Clinics

CircUBE2D2 regulates HMGB1 through miR-885-5p to promote ovarian cancer malignancy

The newly discovered CircUBE2D2 has been shown to abnormally upregulate and promote cancer progression in a variety of cancers. The present study explored circUBE2D2 (hsa_circ_0005728) in Ovarian Cancer (OC) progression. CircUBE2D2, miR-885-5p, and HMGB1 were examined by RT-qPCR or WB. SKOV-3 cell functions (including cell viability, apoptosis, migration, and invasion) were validated using the CCK-8, flow cytometry, scratch assay, and transwell assay, respectively. The direct relationship between miR-885-5p and circUBE2D2 or HMGB1 was confirmed by a dual-luciferase reporter and RNA pull-down analysis. circUBE2D2's role in vivo tumor xenograft experiment was further probed. OC tissue and cell lines had higher circUBE2D2 and HMGB1 and lower miR-885-5p. Mechanically, CircUBE2D2 shared a binding relation with miR-885-5p, while miR-885-5p can directly target HMGB1. Eliminating circUBE2D2 or miR-885-5p induction inhibited OC cell activities. However, these functions were relieved by down-regulating miR-885-5p or HMGB1 induction. Furthermore, circUBE2D2 knockout reduced tumor growth. CircUBE2D2 regulates the expression of HMGB1 by acting as a sponge of ceRNA as miR-885-5p, thereby promoting the control of OC cell proliferation and migration and inhibiting cell apoptosis. Targeting CircUBE2D2 could serve as a new potential treatment strategy for OC.

The relationship of C-Reactive Protein to Albumin Ratio and interval debulking surgery outcome after neoadjuvant chemotherapy in ovarian cancer patients

To investigate the relationship between the changes of C-reactive protein to Albumin Ratio (CAR) levels and Interval Debulking Surgery (IDS) outcome after Neoadjuvant Chemotherapy (NAC) in ovarian cancer patients. A nested case-control study for 209 patients with ovarian cancer who received NAC-IDS therapy from the First Affiliated Hospital of Bengbu Medical College between 2015‒2021 was conducted. Demographic data, laboratory indicators, and imaging examinations were collected. The outcome was regarded as optimal IDS in this study. Univariate and multivariate logistic regression analyses were performed to assess the relationship of CAR before NAC, CAR after NAC and ∆CAR with optimal IDS. The authors also performed the subgroup analysis based on menopausal state. The end time of follow-up was January 24, 2022. A total of 156 patients had been treated with optimal IDS, and 53 with suboptimal IDS. After adjusting age, body mass index, menopausal state, NAC drug, peritoneal perfusion and CAR before NAC, the result showed that CAR after NAC (Odds Ratio [OR = 3.48], 95% Confidence Interval [95% CI 1.28‒9.48], p = 0.015) and ∆CAR (OR = 0.29, 95% CI 0.11‒0.78, p = 0.015) were associated with optimal IDS, respectively. Additionally, the authors found a significant correlation between CAR after NAC and optimal IDS (OR = 3.16, 95% CI 1.07‒9.35, p = 0.038), and ∆CAR and optimal IDS (OR = 0.32, 95% CI 0.11‒0.94, p = 0.038) among ovarian cancer patients with menopause. CAR after NAC and ∆CAR were independent prognostic markers of optimal interval debulking surgery for ovarian cancer patients.

Effect of 3D laparoscopy versus traditional laparotomy on serum tumor markers and coagulation function in patients with early-stage endometrial cancer

To investigate the impact of Three-Dimensional (3D) laparoscopy compared to traditional laparotomy on serum tumor markers and coagulation function in patients diagnosed with early-stage Endometrial Cancer (EC). The authors retrospectively analyzed the clinical data of 75 patients diagnosed with early-stage EC and categorized them into two groups based on the surgical techniques employed. The 3D group consisted of 36 patients who underwent 3D laparoscopic surgery, while the Laparotomy group comprised 39 patients who underwent traditional laparotomy. The authors then compared the alterations in serum tumor markers and coagulation function between the two groups. Postoperatively, serum levels of CA125, CA199, and HE4 were notably reduced in both groups on the third day, with the levels being more diminished in the 3D group than in the Laparotomy Group (p < 0.05). Conversely, FIB levels escalated significantly in both groups on the third-day post-surgery, with a more pronounced increase in the 3D group. Additionally, PT and APTT durations were reduced and were more so in the 3D group than in the laparotomy group (p < 0.05). When juxtaposed with traditional laparotomy, 3D laparoscopic surgery for early-stage EC appears to be more efficacious, characterized by reduced complications, and expedited recovery. It can effectively mitigate serum tumor marker levels, attenuate the inflammatory response and damage to immune function, foster urinary function recovery, and enhance the quality of life. However, it exerts a more significant influence on the patient's coagulation parameters, necessitating meticulous prevention and treatment strategies for thromboembolic events in clinical settings.

LHX1 as a potential biomarker regulates EMT induction and cellular behaviors in uterine corpus endometrial carcinoma

To investigate the expression of LHX1 and its role as a biomarker in the diagnosis and prognosis of Uterine Corpus Endometrial Carcinoma (UCEC). The Cancer Genome Atlas (TCGA) database was used to detect the expression level of LHX1 in UCEC cells and tissues, and to find out the effect of LHX1 on prognosis. Co-expressed genes were then identified by Spearman correlation analysis, and the protein-protein interaction network was constructed using Cytoscape software. The R "clusterProfiler" package was used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A series of in vitro experiments were performed to evaluate LHX1 expression and detect UCEC cell proliferation, invasion, and migration. Western blotting was used to determine the effect of LHX1 on expression levels of Epithelial-Mesenchymal Transition (EMT)-related proteins. LHX1 was upregulated in UCEC tissues and correlated with poor overall survival and disease-specific survival outcomes. Functional enrichment analysis suggested that genes co-expressed with LHX1 were enriched in cell adhesion. The expression of LHX1 was positively correlated with the expression levels of genes related to EMT induction and invasion. LHX1 can enhance the proliferation, migration, and invasion activities of UCEC cells in vitro, and alter the expression levels of EMT-related proteins. LHX1 expression was highly upregulated in UCEC cells and tissues, which was correlated with the prognosis of patients with UCEC. LHX1 may regulate UCEC progression at least in part by modulating EMT induction.

RNA-binding protein with serine-rich domain 1 regulates microsatellite instability of uterine corpus endometrial adenocarcinoma

To determine the role of RNA-binding protein with serine-rich domain 1 (RNPS1) in uterine corpus endometrial carcinoma (UCEC), the role of RNPS1 knockdown in UCEC development in vitro and in vivo, and the relationship between RNPS1 and mismatch repair (MMR) in UCEC. We predicted the potential function of RNPS1 using bioinformatics systems. The expression of RNPS1 in tissues and cell lines was analyzed by western blotting and immunohistochemistry. The expression of RNPS1 in MMR was assessed using bioinformatics and western blotting. The proliferation and apoptosis of UCEC cells were assessed under RNPS1 knockdown conditions, and RNPS1 regulation in MMR was detected by suppressing Notch signaling. Associations between RNPS1 and gene mutations in UCEC and prognosis were analyzed. The RNPS1 level was higher in UCEC tumors than in normal tissues and tumors or RL952 cells. Prognostic outcomes were worse when UCEC showed abundant RNPS1 expression. Lentiviral RNPS1 knockdown weakened tumor cell proliferation and suppressed biomarker expression, reduced the tumor volume, promoted apoptosis in vitro and in vivo, and inhibited UCEC development. Increased MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) levels in MMR after RNPS1 knockdown were reversed by inhibiting Notch signaling. Furthermore, RNPS1 was associated with mutations in NAA11, C2orf57, NUPR1, and other genes involved in UCEC prognosis. RNPS1 may regulate the expression levels of MSH2 and MSH6 in MMR, enhancing the proliferation, development, and prognosis of UCEC through a Notch signaling pathway in UCEC. Our study offers a new method and strategy for delaying UCEC development through modulating MMR.

Is infracolic omentectomy necessary for presumed early-stage Borderline Ovarian Tumors (BOTs)? A retrospective cohort study and meta-analysis

While omentectomy is included in the guidelines for the surgical management of Borderline Ovarian Tumors (BOTs), it is unclear whether removal of a normal-appearing omentum confers a therapeutic advantage. The retrospective cohort study of patients with BOTs evalua0 ted the role of routine omentectomy and was followed by a meta-analysis to enhance the robustness of the findings. Data were obtained from patients treated at three Brazilian reference centers between January 2009 and October 2023. Progression-Free Survival (PFS), risk of death, and recurrence were compared between patients who underwent omentectomy and those who did not. A total of 218 patients with BOTs were assessed: omentectomy was performed in 161 (73.8 %) and not performed in 57 (26.1 %). OS at 60 months was 95.5 % in the omentectomy group and 94.6 % in the non-omentectomy group (HR = 0.97 [95 % CI 0.20‒4.68]; p = 0.96). PFS was 97.2 % and 89.3 %, respectively (HR = 0.42; 95 % CI 0.10‒1.76; p = 0.23). Twelve studies comprising 2996 women with BOT, were included in the systematic review to evaluate the outcomes with and without omentectomy. Relative Risk (RR) of recurrence was 0.94 (95 % CI 0.67‒1.31; p = 0.7) for the non-omentectomy group compared with the omentectomy group. No statistically significant difference was observed, with an RR of 1.98 (95 % CI 0.24‒16.43; p = 0.53) for risk of death and an HR of 1.02 (95 % CI 0.25‒4.15; p = 0.98) for PFS. The retrospective cohort study and meta-analysis showed a low incidence of metastatic disease in the omentum. No effect of omentectomy on OS, PFS, and recurrence in patients with BOT.

Uterine artery doppler and pregnancy-associated plasma protein-A in pregnancies with fibroids

Uterine fibroids affect maternal and neonatal outcomes adversely. Pregnancy-Associated Plasma Protein-A (PAPP-A) and Uterine Artery Doppler (UAD) are used in the first and second trimesters to predict maternal and neonatal outcomes, including maternal preeclampsia, Small-for-Gestational-Age (SGA), and Low Birth Weight (LBW) babies. A retrospective review of medical records over 8-months was carried out for 60-patients who presented to the antenatal outpatient clinic. Inclusion criteria were the identification of fibroids in the first-trimester scan, PAPP-A blood test performed at the first visit, and UAD recorded at 20-weeks scan. Demographic characteristics, clinical parameters, pregnancy-related complications, and obstetric outcomes were extracted for data collection. Data analysis was performed to determine correlations between UAD parameters and PAPP-A levels and fibroid measurements for different fibroid types, and to determine the effect of fibroid presence on actual and estimated fibroid weight. Of 60 included patients, the mean age of patients was 35.8 ± 4.8 years, and each pregnant woman had an average of 2.9 ± 1.7 fibroids, with the majority (73 %) being large (> 5 cm). No complications, such as gestational hypertension, gestational diabetes, preeclampsia, abruption, and preterm birth were reported; only 6 (10 %) of women were sonographically diagnosed with SGA babies, while 2 (3.3 %) babies were LBW. UAD parameters and PAPP-A levels had no significant association with fibroid size (p > 0.05). There is a possible role of UAD and PAPP-A in determining pregnancy outcomes in the presence of fibroids, which needs to be explored by prospective studies.

Magnetic resonance-guided focused ultrasound for uterine fibroids

The uterine leiomyoma is a pelvic solid tumor more frequent in women. The Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) is a technique aimed at diminishing hypermenorrhagia and dysmenorrhea in symptomatic women. To show the effects subsequent to MRgFUS application on symptoms, quality of life, and myoma volume in symptomatic women. Fifty-two patients with symptomatic uterine myomas underwent MRgFUS followed by clinical evaluation, pelvis MRI, and administration of the UFS-QoL questionnaire at 6 months and 12 months to detect symptom improvements and decrease in myoma volume. The mean myoma volume decreased 24 % after 6 months and 42 % after 12 months. The mean score on the UFS-QoL questionnaire increased 54 % after 6 months and 81 % after 12 months. There were no serious complications. Four patients had first-degree burns. No infection cases were reported. Two patients progressed to a myomectomy by surgical hysteroscopy and one of them underwent total hysterectomy 11 months after the MRgFUS treatment. This case series suggests that MRgFUS therapy is viable and effective in reducing symptoms and improving the life quality of symptomatic patients.

Transcriptomics analysis identified ezrin as a potential druggable target in cervical and gastric cancer cells

Cancer genomics and transcriptomics studies have provided a large volume of data that enables to test of hypotheses based on real data from cancer patients. Ezrin (encoded by the EZR gene) is a highly expressed protein in cancer that contributes to linking the actin cytoskeleton to the cell membrane and signal transduction pathways involved in oncogenesis and disease progression. NSC305787 is a pharmacological ezrin inhibitor with potential antineoplastic effects. In the present study, the authors prospected EZR mRNA levels in a pan-cancer analysis and identified potential cancers that could benefit from anti-EZR therapies. This study analyzed TCGA data for 32 cancer types, emphasizing cervical squamous cell carcinoma and stomach adenocarcinoma. It investigated the impact of EZR transcript levels on clinical outcomes and identified differentially expressed genes. Cell lines were treated with NSC305787, and its effects were assessed through various cellular and molecular assays. EZR mRNA levels are highly expressed, and their expression is associated with biologically relevant molecular processes in cervical squamous carcinoma and stomach adenocarcinoma. In cellular models of cervical and gastric cancer, NSC305787 reduces cell viability and clonal growth (p < 0.05). Molecular analyses indicate that the pharmacological inhibition of EZR induces molecular markers of cell death and DNA damage, in addition, to promoting the expression of genes associated with apoptosis and inhibiting the expression of genes related to survival and proliferation. The present findings provide promising evidence that ezrin may be a molecular target in the treatment of cervical and gastric carcinoma.

Pembrolizumab in gestational trophoblastic neoplasia: Systematic review and meta-analysis with sub-group analysis of potential prognostic factors

To assess the performance of pembrolizumab for the treatment of Gestational Trophoblastic Neoplasia (GTN). The Medical Subject Headings related to immunotherapy/pembrolizumab and GTN were used alone or in combination to retrieve relevant articles. The authors searched in EMBASE, MEDLINE/PubMed, Elsevier's Scopus, and Web of Science until November/2024. The authors included any randomized controlled trials, cohort studies, case series, and case reports focusing on pembrolizumab treatment in GTN. Meta-analysis of proportions was carried out employing a random-effects model. The meta-analysis employed the inverse variance method, with the arcsine link function for the analysis of proportional data. All analyses were performed using Stata 18. For all analyses, a p-value < 0.05 indicated statistical significance. This study was registered on PROSPERO (CRD42023493329). A total of 550 studies were identified after a literature search among which 15 original studies were included in the systematic review and in the meta-analysis. Pembrolizumab induced complete sustained remission in 71.59% (95% CI 53.27‒84.78%; I Pembrolizumab seems an effective treatment for patients with high-risk GTN with chemoresistant or relapsed disease, including cases of PSTT/ETT, notwithstanding patient age, time to initiate immunotherapy and whether or not it was associated with chemotherapy.

Self-sampling for HPV genotyping: a study of vaginal and urine collection in Brazilian women with high-grade lesions

In Brazil - a country of continental dimensions with marked socioeconomic disparities - the use of self-collected samples and first-void urine for cervical cancer screening may be particularly valuable. This study aimed to assess the acceptability of two self-sampling approaches - first-void urine collection and vaginal self-sampling - among women diagnosed with high-grade cervical lesions (CIN2+) referred to a tertiary care center. Additionally, the study evaluated the concordance of high-risk HPV (hrHPV) test results obtained from self-collected samples compared to those collected by a healthcare professional. This cross-sectional study included 100 women. Participants completed a structured questionnaire on clinical history, demographics, gynecological and obstetric background. Following an instructional video, they performed self-collection of urine and vaginal samples. All participants then underwent colposcopic examination for lesion assessment and therapeutic planning. HPV DNA testing was conducted, and agreement analysis was performed between sample types. Both urine and vaginal self-collection methods were reported as easy and comfortable. Instructions were considered easy or very easy by nearly all participants for all collection methods. Clinician-collected sampling was associated with higher embarrassment and discomfort. Agreement analysis showed excellent concordance for HPV 16 and other high-risk HPV types between self-collected, urine, and clinician-collected samples, with all comparisons reaching statistical significance. Urine and vaginal self-collection are feasible, acceptable, and reliable methods. Urine sampling was the preferred method in the present study. High concordance with clinician-collected samples confirms their clinical utility, and the positive response to instructional videos highlights the importance of educational support.

Human epidermal growth factor receptor 2 and proliferation Ki-67 biomarkers using a tissue microarray to refine the histopathological subtyping of hydatidiform moles: Limitations and prognostic value

The morphology-based differential diagnosis of Hydatidiform Mole (HM) of the Complete (CHM) and Partial (PHM) types is challenging because of earlier diagnosis of HM owing to the universal application of ultrasound during antenatal care. HMs may present with amplified oncogenes or other gene mutations, resulting in recurrent or neoplastic disease. The cell proliferation markers Ki-67 and HER2 may contribute to the final HM subtype and prognosis. Much is known about the basic mechanisms of HM development; however, other molecular diagnostic and predictive markers need to be investigated. This was an ambispective anatomopathological study of 108 HMs cases. A tissue microarray was used for Ki-67 or HER2 immunostaining analysis. Associations between immunomarker scores and postmolar Gestational Trophoblastic Neoplasia (GTN) were analyzed via Fisher's exact and linear-by-linear association tests. A statistically significant trend toward increased Ki-67 immunostaining in CHM samples was observed. Seventeen HM patients developed GTN, of whom 6 (35 %) had a Ki-67 score of 3+ and 9 (53 %) had Ki-67 score of 2+. Two (12 %) HM patients had a HER2 score of 3+, and 4 (23 %) HM patients had a HER2 score of 2+, of whom 2 (12 %) patients exhibited oncogene amplification by FISH HER2. Ki-67 and HER2 markers may be useful for the diagnosis and prediction of HM development, providing alternative targeted therapies. This study needs to be interpreted with caution due to its small sample size, high sample exclusion rate, and the absence of significant associations between biomarkers and clinical outcomes.

Exploratory unsupervised machine learning of angiogenesis biomarkers in a phase II advanced cervical cancer trial of radiochemotherapy with or without neoadjuvant chemotherapy

In a prospective, randomized phase II study, exploratory data analysis was conducted to evaluate angiogenesis-associated plasma protein levels in patients with locally advanced cervical cancer METHODS: Participants were divided into two groups: Group A received neoadjuvant cisplatin and gemcitabine treatment (NAC) followed by chemoradiation with cisplatin and brachytherapy (CRT), while Group B received only CRT. Plasma samples were collected from patients in Group A at three time points: baseline, after NAC, and after CRT. Group B patients had samples taken at two time points: baseline and after CRT. The study analyzed an angiogenesis-associated panel of plasma proteins, including angiopoietin-2, G-CSF, endothelin-1, FGF-1, FGF-2, follistatin, IL-8, HGF, EGF, HB-EGF, PLGF, VEGF-A, VEGF-C, and VEGF- D. Receiver Operating Characteristic (ROC) analyses assessed the predictive value of baseline biomarkers for 12, 24, and 36-month survival outcomes. Additionally, Principal Component Analysis (PCA) was applied to post-CRT biomarker changes to identify coordinated modulation patterns. PCA was based on normalized delta values and eigenvector loadings, enabling identification of biomarkers aligned with Progression-Free Survival (PFS) and Overall Survival (OS). Significant differences were observed in the levels of HB-EGF, IL-8, PLGF, and VEGF-C between Groups A and B following CRT. Additionally, angiopoietin-2 levels showed a significant increase in Group B only. NAC treatment in Group A appeared to downregulate IL-8. CRT induced significant changes in HB-EGF, IL-8, PLGF, and VEGF-C levels in both groups. Patients in Group B demonstrated improved PFS and OS compared to those in Group A. Despite these differences in survival outcomes, the authors observed no significant intergroup differences in the tested biomarkers after completion of CRT. ROC analysis of baseline angiogenesis biomarkers demonstrated limited predictive sensitivity for survival outcomes. However, PCA of biomarker changes following CRT highlighted VEGF-A, HB-EGF, and angiopoietin-2 as variables associated with PFS and OS. Baseline biomarker levels were not predictive of long-term outcomes. In contrast, CRT alone modulated key angiogenic biomarkers, and post-CRT biomarker changes were associated with improved survival. Such biomarker alterations were not observed following NAC, which was not associated with clinical benefit in this study. These findings underscore the value of dynamic biomarker evaluation and highlight how treatment strategies differentially impact biomarker profiles in advanced cervical cancer.

FOXO3a deregulation in uterine smooth muscle tumors

The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis. The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes. This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated. In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.

TRIM47 promotes ovarian cancer cell proliferation, migration, and invasion by activating STAT3 signaling

Tripartite Motif 47 (TRIM47) protein plays a prominent role in many cancers. This study aimed to investigate the biological roles of TRIM47 in ovarian cancer. TRIM47 was knocked down and overexpressed in ovarian cancer cell lines SKOV3 and OVCAR3, and the effects on proliferation, clone formation, apoptosis, invasion, and growth of xenograft tumors in nude mice were determined. The expression levels of the selected candidates were tested by western blotting and quantitative real-time PCR. TRIM47 knockdown suppressed proliferation and encourages apoptosis of ovarian cancer cells. Similarly, TRIM47 knockdown suppressed ovarian cancer cell invasion, migration, and epithelial-mesenchymal transition. Ovarian cancer cell xenograft assays demonstrated that TRIM47 knockdown significantly inhibited tumor growth. Mechanistically, TRIM47 knockdown suppressed STAT3 phosphorylation and the expression of several downstream genes, including MCL-1, MMP2, and c-MYC. Silencing of STAT3 partially prevented TRIM47-induced tumor cell proliferation and invasion. The present study's findings demonstrate that by activating STAT3 signaling, TRIM47 functions as an oncogene in ovarian cancer. TRIM47, therefore, appears to be a potential target for ovarian cancer prevention and/or therapy.

Apoptosis-related gene expression can predict the response of ovarian cancer cell lines to treatment with recombinant human TRAIL alone or combined with cisplatin

The objectives of this study were to determine the sensitivity of ovarian cancer (OC) cell lines (TOV-21G and SKOV-3) to cisplatin and to the recombinant human TRAIL (rhTRAIL), and to evaluate the expression profile of TNFRSF10B, TNFRSF10C, TP53TG5, MDM2, BAX, BCL-2 and CASPASE-8 genes and their participation in the resistance/susceptibility mechanism of these tumor cell lines. To determine the IC50 values associated with Cisplatin and rhTRAIL, inhibition of cell growth was observed using MTT assays in two human OC cell lines (SKOV-3 and TOV-21G). The analysis of gene expression was performed using quantitative real-time polymerase chain reaction (qRT-PCR). Both cell lines had different susceptibility profiles to the tested drugs. In the SKOV-3 cell line, the IC50 values for cisplatin and for rhTRAIL were 270.83 ug/mL and 196.5 ng/mL, respectively. The same concentrations were used for TOV-21G. Different gene expression profiles were observed in each tested cell line. CASPASE-8 and TNFRSF10B expression levels could predict the response of both the cell lines to rhTRAIL alone or the response to a combination of rhTRAIL and cisplatin. In addition, we observed a relationship between BCL-2 and BAX expression that may be helpful in estimating the proliferation rate of the OC cell lines. SKOV-3 and TOV-21G respond differently to cisplatin and rhTRAIL exposure, and expression of CASPASE-8 and TNFRSF10B are good predictors of responses to these treatments.

Adolescents’ knowledge of HPV and sexually transmitted infections at public high schools in São Paulo: A cross-sectional study

To assess the knowledge of students from public high schools in poor communities about HPV and Sexually Transmitted Infections and their attitude towards and prevention of such diseases. Cross-sectional study with adolescents from public schools of São Paulo - Brazil. Participants were selected for an interview by a randomization program. A questionnaire about knowledge, attitudes, and preventive practices regarding STIs, including HPV, according to sex was administered and answers were analyzed by the Poisson regression model with robust variance. Median age of the 269 participants was 16 years. The majority was of African descent (68.8%, n = 185), most (74%, n = 199) were religious and the vast majority (90.7%, n = 244) lived with their parents. The Poisson regression revealed statistically significant sex-related differences regarding the following questions: "Do you know how it is prevented?" (PR = 1.12 [1.03‒1.23], p = 0.007); "Have you ever been concerned with HPV?" (PR = 1.10 [1.02‒1.19], p = 0.011); "Have you ever sought health care due to concerns about HPV?" (PR = 1.09 [1.04‒1.14], p < 0.001); "Do you know what a Pap Smear is?" (PR = 1.24 [1.13‒1.36], p < 0.001); "Do you know what the cervix is?" (PR = 1.23 [1.13‒1.34], p < 0.001); "Do you know what cervical cancer is?" (PR = 1.13 [1.04‒1.22], p = 0.004). The present results show that adolescents from public schools in poor communities in São Paulo City know little about HPV and cervical cancer. Male adolescents know less than female adolescents and are less concerned with health care.

Prevalence of oncogenic human papillomavirus in pregnant adolescents, association with colpocytological changes, risk factors and obstetric outcomes

The authors aim to carry out an investigation on the impact of cervical oncogenic Human Papillomavirus (HPV) detection in pregnant adolescents, to clarify the prevalence and risk factors, considering the importance and lack of data on this topic in Brazil. A cross-sectional study was conducted with adolescents receiving prenatal care in a tertiary hospital in São Paulo, Brazil, with routine Pap smear and oncogenic HPV detection test in the uterine cervix. The authors sought to associate the results of these tests with demographic and obstetric variables. A total of 303 pregnant adolescents whose mean age was 15.30 ± 1.22 years comprised the study subjects. The frequency of high-risk HPV cervical detection was 50.50%. Multivariate analysis revealed that a large number of partners in their lifetime (OR = 1.27) and having a religion (OR = 2.05) were risk factors for cervical detection of oncogenic HPV, while schooling appeared as a protective factor (OR = 0.85). There was an association between this detection and colpocytological alterations, reaching almost 30% of patients, but without association with obstetric and neonatal outcomes. The prevalence found is one of the highest in Brazil and worldwide. A greater number of partners during their lifetime and having religion were detected as possible factors associated with cervical HPV detection. Detection of cervical HPV-DNA did not influence obstetric and neonatal outcomes. The findings of this study reinforce the need to implement educational measures capable of modifying the incidence of sexually transmitted infections in this population and capable of promoting adherence to HPV vaccination programs.