Cancer Hospital of Shantou University Medical College

Early treatment can effectively ameliorate cognitive decline and slow disease progression in vascular cognitive impairment (VCI). Glymphatic system dysfunction may significantly contribute to the onset and progression of diverse neurodegenerative diseases. To investigate its influence on VCI, we used dynamic contrast-enhanced magnetic resonance imaging to observe the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) in the brains of vascular dementia (VD) model and SHAM rats, and used the Morris water maze and hematoxylin–eosin staining to confirm the predictive value of the glymphatic system for VCI. The clearance rate of the CSF contrast agent, Gd-DOTA, from the brain interstitial space was slower in the VD than in the SHAM group. Behavioral tests showed a robust negative correlation between VCI and retention of Gd-DOTA contrast agents in the hippocampal region of VD rats. Pathology revealed a significant positive correlation between the number of apoptotic neurons in the hippocampal CA1 region and Gd-DOTA retention in the hippocampal region of VD rats. The clearance of brain ISF was hindered in the model rats, indicating that glymphatic system damage contributed to cognitive impairment in this group. Our findings suggest that glymphatic system function may be a predictor of VD development.

N1-Methyladenosine (m1A) is a prevalent RNA modification that governs RNA metabolism, structure, stability, and translation. Yet its cancer-wide landscape and functional impact remain largely unexplored. Here, we delineate the m1A regulatory network in lung squamous cell carcinoma (LUSC). The dominant m1A writer of TRMT6 emerged as the most up-regulated regulator in LUSC through a comprehensive pan-cancer analysis; both TRMT6 expression and global m1A levels significantly distinguished LUSC from normal tissue, serving as potent diagnostic biomarkers. Functionally, TRMT6 installs m1A marks and facilitates their cellular export. Both the in vitro and in vivo experiments reveal that TRMT6 accelerates LUSC proliferation by orchestrating cell-cycle gene expression. Mechanistically, TRMT6 binds cell-cycle transcripts, most notably TOPBP1 and DSN1, promotes the formation of m1A, and stabilizes these mRNAs via the YTHDF3 reader pathway. A single, critical m1A site in each target mRNA is sufficient to boost TOPBP1 and DSN1 expression. Using dCasRx-TRMT6, we further show that site-specific m1A deposition on DSN1 mRNA is a potent strategy to modulate its expression and drive proliferation. Collectively, our findings uncover a previously unrecognized m1A-dependent regulatory axis that underpins LUSC diagnosis and progression.

Current intraoperative cancer diagnosis predominantly relies on frozen section histopathology, which is time-consuming and prone to sampling bias. Development of techniques for intraoperative cancer diagnosis is urgently needed. Notably, malignant tumors manifest distinctive microenvironmental signatures characterized by acidic pH gradients and elevated ATP concentrations, which are important biomarkers for tumor identification. Based on these signatures, a pH/ATP dual-sensitive bioluminescent nanoprobe, d-luciferase-liposome-PEOz (DLPNPs), was engineered using thin-film hydration. The nanoprobe displayed a spherical morphology (∼140 nm in diameter), low pH-dependent activation (pH <6.5), and good biocompatibility in vitro. Ex vivo bioluminescence imaging of freshly resected specimens from five murine tumor models (breast, liver, colon, lung, and tongue) and five human cancer types (breast, colorectal, endometrial, lung, and gastric) demonstrated significantly elevated tumor signals compared to normal tissues. The median tumor-to-background ratios (TBRs) were 21.49 (IQR, 8.86–105.7) in mice and 47.89 (IQR, 5.27–238.9) in humans. The nanoprobe achieved 100% sensitivity and 100% specificity in cancer diagnosis, with an area under the curve (AUC) of 1.00 across all cancer types evaluated in both mouse and human tissues. Microscopic analysis further confirmed precise colocalization between bioluminescent signals and malignant regions. Notably, the entire workflow, from nanoprobe application to image acquisition, requires less than 10 min. These findings indicate that DLPNPs enable rapid and accurate intraoperative tumor diagnosis by leveraging tumor microenvironmental signatures. The multicancer applicability, high TBR, and streamlined workflow indicate that DLPNPs are worthy of further evaluation for clinical translation in future studies with larger sample sizes and more diverse cancer cohorts.

The neoadjuvant chemoradiotherapy (nCRT) might accentuate surgical complications and toxicity in the treatment of locally advanced rectal cancer (LARC) while neoadjuvant chemotherapy (nCT) alone shows promise as an alternative treatment. However, which patients deserve most from the nCT need further clarify. This trial aimed to assess the non-inferiority of nCT with capecitabine plus oxaliplatin (CAPOX) versus nCRT with capecitabine in LARC with uninvolved mesorectal fascia (MRF). Patients with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to receive 4 cycles of CAPOX chemotherapy alone (nCT group) or CRT with concurrent Capecitabine (nCRT group). The primary end point is 3-year locoregional recurrence-free survival (LRRFS). Secondary end points, such as 3-year disease-free survival (DFS), 3-year overall survival (OS), and adverse events (AEs), were also reported. A total of 663 patients were enrolled and 589 patients received the allocated treatment (nCT, n = 300; nCRT, n = 289). LRRFS was analyzed with a median follow-up of 48 months. 3-year LRRFS was 97.4% (95% CI, 95.5 to 99.3) in the nCRT group and 96.3% (95% CI, 94.0 to 98.6) in the nCT group, resulting in a hazard ratio (HR) of 1.40 (95% CI, 0.53 to 3.68). The nCT and nCRT achieved similar 3-year DFS (89.2% v 87.9%; HR, 0.88 [95% CI, 0.54 to 1.44]) and 3-year OS (95.0% v 94.1%; HR, 0.86 [95% CI, 0.42 to 1.76]). The nCT group showed a lower incidence of grade 2 to 4 long-term AEs (16.0% v 26.3%, P = 0.002) and proctitis (33.6% v 41.7%, P = 0.049) compared with nCRT group. The non-inferiority of nCT was not confirmed with a very low incidence of local recurrence in both group. But nCT offers comparable DFS and OS while mitigating the burden of toxicity as compared to nCRT. These insights shed light on a potential paradigm shift in the treatment for LARC with uninvolved MRF.

Abstract Background: RJBC 1501 (NCT02455141) is a prospective phase III study to compare the efficacy and safety of adjuvant epirubicin plus cyclophosphamide (EC) followed by taxanes (T) versus same regimen plus carboplatin (EC-TCb) in early-stage triple negative breast cancer (TNBC). Methods: Patients with node positive or node negative (with tumor size ≥1.0cm) TNBC who received definitive surgery were randomized 1:1 to receive EC-T or EC-TCb. Taxanes consisted of either weekly paclitaxel for 12 doses or docetaxel every 3 weeks for 4 cycles. Carboplatin was given weekly (AUC 2) for 12 doses or every 3 weeks (AUC 5-6) for 4 cycles, concurrent with taxanes. The primary endpoint was disease-free survival (DFS) in the intention-to-treat (ITT) population. Secondary endpoint includes distant DFS (DDFS), overall survival (OS), and safety. Results: Between March 2016 and March 2023, 786 patients were randomized (EC-T: n = 391; EC-TCb: n = 395). Baseline characteristics were balanced: median age ≤50 years (49.6%), T1 stage (46.6%), node-negative (72.3%). A majority of patients (76.5%) received 3-weekly docetaxel. After a median follow up of 4.52 (IQR 2.83 to 6.06) years, 103 events were reported: 62 in the EC-T group and 41 in the EC-TCb group. Addition of carboplatin significantly improved DFS (hazard ratio [HR], 0.66; 95% CI, 0.44 to 0.97, P = 0.034), with 3-year DFS of 89.8% (95%CI 86.8 to 92.9%) for EC-T and 93.1% (95%CI 90.5 to 95.7%) for EC-TCb. EC-TCb regimen was also associated with a superior DDFS (HR, 0.61; 95% CI, 0.38 to 0.98, P = 0.040) and OS (HR, 0.39; 95% CI 0.16 to 0.94, P = 0.029) compared to EC-T treatment. Grade 3-4 adverse events were more frequent among EC-TCb arm (49.9%) than EC-T arm (38.7%), primarily driven by higher rates of neutropenia (47.0% vs 37.8%) and thrombocytopenia (4.5% vs 0%). Other grade 3-4 toxicities were comparable between groups. Conclusion: Adding carboplatin to adjuvant EC-T chemotherapy significantly improves DFS, DDFS, and OS in patients with early-stage TNBC. While additional carboplatin treatment was associated with increased hematologic toxicity, no new safety signals emerged. Citation Format: X. Chen, J. Huang, H. Shi, J. Zhu, W. Wu, G. Ye, Q. He, Y. Shi, A. Zhang, X. Xie, X. Wang, X. Chen, W. Wu, J. Wu, Z. Li, Z. Li, Y. Dai, W. Ren, Q. Shao, Y. Chen, Y. Zeng, M. Pegram, K. Shen. Adjuvant epirubicin plus cyclophosphamide followed by taxanes with or without carboplatin for early stage triple-negative breast cancer (RJBC 1501): a randomized controlled phase III trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF2-03.

The tumor node metastasis (TNM) staging system does not fully capture tumor heterogeneity, underscoring the needs for reliable biomarkers for prognostication in non-metastatic nasopharyngeal carcinoma (NPC). While inflammatory markers have shown potential, the prognostic value of pre-treatment peripheral absolute monocyte count (AMC) in treatment-naive, non-metastatic NPC remains underexplored. This retrospective cohort study analyzed 2,046 patients with newly diagnosed treatment-naive, non-metastatic NPC from 2009 to 2022. The optimal AMC cut-off value (0.63×109/L) for distant metastasis-free survival (DMFS) was determined using maximally selected rank statistics method. Patients were stratified into low AMC (<0.63×109/L, n=1370) and high AMC (≥0.63×109/L, n=676) groups. The primary endpoints were DMFS, bone metastasis-free survival (BMFS), and overall survival (OS). Associations were assessed using Kaplan-Meier analysis, log-rank tests, Cox proportional hazards models, restricted cubic splines (RCS), subgroup analyses and sensitivity analyses. Diagnostic performance was evaluated using time-dependent receiver operating characteristic (tROC) analysis at 1, 3, and 5 years. Over a median follow-up of 77.4 months, distant metastasis, bone metastasis, and death occurred in 13.5%, 6.9%, and 24.2% of patients, respectively. High pre-treatment AMC was independently associated with significantly worse DMFS (hazard ratio [HR]=1.33, 95% confidence interval [CI]: 1.05-1.70, P = 0.020), BMFS (HR = 1.86, 95%CI: 1.33-2.60, P<0.001), and OS (HR = 1.34, 95%CI: 1.11-1.61, P = 0.002) in fully adjusted models. RCS revealed a linear association between AMC and metastasis risk (P for non-linearity >0.05), but a non-linear threshold effect for OS (P for non-linearity=0.011). The risk of all-cause mortality increased with AMC >0.54×109/L, eventually reaching a plateau. Subgroup analyses confirmed the feasibility of AMC's prognostic value across all patient strata (P for interaction>0.05). Time-dependent ROC analysis demonstrated the highest discriminatory accuracy for predicting 1-year bone metastasis (AUC = 0.720), while maintaining moderate prognostic utility for distant metastasis and overall survival across 1 to 5 years. Pre-treatment peripheral AMC ≥0.63×109/L could serve as an independent predictor of metastatic progression, particularly bone metastasis, and reduced survival in treatment-naive, non-metastatic NPC. Being easily obtainable via routine complete blood count, AMC provides significant prognostic value to enhance clinical risk stratification and guide individualized treatment planning.

30 to 70% of patients with positive sentinel lymph nodes (SLNs) in early breast cancer do not develop non-SLN metastases. They are exposed to the potential complications and sequelae of axillary lymph node dissection (ALND) without gaining additional therapeutic benefit. Therefore, a prediction model for non-SLN metastasis is needed. We identified the anatomical location of metastatic SLNs as a key factor for predicting non-SLN status. We retrospectively identified 1,717 consecutive patients who underwent SLN biopsy; 481 SLN-positive patients treated from 2009 to 2019 underwent completion ALND and formed the development cohort, and 113 SLN-positive patients treated from 2020 to 2022 served as a temporal validation cohort. A multivariable logistic regression model was developed and presented as a nomogram. Performance was assessed by discrimination and calibration, and clinical utility by decision curve analysis. The Memorial Sloan Kettering Cancer Center (MSKCC) and Shanghai Cancer Hospital (SCH) models were evaluated for comparison. Multivariate analysis revealed eight independent predictors of non-SLN metastasis: metastatic SLN location, tumor size, multifocality, lymphovascular invasion, extracapsular extension, number of positive and negative SLNs, and size of SLN metastasis. The nomogram based on these variables achieved high discrimination in both the training (AUC = 0.830) and validation (AUC = 0.785) cohorts. In the temporal validation cohort, discrimination was higher than the MSKCC model (AUC= 0.690; P = 0.033) and numerically higher than the SCH model (AUC = 0.716; P = 0.088). At prespecified false-negative rate targets, the model identified 0.9%, 23.0%, and 27.4% of patients as candidates for omitting completion ALND under FNR thresholds of 0%, <5%, and <10%, respectively, and yielded a higher net benefit than the comparator models across clinically relevant risk thresholds. The model also maintained performance in patients with ≥3 positive SLNs (AUC = 0.843). Metastatic SLN location relative to the ICBN is a novel anatomical predictor of non-SLN metastasis. A nomogram incorporating this variable demonstrated good discrimination and clinical utility in a single-center cohort with temporal validation; prospective multicenter validation with standardized ICBN assessment is warranted before broader implementation.

IntroductionJinfu’an Decoction (JFAD), a traditional Chinese medicine, is used to treat lung cancer and has shown significant anti-tumor effects in clinical and experimental studies. This study integrates metabolomics and gut microbiota analysis to elucidate JFAD’s anti-tumor mechanisms.MethodsA suspension of A549-luc cells, approximately 1 × 106 in number, was injected subcutaneously into the right axilla of mice to establish a tumor-bearing nude mouse model. Mice were randomly assigned to four groups: model group (MG), low-dose JFAD (JFAD-L), medium-dose JFAD (JFAD-M), and high-dose JFAD (JFAD-H), receiving treatments via gavage for 21 days. Additionally, three nude mice formed the normal group (NG), receiving no treatment. Changes in gut microbiota and serum metabolites were assessed using 16S rRNA gene sequencing and UHPLC-QE-MS non-targeted metabolomics.ResultsJFAD may help restore the balance of intestinal flora in mice with lung cancer to a more normalized state. Our findings indicate that JFAD increases the abundance of Bacteroidia and decreases the presence of Firmicutes and Clostridia, thereby altering intestinal bacterial composition. Primary metabolic pathways associated with significant differences include nicotinate and nicotinamide metabolism, glycine, serine and threonine metabolism, and pyrimidine metabolism. A key differential metabolite identified was succinic acid, part of the central carbon metabolism pathway in cancer. Succinic acid showed a negative correlation with gut microbiota families Tannerellaceae and Campylobacterota. In the MG group, essential amino acid levels were markedly diminished but were significantly elevated after JFAD-M intervention. KEGG pathway analysis identified these amino acids as being linked to the PI3K/AKT and mTOR signaling pathways.DiscussionJFAD regulates the homeostasis of intestinal flora and influences amino acid and succinic acid metabolism through various pathways. These mechanisms could serve as potential targets for JFAD in inhibiting lung cancer invasion and metastasis.