BACKGROUND: This study aims to compare the efficacy between neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy vs . chemotherapy, and neoadjuvant triplet vs . doublet chemotherapeutic regimens in locally advanced gastric/esophagogastric junction cancer (LAGC). METHODS: We included LAGC patients from 47 hospitals in China's National Cancer Information Database (NCID) from January 2019 to December 2022. Using propensity score matching (PSM), we retrospectively analyzed the efficacy between neoadjuvant ICIs plus chemotherapy vs . chemotherapy alone, and neoadjuvant triplet vs . doublet chemotherapeutic regimens. The primary study result was the pathologic complete response (pCR) rate. The secondary study results were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 1205 LAGC patients were included. After PSM, the ICIs plus chemotherapy and the chemotherapy cohorts had 184 patients each, while the doublet and triplet chemotherapy cohorts had 246 patients each. The pCR rate (14.13% vs . 7.61%, χ2 = 4.039, P = 0.044), and the 2-year (77.60% vs . 61.02%, HR = 0.67, 95% con-fidence interval [CI] 0.43-0.98, P = 0.048) and 3-year (70.55% vs . 61.02%, HR = 0.58, 95% CI 0.32-0.93, P = 0.048) DFS rates in the ICIs plus chemotherapy cohort were improved compared to those in the chemotherapy cohort. No significant increase was observed in the OS rates at both 1 year and 2 years. The pCR rates, DFS rates at 1-3 years, and OS rates at 1-2 years did not differ significantly between the doublet and triplet cohorts, respectively. No differences were observed in postoperative complications between any of the group comparisons. CONCLUSIONS Neoadjuvant ICIs plus chemotherapy improved the pCR rate and 2-3 years DFS rates of LAGC compared to chemotherapy alone, but whether short-term benefit could translate into long-term efficacy is unclear. The triplet regimen was not superior to the doublet regimen in terms of efficacy. The safety after surgery was similar between either ICIs plus chemotherapy and chemotherapy or the triplet and the doublet regimen.
Humans ; Stomach Neoplasms/metabolism* ; Female ; Neoadjuvant Therapy/methods* ; Immune Checkpoint Inhibitors/therapeutic use* ; Male ; Middle Aged ; Propensity Score ; Retrospective Studies ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Disease-Free Survival ; Cohort Studies

Metabolic reprogramming is one of the significant characteristics of malignant tumor development.It provides the tumor with sufficient energy and materials.During the process by which tumor cells acquire metabolic reprogramming,epigenetic changes play a crucial role.N6-methyladenosine(m6A)in mRNA is the most common post-transcriptional modification of mRNA.It regulates the transcription,maturation,translation,and degradation of mRNA.Studies have shown that m6A helps promote the metabolic reprogramming of tumor cells.However,the complete mechanism still requires further research.METTL3 is a key enzyme for m6A methylation that catalyzes m6A progression by forming complexes with other proteins,such as METTL14 and WTAP.Notably,the critical role of METTL3 in the metabolic transition of gastrointestinal tumors has not been given due attention.This article summarizes the specific pathways through which METTL3 affects the reprogramming of cellular glucose metabolism in gastrointestinal tumors.We aimed to clarify the importance of METTL3 in the energy reprogramming of gastrointestinal tumors.

As a highly heterogeneous disease, breast cancer ranks first in new cases and deaths of female malignant tumors. In recent years, the incidence of breast cancer increases and tends to be younger. Early-onset breast cancer (<40 years old) is mostly associated with adverse biological characteristics and poor prognosis. Although immunotherapy and targeted therapy have advances in the treatment of breast cancer, a major challenge of neoplastic resistance to systemic therapy remains. Therefore, early diagnostic markers and potential therapeutic targets with high specificity and sensitivity must be identified. miR-21 affects the occurrence and development of breast cancer by targeting related genes and regulating related signaling pathways (PTEN/PI3K/Akt and NF-κB/ miR-21-5p/PDCD4 signaling pathways). This paper reviews the mechanism and progress of miR-21 in breast cancer.

Antibody-drug conjugates (ADCs) are novel drugs consisting of monoclonal antibodies targeting tumor-specific or tumor-associated antigens coupled with different numbers of payloads via linkers. ADCs have shown promising clinical benefits in the treatment of a variety of malignancies. Small-cell lung cancer (SCLC) is a hypo-differentiated neuroendocrine tumor with an extremely high degree of malignancy. Although SCLC is sensitive to radiotherapy and chemotherapy, it has a poor prognosis due to characteristics such as early susceptibility to metastasis and recurrence. Progress in the treatment of SCLC is very limited, and more durable and effective therapies should be developed to improve prognosis. However, the progress of SCLC-related therapeutic agents has been limited by the lack of specific molecular targets. This article reviews the basic principles and mechanisms of ADCs, highlights the research progress of relevant drugs against some targets in SCLC, and summarizes new targets that may be developed as targeted drugs.

Immunotherapy for gastric cancer has recently received attention. As a result, the guidelines for diagnosis and treatment of advanced gastric cancer have been revised. Many clinical studies have begun to pay attention to perioperative immunotherapy for gastric cancer. This article discusses the perioperative treatment of gastric cancer in the new era of immunity to contribute to the hot issues in this field.

Patients with gastric cancer often have different degrees of dyslipidemia, and the level of lipid changes is closely related to the occurrence, development and prognosis of gastric cancer. The mechanism of lipid metabolism in gastric cancer has also attracted much attention, and it may be related to the reverse cholesterol transport function, antioxidant and anti-inflammatory properties of high-density lipoprotein cholesterol. In addition, statins may reduce the risk of gastric cancer and associated mortality. Further research on the correlation between blood lipid levels and gastric cancer is aimed to provide new ideas for the future prevention and precision diagnosis and treatment of gastric cancer.

Although targeted, immune and other therapeutic strategies have become the first-line standard therapy for patients with advanced lung cancer, acquired drug resistance is still inevitable in most cases. The advent of antibody-drug conjugates (ADC) provides a new choice. ADC is a new anticancer drug formed by the coupling of targeted anti-tumor monoclonal antibodies and cytotoxic drugs. Compared with chemotherapeutic drugs, ADC has the advantages of high tolerance, accurate target recognition and little effect on non-cancer cells, and has shown good clinical benefits in the treatment of a variety of malignant tumors. This article reviews the application of ADC in advanced non-small cell lung cancer.

Objective:To explore the effects of myosteatosis and blood glucose (BG) on postoperative complications in non-diabetic gastric cancer patients receiving supplemental parenteral nutrition (SPN) after gastrectomy.Methods:Patients who underwent radical gastrectomy between March 2017 and June 2021 in the Department of Surgical Oncology, the First Hospital of Lanzhou University were included in this study. Various preoperative inflammatory and nutritional indicators, including skeletal muscle metrics at the third lumbar level on CT, were collected retrospectively. Postoperative BG within 3 days and complications within 30 days were monitored. Patients were divided into two groups according to the presence or absence of myosteatosis (assessed via skeletal muscle density [SMD]) and the differences in postoperative BG and complication incidence were compared. Mediation model was used to analyze the mediating effect of BG in the association between SMD and postoperative complications.Results:A total of 357 patients were included in the study. Compared with the 299(83.8%) patients without myosteatosis , the incidence of hyperglycemia, mean BG, maximal BG, and BG fluctuation while on SPN in the 58(16.2%) patients with myosteatosis were higher, and the comprehensive complication index (CCI) and the incidence of complication were higher ( P<0.05). More importantly, BG showed the mediation effect of -0.0892 in the effect of SMD on CCI ( P<0.05), with the effect size of 19.3％. Conclusion:Myosteatosis and postoperative hyperglycemia are associated with higher incidence of complications, and BG plays an intermediary role in the association between myosteatosis and CCI.

Objective:To explore the alteration of JAK2/STAT3 pathway after carbon ion ( 12C 6+) irradiation and the difference in the infiltration of CD8 + T cells in lung cancer regulated by downstream protein FOXP3. Methods:Significantly altered JAK2/STAT3 pathway and related differentially-expressed genes and proteins such as FOXP3 in lung cancer after carbon ion irradiation were screened based on RNA sequencing analysis in the Lewis tumor model of C57BL/6 mice. The correlation between FOXP3 and major immune cell infiltration in the immune microenvironment of lung cancer was analyzed using the ssGSEA immune infiltration algorithm in the R software "GSVA" and CD8 + T cell infiltration in the immune microenvironment of lung cancer was evaluated based on the carbon ion combined with STAT3 inhibition pathway (niclosamide). Results:The JAK2/STAT3 pathway was inhibited and the expression of related genes and proteins was downregulated in lung cancer after carbon ion irradiation. Immune scoring based on the ssGSEA algorithm showed that FOXP3 expression was significantly negatively correlated with CD8 + T cell infiltration in the immune microenvironment of lung cancer. The role of targeting the JAK2/STAT3 pathway in increasing CD8 + T cell infiltration in lung cancer was further clarified by carbon ion irradiation combined with STAT3 inhibition (niclosamide). Conclusion:Carbon ion irradiation ( 12C 6+) can play a synergistic role with immunotherapy by targeting the JAK2/STAT3 pathway.

Heavy ion radiation has significant radiological and biological advantages over conventional radiation. While directly killing tumor cells, heavy ion beam can reduce immune escape and promote the initiation and activation of effector T cells by inducing immunogenic death of tumor cells, regulating tumor phenotype, enhancing antigen formulation, and changing tumor microenvironment to regulate the immune response. This article will review the immunomodulatory effect of heavy ion beam and the molecular mechanisms associated with immune checkpoint inhibitor therapy.