https://www.jcrph.com/ Journal of Cancer Research and Pharmacology en daily 1 Mon, 01 Dec 2025 00:00:00 +0330 Mon, 01 Dec 2025 00:00:00 +0330 https://www.jcrph.com/article_234173.html Background and Aims: Ovarian cancer treatment is often hindered by cisplatin resistance, frequently mediated by dysregulated apoptosis. This study investigates a novel combination therapy to overcome this resistance by targeting key apoptotic regulators. To evaluate the effects of Listeriolysin O (LLO), alone and in combination with Cis and CFZ, on the mRNA expression of the anti-apoptotic gene Bcl-2 and the pro-apoptotic gene Bax in cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CisR) ovarian cancer cell lines.Methods: A2780S and A2780CisR cells were treated for 72 hours with LLO, Cis, CFZ, and their combinations (Cis/LLO, CFZ/LLO, Cis/CFZ/LLO). The relative mRNA expression levels of Bcl-2 and Bax were quantified using quantitative real-time PCR (qRT-PCR), with normalization to the GAPDH housekeeping gene. Results: LLO monotherapy had a minimal impact on gene expression. In stark contrast, all combination regimens induced significant alterations in the Bcl-2/Bax axis. The triple-combination (Cis/CFZ/LLO) was the most potent, driving Bcl-2 expression down to 10% and 18% of control levels in A2780S and A2780CisR cells, respectively (P<0.01), while concurrently upregulating Bax expression nearly three-fold (2.94 in A2780S, 2.86 in A2780CisR; P<0.01). The two-drug combinations of Cis/LLO and CFZ/LLO also significantly suppressed Bcl-2 and elevated Bax compared to control and LLO-only groups (P<0.05). The overall treatment effect was statistically significant for both genes in both cell lines (p < 0.05).Conclusion: The combination of LLO with cisplatin and carfilzomib promotes a profound pro-apoptotic gene expression profile in ovarian cancer cells by drastically downregulating Bcl-2 and upregulating Bax. This multi-mechanistic strategy, which concurrently targets DNA integrity, proteostasis, and plasma membrane integrity, effectively overcomes cisplatin resistance and represents a highly promising therapeutic approach for chemoresistant ovarian carcinoma. https://www.jcrph.com/article_233516.html Lung cancer is the leading cause of cancer-related mortality globally, primarily due to late-stage diagnosis. There is a paramount need for rapid, non-invasive diagnostic tools. MicroRNAs (miRNAs) have emerged as ideal circulating biomarkers for early detection, but their clinical translation has been hindered by the limitations of conventional detection methods. The recent convergence of miRNA biology with CRISPR-Cas biosensing technology is poised to overcome these barriers. This review synthesizes advancements in CRISPR-based biosensors for detecting lung cancer miRNA biomarkers. We begin by outlining the landscape of lung cancer-associated miRNAs and the clinical validity of miRNA signatures from liquid biopsies. The core of the review critically examines the CRISPR-Cas biosensing architecture, focusing on the distinct mechanisms of Cas13 and Cas12a systems engineered for miRNA detection. We further explore engineering strategies that augment performance, including integration with isothermal amplification and various signal transduction methods. A critical appraisal reveals that these platforms consistently achieve exceptional sensitivity and single-base specificity in detecting targets like miR-21 in clinical samples. Finally, we address prevailing challenges, such as off-target effects and reagent stability, and outline promising future directions, including multiplexed detection, integration with multi-analyte liquid biopsy platforms, and the development of fully automated, handheld devices. We conclude that CRISPR-based miRNA biosensors represent a transformative diagnostic paradigm with immense potential to enable rapid, precise, and accessible early detection of lung cancer, thereby paving the way for improved survival rates. https://www.jcrph.com/article_233928.html Background and Aims: Species within the genus Scrophularia are recognized in traditional medicine for their anti-inflammatory potential. Scrophularia variegata, in particular, has been historically employed for this purpose. This study sought to systematically evaluate the cytotoxic potential of a S. variegate extract against human prostate (PC3) and ovarian (SKOV3) adenocarcinoma cell lines, alongside a preliminary assessment of its antimicrobial activity against clinically relevant resistant strains.Methods: Cytotoxicity was quantified via the MTT assay following exposure of PC3 and SKOV3 cells to the extract. Antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli was determined using standardized micro-broth dilution and disk diffusion methods.Results: The S. variegate extract demonstrated a concentration-dependent cytotoxic effect on both PC3 and SKOV3 cell lines, significantly reducing cell viability. In contrast, the extract did not exhibit measurable antibacterial activity against the tested resistant bacterial strains at the concentrations employed.Conclusion: Our findings indicate that Scrophularia variegate possesses pronounced cytotoxic activity against two distinct human cancer cell lines in vitro, suggesting its constituents may warrant further investigation as potential anticancer agents. The lack of observed antibacterial activity against resistant pathogens, however, highlights the specificity of its biological effects. Future studies are required to isolate the active cytotoxic compounds and elucidate their mechanisms of action. https://www.jcrph.com/article_234386.html Background and Aims: Curcumin, a natural polyphenolic compound from Curcuma longa, exhibits anti-cancer properties by modulating miRNAs and targeting pathways like PI3K/Akt and angiogenesis. This study investigates the effects of curcumin on the expression of miR-21-5p, miR-210-3p, miR-126-3p, and miR-214-3p in HPV-16-positive CaSki cervical cancer cells, and their correlations with PTEN and VEGF.Methods: CaSki cells were cultured and treated with curcumin at a sub-IC50 concentration (80 μM) for 48 hours, determined via MTT assay (IC50 = 96 μM). Total RNA was extracted using TRIzol, and qRT-PCR was used to assess PTEN, VEGF (normalized to GAPDH), and miRNA expression (normalized to U6). Data from nine biological replicates per group were analyzed using Welch’s t-test for comparisons and Pearson’s correlation for relationships.Results: Curcumin significantly upregulated PTEN (1.861 ± SD, p=0.004; ~3.6-fold) and downregulated VEGF (-2.137 ± SD, p=0.006; ~0.23-fold). miRNA modulation included a trend toward miR-21-5p downregulation (-1.024 ± SD, p=0.057; ~0.48-fold), no change in miR-210-3p (p=0.344), and upregulation of miR-126-3p (1.674 ± SD, p=0.003; ~3.2-fold) and miR-214-3p (1.669 ± SD, p=0.019; ~3.2-fold). Correlations revealed miR-21-5p negatively associated with PTEN (r=-0.51, p=0.03) and positively with VEGF (r=0.57, p=0.01); miR-126-3p positively with PTEN (r=0.41, p=0.09) and negatively with VEGF (r=-0.49, p=0.03); miR-214-3p negatively with PTEN (r=-0.36, p=0.14).Conclusions: Curcumin epigenetically modulates miRNAs in CaSki cells, enhancing PTEN and suppressing VEGF through regulatory networks involving miR-21-5p and miR-126-3p. These findings elucidate curcumin's anti-cancer mechanisms and support its potential as an adjunctive therapy for cervical cancer, warranting further in vivo validation. https://www.jcrph.com/article_233929.html Background and Aims: Systematic lymphadenectomy remains integral to the surgical staging of ovarian cancer, yet the procedure carries considerable risk of morbidity. Refining the criteria for lymph node dissection by identifying robust preoperative predictors of metastasis could spare low-risk patients from these associated complications.Methods: In this cross-sectional analysis, we reviewed 66 consecutive cases of epithelial ovarian cancer treated at two tertiary care centers in Tehran from 2019 to 2021. Preoperative clinical, imaging, and serological parameters were documented. All patients underwent comprehensive surgical staging, including lymphadenectomy. Associations between clinicopathological variables and lymph node metastasis were evaluated using chi-square tests, with multivariate logistic regression employed to define independent predictors.Results: Lymph node involvement was present in 26 patients (39.4%). Univariate analysis identified significant correlations between nodal metastasis and younger age (≤50 years), bilateral adnexal involvement, serous histology, grade 3 differentiation, and International Federation of Gynecology and Obstetrics (FIGO) stage 3 disease. On multivariate analysis, each factor retained independent predictive value: age ≤50 years (odds ratio [OR] 3.07, 95% CI 1.02–9.24), bilateral tumors (OR 2.56, 95% CI 0.94–6.95), serous histology (OR 4.38, 95% CI 1.41–13.58), grade 3 (OR 14.25, 95% CI 4.12–49.30), and stage 3 (OR 20.09, 95% CI 5.87–68.79).Conclusion: Our findings confirm that a distinct profile -characterized by younger age, bilaterality, serous histotype, high-grade differentiation, and advanced stage- significantly elevates the risk of lymphatic spread in ovarian carcinoma. Consequently, lymphadenectomy might be safely deferred in a carefully selected subset of patients with opposing low-risk features: age >50 years, unilateral, mucinous, grade 1 tumors confined to stage I. This selective approach could mitigate surgical morbidity while preserving oncologic safety. https://www.jcrph.com/article_232958.html Background and Aims: Dental implants have become essential in restorative dentistry, with surface morphology playing a critical role in enhancing osseointegration, bone regeneration, and long-term stability. Advancements in materials science and surface engineering, particularly micro-rough and nano-textured designs, have revolutionized implant technology to address challenges such as peri-implantitis and implant failure.Methods: This study presents a bibliometric analysis of research trends in dental implant surface morphology from 1999 to 2024, utilizing data extracted from the Web of Science Core Collection. This analysis yielded 2,814 documents, with an annual growth rate of 2.65%. Research output has significantly increased since 2010, driven by technological advancements and a multidisciplinary approach that integrates dentistry, materials science, and bioengineering.Results: The analysis identified leading journals, including Clinical Oral Implants Research and Dental Materials, as major platforms for high-impact studies. Influential contributors include institutions such as the University of Bern and the University of Gothenburg. Geographically, the USA, China, Germany, and Switzerland lead in publication volume, reflecting their robust implant manufacturing industries and research infrastructure. Keyword analysis reveals recurring themes such as "osseointegration," "surface roughness," and "titanium," emphasizing the importance of surface properties in improving implant performance. Emerging trends include nanotechnology, bioactive coatings, and additive manufacturing, highlighting innovative approaches to enhance implant integration.Conclusion: This study underscores the importance of global collaboration, with 28.93% of publications involving international co-authorship. https://www.jcrph.com/article_237016.html Cancer remains a leading cause of morbidity and mortality worldwide, and sustained access to anticancer medicines is indispensable for achieving curative and life prolonging outcomes. Yet global shortages of oncology drugs, especially off patent sterile injectables, have grown in frequency and duration, exposing structural fragilities across manufacturing, economics, regulation, and logistics. This narrative review synthesizes evidence on how scarce anticancer medicines are allocated and distributed during shortages, how systems manage crises, and where artificial intelligence (AI) and quantitative modeling can strengthen resilience. We summarize convergent drivers (quality related production halts, concentrated supplier bases, low margin tendering, demand shocks, regulatory bottlenecks, cold chain constraints, and external disruptions) and their uneven impacts across high income versus low- and middle-income settings. We then integrate multilevel strategies: nationally, early warning systems, critical medicine lists, diversified sourcing, and transparent stockpile release; within health systems, multidisciplinary governance, real time dashboards, conservation practices (dose rounding, vial sharing), internal redistribution, and consistent communication; and at the bedside, ethically grounded triage that prioritizes curative intent, higher expected benefit, and lack of alternatives. We map the emerging AI toolkit, including shortage forecasting, inventory optimization, supplier risk scoring, and digital twins to test allocation policies ex ante, and align it with four modeling families central to decision making under scarcity (mixed integer and stochastic optimization, discrete event and agent-based simulation, reliability and resilience modeling, and decision analytic and ethical frameworks). We conclude with a Prevention, Preparedness, Response, Recovery roadmap that links macro level incentives (resilience-oriented procurement and quality and continuity rewards), meso level data infrastructure and playbooks, and micro level shared decision making. Priorities include harmonized metrics for shortage severity and resilience, prospective evaluations of allocation policies, and cross-country collaboration to ensure that digital and analytic advances enhance equity while reducing the clinical harm of oncology drug shortages. https://www.jcrph.com/article_237017.html Cancer progression is increasingly recognized as a complex, multilevel process shaped by biological heterogeneity, treatment-induced evolution, and constraints at the organizational and health-system levels. Conventional, episode-based decision-making struggles to keep pace with expanding therapeutic options, growing data volumes, and recurrent crises such as pandemics that disrupt cancer pathways. This narrative review proposes a strategic framework for managing cancer progression that integrates novel clinical approaches with artificial intelligence (AI) and modeling across the entire cancer care trajectory and across micro (patient), meso (service), and macro (system) decision levels. We first conceptualize cancer care as a longitudinal continuum, spanning prevention and early detection, diagnosis and staging, primary treatment, surveillance and survivorship, management of recurrence or advanced disease, and palliative and end-of-life care, and argue that progression management requires anticipatory planning across this continuum rather than reactive choices at isolated time points. Within this structure, three pillars are examined in detail: novel therapeutic and organizational approaches (including precision oncology, immunotherapy, advanced radiotherapy, and pathway-based care), AI methods for prediction and decision support, and mechanistic and simulation-based models, including digital twins, for treatment optimization and scenario analysis. We then highlight how AI and modeling can be combined to support crisis management, for example by forecasting backlogs, guiding triage, and testing mitigation strategies during system shocks. Finally, we discuss ethical, legal, and organizational challenges and outline a research agenda for hybrid AI–mechanistic platforms and dynamic digital twins that could shift cancer care from reactive to strategic, learning system management of progression. https://www.jcrph.com/article_234232.html Glioblastoma (GBM) remains the most aggressive and therapeutically refractory primary malignant brain tumor in adults, with mortality rates that have changed little over the past two decades. While numerous genomic and epigenetic alterations have been identified in GBM, its etiological drivers are still poorly understood. Increasingly, evidence suggests that viral infections -particularly those caused by members of the Herpesviridae family- may contribute to GBM pathobiology through onco-modulatory mechanisms rather than classical oncogenic transformation. In this context, we draw attention to the potential role of human cytomegalovirus (CMV) and Epstein–Barr virus (EBV) mono- and coinfection as overlooked contributors to GBM aggressiveness.CMV has been detected in a substantial proportion of GBM tissues, and its gene products are known to modulate a wide array of cellular pathways relevant to tumor progression. CMV-encoded proteins such as IE1, glycoprotein B, and US28 have been shown to activate PI3K/AKT, STAT3, FAK, and hypoxia-related signaling, promoting proliferation, invasion, angiogenesis, and immune evasion. Furthermore, CMV appears capable of inducing telomerase activation in malignant glioma cells, supporting sustained growth and resistance to apoptosis. These findings suggest that CMV does not initiate oncogenesis directly but may enhance the malignant phenotype of GBM cells once tumorigenesis has begun.EBV, another lifelong persistent herpesvirus with recognized oncogenic potential, has also been detected in GBM tissues. EBV-encoded oncoproteins, especially Latent Membrane Protein 1 (LMP1) and LMP2A, activate multiple cancer-related pathways—including NF-κB, MAPK, PI3K/AKT, and JAK/STAT—resulting in enhanced proliferation, epithelial–mesenchymal transition, inflammatory signaling, and chemoresistance. Although EBV’s involvement in GBM is less widely studied than in nasopharyngeal carcinoma or lymphomas, several reports show a statistically significant association between EBV presence and GBM, warranting closer examination.Importantly, coinfection with CMV and EBV has been documented in multiple clinical contexts. Such dual infections can influence viral reactivation, immune cell differentiation, and cytokine responses, thereby reshaping the tumor microenvironment toward a more permissive, immunosuppressive state. Given that each virus independently modulates key oncogenic pathways, their coexistence in GBM tissue raises the possibility of synergistic or additive effects on tumor biology. For example, both viruses can activate STAT3 and PI3K/AKT signaling, inhibit apoptosis through distinct molecular mechanisms, and enhance invasiveness through modulation of cytoskeletal dynamics and inflammatory mediators. These converging activities could collectively intensify the malignant behavior of GBM cells.Despite these observations, the mechanistic interactions between CMV and EBV within GBM remain largely unexplored. It also remains unclear whether sequential infection, simultaneous infection, or virus-virus competition influences the extent of oncogenic signaling. Given that antiviral therapies targeting CMV have demonstrated potential survival benefits in some GBM patients, understanding whether EBV or CMV/EBV coinfection contributes to therapeutic resistance is an urgent priority.We propose that future investigations incorporate models of mono- and coinfection to directly compare their effects on GBM proliferation, apoptosis, invasion, inflammation, and treatment sensitivity. Such studies may uncover viral biomarkers or vulnerabilities that could be exploited therapeutically. Determining whether CMV and EBV act as independent onco-modulators or engage in cooperative interactions could reshape our understanding of GBM pathogenesis and open new avenues for antiviral-based adjunctive therapy.In conclusion, although the presence of CMV and EBV in GBM has been documented for years, the implications of their coexistence remain insufficiently recognised. A renewed focus on the CMV/EBV coinfection axis may help clarify unresolved questions in GBM biology and contribute to the development of more effective therapeutic strategies.