Technology in Cancer Research & Treatment最新文献

IntroductionOsteosarcoma (OS) is a highly aggressive primary bone malignancy with poor prognosis. Histone modifications play crucial roles in tumor progression, but their systematic investigation in OS remains unexplored.MethodsThis study integrated single-cell RNA sequencing data and large-scale clinical information to systematically analyze the spatial heterogeneity of histone modifications in OS and their clinical significance. We employed Seurat for single-cell data analysis, CellChat for cell-cell communication network analysis, and LASSO Cox regression to construct a prognostic model. Additionally, we conducted functional enrichment analysis, immune characteristics analysis, and drug sensitivity prediction.ResultsWe identified five major cell types in the OS microenvironment and discovered significant differences in histone modification levels among different cell types, with osteosarcoma cells and endothelial cells exhibiting higher modification levels. Cell-cell communication network analysis revealed the importance of signaling pathways such as SPP1, CypA, MIF, IGFBP, and VEGF in OS. Based on nine histone modification-related genes, we constructed an efficient prognostic model (AUC values of 0.713, 0.845, and 0.888 for 1-, 3-, and 5-year predictions, respectively), which was validated in an external cohort (AUC = 0.808). Immune microenvironment analysis showed significantly higher proportions of CD8+ T cells and Treg cells in the low-risk group. Drug sensitivity analysis revealed that the low-risk group was more sensitive to Imatinib, Rapamycin, and Sunitinib, while the high-risk group was more sensitive to MAPK pathway inhibitors.ConclusionThis study systematically revealed the spatial heterogeneity of histone modifications in OS and their clinical significance for the first time, proposing an "epigenetic-immune" regulatory network hypothesis and developing a histone modification-based prognostic model. Our proposed "epigenetic-guided personalized medication strategy" provides new insights for precision treatment of OS, potentially significantly improving patient prognosis.

Colorectal cancer (CRC) remains a formidable global health challenge, with the majority of patients exhibiting microsatellite stable (MSS) and proficient mismatch repair (pMMR) tumors that are largely unresponsive to immune checkpoint inhibitors (ICIs). The management of MSS/pMMR CRC remains a clinical challenge due to the intrinsic resistance to ICIs. The innovative strategy of combining cetuximab, an EGFR-targeting monoclonal antibody with immunomodulatory properties, offers a promising strategy to enhance the immunotherapeutic response in MSS/pMMR CRC. This combination therapy is rooted in the complementary therapeutic mechanisms of cetuximab and ICIs, which may synergistically improve overall response rates and durability of response. Although some preclinical and clinical data have suggested additional promising results, there are still some challenges and questions that need to be addressed. Further large-scale, randomized, phase III clinical trials are required to confirm the efficacy and safety of this combination therapy. The ongoing clinical trials evaluating the safety and efficacy of cetuximab-ICI combinations are eagerly anticipated to pave the way for a new era in personalized immunotherapy for MSS/pMMR CRC.

This review summarizes the intricate relationship between the microbiome and cancer initiation and development. Microbiome alterations impact metabolic pathways, immune responses, and gene expression, which can accelerate or mitigate cancer progression. We examine how dysbiosis affects tumor growth, metastasis, and treatment resistance. Additionally, we discuss the potential of microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, to modulate cancer metabolism. These interventions offer the possibility of reversing or controlling cancer progression, enhancing the efficacy of traditional treatments like chemotherapy and immunotherapy. Despite promising developments, challenges remain in identifying key microbial species and pathways and validating microbiome-targeted therapies through large-scale clinical trials. Nonetheless, the intersection of microbiome research and cancer initiation and development presents an exciting frontier for innovative therapies. This review offers a fresh perspective on cancer initiation and development by integrating microbiome insights, highlighting the potential for interdisciplinary research to enhance our understanding of cancer progression and treatment strategies.

IntroductionMultiple targets with varying distances are common in radiotherapy. Reducing treatment time in the plan design helps minimize patient movement and discomfort during the treatment process. This retrospective study aimed to investigate the impact of varying intertarget distances (ITDs) on the dosimetric differences and delivery efficiency of two single-isocenter techniques.MethodsITDs for 15 patients with dual-site vertebral metastases undergoing volume-modulated arc therapy (VMAT) were modified using Matlab 2019a. Distances of 2, 4, 6, 8, and 10 cm were considered. The VMAT plans were designed with a prescription dose of 40 Gy/20f on Infinity Linac and Monaco 5.40.01. Single-isocenter with jaw tracking (VMAT1) and fixed jaw (VMAT2) were compared in terms of dosimetry and delivery efficiency under different ITDs.ResultsResults showed that both VMAT plans exhibited dosimetric parameters meeting clinical requirements. The conformity index (CI) of VMAT1 plans was smaller than that of VMAT2 at ITD = 4, 6, and 8 cm (P = 0.007, 0.020, and 0.039, respectively), with no significant differences in other planning target volume dosimetry parameters. In terms of delivery efficiency, the treatment time of VMAT1 increased significantly when ITD > 2 cm compared with that at ITD = 2 cm (P = 0.000). Conversely, VMAT2 exhibited no significant change in treatment time at different ITDs (P = 0.073). For ITD = 2 cm, the treatment time of VMAT1 was shorter than that of VMAT2, with a median difference of 77 s. For ITD > 2 cm, the treatment time of VMAT2 was shorter than that of VMAT1, with a median difference ranging from 65 s to 121 s.ConclusionThe experimental results showed that the single-isocenter with jaw tracking is recommended in the planning design when ITDs are less than 2 cm. However, for ITDs greater than 2 cm, the single-isocenter with fixed jaw demonstrates high delivery efficiency.5075.

Immunotherapy has emerged as a pivotal advancement in oncological therapeutics, representing a paradigm shift from conventional treatment modalities including surgery, radiotherapy, and chemotherapy. This innovative approach demonstrates considerable clinical potential through its capacity to enhance systemic anti-tumor responses via active or passive immunomodulation. Compared to traditional therapies, immunotherapy offers distinct advantages such as broad applicability, rapid therapeutic onset, and reduced adverse effects. However, critical challenges persist in clinical implementation, particularly concerning treatment safety and efficacy optimization. Current limitations, including drug off-target effects and biological delivery barriers, frequently result in suboptimal therapeutic outcomes and severe complications such as autoimmune disorders and nonspecific inflammation. Recently advancements in drug delivery systems (DDS) present transformative solutions to these challenges. Sophisticated DDS platforms enable precise spatiotemporal delivery of tumor antigens, immunotherapeutic agents, and immunostimulatory molecules, thereby achieving targeted modulation of diverse immune cell populations. This technological innovation not only enhances therapeutic efficacy but also significantly mitigates adverse reactions, while facilitating synergistic combinations with conventional cancer treatments. In this review, we outline the application of new drug delivery platforms in major malignancies (including but not limited to melanoma, non-small cell lung cancer, hormone receptor-positive breast cancer, and hepatocellular carcinoma). We further propose evidence-based optimization strategies for next-generation delivery platforms, aiming to bridge the gap between preclinical development and clinical implementation in cancer immunotherapy.

AimsThis review aims to synthesize the existing literature on palliative radiotherapy (RT) delivered in two daily fractions for patients with advanced cancer, focusing on its impact on symptom alleviation, treatment tolerance, and the implications for clinical practice and future research.MethodsAn international team conducted this narrative review, adhering to SANRA guidelines. Studies published in English on palliative RT delivered in two daily fractions were selected without date restrictions. The literature search, using a combination of specific key terms, led to a comprehensive examination of relevant studies. Data on study objectives, treatment approaches, palliative effectiveness, and toxicity were extracted and qualitatively analyzed.ResultsThe review included 29 publications, showing consistent efficacy in symptom reduction (63.0%-100% palliative response rate) and general tolerability across various cancer types. These studies highlighted the potential radiobiological advantages and practicality of accelerated multi-fractionated regimens, which provide rapid tumor response with reduced late toxicity risks. Furthermore, the logistical benefits of such treatments, including shorter hospital stays and minimized travel requirements, were noted as particularly valuable during challenging times such as recent pandemics.ConclusionsThe evidence supports the integration of evidence-based, accelerated-hypofractionated RT into palliative care strategies, ensuring effective symptom management with minimal patient burden. Future research should focus on comparative studies on single versus multiple-cycle treatments, optimal intervals between treatment cycles, and the integration of advanced RT techniques.

IntroductionRenal cancer, particularly Kidney Renal Clear Cell Carcinoma (KIRC), remains a major clinical challenge due to its aggressive nature and poor prognosis. Identifying reliable biomarkers for tumor progression and survival is critical for improving patient outcomes. This study aimed to investigate the role of Centromere Protein F (CENPF) as a potential prognostic biomarker for renal cancer.MethodData from the TCGA database, including Kidney Chromophobe (KICH), Kidney Renal Papillary Cell Carcinoma (KIRP), and KIRC, were analyzed to identify differentially expressed genes. Molecular Complex Detection (MCODE) was used to identify significant gene modules among upregulated genes, and univariate Cox regression analyses assessed the prognostic value of hub genes. Retrospective qPCR was conducted on tissue and plasma samples from KIRC patients to validate findings. Single-cell sequencing data from the GSE159115 dataset were analyzed, and the CIBERSORT algorithm was applied to evaluate the composition of tumor immune infiltrating cells (TIICs).ResultsCENPF was identified as a hub gene significantly upregulated in renal cancer subtypes, with overexpression linked to worse survival outcomes in KIRC patients. Retrospective qPCR confirmed high CENPF expression was associated with poorer prognosis. Single-cell sequencing revealed that CENPF is predominantly expressed in T-cell clusters. TIIC analysis showed a negative correlation between CENPF and resting mast cells, but positive correlations with follicular helper T-cells and memory-activated CD4T-cells. Prognostic analysis indicated that high follicular helper T-cell expression predicted poorer survival, while high plasma cell expression correlated with better outcomes.ConclusionCENPF plays a critical role in tumor progression and the modulation of the tumor immune microenvironment in KIRC. These findings suggest that CENPF could serve as a valuable prognostic biomarker and potential target for therapeutic intervention in renal cancer.

Background: The prognostic value of the Geriatric 8 (G8) screening score in metastatic renal cell carcinoma (mRCC) patients receiving first-line immunotherapy remains unclear. This study aimed to evaluate the prognostic role of G8 within the context of the Meet-URO classification in mRCC patients treated with first-line ipilimumab-nivolumab.

Methods: This retrospective multicentre study analysed 106 mRCC patients treated with first-line ipilimumab-nivolumab. G8 and Meet-URO scores were calculated before treatment initiation. Primary endpoint was overall survival (OS), defined as duration from first administration of Nivolumab to death. OS was analysed in relation to age groups, G8 scores, and Meet-URO score categories, with data censored for patients still alive at the last follow-up. The secondary endpoint, progression-free survival (PFS), was measured from initiating Nivolumab to the earliest instance of disease progression or death. OS and PFS were assessed using Kaplan-Meier methods and Cox regression analyses. The reporting of this study conforms to the REMARK guidelines.

Results: Patients with G8 > 14 had more favorable IMDC and Meet-URO risk classifications and lower neutrophil-to-lymphocyte ratios. While PFS did not differ significantly between G8 ≤ 14 and >14 groups (1-year 29.3% vs 46.2%, p = 0.2), OS was significantly longer in G8 > 14 group (1-year 76.1% vs 58.6%, p = 0.006). In multivariable analysis, G8 ≤ 14 was independently associated with worse OS (HR 2.36, 95% CI 1.06-5.08, p = 0.03) but not PFS. The Meet-URO score was prognostic for both PFS and OS. In patients ≥70 years, G8 lost its prognostic value, while Meet-URO remained prognostic for OS.

Conclusions: The G8 score is an independent prognostic factor for OS but not PFS in mRCC patients receiving first-line ipilimumab-nivolumab. The Meet-URO score shows consistent prognostic ability for PFS and OS across age groups. These findings suggest that while G8 may be useful for individual patient-level OS prediction, the Meet-URO score may be superior for guiding treatment decisions in clinical practice.

IntroductionUterine sarcoma (US) is an extremely rare and aggressive gynecologic malignancy with a poor overall survival (OS). The efficient prognostic biomarker is currently lacking.MethodsUtilizing a Sweden microarray dataset from the Gene Expression Omnibus (GEO) (GSE119043, n = 50) and a clinical cohort (n = 31) retrospectively collected from Suining Central Hospital, we analyzed β-catenin expression profiles and corresponding clinicopathological characteristics. Immunohistochemistry (IHC) was used to assess β-catenin expression level. Survival analysis was used to assess the relationship between β-catenin expression and prognosis. Gene set enrichment analysis (GSEA) was performed to characterize the specific pathways involved in β-catenin expression.ResultsImmunohistochemistry indicated that β-catenin expression was significantly upregulated in US group compared to both the normal uterine smooth muscle (UNSM) and uterine leiomyoma (ULM) groups (P < .01). IHC also exhibited a significant difference in β-catenin expression levels in four pathological subtypes. Leiomyosarcoma (LMS) and high-grade endometrial stromal sarcoma (HG-ESS) suggested higher levels of β-catenin expression compared with adenosarcoma (AS) or low-grade endometrial stromal sarcoma (LG-ESS), but no statistically significant difference was found in box plot (P > .05). GSEA indicated that transcriptional dysregulation in cancer, Wnt, AMPK, MAPK, PI3K, p53, Ras, and TNF signaling pathway were positively enriched in β-catenin high-expression group. Though survival analysis showed that β-catenin expression level was not associated with survival, low-β-catenin expression group showed a longer median OS compared to high expression group (56.17 months VS 9.60 months) in Sweden microarray dataset. Similar results were also observed for progression-free survival (PFS) in clinical cohort (not reached VS 45.97 months in high-expression group). Tumor type, lymphadenectomy, family history of malignancy and tumor recurrence remained significant predictors of OS, while only tumor type, stage and tumor recurrence had prognostic significance for PFS. Age, tumor size, menopausal status, CA125, adjuvant chemotherapy, and adjuvant radiotherapy, were not associated with survival (P > .05).Conclusionβ-catenin was highly expressed in uterine sarcoma and may be promising as a novel potential biomarker for diagnosis and prognosis.