamomum cassia exhibits antioxidative, apoptotic, and cytostatic properties. These activities have been attributed to the modulation of several biological processes and are beneficial for possible pharmaceutical applications. However, the potential of C. cassia in retarding lung adenocarcinoma cells metastasis remains ambiguous. We determined whether C. cassia extract (CCE) reduces metastasis of human lung adenocarcinoma cells. The results showed that CCE treatment (up to 60 μg/mL) for 24 h exhibited no cytotoxicity on the A549 and H1299 cell lines but inhibited the motility, invasiveness, and migration of these cells by repressing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA)...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29332411/%C3%AE-1-integrin-mediated-multicellular-resistance-in-hepatocellular-carcinoma-through-activation-of-the-fak-akt-pathway
#6
Tao Tian, Chun-Li Li, Xiao Fu, Shu-Hong Wang, Jun Lu, Hui Guo, Yu Yao, Ke-Jun Nan, Yu-Juan Yang
Objective To explore the role and mechanism of β1 integrin in the regulation of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This in vitro study used a liquid overlay technique to obtain multicellular spheroids of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids was observed by optical and electron microscopy. The effects of exposure to 5-fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction of apoptosis were assessed in monolayer cells and multicellular spheroids...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29330550/a-metabolomics-pilot-study-on-desmoid-tumors-and-novel-drug-candidates
#7
Kelly A Mercier, Mushriq Al-Jazrawe, Raymond Poon, Zachery Acuff, Benjamin Alman
Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors that lack the ability to metastasize. There are no directed therapies or standard treatment plan, and chemotherapeutics, radiation, and surgery often have temporary effects. The majority of desmoid tumors are related to T41A and S45F mutations of the beta-catenin encoding gene (CTNNB1). Using broad spectrum metabolomics, differences were investigated between paired normal fibroblast and desmoid tumor cells from affected patients...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330027/selective-estrogen-receptor-modulator-ormeloxifene-suppresses-embryo-implantation-via-inducing-mir-140-and-targeting-insulin-like-growth-factor-1-receptor-in-rat-uterus
#8
Vijay K Sirohi, Kanchan Gupta, Rohit Kumar, Vinay Shukla, Anila Dwivedi
Ormeloxifene, the non-steroidal SERM contraceptive, inhibits endometrial receptivity and embryo implantation via countering nidatory estrogen. However, the molecular mechanism of ormeloxifene action responsible for its contraceptive efficacy still remains unclear. Herein, we aimed to identify the miRNAs modulated under the influence of ormeloxifene and to explore their role in endometrial receptivity and embryo implantation. By doing microRNA sequencing analysis, a total of 168 miRNAs were found to be differentially expressed in uterine tissue of ormeloxifene-treated rats, on day 5 (10:00 h) of pregnancy i...
January 9, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29329077/nano-hydroxyapatite-blasted-titanium-surface-creates-a-biointerface-able-to-govern-src-dependent-osteoblast-metabolism-as-prerequisite-to-ecm-remodeling
#9
Célio J C Fernandes, Fábio Bezerra, Marcel R Ferreira, Amanda F C Andrade, Thais Silva Pinto, Willian F Zambuzzi
Over the last several years, we have focused on the importance of intracellular signaling pathways in dynamically governing the biointerface between pre-osteoblast and surface of biomaterial. Thus, this study investigates the molecular hallmarks involved in the pre-osteoblast relationship with different topography considering Machined (Mc), Dual Acid-Etching (DAE), and nano hydroxyapatite-blasted (nHA) groups. There was substantial differences in topography of titanium surface, considering Atomic Force Microscopy and water contact angle (Mc = 81...
December 28, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29328433/peiminine-serves-as-an-adriamycin-chemosensitizer-in-gastric-cancer-by-modulating-the-egfr-fak-pathway
#10
Qianqian Tang, Yunfei Wang, Lanjing Ma, Meiling Ding, Tingyu Li, Yongzhan Nie, Zhengyi Gu
Gastric cancer (GC) is one of the most common malignancies of the digestive tract. Adriamycin (ADR) has been widely utilized in various chemotherapy regimens for treating GC, yet its long-term application may increase drug resistance resulting in treatment failure. Increasing evidence shows that bioactive natural products can be used as chemotherapeutic sensitizers that can significantly improve chemotherapy sensitivity. Peiminine (PMI) is a biologically active component extracted from Fritillaria walujewii Regel...
January 3, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328428/regulation-of-drug-resistance-and-metastasis-of-gastric-cancer-cells-via-the-microrna647-ank2-axis
#11
Wenlong Cao, Weiyuan Wei, Zexu Zhan, Dongyi Xie, Yubo Xie, Qiang Xiao
Due to a lack of effective methods for early diagnosis, the majority of patients with gastric cancer (GC) are diagnosed during the late stages of the disease, which are often accompanied by metastasis. For these patients, despite being considered an important therapeutic modality in the treatment of cancer, chemotherapy is usually not effective due to multidrug resistance (MDR). The expression levels of MDR/metastasis‑associated genes are regulated by numerous microRNAs (miRNAs/miRs). The expression of miR-647 in GC tissues and SGC7901/VCR cell line (drug resistance to vincristine) was detected by qRT-PCR...
January 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29327435/impact-of-dietary-induced-precocious-gut-maturation-on-cecal-microbiota-and-its-relation-to-the-blood-brain-barrier-during-the-postnatal-period-in-rats
#12
N Marungruang, E Arévalo Sureda, A Lefrançoise, B Weström, M Nyman, O Prykhodko, F Fåk Hållenius
BACKGROUND: Precocious maturation of the gastrointestinal barrier (GIB) in newborn mammals can be induced by dietary provocation, but how this affects the gut microbiota and the gut-brain axis remains unknown. The objective of this study was to investigate effects of induced GIB maturation on gut microbiota composition and blood-brain barrier (BBB) permeability. METHODS: Suckling rats were studied at 72 h after gavage with phytohemagglutinin (PHA) or microbial protease (PT) to induce maturation of GIB...
January 12, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29327067/overexpression-of-nogo-receptor-3-ngr3-correlates-with-poor-prognosis-and-contributes-to-the-migration-of-epithelial-cells-of-nasopharyngeal-carcinoma-patients
#13
Jiang-Yi He, Ping Han, Yu Zhang, Yong-Dong Liu, Shi-Jian Song, Guo-Kai Feng, Yu An, Ai-Jun Zhou, Hong-Bo Wang, Li Yuan, Zhi-Rui Lin, Tian-Liang Xia, Man-Zhi Li, Yan-Min Liu, Xiao-Ming Huang, Hua Zhang, Qian Zhong
Lymph node metastasis (N classification) is one of the most important prognostic factors of nasopharyngeal carcinoma (NPC), and nerve involvement is associated with the transition of the N category in NPC patients. Although the nervous system has been reported to participate in many types of cancer progression, its functions in NPC progression remains unknown. Through analysis of gene profiling data, we demonstrate an enrichment of genes associated with neuronal development and differentiation in NPC tissues and cell lines...
January 11, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29322249/mir-375-inhibits-the-hepatocyte-growth-factor-elicited-migration-of-mesenchymal-stem-cells-by-downregulating-akt-signaling
#14
Lihong He, Xianyao Wang, Naixin Kang, Jianwei Xu, Nan Dai, Xiaojing Xu, Huanxiang Zhang
The migration of mesenchymal stem cells (MSCs) is critical for their use in cell-based therapies. Accumulating evidence suggests that microRNAs are important regulators of MSC migration. Here, we report that the expression of miR-375 was downregulated in MSCs treated with hepatocyte growth factor (HGF), which strongly stimulates the migration of these cells. Overexpression of miR-375 decreased the transfilter migration and the migration velocity of MSCs triggered by HGF. In our efforts to determine the mechanism by which miR-375 affects MSC migration, we found that miR-375 significantly inhibited the activation of Akt by downregulating its phosphorylation at T308 and S473, but had no effect on the activity of mitogen-activated protein kinases...
January 10, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29317819/inhibition-of-cancer-cell-migration-with-cus-msio2-peg-nanoparticles-by-repressing-mmp-2-mmp-9-expression
#15
Guoying Deng, Feng Zhou, Zizheng Wu, Fei Zhang, Kerun Niu, Yingjie Kang, Xijian Liu, Qiugen Wang, Yin Wang, Qian Wang
The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29314097/effect-of-fak-inhibitor-vs-6063-defactinib-on-docetaxel-efficacy-in-prostate-cancer
#16
Hui-Ming Lin, Brian Y Lee, Lesley Castillo, Calan Spielman, Judith Grogan, Nicole K Yeung, James G Kench, Phillip D Stricker, Anne-Maree Haynes, Margaret M Centenera, Lisa M Butler, S Martin Shreeve, Lisa G Horvath, Roger J Daly
BACKGROUND: Docetaxel, the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC) also enhances the survival of patients with metastatic castration-sensitive prostate cancer (CSPC) when combined with androgen-deprivation therapy. Focal Adhesion Kinase (FAK) activation is a mediator of docetaxel resistance in prostate cancer cells. The aim of this study was to investigate the effect of the second generation FAK inhibitor VS-6063 on docetaxel efficacy in pre-clinical CRPC and CSPC models...
January 5, 2018: Prostate
https://www.readbyqxmd.com/read/29311642/hsp90-inhibition-alters-the-chemotherapy-driven-rearrangement-of-the-oncogenic-secretome
#17
Simona di Martino, Carla Azzurra Amoreo, Barbara Nuvoli, Rossella Galati, Sabrina Strano, Francesco Facciolo, Gabriele Alessandrini, Harvey I Pass, Gennaro Ciliberto, Giovanni Blandino, Ruggero De Maria, Mario Cioce
Adaptive resistance to therapy is a hallmark of cancer progression. To date, it is not entirely clear how microenvironmental stimuli would mediate emergence of therapy-resistant cell subpopulations, although a rearrangement of the cancer cell secretome following therapy-induced stress can be pivotal for such a process. Here, by using the highly chemoresistant malignant pleural mesothelioma (MPM) as an experimental model, we unveiled a key contribution of the chaperone HSP90 at assisting a chemotherapy-instigated Senescence-Associated-Secretory-Phenotype (SASP)...
January 9, 2018: Oncogene
https://www.readbyqxmd.com/read/29311227/src-and-confinement-dependent-fak-activation-causes-e-cadherin-relaxation-and-%C3%AE-catenin-activity
#18
Charlène Gayrard, Clément Bernaudin, Théophile Déjardin, Cynthia Seiler, Nicolas Borghi
In epithelia, E-cadherin cytoplasmic tail is under cytoskeleton-generated tension via a link that contains β-catenin. A cotranscription factor, β-catenin, is also active in morphogenetic processes associated with epithelial-to-mesenchymal transition. β-Catenin signaling appears mechanically inducible and was proposed to follow phosphorylation-induced β-catenin release from E-cadherin. Evidence for this mechanism is lacking, and whether E-cadherin tension is involved is unknown. To test this, we combined quantitative fluorescence microscopies with genetic and pharmacological perturbations of epithelial-to-mesenchymal transition-induced cells in culture...
January 8, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29306778/influence-on-proliferation-and-adhesion-of-human-gingival-fibroblasts-from-different-titanium-surface-decontamination-treatments-an-in-vitro-study
#19
Cao Jie, Tong Wang, Pu Yinfei, Tang Zhihui, Meng Huanxin
OBJECTIVES: To investigate the effects of different decontamination treatments on microstructure of titanium (Ti) surface as well as proliferation and adhesion of human gingival fibroblasts (HGFs). MATERIAL AND METHODS: Ti discs with machined (M) and sand blasted, acid etched (SAE) surfaces were treated with five different decontamination treatments: (1) stainless steel curette (SSC), ultrasonic system with (2) straight carbon fiber tip (UCF) or (3) metal tip (UM), (4) rotating Ti brush (RTB), and (5) Er:YAG laser (30 mJ/pulse at 30 Hz)...
December 24, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29306139/structure-of-focal-adhesion-kinase-in-healthy-heart-versus-pathological-cardiac-hypertrophy-a-modeling-and-simulation-study
#20
Pallavi Mohanty, Sonika Bhatnagar
Focal adhesion kinase (FAK) is required for signaling in the heart. S910 phosphorylated FAK is known to cause pathological cardiac hypertrophy. The switching of FAK between its inactive (-i), activated (-a) and hyperactive (-h) state is controlled by phosphorylation. FAK consists of three domains, namely: FERM, Kinase, and FAT joined by linkers L1 and L2. The structural basis of FAK phosphorylation and signaling to the downstream pathways is not understood. In this work, we carried out homology modeling and domain assembly of full length human iFAK and aFAK...
December 19, 2017: Journal of Molecular Graphics & Modelling
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