Search

Ovarian cancer poses a significant threat to patients in its advanced stages, often with limited treatment options available. In such cases, palliative management becomes the primary approach to maintaining a reasonable quality of life. Therefore, the administration of any medication that can benefit patients without a curative option holds potential. Resveratrol, a natural compound known for its in vitro anticancer activities, has generated contrasting results in vivo and human studies. In this study, we aimed to assess the anticancer effects of resveratrol on ovarian cancer cells grown on the chorioallantoic membrane (CAM) of chicken embryos. Two ovarian cancer cell lines, OVCAR-8 and SKOV-3, were cultured in collagen scaffolds for four days before being implanted on the CAM of chicken embryos on day 7. Different doses of resveratrol were applied to the CAM every two days for six days. Subsequently, CAM tissues were excised, fixed, and subjected to histological analysis. Some CAM tumours were extracted to analyse proteins through Western blotting. Our findings indicate that specific doses of resveratrol significantly reduce angiogenic activities, pNF-κB levels, and SLUG protein levels by using immunohistochemistry. These results suggest that resveratrol may have the potential to impact the behaviour of ovarian cancer CAM tumours, thereby warranting further consideration as a complementary treatment option for women with incurable ovarian cancer.

BackgroundMāori are the Indigenous people of Aotearoa (New Zealand). Despite global acceptance that cervical cancer is almost entirely preventable through vaccination and screening, wāhine Māori (Māori women) are more likely to have cervical cancer and 2.5 times more likely to die from it than non-Māori women. Rural Māori residents diagnosed with cervical cancer have worse outcomes than urban residents. Living in rural Aotearoa means experiencing barriers to appropriate and timely health care, resulting from distance, the lack of community resourcing, and low prioritization of rural needs by the health system and government. These barriers are compounded by the current screening processes and referral pathways that create delays at each step. Screening for high-risk human papillomavirus (hrHPV) and point-of-care (POC) testing are scientific advances used globally to prevent cervical cancer. ObjectiveThis study aims to compare acceptability, feasibility, timeliness, referral to, and attendance for colposcopy following hrHPV detection between a community-controlled pathway and standard care. MethodsThis is a cluster randomized crossover trial, with 2 primary care practices (study sites) as clusters. Each site was randomized to implement either pathway 1 or 2, with crossover occurring at 15 months. Pathway 1 (community-controlled pathway) comprises HPV self-testing, 1-hour POC results, face-to-face information, support, and immediate referral to colposcopy for women with a positive test result. Pathway 2 (standard care) comprises HPV self-testing, laboratory analysis, usual results giving, information, support, and standard referral pathways for women with a positive test result. The primary outcome is the proportion of women with hrHPV-positive results having a colposcopy within 20 working days of the HPV test (national performance indicator). Qualitative research will analyze successes and challenges of both pathways from the perspectives of governance groups, clinical staff, women, and their family. This information will directly inform the new National Cervical Screening Program. ResultsIn the first 15-month period, 743 eligible HPV self-tests were performed: 370 in pathway 1 with POC testing and 373 in pathway 2 with laboratory testing. The positivity rate for hrHPV was 7.3% (54/743). Data collection for the second period, qualitative interviews, and analyses are ongoing. ConclusionsThis Māori-centered study combines quantitative and qualitative research to compare 2 clinical pathways from detection of hrHPV to colposcopy. This protocol draws on rural community practices strengths, successfully engaging Māori from a whānau ora (family wellness) approach including kanohi ki te kanohi (face-to-face), kaiāwhina (nonclinical community health workers), and multiple venues for interventions. It will inform the theory and practice of rural models of the use of innovative technology, addressing Māori cervical cancer inequities and facilitating Māori wellness. The findings are anticipated to be applicable to other Indigenous and rural people in high-income countries. Trial RegistrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000553875; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621000553875 International Registered Report Identifier (IRRID)DERR1-10.2196/51643

Introduction The National Cervical Screening Programme (NCSP) will switch from cervical cytology to Human Papillomavirus (HPV) testing as the primary cervical screening modality in 2023. To prepare for rollout an implementation study of HPV testing in primary care commenced in August 2022 in three different geographic regions in NZ. Aims This study explores Primary Care Staff’s experience of using the HPV testing pathway in the ‘Let’s test for HPV’ study so that recommendations can be made to improve the testing process before nationwide roll-out. Method Thirty-nine primary care staff were interviewed across all 17 practices in the Capital and Coast, Canterbury and Whanganui region participating in the ‘Let’s Test For HPV’ study. In total 19 interviews took place which followed a semi-structured approach. These interviews were recorded and transcribed. Template analysis was carried out on transcripts to aid in identifying themes. Results Three key themes, with additional subthemes, were identified. Staff were strongly supportive of the new testing regime. Interviewees identified some issues with the new pathway. Educational needs for both patients and clinicians were identified. Conclusion Primary care staff described the experience of using the HPV testing pathway positively; however, there were requests for ongoing additional support and nationwide rollout to be supported by practitioner and patient education programmes. With the right support this new pathway for cervical cancer screening has the potential to improve access for previously underserved and unserved groups.

Background: A preclinical animal model is an imperative tool for uncovering and understanding the tumourigenic hallmarks of human ovarian cancer; the disease is often lethal because it is commonly diagnosed in the advanced stage, where widespread cancer nodules mainly reside within peritoneal regions. Mouse models as a xenograft tumour host or genetic manipulation ovarian cancer-derived mice are widely used for studying specific hypothesis rationale in ovarian cancer. However, limited information associated with disease progression is obtained from such studies; whether it is the best model to study advanced ovarian cancer phenotype or suitable preclinical biomarkers for detecting and monitoring ovarian cancer progression is under study. This study used an ID-8 syngeneic mouse ovarian cancer model with immunocompetence. We monitored cancer growth and development using combination modalities of cancer-specific cancer antigen-125 (CA-125), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) blood markers, which are well-known for their association with tumour progression in humans. Methods: Ten C57/BL6 female mice were intraperitoneally implanted with ID-8 Trp53 wild-type and monitored the progression of the tumour, until mice developed clinical ascites. Blood was taken at the time of intraperitoneal (IP) implantation (Day 0) and then collected weekly, and levels of biomarkers were analysed with enzyme-linked immunosorbent assay (ELISA). In addition, tumour tissue was collected and proceeded with histological staining. Results: We found that blood biomarkers CA-125, IL-6 and VEGF were not readily correlated with tumour progression. However, these biomarkers were markedly elevated in ascitic fluid at the advanced stage of the disease. Conclusions: We conclude that blood biomarkers in a syngeneic mouse model are, to some extent, not readily found in the blood as opposed to human ovarian cancer. Model anatomical and physiological differences between rodents and humans might explain this discrepancy.

High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18) cervical intraepithelial neoplasia grade 2 lesions differed from other high-risk types (HPV ‘other’). Consistent with other studies, we found that progression to higher-grade disease was more frequent in HPV16/18 lesions when compared with HPV ‘other’ lesions. HPV16/18 lesions were significantly more likely to be indoleamine 2,3,-dioxygenase 1 (IDO1)-positive and were associated with reduced CD8 and FoxP3 T cells in the lesion. In the stroma, reduced Tbet- and CD32-positive cells and increased Blimp1-positive cells were significantly associated with HPV16/18 lesions when compared with HPV ‘other’ types. On analysis of the IDO1-positive tissues, lesional IDO1 was associated with significantly decreased numbers of CD4-, CD8-, and FoxP3-positive cells in the stroma compared with IDO1-negative tissues. These data suggest that IDO1 expression may impair infiltration of CD4, CD8, and FoxP3 cells into the stroma beneath the precancer lesion. Increased expression of IDO1 may contribute to immune avoidance and an increased frequency of disease progression in HPV16- and 18-positive lesions.

BackgroundCervical cancer is caused by high-risk types of human papillomavirus (HPV). Testing for high-risk HPV is a more sensitive screening method than cervical cytology for detecting cervical changes that may lead to cancer. Consistent with recent evidence of efficacy and acceptability, Aotearoa New Zealand plans to introduce HPV testing as the primary approach to screening, replacing cervical cytology, from mid-2023. Any equitable cervical screening programme must be effective across a diverse population, including women that the current programme fails to reach, particularly Māori and those in rural areas. Currently, we do not know the best model for implementing an equitable HPV self-testing screening programme.MethodsThis implementation trial aims to assess whether a universal offer of HPV self-testing (offered to all people eligible for cervical screening) achieves non-inferior screening coverage (equal) to a universal offer of cervical cytology alone (the present programme). The study population is all people aged from 24.5 to 70 years due for cervical screening in a 12-month period (including those whose screening is overdue or who have never had screening). A range of quantitative and qualitative secondary outcomes will be explored, including barriers and facilitators across screening and diagnostic pathways. This study takes place in Te Tai Tokerau/Northland which covers a diverse range of urban and rural areas and has a large Indigenous Māori population. A total of fourteen practices will be involved. Seven practices will offer HPV self-testing universally to approximately 2800 women and will be compared to seven practices providing routine clinical care (offer of cervical cytology) to an approximately equal number of women.DiscussionThis trial will answer important questions about how to implement an equitable, high-quality, effective national programme offering HPV self-testing as the primary screening method for cervical cancer prevention.Trial registrationProspectively registered with the Australian New Zealand Clinical Trials Registry 07/12/2021: ACTRN12621001675819.

Background Cervical cancer is caused by high-risk types of human papillomavirus (HPV). Testing for high-risk HPV is a more sensitive screening method than cervical cytology for detecting cervical changes that may lead to cancer. Consistent with recent evidence of efficacy and acceptability, Aotearoa New Zealand plans to introduce HPV testing as the primary approach to screening, replacing cervical cytology, from mid-2023. Any equitable cervical screening programme must be effective across a diverse population, including women that the current programme fails to reach, particularly Māori and those in rural areas. Currently, we do not know the best model for implementing an equitable HPV self-testing screening programme. Methods This implementation trial aims to assess whether a universal offer of HPV self-testing (offered to all people eligible for cervical screening) achieves non-inferior screening coverage (equal) to a universal offer of cervical cytology alone (the present programme). The study population is all people aged from 24.5 to 70 years due for cervical screening in a 12-month period (including those whose screening is overdue or who have never had screening). A range of quantitative and qualitative secondary outcomes will be explored, including barriers and facilitators across screening and diagnostic pathways. This study takes place in Te Tai Tokerau/Northland which covers a diverse range of urban and rural areas and has a large Indigenous Māori population. A total of fourteen practices will be involved. Seven practices will offer HPV self-testing universally to approximately 2800 women and will be compared to seven practices providing routine clinical care (offer of cervical cytology) to an approximately equal number of women. Discussion This trial will answer important questions about how to implement an equitable, high-quality, effective national programme offering HPV self-testing as the primary screening method for cervical cancer prevention. Trial registration Prospectively registered with the Australian New Zealand Clinical Trials Registry 07/12/2021: ACTRN12621001675819.

Introduction: The economic contributions made by informal carers in the UK per year mount up to £132 billion. This is equivalent to the total amount of the health care costs, yet the health and wellbeing of carers are often not prioritised. This review paper aims to determine the key health impacts of informal caregiving and evaluate support/control methods in the UK. Methods: This thematic review was conducted in accordance with an adapted version of the PRISMA guidelines for systematic reviews. Of the 6,482 articles identified through Pubmed/Medline, CINAHL, SpringerLink, Summon, and grey literature, 38 studies were included in the review. Results: The key health impacts of being an informal carer were identified as musculoskeletal disorders and psychological issues (such as depression, stress and anxiety), which were categorized as ‘high-risk impact’ areas. The review further identified cardiovascular disease and early mortality as ‘low to moderate risk impact’ areas and a thematic area that revolves around positive impacts on health of informal carers. Financial help, proper respite care, availability and accessibility of information and advice, provision of equipment in a timely manner and adequate support networks were found to be key factors useful in minimising musculoskeletal and psychological disorders. Discussion and Conclusions: There is a need for policy makers and program implementers to recognize and accommodate the ever-changing role of carers on different stages of caring. There is also a need to review key health policy documents to include informal carers’ needs and improve support systems available. The lack of evidence-based research on the psycho-physical impacts of caring and the lack of evaluation of services that impact the health of carers also needs to be addressed with priority.

Background: advanced ovarian cancer often presents with ascites. These ascites contain small clusters of cancer cells, which may contribute greatly to the metastatic potential of ovarian cancer in the peritoneal cavity. Therefore, understanding the unique protein expressions of this cell population will provide vital information for the development of tailored, targeted treatment. In this study, we isolate floating ovarian cancer cells from ovarian cancer patient ascitic fluid and use these cells to document that the expression of EGFR/HER-2 proteins may be essential for the growth and survival of these floating cancer cell clusters. Methods: ascitic fluid-derived cells were isolated from ascitic fluid by using Ficoll separation. Cells were cultured in a non-adherent condition for six days. The protein level of EGFR, HER-2, AKT, and ERK and their phosphorylation in ovarian cancer cell lines were determined by immunofluorescence. The immunofluorescent staining for proteins presented in ascitic fluid-derived cells determined the intensity profile of each protein using Carl Zeiss Blue software. Results: Isolated ovarian cancer cells from ascitic fluid have a measurable level of EGFR and HER-2 proteins. The inhibition of EGFR and EGFR/HER-2 positive cells with gefitinib and canertinib selectively disrupts cell viability and the protein level of EGFR, HER-2, AKT and ERK and their respective phosphorylation status. In addition, the dual EGFR/HER-2 inhibitor canertinib demonstrates greater anti-tumour effects than gefitinib in EGFR/HER-2 positive cells. Conclusion: These studies reveal an important role of multiple activation of receptor tyrosine kinases in floating ovarian cancer cells, as well as the importance of a dual EGFR/HER-2 inhibitor used as alternative adjuvant therapy in advanced ovarian cancer patients.