Saikosaponin-d Inhibits the Hepatoma Cells and Enhances Chemosensitivity Through SENP5-Dependent Inhibition of Gli1 SUMOylation Under Hypoxia

Chemosensitivity is one of the key factors affecting the therapeutic effect on cancer, but the clinical application of corresponding drugs is rare. Hypoxia, a common feature of many solid tumors, including hepatocellular carcinoma (HCC), has been associated with resistance to chemotherapy in part through the activation of the Sonic Hedgehog (SHh) pathway. Hypoxia has also been associated with the increased SUMOylation of multiple proteins, including GLI family proteins, which are key mediators of SHh signaling, and has become a promising target to develop drug-resistant drugs for cancer treatment. However, there are few target drugs to abrogate chemotherapy resistance. Saikosaponin-d (Ssd), one of the main bioactive components of Radix bupleuri, has been reported to exert multiple biological effects, including anticancer activity. Here, we first found that Ssd inhibits the malignant phenotype of HCC cells while increasing their sensitivity to the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) drug system under hypoxia in vitro and in vivo. Furthermore, we had explored that GLI family activation and extensive protein SUMOylation were characteristics of HCC cells, and hypoxia could activate the SHh pathway and promote epithelial-mesenchymal transition (EMT), invasion, and chemosensitivity in HCC cells. SUMOylation is required for hypoxia-dependent activation of GLI proteins. Finally, we found that Ssd could reverse the effects promoted by hypoxia, specifically ac...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Conclusions: The constantly increasing prevalence of NAFLD in the general population can contribute to a growing role of NAFLD/NASH in HCC epidemiology. Moreover, some particular challenges specific for patients with liver steatosis may impede proper HCC diagnosis, treatment and follow-up. PMID: 31631714 [PubMed - as supplied by publisher]
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
Source: St. Michael's Hospital News and Media - Category: Hospital Management Tags: Hospital News Source Type: news
Conclusions: SIF + XRT caused changes in patterns of endothelial cell death and survival, proinflammatory molecule release, and adhesion molecule expression at early time points post-XRT associated with early reduction of immune cell recruitment. These findings suggest that SIF could mediate its radioprotective effects in irradiated lungs by limiting excessive immune cell homing via vascular endothelium into damaged lung tissue and curtailing the overall inflammatory response to radiation. PMID: 31633433 [PubMed - as supplied by publisher]
Source: International Journal of Radiation Biology - Category: Radiology Tags: Int J Radiat Biol Source Type: research
This study analyzes the results of laparoscopic nephrectomy for Wilms Tumor (WT) in pediatric age compared with open nephrectomy after 10 years of experience in a single centre. From 1993 in our center of reference for pediatric oncology, 30 patients with WT have been treated. We performed 21 open nephrectomy and in the last 10 years 9 laparoscopic nephrectomy. In all patients treated laparoscopically, the same technique made by the same equip was used. Compared with patients treated by open surgery, we did not find a significant difference in terms of outcome and survival. In the open surgery group, two patients had lung ...
Source: Journal of Biological Regulators and Homeostatic Agents - Category: Biomedical Science Tags: J Biol Regul Homeost Agents Source Type: research
This study aimed to evaluate immunohistochemical expression of cyclin D1 and PSA in breast carcinoma and their relation to prognosis. It includes 79 specimens of breast invasive duct carcinoma. Overall survival time was available for all patients. There is a statistically significant association between positive PSA expression and lower tumor stage, nodal stage and tumor grade and between negative PSA expression and presence of metastasis (P value = .05, 0.01, 0.03 and 0.011, respectively). There is a highly statistically significant association between low percentage of cyclin D1 expression (
Source: Journal of Immunoassay and Immunochemistry - Category: Biochemistry Tags: J Immunoassay Immunochem Source Type: research
Rancho Cordova-based Cesca Therapeutics Inc. says it's launching a joint venture to create a blood bank-style service for immune cells. Cesca (NASDAQ: KOOL) announced its joint venture with Irvine-based HealthBanks Biotech USA Inc. on Tuesday. Both companies are affiliated with Boyalife Group Inc., a Chinese group of stem cell companies. Boyalife bought a 70% stake in Cesca in 2016, and HealthBanks is a subsidiary. The joint vent ure plans to create a facility that would be “among the first immune…
Source: bizjournals.com Health Care:Biotechnology headlines - Category: Biotechnology Authors: Source Type: news
Altered miRNA expression participates in the biological progress of thyroid carcinoma and functions as a diagnostic marker or therapeutic agent. However, the role of miR-7-2-3p is currently unclear. The authors' study was the first investigation of miR-7-2-3p expression level and diagnostic ability in several public databases. Potential target genes were obtained from DIANA Tools, and function enrichment analysis was then performed. Furthermore, the authors examined expression levels of potential targets in the Human Protein Atlas (HPA) and the Cancer Genome Atlas (TCGA). Finally, the potential transcription factors (TFs) ...
Source: IET Systems Biology - Category: Biology Source Type: research
Gulcin Tezcan1, Ekaterina V. Martynova1, Zarema E. Gilazieva1, Alan McIntyre2, Albert A. Rizvanov1 and Svetlana F. Khaiboullina1,3* 1Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia 2Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom 3Department of Microbiology and Immunology, University of Nevada, Reno, Reno, NV, United States Inflammation has a crucial role in protection against various pathogens. The inflammasome is an intracellular multiprotein signaling complex that is linked to pathogen sensing and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions Several model systems are now available to characterize the MSC-tumour interplay in the TME. These offer early promise in establishing robust preclinical platforms for the identification of crucial molecular pathways and for the assessment of clinical efficacy of novel drugs to inhibit cancer development and progression. However, selection of the right model for a given study should be shaped on the purpose, and should also consider fixed biological, biochemical, and biophysical parameters according to the specific tumour type. Finally, in order to get reliable and useful results to be translated to the clinic...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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