Synergic Effect of Metformin and Everolimus on Mitochondrial Dynamics of Renal Cell Carcinoma.

Renal cell carcinoma (RCC) frequently recurs or metastasizes after surgical resection. Everolimus, an mTOR inhibitor, is used as a second-line treatment, but the response of RCC to everolimus is insufficient. Metformin is an antidiabetic drug; recent reports have indicated its anti-cancer effects in various cancers, and it is known to have synergistic effects with other drugs. We investigated the possibility of coadministering everolimus and metformin as an effective treatment for RCC. RCC cells treated with a combination of the two drugs showed significantly inhibited cell viability, cell migration, and invasion, and increased apoptosis compared to those treated with each drug alone. An anti-cancer synergistic effect was also confirmed in the xenograft model. Transcriptome analysis for identifying the underlying mechanism of the combined treatment showed the downregulation of mitochondrial fusion genes and upregulation of mitochondrial fission genes by the combination treatment. Changes in mitochondrial dynamics following the combination treatment were observed using LysoTracker, LysoSensor, and JC-1 staining. In conclusion, the combination of everolimus and metformin inhibited RCC growth by disrupting mitochondrial dynamics. Therefore, we suggest that a treatment combining metformin and everolimus disrupts mitochondrial dynamics in RCC, and may be a novel strategy for RCC treatment.

Remaining Useful Life Prognosis for Turbofan Engine Using Explainable Deep Neural Networks with Dimensionality Reduction.

This study prognoses the remaining useful life of a turbofan engine using a deep learning model, which is essential for the health management of an engine. The proposed deep learning model affords a significantly improved accuracy by organizing networks with a one-dimensional convolutional neural network, long short-term memory, and bidirectional long short-term memory. In particular, this paper investigates two practical and crucial issues in applying the deep learning model for system prognosis. The first is the requirement of numerous sensors for different components, i.e., the curse of dimensionality. Second, the deep neural network cannot identify the problematic component of the turbofan engine due to its "black box" property. This study thus employs dimensionality reduction and Shapley additive explanation (SHAP) techniques. Dimensionality reduction in the model reduces the complexity and prevents overfitting, while maintaining high accuracy. SHAP analyzes and visualizes the black box to identify the sensors. The experimental results demonstrate the high accuracy and efficiency of the proposed model with dimensionality reduction and show that SHAP enhances the explainability in a conventional deep learning model for system prognosis.

Clinical experiences of incidental prostate cancer after transurethral resection of prostate (TURP) according to initial treatment: a study of a Korean high volume center.

PURPOSE: These are the clinical experiences of Korean incidental prostate cancer patients detected by transurethral resection of the prostate according to initial treatment: active surveillance (AS), radical prostatectomy (RP) and hormone therapy (HT). MATERIALS AND METHODS: We retrospectively reviewed the records of 156 incidental prostate cancer patients between 2001 and 2012. The clinicopathologic outcomes were reviewed and follow-up results were obtained. RESULTS: Among 156 patients, 97 (62.2%) had T1a and 59 (37.8%) had T1b. Forty-six (29.5%) received AS, 67 (42.9%) underwent RP, 34 (21.8%) received HT, 4 (2.6%) received radiotherapy, and 5 (3.2%) chose watchful waiting. Of 46 patients on AS, prostate-specific antigen (PSA) progression occurred in 12 (26.1%) patients. Among them, 3 patients refused treatment despite PSA progression. Five patients, who underwent RP as an intervention, all had organ-confined Gleason score ≤6 disease. In 67 patients who underwent RP, 50 (74.6%) patients had insignificant prostate cancer and 8 (11.9%) patients showed unfavorable features. During follow-up, biochemical recurrence occurred in 2 patients. Among 34 patients who received HT, 3 (8.8%) patients had PSA progression. Among 156 patients, 6 patients died due to other causes during follow-up. There were no patients who died due to prostate cancer. CONCLUSION: The clinical outcomes of incidental prostate cancer were satisfactory regardless of the initial treatment. However, according to recent researches and guidelines, immediate definite therapy should be avoided without a careful assessment. We also believe that improved clinical staging is needed for these patients.

Gastrectomy for early gastric cancer is associated with decreased cardiovascular mortality in association with postsurgical metabolic changes.

BACKGROUND: Bariatric surgery effectively induces weight loss and resolves cardiovascular comorbidities in obese patients. We investigated cardiovascular and all-cause mortality in patients who underwent gastrectomies for early gastric cancer (EGC) and analyzed the changes in metabolic parameters after surgery. METHODS: A total of 2,477 patients who underwent gastrectomies for EGC between 1995 and 2004 were enrolled in the study and followed for mortality through 2007. Standardized mortality ratios (SMRs) were calculated using sex- and age-matched mortality in the general Korean population in 2005. Effects of gastrectomy on changes in body weight and metabolic parameters were investigated in 51 of the patients before and after surgery. RESULTS: During the 15,096.4 person-years of follow-up, 244 deaths were recorded. The all-cause mortality was not significantly different from that of the general population (SMR [95 % confidence interval (CI)] = 1.01 [0.89 - 1.14]); however, cardiovascular mortality was significantly lower (SMR = 0.35 [0.22 - 0.53]). In the 51 patients included in the second part of the study, significant reductions in body weight and visceral fat areas occurred after surgery, regardless of whether the patients were previously obese. Triglycerides, LDL-cholesterol, and plasminogen activator inhibitor-1 levels were significantly decreased, whereas HDL-cholesterol and adiponectin levels were increased. Carotid intima-media thickness also was significantly decreased in previously obese and nonobese patients. CONCLUSIONS: Patients with EGC who undergo gastrectomy have a lower cardiovascular mortality but similar all-cause mortality as that of the general population. In these patients, a significant reduction in body weight and visceral fat after surgery may improve impaired lipid metabolism and prevent atherosclerotic changes.