Int J Med Sci
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Introduction: mTOR inhibitors are anticancer agents affecting mTOR/AKT/PI3K pathway that is one of the most important in human cancer cells. Hyperactivation of mTOR/AKT/PI3K and overexpression of this pathway members are frequently reported in uterine sarcoma and carcinosarcoma. Present study is aimed to assess the activity of the two mTOR inhibitors (rapamycin - RAP and sapanisertib - MLN) as a single agent and combined with gemcitabine (GEM, one of substances commonly used in systemic anticancer treatment) in uterine sarcoma and carcinosarcoma in vitro models. ⋯ Leiomyosarcoma cell line (MES-SA) was found sensitive to both mTOR inhibitors. Additive effects in combinations of GEM, RAP and MLN were observed, what makes them promising for future preclinical and clinical trials. Additivity with slight tendency towards antagonism between GEM and MLN observed in MES-SA cell line is unexpected finding and might prompt the mechanistic research aimed to explain this phenomenon.
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Background: Gallbladder cancer (GBC) is the most common malignancy of the biliary system. Early T stage GBC patients with distant metastasis are proven to have a worse prognosis. In this study, our aim was to construct and validate a novel nomogram for predicting distant metastasis in T1 and T2 GBC. ⋯ Through ROC curve analysis, the areas under the ROC curves in the training and validation cohorts were 0.723 and 0.679, respectively. Conclusions: Although some limitations exist in this predictive model, the nomogram revealed the relationship between the clinicopathological characteristics of T1 and T2 GBC patients and the risk of distant metastasis. The novel nomogram will assist in patient counseling and guide treatment decision making for T1 and T2 GBC patients.
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Objective: To identify the interaction between the MYOC Y437H mutation and TGF-β2 in a family with primary open-angle glaucoma (POAG). Methods: The MYOC Y437H mutation was identified in a family with POAG; the family was a fourth-generation family with 27 members, of which 6 members were affected. Analysis focused on the secreted myocilin protein and TGF-β2 found in the aqueous humor. ⋯ This increase in TGF-β2 was also associated with increased cell death in cells carrying the MYOC Y437H mutation. Conclusion: These data collectively suggest that the mutual interaction between glaucomatous MYOC mutation and TGF-β2 contributed to the cell death of TM cells. This relationship also provides a new, therapeutic targets for the treatment of glaucoma.
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Comparative Study
Fit factor of masks used by Physicians in Clinical Settings.
Background: Usually, physicians use filtering respirators in clinical settings to a lesser extent than other simpler surgical masks. The study aim was to determine the fit factor of surgical and other types masks commonly used in clinical settings compared with FFP3 filtering respirators. Materials and Methods: A cross-sectional study was carried out recruiting a total sample of 78 physicians. ⋯ Statistically significant differences (P<0.001) with an effect size from moderate to large (d=0.61-1.00) were shown for fit factors in the different exercises and total scores between surgical and other masks (3.2±5.0) and FFP3 filtering respirators (40.7±37.8). Generally, FFP3 filtering respirators showed a higher fit factor in the different exercises and total scores compared to the commonly used surgical and other types masks in clinical settings. Conclusions: Despite most physicians used surgical masks in clinical settings, filtering FFP3 masks showed a higher fit factor in the different exercises and total scores compared with the used surgical masks and filtering respirators such as FFP1, FFP2 and other types in clinical settings.
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Cardiomyocyte autophagy plays an important role in myocardial ischemia-reperfusion injury (MIRI). P300/CBP-associated factor (PCAF) was involved in the regulation of autophagy. However, the role of PCAF in MIRI is currently unknown. ⋯ Wortmannin, a PI3K/Akt inhibitor, could abrogate the effects of downregulation of PCAF on cardiomyocytes autophagy. These results demonstrated that downregulation of PCAF alleviated MIRI by inhibiting cardiomyocyte autophagy through PI3K/Akt/mTOR signaling pathway. Thus, PCAF may be a potential target for prevention and treatment of MIRI.