Toripalimab combined with targeted therapy and chemotherapy achieves pathologic complete response in gastric carcinoma: A case report.

BACKGROUND: Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma. Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/ adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy. Herein, we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab, Herceptin, and docetaxel, oxaliplatin, calcium folinate, and fluorouracil (FLOT) chemotherapy followed by surgery for human epidermal growth factor receptor 2 (HER2)- and programmed death-ligand 1 (PD-L1)-positive locally advanced gastric carcinoma. We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma. CASE SUMMARY: The patient was diagnosed with locally advanced adenocarcinoma of the cardia. Immunohistochemistry of the baseline tissues suggested that the tissues were HER2- (fluorescent in situ hybridization) and PD-L1-positive (combined positive score = 1). The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin, toripalimab, and FLOT chemotherapy. The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation (proximal stomach), no clear residual tumor (tumor regression grade 0), no regional lymph node metastasis, and negative upper and lower cut ends. The levels of tumor markers were reduced to normal levels after re-examination. With good postoperative recovery, the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered. After the treatment, the patient was monitored every 3 mo with a follow-up of 12 mo (4 times). As of February 27, 2022, he was in a good condition without disease progression. The clinical trial registration number is E2019401. CONCLUSION: There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy; however, most of these studies are phase II studies with small cohorts. According to the results of some current studies, these combined regimens have shown promising results in terms of efficacy and safety. However, the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials, and further exploration of molecular markers for effective populations is required.

Association between periodontal disease, tooth loss and liver diseases risk.

AIM: The purpose of this study is to assess the associations between periodontal disease, tooth loss and liver diseases. MATERIALS AND METHODS: PubMed and Embase databases were utilized to search eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used as effect size to assess the associations between periodontal disease, tooth loss and liver diseases risk. RESULTS: Our results indicated positive associations between periodontal disease and non-alcoholic fatty liver disease (NAFLD) (OR = 1.19, 95% CI = 1.06-1.33), liver cirrhosis (OR = 2.28, 95% CI = 1.50-3.48) and elevated transaminase level risk (OR = 1.08, 95% CI = 1.02-1.15). Moreover, tooth loss could increase NAFLD (OR = 1.33, 95% CI = 1.12- 1.56) and liver cancer risk (OR = 1.34, 95% CI = 1.04-1.74), and every five increment in tooth loss was associated with 5% increased liver cancer risk (OR = 1.05, 95% CI = 1.01 - 1.10) with a linear relationship. In addition, tooth loss had a positive tendency towards liver cirrhosis risk (OR = 2.03, 95% CI = 0.85-4.85) although there was no statistical significance. CONCLUSION: Periodontal disease and tooth loss are positively associated with liver diseases including NAFLD, elevated transaminase level, liver cirrhosis and liver cancer.

Preoperative Anemia or Low Hemoglobin Predicts Poor Prognosis in Gastric Cancer Patients: A Meta-Analysis.

BACKGROUND: The prognostic value of preoperative anemia in gastric cancer remains unclear. Therefore, the purpose of the present study is to evaluate the prognostic value of preoperative anemia in gastric cancer. METHODS: We searched Embase and PubMed databases for relevant studies from inception to March 2018. The prognostic value of preoperative anemia in gastric cancer was determined by calculating the hazard ratio (HR) and the corresponding 95% confidence interval (CI) as effect measures. A random effect model was used in cases in which there was significant heterogeneity; otherwise, a fixed effect model was used. Statistical analyses were performed using Stata software. RESULTS: Seventeen studies involving 13,154 gastric cancer patients were included. The estimated rate of preoperative anemia was 36% (95%CI = 27-44%). The overall survival of preoperative anemia was poor (HR = 1.33, 95%CI = 1.21-1.45). Moreover, disease-free survival was significantly lower in patients with preoperative anemia compared with those without this condition (HR = 1.62, 95%CI = 1.13-2.32). These findings were corroborated by the results of subgroup analyses. CONCLUSIONS: The results indicate that preoperative anemia predicts poor prognosis in gastric cancer, including overall survival and disease-free survival. Therefore, preoperative anemia may be a convenient and cost-effective blood-derived prognostic marker for gastric cancer.

Long non-coding RNA AB007962 is downregulated in gastric cancer and associated with poor prognosis.

A number of previous studies have reported that numerous long non-coding RNAs (lncRNAs) are dysregulated in gastric cancer (GC) and are involved in a series of biological and pathological processes. Total RNA was extracted from the cancerous tissues and matched normal adjacent tissues (NATs) of 96 patients with GC. The expression level of AB007962, a novel lncRNA, was determined by reverse transcription-quantitative polymerase chain reaction. The association between AB007962 expression levels and clinicopathological features were analyzed. Kaplan-Meier curves were also constructed in order to evaluate prognosis. Finally, publicly accessible data from The Cancer Genome Atlas was used to further verify the expression levels and clinical significance of AB007962. In conclusion, it was determined that the expression level of AB007962 was significantly reduced, compared with matched NATs in GC tissues (P=0.003). Survival analysis indicated that patients with intestinal-type GC with a reduced expression of AB007962 had a reduced prognosis, compared with those with an increased expression. AB007962 may be involved in the progression of GC and act as a novel prognostic biomarker for patients with GC, particularly in intestinal-type GC.

Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion.

Thousands of genes have been well demonstrated to play important roles in cancer progression. As genes do not function in isolation, they can be grouped into "networks" based on their interactions. In this study, we discover a network regulating Claudin-4 in gastric cancer. We observe that Claudin-4 is up-regulated in gastric cancer and is associated with poor prognosis. Claudin-4 reinforce proliferation, invasion, and EMT in AGS, HGC-27, and SGC-7901 cells, which could be reversed by miR-596 and miR-3620-3p. In addition, lncRNA-KRTAP5-AS1 and lncRNA-TUBB2A could act as competing endogenous RNAs to affect the function of Claudin-4. Our results suggest that non-coding RNAs play important roles in the regulatory network of Claudin-4. As such, non-coding RNAs should be considered as potential biomarkers and therapeutic targets against gastric cancer.Non-coding RNAs can modify the expression of proteins in cancer networks. Here the authors reveal a regulatory network in gastric cancer whereby claudin-4 expression is reduced by specific miRNAs, which are in turn bound by specific lncRNAs acting as competing endogenous RNAs (ceRNAs), resulting in increased claudin-4 expression.

Which is better for gastric cancer patients, perioperative or adjuvant chemotherapy: a meta-analysis.

BACKGROUND: The preferred chemotherapy method for gastric cancer continues to be matter of debate. We performed a meta-analysis to comparing prognosis and safety between perioperative chemotherapy and adjuvant chemotherapy to identify the better chemotherapy option for gastric cancer. METHODS: We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until February 2016. The main endpoints were prognostic value (hazard ratio [HR] for overall survival [OS] and 1-, 2-, 3-, and 5-year survival rate), response rate of chemotherapy, radical resection rate, post-operative complication rate, and adverse effects of chemotherapy. RESULTS: Five randomized controlled trials and six clinical controlled trials involving 1,240 patients were eligible for analysis. Compared with the adjuvant chemotherapy group, the perioperative chemotherapy group had significantly better prognosis (HR, 0.74; 95 % CI, 0.61 to 0.89; P < 0.01). The difference between the two groups remained significant in the studies that used combination chemotherapy as the neoadjuvant chemotherapy regimen (HR, 0.59; 95 % CI, 0.46 to 0.76; P < 0.01) but were not significant in the studies that used fluoropyrimidine monotherapy (HR, 0.93; 95 % CI, 0.56 to 1.55; P = 0.84). Furthermore, the two groups showed no significant differences in the post-operative complication rates (relative risk, 0.98; 95 % CI, 0.63 to 1.51; P = 0.91) or adverse effects of chemotherapy (P > 0.05 for all adverse effects). CONCLUSION: Perioperative chemotherapy showed improved survival compared to adjuvant chemotherapy for gastric cancer. In addition, combination chemotherapy resulted in better survival compared to monotherapy in the neoadjuvant chemotherapy regimens.

A novel long noncoding RNA-LOWEG is low expressed in gastric cancer and acts as a tumor suppressor by inhibiting cell invasion.

PURPOSE: Long noncoding RNA (lncRNA) have been reported to be involved in the development of multiple cancers. The aim of this study was to report the identification of lncRNA-CTD-2108O9.1, which we have named lncRNA low expressed in gastric cancer (lncRNA-LOWEG), and investigate its role in cancer development. METHODS: Total RNA was extracted from the tissues of 94 patients with GC, one normal gastric epithelial cell line and four GC cell lines. Expression levels of lncRNA-LOWEG were determined by real-time PCR. Moreover, CCK-8 proliferation assay, transwell cell invasion assay and flow cytometry were performed to study the effects of lncRNA-LOWEG on SGC-7901 cell proliferation, cell invasion and cell cycle progression. Lastly, western blot and real-time PCR were used to verify the potential target genes of lncRNA-LOWEG. RESULTS: Significantly reduced expression of lncRNA-LOWEG was found in gastric cancer tissues and cell lines (SGC-7901, AGS, BGC-823 and HG-27) compared with patient-matched nontumorous adjacent tissues (P < 0.01) or the normal gastric cell line GES-1 (P < 0.05). Moreover, the transwell assay showed that the number of cells capable of passing through the Matrigel was significantly reduced after lncRNA-LOWEG transfection (P < 0.05). However, lncRNA-LOWEG overexpression did not significantly influence cell proliferation (P > 0.05) and cell cycle progression (P > 0.05). Lastly, western blot and real-time PCR analysis suggested that lncRNA-LOWEG is positively correlated with the expression of leukemia inhibitory factor receptor (LIFR) gene at the translational level. CONCLUSIONS: LncRNA-LOWEG is a tumor suppressor that inhibits GC cell invasion. And LIFR gene is up-regulated by lncRNA-LOWEG.

Clinicopathologic and Prognostic Value of Serum Carbohydrate Antigen 19-9 in Gastric Cancer: A Meta-Analysis.

BACKGROUND: The clinical value of carbohydrate antigen (CA) 19-9 in gastric cancer is controversial. We evaluated the clinicopathologic and prognostic value of CA 19-9 in gastric cancer. METHODS: A literature search was conducted in PubMed and Embase databases. Odds ratios (ORs), risk ratios (RR), hazard ratios (HRs), and 95% confidence intervals (CIs) were used as effect measures. RESULTS: Thirty-eight studies were included. Results showed that there were significant differences in the incidence of high CA 19-9 levels between stages III/IV and I/II groups (OR = 3.36; 95% CI = 2.34-4.84), the pT3/T4 and pT1/T2 groups (OR = 2.40; 95% CI = 1.60-3.59), the lymph node-positive and node-negative groups (OR = 2.91; 95% CI = 2.21-3.84), the metastasis-positive and metastasis-negative groups (OR = 2.76; 95% CI = 1.12-6.82), and vessel invasion-positive and invasion-negative groups (OR = 1.66; 95% CI = 1.11-2.48). Moreover, CA 19-9 was significantly associated with poor overall survival (HR = 1.83; 95% CI = 1.56-2.15), disease-free survival (HR = 1.85; 95% CI = 1.16-2.95), and disease-specific survival (HR = 1.33; 95% CI = 1.10-1.60) in gastric cancer. CONCLUSIONS: Our meta-analysis showed that CA 19-9 indicates clinicopathologic characteristics of gastric cancer and is associated with a poor prognosis.

Regulatory Roles of Non-Coding RNAs in Colorectal Cancer.

Non-coding RNAs (ncRNAs) have recently gained attention because of their involvement in different biological processes. An increasing number of studies have demonstrated that mutations or abnormal expression of ncRNAs are closely associated with various diseases including cancer. The present review is a comprehensive examination of the aberrant regulation of ncRNAs in colorectal cancer (CRC) and a summary of the current findings on ncRNAs, including long ncRNAs, microRNAs, small interfering RNAs, small nucleolar RNAs, small nuclear RNAs, Piwi-interacting RNAs, and circular RNAs. These ncRNAs might become novel biomarkers and targets as well as potential therapeutic tools for the treatment of CRC in the near future and this review may provide important clues for further research on CRC and for the selection of effective therapeutic targets.