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Probiotics and Antimicrobial Proteins Jun 2024To study how indigenous or probiotic-introduced lactobacilli affect the sensitivity (estimated as the proportion of surviving, apoptotic, and nonapoptotic deaths) of...
To study how indigenous or probiotic-introduced lactobacilli affect the sensitivity (estimated as the proportion of surviving, apoptotic, and nonapoptotic deaths) of vaginal epithelial cells obtained from HPV-negative and HPV-positive patients to oxidative damage. The tendency to resist oxidative damage in vaginal epithelial cells of 147 HPV-positive and 59 HPV-negative patients with physiological or suboptimal levels of Lactobacillus was evaluated. Adaptation of cell to curb the oxidative damage in 146 HPV positive and 41 HPV negative with probiotic (Lacticaseibacillus rhamnosus Lcr35) supplementation and without was studied. Resistance of epithelial cells to damage was measured by the ratio of surviving, apoptotic, and dead nonapoptotic cells after three times of hydrogen peroxide treatment using a kit containing annexin V-fluorescein in combination with propidium iodide. If uninfected epithelial cells were in an environment with a physiological level of lactobacilli for significant duration, then these cells were more resilient to damage, and if they lost their viability, it was mainly due to apoptosis. Probiotic therapy also increased the resistance of uninfected epithelial cells to damage. HPV-infected epithelial cells were less resistant to damage at normal levels of lactobacilli compared with Lactobacillus deficiency. In HPV-positive patients with Lactobacillus deficiency, probiotic therapy decreased the resistance of infected epithelial cells to damage; the increase in cell death was mainly due to apoptosis.
PubMed: 38941060
DOI: 10.1007/s12602-024-10317-0 -
Oncology Reports Aug 2024The prognosis of patients with human papillomavirus (HPV)‑negative cervical cancer is significantly worse than that of patients with HPV‑positive cervical cancer....
The prognosis of patients with human papillomavirus (HPV)‑negative cervical cancer is significantly worse than that of patients with HPV‑positive cervical cancer. Understanding the mechanisms of this is crucial for preventing disease evolution. In the present study, the GV367‑snail family transcriptional repressor 2 (SNAI2) lentiviral vector was constructed and transduced into C‑33A cells. Subsequently, the proliferation of tumor cells was detected using the Cell Counting Kit (CCK)‑8 method. Flow cytometry was used to analyze the cell cycle progression of tumor cells. The glucose consumption of tumor cells was detected using an oxidase assay, and the senescence of tumor cells was detected using beta‑galactosidase staining. The gene expression and the activity of p38 and ERK1/2 were detected using reverse transcription‑quantitative PCR and western blotting, respectively. The C‑33A‑SNAI2 cell line was successfully established. Compared with HeLa and C‑33A‑Wild cells, the proliferation and percentage of G0/G1‑phase cells in the C‑33A‑SNAI2 group were decreased, as detected by the CCK‑8 assay (100±0 vs. 239.1±58.3 vs. 39.7±20.1, P<0.01) and flow cytometry (34.0±7.1% vs. 46.2±10.6% vs. 61.3±5.3%, P<0.05). Compared with the HeLa group, the glucose consumption of the C‑33A‑Wild and C‑33A‑SNAI2 groups was significantly decreased (P<0.01). The results of beta‑galactosidase staining showed that the proportion of beta‑galactosidase‑positive cells in the C‑33A‑SNAI2 group was significantly decreased compared with the C‑33A‑Wild group (P<0.01). Upregulation of SNAI2 enhanced the increase in p21 expression, and the decrease in CDK1, urokinase plasminogen activator receptor (u‑PAR) and cyclin D1 expression in C‑33A cells compared with C‑33A‑Wild cells (P<0.05). In addition, the activities of p38, ERK1/2 and the phosphorylated (p)‑ERK1/2/p‑p38 ratio were decreased in the C‑33A‑SNAI2 group compared with the C‑33A‑Wild and HeLa groups (P<0.05). In conclusion, SNAI2 enhanced HPV‑negative cervical cancer C‑33A cell dormancy, which was characterized by G0/G1 arrest, by the downregulation of u‑PAR expression, and a decrease in the activity of the p‑ERK1/2 and p‑p38MAPK signaling pathways . Cancer recurrence and metastases are responsible for most cancer‑related deaths. Given that SNAI2 is required for enhancing HPV‑negative cervical cancer cell dormancy, regulating this process may promote cervical tumor cells to enter a continuous dormant state, which could be a potential approach for tumor therapy.
Topics: Humans; Uterine Cervical Neoplasms; Female; Snail Family Transcription Factors; Cell Proliferation; Gene Expression Regulation, Neoplastic; MAP Kinase Signaling System; HeLa Cells; Receptors, Urokinase Plasminogen Activator; Cell Line, Tumor; Papillomaviridae; Cellular Senescence; p38 Mitogen-Activated Protein Kinases; Cell Cycle
PubMed: 38940353
DOI: 10.3892/or.2024.8763 -
Frontiers in Bioscience (Landmark... Jun 2024The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the...
BACKGROUND
The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the etiology of the OPSCC to facilitate the administration of effective treatments.
METHODS
This study confers an integrative genomics approach for identifying key oncogenic drivers involved in the OPSCC pathogenesis. The dataset contains RNA-Sequencing (RNA-Seq) samples of 46 Human papillomavirus-positive head and neck squamous cell carcinoma and 25 normal Uvulopalatopharyngoplasty cases. The differential marker selection is performed between the groups with a log2FoldChange (FC) score of 2, adjusted -value < 0.01, and screened 714 genes. The Particle Swarm Optimization (PSO) algorithm selects the candidate gene subset, reducing the size to 73. The state-of-the-art machine learning algorithms are trained with the differentially expressed genes and candidate subsets of PSO.
RESULTS
The analysis of predictive models using Shapley Additive exPlanations revealed that seven genes significantly contribute to the model's performance. These include , , and , which predominantly influence differentiating between sample groups. They were followed in importance by , , , and . The Random Forest and Bayes Net algorithms also achieved perfect validation scores when using PSO features. Furthermore, gene set enrichment analysis, protein-protein interactions, and disease ontology mining revealed a significant association between these genes and the target condition. As indicated by Shapley Additive exPlanations (SHAPs), the survival analysis of three key genes unveiled strong over-expression in the samples from "The Cancer Genome Atlas".
CONCLUSIONS
Our findings elucidate critical oncogenic drivers in OPSCC, offering vital insights for developing targeted therapies and enhancing understanding its pathogenesis.
Topics: Humans; Oropharyngeal Neoplasms; Biomarkers, Tumor; Papillomavirus Infections; Artificial Intelligence; Gene Expression Regulation, Neoplastic; Squamous Cell Carcinoma of Head and Neck; Algorithms; Sequence Analysis, RNA; Machine Learning; Papillomaviridae; Carcinoma, Squamous Cell
PubMed: 38940026
DOI: 10.31083/j.fbl2906220 -
Frontiers in Immunology 2024Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide, with human papillomavirus (HPV) infection contributing to cancer...
Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide, with human papillomavirus (HPV) infection contributing to cancer development. Conventional therapies achieve only limited efficiency, especially in recurrent or metastatic HNSCC. As the immune landscape decisively impacts the survival of patients and treatment efficacy, this study comprehensively investigated the immunological tumor microenvironment (TME) and its association with patient outcome, with special focus on several dendritic cell (DC) and T lymphocyte subpopulations. Therefore, formalin-fixed paraffin-embedded tumor samples of 56 HNSCC patients, who have undergone resection and adjuvant radiotherapy, were analyzed by multiplex immunohistochemistry focusing on the detailed phenotypic characterization and spatial distribution of DCs, CD8 T cells, and T-helper cell subsets in different tumor compartments. Immune cell densities and proportions were correlated with clinical characteristics of the whole HNSCC cohort and different HPV- or hypoxia-associated subcohorts. Tumor stroma was highly infiltrated by plasmacytoid DCs and T lymphocytes. Among the T-helper cells and CD8 T cells, stromal regulatory T cells and intraepithelial exhausted CD8 T cells expressing programmed cell death protein-1 (PD-1) and/or lymphocyte-activation gene-3 (LAG-3) were the predominant phenotypes, indicating an immunosuppressive TME. HPV-associated tumors showed significantly higher infiltration of type I and type II conventional DCs (cDC1, cDC2) as well as several CD8 T cell phenotypes including exhausted, activated, and proliferating T cells. On the contrary, tumors with hypoxia-associated gene signatures exhibited reduced infiltration for these immune cells. By multivariate Cox regression, immune-related prognostic factors were identified. Patient clusters defined by high infiltration of DCs and T lymphocytes combined with HPV positivity or low hypoxia showed significantly prolonged survival. Thereby, cDC1 and CD8 T cells emerged as independent prognostic factors for local and distant recurrence. These results might contribute to the implementation of an immune cell infiltration score predicting HNSCC patients' survival and such patient stratification might improve the design of future individualized radiochemo-(immuno)therapies.
Topics: Humans; Dendritic Cells; Squamous Cell Carcinoma of Head and Neck; Male; Female; CD8-Positive T-Lymphocytes; Middle Aged; Tumor Microenvironment; Head and Neck Neoplasms; Aged; Lymphocytes, Tumor-Infiltrating; Prognosis; Adult; Papillomavirus Infections
PubMed: 38938577
DOI: 10.3389/fimmu.2024.1414298 -
BMC Cancer Jun 2024Primary cervical cancer screening and treating precancerous lesions are effective ways to prevent cervical cancer. However, the coverage rates of human papillomavirus...
BACKGROUND
Primary cervical cancer screening and treating precancerous lesions are effective ways to prevent cervical cancer. However, the coverage rates of human papillomavirus (HPV) vaccines and routine screening are low in most developing countries and even some developed countries. This study aimed to explore the benefit of an artificial intelligence-assisted cytology (AI) system in a screening program for a cervical cancer high-risk population in China.
METHODS
A total of 1231 liquid-based cytology (LBC) slides from women who underwent colposcopy at the Chinese PLA General Hospital from 2018 to 2020 were collected. All women had received a histological diagnosis based on the results of colposcopy and biopsy. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), false-positive rate (FPR), false-negative rate (FNR), overall accuracy (OA), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index (YI) of the AI, LBC, HPV, LBC + HPV, AI + LBC, AI + HPV and HPV Seq LBC screening strategies at low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) thresholds were calculated to assess their effectiveness. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic values of the different screening strategies.
RESULTS
The Se and Sp of the primary AI-alone strategy at the LSIL and HSIL thresholds were superior to those of the LBC + HPV cotesting strategy. Among the screening strategies, the YIs of the AI strategy at the LSIL + threshold and HSIL + threshold were the highest. At the HSIL + threshold, the AI strategy achieved the best result, with an AUC value of 0.621 (95% CI, 0.587-0.654), whereas HPV testing achieved the worst result, with an AUC value of 0.521 (95% CI, 0.484-0.559). Similarly, at the LSIL + threshold, the LBC-based strategy achieved the best result, with an AUC of 0.637 (95% CI, 0.606-0.668), whereas HPV testing achieved the worst result, with an AUC of 0.524 (95% CI, 0.491-0.557). Moreover, the AUCs of the AI and LBC strategies at this threshold were similar (0.631 and 0.637, respectively).
CONCLUSIONS
These results confirmed that AI-only screening was the most authoritative method for diagnosing HSILs and LSILs, improving the accuracy of colposcopy diagnosis, and was more beneficial for patients than traditional LBC + HPV cotesting.
Topics: Humans; Female; Uterine Cervical Neoplasms; Adult; Artificial Intelligence; Early Detection of Cancer; Middle Aged; Papillomavirus Infections; Colposcopy; China; Sensitivity and Specificity; Uterine Cervical Dysplasia; Young Adult; ROC Curve; Cytodiagnosis
PubMed: 38937664
DOI: 10.1186/s12885-024-12532-y -
JCO Global Oncology Jun 2024Cervical cancer fight gains momentum as funders meet in Cartagena with the aim of closing gaps in screening, access to vaccines and treatment.
Cervical cancer fight gains momentum as funders meet in Cartagena with the aim of closing gaps in screening, access to vaccines and treatment.
Topics: Uterine Cervical Neoplasms; Humans; Female; Developing Countries; Papillomavirus Vaccines; Early Detection of Cancer; Papillomavirus Infections
PubMed: 38935885
DOI: 10.1200/GO.24.00147 -
JAMA Oncology Jun 2024
PubMed: 38935364
DOI: 10.1001/jamaoncol.2024.1821 -
AIDS Patient Care and STDs Jun 2024Adolescents and young adults (AYAs) living with HIV have high rates of co-sexually transmitted infections (STIs). During the coronavirus disease (COVID) pandemic, STI...
Adolescents and young adults (AYAs) living with HIV have high rates of co-sexually transmitted infections (STIs). During the coronavirus disease (COVID) pandemic, STI prevention strategies, including access to testing/treatment facilities, availability of health care workers, and condom availability, may have decreased. This study aimed to determine if differences in STI incidence for first infection and reinfection existed between the pre-COVID and COVID eras in a cohort of AYAs living with HIV in Atlanta, GA. Retrospective chart review was conducted for all patients between ages 13 and 24 at the Grady Ponce Clinic. Two eras were identified: a pre-COVID era (January 1, 2009-December31, 2019) and a COVID era (January 1, 2020-June 30, 2021). STIs recorded included gonorrhea, chlamydia, human papillomavirus, syphilis, trichomonas, herpes simplex virus, lymphogranuloma venereum, hepatitis C, bacterial vaginosis, and chancroid. First and recurrent incidence rates for any STIs were reported. Our sample included 766 sexually active AYAs with HIV. A total of 721 patients were included in the pre-COVID era and 583 (80.9%) had at least one STI. A total of 337 patients were included in the COVID era, and 158 had at least one STI (46.9%). The overall first STI incidence rate increased from 42.47 to 58.67 per 100 person-years (PY) and the recurrent STI incidence rate increased from 121.50 to 169.85 per 100 PY from the pre-COVID to the COVID era ( < 0.001). Our study demonstrated significantly higher incidence rates of first and recurrent STIs in AYAs living with HIV in the COVID era. We urge continuation of existing STI prevention programs to avoid secondary clinical and economic adverse effects of increased infections.
Topics: Humans; COVID-19; Female; Incidence; Sexually Transmitted Diseases; Retrospective Studies; HIV Infections; Male; Young Adult; Adolescent; SARS-CoV-2; Georgia; Coinfection; Adult; Sexual Behavior
PubMed: 38935346
DOI: 10.1089/apc.2024.0060 -
Current Opinion in HIV and AIDS Jun 2024To highlight recent data on HPV infection and cervical precancerous lesions in adolescents with HIV, and priorities for primary and secondary HPV prevention.
PURPOSE OF REVIEW
To highlight recent data on HPV infection and cervical precancerous lesions in adolescents with HIV, and priorities for primary and secondary HPV prevention.
RECENT FINDINGS
Incident and persistent high-risk HPV infections and cervical abnormalities are higher among young women with perinatally acquired HIV compared to their HIV-negative peers; data on HPV among males with perinatally acquired HIV are scarce. HPV vaccination is highly effective in preventing HPV-related disease, but antibody titers may decline in people with HIV. It remains unclear if emerging recommendations to reduce vaccine schedules from three doses to two or one dose are appropriate for children and adolescents with perinatally acquired HIV. Due to higher risks of HPV-related cancers, screening guidelines for cervical cancer differ in their frequency and age at initiation for women with HIV, but there are no recommendations for women with perinatally acquired HIV; nor for anal cancer screening for men with perinatally acquired HIV.
SUMMARY
Data on the effectiveness of reduced HPV vaccine schedules in children and adolescents with HIV are needed. Implementation research to guide strategies for vaccination, screening, and treatment should include children, adolescents, and young adults with perinatally acquired HIV to ensure they are not left behind.
PubMed: 38935056
DOI: 10.1097/COH.0000000000000868 -
Indian Journal of Public Health Oct 2023
Gay and Bisexual Men too should not be Left Out/Deprived of Human Papilloma Virus Vaccination in "Cervical Cancer Elimination Programme" in Countries with a High Prevalence of HIV.
Topics: Humans; Male; Papillomavirus Vaccines; HIV Infections; Uterine Cervical Neoplasms; Papillomavirus Infections; Female; Prevalence; Sexual and Gender Minorities; India; Homosexuality, Male; Human Papillomavirus Viruses
PubMed: 38934843
DOI: 10.4103/ijph.ijph_1646_22