Liang Yin

Gastric cancer (GC) remains a leading cause of global cancer mortality, with progression and therapy resistance heavily influenced by the dynamic tumor microenvironment (TME). Despite advances in surgical techniques, chemotherapy, targeted therapy, and immunotherapy, overall survival for advanced disease remains poor, underscoring the need for a deeper understanding of resistance mechanisms. A hallmark of the TME is metabolic reprogramming, which sustains tumor growth and actively shapes an immunosuppressive landscape. This review aims to detail the coordinated metabolic adaptations of GC cells, cancer-associated fibroblasts (CAFs), and immune cells within the TME, focusing on nutrient competition, immunosuppressive metabolite accumulation, and dysregulated lipid metabolism. We analyze how glucose depletion, lactate accumulation, and amino acid deprivation establish a hostile metabolic niche that impairs cytotoxic T lymphocyte (CTL) function while paradoxically supporting regulatory T cells (Tregs), M2-like tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs). We examine four major immunosuppressive metabolic pathways, lactate, adenosine, tryptophan-kynurenine, and arginine and demonstrate their convergence on immune checkpoint upregulation, forming an integrated metabolic-immune checkpoint axis. These pathways establish a self-reinforcing immunosuppressive circuit that drives T cell exhaustion and limits immune checkpoint blockade efficacy. We highlight emerging therapeutic strategies targeting this crosstalk, including inhibitors of glycolysis, glutaminolysis, indoleamine 2,3-dioxygenase 1 (IDO1), and adenosine signaling, often combined with immunotherapy. The metabolic supply-demand mismatch explains why certain interventions can revive effector cells while potentially harming other cell types. Finally, we discuss challenges and future directions, emphasizing the need for spatially resolved metabolic profiling, biomarker-driven patient stratification, and personalized therapies to overcome metabolic immunosuppression and improve clinical outcomes in GC.

Dietary microRNAs have attracted increasing attention in the field of aging research due to their potential regulatory roles, highlighting a novel direction for nutritional strategies in anti-aging interventions.

Introduction: Advanced gastric cancer (AGC) treatment outcomes are improved with PD-1 blockade immunochemotherapy, but predicting responders remains challenging. Cytokines, key immune response regulators, may predict treatment outcomes. Aims: This study investigates the potential of cytokines as predictive biomarkers in AGC patients.Material and methods: In this retrospective analysis, 241 patients with AGC were included, with 136 patients receiving an immunochemotherapy regimen that included PD-1 blockade, while 105 patients constituted the control group receiving chemotherapy alone. Serum levels of various cytokines (IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-1β, IL-17A, IFN-α2, IFN-γ, TNF-α and IL-12p70) were measured using a Luminex after the initiation of treatment.Results: Patients undergoing PD-1 blockade immunochemotherapy demonstrated a significant elevation in the levels of IL-6, IL-8, and IL-17A, especially within the group that exhibited a therapeutic response, when compared to the control group. Notably, among those who responded to the immunochemotherapy, there was a marked reduction in the concentrations of IL-6, IL-8, and IL-17A over the course of the treatment. In contrast, such reductions were not observed in the non-response group. Among the assessed cytokines, the combined evaluation of IL-6, IL-8, and IL-17A, in conjunction with CA-125, demonstrated the highest predictive accuracy for assessing the efficacy of immunochemotherapy in AGC patients.Conclusions: Our study identifies IL-6, IL-8, and IL-17A cytokines as predictive biomarkers for treatment outcomes in AGC patients receiving immunochemotherapy. Combining these cytokines with CA-125 significantly enhances predictive accuracy, enabling tailored treatment strategies to improve patient outcomes.

Background Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with both genetic and environmental risk factors. The PON1 rs854560 (L55M) polymorphism has been implicated in cancer susceptibility through its role in oxidative stress regulation, but its association with CRC remains unclear, particularly in Asian populations. Aim This study aimed to investigate the association between the PON1 rs854560 polymorphism and CRC susceptibility in a Chinese cohort, while assessing its impact on PON1 expression and enzymatic activity. Method A case-control study was conducted on 1,003 CRC patients and 1,303 healthy controls. The impact of the Pon1-rs854560 SNP was assessed by comparing the genotypes of individuals diagnosed with CRC to those of controls without the disease. Results Genotype distribution showed slight differences between the case and control groups. The frequency of the AA genotype was slightly lower in the case group (91.72%) than in the control group (93.71%). The AT genotype was observed at similar frequencies in both groups (8.28% in the case group and 6.14% in the control group). Notably, the TT genotype was absent in the case group but present in 0.15% of the control group. Genotype combination analysis suggested that individuals carrying the AT + TT genotype (8.28%) had a higher susceptibility to CRC compared to those with the AA + AT genotype (100%). Allele frequency analysis revealed a slightly higher frequency of allele T in the case group (8.28%) than in the control group (6.45%). Additionally, lower PON1 mRNA and protein expression were associated with CRC progression, including features such as poorer differentiation, deeper tumor invasion, and vascular, nerve, and lymphatic metastasis. Conclusion The PON1 rs854560 polymorphism influences CRC risk in Chinese individuals, likely through reduced PON1 expression and detoxification capacity. These findings highlight its potential as a genetic biomarker for CRC susceptibility and suggest PON1’s role in tumor progression. Further studies should validate these associations in diverse populations and explore therapeutic strategies targeting PON1 activity.

Inflammatory breast cancer (IBC) is an aggressive and rare form of breast cancer with a poor prognosis. The occurrence of bilateral IBC in a short period of time is extremely rare. In this case report, a 54-year-old woman diagnosed with invasive ductal carcinoma of the left breast underwent lumpectomy, lymph node dissection, chemotherapy, and radiotherapy but opted against trastuzumab treatment. Four years later, she experienced bilateral breast inflammation, skin changes, edema, and heat (calor). Biopsies confirmed breast cancer metastasis to both breasts. Whole-Exome Sequencing revealed genetic mutations, including PIK3CA and C4orf54, in both primary and recurrent tumors, with significant downregulation in the recurrent tumors. KEGG analysis suggested potential enrichment of axon guidance signal pathways in both tumors. The patient showed a partial response after treatment with liposome paclitaxel, along with targeted therapy using trastuzumab and pertuzumab. This case report sheds light on the rare occurrence of bilateral inflammatory breast cancer post-HER-2 treatment and highlights the importance of genetic profiling in understanding the disease. Further research on clinical targets for breast cancer management is warranted.

Background: Mastectomy (MT) and breast conservation surgery (BCS) are two common surgical options for the treatment of locally advanced breast cancer (LABC). Neoadjuvant chemotherapy (NACT) is frequently administered before surgery to shrink tumors and improve surgical outcomes. However, there is a lack of consensus on the optimal surgical approach after NACT and its impact on survival outcomes. Objective: This meta-analysis aims to compare the survival outcomes between MT and BCS in patients treated with NACT. Method: A PRISMA selection was used to identify studies across electronic database such as PubMed, and Cochrane Library from inception until 11^th July, 2023. A total of 10 comparative studies involving a total of 5018 patients were included. Among them, 2898 patients underwent MT while 2120 underwent BCS after receiving NACT. The outcomes assessed were the 5-year overall survival (OS) and 5-year disease-free survival (DFS). The data from the included studies were pooled, and odds ratios (OR) with 95% confidence intervals (CI) were calculated to evaluate the differences between MT and BCS in terms of survival outcomes. Prospero: CRD42024496831. Result: The meta-analysis revealed that patients who underwent MT after NACT had a higher 5-year OS compared to those who underwent BCS (OR 2.68, 95% CI [2.19-3.28; p < 0.00001]). Additionally, the 5-year DFS was significantly better for patients who underwent MT (OR 3.11, 95% CI [1.80-5.38; p < 0.0001]). Conclusion: MT after NACT may be associated with better 5-year OS and DFS compared to BCS.

In this article, we present a rare case of breast metastasis of lung cancer. Chest computed tomography (CT) for a woman in her early 50s indicated right lung malignancy, multiple bone metastases, and an irregular mass in her right breast. Further inquiry into the case history revealed that the patient had been aware of the breast mass for 3 years, without respiratory symptoms. Biopsy of the breast mass suggested estrogen receptor (ER) (+), progesterone receptor (PR) (−), and human epidermal growth factor receptor 2 (HER2) (+ +) breast cancer. The patient was initially diagnosed with breast cancer with lung and bone metastasis. However, comprehensive breast cancer treatment was ineffective, and thyroid transcription factor-1 (TTF-1), napsin A, and cytokeratin 7 (CK7) were evaluated to better understand the origin of the cancer. To the best of our knowledge, this patient had the longest reported disease course from presentation with a breast lump as the first symptom to the final diagnosis of breast metastasis of lung cancer. To provide a better reference for differential diagnosis of ambiguous tumors, we also performed a systematic literature review.