MedComm最新文献

The growing emphasis on precision medicine in the management of solid tumors has underscored the limitations of traditional diagnostic approaches, which often lack sufficient sensitivity or rely on invasive procedures. In contrast, peripheral blood biomarkers provide a minimally invasive, dynamic, and potentially more accurate means for cancer detection and monitoring. The enhancement of detection technology has enabled the incorporation of an increasing number of biomarkers into exploratory clinical trials, which, in turn, have demonstrated immense clinical utility. However, numerous hurdles remain before these biomarkers can be applied in a real clinical setting. This review comprehensively summarizes the clinical utility of key blood-based biomarkers, including circulating tumor cells, circulating tumor DNA, extracellular vesicles, cell-free RNA, peripheral blood mononuclear cells, and proteins. We discuss their biological characteristics, detection methodologies, and recent advances in their clinical applications. Moreover, we highlight the emerging role of new technologies such as artificial intelligence (AI) in decoding complex data and facilitating clinical decision-making. It is expected to establish the overarching concept of the blood biomarker panel and to understand its comparative advantages, which are essential to realize its potential in precision oncology.

FBXW7 (F-box and WD repeat domain-containing 7) is a classic tumor suppressor that promotes ubiquitylation and degradation of various oncoproteins. Although its tumor suppressor role in many types of cancers has been established, whether and how FBXW7 regulates in vivo esophageal tumorigenesis was previously unknown. Here, we report, using genetically modified mouse models, that Fbxw7 inhibits esophageal tumorigenesis induced by the carcinogen 4NQO (4-nitroquinoline N-oxide), but not by Pik3Ca^E545K (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), a frequently mutated gene in human esophageal squamous cell carcinoma (ESCC). Mechanistically, FBXW7 depletion causes the accumulation of SPT6 (suppressor of Ty6), a transcriptional elongation factor, which is a novel substrate of FBXW7. SPT6 acts as a transcriptional co-activator of ΔNp63, which is also a substrate of FBXW7 in ESCC cells. Both SPT6 and ΔNp63, accumulated upon FBXW7 knockdown, contribute to the proliferation of ESCC cells. In clinical human ESCC tissues, the protein levels of SPT6 and FBXW7 are inversely correlated, and high SPT6 levels with low FBXW7 levels predict poorer patient survival. Collectively, FBXW7 acts as a tumor suppressor in ESCC by promoting the degradation of both SPT6 and ΔNp63, and the SPT6-ΔNp63 axis may serve as a therapeutic target for ESCC.

Fertility-preserving treatment (FPT) offers a critical option for young women diagnosed with atypical endometrial hyperplasia (AEH) or early-stage endometrial cancer (EC), however, the commonly used methods for evaluating complete regression (CR) are invasive. This study aimed to develop a non-invasive tool to predict treatment outcomes using radiomics and molecular profiling. We retrospectively analyzed 146 patients with AEH or early EC receiving FPT. Radiomic features extracted from MRI were used to construct a radiomics signature predictive of CR through a machine-learning approach. A radiomics-clinical nomogram integrating radiomics scores with clinical variables demonstrated excellent predictive performance, with area under the curve values of 0.963 and 0.986 in the training and validation cohorts, respectively. Patients stratified into high- and low-score groups based on radiomics scores showed significantly different CR rates, with the high-score group exhibiting a lower likelihood of CR. Single-cell RNA sequencing further confirmed immune alterations in the high-score group, including reduced CD8⁺ T-cells, and elevated levels of M2 macrophages. Bulk RNA sequencing revealed upregulation of oxidative phosphorylation and lipid metabolism pathways, suggesting a metabolically active and immunosuppressive tumor microenvironment. This radiomics-based approach holds promise for guiding individualized FPT strategies for AEH and early EC patients.

Chemotherapy is the mainstay in the treatment of advanced gastric cancer (GC); yet, GC showed diverse responses to first-line chemotherapy regimens and the underlying molecular basis is still not clear. Here, we established a system that combined organoid-based chemotherapy regimen screening and transcriptome-based evaluation to identify underlying molecular signatures of different responses to chemotherapy. We generated 19 GC patient-derived organoids (PDOs) from surgically resected specimens with corresponding histological characteristics of parent tumors and tested all of the five most commonly used first-line chemotherapy regimens. Based on the treatment responses, PDOs were classified into double-sensitive, single-sensitive, and not-sensitive groups. PDOs that responded well to chemotherapy presented high expression levels of the P53 pathway genes and low expression levels of cell proliferative activity genes. Furthermore, the chemotherapy-based tumor classification of GC was established. The GC tumor classification was verified by multi-omics features from the TCGA dataset and public drug response datasets. In conclusion, this study systematically evaluated clinical chemotherapy regimens for GC and identified chemotherapy response-associated molecular signatures based on human GC organoids, which are beneficial to the precise treatments of GC.

Body mass index (BMI) is traditionally used to diagnose overweight and obesity, but it is influenced by physiological variables. This study tested the hypothesis that body weight is nonlinearly related to age and height, and that an optimized multivariate allometric model (OMAM) could correct for these effects and define a new criterion for overweight diagnosis. A total of 1498 Chinese Han adults were enrolled. The normal weight group (BMI < 25.0 kg/m², n = 1224) was divided into subgroup A (n = 857) to develop OMAM equations and determine the threshold, and subgroup B (n = 367) to validate them. The overweight group (BMI ≥ 25.0 kg/m², n = 274) was used to test the new criterion. OMAM corrected the nonlinear influence of age, height, and sex on weight. A corrected weight value $W_C$ >1.1440 was defined as the new threshold. This criterion reclassified 21.9% of overweight individuals as normal weight and reduced false positives, notably lowering the overweight rate to 61.3% in men, while minimizing unnecessary interventions. Compared with BMI, the new criterion showed higher specificity and accuracy in identifying diabetes, hypertension, coronary heart disease, and metabolic syndrome in the external CAPITAL cohort. These findings support the clinical utility of OMAM in overweight screening. Further validation in non-Chinese Han populations is warranted.

Despite the remarkable therapeutic advances achieved with immune checkpoint inhibitors in advanced melanoma, treatment options remain limited for patients with refractory subtypes. This study evaluated a novel combination of DNV3 (anti-LAG-3), toripalimab (anti-PD-1), and chemotherapy (nab-paclitaxel/cisplatin) in 27 Asian patients with unresectable or metastatic melanoma (77.8% [21/27] previously treated with anti-PD-[L]1 and 22.2% [6/27] treatment-naïve mucosal melanoma; subtypes: 13 mucosal, 6 acral, 5 cutaneous, and 3 of unknown primary origin). The regimen achieved an overall response rate (ORR) of 44.4%, which was further elevated to 54.5% in the subgroup of 11 patients with hepatic metastases. Notably, it also demonstrated substantial efficacy in anti-PD-(L)1-resistant cases, with a 42.9% ORR and a median progression-free survival (PFS) of 7.36 months. Among treatment-naïve mucosal melanoma, the ORR reached 50%. At data cutoff, median overall survival remained unreached in all cohorts. Grade ≥3 treatment-related adverse events initially occurred in 55.6% of participants; subsequent dose modification of nab-paclitaxel (from 260 mg/m² to 200 mg/m²) improved tolerability, reducing the incidence of grade ≥3 events to 22.2%. Immune-related toxicities (grade 3-4, 22.2%) were clinically manageable. Therefore, the combination of LAG-3/PD-1 blockade and chemotherapy demonstrated promising efficacy, notably in treatment-naïve mucosal melanoma with liver metastases. (Chinese Clinical Trial Registry number, ChiCTR2400079543).

Antimicrobial resistance represents a significant global health threat, demanding alternative treatments beyond traditional antibiotics. Phage therapy has resurged as a promising solution to address this challenge. This manuscript offers an in-depth examination of phage applications in clinical settings, encompassing the treatment of multidrug-resistant infections, prevention of hospital-acquired infections, and development of phage-based vaccines. Advanced strategies are explored, including phage-antibiotic synergy, biomaterial-enhanced delivery systems to improve phage stability, and the rational design of engineered phages to expand host range and optimize lytic efficacy. Additionally, the application of genetic engineering to broaden phage host ranges and convert temperate phages into lytic variants is discussed. In hospital infection prevention, phages demonstrate substantial potential, such as eliminating bacterial biofilms on medical devices, disinfecting environmental surfaces, and controlling waterborne pathogens in hospital water systems. Furthermore, phages offer a versatile platform for vaccine development, facilitating efficient antigen display and nucleic acid delivery. Despite progress, challenges persist in pharmacokinetics, standardized production, and regulatory approval. This review synthesizes recent preclinical and clinical developments, emphasizing the transformative potential of phage-based therapies while acknowledging the barriers to their clinical implementation.

Companion diagnostics (CDx) plays a pivotal role in precision medicine by enabling personalized treatment plans based on individual biomarker profiles. This approach can enhance therapeutic efficacy in selected indications and may reduce healthcare expenditures. Particularly in oncology, precision targeted therapies targeting pathways such as EGFR, HER2, and programmed death-1/programmed death-ligand 1 have established robust models for biomarker-driven treatment. However, rapid advancements in diagnostic technologies, expanding application scopes, and increasingly complex mechanisms of biomarker resistance are presenting new challenges for CDx. This review comprehensively examines the evolving regulatory landscape, current clinical applications across various solid tumors and hematologic malignancies, and diverse methodological platforms ranging from next-generation sequencing and immunohistochemistry to emerging liquid biopsies and point-of-care testing. It also delves into persistent barriers in CDx development, including tumor heterogeneity, test standardization, trade-offs between tissue biopsy and liquid biopsy, and the economic complexities of codevelopment and reimbursement mechanisms. By synthesizing existing knowledge and projecting future trends, this paper serves as a valuable resource for researchers, regulators, and clinicians. It provides critical insights to guide the synergistic development of drugs and diagnostics, paving the way for their integration into a more dynamic, artificial intelligence-enhanced, and multiomics-driven healthcare ecosystem.

Atherosclerotic cardiovascular diseases (ASCVDs) remain the primary cause of morbidity and mortality. Macrophages are involved in the progression and regression of atherosclerosis, and macrophage amino acid metabolism is important during this process. Here, we identified that the expression of cystine/glutamate antiporter Slc7a11 was upregulated by oxidized low-density lipoprotein, and specifically enhanced in the macrophages of atherosclerotic plaques. Macrophage-specific Slc7a11 overexpression in ApoE null mice (ApoE^{- /-} Slc7a11^MOE ) attenuated atherosclerotic lesions and increased the plaque stability under a 16-week western diet. ApoE^{- /-} Slc7a11^MOE displayed unchanged blood lipids, decreased inflammatory cytokines, and increased antioxidant capacity. Mechanistically, Slc7a11-mediated cystine uptake and glutathione synthesis inhibited the classically activated macrophage (M1) polarization via reducing Stat1 phosphorylation, and promoted alternatively activated macrophage (M2) polarization via enhancing Stat6 phosphorylation. Macrophage-targeting lipid nanoparticles loading with ferrostatin-1, an antioxidant reagent, promotes Slc7a11-mediated glutathione synthesis, also enhanced plaque stability and ameliorated the progression of atherosclerosis. These findings reveal a critical role of Slc7a11 in the phenotypic switch of macrophage and indicate that Slc7a11-mediated amino acid metabolism could be utilized as a novel therapeutic strategy in the prevention of ASCVDs.