Oncology Research最新文献

Background: Liver cancer stem cells (LCSCs) are recognized as pivotal drivers of hepatocellular carcinoma (HCC) progression; however, the molecular mechanisms maintaining their stem-like phenotype remain largely unresolved. This work investigates the role of prefoldin subunit 6-like protein (PFDN6L) in shaping LCSC traits and promoting or restraining HCC progression.

Methods: PFDN6L, a cytoskeleton-associated chaperone, was studied using multiple in vitro assays-cell growth evaluation, cell cycle profiling, and spheroid culture-alongside analyses of stemness-associated markers (SOX2, CD133, CD44). Tumorigenic capacity was assessed in xenograft mouse models, and signaling pathway interrogation was performed to define underlying mechanisms.

Results: In patient samples, higher PFDN6L expression correlated with improved survival outcomes. Forced expression of PFDN6L induced G2/M arrest, diminished sphere formation, and reduced pluripotency marker expression, whereas knockdown accelerated in vivo tumor formation. Mechanistic experiments demonstrated that PFDN6L suppresses malignancy by simultaneously dampening AKT and ERK1/2 activation, thereby impairing oncogenic signaling cascades.

Conclusion: PFDN6L acts as a negative regulator of LCSC-driven tumorigenesis. Its dual blockade of AKT and ERK pathways forms the mechanistic basis of its tumor-suppressive action, supporting its potential as a prognostic biomarker and therapeutic target in HCC.

Immune checkpoint inhibitor (ICI) has limited efficacy in the treatment of immune "cold" tumors. Due to insufficient T cell infiltration and heterogeneous programmed death ligand 1 (PD-L1) expression, the ORR is only 5%-8% compared with 30%-40% of "hot" tumors. This article reviews the synergistic mechanism, clinical efficacy and optimization strategy of oncolytic virus (OVs) combined with ICIs in the treatment of refractory malignant tumors. Systematic analysis of mechanistic interactions across tumor types and clinical trial data demonstrates that OVs transform the immunosuppressive microenvironment by inducing immunogenic cell death and activating innate immunity. Concurrently, ICIs enhance adaptive immunity by reversing T-cell exhaustion and expanding T-cell diversity. Clinical trials in melanoma, head and neck cancer and breast cancer showed superior efficacy. The Objective Response Rate (ORR) of combination therapy was 39%-62%, while the ORR of ICI monotherapy was 18%. Treatment heterogeneity is mainly attributed to virus-related factors, including targeting specificity and replication efficiency, tumor characteristics, such as antigen presenting ability and mutation load, and host immune status, including pre-existing antiviral antibodies and microbiome composition. This combined approach represents a paradigm shift in cancer immunotherapy, which effectively transforms immune "cold" tumors into "hot" tumors through the continuous activation of innate and adaptive immune responses. In the future, it is expected to improve the therapeutic effect of treatment-resistant malignant tumors through the integration of immune regulatory molecules, accurate biomarkers to guide the treatment scheme and triple combination strategy by a new generation of engineering viruses.

Background: E26 transformation-specific (ETS) family transcription factors have confirmed roles in several types of cancers. This study aimed to clarify the role of ETS family transcription factor alterations in gastric cancers.

Methods: This study examines molecular alterations of ETS transcription factors in gastric adenocarcinomas based on an analysis of publicly available cohorts from the Protein Atlas and the Cancer Genome Atlas. The expression and relationships of members of the ETS transcription factor family with other important factors in the process of gastric carcinogenesis were evaluated using the same resources.

Results: mRNA expression levels of ETS family members in gastric carcinoma tissues were variable, with ELF3, ETS2, EHF, ERF, and ELF1 being the family members with the highest expression. Mutations in individual transcription factors of the ETS family were rare in gastric cancers. The family member ELF3 was well expressed in the mRNA level in a subset of gastric cancers (n = 91), and its expression correlated with the expression of other transcription factors involved in gastric cancer pathogenesis, including HNF4A, HNF1A, CDX2, GATA4, GATA6, and EHF. Cancers with high co-expression of ELF3 and HNF4A were frequently chromosomally instability (CIN), intestinal-type adenocarcinomas, and harbored TP53 mutations and WWOX deletions.

Conclusion: Expression of E74 like ETS transcription factor 3 (ELF3), an ETS transcription family member, correlates with expression of other key factors in gastric cancer and confers specific characteristics that may become exploited in targeted therapeutic interventions.

Gastric cancer (GC) is a prevalent malignant tumor globally, with high incidence and mortality rates. Advances in understanding molecular mechanisms underlying GC have highlighted the role of microRNAs (miRNAs) in its initiation, progression, and treatment. The Let-7 family, an important class of miRNAs, is closely associated with the biological behaviors of GC. Aberrant expression of various Let-7 family members in GC patients contributes to disease progression, as they target multiple molecular pathways and participate in diverse regulatory mechanisms throughout GC pathogenesis. This article systematically summarizes the expression patterns of Let-7 family members in GC, explores their influence on GC cell behaviors such as proliferation, invasion, and metastasis through key target gene regulation, and reviews current advances in Let-7-based interventions for GC treatment. It aims to provide foundational insights for a deeper understanding of Let-7-related mechanisms in GC and optimize therapeutic strategies.

Nanomedicine has evolved significantly over the last decades and expanded its applications in pediatric oncology, which represents a special domain with unique patients and distinct requirements. Τhe need for early cancer diagnosis and more effective and targeted therapies aiming to increase the pediatric patients' survival rates and minimize the treatment-related side effects to survivors is profound. Nanoparticles (NPs) come as a beacon of hope to provide sensitive cancer diagnostic tools and assist contrast agents' transport to the malignant tumors. Besides, NPs could be designed to deliver targeted drugs and genes to tumors, minimizing the medicine-related toxicities. Metal and metal oxide NPs could be exploited as sensitizers to enhance chemotherapy and radiotherapy effects. Future research should emphasize pediatric models to gain secure results about NPs' safety and efficiency for pediatric cancer patients. This review presents the recent studies on the use of NPs in pediatric cancer management and highlights their impact on diagnosis, treatment outcomes, and the quality of life of the survivors. The purpose of this study is to investigate the benefits that may arise from the use of NPs in pediatric oncology, address the potential limitations and challenges, and discuss the needs for future research efforts.

Organoid technology, characterized by high fidelity in mimicking the in vivo microenvironment, preservation of tumor heterogeneity, and capacity for high-throughput operations, has emerged as a critical tool in head and neck cancer research. To address clinical challenges in head and neck cancer management-including marked tumor heterogeneity, therapeutic resistance, and significant prognostic variability-this review focuses on four key translational applications of organoid technology: In mechanistic studies, organoid models provide a reliable platform for investigating tumorigenesis, progression, and drug resistance mechanisms. In personalized therapy, organoid-based drug sensitivity testing enables data-driven clinical decision-making. For biomarker discovery, organoids facilitate the identification of novel diagnostic markers and therapeutic targets. With ongoing improvements and standardization of organoid culture systems, this technology holds substantial promise for advancing precision medicine in head and neck cancer, bridging the gap between basic research and clinical practice.

Objectives: Colorectal adenomatous polyps frequently recur after removal and are precursors to colorectal cancer, highlighting the need for effective preventive strategies. This study evaluated the efficacy of probiotic Clostridium butyricum MIYAIRI 588 (CBM588) in preventing colorectal adenoma recurrence in high-risk patients.

Methods: We conducted a randomized, single-blind, two-year crossover trial in patients with a history of adenomatous polyps. Participants received CBM588 in either the first or second year, with the alternate year as observation, and underwent annual surveillance colonoscopies. Outcomes (adenoma recurrence and polyp counts) were analyzed by intention-to-treat (ITT) and per-protocol (PP) approaches.

Results: A total of 398 participants were enrolled. In first-year ITT analysis, the CBM588-first group had a lower mean polyp count (0.78 vs. 1.00) and lower adenoma recurrence rate (30.00% vs. 35.35%) than the control-first group, though these differences were not statistically significant (p = 0.10 and p = 0.26, respectively). In contrast, first-year PP analysis showed significant reductions in the CBM588-first group's mean polyp count (0.80 vs. 1.25, p < 0.05) and adenoma recurrence rate (29.76% vs. 44.71%, p < 0.05) compared to control. After crossover, the group receiving CBM588 in the second year experienced similar benefits, and by year two both groups had comparable outcomes. No carryover effect was evident. The number needed to treat to prevent one adenoma in one year was 19 in ITT and 7 in PP. CBM588 was well tolerated, with no serious adverse events.

Conclusion: CBM588 demonstrated potential to reduce colorectal adenoma recurrence in high-risk patients, supporting its role as a feasible, non-invasive preventive strategy.

Objectives: Metastatic spread to the lung is one of the leading causes of fatal outcomes in thyroid cancer, but the underlying molecular mechanisms remain unclear. To investigate how exosomal microRNA-17-5p (miR-17-5p) promotes lung metastasis in thyroid cancer within the framework of the "seed and soil" hypothesis.

Methods: Serum exosomes from thyroid cancer lung metastasis patients and controls were analyzed for miR-17, which was elevated in metastatic cases. miR-17 was transfected into embryonic lung fibroblasts (MRC-5), and their supernatants were co-cultured with thyroid cancer cells (Cal62). Cell proliferation and migration were evaluated using colony formation, Ki67 staining, and Transwell assays. Interleukin-6 (IL-6)/interleukin-8 (IL-8) levels and nuclear factor kappa-B (NF-κB)/nuclear factor kappa-B repressing factor (NKRF) expression were analysed by enzyme-linked immunosorbent assays (ELISA) and western blot. In vivo models verified the metastatic-promoting effect of miR-17.

Results: miR-17-5p was significantly enriched in serum exosomes of metastatic patients. In MRC-5 cells, it suppressed NKRF, NF-κB signaling, and increased secretion of IL-6 and IL-8, enhancing Cal62 proliferation and migration. Animal experiments confirmed its role in promoting tumor growth and lung metastasis.

Conclusions: Exosomal miR-17-5p remodels the pulmonary microenvironment into a pro-inflammatory niche, facilitating thyroid cancer colonization and offering a potential therapeutic target.

Objectives: Chemotherapy-induced lung inflammation limits the efficacy of anticancer therapies such as gefitinib in non-small cell lung cancer (NSCLC). Glutamic acid-leucine-arginine positive (ELR+) CXC chemokines and their receptors, CXC chemokine receptor 1 and 2 (CXCR1 and CXCR2), mediate both inflammatory responses and tumor progression. This study evaluated the effects of CXCR1/2 antagonism by G31P, a CXC motif chemokine ligand 8 (CXCL8)-mutated peptide, alone or in combination with gefitinib, on lung cancer growth and chemotherapy-induced pulmonary inflammation.

Methods: Human NSCLC cell lines (A549 and H460) were treated with gefitinib and/or G31P. Cell proliferation, apoptosis, and signaling pathways, including protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) phosphorylation, were evaluated by cell counting kit-8 (CCK-8) assay, flow cytometry, and Western blotting. An orthotopic lung tumor xenograft model was established in BALB/c nude mice to evaluate tumor growth, metastasis, cytokine expression, and lung histopathology. A bleomycin-induced lung injury model was also used to assess the anti-inflammatory effects of G31P, with or without gefitinib, by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry of inflammatory markers.

Results: G31P and Gefitinib, either alone or combined, inhibited proliferation and migration of A549 and H460 cells in vitro. Combination treatment effectively reduced AKT and ERK phosphorylation in both cell lines. In vivo, G31P with gefitinib significantly suppressed tumor growth, metastasis, and increased apoptosis. G31P decreased CXCL1 and CXCL2, and tumor necrosis factor-alpha (TNF-α) mRNA levels, lung hydroxyproline content, and myeloperoxidase (MPO) activity in the lungs of mice. In the bleomycin-induced lung injury model, G31P similarly reduced inflammatory responses.

Conclusion: CXCR1/2 antagonism by G31P attenuates chemotherapy-induced pulmonary inflammation and enhances the anti-tumor efficacy of gefitinib in NSCLC. These findings support the therapeutic potential of G31P as an adjuvant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to improve clinical outcomes by limiting inflammation.

The tumor microenvironment (TME) is a complex network composed of non-tumor cells, extracellular matrix, blood vessels, and various molecular signals that surround and profoundly influence tumor progression. As one of the key immune effector cells within the TME, mast cells (MCs) exhibit functional complexity, and their specific roles remain widely debated. Depending on the cancer type, spatial distribution, and interactions with other TME components, MCs can demonstrate dual regulatory capabilities-either promoting or inhibiting tumor growth. This characteristic has made them an important focus in current tumor immunology research. This review aims to systematically review the current understanding of MCs in the TME, with emphasis on their characteristics and functional differences across various tumor types, pathological status, and species. In recent years, advances in the understanding of MC markers, activation mechanisms, and biological functions have made targeting specific MC subsets an emerging therapeutic strategy. By comprehensively examining the origin, activation mechanisms, cellular interactions, and therapeutic regulation of MCs, this review provides new perspectives and a basis for future directions in tumor research and treatment.