Journal of Cancer Research and Clinical Oncology最新文献

Purpose: Physical activity is associated with a lower mortality and recurrence risk in cancer, yet the underlying mechanisms remain unclear. This study aimed to evaluate the effects of running sessions on the tumorigenic potential of prostate cancer cells using a 3D in vitro model.

Methods: Fifteen healthy males completed two outdoor running sessions (5 km and 10 km), interspersed by 1 month of wash-out time. Blood samples were collected before (PRE), immediately after (POST), and 3 h after (POST-3 h) sessions. Human serum (HS) samples were used to stimulate LNCaP and PC3 cell lines in 3D in vitro culture technique. The spheroid formation ability was quantified after 21 days of incubation, using GelCount.

Results: In both prostate cancer cell lines, a reduction in spheroid number was shown, by both running sessions and in all timepoints considered (LNCaP cells: 5 km: - 23.8%; 10 km: - 5.6% POST HS; 5 km: - 37.8%; 10 km: - 34.8% POST-3 h HS; PC3 cells: 5 km: - 14%; 10 km: - 15.9% POST HS; 5 km: - 14.2%; 10 km: - 13% POST-3 h HS). The spheroid volume was reduced by 42.6% (5 km) and 51.1% (10 km) with POST-3 h HS, in LNCaP cells; no significant reduction was observed in PC3 cells. No differences were found between the running sessions, while higher muscle mass, cardiorespiratory fitness and age were associated with greater reductions in spheroid number and volume, especially in LNCaP cells.

Conclusion: Running sessions reduce prostate cancer cell spheroid formation, especially in participants with higher physical fitness. Shorter running distances showed comparable effects to longer ones, highlighting practical implications for real-world exercise prescriptions in oncology.

Background: Retroperitoneal liposarcoma (RLPS) is a mesenchymal-derived malignant tumor characterized by high aggressiveness and a propensity for local recurrence. Emerging evidence implicates aberrant fatty acid metabolism as a key driver of RLPS progression, yet the transcriptional regulators orchestrating this process remain poorly defined.

Methods: Bioinformatics integrating cellular experiments demonstrated the role of fatty acid metabolism in the progression of RLPS. Immunohistochemistry (IHC) and Western blotting (WB) were employed to validate the expression levels of ARNT2, and the role of ARNT2 in tumor progression was demonstrated through CCK8 assays, Transwell invasion assays and wound healing assays. Further experiments confirmed the transcriptional regulatory effect of ARNT2 on STRA6 and demonstrated its control over RLPS progression by modulating intracellular lipid droplet and triglyceride levels.

Results: Here, we identify ARNT2 as a novel oncogenic transcription factor that promotes RLPS growth by transcriptionally upregulating STRA6, thereby reprogramming fatty acid metabolism. Specifically, ARNT2 binds to the STRA6 promoter to enhance its activity, thereby upregulating fatty acid metabolic enzymes and promoting lipid droplet accumulation with elevated triglycerides. This metabolic shift fuels energy production and biomass synthesis in RLPS cells, ultimately accelerating tumor proliferation and invasion.

Conclusion: This study identifies ARNT2 as a transcriptional modulator of fatty acid metabolism pathways, highlighting its potential as a viable molecular target for RLPS therapy.

Background: Adipocytes are engaged in the development and progression of breast cancer (BC). Cancer-associated adipocytes (CAAs) are specific adipocytes located at the invasive front of BC that modulate tumor behaviors. This study aimed to investigate the effect of CAA-derived IL-6 in regulating BC progression.

Methods: Human BC specimens and adipocytes co-cultured with BC cells were used to explore the characteristics of CAAs. Adipocytes and 4T1 cells co-implanted in mouse model and tail vein metastasis model were used to explore the effect of CAAs on malignant progression and immunosuppressive tumor microenvironment (TME) of BC in vivo. The functional assays, flow cytometry, ELISA, miRNAs sequencing and dual-luciferase reporter assay were implemented to investigate the role of CAA-derived IL-6 in regulating programmed cell death protein ligand 1 (PD-L1) expression.

Results: CAAs were present at the invasive front of BC with a de-differentiated fibroblast phenotype. CAAs enhanced the malignant behaviors of 4T1 BC cells in vitro, and promoted 4T1 tumor growth and lung metastasis with decreased CD8⁺T cells and upregulated Tregs. The IHC results of both human BC specimens and xenografts showed that CAAs could upregulate PD-L1 expression in BC. Besides, CAAs could secrete abundant IL-6 and thus enhanced PD-L1 expression in 4T1 cells and tumors. More importantly, CAA-derived IL-6 could activate STAT3, while STAT3 blockade in CAA-cultured 4T1 cells upregulated miRNA-497a-5p expression and downregulated PD-L1 expression. Dual-luciferase reporter assay indicated that PD-L1 was a direct target of miRNA-497a-5p.

Conclusions: Our study demonstrated that CAAs promoted the malignant behaviors of BC and enhanced immunosuppression in TME. Specifically, CAA-derived IL-6 promoted the PD-L1 expression of BC via STAT3/miR-497a-5p signaling, thereby contributing to BC progression.

Background: Cervical cancer remains a major global health challenge, with the highest incidence and mortality rates observed in sub-Saharan Africa. Despite progress in prevention and treatment, the management of advanced and recurrent disease remains difficult.

Aim: This review explores the potential role of cannabinoids in cervical cancer therapy, with a focus on their integration into existing treatment strategies, combination therapies, and nanotechnology-based delivery systems.

Methods: A critical synthesis of preclinical studies and emerging therapeutic approaches was conducted, examining the anticancer properties of cannabinoids, their mechanisms of action, and their application within combination and nanotechnology-based treatment modalities.

Results: Cannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD) demonstrate anticancer effects by inducing apoptosis, inhibiting cell proliferation, and suppressing metastasis. Mechanistic studies highlight their ability to promote oxidative stress, modulate key signalling pathways, and influence immune responses in cervical cancer cells. Combination therapies involving cannabinoids with chemotherapy, radiotherapy, and immunotherapy show enhanced efficacy and reduced drug resistance. Furthermore, nanotechnology-based delivery systems offer advantages including targeted drug release, improved solubility, controlled dosing, and decreased systemic toxicity.

Conclusion: Cannabinoids represent a promising adjunct in cervical cancer management. However, successful clinical translation requires optimisation of formulations, establishment of dosing protocols, and comprehensive safety evaluation. Future research should also explore biomarker-driven personalised medicine approaches. Standardisation, along with addressing regulatory and ethical challenges, will be crucial for the integration of cannabinoid-based therapies into mainstream cervical cancer treatment.

Background: Childhood leukemia is a common malignant tumor worldwide, affecting survival rates and posing medical and public health challenges. Assessing its global burden is essential for informing prevention, treatment, and policy efforts.

Methods: This is a cross-sectional study based on data from the 2021 Global Burden of Disease (GBD) study, covering the years 1990 to 2021 and including 204 countries and regions. We analyzed the incidence, mortality, disability-adjusted life years (DALYs), and estimated annual percentage changes (EAPCs) for childhood leukemia. Subgroup analyses were conducted by age, gender, region, and Socio-Demographic Index (SDI) levels to explore disparities and trends.

Results: Since 1990, the global burden of childhood leukemia has decreased significantly, with a 59.03% reduction in DALYs. Chronic myeloid leukemia (CML) experienced the largest decline, with incidence, mortality, and DALYs reduced by more than 70%. However, disparities persist: boys generally have a higher burden, and acute lymphoblastic leukemia (ALL) remains the most common subtype. East Asia and Andean Latin America reported the highest burden of ALL in 2021. Incidence is highest in high-SDI regions, but mortality rates decrease as SDI increases. Similar trends were observed for DALYs, with better outcomes in high-SDI regions.

Conclusions: Since 1990, childhood leukemia DALYs decreased by 59.03%, with CML showing the largest decline (> 70% in incidence, mortality, and DALYs). ALL remains the most common subtype, with the highest burden in East Asia and Andean Latin America. High-SDI regions report higher incidence but lower mortality, indicating better outcomes than low-SDI regions.

Borowczak et al. recently explored the prognostic role of heat shock proteins HSP27 and HSP70 in laryngeal squamous cell carcinoma (LSCC). Their study demonstrated that lower expression levels of these proteins were linked to significantly reduced overall survival, suggesting potential utility as prognostic biomarkers in this patient population. This work adds important evidence to the limited pool of molecular predictors available for LSCC. However, paradoxical findings, such as the survival advantage observed with higher HSP expression despite their well-known cytoprotective roles, raise questions regarding underlying mechanisms. Factors such as subcellular localization, treatment intensity, and environmental exposures like alcohol consumption may influence these associations. Consequently, further translational research is needed to validate the prognostic significance of HSP27 and HSP70 and to clarify their clinical applicability in LSCC management.

Background: Colorectal cancer (CRC) is common in China, and many postoperative patients experience fear of cancer recurrence (FCR), which negatively affects mental health and quality of life. Predictors of FCR remain underexplored, and traditional regression may overlook complex interactions, whereas random forest (RF) modeling allows robust variable selection.

Purpose: To assess FCR prevalence and identify associated factors using a RF model.

Methods: Between November 2023 and May 2024, 314 postoperative colorectal cancer patients were enrolled at Fudan University Shanghai Cancer Center. Data were collected using the Brief Illness Perception Questionnaire (BIPQ), Cognitive Emotion Regulation Questionnaire (CERQ), Social Support Rating Scale (SSRS), and Social Constraints Scale-15 (SCS-15). Predictors were ranked using a random forest model and confirmed via binary logistic regression.

Results: High FCR was reported by 58.9% of patients. Key predictors (> 5%) included illness perception, negative and positive emotion regulation, social support, social constraints, age, and income. Univariate analyses showed strong associations for BIPQ, CERQ-maladaptive (CERQ-M), SCS-15 (P < 0.001), with income, SSRS, and CERQ-adaptive (CERQ-A) also significant (P < 0.05). Logistic regression confirmed BIPQ, SCS-15, and CERQ-M predicted FCR. Age, despite > 5%, was not independently significant, likely due to adjustment for other psychosocial factors and complex interactions.

Conclusion: A substantial proportion of CRC survivors experience high FCR. Illness perceptions, social constraints, and maladaptive coping are key determinants. Integrating psychosocial screening and targeted interventions into postoperative care may reduce FCR and improve quality of life.

Thoracic spinal segment intradural extramedullary (IDEM) tumors have the risk of disability, and early detection can usually be treated by surgery. The thoracic spinal canal is narrower than the cervical and lumbar spine, with ribs connected on both sides, so the operable space for surgery is narrow, intraoperative exposure is difficult, so it is worthwhile to summarize and improve how to completely resect the thoracic IDEM tumors, and to minimize the surgical-related neurological dysfunction. Currently, most of the surgical approaches are open laminectomy approach and microscopic surgery, and there are few reports about the surgical approach of Unilateral Biportal Endoscopy (UBE). We report a case of significant spinal cord compression due to an IDEM lesion at the T2 vertebral level. A UBE surgery was performed to resect the intraspinal tumor, which was pathologically confirmed as a meningioma. The patient recovered well postoperatively, neurological and imaging success was achieved, and the pathology results confirmed that the tumor was a meningioma, and treatment was completed without adjuvant therapy. The UBE technique can be applied to the treatment of intradural tumors. UBE technique for the treatment of IDEM tumors in the upper thoracic spine is safe and effective and deserves further promotion.

Alkylating agents have represented the first effective drug class in multiple myeloma (MM) but, since the introduction of novel effective drugs, their use has progressively decreased and is currently relegated to autologous stem cell transplant (ASCT) and few other settings. Nevertheless, the combination of melflufen (a peptide-drug conjugate pro-drug of melphalan) and dexamethasone was approved by the U.S. Food & Drug Administration (FDA) for triple-class refractory (TCR) patients after ≥ 4 prior lines of therapy (LOT) following results of HORIZON clinical trial (NCT02963493). This combination was subsequently withdrawn as it was not associated with improved overall survival (OS) as compared to pomalidomide-dexamethasone (OCEAN clinical trial, NCT03151811). However, since a post-hoc analysis showed a benefit in OS for patients without prior ASCT or with a time to progression (TTP) > 36 months after ASCT, the European Medicines Agency (EMA) has approved melflufen-dexamethasone for TCR patients after ≥ 3 LOT, including specification that TTP must be ≥ 3 years in patients with prior ASCT. In this paper, we report three cases of patients receiving the combination melflufen-dexamethasone in the aforementioned clinical trials in three hematologic centers across Europe and achieving exceptionally long responses as compared to the overall enrolled populations, with good tolerability. Further, we discuss the potential use of this chemotherapy-based regimen in the era of novel immunotherapies.