World journal of clinical oncology最新文献

Chemoresistance remains a major challenge in non-small cell lung cancer, especially for cisplatin (DDP)-based therapies, which are a mainstay of treatment. In their study, Dai et al investigate how inflammatory cytokines within the tumor microenvironment contribute to DDP resistance. By analyzing tumor samples from 20 non-small cell lung cancer patients and two resistant cell lines (A549/ DDP and SK-MES-1/DDP), the authors show that increased levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α are linked to resistance. Logistic regression identifies IL-6 and IL-8 as key risk factors. Functional experiments using tocilizumab, an IL-6 receptor antagonist, demonstrate a reduction in DDP half maximum inhibitory concentration, higher apoptosis rates, and decreased migration and invasion in resistant cells. Although the study has certain limitations, such as the analysis of only five inflammatory cytokines in a small, non-stratified patient cohort; it demonstrates that targeting the IL-6 cytokine axis may help overcome DDP resistance. Overall, the study highlights the inflammatory component of the tumor microenvironment as a modifiable driver of chemoresistance and provide a rationale for integrating cytokine blockade into platinum-based chemotherapy regimens to enhance therapeutic response.

Background: The purpose of this paper is to demonstrate a practical stem cell collection method that provides sufficient stem cells for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients despite low peripheral CD34 (pCD34) counts and to describe the benefits of this method for MM patients with limited resources.

Aim: To demonstrate a practical method for stem cell collection.

Methods: Stem cell collection data on the last 300 patients at a community cancer center in Washington were reviewed. We report on the methods of collection, including medications used and timing, used by the blood blank as well as their outcomes. The three MM patients with initially very low pCD34 counts all successfully underwent stem cell collection in a single trip to the transplant center for their ASCT.

Results: Three patients whose pre-collection pCD34 counts were the lowest and less than 2.5 cells/μL were identified. These patients had the commonality of having multiple barriers to transportation and likely would have been able to make only one trip for the stem cell collections.

Conclusion: Despite particularly low pre-collection peripheral blood CD34 counts, successful autologous stem cell collection in MM patients is feasible by routinely adding plerixafor to granulocyte-colony stimulating factor on day 4 of mobilization. There is limited analysis demonstrating that sufficient stem cells for one or more transplants can be collected using this method. This practical and novel approach may benefit the high number of MM patients who face limited resources, finances, long travel times, and social support. These results are highly relevant to physicians treating similar patients.

Sirtuin 3 (SIRT3) is a primary mitochondrial deacetylase. Studies have confirmed that it directly activates mitophagy by modulating mitochondrial protein acetylation. As a key homeostatic mechanism, mitophagy activation alleviates oxidative stress-induced imbalance between cell proliferation and apoptosis, corrects stress-driven mitochondrial metabolic dysfunction, and thus inhibits excessive tumor growth, exerting significant antitumor effects. These functions establish SIRT3 as a key target for regulating mitophagy and cancer therapy. Clinically, strategies centered on its precise regulation may offer a novel direction for gastric cancer (GC) prevention and treatment, with selective activation remaining a critical challenge. SIRT3 could also serve as an auxiliary indicator in clinical guidelines for assessing tumor progression. Given this potential, this mini-review systematically examines SIRT3's mechanisms in regulating mitophagy, its role in GC pathogenesis, and translational prospects for targeting SIRT3 in GC management.

Background: Anaplastic lymphoma kinase (ALK) gene fusion is a molecular subtype of non-small cell lung cancer, representing 4%-6% of lung adenocarcinomas. Axillary lymph node (ALN) metastasis from lung cancer is rare, and massive bleeding from such lesions is an even more unusual and life-threatening complication. This case demonstrates how localized radiotherapy can be used as an effective hemostatic and tumor-controlling measure when conventional interventions fail.

Case summary: A 48-year-old male presented in October 2019 with ALK-positive lung adenocarcinoma and multiple metastases. He received multiple lines of ALK tyrosine kinase inhibitor therapy, whole-brain radiotherapy, stereotactic radiotherapy, chemotherapy, and targeted agents over 4 years and 7 months. In February 2024, rapid enlargement and rupture of a left ALN metastasis caused massive bleeding. Interventional and surgical hemostasis were not feasible. Localized radiotherapy was initiated at 15 Gray in 5 fractions, later increased to a total of 39 Gray in 13 fractions, resulting in rapid bleeding control and partial tumor response. The patient subsequently received chemotherapy, and the axillary lesion healed without recurrent bleeding. However, three months later, he developed severe pneumonia with mixed bacterial, mycobacterial, and fungal infections and died despite intensive care.

Conclusion: Radiotherapy can effectively control bleeding and achieve local tumor control in ALK-positive lung cancer with ruptured ALN metastasis when other treatments are ineffective.

Background: Laryngeal squamous cell carcinoma (LSCC) is a prevalent head and neck malignancy with suboptimal survival rates due to late detection and therapeutic resistance.

Aim: To investigate chaperonin-containing TCP1 subunit 3 (CCT3) expression and its clinical implications, and its effects on LSCC cell growth.

Methods: Systematic data on CCT3 mRNA expression were collected from biomedical databases, and integrated further based on the standardized mean difference and the summary receiver operating characteristic curve. Single-cell RNA-seq data were mined to validate the expression level of CCT3 mRNA. In-house immunohistochemistry was performed to explore the CCT3 protein levels of clinical LSCC samples and their relationship with clinical parameters. The growth function of LSCC cell was analyzed using CRISPR knockout screening. CCT3-related signaling pathway analyses were conducted using gene set enrichment analysis. Protein-protein interaction network construction was performed to identify hub genes.

Results: CCT3 mRNA was significantly overexpressed in 269 LSCC tissues cases across multiple independent datasets (standardized mean difference = 32, area under the curve = 0.93); At the translational level, the in-house immunohistochemical analysis further demonstrated the consistent upregulation of CCT3 protein in 88 cases of LSCC samples (58 non-LSCC samples vs 30 LSCC samples, P = 1.4e^-14). Analysis of clinical parameters showed no significant differences among subgroup. Functional characterization with clustered regularly interspaced short palindromic repeats--mediated gene knockout revealed that depletion of CCT3 potently suppressed LSCC cell viability in vitro. Gene set enrichment analysis indicated that CCT3 was markedly associated with several key oncogenic pathways, including extracellular matrix receptor interaction and cell cycle regulation pathways.

Conclusion: CCT3 upregulation in LSCC may influence cellular growth by regulating related pathways, indicating its potential as a biomarker and therapeutic target for LSCC.

Genitourinary neoplasms, including bladder, prostate, renal, and testicular cancers, represent 25% of all solid tumors worldwide. Great advances have been achieved in the last few decades in diagnostic and therapeutic modalities. Among these, liquid biopsy (LB) technology has evolved during the past few years and offers emerging and novel modalities in the field of oncology. LB is performed by withdrawing bodily fluids (i.e., blood or urine) and looking for circulating tumor DNA, circulating tumor cells, extracellular vesicles, and non-coding RNAs, among others. Over the past years, several technologies have been developed to isolate and analyze the tumor burden. LB is less invasive than traditional biopsies and has many applications, including early screening, providing diagnostic cues, predicting disease severity and survival outcomes, assessing response and resistance to treatment, detecting minimal tumor burden before radiological evidence, and monitoring for disease recurrence. However, multiple challenges still need to be addressed, including reduction in variability between assays, standardization of protocols, and validation in large trials to ensure reliability. This review will focus on the latest advancements in LB applications for diagnostic and prognostic characterization of genitourinary cancers.

Background: Online adaptive radiotherapy (oART) has demonstrated improved target volume coverage and enhanced sparing of surrounding pelvic organs through daily re-optimization based on pretreatment imaging. Recently, iterative cone-beam computed tomography (iCBCT) has been integrated into oART workflows, facilitating precise daily adaptation. However, the dosimetric consequences of intra-fractional variations for clinical target volume (CTV) and organs at risk (OARs) remain insufficiently characterized.

Aim: To investigate intra-fractional CTV and OARs variation and their impact on iCBCT guided daily oART for postoperative cervical and endometrial cancer.

Methods: Seventeen patients treated with daily postoperative iCBCT guided oART with rigorous bladder and rectal preparation protocols were enrolled. CTV and OARs were contoured on pre- and post-treatment iCBCT scans. The average surface distance (ASD), dice similarity coefficient (DSC), and 95% Hausdorff distance (HD) were utilized to evaluate the difference between pre- and post-treatment structures. Dosimetric outcomes for the pretreatment target volumes and OARs were recalculated using posttreatment contours to assess the impact of intra-fractional variation.

Results: A total of 434 treatment fractions were analyzed, with an average interval time of 22 minutes between two iCBCT scans. Minimal variations were observed in the bladder, rectum, and CTV both pre- and post-treatment, with DSC exceeding 0.8. The vaginal CTV exhibited centroid deviations of 0.46 mm anteriorly, 0.11 mm laterally, and 0.58 mm superiorly, along with ASD of 1.69 mm and 95% HD of 6.42 mm. Weak correlations were observed between vaginal CTV posterior-anterior centroid deviations and rectal superior-inferior deviations (P = 0.017). Minimal dosimetric differences were observed pre- and post-treatment, with V_100% for the adapted plan of nodal CTV being 99.94% vs 99.08% and vaginal CTV being 99.97% vs 98.66%.

Conclusion: Daily iCBCT-guided oART with strict bladder and rectal preparation effectively compensates for intra-fractional variations, maintaining CTV coverage and OAR sparing across all treatment fractions.

Background: Nasopharyngeal carcinoma (NPC), exhibiting high incidence in southern China, is linked to genetic and environmental factors. Vitamin D metabolism, involving transport [group-specific component (GC) protein] and activation [25-hydroxylase (CYP2R1) enzyme], may influence NPC susceptibility and radiotherapy response. Polymorphisms in GC and CYP2R1 genes affect protein function and serum 25-hydroxyvitamin D [25(OH)D] levels, and are implicated in other cancers. However, their role in NPC - particularly in high-risk Han Chinese populations - and interaction with vitamin D status remains unclear. This case control study (360 NPC patients, 550 controls) investigates these relationships to inform prevention and personalized therapy.

Aim: To investigate the association between vitamin D binding protein (GC) and CYP2R1 gene polymorphisms with susceptibility to NPC and radiotherapy response.

Methods: A case control study design was adopted, and 360 patients with NPC and 550 healthy controls were included. TaqMan method was used to perform genotyping on GC gene loci rs4588, rs7041, and CYP2R1 gene loci rs10741657, rs12794714. Serum 25(OH)D levels were detected, and the relationship between gene polymorphisms and NPC risk and radiotherapy response was analyzed.

Results: The GC gene rs4588 TT genotype was significantly associated with the risk of NPC in both the codominant model [odds ratio (OR) = 1.68, 95%CI: 1.15-2.45, P = 0.007] and the recessive model (OR = 1.56, 95%CI: 1.02-2.38, P = 0.039). The association between the rs4588 TT genotype and the risk of NPC was more significant in the male subgroup (OR = 1.87, 95%CI: 1.11-3.15, P = 0.019) and the squamous cell carcinoma subgroup (OR = 1.89, 95%CI: 1.19-3.00, P = 0.007). The serum 25(OH)D level of the rs7041 AA genotype carriers was significantly lower than that of the CC genotype (P < 0.001). The CYP2R1 gene rs10741657 AA genotype was associated with higher serum 25(OH)D levels (P = 0.003). The rs12794714 AA genotype was associated with radiotherapy resistance (OR = 1.76, 95%CI: 1.18-2.63, P = 0.005). Stratified analysis showed that the association between rs4588 and rs12794714 was significant only in the subgroup with higher 25(OH)D levels.

Conclusion: GC and CYP2R1 genes polymorphisms are associated with NPC susceptibility and radiotherapy response, and this association may be affected by serum 25(OH)D levels. This study provides a new idea for the prevention and individualized treatment in NPC.

Metabolic syndrome (MetS), characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, has been increasingly recognized as a significant contributor to the development and progression of colorectal cancer (CRC). This review comprehensively summarizes current evidence linking MetS to CRC risk and outcomes from mechanistic, epidemiological, and clinical perspectives. Mechanistic studies suggest that hyperinsulinemia, activation of the insulin-like growth factor axis, chronic systemic inflammation, and adipokine dysregulation create a tumor-promoting environment. Epidemiological data from large-scale cohort studies and meta-analyses consistently demonstrate a positive association between MetS and CRC incidence, with abdominal obesity and hyperglycemia identified as key components. Mendelian randomization studies further support a causal relationship between visceral adiposity and CRC risk. Clinically, MetS is associated with increased risk of recurrence and reduced overall and disease-free survival in CRC patients. Emerging evidence also indicates that persistent metabolic abnormalities may contribute to early-onset CRC. Interventions targeting metabolic health - including lifestyle modification and bariatric surgery - have shown potential in reducing CRC risk and improving outcomes. Despite these advances, heterogeneity in MetS definitions and a paucity of prospective interventional studies limit the generalizability of current findings. Further research is warranted to establish standardized diagnostic criteria, elucidate sex- and age-specific mechanisms, and integrate metabolic profiling into risk stratification frameworks for CRC prevention and management.

Programmed death receptor-1 inhibitors have significantly improved the prognosis of various malignancies. Nevertheless, hyperprogressive disease (HPD), recognized as a severe adverse reaction to immunotherapy, causes a substantial surge in tumor burden and notably shortens the survival of 4%-29% of patients. This article comprehensively reviews the controversies regarding the clinical definition of HPD, its cross-cancer epidemiological features (encompassing gastric cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, etc.), and potential molecular mechanisms (such as MDM2/MDM4 gene amplification, EGFR mutations, and reprogramming of the immune microenvironment). It further delves into biomarker-based predictive models, targeted combination therapy strategies, and salvage treatment alternatives. Ultimately, it puts forward future directions, including the establishment of a multicenter HPD registry database and organoid predictive models, aiming to offer evidence-based guidance for clinical practice.