World journal of clinical oncology最新文献

Pancreatic ductal adenocarcinoma remains largely refractory to current immunotherapies due to a profoundly immunosuppressive tumor microenvironment dominated by regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). These cells form a coordinated network that suppresses cytotoxic T lymphocytes and fosters tumor progression. Key mechanisms include Tregs secreting inhibitory cytokines like transforming growth factor β and interleukin-10, and upregulating immune checkpoints such as cytotoxic T-lymphocyte-associated protein 4 and programmed death 1. MDSCs deplete essential nutrients like arginine and generate reactive oxygen species, while TAMs polarized to an M2 phenotype produce chemokines including C-C motif chemokine ligand 2 and C-X-C motif chemokine ligand 12, which recruit more suppressive cells. Single-cell transcriptomic studies have uncovered prognostically relevant cellular subsets, such as caspase-4-high Tregs, highlighting this heterogeneity. Reciprocal signaling via interleukin-10 and transforming growth factor β creates a self-reinforcing immunosuppressive loop. Emerging therapeutic strategies aim to disrupt this axis by depleting Tregs (e.g., anti-CD25), blocking MDSC recruitment (e.g., CCR2 inhibitors), or reprogramming TAMs (e.g., CD40 agonists), often in combination with programmed death 1/programmed death-ligand 1 blockade. An integrated approach targeting these populations holds promise for converting pancreatic ductal adenocarcinoma into an immunologically responsive tumor.

Tumor dormancy is a fundamental phenomenon in cancer biology, characterized by malignant cells that remain viable but non-proliferative, thereby frequently evading detection and treatment. This review examines the intricate role of the tumor microenvironment (TME) in regulating tumor cell dormancy. The TME encompasses a diverse array of components, including immune cells, extracellular matrix proteins, and soluble factors, all of which contribute to a dynamic interplay that influences tumor cell behavior. Key mechanisms involved in the maintenance of dormancy include immune surveillance, where immune cells can either suppress or promote tumor growth, and extracellular matrix interactions that provide structural support and biochemical signals essential for quiescence. Additionally, microenvironmental conditions such as hypoxia and acidosis impose selective pressures that can favor dormant states over active proliferation. Emerging therapeutic strategies are being explored to target dormant tumor cells, including the use of mesenchymal stem cell therapies, which may modulate the TME to either awaken dormant cells for targeted treatment or maintain their quiescent state to prevent recurrence. Understanding the TME's influence on tumor dormancy not only enhances our comprehension of cancer progression but also opens avenues for innovative treatments aimed at improving patient outcomes by mitigating the risks of recurrence and metastasis. This article aims to provide a comprehensive overview of the current knowledge on TME-mediated tumor dormancy and highlight promising therapeutic strategies for future research.

Pancreatic cancer (PC) represents one of the most formidable challenges in oncology, necessitating continuous innovation in therapeutic strategies. Owing to its pivotal role in PC progression, lipid metabolism, which is characterized by dysregulated cholesterol biosynthesis, altered fatty acid profiles, and lipid-driven immunosuppression, has received increasing attention. These metabolic aberrations fuel tumour growth, chemoresistance, and metastasis while impairing immune surveillance. By targeting lipid pathways, emerging therapies hold promise for disrupting cancer cell survival and redefining PC treatment paradigms.

Military flight personnel face a higher risk of developing thyroid cancer than the general population due to prolonged exposure to unique occupational hazards, including high-altitude hypoxia, ionizing radiation, extreme physiological and psychological stress, and irregular diets and work schedules. Thyroid cancer is also the most common malignant tumor among military flight personnel. Military flight personnel diagnosed with thyroid cancer or experiencing complications during treatment will be grounded, which will severely impact military flight combat effectiveness. To better understand characteristics of this disease among military flight personnel, we conducted a literature review of relevant domestic and international studies. This mini-review summarizes recent research progress on the epidemiology, risk factors, clinical features, diagnosis, prevention, and treatment strategies for thyroid cancer in this cohort. The ultimate aim is to inform targeted preventive and therapeutic measures, establish a multidisciplinary system for early screening, standardized treatment, and aeromedical assessment, thereby safeguarding personnel health and ensuring flight safety.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options, primarily relying on chemotherapy, yet often leading to recurrence due to chemoresistance. Cancer stem cells (CSCs) contribute to tumor heterogeneity, resistance, and poor prognosis, but data in Pakistani populations are scarce. This study hypothesizes that a positive CSC phenotype independently predicts reduced pathological complete response (pCR) and inferior survival outcomes.

Aim: To investigate CSC markers' association with chemotherapy response and survival in Pakistani TNBC patients.

Methods: Retrospective cohort study at Institute of Radiotherapy and Nuclear Medicine, Peshawar, Pakistan, including 256 women with TNBC from January 2015 to December 2022. CSC markers (CD44 high, CD24 low, aldehyde dehydrogenase 1 positive) were assessed via immunohistochemistry on pre-treatment biopsies. Outcomes: pCR to neoadjuvant chemotherapy, overall survival, disease-free survival. Data were analyzed with multivariable logistic regression and Cox proportional hazards models, adjusting for age, tumor grade, and stage.

Results: The CSC-positive phenotype was identified in 26 patients (10.2%). Compared to negative cases, positive cases had lower pCR rates [5.0% vs 51.8%; adjusted odds ratio = 0.05, 95% confidence interval (CI): 0.01-0.39, P = 0.004]. The positive phenotype was associated with poorer overall survival (adjusted hazard ratio = 4.35, 95%CI: 2.43-7.79, P < 0.001), with a median overall survival of 19 months vs 27 months. No association with disease-free survival was observed (hazard ratio = 0.86, 95%CI: 0.43-1.73, P = 0.675).

Conclusion: CSC markers are associated with reduced chemotherapy response and inferior overall survival in Pakistani TNBC patients. These findings suggest their potential as prognostic biomarkers and highlight the need for future research into targeted strategies, such as proteomic profiling and Proteolysis Targeting Chimeras technology, to overcome chemoresistance in this population.

Background: Colorectal cancer (CRC), encompassing both colon and rectal carcinogenesis, is a major health concern. Metastatic CRC (mCRC) is the third most common cancer and the second leading cause of cancer-related death in United States adults. Despite advances in therapy, the 5-year survival rate remains low at 15%. KRAS mutations contribute to treatment resistance by altering the tumor microenvironment, necessitating novel therapeutic approaches.

Aim: To evaluate immunomodulatory and cytotoxic potential of reovirus as an adjuvant therapy in KRAS-mutant-mCRC patients by analyzing gene and cytokine expression.

Methods: Five KRAS-mutant mCRC patients were treated with reovirus. Serum samples were collected at five time points over 15 days. Cytokine levels were measured using enzyme-linked immunosorbent assay, and transcriptomic profiling was performed to assess gene expression. Data were analyzed using the 2^-ΔΔCt method, and statistical significance was determined via two-tailed t-tests (P < 0.05).

Results: Out of 271 genes associated with Janus kinase/signal transducer and activator of transcription, Ras, Wnt, and phosphoinositide 3-kinase- alpha serine/threonine-protein kinase pathways, 85 showed significant modulation. Additionally, 17 of 25 cytokines were significantly altered. Reovirus induced changes in both gene and cytokine expression, suggesting activation of a complex intracellular signaling network.

Conclusion: Reovirus demonstrates potential as an immunomodulatory and cytotoxic adjuvant in KRAS-mutant mCRC by altering key signaling pathways and cytokine profiles. These findings support further investigation into its potential therapeutic contributions.

Tumor heterogeneity is one of the central challenges in oncology, contributing to treatment resistance and disease recurrence. Bulk RNA sequencing has advanced understanding of tumor biology, yet its averaging effect conceals cell type-specific alterations. Single-cell RNA sequencing overcomes this limitation by capturing gene expression and cellular phenotypes with high-resolution, thereby illuminating tumor composition and the surrounding microenvironment. Within this framework, differential abundance (DA) detection has emerged as a powerful strategy to quantify shifts in cell population proportions across conditions. Unlike differential gene expression, DA highlights compositional changes in cellular ecosystems, offering a structural perspective on tumor dynamics. This review introduces the main categories of DA methods in single-cell RNA sequencing analysis, outlining their modeling strategies, assumptions, and representative applications in oncology. We also discuss key challenges, including reliance on clustering quality and batch correction. By linking methodological principles with biological insight, this review clarifies the role of DA detection in single-cell oncology and provides a conceptual framework for integrating compositional analysis into efforts to understand tumor evolution, treatment response, and disease stratification.

Background: An observed correlation between increased colorectal cancer (CRC) incidence in patients with obesity [body mass index (BMI) ≥ 30 kg/m²] has been identified in past literature. However, there has been limited data in recent decades. This, along with a dramatic global increase in obesity rates, exposure to environmental and lifestyle risk factors for CRC development, and large updates to the proposed biological mechanisms underpinning this relationship, warrants an updated review of recent data between CRC and obesity.

Aim: To determine if an updated correlation exists between obesity and the risk of CRC development.

Methods: We evaluated recent data, synthesising pooled estimate effects to determine if an updated correlation exists between obesity and CRC. Observational studies were identified from a range of databases (PubMed, EMBASE, Scopus and the Cochrane database). From the studies identified, sex-stratified meta-analyses were conducted. Additionally, studies included in this review that were unfit for meta-analysis underwent qualitative analysis.

Results: In a pooled sample size of 83506 male participants obtained from six observational studies, a significant positive correlation between obesity and CRC incidence was identified with a hazard ratio (HR) of 1.71 [95% confidence interval (CI): 1.44-2.02]. A pooled sample size of 152043 female participants from six observational studies also revealed a positive correlation with an HR effect of 1.26 (95%CI: 1.03-1.53). Qualitative analysis of studies not included in the meta-analysis consistently supported this relationship for both sexes.

Conclusion: Obesity, diagnosed by a BMI ≥ 30 kg/m², significantly increases the risk of CRC incidence compared to those of a healthy BMI underscoring the importance of focused strategies to prevent obesity as a modifiable risk factor to reduce CRC incidence.

Background: We have previously reported that the cancer/testis antigen Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is frequently expressed in gastric cancer (GC), with a particularly high positivity rate observed in patients with multiple GCs. Thus, we conducted a preliminary study to further investigate the relationship between KK-LC-1 expression and multiple GCs. Specifically, we aimed to explore the potential clinical utility of KK-LC-1 as a biomarker for identifying patients at risk of developing multiple gastric cancers, with a focus on its expression in the initial tumor lesions.

Aim: To investigate the association between KK-LC-1 expression and the development of multiple GCs in a preliminary cohort.

Methods: Among 124 patients (177 lesions) treated for GC at Toho University Medical Center Ohashi Hospital between September 2020 and November 2023, 109 (single cancer: 82; multiple cancers: 27) with available initial tumor specimens were enrolled. KK-LC-1 expression was assessed using immunohistochemistry, and clinicopathological correlations were analyzed using Fisher's exact test. Tumor locations were classified anatomically and analyses were performed, focusing on the initial cancer sites.

Results: In tumors located in the upper stomach, KK-LC-1 expression did not correlate with clinicopathological features. However, in the middle and lower stomach, KK-LC-1 expression was significantly associated with older age, differentiated histological types, and multiple cancers. Notably, all patients with multiple GCs had KK-LC-1-positive tumors (100%) in their initial lesions. The KK-LC-1 positivity rate in the initial tumors of multiple cancers in the middle and lower region was significantly higher than that in solitary cancers. Conversely, the absence of KK-LC-1 expression in a solitary tumor located in the middle and lower region may suggest a reduced risk for the subsequent development of multiple primary cancers.

Conclusion: KK-LC-1 expression in the initial gastric tumors, particularly in the middle and lower stomach regions, may serve as a predictive biomarker for the future development of multiple GCs.

Background: Adult sacrococcygeal teratoma (SCT) is extremely rare in clinical practice, with most cases manifesting as mature cystic types. Given the scarcity of clinical studies and literature on this topic, standardized surgical guidelines for adults are notably absent, and current treatment strategies are predominantly derived from pediatric surgical practices. Furthermore, data on surgical outcomes and risk factors for postoperative dysfunction or recurrence in adult patients remain limited. Continued research on tumor treatment modalities and risk factors is still warranted.

Aim: To assess surgical outcomes and identify risk factors for dysfunction and recurrence in adult mature cystic SCTs.

Methods: We conducted a retrospective analysis of 64 adult patients with mature cystic SCT who received surgical treatment at Shandong Provincial Hospital Affiliated to Shandong First Medical University, from January 2005 to December 2020, ensuring all had complete clinical and follow-up data. We compared the clinical outcomes of three different surgical approaches: Laparoscopic-assisted anterior (Type A), posterior (Type B), and combined laparoscopic-posterior (Type C), evaluating them through perioperative indicators. Univariate and multivariate logistic regression analyses were performed to determine risk factors for postoperative dysfunction and tumor recurrence.

Results: The study incorporated 64 patients, all of whom had been pathologically confirmed to have mature cystic SCTs. The clinical efficacy in adult mature cystic SCTs was not significantly impacted by the various surgical approaches employed. Maximum tumor diameter of 10 cm or more, Altman classification of type III/IV, and intraoperative blood loss of 400 mL or greater were risk factors for postoperative dysfunction (anorectal dysfunction, urinary dysfunction and lower extremity motor dysfunction). The sacrococcyx being left unresected was determined to be an independent risk factor for tumor recurrence.

Conclusion: Surgical approach does not affect outcomes; larger tumors, advanced Altman type, blood loss, and unresected sacrococcyx increase risks of dysfunction and recurrence.