Cancer Medicine最新文献

Background: Advances in cancer therapy have improved survival, but cardiovascular disease (CVD) is now the leading non-cancer cause of death among survivors. Specialized cardio-oncology care mitigates risk, yet access remains limited outside of urban academic centers.

Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) 17 Registries (2000-2021), including 6,467,098 individuals with first primary malignancies. Outcomes were CVD-specific mortality, estimated using standardized mortality ratios (SMRs) and excess absolute risks (EARs). Exposures were county-level urban/rural status, persistent poverty status, and racial composition. Cancer-specific analyses were additionally performed for major cancer sites to assess heterogeneity in county-level disparities.

Results: During follow-up, 394,540 CVD deaths occurred (SMR = 1.11; 95% CI = 1.11, 1.11). Survivors in rural counties (SMR = 1.27), counties with persistent poverty (SMR = 1.35), and those with the highest quartile of Black residents (SMR = 1.15) had significantly higher CVD mortality compared with the general population. The highest risk was observed in rural counties with persistent poverty (SMR = 1.53). Across county groups, CVD mortality peaked within the first year after diagnosis and remained elevated for over a decade in disadvantaged communities. Substantial heterogeneity was found across cancer types in county-level disparities in CVD mortality, with the largest EAR differences observed among survivors of lung and bronchus cancer, followed by corpus uteri, prostate, and urinary bladder cancers.

Conclusions: Cancer survivors experience substantial and sustained excess CVD mortality, with the greatest disparities in rural and persistently impoverished counties. These findings highlight the need to integrate cardiovascular surveillance into survivorship care and expand access to cardio-oncology services in socially vulnerable communities.

Background: Imeglimin (IME) is a novel oral anti-diabetic agent with a similar chemical structure to metformin, which has shown broad-spectrum anti-tumor activity. However, the activity of imeglimin on tumor cells remains unclear. This study investigated the effects of IME on multiple myeloma (MM) cells and explored the underlying mechanisms.

Methods: The effects of IME on MM cell proliferation were evaluated in vitro using MM cell lines and in MM cell-derived xenograft (CDX) models. Seahorse metabolic analyses and RNA-Seq were performed in IME-treated and control MM cell lines. Single-cell transcriptomic data were further analyzed to assess the role of IL-16 in the bone marrow microenvironment.

Results: IME inhibited MM cell proliferation and tumor growth in MM cell-derived xenograft (CDX) models by inducing G1/G0 cell cycle arrest. IME suppressed oxidative phosphorylation and promoted glycolysis. IL-16 mRNA expression was downregulated, and multiple cytokine-cytokine receptor interaction pathways were altered following IME treatment. The anti-MM effect of IME was partly mediated by increased lactate production and decreased IL-16 expression. Single-cell transcriptomic data further demonstrated that IL-16 plays an important role in the bone marrow microenvironment of MM.

Conclusions: These findings suggest that IME may represent a novel approach for targeting IL-16 and energy metabolism in the treatment of MM.

Background: Breast cancer (BC) in men accounts for less than 1% of all BC diagnoses worldwide. Despite its low incidence, the number of men being diagnosed is increasing. Historically perceived as a predominantly female disease, BC in men has received comparatively limited attention.

Aim: This review aims to examine how BC manifests in men and explored the impact of stigma and awareness on diagnosis and prognosis.

Methods: A narrative review of current literature was undertaken, including epidemiological studies, clinical research and psychosocial analyses relating to male BC.

Results: Male BC shares several pathological and molecular features with female BC, but notable differences exist in presentation, tumour biology and treatment considerations. Men are more likely to present at a later stage of disease, often due to low awareness and misconception that BC affects only women. Stigma and limited targeted education further contribute to delayed medical consultation.

Discussion: Although understanding of male BC has improved, challenges remain in early detection and awareness. The gendered perception of BC may discourage men from seeking timely medical advice, leading to more advanced disease at diagnosis and potentially poorer outcomes.

Conclusion: Addressing stigma, increasing public and professional education and promoting clinical research inclusive of men are essential to improving timely diagnosis and outcomes.

Background: Synovial sarcoma (SS) is a rare soft tissue malignancy comprising 5%-10% of all sarcomas, typically affecting young adults. It is characterized by a pathognomonic SS18-SSX gene fusion, with variable histologic subtypes demonstrating epithelial and mesenchymal features. This study investigates the association between epithelial-to-mesenchymal transition (EMT) gene expression and metastatic potential in SS.

Methods: A retrospective, single-institution analysis was conducted using primary tumor specimens from 21 treatment-naïve SS patients. RNA sequencing was performed on formalin-fixed paraffin-embedded (FFPE) tissue to assess gene expression profiles. EMT scores were calculated using three independent methods: Hallmark EMT gene set from GSEA, the 76-gene EMT signature (76GS), and Kolmogorov-Smirnov (KS) testing. Patients were categorized into metastatic and nonmetastatic cohorts, and phenotype-specific survival analyses were conducted.

Results: Tumors from patients who developed metastases showed significant enrichment of EMT-related genes (GSEA NES 1.71, P = 0.025), oxidative phosphorylation, and immune-related pathways. EMT scores were consistently higher (more mesenchymal) in metastatic tumors across all scoring methods. Mesenchymal phenotype was associated with significantly worse overall survival (GSEA log-rank P = 0.0009).

Conclusions: This study demonstrates a correlation between mesenchymal gene expression signatures and increased metastatic risk in SS. EMT status, derived from primary tumor profiling at diagnosis, may serve as a potential prognostic biomarker. These findings support further investigation into EMT as a stratification tool for tailoring treatment intensity and surveillance strategies in SS.

Introduction: Leukaemia is the most common cancer in children, with incidence rates increasing. Chromosomal translocations are considered one of the leukaemia-initiating events; however, the causes of many translocations remain unknown. Epidemiological studies have identified environmental exposures associated with altered risk of childhood leukaemia; however, there is little understanding of the molecular role they play in the aetiology of leukaemia. It is plausible that they contribute to the induction of translocations.

Methods: In this exploratory study, in vitro techniques were used to screen for the induction of translocations in response to environmental exposures suggested to be associated with childhood leukaemia risk that is, caffeine, benzene (smoking/air pollution), cotinine (smoking) and folate. Using physiologically relevant concentrations, NALM6 cells were exposed to each risk factor for up to 96 h. Reverse transcription PCR assays were used to detect common childhood leukaemia-associated translocations, TCF3::PBX1 and RUNX1::RUNX1T1.

Results: Preliminary experiments observed TCF3::PBX1 and RUNX1::RUNX1T1 translocations in benzene and cotinine exposed cells, including concentrations equivalent to passive smoke exposure. TCF3::PBX1 translocations were observed in caffeine-exposed cells at concentrations observed during pregnancy. TCF3::PBX1 and RUNX1::RUNX1T1 translocations were observed in cells grown in varying folic acid concentrations including levels within the normal physiological range.

Conclusions: Our preliminary data provides proof of principle to suggest that environmental factors associated with childhood leukaemia risk have the potential to induce chromosomal translocations. Whilst this study is not designed to estimate in vivo risk or translocation frequency, it has allowed us to demonstrate a biologically plausible mechanism for epidemiological associations. Understanding the risk factors contributing to leukaemia-initiating events will be essential to refine public health policy and tailor prevention strategies.

Purpose: The purpose of this study was to determine the feasibility and acceptability of a Hispanic adapted culturally relevant Exercising Together^© intervention (HACER) through a single-arm pilot in post-treatment Hispanic men with prostate cancer and their caregivers.

Methods: Dyads participated together in a live, remote group-based 12-week exercise intervention with resistance training three times a week. Primary outcomes were intervention feasibility and acceptability. Secondary outcomes were measures of physical and psychosocial health. Assessments were completed at baseline and post-intervention. Mean difference and effect sizes were calculated to determine intervention effects.

Results: Accrual of eligible dyads was 75%. Fourteen eligible dyads were allocated to intervention. Attendance averaged 62%. Retention was 79% with 95% assessment completion. Participants rated HACER as acceptable and 86% would recommend the program to other dyads. Self-reported physical activity level and objective physical function improved for survivors and caregivers, with clinically significant improvement in caregiver depressive symptoms.

Conclusions: HACER was feasible and acceptable with modest improvements in physical and psychosocial health, especially for Hispanic survivors. HACER shows promise as a scalable intervention to improve health outcomes for Hispanic cancer survivors and caregivers when they train together; a larger, fully powered efficacy trial is warranted.

Background: ASXL1 mutation acute myeloid leukemia represents a clinically aggressive subtype with heterogeneous outcomes. Current evidence remains inconclusive regarding the prognostic relevance of the KRAS mutation partner in AML with ASXL1 mutation. The comprehensive mutational landscape and prognostic implications of co-occurring driver mutations remain poorly characterized.

Methods: A total of 2788 consecutive AML patient records were reviewed. A comprehensive clinicogenomic analysis was conducted on 451 AML patients with ASXL1 or KRAS mutations from the discovery cohort (n = 394) and the independent validation cohort (n = 57) to assess the correlation between molecular profiles and clinical outcomes.

Results: The KRAS mutation was observed in 22 (9.9%) AML cases with the ASXL1 mutation. Notably, survival analysis revealed that the ASXL1^mut/KRAS^mut subtype demonstrated trends toward inferior overall survival (OS) and relapse-free survival (RFS) relative to ASXL1 single subgroups. Stratified by mutational status, patients with ASXL1^mut/KRAS^mut exhibited significantly inferior 2-year OS rates (30.5% vs. 59.1% vs. 73.9%; p < 0.001) and short 2-year RFS (32.7% vs. 59.4% vs. 69.5%; p = 0.002) compared to ASXL1^mut/KRAS^wt or ASXL1^wt/KRAS^mut mutation counterparts. This association persisted in the BeatAML invalidation (OS: 0% vs. 43.1% vs. 69.3%; p = 0.026). This association persisted in the PSM analysis. This co-mutation confers an exceptionally poor prognosis comparable to that of TP53 mutations or complex karyotypes. HSCT showed no significant survival benefit after landmark analysis (OS; p = 0.292).

Conclusions: These results demonstrate the independent prognostic value of ASXL1^mut/KRAS^mut co-mutation and define a novel ultra-adverse-risk subtype of acute myeloid leukemia.

Objective: Primary poor graft function (PGF) is a common and serious complication after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This study retrospectively evaluates the efficacy and safety of a novel combination therapy consisting of low-dose decitabine, donor lymphocyte infusion (DLI), and eltrombopag for the treatment of primary PGF subsequent to haplo-HSCT.

Methods: In this analysis of ten patients, decitabine was administered at a dose of 7 mg/m²/day for three consecutive days, followed by DLI on the fifth day and eltrombopag, which was started at 50 mg/day and titrated up to 150 mg. The primary endpoints of the study encompassed hematologic recovery.

Results: Nine patients (90%) achieved a complete response with normalized blood counts, while one patient (10%) showed a partial response with transfusion independence. Adverse events included manageable graft-versus-host disease (GVHD) in four patients.

Conclusion: These findings indicate that this triple therapy represents a promising approach for the management of primary PGF following haplo-HSCT.

Introduction: This study investigates the correlations and risk factors of complications associated with different urinary diversion methods after radical cystectomy (RC) for bladder cancer (BC).

Methods: A retrospective analysis was conducted on 574 bc patients treated between 2012 and 2022. Complications were categorized as early or late occurrences. Multistate Cox regression and stepwise logistic regression models were employed to identify independent predictors. Heat maps were utilized to explore correlations among complications.

Results: Patients undergoing ureterostomy were generally older, had a higher prevalence of comorbidities, and exhibited a greater propensity for late urinary tract infections (UTIs), nephrolithiasis, and anxiety/depression. Bricker conduits were linked to small-bowel obstruction and ureteroenteric strictures, while orthotopic neobladders were associated with incontinence and urinary retention. Diabetes increased risks of urolithiasis and mild bowel obstruction but decreased strictures and reflux. High pathological grade predicted strictures; low hemoglobin increased obstruction and late UTIs. Robot-assisted laparoscopy reduced early UTIs, reflux, and ostomy-related obstruction. Bowel obstruction risk was elevated in patients with higher body mass index or smoking history but was mitigated by robotic approaches. Late UTIs were strongly linked to ureterostomy and heavy smoking.

Conclusion: Ureterostomy raises the risk of UTIs, kidney issues, and psychological disorders, necessitating careful follow-up. Bricker conduits require monitoring for bowel complications, while orthotopic neobladders are linked to incontinence and metabolic problems, demanding careful patient selection. Advanced age, heavy smoking, T4 stage, and long hospital stays are key predictors of complications and should guide preoperative risk assessment. Robot-assisted laparoscopy lessens gastrointestinal and stoma-related events.

Cancer was the second leading cause of death worldwide in 2018 according to WHO. The disease burden continues to grow and has tremendous impacts on families and healthcare systems. Cancer-related fatigue is one of the most distressing symptoms experienced by cancer patients and has adverse impacts on the patients' quality of life and functioning. Both pharmacological and non-pharmacological interventions could be adopted to tackle cancer-related fatigue. Among non-pharmacological interventions, exercise training is recommended by various authorities, such as the American College of Sports Medicine and the National Comprehensive Cancer Network, to manage cancer-related fatigue. In particular, resistance training with moderate-intensity exercise has been proven to be the most effective intervention for alleviating cancer-related fatigue. Chinese martial art that includes moderate-intensity physical training with a strong mind-body component is believed to offer mental well-being and stress reduction benefits in addition to the benefits of traditional resistance training, thus potentially enhancing the overall quality of life of cancer patients. This systematic review and meta-analysis aimed to identify the effectiveness of Chinese martial arts training in reducing cancer-related fatigue in cancer patients. Sixteen randomised controlled trials (RCTs) with 1365 cancer patients were included in this systematic review and meta-analysis. All of the included studies had implemented either Tai Chi or Baduanjin as the martial arts training intervention. The results of the meta-analysis showed that the overall effects of the trainings were not significant (standardised mean difference [SMD]: -0.23, 95% confidence interval [CI]: -0.57 to 0.11, p = 0.19). In the sub-group analysis, martial arts training administered over a shorter intervention period (less than 12 weeks) was found to yield a significant medium-to-large pooled effect size on the reduction of cancer-related fatigue (SMD: -0.77, 95% CI: -1.54 to -0.01, p = 0.05). PROSPERO Registration Number: CRD42023416590.