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.

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.

Cyclin-dependent kinases (CDK4/6) inhibitors play an important role in the management of metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. They act by inhibiting the proteins CDK4 and CDK6, which are implicated in the advancement of the cell cycle and unchecked cell proliferation- the primary causes of the development of cancer. The blocking of these proteins can slow or stop the growth of cancer cells. Palbociclib is a highly active substance in the management of hormone positive, her2neu negative metastatic breast cancer [1].

Methods: A retrospective study was conducted at King Fahad Hospital (Al Jaber Oncology Centre). Sixty-four metastatic, hormone-positive, HER2neu-negative breast cancer cases who received. Palbociclib were included in the study and followed up for a median time of 30 months.

Results: Our study indicated that 58 patients were treated with Palbociclib combined with  letrozole (90.6%), whereas 6 patients (9.4%) were treated with Palbociclib along with  fulvestrant. Neutropenia induced by Palbociclib occurred in 87.5% of cases, whereas  12.5% of cases did not experience neutropenia (8 cases). Regarding neutropenia, our  study showed that 32.1% of the participants experienced grade I neutropenia, while  58.9% had grades II, and 8.9% had grade III neutropenia. A dose reduction of  Palbociclib was implemented in 19 cases (29.7%) throughout the entire treatment  duration.  With the adjustment of the dose of Palbociclib, there was no statistically significant difference between the different doses. The 30-month PFS rate was 75% with the dose of 100 mg, 90.9% with 75 mg, and 97.2% with the dose of 125 mg. Median PFS was not reached. A total of 5 deaths were noted in the entire study group. There was no statistically significant difference in overall survival based on neutropenia grades.

Conclusion: Neutropenia induced by palbociclib and subsequent dose reduction did not impact the disease outcome.

Introduction: Non-Hodgkin lymphoma (NHL) represents a diverse spectrum of lymphoid malignancies, which are defined by abnormal proliferation of lymphocytes and the absence of Reed-Sternberg cells. Both genetic and epigenetic mechanisms play critical roles in the etiology of this group of cancers. In this context, the present study aimed to assess the potential relationship between three specific single nucleotide polymorphisms (SNPs) in the MALAT1 gene namely rs619586 A>G, rs664589 C>G, and rs3200401 C>T and their association with susceptibility to NHL in a population sample from Zahedan, Iran.

Materials and methods: A case-control study design was utilized, comprising 185 individuals diagnosed with NHL (118 men and 67 women; mean age: 45.46 ± 15.44 years) and an equal number of age- and sex-matched healthy controls (106 men and 79 women; mean age: 43.26 ± 12.27 years). Genomic DNA was isolated from peripheral blood leukocytes using the conventional salting-out method. Genotyping for the selected MALAT1 polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system PCR (ARMS-PCR) methodologies. Statistical evaluations were performed using chi-square tests, independent sample t-tests, and logistic regression models to analyze the data.

Results: The rs3200401 C>T polymorphism of the MALAT1 gene was significantly associated with a reduced risk of NHL, suggesting a protective effect (P<0.05). Similarly, the rs619586 A>G variant showed a significant protective association with NHL. In contrast, the rs664589 C>G polymorphism did not show any significant differences in genotype or allele frequencies between NHL patients and healthy subjects (P>0.05).

Conclusion: The findings suggest that MALAT1 gene polymorphisms, particularly rs3200401 and rs619586, as well as the TCG haplotype, may influence susceptibility to non-Hodgkin lymphoma and serve as potential genetic biomarkers. However, further studies involving larger and ethnically diverse cohorts are required to validate these associations.

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.