World journal of clinical oncology最新文献

Gastric carcinoma (GC) is one of the most common and deadly cancers worldwide, ranking fifth in incidence and third in cancer-related mortality. Despite significant advancements in surgical techniques and chemotherapy, the overall prognosis for GC remains poor, primarily due to late-stage diagnosis. Current diagnostic tools, such as endoscopy and biopsy, are invasive and are often utilized only after symptoms arise, leading to missed opportunities for early intervention. Traditional serum tumour markers, such as carcinoembryonic antigen and carbohydrate antigen 19-9, demonstrate limited sensitivity and specificity, particularly in the disease's early stages. GC often diagnosed at advanced stages due to a lack of early, specific biomarkers. Chronic inflammation plays a significant role in gastric carcinogenesis, particularly in cases of Helicobacter pylori-associated gastritis. Pro-inflammatory cytokines have gained attention as potential non-invasive serum biomarkers for early diagnosis and disease monitoring. In recent years, numerous studies have explored the potential of serum cytokines-such as interleukin (IL)-6, tumour necrosis factor-alpha, IL-8 and interferon-gamma-as biomarkers for detecting gastric cancer. Future research integrating cytokine profiling with imaging, endoscopic, or genomic data may revolutionize how we screen and manage GC.

Gastrointestinal malignancies, particularly pancreatobiliary and gastroesophageal cancers, are associated with poor prognosis due to their frequent late-stage diagnosis. Many of these tumors contribute to anorexia-cachexia syndrome and malnutrition, further exacerbating disease progression. Inflammation plays a crucial role in tumor proliferation, and growing evidence suggests that gut microbiome significantly influence inflammatory responses and clinical outcomes in these patients. Additionally, the gut microbiome contributes to carcinogenesis through multiple mechanisms, including DNA damage, activation of oncogenic pathways, and modulation of immune responses. The emerging field of nutritional interventions highlight the microbiome's impact on anticancer drug responses, affecting both chemotherapy and molecular-targeted treatments. Given its pivotal role, microbiome modulation through probiotics, fecal microbiome transplantation, and antibiotics represents a promising approach for cancer prevention and treatment. In this review, we explore the intricate interplay between gut microbiome, inflammation, and nutritional status in gastrointestinal cancers, emphasizing potential therapeutic strategies to improve patient outcomes.

Melanoma is an aggressive type of skin cancer notorious for its resistance to chemotherapy, radiotherapy and immunotherapy, which greatly impacts its lethality. The hedgehog (HH) signaling cascade, originally known for its roles in embryonic development, regulates growth, proliferation and cancer stem cell (CSC) self-renewal. The glioma-associated oncogene homolog (GLI) transcription factors play crucial roles in melanoma. However, oncogenic B-Raf proto-oncogene, serine/threonine kinase (BRAF) steals the spotlight by driving the aberrant activation of HH-GLI1/2 signaling. Oncogenic BRAF-driven HH-GLI1/2 signaling imparts invasive phenotype to melanoma cells and sustains CSC self-renewal. Interestingly, the transcriptional activities of GLI1 and GLI2 are suppressed by acetylation, a process that is counteracted by the deacetylating actions of histone deacetylase (HDAC) 1/2. Therefore, inhibiting HDAC1/2 might keep GLI proteins in inactive acetylated form, thus representing an attractive druggable target. Notably, both HDAC1 and HDAC2 are induced by HH signaling, creating a positive feedback loop where HH signaling upregulates the expression of both HDAC1 and HDAC2. Selective inhibition of BRAF/HH/HDAC/GLI signaling axis is likely to unravel new therapeutic opportunities in melanoma. However, the precise contribution of oncogenic BRAF-driven HH signaling to therapy resistance and CSC renewal remains unclear and requires thorough investigation. In this article, we endeavored to explore the crosstalk between oncogenic BRAF and HH signaling, and the pivotal role this interaction plays in the self-renewal of melanoma stem cells. A better understanding of the molecular mechanisms governing these interactions is essential for improving melanoma treatment strategies and identifying new therapeutic targets.

The urgent necessity for enhanced risk stratification to improve the efficiency of colonoscopy screening is underscored by the fact that colorectal cancer (CRC) continues to be a primary cause of global cancer mortality. Conventional models mostly rely on generalized obesity markers including body mass index (BMI), which does not effectively represent oncogenic risk linked with abdominal obesity. Liu et al undertook a large-scale case-control study comprising 6484 first-time colonoscopy patients at a prominent Chinese hospital between 2020 and 2023 to overcome this restriction. Age, male sex, smoking status, and raised waist-hip ratio (WHR) were found by multivariate logistic regression as independent predictors of advanced colorectal neoplasia (ACN). In a validation cohort of 1891 individuals, a new 7-point risk scoring model was created and stratified into low- (5.0%) ACN prevalence, moderate- (10.3%) and high-risk (17.6%). With C-statistic = 0.66 the model showed better discriminating ability than the Asia-Pacific Colorectal Screening (APCS) score (C-statistic = 0.63) and the BMI-modified APCS model. These results fit newly published data showing central obesity as a major carcinogenic driver via pro-inflammatory visceral adipokine channels. With the use of WHR, patient risk classification is greatly improved, providing a practical tool to make the most of screening resources in the face of rising CRC incidence rates. Finally, multi-ethnic validation is necessary for the WHR-based scoring model to be considered for integration into global CRC preventive frameworks, since it improves the accuracy of ACN risk prediction.

Background: Enhanced recovery after surgery (ERAS) programs provide recommendations for an optimized management of patients undergoing surgery. An ERAS program tailored on surgery for retroperitoneal sarcomas (RPS) may improve patient outcomes and it has still not been established.

Aim: To determine how an ERAS program tailored to RPS surgery can be agreed upon, structured, and implemented.

Methods: Twenty-five candidate items from existing ERAS programs, potentially relevant for RPS surgery, were identified via literature review and expert input. These were included in a questionnaire refined through cognitive interviews and pilot testing. Expert sarcoma surgeons rated each item's relevance and feasibility on a 6-point scale. The survey was recirculated after one year. Intra-observer reproducibility, inter-observer concordance, and agreement with the modal value of the most experienced participants were analyzed.

Results: Thirteen sarcoma surgeons from 6 centers participated in the survey. Although surgeons agreed on several items, their overall concordance was low. After recirculating the survey, the intra-observer reproducibility was low. Interestingly, the median concordance with the reference increased for relevance and decreased for feasibility.

Conclusion: Despite interest in ERAS for RPS, surgeon concordance on item relevance and feasibility remains low, underscoring the need for collaborative efforts toward a standardized, consensus-based protocol.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, primarily due to tumor metastasis. A recent study in the World Journal of Gastrointestinal Oncology identifies charged multivesicular body protein 7 (CHMP7) as a key prognostic factor in CRC. The study showed that CHMP7 expression is significantly lower in patients with CRC with metastasis and in highly metastatic cell lines, correlating with clinical factors like normal tissue, metastatic tumors, pathologic stage, and lymphatic invasion. Higher CHMP7 expression was linked to improved overall survival, highlighting its potential as a predictive biomarker. Gene Set Enrichment Analysis also suggests the role of CHMP7 in metastasis-related pathways, paving the way for further mechanistic studies. This finding challenges current CRC management strategies and calls for larger, prospective studies to validate the role of CHMP7. As a potential target for novel diagnostics and therapies, CHMP7 could advance personalized medicine in CRC, bridging molecular insights with clinical outcomes to improve patient prognosis.

Background: Non-small cell lung cancer (NSCLC) is frequently characterized by poor response to cisplatin (DDP)-based chemotherapy, with increasing evidence suggesting that inflammatory cytokines in the tumor microenvironment contribute to chemoresistance.

Aim: To investigate the role of inflammatory cytokines in DDP resistance and to effect of IL-6 inhibition on chemosensitivity in NSCLC.

Methods: Twenty NSCLC patients were grouped into DDP-sensitive or DDP-resistant cohorts based on their clinical response. Cytokine levels in tumor tissues and NSCLC cell lines, including DDP-resistant A549/DDP and SK-MES-1/DDP, were quantified using enzyme-linked immunosorbent assay. To verify the effects of interleukin (IL)-6 on DDP resistance, NSCLC and resistant cells were treated with IL-6 inhibitors tocilizumab (TCZ), followed by DDP treatment. Cell viability, apoptosis, migration and invasion were detected via cell counting kit-8, flow cytometry, scratch assay, and transwell, respectively.

Results: IL-6, IL-8, and tumor necrosis factor-α levels were significantly elevated in DDP-resistance tissues and cell models compared to sensitive controls (P < 0.05). TCZ treatment significantly reduced the half-maximal inhibitory concentration of DDP in resistant cells, induced apoptosis, and hindered migration and invasion (P < 0.05). IL-6 and IL-8 were identified as key cytokines associated with DDP resistance.

Conclusion: These findings demonstrated that IL-6 and related cytokines contribute to DDP resistance in NSCLC. IL-6 inhibition restores chemosensitivity and may serve as a promising therapeutic strategy in resistant NSCLC.

Pancreatic cancer (PC) remains a highly lethal malignancy worldwide. Increasing evidence indicates that inflammation is a critical factor in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC). Inflammatory cell infiltration within the PDAC tumor microenvironment promotes tumor growth and metastasis, while both local and systemic chronic inflammation is associated with an elevated risk of developing the disease. Given that the same immune cell populations are involved in mediating both inflammatory and immune responses, there exists a close interrelationship between inflammation and immunity in the context of PDAC. Various studies have reported the relationship between inflammation and PC. This review article provided a comprehensive summary of the roles of erythrocyte sedimentation rate, plasma viscosity, procalcitonin, calprotectin, haptoglobin, serum amyloid A, ferritin, and fibrinogen in the pathophysiological mechanisms underlying PC.

Gallbladder cancer (GBC) is a lethal biliary tract malignancy, which is infrequent in most developed countries, but common in many developing countries in specific geographical regions of the world. Non-specific symptoms leading to late diagnosis is one of the primary factors contributing to poor prognosis in GBC. An understanding of the complex relationship between molecular genetics and epidemiological variances in the incidence rates of GBC is thus of utmost importance. Present review summarizes recent updates on population-specific dysregulated genetic expressions in the genesis of GBC, highlighting the pattern of ethno-geographic variations and on advances in targeted therapies conducted till date; points out the lacunae that deserve further attention and suggest possible new directions for future clinical trials in GBC. The review calls for the need of genetic screening of each GBC patients and for more extensive clinical trials on targeted therapies to move towards the goal of personalized medicine, bringing about more favourable survival outcomes.

Colon cancer (CC) laterality (right vs left) is recognized as a key determinant of clinical outcomes and treatment decisions in metastatic CC. Right-sided CC (RCC) often presents in older individuals and is associated with higher rates of Kirsten rat sarcoma viral oncogene homolog and v-raf murine sarcoma viral oncogene homolog B1 mutations and deficient mismatch repair, leading to microsatellite instability-high status. Left-sided CC typically presents in younger individuals, demonstrates a more favorable prognosis, and is often Kirsten rat sarcoma viral oncogene homolog/neuroblastoma RAS viral oncogene homolog/v-raf murine sarcoma viral oncogene homolog B1 wild-type, making it more responsive to anti-epidermal growth factor receptor therapy. RCC typically responds poorly to anti-epidermal growth factor receptor agents; however, it may benefit from triplet chemotherapy (5-fluorouracil + leucovorin + oxaliplatin + irinotecan) with or without anti-angiogenic agents. Comprehensive molecular profiling remains challenging in low-resource settings due to limited access to advanced diagnostic tools. This review explores key epidemiological and molecular differences between RCC and left-sided CC. In the absence of complete genomic data, tumor sidedness can be a helpful guide for making treatment decisions. Here, we propose a practical algorithm that integrates basic immunohistochemistry to assess a tumor's mismatch repair status and laterality, potentially facilitating therapy selection in resource-constrained environments. Recognizing laterality-specific trends in prognosis and treatment response can improve personalized care and outcomes for patients with CC in these environments, highlighting the essential role of cost-effective biomarker strategies.