Volume 27, Issue 5

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, with more than 600,000 deaths expected by 2022. Given that prognosis is heavily influenced by early detection, comprehensive strategies addressing the multifactorial nature of gastric carcinogenesis are urgently needed. This review aims to synthesize current evidence on GC prevention, diagnosis, and predictive modeling, highlighting gaps and future directions. We present an extensive analysis of risk factors, including the role of Helicobacter pylori infection and dysbiosis in the gastric microbiome. Furthermore, we evaluate vaccination strategies, emerging clinical and molecular diagnostic techniques (e.g., serum biomarkers, genomic profiling), and predictive tools leveraging statistical models and artificial intelligence (AI). By integrating these themes, this review provides a multidimensional perspective on GC management, emphasizing translational potential. Our findings underscore the need for tailored screening programs and AI-driven innovations to improve outcomes in high-risk populations.

Periodontal inflammation, a hallmark of periodontitis, has well-known detrimental effects on oral health. Emerging evidence suggests it may also contribute to the development of oral squamous cell carcinoma (OSCC) as well as the progression of oral potentially malignant disorders (OPMDs). Chronic periodontal inflammation may contribute to oncogenesis through multiple mechanisms. The underlying biology involves the inflammatory cytokines production, immune cell infiltration, oxidative stress, and their impact on cellular behavior. Furthermore, low-grade systemic inflammation emerging from microbial dysbiosis may promote cancer cell survival, proliferation, and immune evasion – key processes in carcinogenesis. The interaction between periodontal pathogens and host tissues is closely intertwined with the progression toward epithelial dysplasia, epithelial–mesenchymal transition (EMT), and neoangiogenesis. While most of the evidence supports the association between OSCC and periodontitis, the limitations of these studies, the presence of confounding factors, and conflicting findings call this relationship into question. In this context, this review aims to discuss the most recent evidence regarding the link between periodontitis and oral carcinogenesis, with a particular focus on the ecological and molecular mechanisms underlying epithelial dysplasia, tumor initiation, progression and metastasis, while also providing new perspectives for its prevention and treatment.

Radiation pneumonitis (RP) is a common complication following radiotherapy for thoracic tumors, significantly impacting treatment efficacy and patient quality of life. Identifying and predicting risk factors for RP has become a key research focus. This study aims to summarize current knowledge by analyzing previously published studies and large clinical trials. A systematic literature search was conducted in Embase, PubMed, and Web of Science for publications up to November 1, 2024, using keywords such as “radiation pneumonitis”, “risk factors”, “machine learning”, etc. Inclusion criteria prioritized clinical relevance and methodological rigor. Identified RP-related factors include radiation dose parameters (e.g., V20, mean lung dose [MLD]), clinical characteristics (e.g., age, interstitial lung disease), inflammatory markers (e.g., IL-6, neutrophil-to-lymphocyte ratio [NLR]), and features from imaging and multi-omics analyses. In addition, traditional dosimetric indicators remain central, while recent advances integrate radiomics and artificial intelligence (AI)-driven models to improve predictive accuracy. Despite progress, challenges such as limited sample sizes, lack of standardization, and insufficient multi-center validation persist. Future efforts should prioritize data integration, model optimization, and clinical translation to better predict RP risk and guide individualized interventions.

Glycosylation, a prevalent post-translational modification, involves the enzymatic addition of sugar moieties to specific amino acid residues in proteins. Aberrant glycosylation – stemming from dysregulated glycan-related gene expression – is increasingly recognized as a hallmark of cancer, including hematologic malignancies such as acute myeloid leukemia (AML). This study discusses: (1) glycosylation patterns in AML as biomarkers – AML and related myeloid disorders display specific alterations including enhanced sialylation, fucosylation, O-GlcNAcylation, and truncated O-glycans. These modifications influence cell adhesion, signaling, and disease subtypes, offering diagnostic and prognostic value, (2) therapeutic strategies targeting glycosylation pathways, including receptor glycosylation: approaches include inhibitors of glycosyltransferases, mevalonate-pathway blockers (e.g., statins), glycomimetic compounds, and combination regimens with TKIs or immunotherapies. Early-phase clinical trials support feasibility, and (3) the impact of altered glycosylation on immunosurveillance: abnormal glycan structures interact with lectins (e.g., galectins and siglecs), impairing T and NK cell function and promoting immune escape. Together, these insights support the rationale for developing glycosylation-focused therapeutic approaches to improve AML treatment outcomes.

Objectives Non-small cell lung cancer (NSCLC) treatment is complicated by interactions between cancer and stromal cells, as well as drug resistance linked to ATP-binding cassette (ABC) transporters. While previous studies have explored ABC transporter expression and drug responses in patient-derived NSCLC cultures, the impact of culture duration remains unclear. This study compares short-term and long-term primary culture models to assess how extended culture affects the composition of cancer-stromal cells, ABC transporter expression (ABCB1, ABCC1, ABCG2), and sensitivity to chemotherapy and tyrosine kinase inhibitors (TKIs). Methods Two treatment-naïve NSCLC patients (EGFR wild-type, squamous cell carcinoma) were selected to ensure uniform histology and molecular background for comparative analysis of short- and long-term cultures. An immunofluorescence-based assay using the ImageXpress Pico system and automated image analysis with CellReporterXpress ® software was used to quantify cytotoxicity and ABC transporter expression. Results The findings revealed an increased proportion of cancer cells at the expense of stromal cells throughout the prolonged culture duration (approximately 2- to 3-fold). Extended culture conditions were linked to a significantly higher baseline expression of ABC transporters (e.g., 2- to 3.5-fold increase in ABCB1, ABCC1, and ABCG2 expression in cancer cells) and a marked reduction in sensitivity to chemotherapeutics (e.g., a 22-fold increase in resistance to carboplatin). Conclusions This study shows that culture duration significantly impacts drug response and ABC transporter expression in NSCLC models, highlighting the importance of tailoring culture conditions for ex vivo screening based on the therapeutic class, especially when comparing cytotoxic drugs and TKIs.

Objectives Muscle density (MD), an indicator of myosteatosis that reflects intramuscular adipose tissue infiltration, has been reported as a prognostic factor in cancer patients, while the prediction of MD in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiotherapy (nCRT) remains unknown. This research aims to fill the gap in this type of conclusion. Methods This dual-center retrospective study included 408 patients with LARC who received radical surgery after nCRT. Patients were stratified into low and normal MD groups according to sex-specific quartile values. Pre-nCRT CT scans were applied to measure MD. Univariate and multivariate analyses were used to analyze relationships between MD and short-term outcomes (including tumor regression grade [TRG] and tumor downstaging) and long-term outcomes (including disease-free survival [DFS] and overall survival [OS]). Results Among the 408 patients, 87 (21.3 %) experienced recurrence, and 54 (13.2 %) died by the last follow-up. Low MD was independently associated with poorer DFS (HR=1.709, p=0.024) and OS (HR=2.586, p=0.007). However, MD was not significantly correlated with short-term outcomes such as TRG or tumor downstaging. Conclusions MD is an independent prognostic biomarker for long-term outcomes in LARC patients. Its assessment through routine pre-nCRT CT scans is feasible and cost-effective, making it a potential addition to clinical protocols. Further research is needed to standardize cut-off values and explore underlying mechanisms.

Objectives Pancreatic cancer stem cells (CSCs) are known culprits of recurrent pancreatic ductal adenocarcinoma (PDAC). The disputable presence of CSCs in continuous cell lines has led to an extensive application of patient-derived CSC culture for experimentation. However, obtaining patient biopsies remains a challenge for many laboratories. Here, this study aimed to investigate the presence of CSCs in KRAS-driven PDAC cell lines. Methods Cell viability assays evaluated the cytotoxicity of gemcitabine and vismodegib in PDAC cell lines. Flow cytometry was used to analyse the expression of pancreatic CSC surface markers. Tumoursphere-forming ability was investigated by culturing cells in serum-free and non-adherent conditions in vitro , while the tumourigenicity of PDAC cells was assessed in immunocompromised mice. Molecular events were delineated by Western blotting, and SOX2-expressing cells in tumour xenografts were detected by immunohistochemistry. Results PANC-1 and Capan-2 cell lines showed exceptional chemoresistance, with Capan-2 containing a notable number of putative CSCs that co-expressed CD44, CD24, and CD133 (3.7 % of the total population) and sustained the cytotoxicity of gemcitabine. The Capan-2 cell line harbours tumoursphere-forming cells, of which self-renewal was inhibited by foetal bovine serum. The presence of these cells is consistent with Capan-2 being highly tumourigenic in immunocompromised mice. MAPK, PI3K-AKT, NF-κB, and WNT pathways were activated, and SOX2 expression was upregulated during the self-renewal of putative CSCs. SOX2-expressing cells were correspondingly present in xenografts of highly tumourigenic Capan-2 cell lines. Conclusion The Capan-2 cell line contains a subset of putative CSCs, whose self-renewal is driven by MAPK, PI3K-AKT, NF-κB, and WNT pathways.

Objectives To enhance cancer immunotherapy specificity and evade immune clearance, we developed MGLD (Macrophage membrane/gelatin/laponite/doxorubicin) nanoparticles (≈130 nm) encapsulated with doxorubicin. This system aims to improve tumor targeting, prevent immune clearance, and induce autophagy and immunogenic cell death (ICD) in cancer cells. Methods MGLD nanoparticles were engineered with macrophage membranes to reduce immune system phagocytosis and enhance tumor targeting. In vitro and in vivo assays evaluated the nanoparticles’ accumulation, penetration, cytotoxicity in tumor tissues, and ability to induce immunogenic cell death (ICD). Results MGLD nanoparticles accumulated in tumors, penetrated deep into tissues, and induced ICD. Acidic tumor microenvironment and MMP-2 facilitated rapid DOX release, enhancing anticancer efficacy with minimal macrophage toxicity. MGLD showed excellent stability, pH sensitivity, and negligible in vivo toxicity, stimulating autophagy and ICD. Conclusions The results demonstrate that MGLD nanoparticles are a promising candidate for targeted cancer therapy. This biomimetic system enhances drug targeting and efficacy, overcoming the limitations of conventional chemotherapy and offering a transformative therapeutic strategy.

Objectives Osteosarcoma, a prevalent malignant bone tumor in pediatric and adolescent populations, is characterized by a markedly diverse tumor microenvironment (TME) that complicates therapeutic intervention. Among the key components of the TME, M2 macrophages contribute to immune suppression, tumor progression, and resistance to therapy. This study aims to explore the immune microenvironment of osteosarcoma and identify key immunosuppressive components using integrated transcriptomic analysis. Methods We integrated scRNA-seq (GSE152048) and bulk RNA-seq (TARGET) data to characterize the osteosarcoma tumor microenvironment. Key analyses included cell clustering and annotation (Seurat), pseudotime trajectory (Monocle 2), cell-cell communication (CellChat), and M2 macrophage deconvolution (CIBERSORT, BayesPrism). Gene modules were identified via WGCNA, and drug sensitivity was predicted using oncoPredict. Key genes were validated by qRT-PCR and Western blot. Results Our integrated analysis revealed that M2 macrophage infiltration was significantly associated with an immunosuppressive tumor microenvironment in osteosarcoma. Weighted gene co-expression network analysis (WGCNA) identified gene modules highly correlated with M2 macrophage abundance and immune evasion signatures. Reduced M2 infiltration was linked to altered transcriptional patterns and increased predicted sensitivity to Etoposide and Doxorubicin. Two immune-related genes, PTK2B and PTPRC, were significantly upregulated in osteosarcoma samples and validated by RT-qPCR and Western blotting in U2OS cells. Conclusions This study demonstrates that M2 macrophage infiltration is a defining feature of the osteosarcoma immune microenvironment and is associated with immune suppression. Through integrative transcriptomic analysis, PTK2B and PTPRC were identified as key immune-related genes linked to M2 macrophage abundance and patient prognosis. These results establish a transcriptional basis for the immunosuppressive phenotype in osteosarcoma.

Objectives This study aims to explore the crucial functions of adenosine-related genes (ARGs) in immune activity and the development of ovarian cancer (OC). Methods Adenosine score was calculated by “GSVA” package. Key module genes were identified by weighted correlation network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to select ARGs, which were combined to develop a RiskScore model. Gene set enrichment analysis (GSEA) was conducted for functional enrichment analysis, and immune infiltration in different risk groups was assessed. Somatic mutation was analyzed by MuTect2 and visualized by “maftools” package. The viability, migration, and invasion of two OC cell lines (A2780 and SK-OV-3) were measured by cell counting kit-8 (CCK-8), wound healing, and Transwell assays. Results To accurately predict the prognosis of OC, 9 ARGs ( PIK3CG , VSIG4 , MATK , PIEZO1 , RARRES1 , SELL , S1PR4 , IL18BP and CD40LG ) were identified to construct a RiskScore model. Functional enrichment analysis revealed that immunity-correlated pathways were predominantly enriched in the low-risk group, whereas inflammation-associated pathways were significantly enriched in the high-risk group. In vitro assays revealed a high expression of most of the 9 ARGs in OC cells, except MATK and SELL . Notably, silencing VSIG4 markedly suppressed the proliferation, migration, and invasion of the OC cells. Conclusions This study not only provides novel insights into the prognosis evaluation of patients with OC but also offers possibilities for formulating targeted therapeutic strategies and personalized treatment plans.

Objectives This study aims to assess the diagnostic value of cytopathology evaluation, including morphological examination and cytology-based HPV detection, in head and neck squamous cell carcinoma (HNSCC). Methods We evaluated the diagnostic efficacy of cytopathology for primary HNSCC in 78 patients and compared HPV detection accuracy in primary or metastatic tumors from 132 HNSCC patients using the Aptima mRNA assay on cytological samples vs. p16 IHC on histological samples. To resolve discordances between Aptima HPV testing and p16 IHC, RNAscope in situ hybridization served as the adjudicative assay for HPV status classification. When Aptima HPV assay and p16 IHC results were disconcordant, RNAscope was served as the definitive reference standard. Results Among patients with unsuccessful histological biopsies (7/78, 9.0 %), primarily due to sampling difficulties, the majority (5/7, 71.4 %) were diagnosed using cytology. For patients who had successful histological biopsies but could not be definitively diagnosed by histopathology (13/71, 18.3 %), approximately half (6/13, 46.2 %) had their diagnoses confirmed by cytology. In the HPV detection for 132 primary or metastatic lesions from HNSCC patients, the Aptima mRNA assay showed higher specificity (98.8 vs. 89.2 %, p=0.018) and positive predictive value (98.0 vs. 84.5 %, p=0.020) than p16 IHC, with similar sensitivity (98.0 vs. 100 %, p>0.99) and negative predictive value (98.8 vs. 100 %, p>0.99). Conclusions Cytology is effective in the morphologic diagnosis of primary HNSCC. It can complement preoperative pathological biopsies. The cytology-based Aptima HPV assay improves the accuracy of p16 IHC. Therefore, cytological strategies enable more accurate diagnosis and classification of HNSCC.

Objectives Due to increasing severity of resistance to first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR -mutant non-small cell lung cancer (NSCLC) patients, this study investigated whether artesunate overcomes such resistance specifically to icotinib hydrochloride (icotinib) and explored its mechanisms. Methods We evaluated anti-tumor effects of artesunate in icotinib- and cross-resistant NSCLC models (NCI-H1975, PC-9/GR cells, and NCI-H1975 xenografts). Effects of GAB1 knockdown/overexpression and artesunate on EGFR–Gab1–SHP2–ERK and EGFR–PI3K pathways were analyzed. Clinical correlations between Gab1 and phosphorylated Gab1 (pGab1) expressions and outcomes were analyzed in specimens. Results Artesunate significantly inhibited proliferation and induced apoptosis in resistant EGFR -mutant/T790M+ models. Gab1 overexpression characterized icotinib-resistant cells. GAB1 knockdown suppressed SHP2/phosphorylated ERK (pERK) expression, reducing proliferation and promoting apoptosis. Rescue experiments confirmed that GAB1 overexpression promoted proliferation and suppressed apoptosis via ERK activation. Artesunate downregulated phosphorylated EGFR (pEGFR), pGab1, SHP2, pERK1/2, and total EGFR/Gab1. Downregulated pGab1 was correlated with improved efficacy of first-line EGFR-TKIs and patient prognosis. Patients with low pGab1 expression exhibited significantly prolonged median progression-free survival (PFS; 17.3 vs. 8.8 months, HR=0.345, p<0.001) and a significantly elevated objective response rate (ORR; 83.9 % vs. 31.0 %, p<0.001) compared to those with high pGab1 expression. Conclusions Artesunate overcomes icotinib resistance in NSCLC through suppression of proliferation and activation of apoptosis via the EGFR–Gab1–SHP2–ERK axis. Gab1 regulates resistance via SHP2–ERK, highlighting its therapeutic potential. These findings support artesunate as a clinically translatable agent for overcoming resistance of first-generation EGFR-TKIs.

Objectives The impact of anesthetic drugs on cancer cells is controversial. As propofol and sevoflurane are widely used in gastric cancer surgery, this study aimed to investigate their effects on microRNA (miRNA) expression in plasma extracellular vesicles (EVs) and on circulating gastric cancer cells during surgery. Methods We collected the plasma of 10 patients with gastric adenocarcinoma who were anesthetized with propofol or sevoflurane for sequencing. Differentially expressed miRNAs were screened via DESeq2 and verified by qPCR in another 18 paired samples from nine patients before and after propofol anesthesia. Plasma EVs were stained with PKH26 and cocultured with GES-1 and AGS cells, and miR-122-5p expression was determined. The target genes were analyzed using MiRanda/RNAhybrid/KEGG/KM plotter. Results 19 (13 upregulated/6 downregulated) and 5 (2 upregulated/3 downregulated) differentially expressed miRNAs were identified after propofol and sevoflurane, respectively. MAPK, AKT1, AKT2, and EGFR were the target genes of the propofol-upregulated miRNAs. miR-122-5p expression in the plasma EVs of patients after propofol increased by an average of 6.2-fold (p=0.011). After coculture, hsa-miR-122-5p expression was significantly greater in both the GES-1 and AGS cell lines than in the control group. High expression of the hsa-miR-122-5p target gene PPP2R2D was significantly correlated with reduced overall survival (hazard ratio [HR] = 1.56, p=5.5 × 10 −5 ), whereas high expression of PPP2R5B predicted poorer survival (HR=1.41, p=6.7 × 10 −5 ). Conclusions miR-122-5p in plasma EVs was affected by propofol and serves as an inhibitor of gastric cancer.