Evaluating Global Research on Photodynamic Therapy in Skin Cancer through Bibliometric Analysis 2 2 Photodynamic therapy (PDT) is a potential non-invasive therapeutic option for several cancer types, including skin cancer. Because PDT uses a focused and localized approach to treatment, there has been an increase in interest in researching its use in the management of skin cancer in recent years. In this work, we performed a bibliometric analysis to assess the body of knowledge and developments around PDT in skin cancer. Using information from the Web of Science database, this study used bibliometric research techniques to examine how the field of PDT for skin cancer is developing. To gather pertinent research publications published between January 1991 and July 23, 2023, a methodical search query was developed. Based on the 1654 records that were found, the analysis examined factors including the growth, influence, contributions, top authors, publications, institutions, keywords, research topics, and networks of collaboration between authors, sources, nations, and significant funding organizations. The results showed a steady growth rate of 4.44% for publications. The most productive organization was the University of Sao Paulo, which is in Brazil, and the most prolific author was researcher Haedersdal M. The British Journal of Dermatology, which is published by Wiley in the UK, is very influential in the area as evidenced by its top citation ranking. The study topics were mostly actinic keratosis, basal cell carcinoma, photodynamic treatment, and skin cancer. Notably, the National Cancer Institute of the US NIH was a major backer of scientific study in this field. For academics, physicians, and policymakers engaged in developing and applying PDT for skin cancer therapy, the findings of this study will add to the body of current information and support the use of evidence-based decision-making. 1 25 2025/12/15 1404/9/24 2026/03/23 1405/1/3 Rakhi Issrani Rakhi Issrani Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India. dr.rakhi.issrani@jodent.org Hafiz Muhammad Zeeshan Hafiz Muhammad Zeeshan Department of Computer Science, National College of Business Administration and Economics, Lahore, Pakistan. Abid Iqbal Abid Iqbal Central Library, Prince Sultan University, Rafha Street, Riyadh, Kingdom of Saudi Arabia. Muhammad Nadeem Baig Muhammad Nadeem Baig Department of Preventive Dentistry, College of Dentistry, Jouf University, Sakaka, Kingdom of Saudi Arabia. Photodynamic therapy Photosensitizers Skin cancer ## ##

Current Challenges and Neoantigen-Based Therapy for Glioblastoma Treatment 2 2 Despite common therapies including chemotherapy, surgery, and radiation, glioblastoma (GBM), the most aggressive, challenging, and resistant primary brain metastasis version, has a terrible prognosis when it comes to the survival chances. Although immunotherapy has demonstrated promise in treating a number of malignancies, its effectiveness in GBM is still restricted because of the tumor's extremely immunosuppressive microenvironment. Neoantigen-based treatments target tumor-specific antigens produced by somatic mutations, providing a unique and customized approach. Because tumor cells express these neoantigens exclusively, they are prime candidates for immune identification with the least amount of off-target consequences. Early clinical trials have shown the safety and immunogenicity of strategies like customized cancer vaccines and adoptive cell treatments (ACT). This review explores the potential of neoantigen-based immunotherapy in GBM, highlighting recent advancements, challenges, and future directions for improving treatment efficacy and patient outcomes. 26 39 2025/12/152025/12/26 1404/10/5 2026/03/232026/03/7 1404/12/16 Prithpal Singh Prithpal Singh Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. singhmatrejaprithpal@gmail.com Shilpa Papatrick Shilpa Papatrick Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. Vinod Singh Vinod Singh Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. Neoantigens Glioblastoma Immunotherapy Treatment ## ##

Extracellular Immune Signatures as Prognostic Biomarkers and Liquid-Biopsy Candidates in AML 2 2 Background: Acute myeloid leukemia (AML) has poor long-term survival, necessitating robust prognostic biomarkers. While conventional markers focus on cytogenetics and mutations, immune-extracellular genes suitable for liquid biopsy remain understudied. Methods: RNA-sequencing data from 200 AML patients were analyzed from The Cancer Genome Atlas (TCGA). Univariate Cox regression identified survival-associated genes. Gene Ontology enrichment analysis selected immune and extracellular genes, with Kaplan-Meier analysis validating prognostic significance. REACTOME pathway enrichment revealed biological mechanisms. External validation used GEPIA2. Results: Cox regression identified 201 survival-associated genes (p<0.05): 149 favorable prognosis (HR<1) and 52 poor prognosis (HR>1). Gene Ontology enrichment revealed 29 immune-associated and 9 extracellular genes, with 5 overlapping candidates. Kaplan-Meier analysis confirmed four genes; EPHA10, CD160, BTN2A2, and KLRK1 as significant protective prognostic markers (p<0.05, HR<1). REACTOME analysis highlighted immune signaling pathways including adaptive immune response, natural killer cell-mediated cytotoxicity, and cell surface interactions. External validation demonstrated differential expression in AML versus normal tissues. Conclusion: This study identified EPHA10, CD160, BTN2A2, and KLRK1 as novel immune-extracellular prognostic biomarkers in AML. These genes represent promising candidates for liquid biopsy applications and personalized immunotherapy strategies, offering new perspectives for monitoring immune surveillance and overcoming AML immune evasion. 40 48 2025/12/152025/12/262025/11/9 1404/8/18 2026/03/232026/03/72026/03/7 1404/12/16 Nikoo Saeedi Nikoo Saeedi Student Research Committee, Islamic Azad University, Mashhad Branch, Mashhad, Iran. Ghazaleh Khalili Tanha Ghazaleh Khalili Tanha Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Amir Ali Judaki Amir Ali Judaki Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. magh2022@gmail.com Elham Nazari Elham Nazari Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Elham.nazari@sbmu.ac.ir Acute myeloid leukemia Biomarkers Immune microenvironment Extracellular genes Prognosis TCGA ## ##

Intelligent Clinical Support System for Anemia Detection and Diagnosis 2 2 Anemia is a common worldwide health concern affecting almost 25% of people, including 37% of pregnant women, 40% of children between the age of 6 and 59 months, and 30% of women between the age of 15 and 49 years. Anemia is primarily diagnosed through blood tests that measure hemoglobin levels. However, these conventional diagnostic methods rely on invasive blood sampling, which is costly, time-consuming and inaccessible in resource-limited areas. To address these challenges, this study proposes a non-invasive method for anemia detection using Haar Wavelet Transform for feature extraction from conjunctiva images of patients. The essential statistical features are extracted from the conjunctiva images using Haar Wavelet Transform that captures the crucial information indicating anemia. These extracted Haar features are used for training various machine learning methods like k-Nearest Neighbour, Decision Tree, XGBoost, Gradient Boosting, Random Subspace, and Random Forest. The accuracy achieved through k-Nearest Neighbour, Decision Tree, XGBoost, Gradient Boosting, Random Subspace and Random Forest are 99.18%, 97.66%, 95.08%, 79.25%, 95.55%, and 98.24% respectively. The k-NN method outperformed the others with an accuracy of 99.18%. This remarkable performance suggests that non-invasive machine learning techniques based on conjunctiva image analysis could serve as a promising alternative for anemia detection. 49 63 2025/12/152025/12/262025/11/92025/12/9 1404/9/18 2026/03/232026/03/72026/03/72026/02/18 1404/11/29 Abhishek Rao Rao Abhishek Rao Rao Department of Computer Science & Engineering Madan Mohan Malaviya University of Technology, Gorakhpur Uttar Pradesh 273010 India. Rohit Kumar Tiwari Tiwari Rohit Kumar Tiwari Tiwari Department of Computer Science & Engineering Madan Mohan Malaviya University of Technology, Gorakhpur Uttar Pradesh 273010 India. rohitkushinagar@gmail.com Sushil Kumar Saroj Saroj Sushil Kumar Saroj Saroj Department of Computer Science & Engineering Madan Mohan Malaviya University of Technology, Gorakhpur Uttar Pradesh 273010 India. Anemia Machine Learning Haar Wavelet k-NN Non-Invasive Technique Iron Deficiency ## ##

Integrative In Silico and Experimental Analyses Reveal the Therapeutic Potential of miR-217-5p in Hepatocellular Carcinoma Through KRAS Suppression and p53 Activation 2 2 Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, and dysregulation of microRNAs has been increasingly recognized as a critical driver in its pathogenesis. Among them, miR-217-5p has been reported as a tumor-suppressive miRNA, yet its molecular role and therapeutic potential in HCC remain largely unclear. Methods: In silico analyses were performed using a network pharmacology approach to construct a protein–protein interaction (PPI) network of hepatocellular carcinoma (HCC)-associated genes targeted by miR-217-5p, followed by hub gene identification using CytoHubba. Functional enrichment analyses, including Gene Ontology (GO) and KEGG pathways, were conducted using ShinyGO, while expression and survival analyses were validated using UALCAN, GEPIA2, and the Human Protein Atlas. In vitro validation was performed by delivering miR-217-5p mimics into HepG2 cells using chitosan nanoparticles (CS-NPs), followed by qRT-PCR analysis of endogenous miRNA expression, KRAS suppression, and p53 restoration. Results: A total of 152 potential target genes of miR-217-5p in HCC were identified, which were predominantly enriched in key biological processes related to regulation of cell population proliferation, as well as cancer-associated pathways including PI3K–Akt signaling and hepatocellular carcinoma pathways. PPI analysis, following the removal of disconnected nodes, generated a highly interconnected network comprising 146 nodes and 1042 edges, indicating extensive molecular interactions among the identified targets. Furthermore, hub gene analysis of the PPI network identified PTEN, KRAS, ESR1, HIF1A, and CDH1 as central regulatory genes. Notably, in vitro validation demonstrated that miR-217-5p delivered via chitosan nanoparticles (CS-NPs) successfully restored endogenous miR-217-5p expression and significantly suppressed KRAS expression, exhibiting a strong inverse correlation (r = −0.937, p < 0.0001). In addition, p53 protein levels were markedly increased following treatment. Conclusion: Our findings demonstrate that miR-217-5p exerts tumor-suppressive effects in HCC by directly targeting KRAS and restoring p53 expression. Delivery of miR-217-5p using chitosan nanoparticles represents a promising miRNA replacement therapy strategy and highlights its potential as both a therapeutic agent in HCC. ./files/site1/files/Suppl_Table_1._HCC_Related_Protein_from_Database.xlsx ./files/site1/files/Suppl_Table_2._miR-217-5p_Target_Protein_from_Database.xlsx 64 84 2025/12/152025/12/262025/11/92025/12/92025/12/16 1404/9/25 2026/03/232026/03/72026/03/72026/02/182026/03/15 1404/12/24 Ulfatun Nisa Ulfatun Nisa Traditional health services unit of Sardjito Hospital, Tawangmangu, Indonesia. redfa01@gmail.com Indwiani Astuti Indwiani Astuti Department of Pharmacology and Therapy, Faculty of Medicine Public Health and Nursing. Universitas Gadjah Mada, Yogyakarta, Indonesia Ronny Martien Ronny Martien Department of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia. Dhani Rinaldi Maulana Dhani Rinaldi Maulana Study Program of Biotechnology, Universitas Gadjah Mada, Yogyakarta, Indonesia. Ysrafil Ysrafil Ysrafil Ysrafil Department of Pharmacotherapy, Faculty of Medicine, Universitas Palangka Raya, Palangka Raya, Indonesia ysrafil@med.upr.ac.id Leonny Dwi Rizkita Leonny Dwi Rizkita Department of Pharmacology, Faculty of Medicine, Universitas Ahmad Dahlan, Yogyakarta, Indonesia. MiRNA-217 Chitosan Nanoparticle HCC HepG2 KRAS P53 ## ##

Gallbladder Cancer: An Overview of Epidemiology, Risk Factors, and Novel Approaches in Molecular Screening and Treatment Strategies 2 2 Gallbladder cancer (GBC) is an infrequent type of malignant neoplasm and ranks fifth among gastrointestinal malignancies in the world. However, GBC is prevalent in India, and population-based cancer registries’ (PBCRs) data revealed its higher incidence rate in North India. Due to the fact that the etiology of this cancer is quite complex, the majority of the cases are diagnosed at a very advanced stage owing to a lack of clinical appearance, which is non-specific. The majority of the cases come to light by coincidence at the time of histopathological examination of cholecystectomy. Several risk factors have been reported that may play an important role in the development and progression of GBC. There is a strong association between gallbladder inflammatory diseases (GIDs), including cholelithiasis (gallstones) and GBC. The presence of gallstones increases the risk of GBC more than threefold and appears to be stronger among ethnic groups that have higher rates of GBC. Surgery is the primary treatment that can cure early-stage gallbladder cancer. Apart from surgery, the use of immunotherapy, molecularly targeted medications, and new developments in radiation and chemotherapy (neoadjuvant-adjuvant gemcitabine, cisplatin, and capecitabine) has made gallbladder cancer treatment more promising in recent years, but there is still insufficient evidence to support their ability to improve patient outcomes, so more research is needed to address these issues; therefore, customized care needs to be used. 85 101 2025/12/152025/12/262025/11/92025/12/92025/12/162025/12/18 1404/9/27 2026/03/232026/03/72026/03/72026/02/182026/03/152026/02/14 1404/11/25 Naseem Fatima Naseem Fatima Department of Biochemistry, Era’s Lucknow Medical College and Hospital, Lucknow, India. Syed Tasleem Raza Syed Tasleem Raza Department of Biochemistry, Era’s Lucknow Medical College and Hospital, Lucknow, India. tasleem24@gmail.com Vijay Kumar Vijay Kumar Department of Surgical Oncology, King George’s Medical University, Lucknow, India. Gallbladder Malignancy Epidemiology Risk Factors Prognosis and Treatment Strategy ## ##

Efficacy and Safety of Bacterial-Based Cancer Therapies: A Meta-Analysis of Preclinical and Clinical Studies 2 2 Background: Cancer remains a major global health burden, and while conventional treatments like chemotherapy and immunotherapy have improved outcomes, they are limited by resistance and adverse effects. Bacterial-based cancer therapies (BBCTs) offer a promising alternative due to their tumor-targeting ability, immune modulation, and potential as therapeutic vectors. Objective: This meta-analysis evaluates the efficacy and safety of BBCTs by analyzing tumor growth inhibition (TGI%) in preclinical models and progression-free survival (PFS), overall survival (OS), and optimal response rate (ORR) in clinical studies. Methods: A systematic search of PubMed, Google Scholar, and Cochrane Library was conducted for relevant studies. Data on treatment efficacy and adverse events were extracted and statistically analyzed. Results: BBCTs showed significant tumor suppression and survival benefits over controls. PFS consistently demonstrated tumor growth delay, and some OS values extended beyond 35 units, suggesting long-term benefit. However, variability in outcomes was noted, influenced by bacterial strain, tumor type, and immune response. Safety concerns, including toxicity and immune-related effects, were also observed. Conclusion: BBCTs show strong therapeutic promise, but further clinical validation is needed to improve delivery, consistency, and safety. Personalized, translational research is key to bridging preclinical findings with clinical application. 102 113 2025/12/152025/12/262025/11/92025/12/92025/12/162025/12/182025/12/26 1404/10/5 2026/03/232026/03/72026/03/72026/02/182026/03/152026/02/142026/03/10 1404/12/19 Prithpal Singh Matreja Prithpal Singh Matreja Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. Ajay Kumar Ajay Kumar Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. Vinod Kumar Vinod Kumar Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. Sudhir Singh Sudhir Singh Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. singhdrsudhir4@gmail.com Bacteria-based Carcinoma Tumor Therapeutics Anticancer ## ##

A Review of Newer Pathophysiological Insights into Pediatric Brain Tumors: Revisiting Maintenance and Metronomic Chemotherapy in Resource-Limited Settings 2 2 Pediatric brain tumors remain a leading cause of morbidity and mortality worldwide, with management in developing countries particularly constrained by limited healthcare resources. This review highlights emerging concepts in tumor biology, particularly the roles of the tumor microenvironment (TME) and cancer stem cells (CSCs), which are increasingly recognized as critical drivers of tumor progression and therapy resistance. We summarize current evidence linking these biological mechanisms with therapeutic strategies, emphasizing practical and cost-effective approaches such as metronomic chemotherapy, maintenance chemotherapy, and intrathecal therapy delivered into the cerebrospinal fluid (CSF). While molecular targeted therapies and immunotherapies offer promise; their high costs limit accessibility in low-resource settings. Nevertheless, carefully tailored use may provide long-term benefits. By integrating pathophysiological insights with pragmatic treatment strategies, this review provides a biologically grounded and clinically applicable framework for oncologists practicing in low-resource environments. 113 123 2025/12/152025/12/262025/11/92025/12/92025/12/162025/12/182025/12/262026/01/26 1404/11/6 2026/03/232026/03/72026/03/72026/02/182026/03/152026/02/142026/03/102026/03/13 1404/12/22 Babak Abdolkarimi Babak Abdolkarimi Department of pediatrics, Tehran University of Medical Science, Tehran, Iran. b.abdolkarimi@yahoo.com Sina Goodarzi Sina Goodarzi Lorestan University of Medical Sciences, Khorramabad, Iran. Dina Seyedi Dina Seyedi School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Sahar Arbab Solimani Sahar Arbab Solimani Mahak Hematology Oncology Research Center (Mahak-HORC), Mahak Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Ali Pajouhi Ali Pajouhi Student Research Committee, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran. Pajuhia@yahoo.com Niki Panahi Niki Panahi Health Services Management Department, Science and Research Branch, Islamic Azad University, Tehran, Iran. Morteza Ashrafi Morteza Ashrafi Mahak Hematology Oncology Research Center (Mahak-HORC), Mahak Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Mahyar Nourian Mahyar Nourian Mahak Hematology Oncology Research Center (Mahak-HORC), Mahak Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Pediatric brain tumors Developing countries Tumor microenvironment Metronomic chemotherapy Intrathecal chemotherapy Maintenance chemotherapy Resource-limited settings ## ##

GLUT5 and Cancer Progression: A Systematic Review of High Fructose Diets in Tumor Growth 2 2 Background: The global rise in fructose consumption has raised concerns about its role in cancer biology. Unlike glucose, fructose is selectively transported by GLUT5, which is aberrantly expressed in several malignancies. Enhanced GLUT5 activity may fuel metabolic reprogramming and promote tumor progression, but evidence across experimental and clinical studies remains heterogeneous. Objective: This systematic review aimed to consolidate evidence on the role of GLUT5 in mediating the effects of high fructose intake on tumor growth and to evaluate its potential as a therapeutic target. Methods: Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for studies published between January 2000 and August 2024. Eligible studies included in vitro, in vivo, and clinical investigations assessing GLUT5 expression under high fructose conditions in relation to tumor outcomes. Data extraction and quality assessment were performed independently by two reviewers using the Modified Coleman Methodology Score (MCMS). Results: Thirty-two studies were included (18 in vitro, 10 in vivo, 4 clinical). High fructose exposure consistently upregulated GLUT5 expression, with a 2–3-fold increase in mRNA and protein levels. Elevated GLUT5 correlated with greater tumor volume (+40–60%), higher proliferation rates (+30–50%), and increased invasiveness compared with controls (p < 0.05). Subgroup analyses showed the strongest effects in colorectal and breast cancers, while pancreatic and hepatocellular carcinoma models demonstrated enhanced invasiveness and accelerated onset. Mechanistically, GLUT5-driven fructose uptake activated glycolytic and lipogenic pathways, as well as PI3K/Akt/mTOR signaling and EMT-related changes, supporting tumor aggressiveness. Conclusions: Evidence indicates that a high fructose diet contributes to tumor progression through GLUT5-mediated metabolic reprogramming. While preclinical findings are compelling, clinical validation remains limited. Standardization of fructose dosing protocols, integration of human dietary studies, and evaluation of GLUT5-targeted interventions are urgently needed. GLUT5 holds promise as a biomarker and therapeutic target in fructose-associated oncogenesis. 124 137 2025/12/152025/12/262025/11/92025/12/92025/12/162025/12/182025/12/262026/01/262025/12/6 1404/9/15 2026/03/232026/03/72026/03/72026/02/182026/03/152026/02/142026/03/102026/03/132026/03/14 1404/12/23 Vinod Kumar Singh Vinod Kumar Singh Department of General Medicine, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. drvinodkumarsingh85@gmail.com Prithpal Singh Matreja Prithpal Singh Matreja Department of Pharmacology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. Ajay Kumar Ajay Kumar Department of Pathology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. Seema Awasthi Seema Awasthi Department of Pathology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. GLUT5 Fructose High Fructose Diet Tumor Growth Cancer Metabolism Fructose Transporter Systematic Review ## ##