World journal of clinical oncology最新文献

Fibrosis is marked by the excessive accumulation of extracellular matrix (ECM) components, leading to tissue scarring and progressive loss of organ function. Myofibroblasts, which emerge during tissue repair, are specialized contractile cells exhibiting features of both fibroblasts and smooth muscle cells. Their expression of α-smooth muscle actin facilitates contractile activity, while their persistent activation and overproduction of ECM components contribute significantly to pathological wound contraction and fibrotic progression. Beyond ECM production, myofibroblasts play a significant role in the tumor microenvironment (TME) of various solid tumors. The TME is a complex network of immune cells, blood vessels, ECM components, and stromal cells like fibroblasts and myofibroblasts that surrounds and interacts with cancer cells, thereby influencing tumor growth, progression, and therapy responsiveness. Through these interactions, myofibroblasts modulate inflammation, angiogenesis, and tissue remodeling. Maintaining myofibroblast homeostasis is therefore crucial, as its disruption can drive the onset of chronic fibrotic conditions and malignancies. This review explores preclinical and clinical developments in targeting myofibroblasts in fibrotic and TME across various disease models, including hypertrophic scar, idiopathic pulmonary fibrosis, oral submucous fibrosis, cardiac fibrosis, and the desmoplastic stroma of pancreatic and breast cancers.

Background: Helicobacter pylori (H. pylori) infection is widely considered to be a major risk factor for gastric cancer, contributing to its development through the Correa cascade. Yin Yang 1 (YY1) is a transcription factor that acts as a promoter or suppressor of cancer progression. However, the role of YY1 in the inflammatory transformation associated with H. pylori-induced gastric cancer remains unclear.

Aim: To explore the expression of YY1 in gastric cancer and its impact on cancer progression with H. pylori infection.

Methods: H. pylori bacteria were cocultured with GSE1 cells, AGS cells, and SGC7901 cells, as well as in infected and xenograft mouse models. Expression of YY1, members of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, and epithelial-mesenchymal transition (EMT)-related proteins in gastric cancer was examined using Western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. Survival analysis was performed using the Kaplan-Meier method with the log-rank test. The role of YY1 in gastric cancer cell proliferation was further evaluated through in vitro and in vivo assays.

Results: YY1 was highly expressed in gastric cancer tissues and cells. Kaplan-Meier survival curves indicated that high YY1 expression correlated with a poor prognosis. YY1 expression showed a gradually increasing trend in H. pylori-induced gastritis and gastric tumors. In vivo and in vitro experiments demonstrated that H. pylori infection promoted phosphorylation of JAK2 and STAT3, thereby activating the EMT pathway, in which YY1 played a key role. YY1 and JAK2 interaction was validated by chromatin immunoprecipitation. YY1 knockdown or pharmacological inhibition reversed EMT and suppressed gastric cancer cell proliferation and metastasis.

Conclusion: These results suggest that YY1 plays an important role in progression of H. pylori-induced gastric cancer by activating EMT.

Malignant diseases in both children and adults are a worldwide public health priority with a high socioeconomic burden. Ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6) molecule exhibits divergent expression patterns across different cancers. Its increased expression in some tumors may allow them to escape anti-tumor immune responses, potentially by inducing an immunosuppressive tumor microenvironment and favoring a poorer prognosis. Conversely, in vivo, a mutated ENTPD6 gene may induce effective cytotoxic T cell responses, thereby reducing liver tumor size. Additionally, low expression of ENTPD6 has been related to chemotherapy resistance, whereas specific ENTPD6-derived neoepitopes may potentially enhance the efficacy of immunotherapy. This paper analyses the dual roles and clinical utility of ENTPD6 in cancer.

Background: Primary testicular lymphoma (PTL) is a rare, aggressive malignancy, representing a small fraction of testicular tumors and non-Hodgkin lymphomas, yet it is the most common testicular malignancy in older men. Diffuse large B-cell lymphoma (DLBCL), which is typically the aggressive subtype, dominates PTL and shows diffuse B-cell infiltration. Venous tumor thrombus, uncommon in lymphomas, is uniquely reported in this case of testicular DLBCL with gonadal vein involvement.

Case summary: A 62-year-old man presented with a two-month history of painless left testicular swelling and stiffness. Diagnostic imaging [ultrasonography, computed tomography (CT), and ¹⁸F-fluorodeoxyglucose positron emission tomography/CT (¹⁸F-FDG-PET/CT)] revealed bilateral testicular masses and a gonadal vein tumor thrombus (SUVmax 16.5). Left orchiectomy confirmed DLBCL with CD20, Bcl-2, and MUM1 positivity (Ki-67: approximately 80%). The disease was staged as Ann Arbor stage IVA (International Prognostic Index score 3, high-intermediate risk). The patient received Rituximab, Polatuzumab Vedotin, Cyclophosphamide, Epirubicin, and Prednisolone chemotherapy, completing the first cycle with good tolerability. No adverse events were reported, and follow-up is ongoing to assess long-term outcomes. This case highlights the diagnostic utility of ¹⁸F-FDG-PET/CT and the importance of multidisciplinary management in rare PTL presentations with tumor thrombus.

Conclusion: This case demonstrates the diagnostic complexities of PTL with gonadal vein tumor thrombus, underscoring the importance of considering lymphoma in elderly patients with testicular masses and venous involvement. A multi-disciplinary team including urologists, hematologists, and radiation oncologists is needed to ensure appropriate therapy.

Background: Cancer survivorship is a growing concern globally, yet few studies have explored the quality of life (QoL) outcomes among survivors in the Middle East, particularly in Saudi Arabia.

Aim: To assess QoL using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) and to evaluate the impact of demographic and clinical factors among Saudi cancer survivors.

Methods: We conducted a cross-sectional study of 102 adult cancer survivors recruited from a tertiary hospital in Jeddah, Saudi Arabia. Participants completed the WHOQOL-BREF, which assesses four QoL domains, including physical health, psychological health, social relationships, and environment. Univariate and multivariable robust linear regression models (Huber estimator) were used to identify QoL score predictors, adjusted for key sociodemographic and clinical variables.

Results: The mean participant age was 44.5 years; 72.5% of the participants were female. The mean domain scores were as follows: physical health was 3.05 ± 0.53, psychological health was 3.56 ± 0.79, social relationships was 3.39 ± 0.84, and environment was 3.29 ± 0.74. Socioeconomic and social vulnerability factors, including low income, rental housing, widowed/divorced marital status, and lower education, were independently associated with poorer QoL scores. Residents in rural settings had significantly lower scores in all domains.

Conclusion: Our findings reveal noticeable disparities in QoL among Saudi cancer survivors driven by socioeconomic and demographic factors. These insights underscore the need for context-sensitive survivorship programs in Saudi Arabia, with special attention to social support, mental health, and economic stability.

The gut microbiome plays a pivotal role in immune homeostasis and systemic inflammatory regulation, both of which are critically involved in the pathogenesis and progression of pediatric leukemias. Recent evidence reveals that children with leukemia often exhibit distinct gut microbiome profiles at diagnosis, marked by reduced microbial diversity and the enrichment of pro-inflammatory taxa such as Enterococcus and Streptococcus. This microbial dysbiosis may promote leukemogenesis by disrupting immune regulation and driving chronic inflammation. Chemotherapy significantly alters the gut microbiome, inducing dysbiosis characterized by a loss of beneficial commensals and the dominance of pathobionts. Specific microbial signatures, such as the enrichment of Bacteroides, correlate with reduced inflammation and improved prognosis, underscoring the gut microbiome's prognostic value. Emerging therapies, including dietary adjustments, probiotics, and fecal gut microbiome transplantation, aim to restore microbial balance and reduce treatment-related complications. Moreover, gut microbiome profiling shows potential for identifying biomarkers linked to leukemia predisposition, paving the way for early diagnosis and tailored preventive strategies. This mini-review explores recent advancements in understanding the influence of the gut microbiome on pediatric leukemias, emphasizing its role as both a therapeutic target and a prognostic biomarker. Integrating gut microbiome research into clinical practice may help optimize treatment outcomes and improve quality of life for children with leukemia.

Background: Claudin-6 (CLDN6), a tight junction protein typically restricted to embryonic tissues, is re-expressed in various cancers. However, its prognostic significance in high-grade endometrial carcinoma (HGEC) remains unclear.

Aim: To investigate the expression pattern of CLDN6 in HGEC and assess its correlation with clinicopathological parameters and patient survival.

Methods: Immunohistochemical analysis of CLDN6 expression was performed on formalin-fixed, paraffin-embedded tissues from 80 patients diagnosed with HGEC. Associations between CLDN6 expression and histological subtype, the International Federation of Gynecology and Obstetrics (FIGO) stage, depth of myometrial invasion, lymphovascular space invasion, recurrence, and survival outcomes were statistically analysed. Univariate and multivariate Cox regression models were used to identify independent prognostic factors.

Results: High CLDN6 expression was detected in a subset of HGEC patients and was significantly associated with nonendometrioid histology (P = 0.026), advanced FIGO stage (P = 0.015), deep myometrial invasion (P = 0.038), and recurrence (P = 0.002). While Kaplan-Meier analysis did not reveal a statistically significant difference in disease-free survival or overall survival between the high CLDN6 expression group and the low CLDN6 expression group, multivariate Cox regression revealed that CLDN6 overexpression was an independent predictor of shorter disease-free survival [hazard ratio (HR) = 68.98, P = 0.022] and overall survival (HR = 24.023, P = 0.038).

Conclusion: CLDN6 overexpression is associated with aggressive tumor features and poor clinical outcomes in HGEC, suggesting its utility as a prognostic biomarker and potential therapeutic target.

Organelle integrity and maintenance of protein homeostasis and purpose is essential for fundamental equilibrium and survivability. Autophagy is the primary process which regulates the distribution of different cell loads to lysosomes for destruction and reuse. Extensive research illustrates the protective functions of autophagy against various diseases. Though in cancer, noticeably contrasting functions of autophagy have been evaluated in the prohibition of preliminary tumor evolution vs the continuance and, anabolic and catabolic variations of well-established and invasive tumors. Autophagy possesses numerous roles in tumor microenvironment (TME) establishment and associated immune cells function which is addressed in recent studies. Autophagic machinery which is employed in different autophagy-related pathways contributes to metastatic diseases and are distinct from classical autophagy. Therapeutic strategies based on the inhibition or induction of autophagy and related processes has helped in the designing of efficient anticancer drugs. According to the review, we evaluate and decipher the various purposes of autophagy and its association with autophagy mechanisms in course of tumor development, invasion and progression. We summarize the latest findings involving the role of these activities including tumor cells and TME and define further breakthrough in therapy aiming at autophagic activities in cancer.

Background: Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) represents a distinct molecular cancer subtype that is often associated with a poor prognosis. While perioperative chemotherapy regimens are currently the primary recommendation for locally advanced HER2-positive GC, combination therapies incorporating immune checkpoint inhibitors are under active investigation.

Case summary: The present case describes a patient with locally advanced HER2-positive GC who underwent perioperative treatment with chemotherapy combined with trastuzumab. Although significant tumor shrinkage was observed, surgical pathology results did not confirm the achievement of a pathological complete response. The current treatment strategies for advanced GC were also reviewed. Relevant case reports, retrospective studies, and prospective clinical trials were retrieved for analysis after searching the PubMed/MEDLINE, EMBASE, Cochrane Library, Web of Science, and American Society of Clinical Oncology/European Society for Medical Oncology conference abstracts between 2014 and 2024.

Conclusion: Large-scale phase III clinical trials are needed to verify the efficacy of combined neoadjuvant treatment application for GC.