Clinical & Translational Oncology最新文献

Background: Cadonilimab is a novel PD-1/CTLA-4 bispecific antibody approved for cervical cancer treatment in China in 2022. We conducted a retrospective study to investigate the efficacy and safety of Cadonilimab in patients with recurrent or metastatic gynecological malignancies.

Methods: We retrospectively enrolled 27 patients with recurrent or metastatic gynecological malignancies, confirmed by pathology or cytology between July 2022 and February 2025. All patients received at least two cycles of Cadonilimab. The primary endpoints were objective response rate and disease control rate according to RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

Results: In the enrolled population, the mPFS and mOS were 10.90 months (95% CI: 9.57-12.23) and 52.93 months (95% CI: 19.62-73.38), respectively. Among the first-line patients with advanced cervical cancer, ORR was 66.67% (10/15,95% CI, 41.71 to 84.82), DCR was 100.00% (15/15,95% CI 79.67 to 100.00), the mPFS and mOS were 15.9 months (95% CI: 7.72-24.08) and 46.5 months (95% CI: 19.62-73.38), respectively. There was no significant difference in PFS (P = 0.45, HR: 1.704, 95% CI: 0.38-7.70) and OS (P = 0.91, HR: 1.14, 95% CI: 0.11-11.46) between Cadonilimab-based chemotherapy with or without bevacizumab. In the responder population, 14 (51.85%) patients experienced at least one treatment-related adverse event (TRAE), only 1(3.70%) patient developed grade 3-4 adverse events. No treatment-related deaths occurred during the study.

Conclusion: Cadonilimab-based chemotherapy with or without bevacizumab had a promising efficacy and manageable safety profile in the treatment of recurrent or metastatic gynecological malignancies.

Background: Hepatocellular carcinoma (HCC) is treated with sorafenib as a first-line treatment; however, resistance reduces its clinical effectiveness. It has been demonstrated that CCDC137 influences cell survival and proliferation. However, in HCC, its role in sorafenib resistance has not been thoroughly investigated.

Objective: This study examined how CCDC137 makes HCC cells resistant to sorafenib, with a focus on the Akt/mTOR signaling pathway.

Methods: HCC cell lines resistant to sorafenib (Huh7/sora) were generated by gradually increasing sorafenib concentrations in Huh7 cells. Bioinformatics analysis was performed on the Cancer Genome Atlas (TCGA)-hepatocellular carcinoma (LIHC) dataset and the GSE29721 dataset. The prognostic significance of CCDC137 was verified using Kaplan-Meier survival curves. Using the in vitro cell assays, the consequences of CCDC137 for the migration, apoptosis, invasion, and proliferation of parental HCC cells and sorafenib-resistant cells were assessed. The changes were analyzed using the Western blot test in the AKT/mTOR signaling pathway in resistant cells after CCDC137 knockdown or overexpression.

Results: CCDC137 was significantly elevated in Huh7/sora cells resistant to sorafenib and was linked to a poor outcome for individuals with HCC. CCDC137 knockdown reduced cell viability, induced apoptosis and inhibited migration and invasion in Huh7/sora cells. Conversely, CCDC137 overexpression in Huh7 cells enhanced sorafenib resistance. Mechanistically, CCDC137 activated the Akt/mTOR signaling pathway, AKT inhibition with MK2206 reversed opposition and increased apoptosis in resistant cells.

Conclusion: Through triggering the Akt/mTOR signaling pathway, CCDC137 encourages sorafenib resistance in HCC cells, potentially offering a treatment approach to combat sorafenib resistance in HCC cells.

Despite advances in patients' healthcare, gastric cancer remains a major health concern around the world with a high annual incidence rate and mortality. This highlights the urgent need to develop more effective therapeutic strategies, particularly for patients in advanced stages of the disease. In the recent decade, cellular-based immunotherapy has achieved remarkable successes in various hematologic malignancies and solid tumors. Nonetheless, until now, no cellular-based immunotherapy has been approved for GC patients. This review aims to provide a holistic view of the current state of cellular-based immunotherapy for GC, its existing bottlenecks, and future directions to harness the potential of cellular-based immunotherapy for GC treatment. In this regard, we explore clinical trials of various types of cellular-based immunotherapy, including chimeric antigen receptor (CAR)-engineered cell therapy, T cell receptor (TCR)-engineered T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, cytokine-induced killer (CIK) cell therapy, and dendritic cell (DC) vaccines. For each type of cellular-based immunotherapy, we discuss existing roadblocks to successful treatment and explore potential solutions that may improve efficacy, including novel targets, combination approaches, and biomarker-driven patient selection.

Purpose: Giant thick melanomas (GTMs) are rare tumors characterized by extreme size and depth. We aimed to describe their clinical features and outcomes.

Methods/patients: We retrospectively reviewed eleven patients diagnosed with GTMs at a tertiary dermatology center. GTMs were defined as primary cutaneous melanomas with diameter > 5 cm and Breslow thickness > 4 mm. Tumor size was measured clinically, and all histopathology was reviewed by two dermatopathologists. Clinical, pathological, treatment, and outcome data were extracted from electronic records.

Results: Eleven patients (median age 69 years) presented with large tumors (median diameter 55 mm; median Breslow thickness 12 mm), most often on the trunk or extremities. Over half (54.5%) had stage III-IV disease at diagnosis, and treatments included surgery and systemic therapy. Median overall survival was 13 months, with two long-term survivors.

Conclusions: GTMs are aggressive and frequently diagnosed at advanced stages. Early recognition and multidisciplinary management are essential. Giant thick melanoma (GTM) is a rare entity characterized by aggressive behavior and poor prognosis. We conducted a retrospective descriptive study defining GTM as lesions with a diameter > 5 cm and Breslow thickness > 4 mm. Eleven cases were analyzed (mean age: 68.5 years), with a female predominance and predominant localization on the trunk. The main reasons for consultation were tumor growth, bleeding, and neurological symptoms. At diagnosis, AJCC stages ranged from IIB to IV. During follow-up, seven patients died -five due to melanoma and two from other causes-, while two remain alive and under active follow-up. Median follow-up was 1 year (range 0-15 years; mean 3.5 years). These findings confirm the severity of GTM and highlight the persistence of diagnostic delay. The main limitation of this study is the small sample size.

Purpose: Gastric cancer is a leading cause of cancer-related mortality worldwide, with metastasis being the primary cause of death. Exosomes secreted by tumor cells are key mediators of intercellular communication and can prepare distant sites for metastasis by altering the local microenvironment. We hypothesized that exosomes released by gastric cancer cells deliver cargo that regulates specific proteins in recipient gastric cancer cells, thereby enhancing tumor progression and metastatic potential.

Methods: Human gastric cancer cell lines were treated with exosomes isolated from the conditioned medium of other gastric cancer cells. Differential proteomic analysis was performed to identify proteins significantly altered by exosome treatment. ITGA2 expression was validated in exosome-treated cells and in clinical gastric cancer tissues versus adjacent normal tissues using RT-qPCR and western blotting. The functional role of ITGA2 was assessed by siRNA-mediated knockdown, followed by MTT proliferation assays and fluorometric transwell assays for migration and invasion. A second proteomic analysis was conducted on ITGA2-knockdown versus control cells to identify downstream targets and affected pathways.

Results: Exosome treatment significantly upregulated ITGA2 expression in recipient gastric cancer cells. ITGA2 was also markedly overexpressed in human gastric cancer tissues compared with adjacent normal mucosa. Knockdown of ITGA2 significantly suppressed cell proliferation, migration, and invasion. Proteomic profiling of ITGA2-knockdown cells revealed numerous differentially expressed proteins enriched in pathways related to cell adhesion, motility, extracellular matrix organization, and intercellular signaling.

Conclusion: Exosomes derived from gastric cancer cells induce ITGA2 overexpression in recipient tumor cells, where ITGA2 functions as an oncogene that promotes proliferation, migration, and invasion. The downstream targets of ITGA2 implicate multiple pro-tumorigenic signaling networks, suggesting that the exosomes-ITGA2 axis may represent a novel therapeutic target in gastric cancer progression and metastasis.

Background: Cancer patients often develop life-threatening events that prompt intensive care unit (ICU) admission. However, uncertainty regarding prognosis may hinder timely referral. We compared ICU survival in adults with solid tumors admitted emergently for medical or urgent surgical reasons with that of non-cancer controls.

Methods: We retrospectively analyzed 167 consecutive adults with solid tumors emergently admitted to a mixed ICU in a single center between 2010 and 2016, and compared them with two propensity-matched non-cancer cohorts. We made two 1:1 comparisons: (1) cancer and non-cancer patients matched for age, sex and do-not-intubate order; (2) the same cancer cohort matched additionally for admission diagnosis, maximum SOFA, SAPS II and Charlson Comorbidity Index. Primary outcome was ICU mortality; hospital mortality and 90-day survival were secondary endpoints.

Results: Cancer cases represented 4.8% of all ICU admissions; 54% had metastatic disease, 41% acute respiratory failure, and 28.7% sepsis/shock. When matched only for demographic and functional factors, cancer patients had higher intensive care unit and hospital mortality rates than controls (27.5% vs 10.8%, p < 0.001, and 35.3% vs 16.2%, p < 0.001, respectively). After matching for severity and comorbidity, ICU and hospital mortality no longer differed significantly (27.5% vs 19.8%; p = 0.094, and 35.3% vs 28.7%; p = 0.4). 90-day survival was significantly lower for cancer patients (64.7% vs 80.2%, p < 0.001), but no differences were found with controls matched for severity and comorbidity (64.7% vs 71.3%, p = 0.4).

Conclusions: Solid-tumor patients admitted to the ICU are generally more severely ill and thus present higher crude mortality than non-cancer patients. However, when severity and comorbidity are equivalent, outcomes are similar. Therefore, intensive care should be offered to cancer patients with reversible critical illness and acceptable baseline status, and a cancer diagnosis alone should not be considered a contraindication for ICU admission.

Background: The SEC13 is a multifaceted gene implicated in mTORC1 signaling regulation and the maintenance of genomic stability. Its function in cancer is complex, displaying potential oncogenic as well as potential tumor-suppressive roles across different malignancies. Therefore, this study aimed to investigate SEC13 expression, prognostic value, and its relationship with immune checkpoints across different cancer types.

Methods: Differential expression analysis, diagnostic analysis, and prognostic analysis were analyzed with The Cancer Genome Atlas and Human Protein Atlas database. The potential related genes were analyzed by utilizing Gene Expression Omnibus and clinical breast cancer samples. GO (Gene Ontology) and GSEA (Gene Set Enrichment Analysis) were used to elucidate the potential role of SEC13. TMB (tumor mutation burden), MSI (microsatellite instability), immune checkpoint, and immune cell infiltration were also analyzed to indicate its potential role in immune feature. To validate the functional impact of SEC13, its effects on cell proliferation and cell cycle distribution were assessed using CCK-8 assays and flow cytometry in MDA-MB-231 and MCF7 breast cancer cells following SEC13 knockdown.

Results: SEC13 was highly expressed in 14 tumor types and lowly expressed in 2 tumor types. High expression of SEC13 was associated with worse overall survival, disease-specific survival, and progression-free interval in breast cancer, liver hepatocellular carcinoma, and sarcoma. SEC13 expression was correlated with several co-expressed genes (e.g., MED8, RPN1) and was enriched in cell cycle pathway. Functionally, SEC13 knockdown was found to reduce the S-phase cell proportion and inhibit cell proliferation. In addition, SEC13 exhibited relationships with TMB and MSI, immune checkpoint, and immune cell infiltration.

Conclusion: This study underscores the significant expression differences and prognostic implications of SEC13 in various cancers, emphasizing its potential as a biomarker and therapeutic target.

Background: Programmed death ligand 1 (PD-L1) expression, assessed by the combined positive score (CPS), is an established predictive biomarker for first-line chemo-immunotherapy in metastatic triple-negative breast cancer (mTNBC). In routine practice, CPS testing is heterogeneous and its relationship with outcomes in later-line, sacituzumab govitecan (SG)-treated patients with mTNBC is not well described. We aimed to assess clinicopathological correlates of CPS and its association with survival in this cohort.

Methods: We conducted a retrospective, multicenter study within the Central European Breast Cancer Collaboration (CEBCC)-102 project. CPS was locally assessed by validated immunohistochemistry. Survival outcomes: overall survival (OS), post-metastatic survival (PMS), and metastasis-free interval, were assessed with the Kaplan-Meier method.

Results: Of 303 women from the Czech Republic, Poland, and Slovakia with mTNBC treated with SG in ≥ 2 line, 107 (35.3%) with available CPS results were included in this analysis. CPS was positive (≥ 10) in 51/107 patients (47.7%) without significant demographic or disease-specific differences. During a median follow-up of 40 months, CPS-positive status may suggest worse outcomes in this cohort in multivariate analysis despite partial first-line chemo-immunotherapy exposure: OS 41.6 versus 67.7 months (HR 2.2, 95% CI: 1.1-4.5, p = 0.027) and PMS 20.2 versus 27.1 months (HR = 2.3, 95% CI: 1.2-4.2, p = 0.009).

Conclusions: In this selected cohort, CPS status did not correlate with clinicopathological characteristics, but CPS-positive status was associated with inferior survival outcomes. Given the selection and survivor bias inherent to later-line treatment cohorts and the incomplete availability of CPS, these findings should be considered hypothesis-generating.

Background: Medulloblastoma is similar to other common tumors in the posterior cranial fossa of children in terms of the onset and clinical manifestations. Still, its main treatment methods, surgical methods and prognosis are quite different. Therefore, there is an urgent need for finding biomarkers for differential diagnosis.

Purpose: The purpose of this study was to identify new lipids and differential metabolic pathways by analyzing the significantly different lipids present in the plasma of children with medulloblastoma in comparison to those with other intracranial tumors.

Methods: In this study, 35 patients with medulloblastoma and 32 matched controls were enrolled. Plasma samples and medical records were collected, and untargeted lipidomics analyses were performed using UHPLC-MS/MS.

Results: A total of 97 differential lipids in the plasma of children with medulloblastoma were identified. Seven differential lipids could be potentially useful in medulloblastoma detection and a diagnostic model was established. The metabolic pathway analysis showed that there were significant differences in patients with medulloblastoma in terms of glycerophospholipid metabolism metabolism, sphingolipid metabolism and linoleic acid metabolism pathways.

Conclusion: The difference in plasma lipid markers between medulloblastoma and other intracranial tumors screened in this study may be useful to support and improve the differential diagnosis of medulloblastoma in children.

Purpose: Emerging evidence suggests an association between the systemic immune-inflammation index (SII) and the survival outcomes of individuals with hepatocellular carcinoma (HCC). However, existing research findings are inconsistent, and no definitive conclusions have been reached. This research aimed to explore the predictive accuracy of the SII in patients with HCC.

Methods: Numerous databases, encompassing PubMed, Embase, Web of Science, and Cochrane Library, were thoroughly retrieved from the database inception until January 14, 2025, to identify studies on the correlation between SII and survival outcomes in HCC. Studies were screened according to pre-established eligibility criteria. The primary endpoints included overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS), which were appraised via hazard ratios (HRs) with corresponding 95% confidence intervals (CIs).

Results: 39 high-quality cohort studies involving 47 comparison groups were included in this analysis. As proven by the aggregated data, increased SII was significantly linked to shorter OS (HR = 1.64, 95% CI: 1.45-1.85; p < 0.00001), RFS (HR = 1.68, 95% CI: 1.44-1.96; p < 0.00001), and PFS (HR = 1.48, 95% CI: 1.20-1.82; p = 0.0002) in individuals with HCC. Furthermore, subgroup analyses revealed that age, region, intervention strategy, and SII thresholds affected the validity of SII for predicting the prognosis of HCC.

Conclusion: In HCC patients treated with monotherapy or combination therapy, a higher SII before treatment is significantly associated with shorter OS, RFS, and PFS. SII may serve as an important biological indicator for assessing the prognosis of HCC, providing a critical reference for the scientific and systematic treatment of HCC.