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https://www.readbyqxmd.com/read/29786956/rho-kinase-and-protein-kinase-c-pathways-are-responsible-for-enhanced-carbachol-contraction-in-permeabilized-detrusor-in-a-rat-model-of-cystitis
#1
Merve Denizalti, N Tugba Durlu-Kandilci, G Simsek, T Emrah Bozkurt, Inci Sahin-Erdemli
Interstitial cystitis is a syndrome characterized by detrusor overactivity and chronic inflammation of the bladder. The mechanisms responsible for the altered smooth muscle contractility remain poorly understood. The aim of the study was to investigate the role of intracellular signalling pathways in carbachol-induced detrusor contraction in a rat model of interstitial cystitis. Cyclophosphamide (150 mg/kg, dissolved in saline) was injected to rats (Sprague-Dawley, female, 200-250 g) intraperitoneally once a day on days 1, 4 and 7 to induce interstitial cystitis...
May 22, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29786782/preclinical-impact-of-high-dose-intermittent-antiangiogenic-tyrosine-kinase-inhibitor-pazopanib-in-intrinsically-resistant-tumor-models
#2
Elaine Reguera-Nuñez, Shan Man, Ping Xu, Robert S Kerbel
Antiangiogenic tyrosine kinase inhibitors (TKIs) target vascular endothelial growth factor receptors and other receptor tyrosine kinases. As a result of toxicity, the clinical failures or the modest benefits associated with antiangiogenic TKI therapy may be related in some cases to suboptimal drug dosing and scheduling, thereby facilitating resistance. Most antiangiogenic TKIs, including pazopanib, are administered on a continuous daily basis. Here, instead, we evaluated the impact of increasing the dose and administering the drug intermittently...
May 21, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29786754/regulation-of-interferon-signaling-and-hcv%C3%A2-rna-replication-by-extracellular-matrix
#3
Takuya Kuwashiro, Shinji Iwane, Xia Jinghe, Sachiko Matsuhashi, Yuichiro Eguchi, Keizo Anzai, Kazuma Fujimoto, Toshihiko Mizuta, Naoya Sakamoto, Masanori Ikeda, Nobuyuki Kato, Iwata Ozaki
Although interferon (IFN)‑based treatment of patients with chronic hepatitis C virus (HCV) infection is widely applied, treatment resistance is often observed in patients with advanced liver fibrosis. Given that the molecular mechanisms of IFN resistance in liver fibrosis remain elusive, the present study investigated the effects of extracellular matrix (ECM) on IFN signaling in hepatic cells. The native HuH‑7 human hepatoma cell line and HuH‑7 cells were stably transfected with full‑length HCV‑RNA fused with Renilla luciferase (OR6 cells) were cultured on ECM‑coated dishes or non‑coated plastic dishes (NDs), and treated with human IFN‑α...
May 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786744/mir%C3%A2-133b-regulates-proliferation-and-apoptosis-in-high%C3%A2-glucose%C3%A2-induced-human-retinal-endothelial-cells-by-targeting-ras-homolog-family-member-a
#4
Jun Yao, Jihong Wang, Yong Yao, Kelei Wang, Qianqian Zhou, Ying Tang
The aim of the present study was to investigate the role of microRNA (miR)‑133b in high‑glucose‑induced human retinal endothelial cells (hRECs), particularly regarding its potential targeting of ras homolog family member A (RhoA). To establish the high‑glucose‑induced diabetic retinopathy (DR) model, hRECs were cultured in high‑glucose medium for 1, 2 and 3 days. An Annexin allophycocyanin (APC)/7‑aminoactinomycin D (7‑AAD) staining assay was performed to measure the apoptosis of hRECs. Next, the cells were transfected with miR‑133b inhibitors or mimics, and the cell proliferation and apoptosis were measured by MTT and Annexin‑APC/7‑AAD staining assays, respectively...
May 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786111/high-glucose-suppresses-the-viability-and-proliferation-of-htr%C3%A2-8-svneo-cells-through-regulation-of-the-mir%C3%A2-137-prkaa1-il%C3%A2-6-axis
#5
Hai-Yan Peng, Ming-Qing Li, Hua-Ping Li
The aim of the present study was to investigate the mechanism underlying the high glucose (HG)‑associated regulation of HTR‑8/SVneo cell viability and proliferation during gestational diabetes mellitus (GDM), and to verify the association of microRNA (miR)‑137, protein kinase AMP‑activated catalytic subunit α1 (PRKAA1) and interlukin‑6 (IL‑6). miR‑137‑overexpressing and negative control HTR‑8/SVneo cells were established by lentiviral vector infection. Cell Counting Kit‑8 and colony formation assays were used to analyze the viability and proliferation of HTR‑8/SVneo cells...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786108/mir%C3%A2-494-inhibits-cancer%C3%A2-initiating-cell-phenotypes-and-reverses-resistance-to-lapatinib-by-downregulating-fgfr2-in-her2%C3%A2-positive-gastric-cancer
#6
Yanxia Yu, Xuejuan Yu, Hong Liu, Qingxun Song, Yongmei Yang
In gastric cancer, >15% of cases are associated with the amplification of human epidermal growth factor receptor 2 (HER2), which leads to poor clinical outcomes. Lapatinib, a potent ATP‑competitive inhibitor, is a small, orally active molecule, which inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1. The activation of receptor tyrosine kinases can contribute to lapatinib resistance in HER2‑positive gastric cancer. The aim of the present study was to explore the effects of miR‑494 and FGFR2 in regulation of cancer‑initiating cell phenotypes and therapeutic efficiency of lapatinib in HER2‑positive gastric cancer...
May 16, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786049/lipoxin-a4-ameliorates-lipopolysaccharide-induced-a549-cell-injury-through-upregulation-of-n-myc-downstream-regulated-gene-1
#7
Jun-Zhi Zhang, Zhan-Li Liu, Yao-Xian Zhang, Hai-Jiu Lin, Zhong-Jun Zhang
Background: Lipoxin A4 (LXA4) can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) and acute respiratory distress syndrome through promoting epithelial sodium channel (ENaC) expression in lung epithelial cells. However, how LXA4 promote ENaC expression is still largely elusive. The present study aimed to explore genes and signaling pathway involved in regulating ENaC expression induced by LXA4. Methods: A549 cells were incubated with LPS and LXA4, or in combination, and analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) of ENaC-α/γ...
June 5, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29785630/calcium-channels-rho-kinase-protein-kinase-c-and-phospholipase-c-pathways-mediate-mercury-chloride-induced-myometrial-contractions-in-rats
#8
Swati Koli, Atul Prakash, Soumen Choudhury, Rajesh Mandil, Satish K Garg
Adverse effects of mercury on female reproduction are reported; however, its effect on myogenic activity of uterus and mechanism thereof is obscure. Present study was undertaken to unravel the mechanistic pathways of mercuric chloride (HgCl2 )-induced myometrial contraction in rats. Isometric tension in myometrial strips of rats following in vitro exposure to HgCl2 was recorded using data acquisition system-based physiograph. HgCl2 produced concentration-dependent (10 nM-100 μM) uterotonic effect which was significantly (p < 0...
May 21, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29785576/prognostic-impact-of-the-components-of-progressive-disease-on-survival-after-first-line-tyrosine-kinase-inhibitor-therapy-for-metastatic-renal-cell-carcinoma
#9
Takashi Ikeda, Hiroki Ishihara, Toshio Takagi, Tsunenori Kondo, Kazuhiko Yoshida, Junpei Iizuka, Kazunari Tanabe
BACKGROUND: According to the Response Evaluation Criteria in Solid Tumors (RECIST) classification, progressive disease (PD) is defined as target lesion growth (TLG), unequivocal non-target lesion growth (NTLG), or new lesion appearance (NLA). The prognostic impact of the components of PD in tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC) remains unknown. OBJECTIVE: We retrospectively evaluated the prognostic impact of these PD components on survival in patients with mRCC after first-line TKI therapy...
May 21, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29785284/vinorelbine-induced-regression-of-a-choroidal-metastasis-from-primary-breast-carcinoma
#10
Malvika Arya, Jay S Duker
Background: Various therapeutic options exist to treat choroidal metastatic lesions. However, they are all associated with potential long-term adverse effects. This case report discusses a case of choroidal metastasis from primary breast carcinoma that regressed after single-agent chemotherapy. Case presentation: We report a case of choroidal metastasis from estrogen receptor (ER) positive breast carcinoma that became resistant to endocrine therapy. The primary malignancy was treated with surgical resection and adjuvant chemoradiation, followed by hormone therapy with various agents in combination with kinase inhibitors for ER resistance...
2018: International Journal of Retina and Vitreous
https://www.readbyqxmd.com/read/29785232/effects-of-fasudil-on-patients-with-pulmonary-hypertension-associated-with-left-ventricular-heart-failure-with-preserved-ejection-fraction-a-prospective-intervention-study
#11
Xiang Zhang, Xueming Zhang, Saihua Wang, Jun Luo, Zhihong Zhao, Changzhu Zheng, Jieyan Shen
Background: Pulmonary hypertension due to left ventricular heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly medical problem. The aim of the study was to evaluate the clinical efficacy of fasudil on PH-HFpEF elderly patients and to figure out the subtype of PH-HFpEF which may be the therapeutic object of fasudil. Method: 58 PH-HFpEF elderly patients were enrolled. Patients were diagnosed with passive pulmonary hypertension (PPH) or reactive pulmonary hypertension (RPH) by right heart catheterization and all receiving Rho kinase inhibitor fasudil for 2 weeks...
2018: Canadian Respiratory Journal: Journal of the Canadian Thoracic Society
https://www.readbyqxmd.com/read/29785118/traditional-chinese-medicine-astragalus-polysaccharide-enhanced-antitumor-effects-of-the-angiogenesis-inhibitor-apatinib-in-pancreatic-cancer-cells-on-proliferation-invasiveness-and-apoptosis
#12
Jun Wu, Jing Wang, Qiang Su, Wei Ding, Teng Li, Junxian Yu, Bangwei Cao
Background: Traditional chemotherapy and molecular targeted therapy have shown modest effects on the survival of patients with pancreatic cancer. The current study aimed to investigate the antitumor effects of apatinib, Astragalus polysaccharide (APS), and the combination of both the drugs in pancreatic cancer cells and further explore the molecular mechanisms in vitro. Materials and methods: Expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in human pancreatic cancer cell lines ASPC-1, PANC-1, and SW1990 was detected by Western blotting...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29785088/insight-into-resistance-mechanism-of-anaplastic-lymphoma-kinase-to-alectinib-and-jh-viii-157-02-caused-by-g1202r-solvent-front-mutation
#13
Han Wang, Yao Wang, Wentao Guo, Bin Du, Xiaobing Huang, Riping Wu, Baoyu Yang, Xiaoyan Lin, Yilan Wu
Background: Mutated anaplastic lymphoma kinase (ALK) drives the development of advanced non-small cell lung cancer (NSCLC). Most reported small-molecule inhibitors targeting the ALK domain do not display good inhibition of the G1202R solvent front mutation. The solvent front mutation was assumed to hinder drug binding. However, a different fact could be uncovered by the simulations reported in this study through a structural analog of alectinib (JH-VIII-157-02), which demonstrated potent effects against the G1202R mutation...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29785049/involvement-of-inhibitor-kappa-b-kinase-2-ikk2-in-the-regulation-of-vascular-tone
#14
Youngin Kwon, Soo-Kyoung Choi, Seonhee Byeon, Young-Ho Lee
Inhibitor kappa B kinase 2 (IKK2) plays an essential role in the activation of nuclear factor kappa B (NF-kB). Recently, it has been suggested that IKK2 acts as a myosin light chain kinase (MLCK) and contributes to vasoconstriction in mouse aorta. However, the underlying mechanisms are still unknown. Therefore, we investigated whether IKK2 acts as a MLCK or regulates the activity of myosin light chain phosphatase (MLCP). Pressure myograph was used to measure vascular tone in rat mesenteric arteries. Immunofluorescence staining was performed to identify phosphorylation levels of MLC (ser19), MYPT1 (thr853 and thr696) and CPI-17 (thr38)...
May 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29784900/irak-inhibitor-protects-the-intestinal-tract-of-necrotizing-enterocolitis-by-inhibiting-the-toll-like-receptor-tlr-inflammatory-signaling-pathway-in-rats
#15
Yu Hou, Xin Lu, Yueju Zhang
BACKGROUND The aim of this study was to assess the effects of interleukin-1 (IL-1) receptor associated kinase (IRAK) inhibitors on intestinal injury induced by necrotizing enterocolitis (NEC) in neonatal rats and its regulation on the intestinal Toll-like receptor (TLR) inflammatory signaling pathway. MATERIAL AND METHODS The neonatal rat models of NEC were established though hypoxia-cold stimulation. All rats were divided into 3 groups: an NEC model group (NEC group), an IRAK inhibitor group (IRAKI group), and a normal control group (NC group)...
May 22, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29784750/pregnancy-in-patients-with-chronic-myeloid-leukemia
#16
Ellin Berman
Estimates suggest that nearly 30% of patients diagnosed with chronic myeloid leukemia (CML) are aged <49 years, with approximately half being women. For many of these women, childbearing concerns are a major factor as they initiate treatment with tyrosine kinase inhibitors, which are known to be teratogenic. During her presentation at the NCCN 23rd Annual Conference, Dr. Berman identified the challenges in helping women undergoing treatment for CML who want to have children, and emphasized the importance of an individualized and multidisciplinary approach to management...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784748/emerging-treatment-options-for-acute-lymphoblastic-leukemia-focus-on-car-t-cell-therapy
#17
Patrick A Brown, Bijal Shah
Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of diseases with different morphologic, cytogenetic, and molecular subgroups, some of which have significant therapeutic implications. It typically presents with an aggressive clinical course, and among adults, responds poorly to standard chemotherapy, and carries a high risk for relapse. Despite the significant progress made in inducing remission, frequent relapses remain a challenge. Novel drugs, such as potent later-generation tyrosine kinase inhibitors, antibody-drug conjugates, bispecific monoclonal antibodies, and chimeric antigen receptor (CAR) T-cell therapies, are being investigated in patients with ALL...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784736/targeted-therapy-for-patients-with-metastatic-non-small-cell-lung-cancer
#18
Karen L Reckamp
Molecular testing is recommended for initial diagnosis in patients with non-small cell lung cancer (NSCLC), according to the updated NCCN Guidelines, because targeted therapies are available that can improve patient outcomes. Targeted therapies are currently approved for EGFR mutations, ALK and ROS1 gene rearrangements, and BRAF mutations, with the list of emerging "actionable" targets growing. The 2018 NCCN Guidelines for NSCLC incorporate new therapies, including the EGFR tyrosine kinase inhibitor osimertinib and the ALK inhibitor alectinib, as first-line preferences...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784639/tyrosine-kinase-inhibitor-induced-defects-in-dna-repair-sensitize-flt3-itd-positive-leukemia-cells-to-parp1-inhibitors
#19
Silvia Maifrede, Margaret Nieborowska-Skorska, Katherine Sullivan, Yashodhara Dasgupta, Paulina Podszywalow-Bartnicka, Bac Viet Le, Martyna Solecka, Zhaorui Lian, Elizaveta A Belyaeva, Alina Nersesyan, Marcin M Machnicki, Monika Toma, Nicolas Chatain, Malgorzata Rydzanicz, Huaqing Zhao, Jaroslav Jelinek, Katarzyna Piwocka, Tomasz Sliwinski, Tomasz Stoklosa, Rafal Ploski, Thomas Fischer, Stephen M Sykes, Steffen Koschmieder, Lars Bullinger, Peter Valent, Mariusz Wasik, Jian Huang, Tomasz Skorski
Mutations in the FMS-like tyrosine-kinase 3 (FLT3) such as internal tandem duplications (ITD) can be found in up to 23% of patients with acute myeloid leukemia (AML) and confer a poor prognosis. Current treatment options for FLT3(ITD)-positive AMLs include genotoxic therapy and FLT3 inhibitors (FLT3i), which are rarely curative. PARP1 inhibitors (PARP1i) have been successfully applied to induce synthetic lethality in tumors harboring BRCA1/2 mutations and displaying homologous recombination (HR) deficiency...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29784046/knockdown-of-annexin-a5-restores-gefitinib-sensitivity-by-promoting-g2-m-cell-cycle-arrest
#20
Jian Zhou, Meijia Chang, Jing Li, Tao Fang, Jie Hu, Chunxue Bai
BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, including gefitinib, are first-line drugs against advanced non-small cell lung cancer with activating EGFR mutations. However, the development of resistance to such drugs is a major clinical challenge. METHODS: The role of annexin A5 in resistance to EGFR tyrosine kinase inhibitors was investigated by qPCR and western blot of relevant molecules, by CCK8 and EdU assay of cell proliferation and viability, by annexin V/propidium iodide assay of apoptosis and cell cycle distribution, by JC-1 assay of mitochondrial integrity, and by xenograft assay of tumorigenicity...
May 21, 2018: Respiratory Research
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