Search Results (314)

The 2S LGBTQIA+ (Two-Spirit, Lesbian, Gay, Bisexual, Trans, Queer and/or Questioning, Intersex, Asexual, and additional sexually and gender-diverse self-identities) population often faces barriers to care in the context of cervical cancer screening. With the shift from primary cervical cytology (Papanicolaou test) to primary human papillomavirus (HPV)-DNA testing, it is crucial to examine these populations’ healthcare needs. An intersectionality framework with an anti-oppressive lens is needed to restructure a healthcare system whose systems have traditionally erased the care needs of diverse populations through colonial, racialized, and cis-heteronormative practices. Barriers to cervical screening in 2S LGBTQIA+ populations include stigma, discrimination, limited provider guidance and understanding, and high rates of physical, sexual, and medical trauma. Self-sampling for HPV is a less invasive alternative to traditional Pap tests with a high rate of acceptability. The option to self-sample may increase participation in cervical screening based on improved privacy, comfort, and feelings of empowerment. Organizational, psychosocial, and physical recommendations for practice are shared to create a welcoming environment that reflects the diversity of populations in all aspects of healthcare. Affirmative care aims to make clients feel safe and accommodated by prioritizing dignity and respect as essential elements of eliminating cervical cancer in 2S LGBTQIA+ populations. Full article

Cervical cancer (CC) remains a common malignant tumor that seriously threatens women’s health globally. Gramine (GR), a natural alkaloid derived from plants such as Arundo donax L., exhibits anti-tumor activities, yet its mechanistic actions in CC are still unclear. Here, we integrated cell-based assays, network pharmacology, and multi-omics analysis to systematically investigate the molecular mechanisms underlying GR’s anti-CC effects. In vitro experiments showed that GR significantly inhibited proliferation and migration, induced apoptosis, and triggered G₀/G₁ phase cell cycle arrest in HeLa cells. Integrated multi-omics analysis identified CDK2 as a critical target of GR, with both mRNA and protein levels markedly reduced following treatment. Mechanistically, GR likely suppresses CC progression by modulating the “CYP4A22-AS1/LINC00958–hsa-miR-133b–CDK2” competitive endogenous RNA (ceRNA) axis. Immune analysis indicated positive correlations of CDK2, CYP4A22-AS1, and LINC00958 with the immune checkpoint molecule CD47. Collectively, our findings demonstrate that GR inhibits CC through a ncRNA-mediated suppression of CDK2, leading to reduced HeLa cell proliferation and migration and enhanced apoptosis. These results provide a mechanistic rationale for developing GR as a candidate agent for targeted therapy and immuno-combination strategies in CC. Full article

Early detection of high-risk human papillomavirus (HPV), particularly HPV16 E7, is critical for cervical cancer prevention. Here, we report a novel, portable, and instrument-free biosensing platform that integrates recombinase polymerase amplification (RPA) with CRISPR/Cas12a-mediated detection on a microfluidic paper-based analytical device (μPAD) for colorimetric, visual readout of double-stranded DNA (dsDNA). The μPAD features seven functional zones, including lyophilized RPA and CRISPR reagents, and immobilized streptavidin and anti-FAM antibodies for signal generation. Upon target recognition, Cas12a’s trans-cleavage activity releases biotinylated-FAM-labeled reporters that form a sandwich complex with gold nanoparticle (AuNP)-conjugated anti-FAM antibodies, producing a visible red signal at the test zone. The gray value of the colorimetric signal correlates linearly with target concentration, enabling the quantitative detection of HPV16 E7 dsDNA down to 100 pM within 60 min. The assay demonstrated high accuracy and reproducibility in spiked samples. By combining isothermal amplification, CRISPR specificity, and paper-based microfluidics, this platform offers a rapid, low-cost, and user-friendly solution for point-of-care HPV screening in resource-limited settings. This work advances the integration of CRISPR diagnostics with μPAD, paving the way for scalable point-of-care molecular diagnostics beyond HPV. Full article

Objective: Human Papillomavirus (HPV), a leading cause of sexually transmitted infections (STIs) and various cancers, including cervical cancer, remains prevalent in the US. Despite the HPV vaccine’s effectiveness in preventing persistent HPV infections, vaccination rates remain low. Given the significant role of social media in reaching younger populations, this systematic review examines its influence on adolescents’ and young adults (AYAs) awareness, knowledge, and attitudes toward HPV vaccination. Methods: Following the PRISMA guidelines, we conducted a comprehensive search across six electronic databases (ERIC, APA PsycInfo, Child Development & Adolescent Studies, CINAHL Ultimate, MEDLINE Ultimate, and PubMed) from 2011 to 2024. Empirical studies that examined the association between social media use and HPV were included. Data extraction captured the study’s purpose, design, population, outcome measures, and key results. Results: Seven studies satisfied the review’s inclusion criteria. Our findings reveal mixed effects of social media on AYAs’ knowledge and vaccination intentions. Some studies indicated positive associations between social media interventions and increased vaccination knowledge and intentions, while others found no significant impact. Additionally, exposure to anti-vaccine content was linked to lower vaccination intentions, especially among individuals with lower knowledge who were more vulnerable to misinformation. Interventions incorporating interactive content and loss-framed messaging were more effective in increasing vaccine intentions. Conclusions: This review underscores the potential of social media to influence AYAs knowledge and perceptions regarding HPV vaccination, while also highlighting the challenges posed by misinformation. Further research is needed to optimize social media interventions and combat misinformation to improve vaccination uptake. Full article

Background/Objectives: Cervical cancer remains a major global health challenge, and treatment resistance limits the long-term success of chemotherapy. Drug repurposing strategies offer new opportunities for improving therapeutic outcomes by combining existing agents with established chemotherapeutics. Sitagliptin, a DPP-4 inhibitor commonly used in type 2 diabetes, has recently gained attention for its potential anticancer effects. This study aimed to investigate the cytotoxic, apoptotic, and anti-metastatic effects of sitagliptin and doxorubicin, individually and in combination, on human cervical cancer cells (HeLa), and to determine whether their combined use exerts a synergistic anticancer effect. Methods: HeLa cells were treated for 48 h with increasing concentrations of sitagliptin, doxorubicin, or their combination. Cell viability was assessed using the MTT assay. Apoptosis was evaluated by Annexin V-FITC/PI staining and caspase-8/9 activity assays. Synergy was quantified using the Chou–Talalay method, and Combination Index (CI) values were used to determine synergistic interactions. Intracellular ROS levels were measured using the DCFDA assay. Migration and invasion capacities were analyzed using wound healing and Transwell assays. MMP-1, MMP-2, TIMP-1, and TIMP-2 levels were quantified via ELISA with normalization to viable cell counts. Gene expression levels of PI3K/Akt and MAPK/ERK pathway components were measured by qRT-PCR. Bioinformatic analyses (STRING, GeneMANIA, GO, KEGG) were performed to identify common molecular targets and enriched pathways affected by both agents. Results: The combination of sitagliptin and doxorubicin significantly reduced cell viability and demonstrated a synergistic interaction (CI < 1). Combined treatment induced a marked increase in ROS production and significantly elevated apoptosis rates compared to monotherapies. Caspase-8 and caspase-9 activities were also higher in the combination group. Migration and invasion assays revealed substantial suppression of cell motility and invasive capacity. After normalization to viable cell numbers, MMP and TIMP reductions remained significant, confirming true biological inhibition rather than cell-death–related artifacts. qRT-PCR analyses showed downregulation of Akt and ERK expression, indicating suppression of key survival and proliferation pathways. Bioinformatic analyses supported these findings by highlighting enrichment in apoptotic, oxidative stress, and metastasis-related pathways. Conclusions: Sitagliptin enhances the anticancer efficacy of doxorubicin by amplifying ROS-mediated apoptosis, inhibiting migration and invasion, and modulating PI3K/Akt and MAPK/ERK signaling in cervical cancer cells. The combination exhibits a clear synergistic effect and demonstrates strong potential as a supportive therapeutic strategy. These findings warrant further in vivo and clinical-level investigations to evaluate the translational applicability of sitagliptin in cervical cancer therapy. Full article

Human Papillomavirus (HPV)-related cancers constitute a major global health problem, accounting for 4.5% of all human cancers. Studying the composition of the tumor microenvironment (TME) of HPV-related cancers may help develop therapeutic strategies or identify prognostic biomarkers with potential clinical significance. Among all the components of TME, mast cells (MCs) appear to be particularly relevant in HPV-related tumors. MCs are myeloid-derived immune cells that release a wide range of inflammatory mediators. It is now recognized that these immune cells are important players within the TME, where they can exert both anti- and pro-tumor activities depending on the type of MC-derived inflammatory mediators released. MCs may play an important role in the processes associated with cell transformation, development, and the progression of HPV-associated tumors; however, their specific functions in these neoplasms are not yet fully understood. This review addresses the current state of knowledge on MCs and their contribution to the molecular biology of HPV-related cancers. In addition, it highlights MCs’ roles in the pro- or anti-tumor paradigm and discusses their emerging potential as therapeutic targets or prognostic biomarkers. Full article

Cervical cancer (CC) can be prevented through continuous screening and the timely detection of cervical intraepithelial neoplasia (CIN) using immunohistochemistry techniques to identify biomarker expressions. In a previous study, we proposed nuclear REST loss as a biomarker in precancerous lesions and CC; however, no validated antibodies are available for detecting REST in cytology or cervical tissues. Although we have developed an IgM-type anti-REST monoclonal antibody capable of detecting REST in liquid-based cytology cells, it was not useful for the detection of REST in cervical tissues by immunohistochemistry. The main objective of this study is to generate single-chain variable fragments (scFvs) for the clinical evaluation of REST in cervical tissues from women with CIN and CC. Using RNA from an IgM-producing hybridoma anti-REST, we conducted RT-PCR and PCR to obtain the coding sequences for the variable regions of the heavy and light chains. These sequences were joined with a linker to create a single-chain antibody. The scFv was then cloned into the pSyn1 vector, expressed in E. coli TG1, and purified through chromatography. Subsequently, it was characterized using immunological methods to assess its biological activity and employed to evaluate REST expression in cytological samples and cervical tissues. The anti-REST scFv represents an innovative detection tool that retains the antigen recognition of the parental IgM while overcoming its size limitation, enabling tissue penetration and detection of REST in cervical samples. Its application facilitates the identification of REST in cervical samples, reinforcing REST’s potential as a diagnostic biomarker for CC and CIN. Full article

Pelvic recurrence following radiotherapy for cervical cancer presents a major therapeutic challenge with historically poor prognosis and limited options. This review comprehensively examines the evolving landscape of management strategies for this condition, encompassing both local and systemic approaches. We discuss the roles of salvage surgery and advanced re-irradiation techniques, including stereotactic body radiotherapy and image-guided brachytherapy, highlighting their potential and associated toxicities. A significant focus is placed on the revolution in systemic therapy, particularly the integration of targeted agents—such as anti-angiogenic drugs, PARP inhibitors, and tyrosine kinase inhibitors—and immunotherapy, chiefly immune checkpoint inhibitors like pembrolizumab and cemiplimab. These modalities have demonstrated substantial improvements in survival outcomes in clinical trials. The review underscores the critical shift towards personalized medicine, where treatment selection is increasingly guided by molecular profiling. Finally, we explore future directions, including combination strategies, novel immunotherapies, and emerging technologies, which collectively promise to transform the management of recurrent cervical cancer from palliative control towards the goals of durable remission and functional cure. Full article

The development of antibiotic resistance has become a global health challenge, resulting in approximately 800,000 deaths per year. The rapid rise in multidrug-resistant (MDR) pathogens has prompted an urgent need for antimicrobial alternatives. Punica granatum L. peel has long been valued for its rich bioactive polyphenols with potent antimicrobial properties. In this study, P. granatum L. peel extract (PGPE) was integrated with chitosan nanoparticles (CH-PGPE) to enhance antimicrobial efficacy while minimizing potential cytotoxicity. The antimicrobial potential of PGPE and CH-PGPE was evaluated with agar well diffusion, disk diffusion, and minimum inhibitory concentration (MIC) analyses against standard ATCC and clinical MDR strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. MTT assay evaluated the biocompatibility and anti-proliferative potential of PGPE on ARPE-19 (normal retinal pigment epithelial), HeLa (human cervical cancer), and A549 (human lung carcinoma) cell lines. PGPE exhibited antibacterial activity, and CH-PGPE reduced MIC values by approximately two-fold. Both PGPE and CH-PGPE demonstrated comparable or superior inhibition compared to several conventional antibiotics, particularly against MDR strains. The MTT assay revealed that PGPE was non-cytotoxic to normal ARPE-19 cells, while exhibiting the highest antiproliferative potency against A549 cells and a moderate inhibitory response in HeLa cells. The nanoparticle-supported formulation enhanced the antimicrobial efficacy of PGPE and also exhibited selective anti-proliferative activity against cancer cells without affecting normal cells. Full article

Cervical cancer ranks as a primary contributor to cancer-related deaths in women globally and is the fourth most prevalent malignant neoplasm. Cepharanthine, a naturally occurring biscoclaurine alkaloid extracted from Stephania cepharantha, has demonstrated anticancer and antimetastatic efficacy across multiple cancer types. However, its mechanism of action in cervical cancer remains unexplored. Our results demonstrated that cepharanthine effectively suppressed the proliferation and motility of the CaSki, HeLa, and C33A cell lines. Furthermore, cepharanthine triggered apoptosis through Bcl-2 suppression and increased cleaved-PARP-1, Bax, and cleaved-caspase-3 expression and AMPK/p53 phosphorylation, while inducing G0/G1 phase arrest in CaSki cells and sub-G1 phase arrest in HeLa and C33A cells. Additionally, cepharanthine reduced the mitochondrial membrane potential (∆ψm), compromised mitochondrial functionality, and increased reactive oxygen species (ROS) accumulation, promoting oxidative stress via the modulation of the Nrf2/Keap1 pathway in CaSki, HeLa, and C33A cells, which exhibit an anti-cervical cancer effect. Similarly, cepharanthine markedly reduced tumor progression in C33A BALB/c nude mice, which aligns with the in vitro observations. Collectively, these findings indicate that cepharanthine has potential therapeutic applications in the treatment of cervical cancer and warrants future clinical investigation. Full article

Background/Objectives: A non-toxic nano-platform which can increase drug-loading rate and synergistically increase antitumor effect is very ideal. This study provides the concept that a combination of photothermal therapy with chemotherapy and anti-inflammatory therapy will be achieved by ablation of the local tumor, robust strategies for the suppression of distant tumors with enhanced antitumor therapy outcomes. Methods: In this study, the chemotherapeutic drug cisplatin (DDP) and the anti-inflammatory drug Aspirin-DL-Lysine (ADL) were loaded into a hollow porous nanomaterial zeolitic imidazolate framework-8 (ZIF-8), which was then coated with polydopamine, in order to form near-infrared absorption organic nanoparticles DDP-ADL@ZIF-8@PDA with excellent photothermal conversion efficiency. The antitumor efficacy of the nanodrug was evaluated through physicochemical characterization, cell biology studies, and animal experiments. Results: Photothermal therapy (PTT) of polydopamine combined with DDP and ADL can reduce inflammation and the immunosuppressive tumor microenvironment, and enhance antitumor effect. The results showed that the combined therapy could effectively eliminate the primary tumor, shrink the distant tumor, and inhibit the metastasis of the tumor. PTT in combination with chemotherapy and anti-inflammatory therapy can inhibit the expression of inflammatory factors, significantly reducing tumor immunosuppression by eliminating bone marrow-derived suppressor cells and increasing levels of cytotoxic T lymphocyte. Conclusions: This study successfully developed a DDP-ADL@ZIF-8@PDA nanomedicine for effective drug delivery, synergistic photothermal therapy, and anti-inflammatory attenuated immunotherapy to enhance treatment of human cervical cancer xenografts in mice. Overall, the combination of photothermal therapy with chemotherapy and anti-inflammatory therapy on a nano-platform has great potential for antitumor therapy applications. Full article

Coumarin derivatives, whether natural or synthetic, have attracted considerable interest from medicinal chemists due to their versatile biological properties. Their appealing pharmacological activities—such as anticancer, anti-inflammatory, neuroprotective, anticoagulant, and antioxidant effects—combined with the ease of their synthesis and the ability to introduce chemical modifications at multiple positions have made them a widely explored class of compounds. In the scientific literature, there are many examples. On the other hand, dithiocarbamates, originally employed as pesticides and fungicides in agriculture, have recently emerged as potential therapeutic agents for the treatment of serious diseases such as cancer and microbial infections. Moreover, dithiocarbamates bearing diverse organic functionalities have demonstrated significant antifungal properties against resistant phytopathogenic fungi, presenting a promising approach to combat the growing global issue of fungal resistance. Dithiocarbamates linked to coumarin derivatives have been shown to exhibit cytotoxic activity against various human cancer cell lines, including MGC-803 (gastric), MCF-7 (breast), PC-3 (prostate), EC-109 (esophageal), H460 (non-small cell lung), HCCLM-7 (hepatocellular carcinoma), HeLa (cervical carcinoma), MDA-MB-435S (mammary adenocarcinoma), SW480 (colon carcinoma), and Hep-2 (laryngeal carcinoma). Numerous studies have revealed that the inclusion of a dithiocarbamate moiety can provide central nervous system (CNS) activity, particularly through inhibitory potency and selectivity toward acetylcholinesterase (AChE) and monoamine oxidases (MAO-A and MAO-B). Recently, it has been reported that coumarin–dithiocarbamate derivatives exhibit α-glucosidase inhibitory effects and also possess promising antimicrobial activity. This study presents an overview of recent progress in the chemistry of coumarin–dithiocarbamate derivatives, with a focus on their biological activity. Previous review papers focused on coumarin derivatives as multitarget compounds for neurodegenerative diseases and described various types of compounds, with dithiocarbamate derivatives representing only a small part of them. Our work deals exclusively with coumarin dithiocarbamates and their biological activity. Full article

The red seaweed Jania rubens (J. rubens) is prevalent along the Lebanese coast and has drawn attention for its notable antineoplastic properties. Our previous data showed that its dichloromethane–methanol (DM) extract possesses antioxidant, cytotoxic, and anti-migratory effects on colon cancer cells. In the present study, a GC-MS analysis of DM extract identified a diverse profile of bioactive compounds, including flavonoids and pyrazole derivatives with antioxidant and anticancer activities. In vitro assays demonstrated that the DM extract exerts significant cytotoxic activity against various cancer cell lines, including colon, breast, and cervical types. Further investigation into the underlying molecular mechanisms revealed that the extract induces G2/M cell cycle arrest and reduces the expression of EMT (epithelial–mesenchymal transition) markers, N-cadherin and Twist. In addition, the extract showed anti-metastatic properties through its ability to decrease MMP-2 and MMP-9 activity. Mechanistically, DM caused a substantial reduction in Ten-Eleven Translocation (TET) enzymes TET-1, TET-2, and TET-3, which are essential DNA demethylation regulators, thus decreasing their enzymatic product 5-hydroxymethylcytosine (5-hmC). Interestingly, despite a significant increase in intracellular ROS (reactive oxygen species), suggesting a contribution to cytotoxicity, no substantial change in the biogenesis of promyelocytic leukemia nuclear bodies (PML-NBs) was detected. These findings demonstrate that J. rubens DM extract contains bioactive compounds with multiple anticancer effects, thus making it a promising candidate for developing new therapeutic agents. Full article

Human papillomavirus (HPV) is a major etiological factor in cervical, anal, and oropharyngeal cancers. Although prophylactic vaccines have substantially reduced infection rates, effective therapeutic options for established HPV-associated malignancies remain limited. This review provides an up-to-date overview of emerging strategies to treat HPV-driven tumours. Key approaches include immune checkpoint inhibitors, therapeutic vaccines such as VGX-3100 and PRGN-2012, and gene-editing tools like CRISPR/Cas9. Epigenetic drugs, particularly histone deacetylase inhibitors, show promise in reactivating silenced tumour suppressor genes and enhancing antitumour immunity. In addition, natural bioactive compounds and plant-derived molecules are being explored as complementary anti-HPV agents, while drug repurposing and combination therapies offer cost-effective opportunities to broaden treatment options. We also highlight the role of patient-derived organoid models as powerful platforms for personalized drug screening and functional assessment. By integrating these therapeutic innovations with precision oncology approaches, this review outlines a multidimensional framework aimed at improving clinical outcomes and quality of life for patients with HPV-associated cancers. Full article

Tissue factor (TF), also known as CD142, is a 47 kDa transmembrane glycoprotein belonging to the class II cytokine receptors superfamily. High expression of TF has been reported to be correlated with poor prognosis in various cancers. In this study, we aimed to clarify the cytotoxicity of bi-specific T-cell engagers (BiTE) targeting TF on cervical cancer cell lines. We designed and characterized the novel humanized BiTE targeting TF using an anti-human CD3 single-chain variable fragment (scFv) linked to human TF scFv. TF-Bite replication and potency were assessed in cervical cancer cell lines. The expression of the TF-BiTE and the activation and proliferation of T cells induced along with the T-cell-mediated cytotoxicity were evaluated by flow cytometry in vitro. TF expression was confirmed in SiHa, ME-180, and HeLa cell lines. The TF-BiTE showed potent TF-specific cytotoxicity and induced T-cell activation, proliferation, degranulation, and cytokine release. These effects were not observed in TF-negative control cells. Our findings support TF-BiTE as a promising therapeutic candidate for cervical cancer immunotherapy. Full article