Non-coding RNAs (ncRNAs) are a newly discovered functional RNA different from messenger RNA, which can participate in regulating the occurrence and development of tumors. More and more research results show that ncRNAs can participate in the regulation of gastric cancer (GC) radiotherapy response, and its mechanism may be related to its effect on DNA damage repair, gastric cancer cell stemness, cell apoptosis, activation of epidermal growth factor receptor signaling pathway, etc. This article summarizes the relevant mechanisms of ncRNAs regulating the response to radiotherapy in gastric cancer, which will be directly important for the introduction of ncRNAs particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) into clinical medicine as biomarkers and therapeutic targets.

Radiation resistance remains the leading cause of radiotherapy (RT) failure. The development of tumor-specific targeted sensitizers is key to overcoming radiation resistance. Our early data showed that cancer cell penetration was simulated by internalizing arginine-glycine-aspartic acid (iRGD), and the irradiation efficacy was improved. The present study aims to design and fabricate iRGD-modified red blood cell (RBCs) for tumor targeting and RT enhancement, and to evaluate its safety and efficacy in vivo.

1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-poly ethylene glycol-iRGD (DSPE-PEG-iRGD) was used to modify RBCs by a lipid-insertion method without direct chemical bioconjugation. Fluorescent dyes were used to trace the functional RBCs through confocal microscopy examination. In vitro stability evaluation was performed using cell culture medium incubation for 48 h followed by fluorescence decay assay. Furthermore, a subcutaneous cancer cell mouse model was constructed with MKN-45 cells for target efficacy and RT enhancement evaluation with DSPE-PEG-iRGD-modified RBCs (RBC-iRGD).

Successful construction of RBC-iRGD was verified by the presence of the yellow fluorescence, and an approximately 10⁸ iRGD molecules were labeled on a single RBC. The final RBC-iRGD showed good stability without any hemolytic effects in the cell culture medium. Moreover, higher fluorescence intensity and decreased liver and spleen accumulation could be observed in RBC-iRGD compared to RBC + iRGD in vivo. The RBC-iRGD exerted enhanced radiosensitivity in subcutaneous gastric tumor mice.

The RBC-iRGD exerted good tumor-targeting efficacy and favorable effects for RT enhancement in vivo.

The most common digestive system (DS) cancers, including tumors of the gastrointestinal tract (GIT) such as colorectal cancer (CRC), gastric cancer (GC) and esophageal cancer (EC) as well as tumors of DS accessory organs such as pancreatic and liver cancer, are responsible for more than one-third of all cancer-related deaths worldwide, despite the progress that has been achieved in anticancer therapy. Due to these limitations in treatment strategies, oncological research has taken outstanding steps towards a better understanding of cancer cell biological complexity and heterogeneity. These studies led to new molecular target-driven therapeutic approaches. Different in vivo and in vitro studies have revealed significant expression of B7 homologue 3 (B7-H3) among the most common cancers of the GIT, including CRC, GC, and EC, whereas B7-H3 expression in normal healthy tissue of these organs was shown to be absent or minimal. This molecule is able to influence the biological behavior of GIT tumors through the various immunological and nonimmunological molecular mechanisms, and some of them are shown to be the result of B7-H3-related induction of signal transduction pathways, such as Janus kinase 2/signal transducer and activator of transcription 3, phosphatidylinositol 3-kinase/protein kinase B, extracellular signal-regulated kinase, and nuclear factor-κB. B7-H3 exerts an important role in progression, metastasis and resistance to anticancer therapy in these tumors. In addition, the results of many studies suggest that B7-H3 stimulates immune evasion in GIT tumors by suppressing antitumor immune response. Accordingly, it was observed that experimental depletion or inhibition of B7-H3 in gastrointestinal cancers improved antitumor immune response, impaired tumor progression, invasion, angiogenesis, and metastasis and decreased resistance to anticancer therapy. Finally, the high expression of B7-H3 in most common cancers of the GIT was shown to be associated with poor prognosis. In this review, we summarize the established data from different GIT cancer-related studies and suggest that the B7-H3 molecule could be a promising prognostic biomarker and therapeutic target for anticancer immunotherapy in these tumors.

We aimed to evaluate the safety and effectiveness of image-guided high-dose rate interstitial brachytherapy (iBT) for the treatment of patients with hepatic, lymphatic, and pancreatic metastases originating from gastric cancer, an entity rarely surgically treatable with curative intent.

Twelve patients with a cumulative number of 36 metastases (29 liver, 2 pancreatic, 5 lymph node) from histologically proven gastric adenocarcinoma received iBT between 2010 and 2016 and were retrospectively analyzed. Every patient underwent palliative chemotherapy prior to iBT. The iBT procedure employs a temporarily, intratumorally placed iridium-192 source in a single fraction with the goal of tumor cell eradication. Effectiveness was assessed clinically and by radiologic imaging every three months.

Local tumor control was achieved in 32 of all treated metastases (89%). Four lesions showed a local recurrence after 7 months. Lesion sizes varied from 9 to 102 mm with a median of 20 mm. The median progression-free survival was 6.6 months (range, 1.8-46.8 months). The median overall survival was 11.4 months (range, 5-47 months). One patient suffered a major complication following iBT, hepatic hematoma and abscess (Common Terminology Criteria for Adverse Events grade 3), successfully dealt with by transcutaneous drainage.

iBT is an overall safe procedure, which facilitates high rates of local tumor control in treatment of metastatic gastric adenocarcinoma. Compared with surgical metastasectomy, similar overall survival rates could be achieved in our patient collective after iBT application.

The impact of adjuvant chemotherapy and chemo-radiation therapy in the treatment of resectable gastric cancer remains varied. We sought to define the clinical impact of lymph node ratio on the relative benefit of adjuvant chemotherapy or chemo-radiation therapy among patients having undergone curative-intent resection for gastric cancer.

Using the multi-institutional US Gastric Cancer Collaborative database, 719 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2013 were identified. Patients with metastasis or an R2 margin were excluded. The impact of lymph node ratio on overall survival among patients who received chemotherapy or chemo-radiation therapy was evaluated.

Median patient age was 65 years, and the majority of patients were male (56.2%). The majority of patients underwent either subtotal (40.6%) or total gastrectomy (41.0%), with the remainder undergoing distal gastrectomy or wedge resection (18.4%). On pathology, median tumor size was 4 cm; most patients had a T3 (33.0%) or T4 (27.9%) lesion with lymph node metastasis (59.7%). Margin status was R0 in 92.5% of patients. A total of 325 (45.2%) patients underwent resection alone, 253 (35.2%) patients received 5-FU or capecitabine-based chemo-radiation therapy, whereas the remaining 141 (19.6%) received chemotherapy. Median overall survival was 40.9 months, and 5-year overall survival was 40.3%. According to lymph node ratio categories, 5-year overall survival for patients with a lymph node ratio of 0, 0.01-0.10, >0.10-0.25, >0.25 were 54.1%, 53.1 %, 49.1 % and 19.8 %, respectively. Factors associated with worse overall survival included involvement of the gastroesophageal junction (hazard ratio 1.8), T-stage (3-4: hazard ratio 2.1), lymphovascular invasion (hazard ratio 1.4), and lymph node ratio (>0.25: hazard ratio 2.3; all P < .05). In contrast, receipt of adjuvant chemo-radiation therapy was associated with an improved overall survival in the multivariable model (versus resection alone: hazard ratio 0.40; versus chemotherapy: hazard ratio 0.45, both P < .001). The benefit of chemo-radiation therapy for resected gastric cancer was noted only among patients with lymph node ratio >0.25 (versus resection alone: hazard ratio R 0.34; versus chemotherapy: hazard ratio 0.45, both P < .001). In contrast, there was no noted overall survival benefit of chemotherapy or chemo-radiation therapy among patients with lymph node ratio ≤0.25 (all P > .05).

Adjuvant chemotherapy or chemo-radiation therapy was utilized in more than one-half of patients undergoing curative-intent resection for gastric cancer. Lymph node ratio may be a useful tool to select patients for adjuvant chemo-radiation therapy, because the benefit of chemo-radiation therapy was isolated to patients with greater degrees of lymphatic spread (ie, lymph node ratio >0.25).

Radiotherapy is crucial and substantially contributes to multimodal cancer treatment. The combination of conventional fractionation radiotherapy (CFRT) and systemic therapy has been established as the standard treatment for many cancer types. With advances in linear accelerators and image-guided techniques, high-dose fractionation radiotherapy (HFRT) is increasingly introduced in cancer centers. Clinicians are currently integrating HFRT into multimodality treatment. The shift from CFRT to HFRT reveals different effects on the tumor microenvironment and responses, particularly the immune response. Furthermore, the combination of HFRT and drugs yields different results in different types of tumors or using different treatment schemes. We have reviewed clinical trials and preclinical evidence on the combination of HFRT with drugs, such as chemotherapy, targeted therapy, and immune therapy. Notably, HFRT apparently enhances tumor cell killing and antigen presentation, thus providing opportunities and challenges in treating cancer.

The aim of this study was to assess the significance of the correlation among tissue carcinoembryonic antigen (CEA) expression with serum CEA (sCEA) levels and long-term survival to highlight the clinical prognostic significance of tissue CEA expression in gastric cancer patients.

Immunohistological method and radioimmunoassay were used to assess tissue and sCEA expression, respectively. Univariate and multivariate analyses were performed to determine correlations, and the Kaplan-Meier method was used to investigate the prognostic significance.

Our results demonstrate that tissue CEA in gastric cancer is significantly correlated with preoperative sCEA levels (p = 0.031), depth of invasion (p = 0.001), lymph node metastasis (p < 0.001), distant metastasis (p = 0.001), and TNM staging (p < 0.001). The 5-year survival rates were 67.6, 53.9, and 40.1 % for negatively, moderately, and intensely positively stained tissues (p < 0.001), and 57.0 and 37.9 % for serum with normal and elevated CEA expression (p = 0.031). Multivariate analysis revealed that tissue CEA can be considered an independent prognostic factor. Further analysis illustrated that patients with negative expression in both tissue and serum had better prognosis compared with those positively expressing CEA in both tissue and serum and/or those positively expressing CEA in either tissue or serum (p < 0.001). Our results also demonstrated that patients with negative tissue CEA staining and elevated sCEA expression had a better 5-year survival.

Tissue CEA expression in gastric cancer is directly correlated with sCEA levels and long-term prognosis. Thus, tissue CEA expression can be considered as a useful biomarker to improve the interpretation of sCEA levels in predicting long-term survival.