Gastric cancer (GC) is one of the most malignant tumors and the second leading cause of cancer-related deaths in the world. Luteolin, a flavonoid present in many fruits and green plants, suppresses cancer progression. The effects of luteolin on GC cells and their underlying mechanisms remain unclear. Effects of luteolin on cell proliferation, migration, invasion, and apoptosis were examined in vitro and in vivo by cell counting kit-8 (CCK-8), transwell assays, and flow cytometry, respectively. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blots were performed to evaluate Notch1 signaling and activation of epithelial-mesenchymal transition (EMT) in GC cells treated with or without luteolin. Immunohistochemistry was performed to examine proliferation and Notch1 expression in xenograft tumors. Luteolin significantly inhibited cell proliferation, invasion, and migration in a dose-dependent and time-dependent manner and promoted cell apoptosis. Luteolin reversed EMT by shrinking the cytoskeleton and by inducing the expression of epithelial biomarker E-cadherin and downregulating the mesenchymal biomarkers N-cadherin, vimentin and Snail. Furthermore, Notch1 signaling was inhibited by luteolin, and downregulation of Notch1 had similar effects as luteolin treatment on cell proliferation, migration, and apoptosis. In addition, luteolin suppressed tumor growth in vivo. A higher expression of Notch1 correlated with a poor overall survival and a poor time to first progression. Furthermore, co-immunoprecipitation analysis revealed that activated Notch1 and β-catenin formed a complex and regulated cell proliferation, migration, and invasion. In this study, GC progression was inhibited by luteolin through suppressing Notch1 signaling and reversing EMT, suggesting that luteolin may serve as an effective anti-tumor drug in GC treatment.

Previous observations have established that varicella-zoster virus (VZV) is enveloped in the trans-Golgi network (TGN) in cultures infected with VZV and that the glycoprotein gE is targeted to the TGN by a signal sequence (AYRV) and an acidic TGN signal patch in its cytosolic domain. Neither sequence is present in other VZV glycoproteins. Like gE, gI was targeted to the TGN when it was expressed in transfected cells, suggesting that gI also contains TGN targeting information (colocalized with gE and the AP-1 adaptin complex). In contrast, gB, gC, gH, and gL immunoreactivities were not detected in the TGN when they were expressed individually in transfected cells. In VZV-infected cells, gE, gI, gH, and gL were all concentrated in the TGN. Since VZV glycoproteins that lack targeting sequences (gB, gC, gH, and gL) concentrated in the TGN of infected cells, it is proposed that gE and gI, which have such sequences, serve as navigator glycoproteins, forming complexes that direct the signal-deficient glycoproteins to the TGN.

Objective: We aimed to establish a nomogram for predicting lymph node metastasis in early gastric cancer (EGC) involving human epidermal growth factor receptor 2 (HER2).Methods: We collected clinicopathological data of patients with EGC who underwent radical gastrectomy and D2 lymphadenectomy at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between January 2012 and August 2018. Univariate and multivariate logistic regression analysis were used to examine the relationship between lymph node metastasis and clinicopathological features. A nomogram was constructed based on a multivariate prediction model. Internal validation from the training set was performed using receiver operating characteristic (ROC) and calibration plots to evaluate discrimination and calibration, respectively. External validation from the validation set was utilized to examine the external validity of the prediction model using the ROC plot. A decision curve analysis was used to evaluate the benefit of the treatment.Results: Among 1,212 patients with EGC, 210 (17.32%) presented with lymph node metastasis. Multivariable analysis showed that age, tumor size, submucosal invasion, histological subtype, and HER2 positivity were independent risk factors for lymph node metastasis in EGC. The area under the ROC curve of the model was 0.760 (95% CI: 0.719–0.800) in the training set (n = 794) and 0.771 (95% CI: 0.714–0.828) in the validation set (n = 418). A predictive nomogram was constructed based on a multivariable prediction model. The decision curve showed that using the prediction model to guide treatment had a higher net benefit than using endoscopic submucosal dissection (ESD) absolute criteria over a range of threshold probabilities.Conclusion: A clinical prediction model and an effective nomogram with an integrated HER2 status were used to predict EGC lymph node metastasis with better accuracy and clinical performance.

Background: There is no global consensus on adjuvant chemotherapy (ACT) for pT2N0M0 gastric cancer. We conducted a retrospective study to reveal the role of ACT in such patients.Methods: Patients with pT2N0M0 gastric cancer who underwent radical resection with D2 lymphadenectomy for primary gastric cancer between January 2012 and May 2016 were included. Kaplan–Meier and Cox regression were used to evaluate overall survival (OS), disease-specific survival (DSS) and predictors of prognosis. Stratified analysis based on high-risk factors was conducted.Results: Of enrolled 307 patients, 111 patients underwent surgery alone and 196 patients received ACT. Surgery alone (HR = 2.913, 95% CI: 1.494-5.682, p = 0.002) and total gastrectomy (HR = 2.445, 95% CI: 1.279-4.675, p = 0.007) were independently associated with decreased OS. With the median follow-up of 73.1 months, the 5-year OS rate was 87.9% and 5-year DSS rate was 91.8%. Patients receiving ACT showed a better 5-year OS rate (92.9 vs. 79.3%, p < 0.001) and DSS rate (96.8 vs. 83.0%, p < 0.001) than patients underwent surgery alone. Patients receiving monotherapy (n = 130) had a relatively poor prognosis compared to patients receiving dual-drug (n = 66) without a significant difference (92.3 vs. 93.9%, p = 0.637). In patients without high-risk factors based on the Chinese Society of Clinical Oncology (CSCO) Guidelines, ACT also provided survival benefit (96.0 vs 82.9%, p = 0.038).Conclusions: ACT was accompanied with higher 5-year OS and DSS rates of patients with pT2N0M0 gastric cancer. Patients with pT2N0M0 gastric cancer, regardless of high-risk factors based on the CSCO guidelines, might be considered candidates for ACT. In regard to the therapy regimen, monotherapy might be the optimal choice, considering the adverse events.

Background: Preoperative chemotherapy (PCT) has been considered an important treatment for advanced gastric cancer (AGC). The tumor regression grade (TRG) system is an effective tool for the assessment of patient responses to PCT. Pathological complete response (TRG = 0) of the primary tumor is an excellent predictor of better prognosis. However, which patients could achieve pathological complete response (TRG = 0) after chemotherapy is still unknown. The study aimed to find predictors of TRG = 0 in AGC.Methods: A total of 304 patients with advanced gastric cancer from July 2009 to November 2018 were enrolled retrospectively. All patients were randomly assigned (2:1) to training and internal validation groups. In addition, 124 AGC patients receiving PCT from December 2018 to June 2020 were included prospectively in the external validation cohort. A prediction model for TRG = 0 was established based on four predictors in the training group and was validated in the internal and external validation groups.Results: Through univariate and multivariate analyses, we found that CA199, CA724, tumor differentiation and short axis of the largest regional lymph node (LNmax) were independent predictors of TRG = 0. Based on the four predictors, we established a prediction model for TRG = 0. The AUC values of the prediction model in the training, internal and external validation groups were 0.84, 0.73 and 0.82, respectively.Conclusions: We found that CA199, CA724, tumor differentiation and LNmax were associated with pathological response in advanced gastric cancer. The prediction model could provide guidance for clinical work.

Objective: To quantify the potential benefit of adjuvant chemotherapy (ACT) with respect to survival, and to identify factors for predicting prognoses in early gastric cancer patients. Methods: Patients with pT1 gastric cancer (GC) who underwent radical resection with D2 lymphadenectomy were retrospectively analyzed. Based on lymph node metastasis (LNM) status and treatment regimens, patients were classified into groups, and clinicopathological variables, overall survival (OS), and disease-specific survival (DSS) were compared. Results: Of 1,050 enrolled patients, 151 patients (14.4%) had a positive LNM status. Submucosal invasion, undifferentiated state, tumor size > 2 cm, ulceration, and lymphovascular invasion were independent risk factors for LNM using multivariate analyses. The 5-year OS of all patients was 96.4%. HER2 positive, perineural invasion, and LNM were independent factors for worse survival. Patients with pT1N3 GC had a worse 5-year OS and DSS than pT1N0, pT1N1, and pT1N2 patients (P < 0.001). The 5-year OS and DSS for pT1N1 patients showed no significant difference between ACT and surgery only patients. For pT1N2 patients, the 5-year OS and DSS showed no significant difference between S-1 and Xelox treatments. For pT1N3 patients, 7 (36.8%) received S-1, while 12 (63.2%) received Xelox treatment. Patients receiving Xelox treatment showed a better 5-year OS (75.0% vs. 14.3%) and DSS (81.8% vs. 20.0%) than patients receiving S-1 (P < 0.05). Conclusions: Curative surgery only was adequate for patients with pT1N0 and pT1N1. Xelox showed no survival benefits for pT1N2 patients. Therefore, S-1 is the optimal choice for pT1N2 patients, when considering adverse effects. Xelox is recommended for pT1N3 patients.