BMC Cancer最新文献

Background: Cancer in the cervical region of the uterus is a major health issue for women. A live bacterial vector therapeutic vaccine is genetically engineered to stimulate a targeted immune response by integrating the target antigen gene into a live, attenuated vector. Listeria has become a focal point for bacterial vaccine vectors, owing to its distinctive intracellular parasitism and ability to process and present antigens. Antibiotic-resistant plasmids in vaccines present a dual risk, including the promotion of antibiotic resistance and in vivo instability. The implementation of a balanced lethal system can effectively mitigate both challenges.

Methods: We constructed therapeutic vaccinations for cervical cancer with dual-species Listeria vectors-attenuated Listeria monocytogenes (LM) with act A/plc B/dal/dat deletion (LM∆∆dd) and recombinant Listeria ivanovii (LI) whose hemolysin gene (ilo) is substituted with the hly gene of LM and with dal/dat deletion (LI∆ilo::hly∆∆dd). Recombinant Listeria-vectored therapeutic vaccines for cervical cancer, expressing HPV6/11/16/18 E6E7 proteins, were constructed based on the balanced lethal system. The basic biological characteristics of the vaccines were described. The vaccinations were evaluated for biosafety, stability, and immunogenicity in mice, and their efficacy was assessed in subcutaneous HPV16/18 E6/E7-expressing tumor models.

Results: This study demonstrates that recombinant Listeria expressing multivalent HPV E6/E7 proteins exhibit broad-spectrum anti-tumor effects against cervical cancer models. The study showed that the vaccination strains effectively expressed multivalent HPV antigen, exhibited plasmid stability in vitro, and had no significant impact on biochemical reactions and hemolytic activity. In mice, the vaccine strain was biologically safe, and the plasmid remained stable in vivo. A heterologous immunization strategy-LM prime-LI boost-LM final-was employed to immunize the mice, resulting in a robust, antigen-specific cellular immune response. In the subcutaneous HPV16/18 E6/E7-expressing tumor models, this vaccination protocol achieved complete tumor cure rates of 30% and 40%, respectively, and significantly extended the median survival time.

Conclusions: Our objective was to evaluate the efficacy of the vaccine against subcutaneous HPV16/18 E6/E7-expressing tumor models, enhance its safety profile, and co-express multivalent HPV antigens to target a broader range of cervical cancer types.

Gliomas are primary malignant brain tumors with poor prognosis. Conventional therapies have achieved limited improvements, and there is an urgent need for new treatments. Homologous recombination repair (HRR) defects are observed in many types of cancer and confer increased sensitivity to platinum-based chemotherapies and poly-ADP ribose polymerase (PARP) inhibitors. To our knowledge, HRR mutations in gliomas have not been extensively reported. To this end, we analyzed alterations in 39 HRR related genes and divided patients with glioma into different groups according to HRR LOF mutation status. We then analyzed the differences in genetic mutation landscape, TMB, CNV burden, prognosis, and immune-related features between the HRR-LOF group and the NonHRR-LOF group. The results demonstrated that compared to the non-HRR-LOF group, the HRR-LOF group exhibited a higher mutation frequency of IDH1, increased TMB, and poor prognosis in IDH-mutant patients. In summary, gliomas patients with HRR LOF have relatively more unstable genomes and might benefit from the combination and sequential use of PARP inhibitors, radiotherapy, and immunotherapy.

Background: Complement Factor H (CFH) has been reported as an indispensable role in innate and adaptive immunity. Despite increasing interest in CFH, its clinicopathological implications and immunological mechanisms across different cancers remain unclear and are currently under debate.

Methods: Investigating the function of CFH in 23 tumor types using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), The Tumor Immune Estimation Resource 2.0 (TIMER2.0) database, cBioportal, Human Protein Atlas (HPA). Then using Cell Counting Kit-8 (CCK8) assay, plate colony formation assay, and wound healing assay to detect the biological function of CFH in vitro.

Results: CFH exhibited dysregulated expression across multiple cancers, with associations observed between its expression levels, immune cell infiltration, clinical stage, and immune subtype. Additionally, CFH was critically involved in shaping the tumor microenvironment and regulating immune responses. The upregulated expression level of CFH was significantly related to tumor-infiltrating immune cells (TICs), tumor mutational burden (TMB), and microsatellite instability (MSI). Functionally, we found that knockdown of CFH could inhibit the tumor cell proliferation and invasion.

Conclusions: This study implies the potential prognostic and immunological role of CFH in various cancers, and CFH could act as a biomarker for tumor immunotherapy.

Objective: This study aimed to develop scientific and standard evaluation indicators related to bladder dysfunction after cervical cancer surgery, providing a reference for clinical nurses in China.

Methods: According to the framework of the Nursing Outcomes Classification (3rd edition), nursing outcomes and indicators were screened through a literature review and clinical investigation. Subsequently, the Delphi expert consultation method was used to revise and determine the core outcomes and indicators.

Results: A total of 28 experts participated in the correspondence consultation. The valid recovery rates for the two rounds were 93.33% and 100%, respectively. The expert authority coefficient averaged 0.90, and the Kendall harmony coefficient ranged between 0.216 and 0.352 (P < 0.05). Finally, 7 core nursing outcomes and 57 indicators were identified for patients with bladder dysfunction after cervical cancer surgery.

Conclusion: The revised core nursing outcomes and indicators are valuable for developing specialized nursing measures and evaluating nursing outcomes for patients with bladder dysfunction after cervical cancer surgery. Additionally, they provide a reference for promoting standardized nursing language in China.

Background: Fibroblast growth factor receptor 4 (FGFR4) is overexpressed in up to 50% of pancreatic ductal adenocarcinoma (PDAC) cases. BLU9931, a selective FGFR4 inhibitor, exerts cytotoxic effects on PDAC cells and induces cellular senescence. This study aimed to investigate the effects of BLU554, another selective FGFR4 inhibitor, whose efficacy and safety in hepatocellular carcinoma has been proven in clinical trials, on PDAC cell lines.

Methods: BLU554 was applied to PDAC cell lines, and cytotoxicity in PK-1 and T3M-4 cells was assessed by counting viable cells. BLU554-induced senescence was detected using γH2AX immunocytochemical staining; qualitative polymerase chain reaction (qPCR) analysis of CDKN1A, LMNB1, and senescence-associated secretory phenotype (SASP) factors; transmission electron microscopy of lysosomal structures and numbers; and the senescence-associated-β-galactosidase assay. In addition, we assessed whether dasatinib and quercetin, two representative senolytic agents, could reduce the viability of BLU554-treated cells, using an ATP assay.

Results: BLU554 suppressed the growth of PK-1 and T3M-4 cells, which express high FGFR4 levels, with a stronger effect in T3M-4 cells. Cellular senescence, which can be triggered by chemotherapy-induced stress, was induced in both PK-1 and T3M-4 cells, as evidenced by elevated γH2AX expression. Treatment with BLU554 increased the number of PDAC cells exhibiting lysosomal enzyme activity abnormalities, as indicated by SA-β-galactosidase staining. The number of PDAC cells showing lysosomal morphological alterations, observed under transmission electron microscopy, also increased. Increased CDKN1A and decreased LMNB1 mRNA levels, combined with changes in the expression of SASP factors, further confirmed the induction of cellular senescence. Application of the senolytic drugs dasatinib or quercetin significantly reduced the viability of BLU554-treated cells, which are associated with increased malignancy.

Conclusions: This two-step strategy may represent a novel therapeutic approach for the treatment of therapy-resistant PDAC through senescence induction and subsequent senolysis.

Background: Undernutrition contributes to nearly half of global cancer-related deaths. In Ethiopia, previous studies using the Subjective Global Assessment (SGA) have reported an undernutrition prevalence of 30-60% among cancer patients. The Global Leadership Initiative on Malnutrition (GLIM) criteria offer a standardized, evidence-based approach by combining phenotypic and etiologic factors. However, their application and related evidence remain limited in Ethiopia, particularly in Bahir Dar City.

Objective: To assess the prevalence of undernutrition and its associated factors among adult cancer patients receiving follow-up care at public referral hospitals in Bahir Dar City, Northwest Ethiopia, in 2024.

Methods: An institution-based cross-sectional study was conducted among 403 cancer patients on follow-up at Felege Hiwot and Tibebe Ghion Comprehensive Specialized Hospitals from June 8 to July 8, 2024. Participants were selected using a simple random sampling technique. Data were collected via face-to-face interviews using a structured questionnaire and through chart reviews. Anthropometric measurements, dietary intake, and clinical data were used to assess undernutrition based on the GLIM criteria. Data were entered using the KoboToolbox and analyzed with SPSS version 26. Bivariable and multivariable binary logistic regression analyses were conducted to identify factors associated with undernutrition. Statistical significance was determined at a 95% confidence interval (CI) and p-value < 0.05.

Results: The study included 393 participants, yielding a response rate of 97.8%. The prevalence of undernutrition among adult cancer patients was 50.3% (95% CI: 44.4%-55.5%), with 31.5% classified as severely undernourished and 18.8% as moderately undernourished. Multivariable analysis identified four factors significantly associated with undernutrition: loss of appetite (AOR = 18.21, 95% CI: 10.01-33.12), presence of chronic comorbidities (AOR = 3.86, 95% CI: 1.67-8.94), female sex (AOR = 2.17, 95% CI: 1.17-4.03), and larger tumor size, with the highest risk observed in T4 tumors (AOR = 17.98, 95% CI: 6.45-29.19).

Conclusion: Undernutrition was common among adult cancer patients in Bahir Dar City, with loss of appetite, female sex, tumor size, and comorbidities as significant predictors. Early application of the GLIM criteria, management of treatment-related symptoms, and targeted nutrition interventions for high-risk groups, particularly women, are recommended to improve patient outcomes.

Clinical trial number: Not applicable.