Cervical Cancer Research Articles

Study on artificial intelligence recognition pre-processing algorithm for cervical cancer

INTRODUCTION: Cervical cancer is the most common malignant tumor in the female reproductive system, with the number of deaths due to cervical cancer in developing countries accounting for 80% of the global total. In China, the incidence rate of cervical cancer is increasing year by year. At present, the commonly used methods for cervical cancer screening include TCT, HPV testing, TCT+HPV combined testing, FRD, and VIA/VILI. Among them, although TCT+HPV combined testing has high sensitivity and specificity, it is costly and time-consuming. VIA/VILI screening is cost-effective, easy to operate, and suitable for promotion in economically underdeveloped areas.However, VIA/VILI screening relies on the subjective judgment of doctors, so its accuracy is relatively low in rural areas of China with a large population and a lack of well-trained doctors. To address this issue, computer-aided diagnosis (CAD) technology is needed to improve the accuracy and reliability of VIA/VILI screening. OBJECTIVES: The implementation of artificial intelligence (AI)-based Visual Inspection with Acetic acid (VIA) screening and computer-aided diagnosis has the potential to significantly reduce the cost of cervical cancer screenings and increase the coverage rate of cervical cancer screenings, thus reducing the incidence rate of the disease. To this end, we have developed an AI preprocessing algorithm aimed at improving the accuracy of AI in detecting cervical cancer. METHODS: Initially, the algorithm maps images to the YCrCb and Lab color spaces. Unlike traditional enhancement methods that mainly focus on the luminance channel, our method primarily enhances the Cr channel in the YCrCb color space and a channel in the Lab color space. This paper innovatively proposes the LT_CLAHE algorithm to enhance the Cr channel, obtaining an enhanced image with a bias towards blue-green colors, and uses the WLS algorithm to enhance the a channel, obtaining an enhanced image with a bias towards red colors. Subsequently, the enhanced images from both color spaces are fused to eliminate color distortion. RESULTS: Experimental results show that our method significantly enhances the texture of lesions and outperforms traditional methods across various objective indicators. When the enhanced images from this paper are used as input for neural networks, there is also a significant increase in the accuracy of neural network detection.

Cisplatin-encapsulated TRAIL-engineered exosomes from human chorion-derived MSCs for targeted cervical cancer therapy

BackgroundCisplatin (DDP) is an efficacious and widely applied chemotherapeutic drug for cervical cancer patients who are diagnosed as metastatic and inoperable, or desiring fertility preservation. Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) selectively triggers cancer cells apoptosis by binding to cognate death receptors (DR4 and DR5). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been regarded as ideal drug carriers on account of their nanoscale, low toxicity, low immunogenicity, high stability, biodegradability, and abundant sources.MethodsHuman chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCsTRAIL) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-ExoTRAIL) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-ExoTRAIL) were fabricated by loading DDP into hCD-MSCs-ExoTRAIL via electroporation. The CCK-8 assay and flow cytometry were conducted to explore the proliferation and apoptosis of cervical cancer cells (SiHa and HeLa), respectively. Cervical cancer-bearing nude mice were constructed to examine the antitumor activity and biosafety of DDP & hCD-MSCs-ExoTRAIL in vivo.ResultsCompared with hCD-MSCs-Exo, hCD-MSCs-ExoTRAIL weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-ExoTRAIL were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-ExoTRAIL alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-ExoTRAIL evidently hampered tumor growth, and its role in inducing apoptosis was mechanistically associated with JNK/p-c-Jun activation and survivin suppression. Moreover, DDP & hCD-MSCs-ExoTRAIL showed favorable biosafety in vivo.ConclusionsDDP & hCD-MSCs-ExoTRAIL nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice.Graphical abstract

ZNF281 Facilitates the Invasion of Cervical Cancer Cell Both In Vivo and In Vitro †

Background: Cervical cancer is the fourth most common cancer among women worldwide. The zinc finger transcription factor 281 (ZNF281)/ZBP-99 protein specifically binds to GC-rich DNA sequences and regulates gene expression, and it has been shown to promote tumor progression. In this study, we aim to investigate the function and molecular mechanism of ZNF281 in uterine cervical carcinoma. Methods: We conducted immunohistochemistry and Western blot assays to determine the expression of ZNF281 in eight human cervical cancer tissues. And, xenograft experiments involving the injection of HeLa cells into nude mice was used to determine the function of ZNF281 on proliferation. Transwell assays were used to detect the migration and invasion of HeLa cells after indicated that ZNF281 overexpression. Results: Our results indicated that ZNF281 protein levels were higher in cervical cancer tissues compared to normal cervical tissues. Additionally, ZNF281 was expressed in human cervical carcinoma cell lines, including HeLa, SiHa, C-33 A, CaSki, and HT-3, and is localized in both the cell nucleus and cytoplasm. ZNF281 overexpression did not influence HeLa cell proliferation or tumor size in situ. Moreover, nude mice injected with ZNF281-overexpressing cell lines developed more tumor lesions in the lungs compared to those injected with control cell lines. Conclusions: These findings suggest that ZNF281 is associated with tumor metastasis without affecting cell proliferation, both in vivo and in vitro.

MiR-525-5p modulates cell proliferation, cell cycle, and apoptosis in Burkitt's lymphoma by targeting MyD88 and regulating the NF-κB signaling pathway.

MiR-525-5p functions as an oncomiRNA or tumor suppressor, and has been reported in various cancer types, including laryngeal squamous cell carcinoma, glioma, breast cancer, and cervical cancer. However, the biological functions and precise mechanisms of miR-525-5p remain unclarified in Burkitt's lymphoma (BL). This study aimed to explore the roles of miR-525-5p in BL, with the goal of ascertaining its regulatory effects on the nuclear factor-kappaB (NF-κB) signaling pathway by targeting Myeloid differentiation factor 88 (MyD88). The expression levels of miR-525-5p and MyD88 were measured by quantitative real-time PCR and immunohistochemical staining, respectively. The effects of miR-525-5p overexpression on BL cell proliferation, colony-forming, and migration were evaluated by cell counting kit-8, soft agar colony-forming, and transwell assays, while cell cycle and cell apoptosis were analyzed by flow cytometry. Possible interactions between miR-525-5p and MyD88 was examined via luciferase reporter assay. The expression of MyD88 and NF-κB signaling pathway-related proteins, including p65, p-p65, IκBa, and p-ΙκBa was determined by western blotting. BL cells overexpressing miR-525-5p were treated with phorbol 12-myristate 13-acetate (PMA), and Hoechst 33258 staining and Calcein AM/EthD-I staining were used to analyze the changes in chemotherapy sensitivity of BL cells to doxorubicin (DOX). Compared with reactive lymphoid hyperplasia, miR-525-5p was dramatically downregulated in BL tissues, while the rate of MyD88 protein positivity was significantly increased. Upregulation of miR-525-5p suppressed cell proliferation, colony-forming, and migration, induced cell cycle arrest and apoptosis, and enhanced the chemosensitivity to DOX in BL cells. MiR-525-5p targeted MyD88 to inhibit the activation of NF-κB signaling pathway. PMA treatment reactivated the NF-κB pathway and reversed apoptosis mediated by miR-525-5p overexpression. These findings revealed that miR-525-5p acts as a tumor suppressor, targeting MyD88 to modulate proliferation, cell cycle progression, and apoptosis in BL cells by regulation of NF-κB signaling pathway.

Temporal Trends in Knowledge of Human Papillomavirus and Associated Oropharyngeal Cancer Following Expanded Vaccination Eligibility.

Human papillomavirus (HPV) is a significant driver of elevated risk for oropharyngeal squamous cell carcinoma (OPSCC). In 2018, HPV vaccination eligibility was expanded to men and women aged 27 to 45. We evaluated changes in awareness of HPV, its association with OPSCC, and HPV vaccination among all US adults between 2018 and 2020, focusing on those aged 27 to 45. Cross-sectional survey cycles. The Health Information National Trends Survey (HINTS). The HINTS, a nationally representative survey of US adults, was queried. A total of 3504 adults in 2018 and 3865 adults in 2020 were assessed for knowledge of HPV, its vaccine, its association with OPSCC, and changes in awareness between 2018 and 2020. Statistical significance was set at P < .05. Most respondents were aware of HPV (2018: 60.8%; 2020: 64.8%) and its vaccine (2018: 60.8%; 2020: 61.6%). A significant decrease in awareness of the association between HPV and cervical cancer was seen between 2018 and 2020 (75.0% vs 70.2%, P = .028). Knowledge of HPV+ OPSCC was poor and did not change over time (2018: 27.0%, 2020: 29.5%). Statistically significant increases in HPV awareness between 2018 and 2020 were found for individuals who reported completing high school as their highest level of education (P = .009), Caucasians (P = .013), males (P = .024), and those making more than $200,000 annually (P = .022). Knowledge of the association between HPV and OPSCC remained poor despite expanded vaccine eligibility. Public health education on the association may increase awareness for groups likely to benefit from vaccination.

Nationwide cohort study on the risk of high-grade cervical dysplasia and carcinoma after conservative treatment or hysterectomy for adenocarcinoma in situ.

Internationally, little consensus exists about the best treatment for cervical adenocarcinoma in situ (AIS). This study aimed to determine the incidence of recurrent high-grade cervical dysplasia and development of local cervical cancer after treatment for AIS. This nationwide, retrospective cohort study included patients with AIS, who were treated by a large loop excision of the transformation zone (LLETZ), cold-knife conization (CKC), or hysterectomy between January 1, 1990 and December 31, 2021 in the Netherlands. Pathology reports were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were the cumulative incidences of high-grade cervical dysplasia (cervical intraepithelial neoplasia grade 2 or 3, and AIS) and local cervical cancer up to 20 years after primary treatment. In total, 4243 patients with AIS were included. The primary treatment was a LLETZ, CKC, or hysterectomy in 1593, 2118, and 532 patients, respectively. The incidence of recurrent high-grade cervical dysplasia after LLETZ (10.5%; 95%CI: 8.6-12.3) was higher than after CKC (5.5%; 95%CI: 4.4-6.6, p <.0001). When a radical excision, that is, surgical margins free of dysplasia at end of treatment, was achieved, the incidence of recurrent high-grade dysplasia and local cervical cancer did not differ between LLETZ (5.6% [95%CI: 3.3-7.9] and 1.9% [95%CI: 0-4.4]) and CKC (4.7% [95%CI: 3.5-5.8], p = .631 and 1.5% [95%CI: 0.7-2.3], p = .918). After hysterectomy, none of the patients developed cervical dysplasia or local cervical cancer. Conservative treatment for AIS can be considered a safe and final treatment modality when a radical excision is achieved.

Curculigosides J–K and curcorchidihydrobenzofuran A, a dihydrobenzofuran with anti-proliferative properties from Curculigo orchioides

Phytochemical investigation of the rhizomes and the leaves of Curculigo orchioides led to the isolation of fourteen compounds. They consist of one undescribed dihydrobenzofuran, curcorchidihydrobenzofuran A (1), two undescribed benzyl benzoate glycosides, curculigoside J (2) and K (3), and eleven known compounds (4–14). The structures of the isolated compounds were elucidated by thorough analysis of spectroscopic (IR, NMR and ECD) and spectrometric (MS) data. Compound 1 displayed significant anti-proliferative activities against cervical cancer cells (HelaS3, IC50 = 3.6 µM) and breast cancer cells (MCF-7, IC50 = 13.9 µM) while showing moderate activities against lung cancer cells (A549, IC50 = 29.8 µM). Importantly, it was non-toxic to Vero cells. Compound 1 also inhibited the tyrosinase enzyme in a moderate manner (IC50 = 120.8 µM). Eventually, its permethylated synthetic analog 1a showed a significant suppression of lipopolysaccharide (LPS)-induced NO production in murine macrophage RAW 264.7 (IC50 = 23.4 µM).

Content Analysis of Human Papilloma Virus Vaccine-Related Videos on YouTube in Japan

This study aimed to describe the YouTube content on Human Papilloma Virus (HPV) vaccines by analyzing the related Japanese videos in context of the account characteristics, attitude toward the vaccine, and thumbnail characteristics. Relevant videos with keywords “HPV vaccine” and “cervical cancer vaccine” uploaded before November 11, 2021 were collected and coded. The findings showed that as of November 11, 2021, positive and negative attitude videos regarding HPV vaccines accounted for approximately 44% of Japanese YouTube videos. In the year 2013, an increase in negative videos was observed, while from 2019 onwards, majority of the videos uploaded showed positive attitudes toward the vaccine. Videos with negative tones generally used the term "cervical cancer vaccines.” Most negative videos were uploaded by individual accounts, whereas all videos uploaded by medical workers were positive or neutral. Only four videos mentioned side effect compensation. The most frequently used thumbnails were photographs of people who appeared in the videos. Compared to English YouTube, there are fewer anti-vaccine videos in Japan, and there is also a lack of videos uploaded by credible authorities. Future research focusing on other platforms and the accuracy of video content should be included.

Quadrivalent HPV (4vHPV) vaccine immunogenicity and safety in women using immunosuppressive drugs due to solid organ transplant

IntroductionImmunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC).MethodsOpen-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study.Results125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) (p&amp;lt;0.001). Antibody GMCs of all four HPV vaccine types were also significantly lower in SOT (p&amp;lt;0.001). Pain in the injection site and headache were the most frequent adverse event in both groups. Local pain was more frequent in immunocompetent women than in SOT recipients. Rates of other AEs were comparable in both groups.Conclusion4vHPV vaccine was well-tolerated by SOT recipients. We found strong evidence of lower humoral immune responses to 4vHPV vaccine in SOT compared to immunocompetent women, which strengthen recommendation of routine cervical cancer screening in SOT recipients regardless of HPV vaccination status.

Unsupervised cervical cell instance segmentation method integrating cellular characteristics.

Cell instance segmentation is a key technology for cervical cancer auxiliary diagnosis systems. However, pixel-level annotation is time-consuming and labor-intensive, making it difficult to obtain a large amount of annotated data. This results in the model not being fully trained. In response to these problems, this paper proposes an unsupervised cervical cell instance segmentation method that integrates cell characteristics. Cervical cells have a clear corresponding structure between the nucleus and cytoplasm. This method fully takes this feature into account by building a dual-flow framework to locate the nucleus and cytoplasm and generate high-quality pseudo-labels. In the nucleus segmentation stage, the position and range of the nucleus are determined using the standard cell-restricted nucleus segmentation method. In the cytoplasm segmentation stage, a multi-angle collaborative segmentation method is used to achieve the positioning of the cytoplasm. First, taking advantage of the self-similarity characteristics of pixel blocks in cells, a cytoplasmic segmentation method based on self-similarity map iteration is proposed. The pixel blocks are mapped from the perspective of local details, and the iterative segmentation is repeated. Secondly, using low-level features such as cell color and shape, a self-supervised heatmap-aware cytoplasm segmentation method is proposed to obtain the activation map of the cytoplasm from the perspective of global attention. The two methods are fused to determine cytoplasmic regions, and combined with nuclear locations, high-quality pseudo-labels are generated. These pseudo-labels are used to train the model cyclically, and the loss strategy is used to encourage the model to discover new object masks, thereby obtaining a segmentation model with better performance. Experimental results show that this method achieves good results in cytoplasm segmentation. On the three datasets of ISBI, MS_CellSeg, and Cx22, 54.32%, 44.64%, and 66.52% AJI were obtained, respectively, which is better than other typical unsupervised methods selected in this article.

Primary Care Practice Telehealth Use and Low-Value Care Services

The rapid expansion of telehealth transformed how primary care practices deliver care; however, uncertainties about the quality of telehealth-delivered care compared with in-person care remain. While there are concerns that increased telehealth may introduce wasteful care, how telehealth affects the delivery of low-value care is unknown. To examine whether a primary care practice's level of telehealth use is associated with changes in the rates of low-value care. This retrospective cohort study using a difference-in-differences study design was conducted from January 1, 2019, to December 31, 2022, using Medicare fee-for-service claims data. Participants were Medicare beneficiaries attributed to primary care practices in Michigan. Low, medium, or high tertile of practice-level telehealth use. Low-value care was assessed using 8 claims-based measures relevant to primary care, grouped into 4 main categories: office-based, laboratory-based, imaging-based, and mixed-modality services. Poisson regression models were used to estimate the association between practice-level telehealth use and rates of low-value care services, controlling for practice-level characteristics. A total of 577 928 beneficiaries (332 100 [57%] women; mean [SD] age, 76 [8] years) attributed to 2552 primary care practices were included in the study. After adjusting for practice-level characteristics and baseline differences in low-value care rates between telehealth use groups, high practice-level telehealth use was associated with lower rates of low-value cervical cancer screening (-2.9 [95% CI, -5.3 to -0.4] services per 1000 beneficiaries) and lower rates of low-value thyroid testing (-40 [95% CI, -70 to -9] tests per 1000 beneficiaries) compared with low practice-level telehealth use. Of the other 6 outcomes examined, there was no association between practice-level telehealth use and rates of low-value care services. In this cohort study of Medicare fee-for-service beneficiaries who received care from primary care practices in Michigan, some low-value care services (ie, cervical cancer screening among women older than 65 years and low-value thyroid testing) were lower among practices with high telehealth use, and there was no association between practice-level telehealth use in rates of most other low-value care services not delivered in the office. As telehealth continues to be an important part of care delivery, evaluating how it may encourage or discourage low-value care services is critical to understanding its impact on quality of care.

Comprehensive Analysis of the Significance of Cyclin Dependent Kinase Inhibitor Genes in the Prognosis of Cervical Cancer

Comprehensive Analysis of the Significance of Cyclin Dependent Kinase Inhibitor Genes in the Prognosis of Cervical Cancer

Elucidating the anticancerous efficacy of genistein via modulating HPV (E7 and E6) oncogenes expression and apoptotic induction in cervical cancer cells.

In recent years, genistein has garnered increased interest for its ability to inhibit numerous deregulated targets associated with cancer progression and induction of programmed cell death and antiproliferative activities in human carcinoma cells. Cancer etiology is influenced via multiple disrupted signaling pathways. This study therefore directed toward investigating genistein efficacy in modulating mRNA expression levels of two crucial Human Pappiloma Virus (HPV) (E7 and E6) oncogenes for cancer treatment. Moreover, the inhibitory effects of genistein for HPV (E7 and E6) oncogenes in cervical carcinoma have not yet been reported. Current study investigated inhibitory potential of genistein in HPV (E7 and E6) oncogenes in HeLa cells. These oncogenes are known to deactivate many tumor suppressor proteins (p53 and pRB). Genistein therapy resulted in decreased cell proliferation and increased cell accumulation in the G (G0/G1) phase in HeLa cell lines. In addition, genistein therapy has resulted in the suppression of HPV (E7 and E6) gene expression and simultaneously increasing expression levels of p53 and pRB mRNA levels. As a consequence, there has been an activation of a series of caspases (3, 8, and 9), resulting in their cleavage. Consequently, our data suggests that genistein could be a powerful candidate for treating cervical cancer by targeting two important oncogenes involved in viral development. However, more in vitro research on primary cervical cancer cells is required to validate the clinically relevant efficacy of genistein against cervical cancer.

A Systematic Literature Review of Modelling Approaches to Evaluate the Cost Effectiveness of PET/CT for Therapy Response Monitoring in Oncology.

This systematic literature review addresses model-based cost-effectiveness studies for therapy response monitoring with positron emission tomography (PET) generally combined with low-dose computed tomography (CT) for various cancer types. Given the known heterogeneity in therapy response events, studies should consider patient-level modelling rather than cohort-based modelling because of its flexibility in handling these events and the time to events. This review aims to identify the modelling methods used and includes a systematic assessment of the assumptions made in the current literature. This study was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Information sources included electronic bibliographic databases, reference lists of review articles and contact with experts in the fields of nuclear medicine, health technology assessment and health economics. Eligibility criteria included peer-reviewed scientific publications and published grey literature. Literature searches, screening and critical appraisal were conducted by two reviewers independently. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) were used to assess the methodological quality. The Bias in Economic Evaluation (ECOBIAS) checklist was used to determine the risk of bias in the included publications. The search results included 2959 publications. The number of publications included for data extraction and synthesis was ten, representing eight unique studies. These studies addressed patients with lymphoma, advanced head and neck cancers, brain tumours, non-small cell lung cancer and cervical cancer. All studies addressed response to chemotherapy. No study evaluated response to immunotherapy. Most studies positioned PET/CT as an add-on modality and one study positioned PET/CT as a replacement for conventional imaging (X-ray and contrast-enhanced CT). Three studies reported decision-tree structures, four studies reported cohort-level state-transition models and one study reported a partitioned survival model. No patient-level models were reported. The simulation horizons adopted ranged from 1 year to lifetime. Most studies reported a probabilistic analysis, whereas two studies reported a deterministic analysis only. Two studies conducted a value of information analysis. Multiple studies did not adequately discuss model-specific aspects of bias. Most importantly and regularly observed were a high risk of structural assumptions bias, limited simulation horizon bias and wrong model bias. Model-based cost-effectiveness analysis for therapy response monitoring with PET/CT was based on cohorts of patients instead of individual patients in the current literature. Therefore, the heterogeneity in therapy response events was commonly not addressed appropriately. Further research should include more advanced and patient-level modelling approaches to accurately represent the complex context of clinical practice and, therefore, to be meaningful to support decision making. This review is registered in PROSPERO, the international prospective register of systematic reviews funded by the National Institute for Health Research, with CRD42023402581.

Cryoablation synergizes with anti-PD-1 immunotherapy induces an effective abscopal effect in murine model of cervical cancer

BackgroundImmune checkpoint inhibitors (ICIs), especially anti-PD-1/PD-L1 antibodies, have emerged as promising therapeutic options for cervical cancer. However, the efficacy of anti-PD-1 antibody monotherapy is limited. Cryoablation could elicit an anti-tumor immune response, thereby presenting itself as a potential approach to augment the response of ICIs. The aim of our study was to investigate the systemic immunological effects of cryoablation and the potential synergistic anti-tumor effects of cryoablation and anti-PD-1 antibody in cervical cancer. MethodsWe established U14 murine bilateral subcutaneous cervical cancer model, wherein the primary tumors were treated with cryoablation. Flow cytometry, immunohistochemistry and RNA-seq were used to analyze the immune cell infiltration and immune-associated pathways in the secondary tumor. ResultsOur study revealed that cryoablation reprogrammed the immune landscape, leading to an enhanced infiltration of CD8+ T cell in distant tumors. Cryoablation created a conducive environment for increasing the efficacy of anti-PD-1 immunotherapy. Cryoablation in combination with anti-PD-1 antibody inhibited distant tumors growth and improved mouse survival. Mechanistically, this combination therapy could augment the infiltration of CD8+ T cells, CD4+ T cells, dendritic cells and M1-like tumor-associated macrophages, enhance multiple aspects of antitumor immune response, and reduce immunosuppressive cells such as M2-like tumor-associated macrophages and myeloid-derived suppressor cells in distant tumors. ConclusionsCombination therapy with cryoablation and anti-PD-1 antibody induces an effective abscopal effect in murine model of cervical cancer and may be a novel therapeutic approach for patients with advanced/recurrent cervical cancer.

3D-printed brachytherapy in patients with cervical cancer: improving efficacy and safety outcomes

ObjectiveThis study aims to evaluate the efficacy and safety of 3D printing technology in brachytherapy for cervical cancer, comparing its outcomes with conventional free hand implantation brachytherapy.MethodsA total of 50 cervical cancer patients treated at the First Affiliated Hospital of Gannan Medical College from January 2019 to July 2023 were included in this study. Patients were divided into two groups: 25 patients received intensity-modulated radiotherapy (IMRT) combined with 3D-printed brachytherapy, and 25 patients underwent IMRT combined with free hand brachytherapy implantation. Key indicators analyzed included short-term therapeutic effects, survival outcomes, operation times, the number of CT scans, the number of needles inserted, dosimetric parameters, and complications.ResultsThe use of 3D-printed brachytherapy significantly improved the safety of radiation therapy operations, especially for large tumors (≥ 30 mm), by providing more precise dose distribution and reducing the radiation doses received by critical organs such as the bladder and rectum. Compared to the artificial implant group (88% prevalence), the 3D-printed brachytherapy group showed a significantly lower incidence of radiation enteritis (29.2% prevalence, p < 0.001). There were no significant differences in other complications between the two groups. For instance, the incidence of radiation cystitis was relatively high in the 3D-printed brachytherapy group (79.2% prevalence) compared to the artificial implant group (64% prevalence, p = 0.240). The median follow-up period in this study was 22.5 months [IQR 18–29]. Among the 49 patients included, 43 had cervical squamous carcinoma and 6 had cervical adenocarcinoma. Short-term therapeutic response rates were comparable, with no significant difference in overall survival observed between the two groups.Conclusion3D-printed brachytherapy offers a more effective and safer therapeutic option for patients with cervical cancer, particularly for those with large tumors or complex anatomical structures.

Regulatory Mechanism of Protein Crotonylation and Its Relationship with Cancer.

Crotonylation is a recently discovered protein acyl modification that shares many enzymes with acetylation. However, it possesses a distinct regulatory mechanism and biological function due to its unique crotonyl structure. Since the discovery of crotonylation in 2011, numerous crotonylation sites have been identified in both histones and other proteins. In recent studies, crotonylation was found to play a role in various diseases and biological processes. This paper reviews the initial discovery and regulatory mechanisms of crotonylation, including various writer, reader, and eraser proteins. Finally, we emphasize the relationship of dysregulated protein crotonylation with eight common malignancies, including cervical, prostate, liver, and lung cancer, providing new potential therapeutic targets.

Premature adoption of adjuvant chemotherapy for locally advanced cervical carcinoma before the OUTBACK trial: cautionary tale on outcomes.

The aim of this study was to investigate the use and outcomes of adjuvant chemotherapy for patients with locally advanced cervical carcinoma receiving definitive chemoradiation. The National Cancer Database was accessed, and patients diagnosed between 2004 and 2015 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2-IVA disease who underwent definitive chemoradiation were selected. Patients who received radio-sensitizing single agent chemotherapy and those who received adjuvant multi-agent chemotherapy were identified. Overall survival was evaluated following generation of Kaplan-Meier curves while a Cox model was constructed to control for confounders. A total of 9895 patients were identified; 1003 (10.1%) received multi-agent adjuvant chemotherapy. Patients who received adjuvant chemotherapy were less likely to receive brachytherapy (60.9% vs 68.4%, p<0.001). Rate of adjuvant chemotherapy was higher among patients with stage IVA (18.1%) and stage III (11.9%) disease compared with those with stage II (8.4%) and stage IB2 (7.2%) disease (p<0.001). After controlling for confounders, administration of adjuvant chemotherapy was not associated with a survival benefit (hazard ratio 1.09, 95% confidence interval 0.98 to 1.20). Following stratification by disease stage, there was no survival benefit of patients who received adjuvant chemotherapy compared with those who did not; stage IB (p=0.002; 5 year overall survival 59.2% vs 74.9% favoring chemoradiation alone), stage II (p=0.41; 5 year overall survival 63.8% vs 67.6%, respectively), stage III (p=0.52; 5 year overall survival 48% vs 47.8%, respectively), or stage IVA disease (p=0.27; 5 year overall survival 29.5% vs 34.3%, respectively). In the US, approximately 1 in 10 patients with locally advanced cervical carcinoma who underwent definitive chemoradiation also received adjuvant chemotherapy that was not associated with improvement in overall survival.

CircVIRMA enhances cell malignant behavior by governing the miR-452-5p/CREBRF pathway in cervical cancer.

Our current study aimed to investigate the role and mechanism of circVIRMA in cervical cancer (CC) progression. CircVIRMA, microRNA-452-5p (miR-452-5p) and CREB3 regulatory factor (CREBRF) mRNA levels were examined in CC via quantitative real-time PCR (qRT-PCR). The protein level of CREBRF in CC was checked by Western blot. Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, cell cycle, flow cytometry and transwell assays were conducted to estimate the effects of circVIRMA on malignant phenotypes of CC tumors. Western blot was used to measure related marker protein levels. The interaction between miR-452-5p and circVIRMA or CREBRF was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Xenograft assay was used to assess the effect of circVIRMA on tumor growth in vivo. Immunohistochemistry (IHC) assay was performed to detect Ki-67 expression in tissues of mice. CircVIRMA and CREBRF levels were upregulated, while miR-452-5p was downregulated in CC tissues and cells. CircVIRMA silencing restrained CC cell proliferation, migration and invasion whereas induced apoptosis in vitro. In addition circVIRMA knockdown markedly attenuated xenograft tumor growth in vivo. circVIRMA was an efficient molecular sponge for miR-452-5p, and negatively regulated miR-452-5p expression. circVIRMA regulated CREBRF expression to modulate CC progression via miR-452-5p. MiR-452-5p downregulation reversed the effects of circVIRMA knockdown on CC progression. MiR-452-5p directly targeted CREBRF, and CREBRF overexpression partly restored the impact of miR-452-5p mimics on CC progression. circVIRMA mediated CC progression via regulating miR-452-5p/CREBRF axis, providing a novel therapeutic target for CC treatment.

Identification and validation of miR-21 key genes in cervical cancer through an integrated bioinformatics approach

Cervical cancer is one of the most prevalent female reproductive cancers. miR-21 is a multi-target oncomiR that has shown its potential in regulating several cancers including colon, pancreatic, breast, prostate, ovarian, and cervical cancer. However, the signaling network of miR-21 remains underexplored, and only a limited number of miR-21 gene targets in cervical cancer have been reported. In this context, the present study was undertaken to evaluate the role of miR-21 in cervical cancer by combining in silico analysis with in vitro validation in cervical cancer cells. The miR-21 target genes were predicted using four different prediction tools: miRwalk, DIANA, miRDBs, and TargetScan. A total of 113 overlapping target genes, common in at least three of the prediction tools, were shortlisted and subjected to functional enrichment analysis. The analysis predicted that JAK-STAT, MAPK, neurotrophin, and Ras signaling pathways are significantly (p≤0.05) targeted by miR-21. The MCODE plugin identified the potential cluster in the protein-protein interaction network based on the highest degree of connectivity. After GEPIA2 validation of all 20 hub genes, NTF3, LIFR, and IL-6R were shortlisted for validation in cervical cancer cell lines. The results showed that NTF3, LIFR, and IL-6R were significantly upregulated in the miR-21 knockdown CaSki cell lines in 6.27, 1.92 and 1.71 folds (p≤0.01), respectively. Similarly, in HeLa cell lines expression of NTF3, LIFR, and IL-6R were overexpressed in 4,06, 5.65, 2.42 folds (p≤0.001), respectively. confirming the role of miR-21 in regulating the expression of these genes. Additionally, the knockdown of miR-21 significantly inhibited the secretion of matrix metalloproteinases by CaSki cells. These results highlight that miR-21 could be a potential therapeutic target for cervical cancer, although further preclinical and clinical studies are required to validate its role and efficacy.