World journal of clinical oncology最新文献

Imaging evaluation of lymph node metastasis and infiltration faces problems such as low artificial outline efficiency and insufficient consistency. Deep learning technology based on convolutional neural networks has greatly improved the technical effect of radiomics in lymph node pathological characteristics analysis and efficacy monitoring through automatic lymph node detection, precise segmentation and three-dimensional reconstruction algorithms. This review focuses on the automatic lymph node segmentation model, treatment response prediction algorithm and benign and malignant differential diagnosis system for multimodal imaging, in order to provide a basis for further research on artificial intelligence to assist lymph node disease management and clinical decision-making, and provide a reference for promoting the construction of a system for accurate diagnosis, personalized treatment and prognostic evaluation of lymph node-related diseases.

Proteases are essential for homeostasis, and their primary function is proteolytic in extracellular and intracellular compartments. The deregulation of expression, abundance, and activity of proteases has been related to several pathologies, including cancer. This deregulation contributes to their pro-tumorigenic activity since they participate in the degradation of extracellular matrix components and adhesion molecules, and the activation of growth factors. However, some proteases, such as ADAM metallopeptidase with thrombospondin type 1 motif 8 and kallikrein-related peptidases 5 and 10, have emerged as tumor suppressors due to their antitumoral actions in specific cancer contexts. In this article, we discuss the antitumoral effects of ADAM metallopeptidase with thrombospondin type 1 motif 8, kallikrein-related peptidases 5 and 10 that have been described to date, suggesting their potential use as novel biomarkers and therapeutic targets in cancer.

Background: MicroRNAs play a key role in regulating gene expression in human cells. Single-nucleotide variants in these molecules have been linked to cancer development, particularly breast cancer (BrC).

Aim: To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.

Methods: This case-control study included 71 women diagnosed with BrC and 215 women without BrC. Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay. Multiple genetic models - dominant, recessive, over-dominant, additive, and multiple comparison - were applied to assess the risk.

Results: The over-dominant model showed that the C/T genotype of MIR196A2 (rs11614913) is a protective factor against the ductal histological subtype of BrC in women from western Mexico [odds ratio (OR) = 0.4687, 95% confidence interval (CI): 0.2205-0.9963, P = 0.0489]. A protective effect was also observed for the C/A genotype (OR = 0.2612, 95%CI: 0.0900-0.7582, P = 0.0135) and A allele (OR = 0.2826, 95%CI: 0.0993-0.8044, P = 0.0179) of MIR618 (rs2682818). No significant association was found between MIR200C (rs73262897) and BrC risk.

Conclusion: The C/T genotype of rs11614913 in MIR196A2, and C/A genotype and A allele of rs2682818 in MIR618, are associated with a protective effect against BrC in women from western Mexico.

Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity. However, its clinical relevance is still not explicit, limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application. This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges. Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin's therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability. Although its molecular targets remain undefined, evidence indicates that cardamonin can inhibit various signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells, mammalian target of rapamycin, signal transducer and activator of transcription 3, and Wnt/β-catenin. The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials. Despite these limitations, cardamonin has, however, demonstrated antiproliferative, anti-metastatic, and chemosensitizing effects, mainly against breast, colorectal, and ovarian cancers. Nevertheless, exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.

Background: Breast cancer is a prevalent malignant tumor among women. Despite significant advancements in the development and implementation of various anti-breast cancer therapies, enhancing the efficacy of these drugs while minimizing their toxicity remains a challenge.

Aim: To explore the functional impact of the targeted long chain non-coding RNA (LncRNA) of Chidamide on the activity of natural killer (NK) cells via programmed death-ligand 1 (PD-L1), particularly focusing on the mechanisms by which NK cells influence breast cancer cells.

Methods: This study screened the positive LncRNA molecule Linc01010 through high-throughput sequencing, which can counteract the pharmacological effects of Chidamide. Luciferase localization analysis revealed that the Linc01010 fragment was situated in the proximal exon 4-3 region, identified as its functionally active region. Electrophoretic mobility shift assays and RNA-protein pull-down experiments demonstrated the interaction between Chidamide-induced Linc01010 expression and the target protein mitogen-activated protein kinase kinase 6 (MKK6). Western blotting and quantitative polymerase chain reaction analyses indicated that Chidamide enhanced the expression of the downstream effector PD-L1 by activating the corresponding p38-mitogen-activated protein kinases pathway.

Results: While investigating the effects of the Chidamide-Linc01010-MKK6-PD-L1 axis on the immune cell line NK-92, we observed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) secretion was significantly inhibited by this response axis. Furthermore, reducing TRAIL secretion within the tumor microenvironment diminished the death effects in breast cancer cells induced by Chidamide.

Conclusion: Our study provides a robust foundation for improving the effectiveness of current anti-breast cancer medications and for identifying new targets related to drug resistance.

This article comments on the article by Rana and Prajapati published in the recent issue. Cancer remains the most formidable public health problem and contributes to significant mortality worldwide. Tumor heterogeneity, toxicity and acquired resistance limit the efficacy of widely used cancer therapies such as radiotherapy, chemotherapy, gene therapy, and immunotherapy. Regulated cell death maintains cellular homeostasis and is a primary hallmark of cancer. Review by Rana and Prajapati discusses the mechanistic regulation of ferroptosis, autophagy, and mitochondrial dynamics in cancer and highlights the therapeutic possibilities of these regulated cell death pathways for developing more effective and targeted cancer therapies, mainly for aggressive and drug-resistant tumors. Considering the important regulatory role of ferroptosis, autophagy and its dynamic interplay with mitochondrial metabolism in tumor pathogenesis, therapy resistance and metastasis, reshaping of the tumor microenvironment with modulations in autophagy and mitochondrial function could sensitize ferroptosis-resistant tumors to anticancer drugs thereby increase the therapeutic efficacy of existing treatment regimens. Deeper understanding of the crosstalk may lead to the identification of non-invasive biomarkers for detecting ferroptosis-sensitive and resistant tumors, prediction of treatment response and the development of clinically translatable pharmacological strategies to maximize patient benefit while minimizing adverse outcomes.

Background: Thermal ablation (TA), including radiofrequency ablation and microwave ablation, is a commonly used curative treatment for single small hepatocellular carcinoma (sHCC). The relative advantages of TA and surgical resection (SR) in terms of long-term survival remain controversial.

Aim: To compare their long-term efficacy in this patient population.

Methods: This population-based retrospective cohort study included 257 patients who received a first diagnosis of single sHCC and underwent SR or TA from January 2012 to September 2017. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS).

Results: The average follow-up duration was 11.4 years. The 1-, 3-, 5-, and 10-year OS rates were 95.8%, 86.0%, 82.5%, and 74.2% in the SR group vs 97.4%, 85.8%, 78.6%, and 65.6% in the TA group, with the median OS not yet reached. The 1-, 3-, 5-, and 10-year RFS rates were 79.8%, 59.6%, 46.2%, and 24.7% in the SR group vs 83.9%, 61.5%, 47.9%, and 41.2% in the TA group, with median RFS values of 3.95 and 4.63 years, respectively. No significant differences in OS or RFS were observed overall (OS: P = 0.244; RFS: P = 0.180), but in patients ≤ 60 years, TA led to a higher RFS than SR (P = 0.021). Multivariate analysis identified age, tumor differentiation grade, and Child-Pugh classification as independent risk factors for OS, whereas age and differentiation grade were significant risk factors for RFS.

Conclusion: In patients with single sHCC, SR, and TA offered comparable long-term efficacy. However, TA showed superior RFS in patients ≤ 60 years, suggesting that TA may be a reasonable option for younger patients, pending confirmation by prospective studies.

In this article we commented on an article published recently by Jiao et al. This retrospective study confirmed that the triple therapy of transarterial chemoembolization (TACE) combined with programmed death protein ligand 1 inhibitors and molecular targeted therapy can significantly reverse TACE resistance in advanced hepatocellular carcinoma. Compared with TACE alone, the triple therapy reduced the resistance rate from 38.8% to 9.7% and increased the median progression-free survival and median overall survival by 92.3% and 26.8%, respectively. TACE induces tumor antigen release and upregulates programmed death protein ligand 1, activating the effect of immune checkpoint inhibitors while molecular targeted therapy inhibits postembolization vascular regeneration, forming a dynamic synergistic network of embolization-immune activation-vascular inhibition. The maximum tumor diameter, capsule loss, and bilateral distribution were identified as independent predictors. This study provided level I evidence and promoted the transformation of advanced hepatocellular carcinoma treatment from single local intervention to an integrated model of local control-systemic treatment. In the future it will be necessary to analyze the dynamic evolution rules of the tumor microenvironment through cross-omics strategies, further explore biomarkers, optimize treatment sequences, and conduct multicenter prospective trials to verify long-term survival benefits and guide the optimization of individualized sequential treatment.

Current experimental models struggle to simulate the complex process of the transformation from atrophic gastritis to gastric cancer, while gastric organoid technology, especially region-specific modeling, provides a more precise in vitro platform for studying this carcinogenic mechanism. Helicobacter pylori activates carcinogenic signaling pathways through virulence factors, inducing DNA damage, epigenetic dysregulation, and immune microenvironment imbalance, driving inflammation-cancer conversion. Intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia serve as critical precursor lesions, gradually developing into dysplasia and adenocarcinoma under the influence of chronic inflammation and genetic instability through intestinal cell transformation and high trefoil factor 2-expressing cell expansion. The immune suppression, metabolic reprogramming, and matrix remodeling within the tumor microenvironment collaboratively create a pro-cancer ecosystem that accelerates inflammation-carcinogenesis transformation. The gastric organoid model successfully simulates the spatiotemporal dynamics of the carcinogenesis process in atrophic gastritis, and its future integration with single-cell omics, real-time imaging technologies, and artificial intelligence technologies could provide a more precise platform for elucidating molecular mechanisms and screening intervention strategies. These advances position gastric organoids as pivotal tools for clinical translation, enabling personalized risk stratification, early intervention targeting precancerous transitions, and ex vivo prediction of patient-specific therapeutic responses to guide precision management of gastric cancer.

The interaction between the lactate receptor GPR81 (also known as hydroxycarboxylic acid receptor 1, or HCAR1) and Splicing Factor Proline- and Glutamine-Rich protein promotes the tumor cell malignancy. GPR81 nuclear translocation plays an important role in driving cancer progression and could serve as a potential therapeutic target. Yang et al concluded in their study that lactate and its receptor, GPR81, play crucial roles in cancer progression, and are key players in linking the lactate-rich tumor microenvironment to cancer cell behavior. The ability of nuclear GPR81 to directly regulate gene expression, combined with extracellular matrix -mediated mechanical signaling, creates a potentially robust system for the coordinated adaptation and survival of cancer cells. Understanding these interactions could lead to the discovery of new therapeutic targets and improved treatment strategies for cancer.