Asian Pacific Journal of Cancer Prevention最新文献

Objective: Hepatocellular carcinoma (HCC), the most common form of liver cancer, often develops in individuals with chronic liver diseases, especially cirrhosis. Cisplatin (Cisp), a chemotherapy agent commonly used in HCC treatment, is effective but is known to damage normal cells, including fibroblasts. Hesperetin (HST), a citrus flavanone found abundantly in citrus fruits, has demonstrated antioxidant, anti-inflammatory, and anticancer properties. This study aimed to investigate the synergistic cytotoxic effects and selective induction of senescence by HST in combination with Cisp in HepG2 cancer cells and NIH-3T3 fibroblast cells.

Methods: The cytotoxic effects of HST were assessed using the MTT assay to determine cell viability. The antiproliferative properties were evaluated using colony formation assays. Senescence was assessed using SA-β-gal staining, while flow cytometry was used to analyze cell cycle distribution and apoptosis. Protein expression related to proliferation and apoptosis was determined via Western blot analysis.

Results: MTT assay results indicated that both HST and Cisp reduced HepG2 cell viability in a dose-dependent manner, with IC₅₀ values of 258 ± 2.47 µM and 5 ± 1.83 µM, respectively. Their combination (HST: 33-130 µM; Cisp: 0.6-2.5 µM) showed synergistic effects (combination index, CI < 1) co-treatment with HST (65 and 130 µM) significantly enhanced senescence in HepG2 cells. Clonogenic assays showed inhibition of colony formation, supported by reduced expression of p-ERK1/2 and Cyclin D1. Flow cytometry revealed increased apoptosis and G2/M phase arrest, with upregulation of Bax and caspase-3, and downregulation of Bcl-xL. In NIH-3T3 cells, HST showed minimal cytotoxicity (IC50 > 500 µM), and co-treatment with Cisp reduced senescence markers.

Conclusion: These results suggest that HST and Cisp co-treatment synergistically reduces cancer cell viability while protecting normal fibroblasts from senescence, supporting its potential as a co-chemotherapeutic agent in HCC treatment, while also serving as a protective agent against senescence in healthy tissues.

Objective: TMEPAI (transmembrane prostate androgen-induced protein) is one of the proteins associated with the resistance of triple-negative breast cancer (TNBC) to various cytotoxic medicines. However, it has remained uncertain how TMEPAI mechanistically contributes to TNBC resistance to paclitaxel. Thus, this study aimed to investigate the effect and possible mechanism of TMEPAI gene editing via CRISPR-Cas9 on the response of triple-negative breast cancer cells to paclitaxel.

Methods: The present study was conducted on wild-type triple-negative breast cancer cells (BT-549) and BT-549 cells with TMEPAI knocked out using CRISPR-Cas9. Both cell types underwent treatment with TGF-β, followed by paclitaxel, and were evaluated for cell viability and the expression of cell proliferation, apoptosis, drug efflux transporters, and epithelial-mesenchymal transition markers.

Result: TMEPAI knock-out cells exhibited a markedly increased susceptibility to paclitaxel, as characterized by decreased viability and elevated expression of pro-apoptotic genes (Bax, caspase-3, caspase-9), as well as a reduction in anti-apoptotic markers (Bcl-2). The presence of TMEPAI perpetuated the phosphorylation of AKT (pAKT/AKT), elevated the expression of drug efflux transporters (particularly P-glycoprotein and MRP-1), and facilitated epithelial-mesenchymal transition (EMT), as evidenced by increased levels of Snail, Zeb1, and Twist. All these effects were diminished in TMEPAI-knock-out triple-negative breast cancer cells.

Conclusion: TMEPAI appears to facilitate paclitaxel resistance in triple-negative breast cancer cells by promoting cell survival signaling, inhibiting apoptosis, enhancing drug efflux, and initiating epithelial-mesenchymal transition (EMT). Targeting TMEPAI may be a viable approach to overcoming resistance and improving treatment outcomes in triple-negative breast cancer cells.

Objective: The aim of our study is to compare CD4+ & CD8+ T lymphocytes in the cervical tumor tissue with those in peripheral blood in patients with carcinoma cervix and to access thier association with known prognostic factors. The study also aims to investigate the association between tumor infiltrating lymphocytes (TILs) and the HPV status of the patients.

Methods: In this prospective study, 42 patients with locally advanced squamous cell carcinoma of cervix were included. Percentages of CD4+ and CD8+ T lymphocytes were obtained using flow cytometry-based method from single-cell suspension prepared from simultaneously collected tumor tissue and peripheral blood samples. DNA extracted from tumor tissue was analysed to detect HPV16 (Human Papillomavirus 16) and HPV18 infection. T lymphocyte subsets in blood and tumor tissue were compared. The association of T lymphocytes with known prognostic factors and HPV status of the tumor was examined.

Result: Both CD4+ and CD8+ T cells were significantly higher in peripheral blood compared to tumor tissue (p < 0.001). The CD4/CD8 ratio was reversed in tumor tissue compared to peripheral blood due to relatively lower reduction of CD8+ cells compared to CD4+ cells in tumor tissue. No significant association of T lymphocyte subpopulation was found with known prognostic parameters of cervical cancer. CD4+ and CD8+ T lymphocyte infiltration was significantly higher in tumor with HPV16 infection (p < 0.05). A significant alteration of CD4/CD8 ratio was observed for HPV18 positive tumors (p < 0.05).

Conclusion: Our study demonstrates that both CD4+ and CD8+ T lymphocyte, which are major component of TILs, are significantly lower in tumor tissue compared to peripheral blood in locally advanced cervical cancer. No association was observed between T lymphocyte subpopulations and major prognostic factors of cervical cancer. The enhanced TILs observed in HPV-associated cervical cancer represents a significant alteration with promising therapeutic applications.

Objective: The aim of this study was to examine melatonin as a potential adjunct therapy for managing treatment-related symptoms in prostate cancer patients, particularly those undergoing androgen deprivation therapy (ADT).

Methods: In light of the increasing incidence of prostate cancer among younger males, this randomized, double-blind, placebo-controlled clinical trial was conducted at the Hematology-Oncology Center of Omid Hospital in Isfahan, Iran, between October 2019 and October 2020. Forty-one prostate cancer patients experiencing hot flashes or sexual dysfunction due to ADT were randomly assigned to receive either melatonin (3 mg twice daily) or a placebo for four weeks. Symptom assessment was performed using the Hot Flash Diary, the International Index of Erectile Function (IIEF), and the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.

Result: The results showed a statistically significant improvement in FACT-P scores within the melatonin group (P < 0.05), while erectile function scores increased modestly in both groups without reaching statistical significance (P > 0.05). The most pronounced effect was observed in the reduction of the frequency of mild hot flashes in the melatonin group, with significant improvements noted by week four (P < 0.05). Melatonin was well tolerated, with no clinically significant adverse events reported. These findings suggest that melatonin may effectively alleviate vasomotor symptoms and enhance the quality of life in prostate cancer patients undergoing ADT. However, its impact on sexual function remains inconclusive.

Conclusion: Further large-scale, long-term studies incorporating mechanistic endpoints are needed to validate these findings and inform clinical guidelines for melatonin use in supportive prostate cancer care.

Objective: There is an urgent need to investigate the molecular mechanisms underlying the invasion and metastasis of bladder cancer to develop more effective therapeutic strategies and thereby reduce tumor-related morbidity and mortality. This study aimed to evaluate the prognostic significance of ZEB1 expression in bladder carcinoma (BC) and its association with tumor-associated macrophages (TAMs) within the tumor microenvironment (TME).

Methods: A retrospective analysis was conducted on 48 patients with muscle-invasive bladder carcinoma (MIBC) who underwent radical cystectomy. Immunohistochemical staining for ZEB1 and CD163 was performed, followed by statistical analysis to assess their association with various clinicopathological parameters, including survival outcomes.

Results: High ZEB1 expression was significantly correlated with lymphovascular invasion, tumor necrosis, advanced disease stage, and nodal metastasis. Furthermore, elevated ZEB1 expression was associated with significantly worse 3-year overall survival (OS) and disease-free survival (DFS). Similarly, a high density of CD163+TAMs within TME was associated with adverse clinicopathological parameters and poor survival outcomes. Notably, a strong positive correlation was observed between ZEB1 expression and the density of CD163+ TAMs within the TME of BC. Multivariate analysis identified ZEB1 expression as an independent predictor of recurrence and nodal metastasis.

Conclusion: Elevated ZEB1 expression is strongly associated with poor prognosis in BC and closely correlated with an increased density of CD163+TAMs, further contributing to adverse outcomes. These findings highlight the potential of ZEB1 as a prognostic biomarker and underscore the therapeutic relevance of targeting TAMs in the management of BC.

Background: Early bony invasion in oral squamous cell carcinoma (OSCC) often remains undetected by conventional CT imaging. Bone turnover markers like N-telopeptide (NTx) and C-telopeptide (CTx) may serve as sensitive biomarkers for subclinical bone involvement.

Objective: To evaluate the potential of serum NTx and CTx levels as diagnostic markers for early bony invasion in OSCC patients whose CT scans showed no radiological evidence of bone involvement.

Methods: A prospective observational study was conducted on 50 OSCC patients with negative CT reports for bone invasion. Serum NTx and CTx levels were measured using ELISA. Based on biomarker levels, patients were categorized into two groups: Group A (elevated NTx and/or CTx) and Group B (normal levels). Statistical comparisons, ROC curve analysis, and logistic regression were employed to assess the diagnostic potential of these biomarkers.

Results: Group A (n = 25) showed significantly elevated levels of serum NTx (mean ± SD: 20.4 ± 4.1 nM BCE) and CTx (860 ± 130 ng/L) compared to Group B (NTx: 11.5 ± 2.9 nM BCE; CTx: 540 ± 110 ng/L), with p < 0.001. ROC analysis (receiver operating characteristic) revealed AUCs ( area under the curve) of 0.902 for NTx and 0.928 for CTx, suggesting excellent diagnostic accuracy. Logistic regression confirmed serum NTx and CTx as independent predictors of probable microinvasion. A subgroup analysis based on tumor histopathology revealed NTx to be more sensitive in moderately differentiated tumors, while CTx was more sensitive in poorly differentiated tumors.

Conclusion: Elevated serum levels of NTx and CTx in OSCC patients with negative CT scans may indicate early bony microinvasion. Incorporating biomarker screening into diagnostic protocols could enhance treatment planning and reduce recurrence.

Objective: Lung cancer is among the most lethal cancers worldwide and ranks as the third leading cause of cancer-related deaths in Uzbekistan. Despite its growing burden, public knowledge and participation in early screening remain poorly understood in the region. This study aimed to assess general awareness, attitudes, and practices related to lung cancer and its screening among the adult population of Uzbekistan.

Methods: A cross-sectional survey was conducted between January 25 and February 3, 2025, involving 561 participants from all 14 regions of Uzbekistan. A structured, validated questionnaire was used to assess socio-demographic data, lung cancer knowledge, risk perception, and willingness to participate in screening. Descriptive statistics, chi-square tests, t-tests, ANOVA, and multivariable analysis, such as linear regression and logistic regression were employed to examine associations between knowledge scores and demographic variables. Knowledge was categorized as poor, moderate, or good.

Results: Only 4% of participants demonstrated good knowledge, while 79% had poor knowledge about lung cancer and its early detection. Although 73.2% recognized smoking as a major risk factor, only 37.4% were aware of early screening methods such as low-dose computed tomography (LDCT). Higher knowledge scores were significantly associated with older age, higher education, income, and urban residence (p < 0.05). Gender and smoking status were not significantly correlated with knowledge levels.

Conclusions: This nationally representative study reveals substantial gaps in public awareness of lung cancer and its screening in Uzbekistan. Targeted public health interventions focusing on youth, rural populations, and individuals with lower educational backgrounds are urgently needed. Expanding educational outreach and increasing access to early detection services may significantly improve outcomes and reduce mortality in high-risk populations.

Background: Globally, Oral Cancer alone is responsible for more than 6 million deaths each year, with nearly 10 million new cases diagnosed annually. India alone accounts for one-third of the world's oral cancer cases. India is considered as the oral cancer capital of the world, with an estimated 1% of the population having oral premalignant lesions.  Early detection of oral precancerous lesions is practically possible and associated with a high expectation of the prevention of deformity, relapse, and mortality. The present study aims to estimate the magnitude of oral precancerous lesions and conditions among the rural population of Karnataka, India.

Methods: A community-based analytical cross-sectional study was conducted among the 6010 rural population of Belgaum. Participants were recruited through stratified cluster random sampling and were screened for oral precancerous lesions and conditions through visual examination and toluidine blue application. The data on socio-demographic variables, tobacco consumption, medical & dental history was collected and analyzed using IBM SPSS version 22. Logistic regression and Chi-square test were used to analyze inferential data at 95% confidence interval. Descriptive data were analyzed using percentage and proportion.

Results: The majority of participants were females (53.9%), and the mean age was 40 years. The prevalence of precancerous lesions and conditions was 16.38%. Among them, 4.5% had tobacco pouch keratosis, and 4.4% Oral Sub Mucous Fibrosis (OSMF). Age was associated with all types of lesions and conditions and similarly, cigarette and bidi smoking are associated with smoker's palate.  4.2% leukoplakia and smoker's palate were found in 1.6%. A high prevalence of Smokeless tobacco consumption was found, and among them, gutkha was most commonly used. These lesions were associated with age, education, tobacco, type of diet and sharp cusps.

Conclusion: The overall prevalence of precancerous lesions and conditions was high. It was high among the elderly, except for OSMF which was more prevalent among the younger age group.