3,208 research outputs found
A Potential Role of Yc-1 on the Inhibition of Cytokine Release in Peripheral Blood Mononuclear Leukocytes and Endotoxemic Mouse Models
No full textTo evaluate the anti-sepsis potential of YC-1,we have examined the effect of YC-1 on the regulation of cytokine production in human leukocytes and endotoxemic mice. The data demonstrated thatYC-1 showed a preferential inhibition on proinflammatory cytokine production without inhibition of cell growth or induction of cytotoxicity in human leukocytes. On the other hand, in the septic mouse model, treatment with an intraperitoneal application of LPS caused a cumulative death within 27 hours.The post- treatment administration of YC-1 significantly increased the survival rate in endotoxemic mice. Furthermore, several mediators were detected and the data showed thatYC-1 profoundly blocked LPS-induced NO as well asTNF-α production, and prevented lung damage by histological examination. Samples from the animal model showed that LPS-induced NF- κ B/DNA binding activity and consequent up-regulation of iNOS expression in tissues were abolished by post-administration of YC-1.Furthermore,YC-1,by itself,did not modify cGMP content while significantly inhibit LPS-induced cGMP formation, suggesting thatYC-1-mediated effect was not through a cGMP- elevating pathway.Taken together, it is evident that the post-treatment administration of YC-1 after LPS application significantly inhibits NF- κ B activation, iNOS expression, NO over-production, and cytokine release reaction resulting in an improved survival rate in endotoxemic mice. It is suggested thatYC-1 may be a potential agent for the therapeutic treatment of sepsis
Video-assisted thoracoscopic surgery for the diagnosis of patients with hilar and mediastinal lymphadenopathy.
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YC-1 induces G
No full textOral cancer is a serious and fatal disease. Cisplatin is the first line of chemotherapeutic agent for oral cancer therapy. However, the development of drug resistance and severe side effects cause tremendous problems clinically. In this study, we investigated the pharmacologic mechanisms of YC-1 on cisplatin-resistant human oral cancer cell line, CAR. Our results indicated that YC-1 induced a concentration-dependent and time-dependent decrease in viability of CAR cells analyzed by MTT assay. Real-time image analysis of CAR cells by IncuCyte™ Kinetic Live Cell Imaging System demonstrated that YC-1 inhibited cell proliferation and reduced cell confluence in a time-dependent manner. Results from flow cytometric analysis revealed that YC-1 promoted G0/G1 phase arrest and provoked apoptosis in CAR cells. The effects of cell cycle arrest by YC-1 were further supported by up-regulation of p21 and down-regulation of cyclin A, D, E and CDK2 protein levels. TUNEL staining showed that YC-1 caused DNA fragmentation, a late stage feature of apoptosis. In addition, YC-1 increased the activities of caspase-9 and caspase-3, disrupted the mitochondrial membrane potential (AYm) and stimulated ROS production in CAR cells. The protein levels of cytochrome c, Bax and Bak were elevated while Bcl-2 protein expression was attenuated in YC-1-treated CAR cells. In summary, YC-1 suppressed the viability of cisplatin-resistant CAR cells through inhibiting cell proliferation, arresting cell cycle at G0/G1 phase and triggering mitochondria-mediated apoptosis. Our results provide evidences to support the potentially therapeutic application of YC-1 on fighting against drug resistant oral cancer in the future
Suppression of Radiation Induced Pulmonary Metastasis by Yc-1 through Inhibition of Cancer Cell Invasion and Adhesion Capabilities in a Mouse Model
No full textPurpose/Objective: Metastasis has been the lethal factor in cancer patients. YC-1, 3-(5′-hydroxymethyl-2′-furyl)-1- benzylindazole, an agent developed for circulatory disorders by inhibiting platelet aggregation and vascular contraction , was found to inhibit hypoxia inducible factor-1 (HIF-1) activity. HIF-1 is a stress protein during radiation and modulates genes associated with cancer invasion and metastasis. With HIF-1 as a molecular target of YC-1, we try to clarify the therapeutic effect and mechanism of YC-1 on radiation induced cancer metastasis. Materials/Methods: An established animal model with radiation induced pulmonary metastasis was used in this study. The right thighs of thirty-two C57BL/6 mice were injected subcutaneously with 1× 106 Lewis lung carcinoma (LLC-LM) cells. Animals were randomized to one of the four groups, including no treatment (Control), radiation with 50 Gy in five 10 Gy daily fractions (RT), radiation with 50 Gy in five 10 Gy daily fractions and YC-1 (RT+YC-1), and YC-1 alone (YC-1). Radiation with cobalt -60 started 7 days after LLC-LM cell implantation. YC-1 (10mg/kg/day) was given orally from 3 days before radiation to the last day of the study. The animals were sacrificed 14 days after radiation. The serial sections of both lungs in each mouse were taken for the number of pulmonary metastasis. Besides, LLC-LM cells were in vitro treated with 5 to 20 uM of YC-1 for cytotoxicity test in MTT assay, with non-toxic dose of YC-1 used in the subsequent adhesion and invasion assay. Metalloprotease (MMP )-2 activities were determined by gelatin zymography assay and RT-PCR. Level of focal adhesion kinase (FAK) phosphorylation was determined by western blot. Results: The eradication of a primary LLC-LM was followed by the rapid growth of pulmonary metastasis within 14 days after radiation. Radiation to the thigh tumor induced pulmonary metastasis significantly ( Control vs. RT, p<0.001). Pulmonary metastases was significantly reduced with the addition of YC-1 to radiation (RT vs. RT+YC-1, p<0.001). YC- 1 itself did not have any impact on pulmonary metastasis ( Control vs. YC-1, p=0.883). The body weight of mice with radiation alone was lower than the other groups, but the difference was not statistically significant. The gelatin zymography with mouse urine samples showed that the level of MMP-2 activity, correlated with tumor growth, was much lower in YC-1 treated groups. The in vitro study showed YC-1 significantly inhibited radiation induced LLC-LM cell invasion on matrigel coated Boyden chamber, MMP-2 expression , and serum induced FAK phosphorylation. Conclusions: YC-1 inhibited radiation induced lung metastasis not only through the mechanism of HIF-1 related tumor angiogenesis but also by inhibiting cancer cell invasion and adhesion capabilities
Acute upper airway obstruction from acquired angioedema
No full textC1 esterase inhibitor deficiency is an unusual cause of acute upper airway angioedema. This case of angioedema is secondary to acquired C1 esterase inhibitor deficiency associated with neoplastic disease and triggered by the use of angiotensin converting enzyme inhibitors. It was sufficiently severe to require emergency airway management. A guide to the evaluation and management of angioedema is presented.William YC Cheng, William B Smith and W John Russel
Myofascial pain syndrome of quadratus lumborum with ankylosing spondylitis mimicking herniation of lumbar intervertebral disc: a case report.
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sj-docx-1-obm-10.1177_1753495X231163351 - Supplemental material for Walking the walk to include pregnant participants in non-obstetric clinical trials: Insights from the SNAP Trial
No full textSupplemental material, sj-docx-1-obm-10.1177_1753495X231163351 for Walking the walk to include pregnant participants in non-obstetric clinical trials: Insights from the SNAP Trial by Isabelle Malhamé, Erica Hardy, Matthew P Cheng, Steven YC Tong and Asha C Bowen in Obstetric Medicine</p
Somatic mutations in epidermal growth factor receptor underlying complete responsiveness to gefitinib in a taiwanese female patient with metastatic adenocarcinoma of lung.
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