Identification of a Novel Bcl-2 Inhibitor by Ligand-Based Screening and Investigation of Its Anti-cancer Effect on Human Breast Cancer Cells

In conclusion, we identified a novel Bcl-2 inhibitor by QSAR screening, which exerted significant cytotoxic activity in breast cancer cells through inducing mitochondria-mediated apoptosis. Introduction Apoptosis is a process of cellular suicide through which unwanted or unhealthy cells are eliminated during organism development or cellular stress (Reed, 2002; Fernald and Kurokawa, 2013). Deregulated apoptosis is a characteristic of cancers (Doi et al., 2012; Roizen, 2012). The B-cell lymphoma-2 (Bcl-2) family is composed of pro- and anti-apoptotic proteins, plays pivotal role in the mitochondrial pathway of apoptosis by promoting the release of cytochrome c and Smac (Second mitochondrial-derived activator of caspases) into the cytosol, resulting in caspase-dependent cell death (Day et al., 2008; Bai and Wang, 2013). The pro-apoptotic proteins of Bcl-2 family include Bak and Bax, the multi-domain proteins, and Bim, Bid, Puma, and Noxa, the BH3 domain only proteins (Fulda, 2013). The most prominent anti-apoptotic proteins contain Bcl-xl, Bcl-2, and Mcl-1 (Oltersdorf et al., 2005). The BH3-only proteins stimulate apoptosis either by interacting with Bak and Bax or by binding to the anti-apoptotic proteins to release Bax and Bak (Martin and Dowsett, 2013). Therefore, the cell survival or death is largely determined by the ratio of Bcl-2 family anti- and pro-apoptotic proteins. In most tumor tissues and cancer cell lines, the anti-apoptotic Bcl-2 proteins are frequently hig...
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
Authors: Beylacq L, Baer E, Choquet O, Dupre HL, Capdevila X Abstract BACKGROUND: Ultrasound-guided axillary block is widely used in daily practice for upper limb orthopedic surgery. A simple, safe, efficacious and time-saving technique is mandatory to optimize surgical turnover and costs. In this perspective, we compared, in a randomized, single-blinded study, a standardized perifascial technique and the selective perineural technique. METHODS: Forty-two patients scheduled for elective hand surgery were randomly assigned to receive 20 ml of 10 mg/mL mepivacaïne, either selectively around each of the radia...
Source: Minerva Anestesiologica - Category: Anesthesiology Tags: Minerva Anestesiol Source Type: research
CONCLUSIONS: Perioperative, i.v. lidocaine administration influences postoperative serum concentrations of endocannabinoids and NAEs in children. PMID: 31630508 [PubMed - as supplied by publisher]
Source: Minerva Anestesiologica - Category: Anesthesiology Tags: Minerva Anestesiol Source Type: research
Catheter use in regional anesthesia: pros &cons. Minerva Anestesiol. 2019 Oct 14;: Authors: Capdevila X, Iohom G, Choquet O, Delaney P, Apan A Abstract Continuous peripheral nerve blocks refer to a local anesthetic solution administered via perineurally placed catheters in an effort to extend the benefits of a single-shot peripheral nerve block. They offer several advantages in the postoperative period including excellent analgesia, reduced opioid consumption and associated side effects, enhanced rehabilitation and improved patient satisfaction. The current trend towards less invasive, one-day surg...
Source: Minerva Anestesiologica - Category: Anesthesiology Tags: Minerva Anestesiol Source Type: research
Authors: Romagnoli S, Franchi F, Ricci Z Abstract Individual response to sedatives and hypnotics is characterized by high variability and the identification of a personalized dose during anesthesia in the operating room and during sedation in the intensive care unit may have beneficial effects. Although the brain is the main target of general intravenous and inhaled anesthetic agents, electroencephalography (EEG) is not routinely utilized to explore cerebral response to sedation and anesthesia probably because EEG trace reading is complex and requires encephalographers' skills. Automated processing algorithms (proc...
Source: Minerva Anestesiologica - Category: Anesthesiology Tags: Minerva Anestesiol Source Type: research
DISCUSSION: On the basis of the findings, this study showed evidence that increase in NPS burden (reflected by increase in NPI) over time predicts conversion to AD, whereas stability of symptoms (reflected by stable NPI score) favors nonconversion. Further study should investigate the underlying mechanisms that drive both NPS burden and cognitive decline. PMID: 31633557 [PubMed - as supplied by publisher]
Source: Alzheimer Disease and Associated Disorders - Category: Psychiatry Tags: Alzheimer Dis Assoc Disord Source Type: research
CONCLUSIONS: In elderly individuals with T1DM, we found associations between dLOC and cognition overall and in men but not women. Underlying sex differences should be considered in future research or interventions on psychosocial characteristics for cognition. PMID: 31633555 [PubMed - as supplied by publisher]
Source: Alzheimer Disease and Associated Disorders - Category: Psychiatry Tags: Alzheimer Dis Assoc Disord Source Type: research
CLINICS IN PERINATOLOGY
Source: Clinics in Perinatology - Category: Perinatology & Neonatology Authors: Source Type: research
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