Risk factors for postoperative recurrence in patients with stage II colorectal cancer.

BACKGROUND: Recurrences are the main reasons for unfavorable outcomes for patients with stage II colorectal cancer (CRC). To obtain a clear understanding of the high-risk factors, further investigation is warranted. The present study aimed to analyze the risk factors associated with postoperative recurrence in patients with stage II CRC. METHODS: Eligible patients with pathologically confirmed stage II CRC were enrolled in the study retrospectively based on a prospectively maintained database from April 2008 to March 2019. The Kaplan-Meier method were used to calculate the overall survival (OS) rate and the cumulative recurrence rate. Univariate and multivariable Cox regression analyses were performed to identify risk factors for recurrence. RESULTS: There were 2515 patients included, of whom 233 (9.3%) developed local or distant recurrence. Recurrence was associated with a significantly worse 5-year OS (45.4% vs. 95.5%, p < 0.0001). The 5-year cumulative recurrence rate was 13.0% in patients with stage II CRC. On multivariable Cox analysis, tumor size (Hazard Ratio (HR) [95% confidence interval (CI)] = 1.79[1.38, 2.33]), preoperative carbohydrate antigen (CA) 125 level (HR [95% CI] = 1.78[1.17, 2.70]), preoperative CA 199 level (HR [95% CI] = 1.56[1.09, 2.22]), and ulcerating tumor (HR [95% CI] = 1.61[1.19, 2.17]) were found to be associated with postoperative recurrence. Adjuvant chemotherapy was associated with a lower cumulative recurrence rate in patients with these risk factors (p = 0.00096). CONCLUSION: The tumor diameter, preoperative CA125 level, preoperative CA199 level, and an ulcerative tumor can predict postoperative recurrence in patients with stage II CRC, and postoperative chemotherapy could reduce the cumulative recurrence rate in patients with these high-risk factors.

SIRGs score may be a predictor of prognosis and immunotherapy response for esophagogastric junction adenocarcinoma.

Background: Esophagogastric junction adenocarcinoma (EGJA) is a special malignant tumor with unknown biological behavior. PD-1 checkpoint inhibitors have been recommended as first-line treatment for advanced EGJA patients. However, the biomarkers for predicting immunotherapy response remain controversial. Methods: We identified stromal immune-related genes (SIRGs) by ESTIMATE from the TCGA-EGJA dataset and constructed a signature score. In addition, survival analysis was performed in both the TCGA cohort and GEO cohort. Subsequently, we explored the differences in tumor-infiltrating immune cells, immune subtypes, immune-related functions, tumor mutation burden (TMB), immune checkpoint gene expression, immunophenoscore (IPS) between the high SIRGs score and low SIRGs score groups. Finally, two validation cohorts of patients who had accepted immunotherapy was used to verify the value of SIRGs score in predicting immunotherapy response. Results: Eight of the SIRGs were selected by LASSO regression to construct a signature score (SIRGs score). Univariate and multivariate analyses in the TCGA and GEO cohort suggested that SIRGs score was an independent risk factor for the overall survival (OS) and it could increase the accuracy of clinical prediction models for survival. However, in the high SIRGs score group, patients had more immune cell infiltration, more active immune-related functions, higher immune checkpoint gene expression and higher IPS-PD1 and IPS-PD1-CTLA4 scores, which indicate a better response to immunotherapy. The external validation illustrated that high SIRGs score was significantly associated with immunotherapy response and immune checkpoint inhibitors (ICIs) can improve OS in patients with high SIRGs score. Conclusion: The SIRGs score may be a predictor of the prognosis and immune-therapy response for esophagogastric junction adenocarcinoma.

Indications for Adjuvant Chemotherapy in Stage II Gastric Cancer After D2 Gastrectomy-A Chinese Multicenter Study.

BACKGROUND: The benefit of adjuvant chemotherapy (AC) for patients with stage II gastric cancer remains controversial. This study aimed to explore the indications for adjuvant chemotherapy in patients with stage II gastric cancer by constructing an individual prediction model. PATIENTS AND METHODS: In this Chinese multicenter study, a total of 1012 patients with stage II gastric cancer after D2 radical gastrectomy were retrospectively analyzed. All patients were randomly assigned to a training cohort (n = 674) or a validation cohort (n = 338). A nomogram was constructed according to the training cohort. Concordance index (C-index), the area under the receiver operating characteristic (ROC) curves (AUC), calibration curves, and decision curve analysis (DCA) were applied to evaluate the performance of the nomogram. ROC curves and stratified survival were used to determine the patients' cutoff score for a benefit from adjuvant chemotherapy. An additional 338 patients were used as a validation cohort to validate the feasibility of using this nomogram to guide individualized therapy for patients with stage II gastric cancer. RESULTS: Univariate and multivariate analyses illustrated that age, sex, tumor location, size, carcinoembryonic antigen (CEA), hemoglobin (HB), and T stage were independent prognostic factors for overall survival (OS), and they were used to establish a nomogram. The cutoff value was determined by ROC curve analysis, and patients were divided into a high-risk group (< 239 points) and a low-risk group (≥ 239 points). There was no significant difference in the OS of low-risk patients in either the training cohort or the validation cohort. However, the OS of high-risk patients in the AC group was better than that of patients in the surgery-only group. CONCLUSIONS: This prediction model can be applied to guide treatment of patients with stage II gastric cancer. High-risk patients (< 239 points) are likely to benefit from AC after D2 radical gastrectomy.

Bridged cassane derivatives from the seeds of Caesalpinia sappan L. and their cytotoxic activities.

Two undescribed nitrogen bridged cassane alkaloids (caesanamides A-B) and five undescribed oxygen bridged cassane diterpenoids (caesalpinins JA-JE), together with six known analogs, were isolated and identified from the seeds of Caesalpinia sappan. Their structures, including the absolute configurations, were unequivocally elucidated by the analysis of comprehensive spectroscopic data, ECD calculations, single-crystal X-ray diffraction and the CASE algorithm. Among them, caesanamides A and B represent the first examples of cassane alkaloids bearing unique ring systems of an amide bridge between C-19/C-20 incorporating a 1,3-oxazolidine (6/6/6/5/6/5) or a 7-one-1,3-oxazepine (6/6/6/5/6/7). Caesalpinin JA is an A/B cis-20-norcassane diterpenoid with a rare five-membered oxygen bridge between C-10/C-18. Biological evaluation showed that cassane alkaloids exhibited significant cytotoxicity against HepG2 cells with IC50 values of 13.48 ± 1.07 µM (caesanamide A), 18.91 ± 0.98 µM (caesanamide B), and 7.82 ± 0.65 µM (caesanine B). Further flow cytometry analysis revealed that caesanine B could cause G0G1 cell cycle arrest and promote apoptosis in a dose- and time-dependent manner in HepG2 cells.

Isolation and structure elucidation of two new cassane derivatives from the seed kernels of Caesalpinia sinensis.

Two new cassane-type derivatives (1-2), together with three known compounds (3-5), were isolated from the seed kernels of Caesalpinia sinensis. Their structures were elucidated on the basis of interpretation of comprehensive spectroscopic data, including HRESIMS and 1D/2D NMR spectroscopy, and the absolute configuration were established by means of ECD calculation. Compound 2, possessing a 16-degradative cassane skeleton, was rarely encountered in cassane diterpenoids isolated from the genus Caesalpinia. All compounds were evaluated for their anti-inflammatory activities against the overproduction of NO in LPS-stimulated RAW 264.7 macrophages, and compounds 1-5 could inhibit production of NO at the concentration of 50 µM.

EEG signal classification based on SVM with improved squirrel search algorithm.

Electroencephalography (EEG) is a complex bioelectrical signal. Analysis of which can provide researchers with useful physiological information. In order to recognize and classify EEG signals, a pattern recognition method for optimizing the support vector machine (SVM) by using improved squirrel search algorithm (ISSA) is proposed. The EEG signal is preprocessed, with its time domain features being extracted and directed to the SVM as feature vectors for classification and identification. In this paper, the method of good point set is used to initialize the population position, chaos and reverse learning mechanism are introduced into the algorithm. The performance test of the improved squirrel algorithm (ISSA) is carried out by using the benchmark function. As can be seen from the statistical analysis of the results, the exploration ability and convergence speed of the algorithm are improved. This is then used to optimize SVM parameters. ISSA-SVM model is established and built for classification of EEG signals, compared with other common SVM parameter optimization models. For data sets, the average classification accuracy of this method is 85.9%. This result is an improvement of 2-5% over the comparison method.

Retigeric acid B-induced mitophagy by oxidative stress attenuates cell death against prostate cancer cells in vitro.

AIM: Retigeric acid B (RAB), a pentacyclic triterpenic acid from Lobaria kurokawae Yoshim, has been found to induce apoptosis in prostate cancer cells. The aim of this study was to investigate the roles of mitochondrial damage-caused mitophagy in RAB-induced prostate cancer cell death in vitro. METHODS: Human prostate cancer PC3 and LNCaP cells were tested. Cell viability was analyzed with MTT assay. Cell apoptosis, ROS level and mitochondrial transmembrane potential (mtΔψ) were measured with flow cytometry. Autophagy- and apoptosis-related proteins were studied using Western blotting. GFP-LC3B puncta, mitochondrial swelling and mitophagy were examined morphologically. Quantitative RT-PCR was used to measure LC3B mRNA level, and siRNA was used to knock down LC3BII. RESULTS: In both PC3 and LNCaP cells, RAB (15 µmol/L) increased ROS accumulation and decreased mtΔψ in a time-dependent manner. Furthermore, RAB induced mitochondrial swelling and mitophagy, significantly increased LC3B expression and conversion of LC3BI to LC3BII, and the elimination of mitochondria by LC3BII-containing autophagolysosomes. In addition, RAB suppressed the PI3K/Akt/mTOR pathway activation. Pretreatment of PC3 cells with autophagy inhibitor 3-MA (5 mmol/L) or the lysosomal protease inhibitor CQ (10 µmol/L) significantly increased RAB-induced apoptosis. Similar results were obtained in RAB-treated PC3 cells with LC3B knocked down. CONCLUSION: RAB induces mitochondrial damage and mitophagy that attenuates RAB-induced prostate cancer cell death. Thus, suppression of mitophagy might be a potential strategy for improving the chemotherapeutic effects of RAB.