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Asian Pacific Journal Of Cancer Prevention[JOURNAL]

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Synergistic Deep Learning Fusion for Precision Lung Cancer Staging.

P S, Albert AJ, M M … +2 more , G G, S R

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345183 · Publisher ↗

OBJECTIVE: To develop and evaluate an automated deep learning-based lung cancer staging system using computed tomography (CT) scan images. METHODS: CT scan images were obtained from publicly available datasets (LIDC-IDRI... OBJECTIVE: To develop and evaluate an automated deep learning-based lung cancer staging system using computed tomography (CT) scan images. METHODS: CT scan images were obtained from publicly available datasets (LIDC-IDRI/TCIA) comprising 1,018 patient scans. The dataset consisted of three subsets, which were: training (70 percent of total), validation (15 percent), and testing (15 percent). Lung region segmentation, anisotropic filtering, and data augmentation were used as preprocessing. To classify lung cancer stages, a customized CNN network based on multi-scale feature extraction and softmax-enabled probabilistic output was trained. Statistical confidence intervals, F1-score, ROC-AUC, recall, accuracy, and precision were used to test the performance of the model. RESULTS: Using an area under the curve (AUC) of 0.98 (Stage I), 0.96 (Stage II), 0.95 (Stage III) and 0.97 (Stage IV) the proposed model indicates a total classification of 93.0 (95% CI: 91.2-94.8). Statistical analysis revealed a significant improvement compared to baseline CNN models (p < 0.05). Compared with state-of-the-art techniques, quantitative comparisons showed either equivalent performance or slightly higher performance, particularly in separating between early-stage (I-II) and advanced-stage (III-IV) disease. CONCLUSION: The findings demonstrate that the suggested CNN-based architecture can effectively and precisely classify the stage of lung cancer based on CT images, which assists in automated clinical decision-making and enhances the early detection process.

Genomic Landscape of Oral Squamous Cell Carcinoma in Never Smokers and Never Drinkers.

George S, Anantharaman D

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345182 · Publisher ↗

OBJECTIVE: To identify the mutational landscape of oral cancers of unknown etiology by leveraging publicly available datasets. METHODS: Oral cancer mutation data in TCGA were accessed to identify never-smoking and never-... OBJECTIVE: To identify the mutational landscape of oral cancers of unknown etiology by leveraging publicly available datasets. METHODS: Oral cancer mutation data in TCGA were accessed to identify never-smoking and never-alcohol-drinking subjects with genomic, epigenomic, and transcriptomic data. Habit-free participants within published individual whole-exome sequencing studies of oral cancer were examined as the replication dataset. RESULTS: Somatic mutation analysis of 42 habit-free TCGA oral cancer subjects revealed MUC16 and MUC5B as recurrent mutational targets in 30% of all habit-free oral cancers; the highest after previously reported oral cancer genes such as TP53, CASP8, CDKN2A, NOTCH1. Comparison against other habit-free oral cancers not only confirmed these observations but also identified additional mucin genes as frequent mutational targets, supporting their potential causal role. Gene expression and immune fraction analysis of bulk transcriptomic data showed that habit-free oral cancers were enriched for the expression of mesenchymal genes and in T-regulatory cells. CONCLUSION: Together, these data suggest that mucin genes, specifically MUC16 and MUC5B, are important for oral carcinogenesis in the absence of tobacco and alcohol. These results are relevant given the increasing clinical utility of mucins as druggable targets in cancer, particularly MUC16.

Gut Microbiota Modulation via Synbiotics: A Perspective for Boosting Antitumor Immunity and Inactivating Carcinogens in Early Life.

Lutfiana NC, Purnomo AS, Purnomo ASN … +1 more , Purnomo AF

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345181 · Publisher ↗

OBJECTIVE: Children are highly susceptible to infections and long-term health risks due to their immature immune systems, which typically develop fully around the age of 12. While early infections generate T and B memory... OBJECTIVE: Children are highly susceptible to infections and long-term health risks due to their immature immune systems, which typically develop fully around the age of 12. While early infections generate T and B memory cells, establishing a robust immune foundation is crucial not only for combating pathogens but also for preventing carcinogenesis in later life. Synbiotics, a synergistic combination of probiotics and prebiotics, offer a promising strategy to modulate the gastrointestinal microenvironment. METHOD: This article proposes that synbiotic supplementation provides dual benefits: enhancing immediate immunity and offering potential chemopreventive effects. RESULT: Mechanistically, synbiotics maintain microbial balance (increasing Lactobacillus and Bifidobacterium), which leads to (1) increased production of artificial endogenous immunoglobulins [Ma1.1][Ma1.2]like IgG to neutralize toxins and pathogens; (2) inactivation of cancer-causing chemicals and reduction of unwanted metabolite concentrations; and (3) enhancement of Natural Killer (NK) cell activity and antioxidant capacity, which are vital for tumor surveillance and reducing oxidative stress. By modulating the gut microbiota, synbiotics not only boost IgG levels to prevent common infections but also strengthen the body's defense against mutagenic agents. CONCLUSION: This opinion article summarizes clinical and preclinical findings to highlight the efficacy of synbiotics as a comprehensive immune booster and a potential agent for early cancer prevention strategies.

Temporal Hematologic Alterations in Women Receiving Pharmacotherapy for Breast Cancer: A Prospective Analysis.

Sutanto H, Savitri M, Ashariati A … +5 more , Hendarsih E, Romadhon PZ, Diansyah MN, Amrita PNA, Bintoro SUY

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345180 · Publisher ↗

BACKGROUND: Breast cancer pharmacotherapy commonly results in hematologic toxicity and systemic inflammatory shifts that may compromise treatment tolerance. This study evaluated baseline hematologic characteristics and e... BACKGROUND: Breast cancer pharmacotherapy commonly results in hematologic toxicity and systemic inflammatory shifts that may compromise treatment tolerance. This study evaluated baseline hematologic characteristics and early hematologic changes following pharmacotherapy among patients treated in second-referral centers in Indonesia. METHODS: This prospective cohort study enrolled 106 women with confirmed breast cancer between January and October 2025. Hematologic evaluations were performed before treatment and at Weeks 1 and 3. Assessed parameters included hemoglobin, leukocyte and platelet counts, differential counts, the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and the pan-immune-inflammation value (PIV). Friedman's two-way analysis of variance by ranks was used for pre-post comparisons. Subgroup comparisons between survivors and non-survivors used Mann-Whitney U tests. RESULTS: The mean age was 51.9 ± 9.7 years, with most patients presenting with locally advanced disease (58.5%) and invasive ductal carcinoma (84%). Baseline hemoglobin averaged 11.9 g/dL and leukocyte count 7.5 × 10³/µL. Marked hematologic suppression occurred after therapy: leukocyte and absolute neutrophil counts declined significantly at week 1 with partial recovery by week 3 (p <0.001). Inflammatory indices showed substantial fluctuations, with significant changes in PLR, MLR, and PIV (all p <0.001). Anemia increased from 51.9% at baseline to 74.0% post-therapy. Neutropenia occurred in 1.9% at baseline, 41.7% at week 1, and 1.1% at week 3. Among survival subgroups, only MLR differed significantly (p = 0.043). CONCLUSION: The mean age was 51.9 ± 9.7 years, with most patients presenting with locally advanced disease (58.5%) and invasive ductal carcinoma (84%). Baseline hemoglobin averaged 11.9 g/dL and leukocyte count 7.5 × 10³/µL. Marked hematologic suppression occurred after therapy: leukocyte and absolute neutrophil counts declined significantly at week 1 with partial recovery by week 3 (p <0.001). Inflammatory indices showed substantial fluctuations, with significant changes in PLR, MLR, and PIV (all p <0.001). Anemia increased from 51.9% at baseline to 74.0% post-therapy. Neutropenia occurred in 1.9% at baseline, 41.7% at week 1, and 1.1% at week 3. Among survival subgroups, only MLR differed significantly (p = 0.043).

Upstaging of Operable Adenocarcinoma of the Stomach and Gastroesophageal Junction Following Staging Laparoscopy (SL): High-Risk Clinicopathological Features Requisite for Mandatory SL.

Mathad AS, Patil R, Goyal D … +6 more , Usman N, S Shetty P, K P, Ishwar Hegde A, Palod A, An Kumar N

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345179 · Publisher ↗

BACKGROUND: Accurate staging is paramount in optimizing outcomes for patients with operable adenocarcinoma of the stomach and gastroesophageal junction (GEJ). Cross-sectional imaging frequently underestimates the true ex... BACKGROUND: Accurate staging is paramount in optimizing outcomes for patients with operable adenocarcinoma of the stomach and gastroesophageal junction (GEJ). Cross-sectional imaging frequently underestimates the true extent of disease, particularly occult peritoneal metastases. Adding Staging laparoscopy (SL) enhances diagnostic precision, but its universal application remains debated. Identifying clinicopathological predictors of upstaging may enable the selective yet mandatory use of SL in high-risk subgroups. METHODS: In this single-centre retrospective study, we analysed 182 patients with clinically operable adenocarcinoma of the stomach and GEJ who underwent SL as part of their staging work-up between June 2018 and December 2024. Clinical, radiological, and pathological variables were assessed to determine their association with upstaging. The primary endpoint was the detection of unsuspected metastatic disease or positive peritoneal cytology on SL. The secondary endpoint was to identify independent predictors of upstaging using multivariate logistic regression. RESULTS: Of 182 patients evaluated, 37 patients (20.3%) were upstaged on SL, precluding curative-intent surgery. The most common route of upstaging was detection of peritoneal metastases 33(18.1%) and the rest of the patient had isolated positive cytology 4 (2.2%). High-risk features significantly associated with upstaging included minimal ascites (OR 5.87, p<0.001), signet ring cell histology (OR 4.15, p=0.007), linitis plastica morphology (OR 3.42, p=0.002), and tumor thickness ≥15 mm (OR 2.21, p=0.034). Notably, radiologically node-negative patients with none of the high-risk features had a low probability of upstaging. A risk-stratified algorithm based on these parameters improved the diagnostic yield of SL and reduced non-therapeutic laparotomies. CONCLUSION: Universal incorporation of staging laparoscopy into treatment algorithms for operable gastric and GEJ adenocarcinoma is challenging in many settings due to resource and economic constraints. While established guidelines endorse SL in selected scenarios, our findings suggest that, in addition to these proven indications, the consideration of SL in patients with linitis plastica morphology, tumour thickness >15 mm, signet ring cell carcinoma histology, and even mild ascites can further refine the staging accuracy. Targeting these high-risk subgroups enables a more personalised treatment approach, maximises the detection of occult metastases, and, importantly, reduces the incidence of non-therapeutic laparotomies.

Gene Expression Alterations of TIMP3, ELASTIN, K-RAS, and BRAF in Colorectal Cancer Patients with H. pylori Infection.

Zeadan AM, Mousaa T, Abdullah AR

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345178 · Publisher ↗

OBJECTIVE: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related mortality worldwide, with over 1.9 million new cases and 0.9 million deaths reported in 2020. The role... OBJECTIVE: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related mortality worldwide, with over 1.9 million new cases and 0.9 million deaths reported in 2020. The role of Helicobacter pylori infection in CRC pathogenesis remains a significant area of research. This study aimed to investigate the association between H. pylori infection, and genetic alterations in CRC patients. METHODS: A total of 110 blood and tissue biopsy samples were collected from CRC patients at Ghazi AL-Hariri Specialized Surgery Hospital in Baghdad, Iraq, between November 2023 and August 2024. An additional 36 samples from non-cancer patients were used as controls. Enzyme-linked immunosorbent assay (ELISA) was employed to detect H. pylori-specific immunoglobulins (IgG). Gene expression analysis of ELASTIN, TIMP3, K-RAS, and BRAF was performed using RT-qPCR. RESULTS: The study found that H. pylori infection was present in 79.5% of CRC patients, with significant IgG seropositivity (p < 0.05). Gene expression analysis revealed a significant downregulation of TIMP3 and alterations in ELASTIN, K-RAS, and BRAF (p < 0.01). CONCLUSION: In conclusion, chronic H. pylori infection may contribute to CRC pathogenesis through sustained inflammation and genetic dysregulation. The study highlights TIMP3 suppression as a potential factor in CRC progression, warranting further investigation into its clinical implications.

Vitamin D3 Supplementation Modulates C-MYC/VEGF and Improves Chemotherapy Outcomes in Metastatic CRC Patients: Integrated Clinical-Mechanistic Evidence.

Rahman AMA, Hassan NA, Hamza MS … +4 more , Gaber N, Omran MM, Shouman SA, Khallaf SM

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345177 · Publisher ↗

OBJECTIVE: Systemic chemotherapy with fluoropyrimidine regimens is the cornerstone of management for unresectable metastatic colorectal cancer (CRC). This study aimed to evaluate the clinical outcomes and potential molec... OBJECTIVE: Systemic chemotherapy with fluoropyrimidine regimens is the cornerstone of management for unresectable metastatic colorectal cancer (CRC). This study aimed to evaluate the clinical outcomes and potential molecular mechanisms of adding vitamin D3 supplementation to fluoropyrimidine-based chemotherapy in metastatic CRC patients. METHODS: This study evaluated the clinical effects of vitamin D3 addition to fluoropyrimidine therapy. Serum vitamin D3 levels and expression of vascular endothelial growth factor (VEGF) and cellular myelocytomatosis (C-Myc) were determined at baseline and after two months of therapy. Clinical endpoints such as overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed. RESULTS: Patients supplemented with vitamin D3 had a significant rise in the median vitamin D3 levels after two months (8 (6-14) to 13.5 (8-16.3) ng/mL; Δ +5.5 (3-8); Wilcoxon p<0.001), whereas those in the control group, who did not receive supplementation, experienced a decline in median vitamin D3 levels (11 (8-14.3) to 9 (8-16.3) ng/mL; Δ -2 (-4 to +1); Wilcoxon p=0.01). Supplementation was also associated with greater downregulation of VEGF and C-Myc expression (p<0.05). The overall response rate was higher in the vitamin D3 group of patients (63.3% vs. 25.8%; p<0.01), and median PFS was significantly prolonged (9.1 vs. 6.5 months; p=0.028). CONCLUSION: Our study suggests that vitamin D3 enhances fluoropyrimidine efficacy in metastatic CRC patients by modulating angiogenesis and proliferation pathways, supporting its potential as a safe, low-cost adjunct to chemotherapy.

Blood-Based vs. Tissue-Based mRNA Expression of Thymidylate Synthase, Dihydropyrimidine Dehydrogenase, and Methylenetetrahydrofolate Reductase: A Prospective Study to Predict the Neoadjuvant CAPEOX Response in Advanced Colorectal Cancer.

Tahiya ECI, Lusikooy RE, Patellongi I … +7 more , Warsinggih W, Uwuratuw JA, Syarifuddin E, Labeda I, Sampetoding S, Kusuma MI, Faruk M

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345176 · Publisher ↗

BACKGROUND: Fluoropyrimidine-based chemotherapy is a fundamental treatment for colorectal cancer (CRC), yet its therapeutic efficacy is often limited by significant inter-individual variability. Enzymes involved in 5-flu... BACKGROUND: Fluoropyrimidine-based chemotherapy is a fundamental treatment for colorectal cancer (CRC), yet its therapeutic efficacy is often limited by significant inter-individual variability. Enzymes involved in 5-fluorouracil (5-FU) metabolism thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and methylenetetrahydrofolate reductase (MTHFR) are critical determinants of drug response. This study aimed to evaluate the molecular correlation between TS, DPD, and MTHFR mRNA expression in paired tumor tissue and peripheral blood samples, while simultaneously developing and validating a non-invasive predictive nomogram to forecast therapeutic response to neoadjuvant CAPEOX (capecitabine-oxaliplatin) chemotherapy in advanced CRC. METHODS: A prospective cohort study was conducted on 36 patients with stage III-IV CRC receiving CAPEOX. mRNA expression of TS, DPD, and MTHFR was quantified using qRT-PCR from paired tumor and peripheral blood samples. Chemotherapy response was evaluated using RECIST 1.1 criteria. Statistical analyses included Spearman correlation, the Mann-Whitney U test, and multivariate logistic regression. A nomogram was constructed based on significant predictors. RESULTS: DPD and MTHFR expression levels were significantly lower in responders than in non-responders (p < 0.001), while TS expression showed no significant difference. Gene expression in tissue and blood was strongly correlated (r = 0.820 for TS, r = 0.658 for DPD, and r = 0.623 for MTHFR; all p < 0.001). Multivariate analysis identified blood-based DPD and MTHFR expression as independent predictors of response. The predictive nomogram demonstrated excellent discrimination (AUC = 0.932). CONCLUSION: Lower DPD and MTHFR expression predicts a favorable response to neoadjuvant CAPEOX in advanced CRC. These biomarkers offer a promising, non-invasive approach to personalizing treatment strategies potentially enhancing therapeutic efficacy while minimizing unnecessary toxicity.

Molecular and Lifestyle Determinants of Oral Squamous Cell Carcinoma in Bangladesh: Dietary Patterns Independent of HPV and TERT Promoter Mutations.

Liza RA, Raheem E, Akter S … +6 more , Hasan MN, Jamil AH, Thufayal AA, Alam MM, Islam A, Karim MR

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345175 · Publisher ↗

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer globally and constitutes a major public health burden in Bangladesh, with approximately 7.5% of all cancer-related deaths. Although tobac... BACKGROUND: Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer globally and constitutes a major public health burden in Bangladesh, with approximately 7.5% of all cancer-related deaths. Although tobacco and betel-quid use are recognized risk factors, dietary patterns may also contribute to OSCC development. OBJECTIVE: This study investigated the association of lifestyle and dietary factors with OSCC in Bangladeshi patients and explored the potential involvement of TERT promoter mutations and human papillomavirus (HPV) infection. METHODS: A hospital-based, case-control study was conducted involving 47 histopathologically confirmed OSCC patients and 100 age- and sex-matched healthy controls without cancer or chronic illness. Sociodemographic, lifestyle, and dietary data were collected through a structured questionnaire. Tumor DNA was analyzed for TERT promoter mutations and HPV DNA using PCR and Sanger sequencing. Statistical analyses were performed using multivariable logistic regression to identify significant associations. RESULTS: Excessive betel-quid chewing was strongly associated with OSCC (p < 0.01). Among 39 sequenced OSCC samples, 25 single-nucleotide polymorphisms (SNPs) at position -245 (A>G) and one hotspot mutation at position -124 (G>A) of the TERT promoter were identified substantially lower than frequencies reported in other populations. No HPV DNA was detected in any sample. Certain dietary patterns such as low fruit and vegetable intake and high consumption of betel quid were linked to increased OSCC risk. CONCLUSION: Our findings suggest that, in Bangladeshi patients, specific dietary and lifestyle factors, rather than HPV infection or TERT promoter mutations, contribute significantly to OSCC development. Targeted public health strategies emphasizing nutritional awareness and cessation of betel-quid use are recommended.

Combined Diagnostic Utility of Serum CA15-3 and Routine Hematological Indicators for Breast Cancer Differentiation in an Iraqi Cohort.

Mohaibes MJ, Al-Khafaji M, Muhaibes F

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345174 · Publisher ↗

BACKGROUND: Breast cancer (BC) is a leading cause of mortality among Iraqi women, underscoring the need for accessible diagnostic tools. This study evaluates the combined utility of the tumor marker CA15-3 and routine he... BACKGROUND: Breast cancer (BC) is a leading cause of mortality among Iraqi women, underscoring the need for accessible diagnostic tools. This study evaluates the combined utility of the tumor marker CA15-3 and routine hematological parameters as an adjunctive tool for distinguishing between treatment-naïve BC patients with a pre-existing diagnosis and healthy individuals. METHODS: In this case-control study, 100 female BC patients (Group I) and 50 healthy controls (Group II) were recruited. Serum CA15-3 levels were measured using electrochemiluminescence immunoassay (ECLIA), and a complete blood count was performed. Statistical analyses included independent t-tests, ROC curve analysis, and logistic regression to develop a combined diagnostic model. All BC patients were treatment-naïve and were required to submit blood samples prior to undergoing any surgical procedure, although they had already been diagnosed. RESULTS: CA15-3 levels were significantly higher in BC patients (26.1 ± 7.5 U/mL) than in controls (7.54 ± 2.6 U/mL; P < 0.001). Significant differences were also observed in white blood cell (WBC), red blood cell (RBC), lymphocyte, and platelet counts (all P < 0.05). ROC analysis showed excellent diagnostic performance for CA15-3 alone (AUC = 0.98). A combined model integrating CA15-3 with the four hematological parameters achieved a superior AUC of 0.99, with 96% sensitivity and specificity. CONCLUSION: Elevated CA15-3 is confirmed as a key diagnostic marker for BC. Integrating CA15-3 with specific, routinely measured hematological indicators provides an improved, accessible, and cost-effective adjunctive tool for differentiating treatment-naïve BC patients from healthy individuals. This approach may be particularly useful for triaging patients with suspicious symptoms or monitoring those with established diagnoses.

Prognostic and Clinical Significance of Circulating Cystatin C Levels in Cancer Patients: A Meta-Analysis.

Tory S, Hasan MM, Arslan YK … +2 more , Saygideger Y, Tutar Y

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345173 · Publisher ↗

BACKGROUND: Cystatin C (CysC) exhibits both tumor-promoting and tumor-suppressing effects. Although elevated circulating CysC levels have been reported in multiple cancer types, studies assessing its prognostic value hav... BACKGROUND: Cystatin C (CysC) exhibits both tumor-promoting and tumor-suppressing effects. Although elevated circulating CysC levels have been reported in multiple cancer types, studies assessing its prognostic value have produced conflicting results. This study aims to resolve these discrepancies and clarify the role of CysC as a prognostic marker. METHODS: A literature search was conducted in multiple databases. The pooled Hazard Ratio (HR) with a 95% confidence interval (CI) was calculated to assess the prognostic significance of CysC, while the Odds Ratio (OR) with a 95% CI was used to evaluate its clinicopathological associations in various cancers. Sources of heterogeneity were identified by performing subgroup and meta-regression analyses. The study was registered in PROSPERO. RESULTS: Twelve studies comprising 7678 patients were included in the analysis. The study found that elevated CysC levels were associated with worse overall survival (OS); pooled HR = 1.60, 95% CI = 1.22-2.10; p = 0.0006, I² = 84%. Subgroup analyses indicated that renal cancer, follow-up time >2.5 years, and study location (China) were linked to worse survival, and all subgroups contributed to significant heterogeneity. Sensitivity analysis confirmed the robustness of the pooled results. Additionally, CysC levels correlated with T stage, N stage, TNM stage, and sex, but not with smoking. CONCLUSION: Elevated CysC is associated with worse overall survival, but significant heterogeneity warrants cautious interpretation.

HCC-miR: A Simple, Noninvasive, and Sensitive Model for Early Diagnosis of HCV-Associated Hepatocellular Carcinoma.

Ayad M, Saleh H, El-Mezayen HA … +2 more , El-Kassas M, El-Sharkawy A

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345172 · Publisher ↗

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a major cause of cancer-related mortality worldwide. Chronic hepatitis C virus (HCV) infection remains the predominant etiologica... BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a major cause of cancer-related mortality worldwide. Chronic hepatitis C virus (HCV) infection remains the predominant etiological factor in Egypt. The limited sensitivity and specificity of alpha-fetoprotein (AFP) continue to hinder early HCC detection. This study aimed to assess the diagnostic significance of circulating microRNA-155 (miRNA-155) expression in HCV-related HCC and to develop a novel, noninvasive diagnostic model combining miRNA-155 with routine biomarkers.  Methods: A total of 42 HCV-positive HCC patients, 83 patients with liver cirrhosis (LC), and 20 healthy controls were enrolled. Clinical, hematologic, and biochemical parameters were analyzed. Circulating miRNA-155 levels were quantified by quantitative real-time PCR and normalized to U6 RNA. Receiver operating characteristic (ROC) curve analysis and multivariate discriminant analyses were used to develop a composite diagnostic model integrating AFP, albumin, platelet count, INR, AST/ALT ratio, and miRNA-155, designated the HCC-miR Score. RESULTS: Liver function tests and hematologic indices showed progressive deterioration from controls to LC and HCC groups. miRNA-155 expression was significantly elevated in HCC (6.71 ° 3.38) compared with LC (5.44 ° 2.31) and controls (1.27 ° 0.68) (p < 0.0001). The HCC-miR Score demonstrated superior diagnostic accuracy (AUC = 0.753) to AFP alone (AUC = 0.713), achieving 100% sensitivity and 68% specificity at a cutoff value of 0.32. The model effectively discriminated early-stage, small-sized, and well-differentiated tumors from cirrhotic cases, outperforming AFP across all subgroups. CONCLUSION: Circulating miRNA-155 is markedly upregulated in HCV-related HCC and correlates strongly with disease progression. The novel HCC-miR Score represents a simple, sensitive, and noninvasive model for the early diagnosis of HCC in high-risk HCV patients.

Reliability and Validity Assessment of the General Medication Adherence Scale among Breast Cancer Patients in Pakistan.

Noreen D, Shakeel S, Rahim N … +5 more , Shamim S, Anjum F, Zehra A, Haider G, Shakeel Ahmed A

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345171 · Publisher ↗

BACKGROUND: Adherence rates to adjuvant therapy for breast cancer are often suboptimal, which raises the risk of recurrence, lowers survival rates, and increases healthcare expenses. The present study aimed to assess the... BACKGROUND: Adherence rates to adjuvant therapy for breast cancer are often suboptimal, which raises the risk of recurrence, lowers survival rates, and increases healthcare expenses. The present study aimed to assess the validity and reliability of the General Medication Adherence Scale (GMAS) in identifying adherence to adjuvant cancer therapy (ACT) in breast cancer patients. METHOD: A prospective, cross-sectional study was conducted on breast cancer patients using the Urdu version of the GMAS. Reliability was assessed using Cronbach's alpha (α) and inter-item correlations. The instrument was subjected to principal component factor analysis (PCFA) with varimax rotation. Exploratory factor analysis (EFA) and PCFA were performed using IBM SPSS version 23, while confirmatory factor analysis (CFA) was carried out using IBM AMOS version 25. RESULTS: Cronbach's alpha of the GMAS was found to be 0.882, confirming that the scale has good reliability. The mean score was significantly different among items ensuring the significance of each item in the GMAS scale (Tukey's test p< 0.0001; Chi-square=38.825, p< 0.0001). A total of 204 female responses were recorded; the mean age was 41.2±9.5 years. It was observed that n=95 (46.5%) of patients showed partial adherence whereas n=76 (37.2%) patients were highly adherent to ACT. The probability of patients' adhering to their therapy was greater among those who were employed [OR = 1.95, 95% CI (1.27, 2.62)] and have higher level of education [OR = 2.93, 95% CI (1.39, 4.46)]. The potential reasons for non-adherence were the cost of treatment n=44 (21.5%), adverse effects n=33 (16.1%), depression and emotional stress n=32 (15.6%). CONCLUSIONS: The Urdu version of GMAS, validated with good internal reliability, proved to be a feasible and accurate tool for measuring adherence among breast cancer patients.

Sodium Butyrate Activity in Colorectal Cancer under Hypoxia: A Potential Role for Carbonic Anhydrase IX.

Alayssami H, Hachim MY, Senok A … +1 more , Moussa S

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345170 · Publisher ↗

BACKGROUND/AIM: Hypoxia poses a significant challenge to cancer therapy. The impact of hypoxia on butyrate, a gut metabolite that has anti-colorectal-cancer properties, is unclear. Thus, the aim of this study was to dete... BACKGROUND/AIM: Hypoxia poses a significant challenge to cancer therapy. The impact of hypoxia on butyrate, a gut metabolite that has anti-colorectal-cancer properties, is unclear. Thus, the aim of this study was to determine the activity of sodium butyrate (NaB) under hypoxic conditions. Furthermore, this study was the first to investigate the potential of carbonic anhydrase IX (CA IX), a hypoxia-regulated gene, as a target for NaB. MATERIALS AND METHODS:  The Caco-2 and HT-29 colorectal cancer cell lines were exposed to 0, 5, 10, 15, and 20 mM NaB under hypoxic and normoxic conditions for 24 and 48 hours. We assessed cell viability and clonogenicity rates using an MTT assay and a colony-forming assay, respectively. RT-PCR was used to measure the effect of NaB on CA IX expression level. RESULTS: After 24 hours of treatment with NaB, the percentage of viable HT-29 cells decreased under normoxic conditions, while it remained unchanged under hypoxic conditions. After 48 hours, the percentage of viable HT-29 cells decreased under both oxygen conditions. The viability of normoxic and hypoxic Caco-2 cells was only reduced after 48 hours of NaB application. Interestingly, NaB significantly reduced the number of HT-29 and Caco-2 colonies in normoxic and hypoxic conditions. NaB significantly decreased CA IX mRNA expression level in HT-29 hypoxic cells after 48 hours (p <0.0001), but not after 24 hours. CONCLUSION: At the beginning, hypoxia caused an alteration in the anti-colorectal-cancer activity of NaB, which then returned to normal. Our data revealed the novel finding that NaB downregulates CA IX, suggesting a potential therapeutic strategy for colorectal cancer that targets tumor metabolism and pH regulation.

The Anticancer Effects of Salvia palaestina Essential Oil Grown in Iraq.

Abdulmohsin H, Qasim M

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345169 · Publisher ↗

OBJECTIVE: This preliminary in vitro study aimed to isolate the essential oil of Salvia palaestina and evaluate its cytotoxic activity against SKG-T4 and A2780 cancer cell lines. METHODS: The aerial parts of the plant we... OBJECTIVE: This preliminary in vitro study aimed to isolate the essential oil of Salvia palaestina and evaluate its cytotoxic activity against SKG-T4 and A2780 cancer cell lines. METHODS: The aerial parts of the plant were air dried, ground, and subjected to hydrodistillation using a Clevenger type apparatus for 3 hours. The obtained oil was dried over anhydrous sodium sulfate and stored at +4°C in the dark until use. GC/MS analysis was performed to identify the major phytochemical constituents. Cytotoxicity was assessed using a colorimetric MTT assay on esophageal SKG-T4 and ovarian A2780 cancer cell lines, with normal human fibroblasts (NHF) serving as the control. Cells were treated with serial concentrations of S. palaestina essential oil (100, 50, 25, 12.5, 6.25, 3.12 µl/ml) for 72 hours. Data were analyzed using GraphPad Prism software (version 8). RESULT: Treatment with the essential oil resulted in decreased cell viability in a concentration dependent manner. At 100µl/ml, cytotoxicity reached 62.8% in SKG-T4 cells and 52.3% in A2780 cells. The IC₅₀ values were 57.9µl/ml for SKG-T4 and 72.9µl/ml for A2780 cells, indicating notable anti cancer potential. The essential oil was slightly more potent in SKG-T4 cells and exhibited considerably lower cytotoxicity toward NHF cells, where 100µl/ml caused 27.2% cytotoxicity, with an IC₅₀ of 492.1µl/ml. The safety index (SI = IC₅₀₍non cancer₎ / IC₅₀₍cancer₎) was 8.5 for SKG-T4 and 6.8 for A2780, demonstrating greater selectivity toward cancer cells. Microscopic examination revealed morphological features of apoptosis, including cell shrinkage, membrane blebbing, and apoptotic body formation. GC/MS analysis showed limonene as the major constituent (73.05%), along with other phytochemicals with known anti cancer properties. CONCLUSION: The essential oil of Salvia palaestina demonstrates promising anti cancer activity, characterized by concentration dependent cytotoxicity and a favorable safety index, supporting its potential as a selective anticancer agent.

Melatonin Receptors in Uterine Leiomyomas: An Immunohistochemical Study.

Sayed RMS, A Taha AA, Mohamed AW … +3 more , Refaie SM, Newira MA, Mohammed H

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345168 · Publisher ↗

BACKGROUND: Uterine leiomyomas are the most common benign tumors in women of reproductive age, often causing significant symptoms such as abnormal bleeding, pain, and infertility. Melatonin, a hormone with anti-prolifera... BACKGROUND: Uterine leiomyomas are the most common benign tumors in women of reproductive age, often causing significant symptoms such as abnormal bleeding, pain, and infertility. Melatonin, a hormone with anti-proliferative and oncostatic properties, has been studied; however, its effects on uterine leiomyomas remain unclear. OBJECTIVE: This study aimed to evaluate the immunohistochemical expression of melatonin receptors MT1 and MT2 in uterine leiomyomas compared to normal myometrium, and to correlate their expression with clinical and histopathological features. METHODS: A case-control study was conducted on ninety cases retrieved (60 leiomyoma cases, thirty normal myometrium controls). Immunohistochemical staining was performed to assess the expression of MT1 and MT2 receptors. Clinical data were collected, and statistical analyses were conducted to evaluate associations between receptor expression and demographic, clinical, and histological features. RESULTS: MT1 and MT2 were significantly overexpressed in leiomyomas compared to controls (MT1: 70% vs. 30%, p < 0.0001; MT2: 60% vs. 16.7%, p < 0.0001). A strong positive correlation was observed between MT1 and MT2 expression (r = 0.6, p < 0.0001). MT1 score varied significantly with age (p = 0.03), tumor location (p = 0.04), and presenting symptoms (p = 0.03), while MT2 expression was positively associated with the number of lesions (p = 0.033). CONCLUSION: Melatonin receptors MT1 and MT2 are significantly upregulated in uterine leiomyomas, suggesting a potential role in their pathogenesis. These findings support further investigation into melatonin-based therapies as adjunctive treatments for leiomyomas.

Novel Anticancer Mechanism of Chamuangone through the Inhibition of Oncogenic Protein-Driven Oxidative Stress.

Thianthong W, Srichainan T, Shuntawiwat B … +6 more , Laprom S, Chiangsaen P, Kongpetch S, Choowongkomon K, Panichayupakaranant P, Samatiwat P

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345167 · Publisher ↗

OBJECTIVE: To evaluate the anticancer mechanisms of Chamuangone against cholangiocarcinoma (CCA) cells. METHODS: Chamuangone was tested for cytotoxicity against KKU-100 and KKU-452 cells for 24 and 48 h. Apoptosis, cell... OBJECTIVE: To evaluate the anticancer mechanisms of Chamuangone against cholangiocarcinoma (CCA) cells. METHODS: Chamuangone was tested for cytotoxicity against KKU-100 and KKU-452 cells for 24 and 48 h. Apoptosis, cell proliferation, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were assessed using Annexin V, Ki-67, JC-1 assays, and DCFH-DA fluorescence probe, respectively. Oncology proteins expression was measured. RESULTS: Chamuangone inhibited CCA cell growth in a dose- and time- dependent manner, with IC50 values in KKU- 100 cells of 1.175 and 0.331 μg/mL at 24 and 48 hours, respectively; in KKU- 452 cells, the IC50 values were 1.208 and 0.428 μg/mL. Consequently, Chamuangone at 1.5 and 3.0 μg/mL effectively induced both early and late apoptosis in a statistically significant manner, which correlated with a marked reduction in cell proliferation, as evidenced by the decrease in Ki-67 positive populations to 49.04% and 17.02%, respectively. Chamuangone at concentrations of 0.75, 1.5, and 3.0 μg/mL significantly induced mitochondrial dysfunction by reducing the Red/Green fluorescence ratio across all time points (3-24 h), indicating a loss of mitochondrial membrane potential that triggers apoptosis. The induction of intracellular oxidative stress was  indicated by a significant increase in the high-dose group of Chamuangone. Moreover, it also suppressed the expression of key ROS- and oxidative stress-associated oncogenic proteins, including Carbonic Anhydrase IX, Enolase2, CXCL8/IL-8, Galectin-3, EGFR/ErbB1, Progranulin, FGF basic, Dkk-1, p27/kip1, Mesothelin, Survivin, leading to redox imbalance and apoptosis in KKU-100 cells. CONCLUSION: Chamuangone inhibits CCA cell proliferation by inducing apoptosis through mechanisms involving the suppression of the Ki67, loss of mitochondrial membrane potential, intracellular ROS accumulation, and downregulation of oncogenic-related proteins involved in proliferation, survival, angiogenesis, and oxidative stress. Thus, Chamuangone has significant potential as a lead compound for the development of novel CCA therapeutics.

Unit Cost Analysis of Allogeneic Hematopoietic Stem Cell Transplantation at Dr. Kariadi General Hospital, Semarang, Indonesia.

Santosa D, Suryawati C, Sriatmi A

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345166 · Publisher ↗

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for hematologic malignancies, yet access in Indonesia remains limited due to high costs and its exclusion from the national health insura... BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for hematologic malignancies, yet access in Indonesia remains limited due to high costs and its exclusion from the national health insurance scheme. This study determined the unit cost of allogeneic HSCT at Dr. Kariadi General Hospital using the activity-based costing (ABC) approach. METHODS: A mixed-method design combined retrospective cost data from three donor-recipient pairs that received HSCT during the January 2023 - December 2024 period and thematic analysis of qualitative interviews with clinical and administrative staff. Costs were categorized as direct and indirect, mapped along the HSCT clinical pathway, and analyzed descriptively. RESULTS: The total unit cost of allogeneic HSCT was IDR 377,978,399, comprising IDR 297,063,048 for recipients and IDR 80,915,351 for donors. Post-transplant care was the major cost driver among recipients (IDR 157,843,439), while harvesting represented the highest donor-related cost (IDR 37,819,185). However, comparison with current hospital tariffs demonstrated CRRs of 218.8-239.0% for recipients and 113.7-123.6% for donors, suggesting that existing tariff packages exceed the estimated unit costs and may generate a financial surplus. CONCLUSIONS: The ABC method effectively identified major cost components and financial gaps, highlighting the need for updated reimbursement models and BPJS coverage inclusion to ensure long-term HSCT program sustainability in Indonesia.

Synergistic Effect of Caffeic Acid Phenethyl Ester and Deuterium Oxide in Colon Cancer: An In Vitro Evaluation.

Darama G, Bora Ö, Bostancı F … +4 more , Mehdizadehtapeh L, Andaç S, Tekiner İH, Abdik H

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345165 · Publisher ↗

OBJECTIVE: Caffeic acid phenethyl ester (CAPE) and deuterium oxide (D2O), known as heavy water, have anticancer properties. However, their combined effects in colon cancer have not been addressed yet. This study aimed to... OBJECTIVE: Caffeic acid phenethyl ester (CAPE) and deuterium oxide (D2O), known as heavy water, have anticancer properties. However, their combined effects in colon cancer have not been addressed yet. This study aimed to evaluate the synergistic effects of CAPE and D2O in colon cancer using in vitro techniques. METHODS: The cancer cells (HCT-116) were treated with CAPE and D2O alone and in combination to evaluate their cell viability (CV), induction of apoptosis, expression levels of tumor proliferative (AKT, NF-κB, CCND1), tumor suppressor (p16, BAX, TP53, p21) genes, and colony-forming ability, respectively. RESULT: The combined treatment of 10 µM CAPE and 30% D₂O in human colon cancer cells (HCT-116) were significantly: (i)cytotoxic on the CV; (i)induced apoptosis, (iii)downregulated the expression of AKT, NF-κB and CCND1 while upregulated the expression of p16, BAX, and TP53, without altering p21 level, and (iv)suppressed the cells' colony forming ability, respectively (p<0.05). CONCLUSION: Overall, CAPE and D₂O may be an effective adjuvant for enhancing therapeutic efficacy in colon cancer. However, further research is needed to determine whether their synergistic effects are also selective in other malignancies, as well as with their toxicokinetic potential.

Orange Peel Extract-Mediated Green Synthesis of PEG-Modified ZnO Nanoparticles: Structural Characterization, Biocompatibility, and Anticancer Efficacy.

Kodali M, Kaloni S, M R … +1 more , Girigoswami K

Asian Pac J Cancer Prev · 2026 Jun · PMID 42345164 · Publisher ↗

OBJECTIVES: Engineered nanomaterials could potentially interact with biomolecules and intracellular processes, as many biological activities take place at the nanoscale level. Conventional anticancer therapies have sever... OBJECTIVES: Engineered nanomaterials could potentially interact with biomolecules and intracellular processes, as many biological activities take place at the nanoscale level. Conventional anticancer therapies have several limitations, which warrant the introduction of alternative cancer cell killing agents. METHODS: In the present study, we have synthesized ZnO nanoparticles using orange peel extract and encapsulated them inside polyethylene glycol (PEG), a biocompatible polymer (PEG-ZnO-OP). Different characterization techniques were performed to ensure the proper synthesis of the nanoparticles. The biocompatibility was assessed by the MTT assay using normal fibroblast cells, 3T3L1, hemolysis assay, and zebrafish embryo studies. Finally, the anticancer activity in vitro was estimated by the MTT assay in the lung cancer cell line. RESULTS: The hydrodynamic diameter and zeta potential were 43 nm and -20 mV, respectively, showing an ultrasmall size and moderate stability in an aqueous environment. The XRD data suggested a good crystalline structure; SEM and EDX showed size distribution between 81 nm and 143 nm, and the presence of Zn and O, along with other trace elements, was probably contributed by the orange peel extract. The PEG-ZnO-OP nanoparticles were highly biocompatible up to a dose of 50 μg/mL, as assessed both in vitro and in vivo. Further, the anticancer activity showed a high cell killing effect with an IC50 value of 43.88 μg/ml. CONCLUSION: This study demonstrated that our synthesized PEG-ZnO-OP nanoparticles were safe to administer and could cause significant cancer cell killing. Future studies involving the anticancer effect in other cell lines and animal models need further exploration.
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