Treatment Of Cervical Cancer Research Articles

Targeted Delivery of SmacN7 Peptide Induces Immunogenic Cell Death in Cervical Cancer Treatment.

Cervical cancer is a common tumor in women and one of the common causes of cancer death in women. Due to the aggressive and non-specific nature of traditional chemotherapy, there is a growing need for new treatment modalities. Currently, tumor immunotherapy is increasingly garnering attention as a disruptive treatment approach. Therefore, we constructed CCTP-SmacN7, a delivery system capable of releasing active molecules in the tumor microenvironment. CCTP-SmacN7 can not only inhibit tumor proliferation and migration, but also induce tumors to produce large amounts of reactive oxygen species. The production of reactive oxygen species can activate tumors to release or expose damage-associated molecular patterns, promote DC cell maturation, and ultimately activate T cells. Here, we present an innovative targeted treatment approach for cervical cancer. While inducing tumor immunogenic cell death, this program can also improve the tumor microenvironment and initiate the tumor immune cycle.

Focus Groups With Guatemalan Community Leaders About Barriers to Cervical Cancer Prevention and Control.

Cervical cancer is the leading cause of cancer-related death among Latin American women, including Guatemalans. This is troubling, given we have a vaccine, screening tool, and treatment for this preventable disease. Human papillomavirus (HPV) causes most cervical cancer. HPV self-testing is a viable option for women in low-resource areas, such as Guatemala. More information is needed about barriers to HPV self-testing. We conducted four focus groups (N = 43) in three locations in San Raymundo with female community leaders to assess the lived experience of their attitudes, practices, and knowledge about cervical cancer. Participants shared barriers they face receiving Pap tests, the HPV vaccine, and self-testing for HPV. We concluded culturally targeted information is needed about cervical cancer prevention, screening, and treatment. Policies should include outreach to marginalized populations in remote areas with low-literacy indigenous Mayans. Practices should include partnerships with lay midwives and health promoters to help Guatemalan women self-test for HPV.

Editorial Comment: Key Elements of Pelvic MRI in Assessing the Feasibility of Fertility-Sparing Treatments for Early-Stage Endometrial and Cervical Cancers.

Editorial Comment: Key Elements of Pelvic MRI in Assessing the Feasibility of Fertility-Sparing Treatments for Early-Stage Endometrial and Cervical Cancers.

Advancing the Fight Against Cervical Cancer: The Promise of Therapeutic HPV Vaccines.

Human papillomavirus (HPV) is a major global health issue and is recognized as the leading cause of cervical cancer. While prophylactic vaccination programs have led to substantial reductions in both HPV infection rates and cervical cancer incidence, considerable burdens of HPV-related diseases persist, particularly in developing countries with inadequate vaccine coverage and uptake. The development of therapeutic vaccines for HPV represents an emerging strategy that has the potential to bolster the fight against cervical cancer. Unlike current prophylactic vaccines designed to prevent new infections, therapeutic vaccines aim to eradicate or treat existing HPV infections, as well as HPV-associated precancers and cancers. This review focuses on clinical studies involving therapeutic HPV vaccines for cervical cancer, specifically in three key areas: the treatment of cervical intraepithelial neoplasia; the treatment of cervical cancer in combination with or without chemotherapy, radiotherapy, or immune checkpoint inhibitors; and the role of prophylaxis following completion of treatment. Currently, there are no approved therapeutic HPV vaccines worldwide; however, active progress is being made in clinical research and development using multiple platforms such as peptides, proteins, DNA, RNA, bacterial vectors, viral vectors, and cell-based, each offering relative advantages and limitations for delivering HPV antigens and generating targeted immune responses. We outline preferred vaccine parameters, including indications, target populations, safety considerations, efficacy considerations, and immunization strategies. Lastly, we emphasize that therapeutic vaccines for HPV that are currently under development could be an important new tool in fighting against cervical cancer.

Enhanced targeted treatment of cervical cancer using nanoparticle-based doxycycline delivery system

This study investigates a nanoparticle-based doxycycline (DOX) delivery system targeting cervical cancer cells via the CD44 receptor. Molecular docking revealed a strong binding affinity between hyaluronic acid (HA) and CD44 (binding energy: -7.2 kJ/mol). Characterization of the HA-Chitosan nanoparticles showed a particle size of 284.6 nm, a zeta potential of 16.9 mV, and a polydispersity index of 0.314, with SEM confirming smooth surface morphology. The encapsulation efficiency of DOX-loaded nanoparticles was 89.32%, exhibiting a sustained release profile, with 67.45% released over 72 h in acidic conditions (pH 5.5). Cytotoxicity assays demonstrated a significant reduction in HeLa cell viability to 22% at 72 h, compared to 67% in normal HEK cells. Stability tests confirmed the maintenance of nanoparticle integrity and a consistent drug release profile over three months. Cell migration was reduced by 45%, and RT-PCR analysis revealed a 53% downregulation of TNF-α expression, suggesting effective targeting of inflammatory pathways. These results underscore the potential of HA-Chitosan-based DOX nanoparticles in improving cervical cancer treatment through enhanced targeted delivery and inhibition of tumor-promoting mechanisms.

Development and pilot testing of INTERVENER, a web-based tool to match barriers to the cancer continuum organization to evidence-based interventions

BackgroundBarriers to the cancer continuum organization and interventions to approach them have been identified; however, there is a lack of a tool matching them. Our aim was to develop a web-based tool to identify the main barriers to the process of the cancer continuum organization, and propose matched evidence-based interventions (EBI) to overcome them.MethodsA questionnaire on barriers at six steps of the process of the cancer continuum organization was answered by collaborators. Each question included several options of barriers to be ranked. Barriers were organized in a framework based on the Tanahashi conceptual model, and were categorized in these dimensions: availability of services, accessibility, affordability, acceptability, user-provider interaction, governance, protocols and guidelines, information system, and quality assurance. Systematic searches were conducted on interventions for breast, cervical and colorectal cancer. Interventions were matched with the barriers they helped to overcome, and were classified in one of these groups for each barrier and cancer site: EBI as a single strategy, EBI within a multicomponent strategy, limited-evidence interventions, and macro level approaches. Barriers and interventions were matched on a web-based tool named INTERVENER, that allows the selection of up to 3 barriers for each step. It displays the visual representation of the selected barriers, the size of each dimension being proportional with the importance of that dimension as a barrier. Experts on different aspects of screening and cancer sites provided feedback on the tool. Collaborators from 41 countries worldwide tested it.ResultsThe tool matched 81 barriers with over 60 interventions. Collaborators reported the webpage to be organized logically (N = 17, 94%) and clearly formatted (N = 15, 83%). The tool was found useful for conducting a situational analysis of the barriers to cancer screening (N = 16, 89%), facilitating discussion with stakeholders on prioritization of interventions (N = 15, 83%), and planning their implementation (N = 15, 83%).ConclusionThis tool supports countries in conducting a systematic assessment of barriers, including their prioritization, and identifying EBI to overcome them, ultimately facilitating reduction of health inequalities. This tool can support governments, policymakers, managers, and healthcare providers to make better informed decisions to improve their cancer screening programmes.

CBX2 promotes cervical cancer cell proliferation and resistance to DNA-damaging treatment via maintaining cancer stemness.

Cervical cancer is the fourth most common malignancy and the fourth leading cause of cancer-related death among women. Advanced stages and resistance to treatment in cervical cancer induce cancer-related deaths. Although epigenetics has been known to plays a vital role in tumor progression and resistance, the function of epigenetic regulators in cervical cancer is an area of investigation. In this study, we focused on an epigenetic regulator, polycomb repressor complex 1 (PRC1) in cervical cancer. Through bioinformatics analysis and immunochemistry, we subsequently identified CBX2, the deregulated subunit of PRC1, which is up-regulated in cervical cancer and associated with poor prognosis and unfavorable clinicopathological characteristics. We provided functional evidence demonstrating that CBX2 promoted cervical cancer cell proliferation. Furthermore, CBX2 exhibited an anti-apoptotic effect, which induced resistance to cisplatin and ionizing radiation in cervical cancer cells. Moreover, CBX2 was involved in maintaining cancer stemness. These findings suggest CBX2 plays an important role in cervical cancer progression and resistance to treatment, and may serve as a potential biomarker for prognosis and resistance as well as a potential therapeutic target.

Role of MRI in Assessing the Feasibility of Fertility-Sparing Treatments for Early-Stage Endometrial and Cervical Cancers.

Fertility-sparing treatment (FST) has become a key aspect of managing gynecologic cancers in reproductive-age patients who wish to preserve fertility. Several leading clinical societies, including the European Society of Gynecological Oncology, the European Society for Radiotherapy and Oncology, the European Society of Pathology, and the European Society of Human Reproduction and Embryology, have recently published evidence-based guidelines on fertility-sparing strategies and posttreatment surveillance of patients with early-stage gynecologic cancers, in particular endometrial and cervical cancers. These guidelines highlight MRI as essential to initial patient selection and follow-up. Properly tailored pelvic MRI protocols and clear MRI reports are key to performing accurate staging, assessing eligibility, and confirming the initial and ongoing feasibility of FST. Accordingly, radiologists, particularly those specializing in gynecologic imaging, play a critical role in the multidisciplinary approach to FST. They should be well-versed in FST eligibility criteria and key MRI finding before and after FST, ensuring these details are comprehensively communicated in structured MRI reports.

Barriers to early diagnosis and treatment of cervical cancer in Addis Ababa, Ethiopia: qualitative study

ObjectiveCervical cancer remains the most diagnosed and deadly cancer among women in low and middle income countries, including Ethiopia, although it can be controlled if detected and treated early. However,...

Advances in human papillomavirus detection for cervical cancer screening and diagnosis: challenges of conventional methods and opportunities for emergent tools.

Human papillomavirus (HPV) infection is the main cause of cervical cancer and other cancers such as anogenital and oropharyngeal cancers. The prevention screening and treatment of cervical cancer has remained one of the top priorities of the World Health Organization (WHO). In 2020, the WHO came up with the 90-70-90 strategy aimed at eliminating cervical cancers as a public health problem by the year 2030. One of the key priorities of this strategy is the recommendation for countries to ensure that 70% of their women are screened using a high-performance test by the age of 35, and again by the age of 45. Over the years, several traditional methods (notably, Pap smear and nucleic acid-based techniques) have been used for the detection of cervical cancer. While these methods have significantly reduced the incidence of cervical cancer and death, they still come short of excellence for the total eradication of HPV infection. The challenges include low sensitivity, low specificity, poor reproducibility, the need for high-level specialists, and the high cost of access to the facilities, to mention a few. Interestingly, however, several efforts are being made today to mitigate these challenges. In this review, we discussed the pros and cons of the traditional screening and testing of HPV infections, the efforts being made to improve their performances, and the emergent tools (especially, the electrochemical methods) that promise to revolutionize the screening and testing of HPV infections. The main aim of the review is to provide some novel clues to researchers that would allow for the development of high-performance, affordable, and triage-suitable electrochemical-based diagnostic tools for HPV and cervical cancer.

Toripalimab combined with bevacizumab plus chemotherapy as first-line treatment for refractory recurrent or metastatic cervical cancer: a single-arm, open-label, phase II study (JS001-ISS-CO214).

To evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC). Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3-28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6-95.3) and the DCR was 95.8% (95% CI=78.9-99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4-34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed. Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative first-line treatment option for patients with R/M CC. ClinicalTrials.gov Identifier: NCT04973904.

Exploration of key pathogenic mechanisms and potential intervention targets of the traditional Chinese medicine Coptis chinensis in the treatment of cervical cancer based on network pharmacology and molecular docking techniques

Exploration of key pathogenic mechanisms and potential intervention targets of the traditional Chinese medicine Coptis chinensis in the treatment of cervical cancer based on network pharmacology and molecular docking techniques

Antiproliferative Activity of New Bis-Thionaphthoquinones in Cervical Cancer

Over the past decades, natural products have been a primary source of anticancer agents. Naphthoquinones, a large class of secondary metabolites, exhibit known anticancer activity. Thionaphthoquinones, which are naphthoquinones with added thiol groups, have demonstrated similar potential to their precursors. Cervical cancer is the third most common and fourth most lethal type of cancer among women worldwide. This study aimed to investigate the antiproliferative activity of new bis-thionaphthoquinones in cervical cancer cells. Five new molecules (D1-D5) were synthesized via multicomponent reaction and characterized by mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate antiproliferative activity in HeLa and NIH3T3 cells. Flow cytometry was employed to analyze deoxyribonucleic acid (DNA) fragmentation. PharmMapper was utilized for target fishing. Among the tested molecules, bis-thionaphthoquinone D4 exhibited the highest potency and selectivity, with a half maximal inhibitory concentration (IC50) of 42.7 μM and a selectivity index of 2.05. Additionally, it also induced DNA fragmentation, suggesting its potential to induce cell death. Carbonic anhydrase II was identified as the most likely target for D4. Therefore, bis-thionaphthoquinone D4 demonstrated both potency and selectivity, making it a promising drug candidate for the treatment of cervical cancer.

Dosimetric differences between online adapt-to-position and offline adapt-to-shape plans for adaptive radiotherapy in cervical cancer

Radiation therapy plays a significant role in the treatment of cervical cancer. Additionally, more adaptive workflows using ATP are being implemented in the daily radiotherapy of our organization. Herein, we aimed to investigate the dosimetric differences between online ATP and offline ATS plans for magnetic resonance (MR)-guided adaptive radiotherapy in patients with cervical cancer and determine radiotherapy modalities that address clinical requirements. In total, 25 patients with cervical cancer were enrolled in this study, with 13 in the radical radiotherapy group and 12 in post-operative radiotherapy group. We aimed for the clinical target volume (CTV) to be covered by 95 – 100% of the prescribed dose (50 Gy/25 sessions/5 weeks). MR-Linac was performed daily during treatment, and the images were rigidly aligned with the local computed tomography to generate an online ATP plan. MR images acquired during the first three sessions were selected to recontour the CTV and organs at risk (OAR). Furthermore, an offline ATS plan was generated. In the radical radiotherapy group, the CTV, D98, D95 (5024.65 ± 23.34 vs. 4995.50 ± 14.99 cGy), and Dmean of the ATS were superior compared with those of the ATP. The Dmax was lower in the ATS plan than in the ATP plan. In the post-operative radiotherapy group, the CTV, Dmean, D98, and D95 (5052.61 ± 67.87 vs. 5014.41 ± 24.68 cGy) were better in the ATS plan than in the ATP plan. When evaluating the OAR in the radical radiotherapy group, the minimum doses to the bladder and rectum were greater in the ATS plan than in the ATP plan. In the post-operative radiotherapy group, the V20 of the bladder and rectum were lower in the ATS plan than in the ATP plan. Therefore, ATS is well suited for post-operative radiotherapy, whereas ATP is better suited for radical radiotherapy. Furthermore, ATP can effectively address the clinical requirements of daily workflows.

Minimally invasive vs. open surgery: comparison of surgical complications in radical hysterectomy for cervical cancer

Cervical cancer remains a significant global health concern, ranking as the third most prevalent malignancy and the second leading cause of cancer-related mortality among women in the United States. Early-stage cervical cancer is typically managed with radical hysterectomy, traditionally performed via open abdominal or vaginal approaches. Minimally invasive radical hysterectomy (MIS-RH) was introduced in 1993, yet findings from the laparoscopic approach to cervical cancer (LACC) trial have raised substantial concerns regarding the oncologic safety of the laparoscopic approach. As a result, abdominal radical hysterectomy (ARH) has been reaffirmed as the standard of care in surgical practice for cervical cancer. Despite this shift, some studies suggest that minimally invasive surgery (MIS), specifically laparoscopic radical hysterectomy (LRH), may be associated with fewer perioperative complications compared to open surgery. However, other studies report no significant differences in complication rates when comparing LRH to ARH. Persistent challenges in adopting MIS for cervical cancer treatment include the complexity of these procedures, extended learning curves, and increased costs. This narrative review provides a comprehensive comparison of LRH and ARH complications, offering insights into their safety, efficacy, and overall benefits to advance the ongoing discussion on optimal surgical approaches for cervical cancer treatment.

LncRNA PGM5-AS1 Impairs the Resistance of Cervical Cancer to Cisplatin by Regulating the Hippo and PI3K-AKT Pathways.

Cisplatin, a platinum-based chemotherapeutic agent, can be used to treat cervical cancer (CC), but cisplatin resistance is increased during the cisplatin treatment. Long non-coding RNA PGM5-AS1 reportedly participates in CC tumorigenesis; however, its role in CC patients with cisplatin resistance has not been revealed. The present aimed to examine the role of PGM5-AS1 in modulating cisplatin resistance in CC. The PGM5-AS1 expression in CC tissues from 29 patients was quantified using quantitative reverse transcription-polymerase chain reaction. The cisplatin-resistant CC cells were constructed by using increasing cisplatin concentrations. The effects of cisplatin resistance interacting with PGM5-AS1 on CC cell malignancy were confirmed by performing Cell Counting Kit 8, colony formation, wound healing, and transwell assays. The key proteins of the Hippo and PI3K-AKT signaling pathways were evaluated by Western blotting. PGM5-AS1 with low expression in CC tissues was correlated to higher International Federation of Gynecology and Obstetrics stage, poor differentiation, lymph node metastasis, and cisplatin resistance. PGM5-AS1 overexpression suppressed the proliferation, migration, and invasion abilities of cisplatin-resistant CC cells. Additionally, PGM5-AS1 overexpression in cisplatin-resistant CC cells could induce the activation of the Hippo signaling pathway and the inactivation of the PI3K-AKT signaling pathway. PGM5-AS1 enhanced the CC cell's sensitivity to cisplatin by activating the Hippo signaling pathway and inactivating the PI3K-AKT signaling pathway. Our study data may provide a novel therapeutic biomarker to overcome cisplatin resistance in CC treatment.

New cheaper human papilloma virus mass screening strategy reduces cervical cancer incidence in Changsha city: A clinical trial

BACKGROUND Cervical cancer is the second leading cause of death in women worldwide, second only to breast cancer. Around 80% of women have been infected with human papillomavirus (HPV) in their lifetime. Early screening and treatment are effective means of preventing cervical cancer, but due to economic reasons, many parts of the world do not have free screening programs to protect women’s health. AIM To increase HPV cervical cancer screening in Changsha and reduce the incidence of cervical cancer. METHODS Cervical cancer screening included gynecological examination, vaginal secretion examination and HPV high-risk typing testing. Cervical cytology examination (ThinPrep cytology test) was performed for individuals who test positive for HPV types other than 16 and 18. Vaginal colposcopy examination was performed for HPV16 and 18 positive individuals, as well as for those who were positive for ThinPrep cytology test. If the results of vaginal colposcopy examination were abnormal, histopathological examination was performed. We conducted a cost-benefit analysis after 4 years. RESULTS From 2019 to 2022, 523437 women aged 35-64 years in Changsha city were screened and 73313 were positive, with a 14% positive rate. The detection rate of precancerous lesions of cervical cancer was 0.6% and the detection rate of cervical cancer was 0.037%. Among 311212 patients who underwent two cancers examinations, the incidence rate was reduced by more than half in the second examination. The average screening cost per woman was 120 RMB. The average cost of detecting early cases was 10619 RMB, with an early detection cost coefficient of 0.083. CONCLUSION Our screening strategy was effective and cost-effective, making it valuable for early diagnosis and treatment of cervical cancer. It is worth promoting in economically limited areas.

Efficacy and safety of camrelizumab for the treatment of cervical cancer: a systematic review and meta-analysis.

Cervical cancer (CC) is a prevalent malignancy in women and ranks fourth in global cancer-related mortality. The prognosis for women with metastatic or recurring cervical cancer is unfavorable. Camrelizumab is a humanized high-affinity IgG4-kappa monoclonal antibody targeting programmed cell death 1 (PD-1), which has been progressively documented as a therapy for advanced cervical cancer with good result metrics. Nonetheless, a comprehensive investigation of Camrelizumab's efficacy in treating cervical cancer has yet to be conducted. We conducted a search across PubMed, Ovid Medline, Embase, Web of Science, Cochrane Library, Scopus, ProQuest, CNKI, Wan Fang, VIP database, and CBMdisc, restricting the establishment date of the databases to October 2024. The ROBINS-I Scale was utilized to evaluate the methodological quality of the included studies. Furthermore, information about CR, PR, SD, PD, ORR, DCR, median OS, median PFS, adverse events (AEs), and other relevant data was obtained. A meta-analysis was performed utilizing a random-effects model and effect size for illness. This meta-analysis included six trials, including 238 people with CC. The aggregated outcomes for patients were as follows: CR (0.097, 95% CI: 0.032-0.186), PR (0.465, 95% CI: 0.291-0.638), SD (0.264, 95% CI: 0.124-0.403), PD (0.174, 95% CI: 0.051-0.296), ORR (0.577, 95% CI: 0.354-0.799), DCR (0.784, 95% CI: 0.652-0.916), AEs (all grades: 0.836, 95% CI: 0.629-1.000, ≥grade III: 0.472, 95% CI: 0.111-0.834). The predominant treatment-related adverse events included anemia (≤grade II: 0.295, 95% CI: 0.187-0.402; ≥grade III: 0.124, 95% CI: 0.018-0.230), elevated aspartate aminotransferase (≤grade II: 0.196, 95% CI: 0.013-0.380; ≥grade III: 0.030, 95% CI: 0.007-0.053), neutropenia (≤grade II: 0.206, 95% CI: 0.150-0.261; ≥grade III: 0.114, 95% CI: 0.066-0.162), thrombocytopenia (≤grade II: 0.295, 95% CI: 0.187-0.402), and fatigue (≤grade II: 0.174, 95% CI: 0.046-0.303). This meta-analysis demonstrates that camrelizumab is efficacious and well-tolerated in patients with cervical cancer. https://www.crd.york.ac.uk/prospero/, identifier CRD42024527065.

Expression profile of cellular microRNAs and their potential role in cervical cancer

Background. Cervical cancer (CC) is the fourth leading cause of cancer-related morbidity and mortality among women. Despite the established etiologic factor of cervical cancer, especially high-risk human papillomavirus (HPV, human papillomavirus) and available vaccine prophylaxis, the issue persists both in understanding the mechanism of HPV-associated carcinogenesis and in developing new approaches for diagnosis and treatment of cervical cancer. Epigenetic regulation of gene expression by means of microRNAs plays an important role in the pathogenesis of cervical cancer. Therefore, the search for new differentially expressed microRNAs in order to reveal new mechanisms of HPV-associated transformation of tumor cells is of high priority. AIM: To explore microRNAs with differentiated expression in the cervical cancer tissue and to assess the functional potential of their detection in silico. MATERIALS AND METHODS: The spectrum of microRNAs characterizing by modified expression in the tumor tissue of HPV16-positive squamous cell carcinomas of the cervix was determined using NGS sequencing (Next Generation Sequencing) of tumor tissue and of apparently unchanged adjacent epithelium obtained with the use of microdissection. Potential target genes of the investigated microRNAs were identified using MirTargetLink, Tarbase v9.0, and LinkedOmics services. Gene Set Enrichment Analysis was performed using Metascape. The relations between the level of microRNA expression and clinical SCC features (according to TCGA data, CESC sample) were searched using USCS Xena service. RESULTS: NGS-sequencing of paired HPV16-positive specimens of tumor tissue and normal cervical tissue resulted in the identification of 42 differentially expressed microRNAs. Specifically, the levels of 22 microRNAs in the tumor tissue were higher than in the apparently normal adjacent epithelium, while 20 microRNAs demonstrated lower levels in the tumor specimens. Analysis of the potential targets of significant microRNAs revealed multiple functional gene categories, potentially involved in carcinogenesis as well as an association with clinical features. We showed that increased expression levels of microRNA-20b in the tumor tissue correlated with the risk of distant metastases, whereas the lower levels of microRNA-218-1 and microRNA -218-2 were associated with unfavorable prognosis of disease. With regard to microRNA-363, -615, and -769, their increase in cervical cancer was described for the first time, and the potential targets and signaling pathways associated with THEIR EXPRESSION LEVELS WERE IDENTIFIED. CONCLUSION: The search for differentially expressed microRNAs in cervical cancer has revealed a spectrum of microRNAs with potentially important role in the process of malignant transformation and persistence of tumor phenotype. In addition to microRNAs demonstrating functional characteristics described in the world literature, we found microRNAs that play an unknown role in cervical cancer. In this relation, the potentially relevant targets were identified that could be helpful in understanding the mechanisms of carcinogenesis. The data obtained may form the basis for the development of new approaches to the diagnosis and therapy of SCC.

Qiu's Cervical Prescription inhibit the invasion and growth of cervical cancer through LncRNA ATB/miR-126 pathway.

Cervical cancer (CC) is one of the most deadly cancers in women, its current treatments still result in poor outcomes and developing the novel targets and therapeutic strategies are urgently needed. Qiu's Cervical Prescription (QCP) is one of the traditional Chinese medicines used in the treatment of cervical cancer in China. Although its curative effect is remarkable, the internal mechanism of its treatment is still poorly understood. Recent studies have shown that LncRNA ATB might be used as a new proliferation marker for cancer diagnosis and prognosis. This study aimed to investigate the possible mechanism of action of QCP in the treatment of cervical cancer. The functional assays of migration and invasion in vitro using transwell assays and wound healing assays was performed to confirm the pro-carcinogenic effect of LncRNA ATB, and the changes of migration and invasion of HeLa cells were observed after treatment with QCP containing drug serum. The changes in tumor volume, general condition of transplanted tumor-bearing mice and expression of LncRNA ATB pathway-related proteins were detected by qPCR, Western blotting and HE staining after treatment with the QCP. We induced LncRNA ATB knockdown and overexpression in cervical cancer cell lines and detected the biological behavior changes in vitro. Furthermore, we established murine models using stable LncRNA ATB-shRNA HeLa cells or overexpression LncRNA ATB cells or normal Hela cells with QCP to evaluate how suppression of LncRNA ATB affects tumor growth. We showed that potential mechanism of QCP in the treatment of cervical cancer may be through inhibition of the LncRNA ATB/miR-126/TGFβ1 signaling axis. In conclusion, QCP may be a promising approach for the treatment of CC.