American journal of cancer research最新文献

ITGB6, the gene encoding the β6 subunit of integrin αvβ6, is a potent prognostic marker across multiple cancer types. As a major activator of latent TGFβ and a potent modulator of the tumor immune environment, αvβ6, and consequently, ITGB6, has considerable therapeutic implications. ITGB6 is highly upregulated in squamous cell carcinomas and pancreatic adenocarcinomas, where it disrupts tumor-immune cell signaling. We identify ITGB6 as a potent clinical prognostic marker of anti-tumor immune response and were able to recapitulate the immune-mediated anti-tumor effect of ITGB6 in pre-clinical mouse models. Genetic knockout of ITGB6 in heterotopically-injected head and neck squamous cell carcinoma and pancreatic adenocarcinoma cell lines shows markedly reduced tumor progression and immunogenic cytokine profiles in immunocompetent mice. Additionally, co-cultures of human head and neck squamous cell carcinoma and pancreatic adenocarcinoma with human T-cells show increased T-cell killing upon cancer cell ITGB6 inhibition. Colony formation experiments give further evidence that the reduced tumor growth observed upon ITGB6 inhibition in vivo is through immunological clearance of cancer cells and not merely through intrinsic factors. Analysis of The Cancer Genome Atlas (TCGA) reveals the high prognostic value of ITGB6 on overall survival and that high ITGB6 expression in patients is associated with an inferior response to α-PD-1 and α-PD-L1 immune checkpoint blockade. The potent anti-tumor immune response observed both in vitro and in vivo upon ITGB6 inhibition, combined with analysis of RNA-seq data from immune checkpoint blockade-treated patients, encourages the development of ITGB6 blockade and immunotherapy combination regimens. Further pre-clinical studies should facilitate translation of our findings into therapeutic clinical trials for treating immunotherapy-resistant cancers.

Objective: This study aimed to investigate the mechanism underlying the role of Zinc finger protein 710 (ZNF710) in gastric cancer (GC).

Methods: The level of ZNF710 expression in GC and its prognosis were examined based on the public databases and clinical samples. Cell models of lentivirus-mediated overexpression (oeZNF710) and knockdown (shZNF710) of ZNF710 were developed on the AGS and HGC-27 GC cell lines. The biological behaviors of these cells were analysed systematically, comprising proliferation (as measured by CCK-8 assay and plate cloning experiment), apoptosis (measured by flow cytometry), and migration (measured by Transwell assay). To confirm the expression of the main proteins of the Wnt/β-catenin system, western blotting analysis was conducted. Besides, functional rescue experiments of Wnt signaling agonist SKL2001 and Wnt signaling inhibitor XAV939 were performed. The in vivo activity of ZNF710 was tested in a nude mouse subcutaneous xenograft model.

Results: The expression of ZNF710 was significantly increased in GC tissues and cell lines compared to standard controls, whereas high levels of ZNF710 were associated with a poor prognosis in GC patients. ZNF710 knockdown of HGC-27 cells significantly reduced cell proliferation, migration, and invasion and increased apoptosis. On the contrary, overexpression of ZNF710 in AGS cells produced the reverse effects. Mechanistically, ZNF710 overexpression increased the expression of Wnt/β-catenin pathway-related regulatory proteins, and ZNF710 knockdown reduced their expression.

Conclusion: ZNF710 is highly expressed in GC and promotes GC cell proliferation, migration, and invasion while inhibiting apoptosis by activating the Wnt/β-catenin pathway, suggesting it may serve as a potential therapeutic target for GC.

[This corrects the article on p. 2752 in vol. 10, PMID: 33042615.].

Background: The principal established therapeutic option for localized prostate cancer is the robotic-assisted radical prostatectomy (RARP) over the laparoscopic radical prostatectomy (LRP). Robust data from Chinese hospitals is limited, and the effect of surgeon experience is often overlooked.

Objective: This study retrospectively compares outcomes between RARP and LRP, evaluating the impact of surgeon experience.

Methods: The clinical information of 252 patients who underwent RARP or LRP between 2019 and 2023 was retrospectively analysed. Multivariable regression models, for both patient characteristics and surgeon volume, were employed to evaluate perioperative metrics, complications, positive surgical margins (PSM), continence, and patient-reported outcomes.

Results: RARP demonstrated superior advantages, including a shorter operative time (154.9±28.3 vs. 169.2±23.9 minutes, P<0.001), less blood loss (172.5±56.8 vs. 306.8±82.2 mL, P<0.001), and a shorter hospital stay (2.3 vs. 3.9 days, P<0.001). Multivariable analysis revealed that both surgical approaches and surgeon volume were predictors of outcomes: 66% lower odds of PSM (OR: 0.34, P=0.009) in the RARP group, while high-volume surgeons demonstrated 96% lower odds of PSM compared to low-volume surgeons (OR: 0.039, P<0.001). RARP patients experienced fewer complications (25.4% vs. 39.7%, P=0.016) and a higher continence recovery at 12 months (95.2% vs. 80.2%, P=0.001). Regarding patient-reported outcomes, RARP was consistently favored across all domains (P<0.01).

Conclusion: While preserving comparable functional and short-period cancer-related outcomes, RARP outperformed LRP in perioperative outcomes and patients' quality of life. These findings demonstrate that both surgical technology and surgeon volume are critical, independent determinants of surgical quality. The optimal outcomes are achieved by pairing advanced robotic technology with high-volume surgical expertise.

Interleukin enhancer binding factor 2 (ILF2) has been confirmed to drive the progression and proliferation of multiple malignancies, but the expression and function of ILF2 in colorectal cancer (CRC) remain to be elucidated. In this study, the expression of ILF2 in CRC tissues was evaluated by the public tumor databases, quantitative reverse transcription PCR (qRT-PCR) and tissue array analyses. ILF2 was found to be elevated in CRC, and was predicted to serve as a negative index for patients. Subsequently, cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay and colony formation, and tumor growth was evaluated by establishing xenografted mouse models. Our results showed that knockout of ILF2 markedly inhibited cell proliferation and tumor growth of CRC. Moreover, we found ILF2 was ubiquitinated, and further co-immunoprecipitation (Co-IP) coupled with liquid chromatography-tandem mass spectrometry analysis indicated that ILF2 may be a novel substrate of the deubiquitinating enzyme ubiquitin specific peptidase 5 (USP5). Further reciprocal Co-IP assays confirmed that ILF2 interacted with USP5. Enforced expression of USP5 reduced ubiquitinated ILF2 and increased ILF2 level, whereas catalytic inactive USP5 did not. While USP5 inhibitor WP1130 downregulated ILF2 and inhibited CRC cell growth, the effects were markedly abolished by ILF2 overexpression. These data demonstrate that the USP5/ILF2 axis mediates the tumorigenesis of CRC, which highlights the USP5/ILF2 axis as a promising therapeutic target for CRC treatment.

[This retracts the article on p. 2209 in vol. 7, PMID: 29218245.].

Background: Information asymmetry between healthcare providers and patients undergoing lung cancer surgery can result in reduced treatment engagement, lower admission satisfaction, and a greater risk of medical disputes, particularly regarding the transition to the intensive care unit (ICU). This study aims to map the ICU pre-experience pattern by first identifying, along a timeline of key ICU stages, the specific information that patients awaiting lung-cancer surgery and their families require during the peri-ICU period.

Methods: A qualitative study was conducted by purposive sampling at the Lung Cancer Center of West China Hospital, Sichuan University. Semistructured interviews were held with 36 participants (17 patients and 19 families). The interview transcripts were analyzed by content analysis with NVivo 12.0 software.

Results: The analysis identified a structured hierarchy of information needs, comprising 2 first-level themes, 4 second-level themes, and 13 third-level themes. The core finding was that patients' information needs were greater than those of their families. Patients were predominantly concerned about postoperative care and their physical perceptions. In contrast, families focused more on process-oriented information, such as the ICU transfer process and required signatures before admission, as well as the patient's surgical outcomes and treatment process after admission.

Conclusion: Patients and their families have comprehensive yet distinct information needs prior to ICU admission. Healthcare providers are their primary information source, underscoring the necessity for a structured, proactive, and patient-centered approach to information delivery. These findings provide a foundational framework for developing an "ICU pre-experience" pattern to mitigate uncertainty and improve nursing quality.

Gliomas, particularly glioblastoma multiforme (GBM), represent the most prevalent primary intracranial malignancies, characterized by high invasiveness, aggressive proliferation, and poor clinical outcomes. Recent studies have highlighted the critical role of tumor microenvironment interactions and cellular stress responses, including endoplasmic reticulum (ER) stress, in modulating glioma progression. While ER stress can induce autophagy and apoptosis, glioma cells exhibit remarkable plasticity, adapting to stress conditions and exploiting them to promote survival and self-renewal, thereby contributing to therapeutic resistance. In this study, we established an individualized ER stress risk score using glioma transcriptomic data, demonstrating its association with adverse prognosis, aggressive molecular subtypes, and pro-tumorigenic biological functions. Through systematic screening, we identified DERL3 as a core effector gene mediating ER stress adaptation. Functional validation revealed that DERL3 drove glioma proliferation and invasion by binding to and stabilizing Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), consequently activating the NF-κB signaling pathway. These findings elucidate the DERL3-HNRNPA2B1-NF-κB axis as a critical mechanistic link between ER stress adaptation and glioma malignancy. Targeting this axis may offer novel therapeutic strategies to overcome treatment resistance, providing significant translational potential for improving glioma management. This study advances our understanding of stress response mechanisms in tumorigenesis and underscores the clinical relevance of ER stress-related pathways in precision oncology.

[This corrects the article on p. 1751 in vol. 5, PMID: 26175943.].

Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) remains a therapeutic challenge with poor prognosis. Selinexor, a selective inhibitor of nuclear export (XPO1), has shown activity in this setting. We retrospectively evaluated the efficacy and safety of selinexor combined with R-GDP (rituximab, gemcitabine, dexamethasone, and cisplatin) as second-line therapy in 22 patients with R/R DLBCL treated at Fudan University Shanghai Cancer Center between January 2023 and August 2023. Patients were scheduled to receive 3 cycles of selinexor plus R-GDP, and subsequently followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, or alternative regimens, as appropriate. At a median follow-up of 25.5 months, the selinexor plus R-GDP regimen yielded an overall response rate of 52.4% in patients with R/R DLBCL. The median overall survival (OS) was 26.9 months (95% CI, 12.1-not reached), with 1- and 2-year OS rates of 67.6% and 52.3%. The median progression-free survival (PFS) was 7.7 months (95% CI, 2.27-not reached). Survival outcomes were significantly influenced by subsequent therapy: patients bridged to ASCT or CAR-T therapy had significantly longer OS (P=0.0217) and PFS (P=0.0029) than those receiving other treatments. The median OS was not reached in the ASCT group, 26.9 months (95% CI, 15.9-not reached) in the CAR-T group, and 11.2 months (95% CI, 10.2-not reached) in patients receiving other therapies. The median PFS was not reached for ASCT or CAR-T group, compared with 2.2 months (95% CI, 2.1-not reached) in patients receiving other therapies. Additionally, patients with relapsed disease exhibited a significantly longer median PFS than those with primary refractory disease (not reached vs 2.82 months, [95% CI, 2.17-not reached]; P=0.0072). No significant difference in OS was observed between these two groups (P=0.2323). Common adverse events included thrombocytopenia (100%), fatigue (59%), neutropenia (45%), anemia (45%), and pneumonia (23%), while were manageable through supportive care or temporary dose interruption. In this real-world analysis, selinexor combined with R-GDP demonstrated modest efficacy in R/R DLBCL, while highlighting the importance of optimizing subsequent sequencing with ASCT or CAR-T therapy.