Asian Pacific Journal of Cancer Prevention最新文献

Background: Locally advanced breast cancer (LABC) requires a multimodal approach, often starting with neoadjuvant chemotherapy (NACT) to reduce tumor size. However, response to NACT in LABC is highly variable. Predictive biomarkers such as HER-2 and Survivin may have the potential to predict treatment response and prognosis. This study aims to analyze the relationship between Survivin and HER-2 expression and the clinical response to NACT in LABC patients.

Methods: In this prospective cohort study, we enrolled 56 female LABC patients scheduled for a Taxane, Adriamycin, and Cyclophosphamide NACT regimen. Pre-treatment biopsy tissues were examined for Survivin and HER-2 expression via immunohistochemistry. Clinical response was evaluated after three cycles using the RECIST criteria. Data were analyzed using the Chi-Square test and multivariate logistic regression.

Results: High Survivin expression was found in 32/56 (57.1%) participants and positive HER-2 expression in 28/56 (50%). A significant correlation was found between high Survivin expression and HER-2 positivity (p=0.007). High Survivin expression (p<0.001; PR=4.688; 95% CI: 1.881-11.682) and HER-2 positivity (p<0.001; PR=5.585; 95% CI: 2.227-14.012) were significantly associated with poor chemotherapy response (non-response). Multivariate analysis showed that Survivin (OR=0.032; p=0.002) and HER-2 (OR=0.022; p=0.001) were significant independent predictors of chemotherapy response.

Conclusion: Survivin and HER-2 expression are significantly associated and serve as independent predictors of poor response to NACT in LABC patients. Evaluation of these biomarkers could be crucial in risk stratification and the personalization of therapy.

Background: Clausenidin is a pyranocoumarin that was isolated from the roots of Clausena excavata Burm. Previously, the pure clausenidin crystals were successfully used to treat HepG2 cells (liver cancer) in vitro; however, no in vivo study had been conducted to support these findings. Therefore, the current study was designed to investigate the in vivo anti-liver cancer effect of pure clausenidin in hepatocellular carcinoma-induced BALB/c mice.

Method: DNA fragmentation, caspases, and histological assays were conducted to evaluate the cytotoxic effect of the pure clausenidin, while real-time qPCR was performed to monitor the expression of apoptosis-inducing genes in the clausenidin-treated mice.

Result: Clausenidin significantly (p<0.05) decreased the liver damage-induced levels of alanine and aspartate aminotransferases and also caused fragmentation of the genomic DNA of the tumors. This was followed by a significant increase (p<0.05) in the expression of caspases 3, 8 and 9 proteins in the clausenidin-treated mice. In addition, clausenidin upregulated the expression of  pro-apoptotic genes associated with the extrinsic and intrinsic pathways. However, it was observed that clausenidin may have inhibited angiogenesis by downregulating the expression of the VEGF gene in the treated mice.

Conclusion: Therefore, clausenidin can be potentially used as an anti-liver cancer agent.

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide, with limited genetic data available on Middle Eastern populations. This study investigated four novel genetic variants CYPHER rs7834621, METOX1 rs9284659, DRUGRES2 rs4521739, and TOXMET3 rs8823471 for their association with lung cancer risk and treatment response in Iraqi patients.

Methods: Between January 2024 and September 2024, we recruited 265 tissue-confirmed lung cancer patients and 310 healthy controls from Al-Diwaniyah Teaching Hospital. DNA was extracted from blood samples and genotyped using tetra-ARMS-PCR. Logistic regression was used to analyze variant-cancer risk associations. Pharmacogenetic analysis included 198 patients receiving trastuzumab, doxorubicin, paclitaxel, and cyclophosphamide chemotherapy, with response measured by RECIST criteria.

Results: All four genetic variants showed significant associations with lung cancer risk. The CYPHER rs7834621 GG genotype was associated with the highest disease risk (adjusted OR = 2.21, 95% CI: 1.31-3.73, p = 0.003). Allele frequencies were population-specific when compared to other cohorts. Pharmacogenetic analysis revealed treatment response associations, with DRUGRES2 rs4521739 TT genotype demonstrating superior response rates compared to CC genotype (68.4% vs 31.6%, p < 0.001). Haplotype analysis identified specific gene combinations that increased disease susceptibility.

Conclusions: These novel SNPs are associated with both lung cancer risk and treatment response in Iraqi patients, potentially serving as biomarkers for risk stratification and personalized therapy guidance in this population.

Background: Colorectal cancer (CRC) is a growing global health concern. This study focuses on evaluating the gene expression of FGF2, CARMA3, and MicroRNA205 (miR205) as potential blood-based biomarkers for early CRC diagnosis by distinguishing patients from healthy controls.

Materials and methods: Blood samples from 80 colorectal cancer (CRC) patients and 40 healthy controls were analyzed using qRT- PCR to measure target gene expression. ROC curve analysis was performed to evaluate diagnostic accuracy, including sensitivity, specificity, and Area Under the Curve (AUC) values.

Results: MicroRNA-205 revealed downregulation in CRC patients, with an AUC of 0.7, sensitivity of 91%, and specificity of 58%. AUC values for Fibroblast Growth Factor 2 (FGF2) and Caspase Recruitment Domain Family Member 3 (CARMA3) were 0.74 and 0.77, respectively, indicating differential expression. All markers displayed modest specificity, but CARMA3 showed the highest diagnostic accuracy with 95% sensitivity. Gene expression fold change for miR-205 showed downregulation 0.3, FGF2 also showed downregulation 0.4 and CARMA3 showed slight upregulation 1.2.

Conclusion: The results suggest that miR-205, FGF2, and CARMA3 may serve as potential biomarkers for the identification of colorectal cancer (CRC), particularly when used in multi-marker panels to improve diagnostic accuracy. Their clinical utility should be confirmed through additional validation in larger cohorts.

Objective: Chronic myeloid leukemia (CML) is characterized by the translocation of chromosomes 9 and 22, resulting in the BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) have markedly improved CML outcomes. Yet, resistance may develop due to mutations in the BCR-ABL kinase domain, particularly in the ATP-binding loop (P-loop), activation loop (A-loop), catalytic domain, and direct binding site. This study aimed to evaluate the relationship between BCR-ABL kinase domain mutations, hematological response, and overall survival among CML patients receiving TKI therapy at Wahidin Sudirohusodo General Hospital, Makassar.

Methods: A prospective cohort study was conducted from March 2022 to July 2023 at the Hematology-Oncology outpatient clinic. Among 312 patients, 22 were classified as non-responders (no hematological response within three months) and 290 as responders. Forty-four patients (22 responders and 22 non-responders) underwent mutation analysis, and survival outcomes were compared. Statistical analysis was performed using SPSS.

Results: Of the 44 patients, 11 harbored BCR-ABL mutations: S348L (n=6), T315I (n=4), and Y253F (n=1). All mutations were identified exclusively in the non-responder group. Mortality was significantly higher in non-responders than responders (p<0.05), and among non-responders with mutations compared to those without (p<0.01). Six-month survival rates were 65% for S348L, 50% for T315I, and 0% for Y253F, though survival differences between mutation types were not statistically significant (p=0,641).

Conclusion: CML patients achieving early hematological response to TKI therapy had significantly better survival outcomes. In contrast, non-responders, particularly those harboring BCR-ABL kinase domain mutations, demonstrated poorer survival. The S348L mutation was the most common variant in this cohort. Early mutation detection may help guide therapeutic adjustments and improve outcomes in TKI-resistant CML.

Objective: SALL4 (Spalt-like transcription factor 4) is a stem cell transcription factor that is reactivated in various tumor tissues and has a proven pro-metastatic role in colorectal cancer (CRC). However, the mechanism of its reactivation in CRC remains elusive. fascin is an actin-bundling protein linked to CRC progression. Independent of this activity, fascin regulates stemness and embryonic stem cell-related genes in some cancers. Data on the role of fascin in regulating stem cell transcription factors in CRC are scarce, and the relationship between fascin and SALL4 expression in CRC has not been investigated. This study aims to evaluate the immunohistochemical expression of SALL4 and fascin in fifty-four CRC cases and their relationship with clinicopathological parameters.

Methods: The expression of SALL4 and Fascin determined using immunohistochemistry in 54 paraffin-embedded colectomy specimens from patients with primary colorectal adenocarcinoma.

Result: SALL4-positive expression was detected in 9 cases (16.7%), while moderate-to-high fascin expression was found in 21 cases (38.9%). A significant positive relationship was identified between SALL4 expression and lymphovascular invasion (LVI) (P = 0.033). Moderate-to-high fascin expression was significantly associated with advanced pathological tumor (pT) stage (P = 0.023), lymph node (LN) spread (P = 0.031), and LVI (P = 0.010). Furthermore, a significant association was observed between SALL4 positivity and moderate-to-high fascin expression (P = 0.009).

Conclusion: This is the first study to demonstrate a significant association between SALL4 and fascin expression in CRC patients, suggesting a potential interplay between them. Both proteins may represent potential markers of CRC progression. Molecular studies are required to further investigate the interaction between SALL4 and fascin in CRC.

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.

Background: Human papillomavirus (HPV) is the most prevalent sexually transmitted infection globally and is causally related to anogenital and oral cancers, with 311,000 associated deaths recorded in men and women every year. The presence of oncogenic HPV genotypes in anogenital warts is reported by few studies, while many groups have reported an associated higher risk of anogenital and other cancers in patients with anogenital warts. This study aimed to detect HPV16 and HPV18 DNA and mRNA markers in anogenital warts to assess infection and viral persistence.

Method: A cross-sectional study design was adopted to enroll 50 consenting men and women presenting with anogenital warts at the dermatology clinics of two existing referral hospitals in Sikkim. Samples were processed for DNA and RNA extraction, cDNA conversion, followed by qPCR-based amplification for HPV16 and HPV18 E6/E7 DNA and mRNA.

Result: High presence of E6/E7 genes of HPV16 and HPV18 with DNA and mRNA was observed in the exfoliated anogenital warts tissue samples, evaluated using quantitative PCR (qPCR). HPV16E6 and HPV18E6 DNA was present in 75.5% (37/49) and 26.6% (13/49) of the samples, while HPV16E6 and HPV18E6 mRNA was present in 62.0% (31/50) and 52.0% (26/50) of the samples, respectively, 18.0% (9/50) of the samples tested positive for HPV16E7 mRNA, while none were positive for HPV18E7 mRNA.

Conclusion: High prevalence of HPV16 and HPV18 seen in males and females with Anogenital warts in the present study re-emphasizes the significance of including men in HPV screening and vaccination programs, and importance of testing oncogenic HPV genotypes in anogenital warts to improve the overall reduction of clinical manifestations associated with HPV.

Background: The potential link between ambient air pollution and brain tumor incidence remains poorly understood, despite growing concern about environmental exposures and neurological health. While air pollutants are established carcinogens for several cancer types, their role in central nervous system (CNS) tumorigenesis has not been definitively established.

Aim: This study aims to systematically evaluate and quantitatively synthesize the epidemiological evidence on the association between long-term exposure to ambient air pollution and the risk of brain tumors, including gliomas and meningiomas.

Methods: A comprehensive literature search was conducted across PubMed, Embase, Scopus, Web of Science, and ProQuest (up to October 1, 2024), identifying observational studies assessing associations between air pollution and brain tumor incidence. Eligible studies were screened, data were extracted, and study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analyses were performed to estimate pooled relative risks (RR) for specific pollutants (PM2.5, NOx, NO2), and traffic proximity. Subgroup analyses and publication bias assessments were also conducted.

Results: Eight studies met inclusion criteria, with five contributing to the meta-analysis. Pooled estimates indicated an association between long-term exposure to NO2 and brain tumors (RR = 1.06; 95% CI: 1.01-1.11). PM2.5 exposure showed a higher but more variable association (RR = 1.63; 95% CI: 1.04-2.55), while NOx (RR = 1.16; 95% CI: 0.93-1.45) and traffic proximity (RR = 1.07; 95% CI: 0.99-1.16) demonstrated weaker or borderline associations. Subgroup analyses suggested slightly stronger associations for meningioma than glioma. Significant heterogeneity was observed across studies, but no clear evidence of publication bias was detected.

Conclusions: This systematic review and meta-analysis provides suggestive evidence that long-term exposure to traffic-related air pollutants may be associated with a modestly increased risk of brain tumors. While results are not conclusive, the widespread exposure to these pollutants and the observed trends underscore the importance of further research using refined exposure assessments and tumor subtype-specific analyses.