Asian Pacific Journal of Cancer Biology

Unveiling the Challenge: Head and Neck Cancers in Teenage and Young Adult Population – A Tertiary Cancer Centre Experience

Ramanaiah Kaluvoya — 2026-01-07

Background: Head and neck squamous cell carcinoma (HNSCC) in the Teenage and Young Adult (TYA) population (15-29 years) is under-reported in literature, especially in low-resource settings like India. This study aims to analyse the clinical characteristics, treatment patterns, and outcomes of HNSCC in this age group.

Methods: A retrospective analysis was conducted on 46 TYA patients diagnosed with HNSCC at our institution between January 2011 and December 2013. Patients were evaluated based on clinical history, imaging, and biopsy, and treated as per multidisciplinary tumor board recommendations. Treatment modalities included surgery, chemo radiation, and palliative care. Survival outcomes were analysed using Kaplan-Meier curves.

Results: Among the 46 patients, the majority were male (65%), with the most common primary sites being the oral cavity (39%) and hypopharynx (28%). Locally advanced disease (Stage III and IV) was predominant in 82% of cases. Tobacco use, especially in smokeless forms, was a significant risk factor, present in 39% of patients. Overall survival (OS) at 3 and 5 years was 50% and 48%, respectively, with oral cavity and hypopharyngeal cancers showing poorer outcomes. The most common toxicities were neutropenia and skin reactions, which were consistent with published data.

Conclusions: HNSCC in the TYA age group is typically diagnosed at an advanced stage and is associated with poor outcomes. Tobacco consumption remains a major risk factor. Early detection through screening and public health campaigns to reduce tobacco use are critical to improving prognosis in this population.

Assessing the Synergistic Anticancer impact of Metronidazole and Ciprofloxacin in Cervical Cancer: MAPK-RAS Pathway as a Key Mechanism

Anas K. Awn — 2026-01-07

Objective: This study assessed the anticancer impact of the Metronidazole-Ciprofloxacin mixture, focusing on its molecular mechanism by examining its ability to target the Ras-MAPK signaling pathway.

Methods: The MTT assay evaluated the anticancer and safety properties of a Metronidazole-Ciprofloxacin mixture. HeLa cells and human-derived adipose tissue (NHF) cell lines were used in two incubations for 24 and 72 hours, with concentrations ranging from 0.1 to 1000 µg/ml for each treatment. Cisplatin was employed for comparative purposes. The combination index CI and the selective toxicity index SI were used to assess the possible synergistic effects of the mixture’s ingredients and selective toxicity. Computational molecular docking simulations were utilized to investigate the binding affinity of the mixture ingredients to various kinase signal proteins within the MAPK-RAS pathway.

Results: The MTT assay demonstrated that metronidazole, ciprofloxacin, cisplatin, and the mixture inhibit cervical cancer growth, with the mixture having a significantly greater impact than the others. The mixture showed a lesser effect on the viability of the NHF cell line and exhibited a favorable selectivity index compared to cisplatin. Additionally, the CI suggests that the medications act synergistically when used together. The molecular docking study revealed that the optimal interactions were between ciprofloxacin and RAS GTPase, and metronidazole and ERK2 kinase, with docking scores of -7.3 kcal/mol and -6.3 kcal/mol, respectively.

Conclusion: Regarding the study outcomes and the well-known pharmacokinetic and safety profiles of the mixture ingredients, the metronidazole-ciprofloxacin mixture presents an attractive and safer alternative for treating cervical cancer.

Co-expression of BCL2 and C-MYC as a Potential Predictive Factor of Survival in Diffuse Large B Cell Lymphoma with Rituximab-Based Chemotherapy

Kun Salimah — 2026-01-07

Objective: Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous disease with varying aggressiveness and response to therapy. The co-expression of BCL2 and C-MYC has been reported to hold prognostic value for disease outcomes. This study aimed to determine the proportion of DLBCL patients with co-expression of BCL2 and C-MYC at Dr. Sardjito Hospital and evaluate its association with clinicopathological features and survival.

Methods: This retrospective cohort study included 72 DLBCL patients treated with rituximab-based chemotherapy between January 2017 and December 2019. The co-expression of BCL2 and C-MYC was evaluated using immunohistochemistry. The Kaplan-Meier method was used along with the log-rank test to assess 5 years overall survival and to compare the two groups. Cox proportional hazards regression was applied to identify factors affecting survival.

Result: The proportion of patients with BCL2 and C-MYC co-expression was 12.5% (9/72 patients). These patients exhibited a trend toward poorer survival compared to those without co-expression (median OS: 26 months [95% CI: 0.000–52.296] vs. 71 months [95% CI: 55.057–86.943]; p = 0.156). However, the co-expression of BCL2 and C-MYC did not demonstrate predictive value for 5-year survival in DLBCL patients receiving rituximab-based chemotherapy.

Conclusion: DLBCL patients with BCL2 and C-MYC coexpression demonstrated a trend toward shorter survival compared to those without co-expression. However, this co-expression was not identified as an independent prognostic factor for 5-year survival in DLBCL patients treated with rituximab-based chemotherapy.

Study to Analyze the Dosimetric Characteristics of High Dose Rate Flattening Filter-Free Beam from different Linear Accelerators

Palanivelu D — 2026-01-07

Background: Numerous radiation-generating devices produce flattening filter-free (FFF) beams for treating cancer patients clinically, while all those machines produce FFF beams, they differ in their treatment head, collimation system, Multi leaf collimator (MLC) configurations, MLC speed, gantry speed, and dose rate. Objective of this study was to compare dosimetric characteristics of FFF beams used in different linear accelerators (Linacs) from multiple radiotherapy centres.

Methods: Dosimetric data for 6MV FFF and 10MV FFF beams from Elekta Versa HD™ (EVH1 & EVH2), Varian TrueBeam™ (VT1 & VT2), and 6MV FFF from Varian Halcyon™ (VH1 & VH2) were analyzed. This study compared different dosimetric parameters included depth of maximum dose (Dmax), beam quality index, percentage depth dose (PDD), beam profiles, penumbra, off-axis ratio, percentage surface dose (PSD), head leakage, and multi-leaf collimator (MLC) leakage.

Results: The VH showed significantly lower MLC transmission (0.007–0.03%) compared to VT (1.21–1.23%) and EVH (0.23–0.34%). PSD for a 30×30 cm² field was lower in EVH (37.1–38.4%) than VT (49.3–51.1%) but higher for a 28×28 cm² field in VH (66.2–69.1%). Head leakage showed no major differences, with values in the patient plane of 0.004–0.014% (EVH), 0.005-0.03% (VT), and 0.012–0.10% (VH); and other than patient plane of 0.02–0.10% (EVH), 0.007% (VT), and 0.012–0.209% (VH). Penumbra was slightly lesser in VH (8.9 mm) than VT (9.5 mm) and EVH (9.8 mm). VH exhibited excellent MLC shielding and a narrower penumbra, ensuring better conformity and minimal leakage. EVH had lower PSD, offering improved skin sparing. VT showed higher MLC transmission, indicating slightly higher out-of-field dose. Head leakage was lesser for all machines, confirming effective shielding design.

Conclusion: Overall analysis shows clear performance variations among the evaluated linac platforms. EVH exhibited a higher energy spectrum, while VH and VT demonstrated slightly lower values. VH showed the lowest MLC leakage. Comprehensive dosimetric comparisons are essential when commissioning FFF linacs. Machine specific parameter must be assessed and optimized for clinical needs. Such evaluations are key for advanced radiotherapy quality. Centres should consider these technical details in commissioning and deployment.

Prognostic Significance of Claudin-4 in Relation to Key Tumor Budding and Invasion Parameters in Colorectal Adenocarcinoma

Ririn Endah Puspitasari — 2026-01-07

Objective: Colorectal cancer (CRC) is a major global health burden. Claudin-4, a tight junction protein preserving epithelial cohesion, has paradoxically been implicated in tumor progression. Its prognostic role in CRC remains unclear, particularly regarding histopathological grade, tumor budding, tumor-infiltrating lymphocytes (TILs), and deep invasion. This study aimed to clarify these associations.

Methods: This cross-sectional study included 95 formalin-fixed, paraffin-embedded colorectal adenocarcinoma specimens obtained from 2022 to 2024. Claudin-4 expression was assessed immunohistochemically using the TIS. Tumor budding was evaluated according to ITBCC 2016, TILs based on ITWG criteria, histopathological grade using the WHO classification, and deep invasion (pT1–pT3) based on the AJCC 8th edition. Statistical analysis was performed with Chi-square, Mann–Whitney, and Kruskal–Wallis tests.

Results: Strong Claudin-4 expression was found in 47.4% of cases. Expression correlated significantly with tumor budding (p = 0.038) and deep invasion (p = 0.038), but not with histopathological grade (p = 0.113) or TILs (p = 0.170). Mean TIS values showed a non-significant upward trend with grade and TIL density.

Conclusion: Claudin-4 is significantly associated with markers of invasiveness, supporting its value as a prognostic biomarker of tumor aggressiveness in colorectal adenocarcinoma.

The Effect of EPS of Biofilm on Expression of Bax and Bcl-2 Genes in Human Cervical Carcinoma Cell Line (HeLa)

Iman A. Bachay — 2026-01-07

Background: The third most common malignancy in women is cervical carcinoma (CC). worldwide and remains a major reason of cancer-related losses. between females. Even though the availability of conventional therapies, their efficacy is often limited, which has encouraged the search for novel agents that selectively target cancer cells. Recent studies suggest that bacterial biofilms may possess anticancer activity.

Objective: Establish exopolysaccharides (EPS) as promising candidates for natural, cost-effective, and biologically compatible cancer therapies.

Methods: In this study, the cytotoxic influence of extracellular polymeric substances (EPS) derived from Pseudomonas aeruginosa biofilms was assessed on HeLa cervical cancer cells via the methyl thiazolyl tetrazolium (MTT) test to calculate the IC50, or half-maximal inhibitory concentration. Following EPS treatment, apoptotic markers were analyzed by real-time PCR.

Results: EPS exposure led to a significant, dose-dependent inhibition of HeLa cell proliferation matched to Vero cells (p<0.05). Furthermore, cervical cancer cells treated with EPS exhibited a marked rise in the expression of the pro-apoptotic gene Bax and a concomitant reduction in the expression of the anti-apoptotic gene Bcl-2 (p<0.05).

Conclusion: These outcomes indicate that EPS can induce apoptosis in HeLa cells, as reflected by the upregulation of Bax and the downregulation of Bcl-2. This highlights the potential of EPS such as a promising candidate for the development of novel anticancer therapies for cervical cancer.

High-level Chemoresistance in Paclitaxel-resistant C-33A Cells Involves the Alteration of Multiple Signaling Pathways and the Drug Efflux Phenotype by Modulating Coding and Long Non-coding RNAs

Marcela Martínez-Valenzuela — 2026-01-07

Background: In chemoresistance, a variety of oncogenic signaling pathways can be activated and interconnected to combat drug toxicity, making anticancer pharmacological strategies complex.
Objective: This study aimed to generate a paclitaxel-chemoresistant cancer cell line scaffold and explore its mechanisms of chemoresistance.

Materials and methods: Total RNAs from C-33A and C-33A RPTX (paclitaxel-resistant) cells were sequenced to determine the transcriptome of coding and long non-coding RNAs (lncRNAs). Enrichment analysis of differentially expressed genes (DEGs) was conducted. Flow cytometry was performed to analyze doxorubicin accumulation in C-33A RPTX cells.

Results: C33-A RPTX cells achieved a resistance index of 55. 1332 genes were differentially expressed (log2 fold-change>1). Gene ontology (GO) analysis revealed that biological processes, such as angiogenesis and mesenchymal development, were altered, while the mainly altered cellular components were from the extracellular matrix (ECM). Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that signaling pathways, including PI3K/Akt, MAPK, Calcium, ECM-receptor, Rap1, EGFR tyrosine kinase inhibitor resistance, tight junction, and platinum drug resistance, were altered by coding RNAs or long non-coding RNAs (lncRNAs). Finally, the overexpression of the ABCB1 gene in C-33A RPTX cells correlated with a drug efflux phenotype, as evidenced by reduced cellular accumulation of the reporter drug doxorubicin. Alterations in signaling pathways recognized as relevant to chemoresistance and increased drug efflux, driven by changes in the expression patterns of coding RNAs and lncRNAs, may be cooperating to establish resistance to paclitaxel in C-33A RPTX cells.

Conclusions: This C-33A RPTX model provides a new experimental platform to study the molecular mechanisms of chemoresistance in cervical cancer. The study integrates both coding and non-coding RNAs, revealing their coordinated alteration in chemoresistance-related signaling pathways. Thus, this dual-level analysis represents a novel systems-level insight into paclitaxel resistance. Beyond descriptive transcriptomics, this resistant model is proposed as a biological platform for testing novel antineoplastic compounds and exploring their mechanisms of action, giving it translational application.

Lunasin‑Rich Soybean Extract Attenuates MMP‑9 Expression in an AOM/DSS Mouse Model of Colitis‑Associated Colorectal Cancer

Muhammad Ikhsanul Azizi — 2026-01-07

Background: Colorectal cancer (CRC) ranks as the third most common malignancy globally and is strongly associated with chronic inflammation, particularly colitis-associated cancer (CAC). Matrix metalloproteinase-9 (MMP-9) is a key enzyme in tumor invasion, angiogenesis, and metastasis. Lunasin, a 44–amino acid peptide derived from soybeans, exhibits anti-inflammatory and anticancer activities, but its role in modulating MMP-9 in CAC remains unclear.

Methods: Thirty male Swiss Webster mice (12 weeks, ~25 g) were randomly assigned to six groups: normal control, negative control, positive control, and three lunasin-rich soybean extract (LRSE) groups (250, 300, 350 mg/kg). CAC was induced using a single intraperitoneal injection of azoxymethane (10 mg/kg) followed by 2% dextran sodium sulfate in drinking water for 7 days. Treatments were given orally for 4 weeks. Colon tissues were collected, and MMP-9 expression was assessed by immunohistochemistry and quantified using the H-score. Data were analyzed with Welch’s ANOVA and Games–Howell post hoc test.

Results: Azoxymethane/Dextran sodium sulfate (AOM/DSS) significantly increased MMP-9 expression compared with normal controls (p < 0.001). Aspirin reduced MMP-9 expression relative to the negative control (p = 0.001). LRSE significantly decreased MMP-9 expression at doses of 250 mg/kg (p = 0.048) and 350 mg/kg (p = 0.001), while the 300 mg/kg dose showed no significant effect. The inhibitory effect of LRSE did not display a clear dose–response pattern.

Conclusion: LRSE significantly reduced MMP-9 expression in an AOM/DSS-induced CAC mouse model, supporting its potential as a natural chemopreventive agent. Further research with larger cohorts and molecular pathway analyses is warranted.

Synergistic Cytotoxicity of Cisplatin Combined with Curcumin and Green Tea Extract via Nanoliposomal Co-Delivery in Oral Squamous Cell Carcinoma

Mahsa Yousefi — 2026-01-07

Background: Oral squamous cell carcinoma (OSCC) remains one of the most prevalent malignancies worldwide, with cisplatin-based chemotherapy limited by systemic toxicity and drug resistance. The present study aimed to enhance cisplatin efficacy through nanoliposomal co-delivery with natural antioxidants curcumin (Cur) and green tea extract (epigallocatechin gallate, EGCG).

Methods: Nanoliposomes were prepared via the thin-film hydration technique followed by sonication and extrusion, generating six formulations: cisplatin-loaded (L-Cis), curcumin-loaded (L-Cur), green tea extract-loaded (L-EGCG), cisplatin + curcumin (L-Cis/Cur), cisplatin + green tea extract (L-Cis/EGCG), and triple co-loaded nanoliposomes containing cisplatin, curcumin, and EGCG (L-Cis/Cur/EGCG) prepared according to a 1:6:6 molar ratio.

Results: Physicochemical characterization revealed nanoscale particle size (212–279 nm), uniform distribution (PDI < 0.3), negative zeta potential (−19 to −23 mV), and high encapsulation efficiencies (69–84%). Scanning electron microscopy confirmed spherical morphology with smooth, homogeneous surfaces. The MTT assay demonstrated that co-loaded and triple-loaded liposomes exhibited significantly higher cytotoxicity than single-drug formulations (p < 0.001). While L-Cis reduced cell viability to approximately 50%, L-Cur and L-EGCG showed moderate effects (~65–70% viability). Co-formulations (L-Cis/Cur and L-Cis/EGCG) further decreased viability to 25–30%, and the triple co-loaded L-Cis/Cur/EGCG (1:6:6) formulation induced the strongest cytotoxic response, consistent with synergistic drug interaction. Live/Dead fluorescence imaging corroborated these findings, showing an elevated proportion of PI-positive apoptotic cells in the co-delivery groups, particularly in the triple-loaded syste.

Conclusion: Collectively, these results demonstrate that nanoliposomal co-encapsulation of cisplatin with curcumin and green tea extract enhances cytotoxic efficacy and apoptotic activity in OSCC cells compared to single-agent systems. The optimized L-Cis/Cur/EGCG (1:6:6) formulation exhibited the most favorable physicochemical properties and biological performance, highlighting its potential as a synergistic nanocarrier platform for oral cancer therapy with improved efficacy and reduced systemic toxicity.

The Inflammatory Bone Marrow Milieu: An Association Between CML Disease Activity, Systemic Inflammation, and Bone Turnover Independent of Vitamin D

Mohammed Amer Fayyadh — 2026-01-07

Background: Metabolic bone disease is a recognized complication of Chronic Myeloid Leukemia (CML), often linked to tyrosine kinase inhibitor (TKI) therapy or vitamin D deficiency. The ‘Inflammatory Bone Marrow Niche’ hypothesis suggests the leukemic microenvironment may independently disrupt bone metabolism.

Objective: To investigate whether markers of chronic myeloid leukemia (CML) disease burden, such as lactate dehydrogenase (LDH), and markers of inflammation and iron homeostasis, including ferritin and interleukins, are associated with bone turnover markers parathyroid hormone (PTH) and alkaline phosphatase (ALP) after controlling for vitamin D levels.

Patients and Methods: This retrospective cross-sectional study involved 90 adult patients with chronic myeloid leukemia (CML) who were receiving tyrosine kinase inhibitor (TKI) therapy for at least 12 months at the Oncology Teaching Hospital, Baghdad, Iraq. Data were collected from January to September 2024 through patient records, measuring serum levels of vitamin D3, LDH, ferritin, PTH, and ALP. An inflammatory score was calculated using IL-6 and IL-1β, and multiple linear regression analyses were performed to identify independent associations.

Results: Multiple linear regression analysis identified lactate dehydrogenase (LDH) (β=0.35, p=0.003) and the inflammatory composite score (β=0.28, p=0.012) as significant, independent predictors of elevated alkaline phosphatase (ALP). Furthermore, ferritin levels were found to be a significant positive predictor of parathyroid hormone (PTH) levels (β = 0.31, p = 0.008). These associations remained statistically significant after adjusting for vitamin D3, which did not emerge as a significant predictor in either model.

Conclusion: This study provides a novel perspective, suggesting the leukemic microenvironment may be a key contributor to bone dysregulation in CML. The findings challenge traditional paradigms by indicating that bone health may also be influenced not only by calcium homeostasis and drug toxicity but also by disease-related molecular interactions. Monitoring inflammatory biomarkers could enhance risk stratification, facilitating comprehensive management of hematological and skeletal health.

Investigation of Low-Level Laser Radiation Effects on Blood Smears Haematological Indices in Breast Carcinoma Patients: Interpretation of Cellular Answers and Clinical Manifestations

Bushra Radhi Hussein — 2026-01-07

Background: Low-level laser therapy (LLLT) is able to modulate cellular and immune reactions in clinical conditions.

Objective: The purpose of the present investigation was to evaluate the effect of LLLT on blood smear hematological parameters in patients with breast carcinoma.

Methods: Red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin content, and platelet count were measured in control and in laser-irradiated samples for different exposure times.”

Results: Time-dependent increase in RBC number and hemoglobin was observed, peaking at 1 minute of exposure. WBC and platelet numbers were insignificantly altered. Morphological examination, on the other hand, revealed the increased percentage of reactive lymphocytes, indicating immune cell activation.

Conclusion: The results suggest that LLLT influences cellular shape but not leukocyte numbers to a great extent, suggesting potential immunomodulatory effects that warrant further investigation in vivo.

Decoding the UICC 9th Edition TNM Staging in Head and Neck Cancer: Key Updates for Clinical Practice

Janmenjoy Mondal — 2026-01-07

Accurate cancer staging is fundamental to treatment planning, outcome prediction, clinical research, and policy development. The Union for International Cancer Control (UICC) 9th edition TNM classification introduces several key updates in head and neck squamous cell carcinoma (HNSCC). These include the incorporation of extranodal extension (ENE) into nodal staging for nasopharyngeal carcinoma (NPC) and HPV-associated oropharyngeal carcinoma, restructuring of stage grouping in NPC with stage IV now restricted to distant metastasis, modifications to both T and N categories in salivary gland carcinoma, and the addition of parathyroid carcinoma as a newly staged entity. These refinements aim to improve risk stratification and provide a framework for more precise and personalized treatment strategies. This review summarizes the major and minor changes and discusses their clinical implications, while emphasizing the need for further evidence to validate the prognostic utility of these recommendations.

From ROS to Tumorigenesis: Understanding the Oxidative Pathways in Cervical Cancer Progression

Montadher Ali Mahdi — 2026-01-07

Cervical cancer remains a leading cause of cancer-related morbidity and mortality among women worldwide. Although persistent infection with high-risk human papillomaviruses (HPV) constitutes the principal etiological agent, accumulating evidence implicates oxidative stress as a pivotal co-factor in the initiation, promotion, and progression of cervical carcinogenesis. Reactive oxygen species (ROS), generated endogenously and exogenously, inflict cumulative genetic and epigenetic alterations, foster a pro-inflammatory tumor microenvironment, and promote malignant transformation. While endogenous antioxidant defense mechanisms initially mitigate ROS-mediated damage, their failure or exhaustion during disease evolution facilitates tumor progression and therapeutic resistance. This review critically examines the intricate interplay between oxidative stress and antioxidant responses throughout the stages of cervical cancer development. Furthermore, it explores emerging redox-targeted therapeutic strategies, emphasizing the dualistic role of antioxidants in cervical neoplasia and the challenges of modulating oxidative balance in clinical settings. A deeper understanding of redox dynamics may inform novel preventive and therapeutic interventions against cervical cancer.