Sexual Reproductive Health and Rights Repository (Aga Khan University)
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CD73 promotes cervical cancer growth via EGFR/AKT1 pathway
Full text linkBackground:
Cervical cancer ranks third in cancer incidence worldwide and is the most frequent gynecological cancer in developing countries. To expore the molecular mechanism of cervical cancer and to find effective treatment have become the focus of medical workers. CD73 has been implicated in the progression of many cancers. However, the study of CD73 in cervical cancer has not been reported. The aim of this study was to identify the effect and mechanism of CD73 overexpression on cervical cancer growth in vitro and in vivo.
Methods:
Cervical cancer cell models with CD73 overexpression were construction by using lentiviruses infection in Hela and SiHa cells. Cell’s proliferation was investigated by using xCELLigence real-time cell analysis (RTCA) system. Murine xenograft models were used to evaluate the effect of CD73 overexpression on tumor growth in vivo. Small interfering RNA (siRNA) transfection were used to suppress expression levels of EGFR and AKT1. Cell cycle and apoptosis were evaluated by flow cytometry (FCM).
Results:
CD73 overexpression significantly promoted cervical cancer cells proliferation in vitro and tumor growth in vivo. The expression levels of EGFR and AKT1 were significantly increased in cell models and transplanted tumor tissues with CD73 overexpression. And moreover, knockdown of EGFR and AKT1 could inhibit proliferation of CD73 overexpressed cell models via inducing cell apoptosis and cell cycles increased in G2/M phase and reduction of G1 phase. Furthermore, the expression levels of CDK2, CDK3 and CDKN1A, which are cell cycle regulated molecules, were significantly increased in CD73 overexpressed cells with EGFR/AKT1 knockdown.
Conclusions:
Our data demonstrated that CD73 overexpression promote cervical cancer growth in vitro and in vivo, via activating EGFR/AKT1 pathway
DNA methylation of miR-138 regulates cell proliferation and EMT in cervical cancer by targeting EZH2
Full text linkBackground:
Emerging evidence has identified miR-138 as a tumor suppressor that can suppress the proliferation of various cancers. Meanwhile, the cause of abnormal miR-138 expression in cervical cancer remains uncertain. This study clarified the mechanism by which miR-138 regulates proliferation, invasion, metastasis, and EMT in cervical cancer cells.
Results:
miR-138 expression in human cervical cancer and adjacent normal tissue was measured using qPCR. SiHa and C33A cells were used to determine the function of miR-138 via miR-138 mimic or inhibitor transfection, followed by wound healing, Cell Counting Kit-8, flow cytometry, and Transwell assays. Epithelial and mesenchymal marker expression was analyzed using Western blotting. DNA methylation in the miR-138 promoter was examined using bisulfite sequencing PCR. The downstream target genes of miR-138 were identified via bioinformatics analysis and luciferase reporter assays. A tumor xenograft model was employed to validate DNA methylation-induced miR-138 downregulation and tumor growth inhibition in cervical cancer in vivo. miR-138 levels were significantly lower in cervical cancer tissues than in adjacent control tissues. Furthermore, lower miR-138 expression and higher CpG methylation in the miR-138 promoter were identified in lymph node-positive metastatic cervical cancer tumors versus that in non-metastatic tumor tissues. Upon miR-138 overexpression, cell proliferation, metastasis, invasion, and EMT were suppressed. miR-138 agomir transfection and demethylating drug treatment significantly inhibited cervical tumor growth and EMT in tumor xenograft models. DNA methylation inhibited miR-138 transcription, and enhancer of zeste homolog 2 (EZH2) downregulation mediated the tumor suppressor function of miR-138 in cervical cancer.
Conclusion:
We demonstrated that miR-138 suppresses tumor progression by targeting EZH2 in cervical cancer and uncovered the role of DNA methylation in the miR-138 promoter in its downregulation. These findings demonstrated the potential of miR-138 to predict disease metastasis and/or function as a therapeutic target in cervical cancer
Researching students’ experiences of sexual and gender-based violence and harassment: reflections and recommendations from surveys of three UK HEIS
Full text linkIn the US, ‘campus climate surveys’ are an established measure of the prevalence of, and students’ awareness of and attitudes to sexual and gender-based violence and harassment (SGBVH). They are regularly carried out by universities to assist SGBVH prevention and responses. Such surveys have only recently started to be carried out within UK higher education institutions (HEIs) and the three authors of this article all independently undertook such surveys in different HEIs. Comparing our experiences of undertaking these surveys across three HEIs allows us to explore similarities and differences in our experiences of this type of research, in particular the challenges which arose in carrying out such research in three very different types of HEI. This article presents reflections on the methodological and political challenges of such work. We discuss our rationales for initiating these projects, the methodological approaches we employed, the governance structures navigated in pursuing the research and the difficulties that arose in conducting and reporting on the research. This article will be of interest to academics, activists, and policy-makers—domestically and internationally—who wish to carry out such research. By comparing approaches, we draw attention to issues and potential impediments of relevance to others wanting to embark on similar work within their own HEI. View Full-Tex
The more you know, the less you stress: menstrual health literacy in schools reduces menstruation-related stress and increases self-efficacy for very young adolescent girls in Mexico
Full text linkImproving the menstrual health literacy of girls and boys is a key strategy within a holistic framework of Save the Children's school health and comprehensive sexuality education programming. As menstrual health is an emerging area of study and programming, Save the Children continues to learn and adjust its interventions using program evaluations and rigorous monitoring. This paper will examine program-monitoring data from three cohorts, representing 47 public schools in Mexico City, Puebla, and Mérida, Mexico. The study focuses on female students in 5th and 6th grade who participated in We See Equal, a school-based program centered on gender equality and puberty education, between September 2018 and December 2019. This study used a cross-sectional quantitative cohort approach to document changes in girls' experiences and perceptions around managing menstruation in school. The analysis compares girls' knowledge and experiences before and after participation in We See Equal to understand how knowledge changes over the program and how those changes may contribute to menstruation-related school engagement, stress, and self-efficacy (MENSES) outcomes. Multivariate regression models explored relationships between MENSES outcomes, knowledge and socioeconomic status (SES). Overall, results show that the more knowledge girls acquired, the higher their self-efficacy score and the lower their stress score, however, certain MHH knowledge was more predictive of MENSES outcomes and varied by SES. Among girls from lower SES, we observed significant relationships between knowing what their period was prior to menarche and the three MENSES outcomes. Decreases in menstruation-related stress were driven by items related to the practical knowledge of how to dispose of sanitary pads and reduced feelings of nervousness on days they had their period at school. Increases in self-efficacy were primarily driven by girls' confidence in their ability to track their period from month to month, feelings that they could still do well on an exam if they had their period at school, and security that they could ask a friend to lend them a pad if they needed one. Implications for future menstrual health literacy programming and targeting populations for menstrual health education, as well as priorities for future research will be discussed
Using social media to change gender norms : an experiment within facebook messenger in India
Full text linkThis paper experimentally tests the effectiveness of two short edutainment campaigns (under 25 minutes) delivered through Facebook Messenger at reshaping gender norms and reducing social acceptability of violence against women in India. Participants were randomly assigned to watch video clips with implicit or explicit messaging formats (respectively a humorous fake reality television drama or a docuseries with clear calls to action). After one week, the intent-to-treat effects of the implicit format on knowledge, gender norms, and acceptability of violence against women oscillated between 0.16 and 0.21 standard deviations yet impacts diminished after four months. By contrast, the explicit format was more impactful in the short term in increasing willingness to share video clips with friends and promoting online information-seeking behaviors. In the medium term, individuals who were exposed to the docuseries were 91 percent (7.5 percentage points) more likely to add a frame against violence against women in their Facebook profile picture, a public display of their disapproval of this harmful practice. The general lack of heterogeneous effects across social status indicators suggests social media as a potential medium for reaching different online populations, including vulnerable ones
Cervical cancer prevention in El Salvador: gains to date and challenges for the future
Full text linkSimple Summary:
Cervical cancer is a leading cause of death for women in low-resource areas around the world. However, the disease can be prevented through vaccination, screening, and early treatment. Recently, the World Health Organization released a strategy with the goal of eliminating cervical cancer through a combination of these three preventive strategies. In El Salvador, a screening program has been in place for some years, and vaccination is in its early stages. Here, we describe the Salvadoran experience and discuss successes to date and challenges for the future. We also provide recommendations that may be helpful for other countries working to meet the WHO elimination goals.
Abstract:
Cervical cancer is preventable through vaccination, early detection, and the treatment of pre-cancerous lesions. However, global inequalities mean that the disease remains a leading cause of cancer death around the world, with over 80% of new cases and 90% of deaths occurring in low- and middle-income countries (LMICs). In El Salvador, joint efforts between the Ministry of Health (MoH) and the non-profit organization Basic Health International (BHI) have been in place since 2008, with the goal of reducing the country’s disease burden. While the World Health Organization’s (WHO) call to action to eliminate cervical cancer provided worldwide momentum to implement new public health initiatives, the COVID-19 pandemic disrupted ongoing programs and jeopardized plans for the future. The purpose of this manuscript is to describe the progress that El Salvador has achieved in improving cervical cancer prevention, the impact of the pandemic on current strategies, and potential solutions that can help the country meet the WHO’s strategic targets by 2030 to accelerate the elimination of cervical cancer
A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer
Full text linkBackground:
We evaluated the non-inferiority of nedaplatin-based and cisplatin-based concurrent chemoradiotherapy in cervical cancer patients.
Design:
Patients aged 28-82 years with pathologically diagnosed cervical cancer (stage IB-IVA) were randomly chosen for the study. Patients in both the cisplatin and nedaplatin groups received radiotherapy and weekly intravenous nedaplatin 30 mg/m2 or cisplatin 40 mg/m2 concurrently.
Results:
One hundred and sixty patients who received treatment between 10 May 2018 and 31 August 2020 were included. The 3-year overall survival in the nedaplatin group (median 30.5 months) was not significantly different from that in the cisplatin group (28.5 months; hazard ratio 0.131, 95% confidence interval 0.016-1.068; P = 0.058). No significant differences in hematological toxicity were observed between the two groups. Vomiting (40 versus 61), nausea (44 versus 67), and anorexia (52 versus 71) were more common in the cisplatin group whereas effects on liver function, including total bilirubin (7 versus 3), alanine aminotransferase (7 versus 2), and aspartate aminotransferase (6 versus 2), were more common in the nedaplatin group. Four patients in the cisplatin group had grade I creatinine elevation, whereas none in the nedaplatin group had abnormal creatinine levels. Two patients in the nedaplatin group discontinued concurrent chemotherapy because of infusion, and one patient in the cisplatin group discontinued treatment because of infusion-induced dizziness.
Conclusions:
Our findings suggest that nedaplatin has a milder gastrointestinal reaction but a more significant effect on liver function than cisplatin. In patients with cervical cancer, nedaplatin-based concurrent chemoradiotherapy could serve as an alternative treatment to cisplatin
Interest in co-located reproductive and sexual health services among women and men receiving medication for opioid use disorder in an outpatient treatment clinic
Full text linkIntroduction:
Reproductive and sexual health (RSH) are core components of comprehensive care, yet often omitted in addiction treatment. We characterize knowledge of and interest in RSH services and contraceptive method awareness and use in a rural, Appalachian outpatient clinic.
Materials and Methods:
Between September 2016 and April 2018, a convenience sample of 225 patients receiving treatment for opioid use disorder at an outpatient buprenorphine/naloxone clinic was collected. Participants completed a cross-sectional RSH survey that included demographics, interest in RSH service integration, contraceptive use, and contraceptive knowledge.
Results:
A total of 212 people (126 non-pregnant women, 29 pregnant women, and 57 men) completed the survey of whom 45.8% indicated interest in adding RSH services. Services of interest include regular physical exams (44.8%), STI/STD testing (41.0%), and contraception education and administration (38.2%). There were no significant differences between interest in co-located services between women and men (P = 0.327). Current contraceptive use was low (17.9–30.9%) among women and men. Contraceptive method awareness was 43.3% for high efficacy methods and 50.0% for medium efficacy methods. Women and currently pregnant women knew more total, high, and medium efficacy contraceptive method than men (P = 0.029).
Discussion:
Both women and men in this sample are interested in co-located RSH services. Current contraceptive use was low among participants. Contraceptive knowledge was lower among men compared to women, and generally low. Providing co-located RSH services may facilitate RSH education, contraceptive method uptake, and promote engagement across various RSH domains
Navigating multiple pandemics: a critical analysis of the impact of covid-19 policy responses on gender-based violence services
Full text linkCOVID-19 illustrated what governments can do to mobilise against a global threat. Despite the strong governmental response to COVID-19 in Canada, another ‘pandemic’, gender-based violence (GBV), has been causing grave harm with generally insufficient policy responses. Using interpretive description methodology, 26 interviews were conducted with shelter staff and 5 focus groups with 24 executive directors (EDs) from GBV service organizations in Ontario, Canada. Five main themes were identified and explored, namely that: (1) there are in fact four pandemics at play; (2) the interplay of pandemics amplified existing systemic weaknesses; (3) the key role of informal partnerships and community support, (4) temporary changes in patterns of funding allocation; and (5) exhaustion as a consequence of addressing multiple and concurrent pandemics. Implications and recommendations for researchers, policy makers, and the GBV sector are discussed