Cervical Cancer Therapy Research Articles

Designing a Novel Multiepitope Vaccine from the Human Papilloma Virus E1 and E2 Proteins for Indonesia with Immunoinformatics and Molecular Dynamics Approaches.

One of the deadliest malignant cancer in women globally is cervical cancer. Specifically, cervical cancer is the second most common type of cancer in Indonesia. The main infectious agent of cervical cancer is the human papilloma virus (HPV). Although licensed prophylactic vaccines are available, cervical cancer cases are on the rise. Therapy using multiepitope-based vaccines is a very promising therapy for cervical cancer. This study aimed to develop a multiepitope vaccine based on the E1 and E2 proteins of HPV 16, 18, 45, and 52 using in silico. In this study, we develop a novel multiepitope vaccine candidate using an immunoinformatic approach. We predicted the epitopes of the cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) and evaluated their immunogenic properties. Population coverage analysis of qualified epitopes was conducted to determine the successful use of the vaccine worldwide. The epitopes were constructed into a multiepitope vaccine by using AAY linkers between the CTL epitopes and GPGPG linkers between the HTL epitopes. The tertiary structure of the multiepitope vaccine was modeled with AlphaFold and was evaluated by Prosa-web. The results of vaccine construction were analyzed for B-cell epitope prediction, molecular docking with Toll like receptor-4 (TLR4), and molecular dynamics simulation. The results of epitope prediction obtained 4 CTL epitopes and 7 HTL epitopes that are eligible for construction of multiepitope vaccines. Prediction of the physicochemical properties of multiepitope vaccines obtained good results for recombinant protein production. The interaction showed that the interaction of the multiepitope vaccine-TLR4 complex is stable based on the binding free energy value -106.5 kcal/mol. The results of the immune response simulation show that multiepitope vaccine candidates could activate the adaptive and humoral immune systems and generate long-term B-cell memory. According to these results, the development of a multiepitope vaccine with a reverse vaccinology approach is a breakthrough to develop potential cervical cancer therapeutic vaccines.

Prediction of radiation complications by determining the blood oxidation processes in cervical cancer patients under chemoradiotherapy

Background. Radiotherapy (RT) is one of the principal methods in cancer management, and its administration in oncology practice is much wider nowadays because of the increased incidence of newly diagnosed cancer cases with wide spread and aggressive course of tumor process, and also in view of organ-sparing strategies in the combined treatment. However, the radiation reactions, especially local ones in rectum or bladder, can’t be completely avoided even using the most advanced radiotherapy facilities and dosimetry planning. Therefore, at present time not only technical modernization, but also the progress in radiobiology should be considered. Given the cytotoxic properties of some anticancer drugs, they are used in the combined therapy of cervical cancer (CC) to receive a radiosensitizing effect on the malignant cells. In particular, cisplatin inhibits reparative processes by affecting the enzymes involved in restoring the integrity of DNA or chromosome structure. Administration of the combined radiation and chemotherapy leads not only to an increase in the percentage of tumor regression, but also to an increase in the number of radiation injuries to healthy tissues. Therefore, prediction of such injuries, research and development of means of their prevention and treatment in the regimen of chemoradiotherapy (ChRT) of CC is extremely urgent and remains an unsolved problem to date. Purpose. Development of personalized approaches in ChRT in CC patients by studying its efficiency, assessing its toxicity, and predicting radiation injuries according to the data of blood oxidative processes in patients. Materials and methods. The combined radiotherapy (CRT) and ChRT were administered to the stage IIB–IIIB CC (T2b-3bN0-1M0) patients (n = 105) at the National Cancer Institute. Patients aged 25–75 years were divided into two groups: the study group and the comparison group. Complex clinical examination was conducted prior to treatment featuring the assay of tumor parameters, state of «critical organs». At the stage I of CRT regimen, conformal irradiation on pelvis minor was delivered at the electron linear accelerator «Clinac 2100 CD» with an energy of 6 MeV per area of pelvis minor with single radiation dose (SRD) of 2.0 Gy and total radiation dose (TRD) of up to 46 Gy. Patients in the study group received the CRT along with administration of chemoradiomodifying agent cisplatin 40 mg/m2 once a week intravenously (drip-feed), patients in the comparison group received no radiomodifier. At the stage II of CRT regimen, an intracavitary brachytherapy (ICBT) was administered to the CC patients at the gamma therapy equipment «AGAT-VU» using 60Co (high dose rate – HDR) sources in the mode of SRD of 5 Gy 2 times a week, 7–8 fractions, and TRD of 35–40 Gy at p. A. The TRD in total was 77–89 Gy at the p. A and 54–60 Gy at p. B. Administration of cisplatin 40 mg/m2 at the stage II of CRT was continued in the study group once a week intravenously (drip-feed), total dose of up to 200–300 mg. Radiobiological studies were performed on the peripheral blood samples from the CC patients (n = 39) before and after ChRT. The control group consisted of healthy women of the appropriate age. Blood was sampled into the special 6 ml Vacutainer type tubes with an anticoagulant according to the manufacturer’s instructions (BioReagent). Intensity of generation of О• 2– in PBL was evaluated by the chemiluminescence method using the lucigenin indicator, which, as a result of reacting with О• 2–, emits light quanta recorded by the device. Measurements were carried out on the AutoLumat LB 953 device (Germany) with appropriate corrections made to the methodology. Results and discussion. Effectiveness of CRT in CC patients was evaluated according to regression of the primary tumor focus (clinical, ultrasound, MRI or SCT data) and presence/absence of toxic manifestations of treatment following the criteria for evaluating the solid tumors regression according to the Response Evaluation Criteria in Solid Tumor (RECIST). Conclusions. The results of the study indicate that chemoradiotherapy contributes to pronounced regression of cervical tumors and does not increase toxicity of treatment due to timely correction of complications.

Teknik Terapi Radiasi 3DCRT Pada Kasus Kanker Serviks Dengan Studi Literatur

Research with literature studies is still rarely carried out, therefore in this article we want to know about the External Radiation Radiotherapy Technique in Cervical Cancer Cases with 3D-CRT (3-Dimensional Conformal Radiation Therapy): This literature discusses the application of the 3D-CRT external radiation radiotherapy technique in treatment cervical cancer. 3D-CRT is a method that allows external radiation exposure from more than one side,possiblemore appropriate radiation dose according to the shape and location of the tumor. This study also lists other techniques such as Brachytherapy, IMRT, and 2D in the treatment of cervical cancer. Photon Dose Distribution Using 3D-CRT and IMRT Techniques in Cervical Cancer Therapy: This research discusses photon dose distribution in the Treatment Planning System (TPS) using 3DCRT and IMRT techniques for cervical cancer therapy. This provides insight into the comparison between the two techniques in delivering appropriate radiation doses to the tumor target. 6 MV Energy Linac Radiotherapy Against Cervical Cancer: This journal discusses the use of radiotherapy on a Linac aircraft with a 6 MV energy photon beam using the 3DCRT technique in the treatment of cervical cancer. This technique helps deliver the right dose of radiation according to the target area. The literature above provides information about external radiotherapy techniques, including 3D-CRT, in the treatment of cervical cancer. They help understand the role and application of this technique in cervical cancer treatment.

Cervical Cancer Treatment Update: A Society of Gynecologic Oncology Clinical Practice Statement

ABSTRACT Despite increased screening and human papillomavirus (HPV) vaccination in high-income countries, cervical cancer represents the fourth most diagnosed cancer in women worldwide and the second highest cause of cancer mortality among women in low- and middle-income countries. This clinical practice statement describes therapies for cervical cancer by treatment setting, as well as quality of life, financial toxicity, and disparities associated with the disease. Persistent HPV infection, particularly types 16 and 18, are the main factor in the development of cervical cancer. High-risk HPV variants integrate HPV DNA into the host genome to upregulate two viral oncoproteins, E6 and E7, which in turn inhibit the tumor suppressor proteins p53 and Rb. Certain driver mutations including PIK3CA, KRAS, and EGFR are frequently seen in cervical cancer, however further research is needed to identify an actionable biomarker based on targetable oncogenic alterations. Locally advanced cervical cancer is defined as clinically visible tumor exceeding 4 cm or invading beyond the cervix, extending to the pelvic sidewalls, vagina, bladder, rectum, or involving pelvic and/or paraaortic lymph nodes. Standard treatment for locally advanced cervical cancer is external beam radiation therapy and concurrent weekly cisplatin. Standard treatment for advanced, recurrent, or metastatic cervical cancer is cisplatin, paclitaxel, and bevacizumab (possibly adding pembrolizumab). Several studies have shown that checkpoint inhibitors, when combined or sequenced with chemoradiation, may provide survival benefit in both locally advanced and recurrent/metastatic cervical cancer. Given these findings, immunotherapy should be incorporated in treatment of advanced or recurrent disease. Negative effects on quality of life (QOL) in patients with cervical cancer often begin in people who receive negative Papanicolaou test results or positive HPV DNA tests. Negative body image, self-esteem, and relationships with partners contribute to an overall decrease in QoL. Surgical, radiation-induced, and chemotherapy-induced treatment effects further impact survivors’ physical health, body-image, and sexual function. Economic burdens of cancer diagnosis and treatment may disproportionally affect cervical cancer patients due to the intensity of curative treatment, decreases in QoL and functional status, and unique population including younger patients, those with poor access to health care at baseline, and those who identify as racial or ethnic minorities.

Advanced detection of cervical cancer biomarkers using engineered filamentous phage nanofibers.

Cervical cancer is a major global health concern, characterized by its high incidence and mortality rates. The detection of tumor markers is crucial for managing cancer, making treatment decisions, and monitoring disease progression. Vascular endothelial growth factor (VEGF) and programmed death-ligand 1 (PDL-1) are key targets in cervical cancer therapy and valuable biomarkers in predicting treatment response and prognosis. In this study, we found that combining the measurement of VEGF and soluble PDL-1 can be used for diagnosing and evaluating the progression of cervical cancer. To explore a more convenient approach for detecting and assessing cervical cancer, we designed and prepared an engineered fd bacteriophage, a human-safe viral nanofiber, equipped with two peptides targeting VEGF and PD-L1. The dual-display phage nanofiber specifically recognizes and binds to both proteins. Utilizing this nanofiber as a novel capture agent, we developed a new enzyme-linked immunosorbent assay (ELISA) method. This method shows significantly enhanced detection sensitivity compared to conventional ELISA methods, which use either anti-VEGF or anti-PD-L1 antibodies as capture agents. Therefore, the phage dual-display nanofiber presents significant potential in detecting cancer markers, evaluating medication efficacy, and advancing immunotherapy drug development. KEY POINTS: • The combined measurement of VEGF and soluble Programmed Death-Ligand 1(sPD-L1) demonstrates an additive effect in the diagnosis of cervical cancer. Fd phage nanofibers have been ingeniously engineered to display peptides that bind to VEGF and PD-L1, enabling the simultaneous detection of both proteins within a single assay • Genetically engineered phage nanofibers, adorned with two distinct peptides, can be utilized for the diagnosis and prognosis of cancer and can be mass-produced cost-effectively through bacterial infections • Employing dual-display fd phage nanofibers as capture probes, the phage ELISA method exhibited significantly enhanced detection sensitivity compared to traditional sandwich ELISA. Furthermore, phage ELISA facilitates the detection of a single protein or the simultaneous detection of multiple proteins, rendering them powerful tools for protein analysis and diagnosis across various fields, including cancer research.

Analysis of the current state of cervical cancer prevention awareness and its influencing factors among rural women in Luohe City.

The purpose of this cross-sectional study was to identify the current awareness about cervical cancer prevention among rural women in Luohe City as well as its potential influencing factors. Meanwhile, these data were expected to provide a theoretical basis for Luohe future cervical cancer prevention and therapy. Based on geographical distribution, 40 villages in Luohe City were randomly selected, and questionnaires were given to women in each village. In this study, a total of 4665 questionnaires were distributed, and 4561 valid questionnaires were returned, with a recovery rate of 97.98%. The average score was 4.06 ± 2.46 out of 10. It was found that women had a high awareness rate of cervical cancer screening (55.25%) but a low awareness rate of human papillomavirus (HPV) and HPV vaccine (10.17%). Moreover, univariate and multivariable analyses showed that age > 45 years, low household income, low education level, being a farmer, spouse unemployment, no pregnancy or birth delivery history, no family or personal history of cervical disease, and no previous complimentary 2-cancer screening (i.e., breast cancer and cervical cancer) were all factors influencing the cognitive level of rural women in Luohe City (P < .05). However, ethnicity, marital status, and spouse education level were not correlated with cognitive level (P > .05). In conclusion, low awareness of cervical cancer prevention among rural women in Luohe was correlated with individual, family, and social factors. So it was recommended to cultivate the rural population knowledge, optimize screening strategies, and conduct targeted cervical cancer prevention and treatment in rural regions.

Gold nanoparticles (AuNPs) decrease the viability of cervical cancer cells by inducing the BAX gene and activating antioxidant enzymes.

Cervical Cancer (CC), a leading cause of female mortality worldwide, demonstrates a direct association with high-risk human papillomavirus (HPV) infections. However, not all CC patients exhibit HPV infection, suggesting additional predisposing factors. Recently, disturbances in the oxidant-antioxidant balance have been implicated in CC development. This study explores the impact of gold nanoparticles (AuNPs) on the survival and antioxidant capacity of HeLa cells, aiming to contribute to novel CC therapy approaches. Synthesized and characterized AuNPs (25.5nm, uniform distribution according to the DLS analysis) were administered to HeLa cells at varying concentrations. After 24h, cell viability was assessed using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) (MTT) assay. Real-time PCR measured expression levels of apoptosis-related genes (BCL2 associated X (BAX) and p53). Catalase and superoxide dismutase (SOD) activities, key antioxidant enzymes, were also evaluated post-AuNP treatment. AuNPs dose-dependently reduced HeLa cell viability, with an IC50 value of 113µg/ml. BAX gene expression significantly increased, indicating pro-apoptotic effects. Moreover, enzyme activities significantly rose under AuNP influence. AuNPs demonstrated the potential to induce HeLa cell death by upregulating pro-apoptotic BAX gene expression and altering antioxidant system enzyme activities. These findings underscore the promise of AuNPs as a therapeutic avenue for CC, emphasizing their impact on crucial cellular processes involved in cancer progression.

Predicting the recurrence of usual-type cervical adenocarcinoma using a nomogram based on clinical and pathological factors: a retrospective observational study.

Usual-type cervical adenocarcinoma is the most frequent type of adenocarcinoma, and its prevalence is increasing worldwide. Tumor recurrence is the leading cause of mortality; therefore, recognizing the risk factors for cervical cancer recurrence and providing effective therapy for recurrent cervical cancer are critical steps in increasing patient survival rates. This study aimed to retrospectively analyze the clinicopathological data of patients with usual-type cervical adenocarcinoma by combining the diagnosis and treatment records after the initial treatment and recurrence. We retrospectively analyzed patients diagnosed with usual-type cervical adenocarcinoma who underwent radical hysterectomy and pelvic lymph node dissection at Shengjing Hospital of China Medical University between June 2013 and June 2022. We constructed a nomogram-based postoperative recurrence prediction model, internally evaluated its efficacy, and performed internal validation. This study included 395 participants, including 87 individuals with recurrence. At a 7:3 ratio, the 395 patients were divided into two groups: a training set (n = 276) and a validation set (n = 119). The training set was subjected to univariate analysis, and the risk variables for recurrence included smoking, ovarian metastasis, International Federation of Gynaecology and Obstetrics (FIGO) staging, lymphovascular space invasion, perineural invasion, depth of muscular invasion, tumor size, lymph node metastasis, and postoperative HPV infection months. The aforementioned components were analyzed using logistic regression analysis, and the results showed that the postoperative HPV infection month, tumor size, perineural invasion, and FIGO stage were independent risk factors for postoperative recurrence (p<0.05). The aforementioned model was represented as a nomogram. The training and validation set consistency indices, calculated using the bootstrap method of internal validation, were 0.88 and 0.86, respectively. The model constructed in this study predicted the postoperative recurrence of usual-type cervical cancer, as indicated by the receiver operating characteristic curve. The model demonstrated good performance, as evidenced by the area under the curve, sensitivity, and specificity values of 0.90, 0.859, and 0.844, respectively. Based on the FIGO staging, peripheral nerve invasion, tumor size, and months of postoperative HPV infection, the predictive model and nomogram for postoperative recurrence of usual-type cervical adenocarcinoma are precise and effective. More extensive stratified evaluations of the risk of cervical adenocarcinoma recurrence are still required, as is a thorough assessment of postoperative recurrence in the future.

RACK1 promotes the occurrence and progression of cervical carcinoma.

RACK1 has been identified as a multifunctional cytosolic protein, and plays a pivotal role in multiple biological responses involved in several kinds of tumors, while its effect in cervical cancer has not been well elucidated yet. The study aimed to investigate the role of RACK1 in cervical cancer occurrence and progression. The expression of RACK1 in cervical specimens was measured by immunohistochemical staining and Western blot assay. Transgenic mice were used to detect the role of RACK1 in modulating tumorigenesis invivo. Cervical carcinoma cell lines were used to explore the underlying mechanisms of RACK1 on the behaviors of tumor cells invitro. We found that RACK1 expression was upregulated in cancer tissues compared with adjacent tissues, and its expression was gradually increased from cervictis, and cervical intraepithelial neoplasis (CIN) to carcinoma. Genetic overexpression of RACK1 facilitated tumor formation and growth in nude mice. Mechanism studies disclosed that RACK1 over-expression prolonged the G0 /G1 phase by up-regulating the expression of cyclinD1, down-regulating p21 and p27 probably by modulating the phosphorylation of AKT. Taken together, we concluded that RACK1 stimulates tumorigenesis and progression of cervical cancer via modulating the proliferation of tumor cells, implying that targeting RACK1 may serve as a promising method for cervical cancer therapy.

Unveiling diagnostic and therapeutic strategies for cervical cancer: biomarker discovery through proteomics approaches and exploring the role of cervical cancer stem cells.

Cervical cancer (CC) is a major global health problem and leading cause of cancer deaths among women worldwide. Early detection through screening programs has reduced mortality; however, screening compliance remains low. Identifying non-invasive biomarkers through proteomics for diagnosis and monitoring response to treatment could improve patient outcomes. Here we review recent proteomics studies which have uncovered biomarkers and potential drug targets for CC. Additionally, we explore into the role of cervical cancer stem cells and their potential implications in driving CC progression and therapy resistance. Although challenges remain, proteomics has the potential to revolutionize the field of cervical cancer research and improve patient outcomes.

Vaccination and modern therapy of cervical cancer

Cervical cancer is the fourth most common cancer in women worldwide and is responsible for over 300 thousand deaths worldwide. The causative agent of cervical cancer is persistent infection with high-risk human papillomavirus subtypes, and viral oncoproteins E 5, E 6, and E 7 interact with human factors to induce and maintain a malignant phenotype. This review describes the mechanisms behind the onset and development of cervical cancer and discusses in detail promising and effective new treatment options for cervical cancer, including immunotherapy, targeted therapy and combination therapy.

Hemophagocytic lymphohistiocytosis following pembrolizumab and bevacizumab combination therapy for cervical cancer: a case report and systematic review

BackgroundProgrammed cell death protein 1 (PD-1) checkpoint inhibitors such as pembrolizumab are novel therapeutics used to treat various advanced malignancies. Immune-related adverse events are common, among the most serious of these toxicities is hemophagocytic lymphohistiocytosis (HLH), which is a life-threatening disorder of unbridled immune activation but has not been properly established.MethodsWe have procured the first case of hemophagocytic lymphohistiocytosis as an aftermath of treatment with pembrolizumab from the Sir Run Run Shaw Hospital, Zhejiang University, China. In a pursuit to enhance the understanding of this condition, a comprehensive systematic review was performed encompassing all reported instances of ICI-associated Hemophagocytic lymphohistiocytosis within the realms of PubMed and Embase databases.ResultsWe detail the recovery of a cervical cancer patient with a history of psoriasis who developed HLH after combined pembrolizumab and bevacizumab treatment. Remarkably, tumor lesions exhibited substantial and sustained regression. From an analysis of 52 identified Immune Checkpoint Inhibitor (ICI)-related HLH cases, we discovered that HLH often occurred within the first two treatment cycles and approximately 20% of these patients had a history of autoimmune-related diseases. Despite a 15% mortality rate, the majority of patients experienced positive outcomes. Notably, in instances of recovery from HLH, 80% showed positive tumor outcomes. Even after discontinuation of ICI treatment, tumor control persisted in some cases.ConclusionWe identified the first case of HLH caused by ICI treatment in cervical cancer and summarized the possible occurrence factors of these cases, the treatment outcomes of HLH, and the impact on tumor outcomes.

Improving prediction of cervical cancer using KNN imputer and multi-model ensemble learning.

Cervical cancer is a leading cause of women's mortality, emphasizing the need for early diagnosis and effective treatment. In line with the imperative of early intervention, the automated identification of cervical cancer has emerged as a promising avenue, leveraging machine learning techniques to enhance both the speed and accuracy of diagnosis. However, an inherent challenge in the development of these automated systems is the presence of missing values in the datasets commonly used for cervical cancer detection. Missing data can significantly impact the performance of machine learning models, potentially leading to inaccurate or unreliable results. This study addresses a critical challenge in automated cervical cancer identification-handling missing data in datasets. The study present a novel approach that combines three machine learning models into a stacked ensemble voting classifier, complemented by the use of a KNN Imputer to manage missing values. The proposed model achieves remarkable results with an accuracy of 0.9941, precision of 0.98, recall of 0.96, and an F1 score of 0.97. This study examines three distinct scenarios: one involving the deletion of missing values, another utilizing KNN imputation, and a third employing PCA for imputing missing values. This research has significant implications for the medical field, offering medical experts a powerful tool for more accurate cervical cancer therapy and enhancing the overall effectiveness of testing procedures. By addressing missing data challenges and achieving high accuracy, this work represents a valuable contribution to cervical cancer detection, ultimately aiming to reduce the impact of this disease on women's health and healthcare systems.

Evolving standards and future directions for systemic therapies in cervical cancer.

Several groundbreaking clinical trials with the potential to transform the management paradigm of both locally advanced and persistent, recurrent, or metastatic cervical cancers have been presented in 2023. This review describes the reported data from INTERLACE and KEYNOTE-A18 in the locally advanced setting, as well as BEATcc, innovaTV 301 and DESTINY-PanTumor02 for advanced disease. The practice implications of their positive results are interpreted in the context of global health considerations, and updated treatment algorithms are proposed. Furthermore, emerging trends in drug development for cervical cancer are discussed. As the routine use of immune checkpoint inhibitors (ICIs) for curative and palliative indications increases in the foreseeable future, patients whose cervical cancers which persist, relapse or progress after prior ICI exposure will represent an area of unmet clinical need and form the key target population for next-generation trials. Future research will help shape oncologists' approaches in the optimal selection, sequencing and re-treatment or rechallenge of immuno-oncology agents and/or antibody-drug conjugates in women with cervical cancer.

Retinoids: Molecular Aspects and Treatment in Premalignant Lesions and Cervical Cancer.

Persistent infection with high-risk human papillomavirus remains the primary factor associated with the progression of cervical squamous intraepithelial lesions and the development of cervical cancer. Nevertheless, a combination of factors, including genetic predisposition, immune response, hormonal influences, and nutritional status, contribute synergistically to the development of cervical cancer. Among the various factors involved in the pathogenesis and therapy of cervical cancer, retinoids have gained considerable attention due to their multifaceted roles in different cellular processes. This review investigates defects within the vitamin A metabolism pathway and their correlation with cervical cancer. Additionally, it integrates epidemiological and experimental findings to discuss the potential utility of retinoid-based therapies, either alone or combined with other therapies, as agents against premalignant lesions and cervical cancer.

CAFs-derived exosomes promote the development of cervical cancer by regulating miR-18a-5p-TMEM170B signaling axis

Mounting studies have showed that tumor microenvironment (TME) is crucial for cervical cancer (CC), and cancer-related fibroblasts (CAFs) play a major role in it. Recently, exosomal miRNAs secreted by CAFs have been found to be potential targets for cancer diagnosis and therapy. In this paper, we aimed to investigate the function of CAFs-mediated exosome miR-18a-5p (CAFs-exo-miR-18a-5p) in CC. First, in combination with bioinformatic data analysis of the GEO database (GSE86100) and RT-qPCR of CC clinical tissue samples and cell lines, miR-18a-5p was discovered to be markedly up-regulated in CC. Next, CAFs-secreted exosomes were isolated and it was found that miR-18a-5p expression was dramatically promoted in CC cell lines when treated with CAFs-exos. The CAFs-exo-miR-18a-5p was then elucidated to stimulate the proliferation and migration and inhibit the apoptosis of CC cells. In order to clarify the underlying mechanism, we further screened the target genes of miR-18a-5p. TMEM170B was selected by bioinformatic data analysis of online databases combined with RT-qPCR of CC clinical tissues and cells. Luciferase reporter gene analysis combined with molecular biology experiments further elucidated that miR-18a-5p suppressed TMEM170B expression in CC. Finally, both cell and animal experiments demonstrated that TMEM170B over-expression attenuated the oncogenic effect of CAFs-exo-miR-18a-5p. In conclusion, our study indicates that CAFs-mediated exosome miR-18a-5p promotes the initiation and development of CC by suppressing TMEM170B signaling axis, which provides a possible direction for the diagnosis and therapy of CC.

LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis.

At present, the role of many long non-coding RNAs (lncRNAs) as tumor suppressors in the formation and development of cervical cancer (CC) has been studied. However, lncRNA prostate cancer gene expression marker 1 (PCGEM1), whose high expression not only aggravates ovarian cancer but also can induce tumorigenesis and endometrial cancer progression, has not been studied in CC. The objective of this study was to investigate the expression and the underlying role of PCGEM1 in CC. The relative expression of PCGEM1 in CC cells was detected by real-time PCR. After the suppression of PCGEM1 expression by shRNA, the changes in the proliferation, migration, and invasion capacities were detected via CCK-8 assay, EdU assay, and colony formation assay wound healing assay. Transwell assay and the changes in expressions of epithelial-to-mesenchymal transition (EMT) markers were determined by western blot and immunofluorescence. The interplay among PCGEM1, miR-642a-5p, and kinesin family member 5B (KIF5B) was confirmed by bioinformatics analyses and luciferase reporter assay. Results showed that PCGEM1 expressions were up-regulated within CC cells. Cell viabilities, migration, and invasion were remarkably reduced after the suppression of PCGEM1 expression by shRNA in Hela and SiHa cells. N-cadherin was silenced, but E-cadherin expression was elevated by sh-PCGEM1. Moreover, by sponging miR-642a-5p in CC, PCGEM1 was verified as a competitive endogenous RNA (ceRNA) that modulates KIF5B levels. MiR-642a-5p down-regulation partially rescued sh-PCGEM1's inhibitory effects on cell proliferation, migration, invasion, and EMT process. In conclusion, the PCGEM1/miR-642a-5p/KIF5B signaling axis might be a novel therapeutic target in CC. This study provides a research basis and new direction for targeted therapy of CC.

(Nano)biotechnological approaches in the treatment of cervical cancer: integration of engineering and biology.

Cervical cancer is one of the most malignant gynaecological tumors characterised with the aggressive behaviour of the tumor cells. In spite of the development of different strategies for the treatment of cervical cancer, the tumor cells have developed resistance to conventional therapeutics. On the other hand, nanoparticles have been recently applied for the treatment of human cancers through delivery of drugs and facilitate tumor suppression. The stimuli-sensitive nanostructures can improve the release of therapeutics at the tumor site. In the present review, the nanostructures for the treatment of cervical cancer are discussed. Nanostructures can deliver both chemotherapy drugs and natural compounds to increase anti-cancer activity and prevent drug resistance in cervical tumor. Moreover, the genetic tools such as siRNA can be delivered by nanoparticles to enhance their accumulation at tumor site. In order to enhance selectivity, the stimuli-responsive nanoparticles such as pH- and redox-responsive nanocarriers have been developed to suppress cervical tumor. Moreover, nanoparticles can induce photo-thermal and photodynamic therapy to accelerate cell death in cervical tumor. In addition, nanobiotechnology demonstrates tremendous potential in the treatment of cervical cancer, especially in the context of tumor immunotherapy. Overall, metal-, carbon-, lipid- and polymer-based nanostructures have been utilized in cervical cancer therapy. Finally, hydrogels have been developed as novel kinds of carriers to encapsulate therapeutics and improve anti-cancer activity.

Inhibition of Wnt/β-catenin signaling by monensin in cervical cancer.

The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.

Cytotoxic and Anti-Cervical Cancer Effects of the Camellia sinensis Byproducts from Various Kenyan Factories

Cervical cancer is a significant global health challenge and necessitates the search for innovative and patient-friendly therapies due to the limitations and challenges posed by conventional treatments. This study explored the largely overlooked potential of Camellia sinensis processing wastes as a natural source for developing effective and safe anticancer compounds. Tea waste samples from Kenyan processing facilities demonstrated concentration-dependent cytotoxic effects on normal epithelial cells (Vero), with the fluff sample from Chelal displaying superior efficacy. Median inhibitory concentration (IC50) values highlighted the potency of the samples, especially the fluff sample from Chelal (IC50: 483.99µg/ml). Selectivity indices revealed favorable safety profiles, indicating selective potential anticancer effects against cervical cancer cells. This study contributes substantively to understanding tea waste’s anticancer potential, providing valuable insights for drug development. The study offers a foundation for continued research into sustainable and impactful anticancer drug discovery, emphasizing specific results that pinpoint promising tea waste samples and their potential applications in cervical cancer therapy and anticancer drug development.