Radiofrequency driving antitumor effect of graphene oxide-based nanocomposites: a Hill model analysis.

Aim: This report proposes using the Hill model to assess the benchmark dose, the 50% lethal dose, the cooperativity and the dissociation constant while analyzing cell viability data using nanomaterials to evaluate the antitumor potential while combined with radiofrequency therapy. Materials & methods: A nanocomposite was synthesized (graphene oxide-polyethyleneimine-gold) and the viability was evaluated using two tumor cell lines, namely LLC-WRC-256 and B16-F10. Results: Our findings demonstrated that while the nanocomposite is biocompatible against the LLC-WRC-256 and B16-F10 cancer cell lines in the absence of radiofrequency, the application of radiofrequency enhances the cell toxicity by orders of magnitude. Conclusion: This result points to prospective studies with the tested cell lines using tumor animal models.

Co-designed, culturally tailored cervical screening education with migrant and refugee women in Australia: a feasibility study.

BACKGROUND: Participation of culturally and linguistically diverse (CALD) women from migrant and refugee backgrounds in cervical screening is crucial to eliminate cervical cancer as a public health problem within the next 20 years. However, CALD women report low participation in cervical screening. Barriers to participation can be addressed with culturally tailored, community-based programs. There is a need for research to explore the process, feasibility, acceptability and barriers to cultural tailoring in the delivery and evaluation of cervical screening health education. METHODS: CALD community health workers took part in a 2 day training program then co-designed, culturally tailored and co-facilitated cervical screening health promotion forums within their communities. Forums were delivered to a total of seven groups, involving 12 sessions and 71 CALD women. The forums were evaluated for feasibility, acceptability, implementation and effectiveness using a survey, interviews and observations. Data were collected from CALD women, facilitators and researchers. RESULTS: The co-design and co-delivery of cervical screening health promotion forums was time and resource intensive however allowed for deeper cultural tailoring resulting in engagement with 'hard to reach' CALD women, improved health literacy and intention to screen. Flexibility in the intervention implementation was crucial to ensure forums were responsive to community interests and needs. Online delivery of the forums in response to the COVID-19 pandemic was acceptable to most groups. CONCLUSIONS: Co-designed, culturally tailored cervical screening health promotion forums are feasible and acceptable to CALD women, in both face-to-face and online formats. Adjustments to the intervention protocol were recommended to improve future implementation.

Parametric evaluation of impedance curve in radiofrequency ablation: A quantitative description of the asymmetry and dynamic variation of impedance in bovine ex vivo model.

Radiofrequency ablation (RFA) is a treatment for liver tumors with advantages over the traditional treatment of surgical resection. This procedure has the shortest recovery time in early stage tumors. The objective of this study is to parameterize the impedance curve of the RFA procedure in an ex vivo model by defining seven parameters (t1/2, tminimum, tend, Zinitial, Z1/2, Zminimum and Zend). Based on these parameters, three performance indices are defined: one to identify the magnitude of impedance curve asymmetry (δ), one Drop ratio (DR) describing the percentage of impedance decrease until the minimum impedance point is reached, and Ascent Ratio (AR) describing the magnitude of increase in impedance from the minimum impedance point to its maximum point. Fifty ablations were performed in a bovine ex vivo model to measure and evaluate the proposed parameters and performance index. The results show that the groups had an average δ of 29.02%, DR of 22.41%, and AR of 545.33% for RFA without the use of saline or deionized solutions. The saline solution and deionized water-cooled groups indicated the correlation of performance indices δ, DR, and AR with the obtained final ablation volume. Therefore, by controlling these parameters and indices, lower recurrence is achieved.

Nuclear softening is essential for protease-independent migration.

During amoeboidal migration, cancer cells migrate in a protease-independent manner by squeezing through pre-existing gaps in the extracellular matrix (ECM). However, the extent to which cells alter their physical properties in order to sustain this mode of migration remains unclear. Here, we address this question by documenting biophysical changes in the properties of highly invasive MDA-MB-231 and HT-1080 cells upon inhibition of pericellular proteolysis. Remarkably, treatment with the broad spectrum MMP inhibitor GM6001 not only induces cell rounding and loss of actomyosin contractility, but also induces nuclear softening via increased phosphorylation of the nuclear membrane protein lamin A/C. Though nuclear softening is necessary for sustaining migration through sub-nuclear sized transwell pores, it is not sufficient. In addition, baseline levels of contractility mediating pore entry and peri-nuclear actin inside the pores mediating pore migration are also required. Taken together, our results suggest that protease-independent migration through sub-nuclear sized pre-existing tracks is enabled by deformation of a softened nucleus by contractility and the peri-nuclear actin network.

Roll-Off Displacement in Ex Vivo Experiments of RF Ablation With Refrigerated Saline Solution and Refrigerated Deionized Water.

OBJECTIVE: The recurrence rate in the treatment of liver tumors using radio frequency ablation (RFA) is often related to incomplete tissue necrosis and consequently the limitation in the ablation volume. This paper proposes an ablation protocol combined with the infusion of saline solution and deionized water aiming at achieving a time displacement in the roll-off occurrence and consequently increasing the volume of ablation. METHODS: An infusion of saline solution and deionized water at 5 and 23  °C was performed to evaluate the influence of these liquids on the RFA procedure in ex vivo bovine liver pieces. The obtained results were used to propose a mathematical model of the roll-off phenomenon by means of the system identification techniques. RESULTS: The RFA combined with the infusion of saline solution 0.9% at 5  °C presented optimal results, with a time delay of the roll-off occurrence in 27.8% compared to pure RFA ( p = 0.002) and an increase in the necrotic volume of 51.2% ( p = 0.0002). Two Box-Jenkins models were obtained to describe the roll-off phenomenon: 1) pure RFA; and 2) RFA combined with the saline solution 0.9% at 5  °C. CONCLUSION: The RFA therapy combined with the saline solution 0.9% at 5  °C increases the time range to the roll-off occurrence, leading to higher necrosis volumes in ex vivo bovine liver samples. The development of a mathematical model to describe the roll-off behavior demonstrated that the transient response is improved by the infusion of the saline solution 0.9% at 5  °C.

Soft drug-resistant ovarian cancer cells migrate via two distinct mechanisms utilizing myosin II-based contractility.

The failure of chemotherapeutic drugs in treatment of various cancers is attributed to the acquisition of drug resistance. However, the migration mechanisms of drug-resistant cancer cells remain incompletely understood. Here we address this question from a biophysical perspective by mapping the phenotypic alterations in ovarian cancer cells (OCCs) resistant to cisplatin and paclitaxel. We show that cisplatin-resistant (CisR), paclitaxel-resistant (PacR) and dual drug-resistant (i.e., resistant to both drugs) OCCs are more contractile and softer than drug-sensitive cells. Protease inhibition suppresses invasion of CisR cells but not of PacR cells, indicative of a protease-dependent mode of migration in CisR cells and a protease-independent mode of migration in PacR. Despite these differences, actomyosin contractility, mediated by the RhoA-ROCK2-Myosin II signaling pathway, regulates both modes of migration. Confined migration experiments establish the role of myosin IIA and IIB in mediating nuclear translocation and regulation of proteolytic activity. Collectively, our results highlight the importance of myosin II as a potential therapeutic target for treatment of drug-resistant ovarian cancer cells.

MMP proteolytic activity regulates cancer invasiveness by modulating integrins.

Cancer invasion through dense extracellular matrices (ECMs) is mediated by matrix metalloproteinases (MMPs) which degrade the ECM thereby creating paths for migration. However, how this degradation influences the phenotype of cancer cells is not fully clear. Here we address this question by probing the function of MMPs in regulating biophysical properties of cancer cells relevant to invasion. We show that MMP catalytic activity regulates cell spreading, motility, contractility and cortical stiffness by stabilizing integrins at the membrane and activating focal adhesion kinase. Interestingly, cell rounding and cell softening on stiff gels induced by MMP inhibition is attenuated on MMP pre-conditioned surfaces. Together, our results suggest that MMP catalytic activity regulates invasiveness of cancer cells by modulating integrins.

"In My Culture, We Don't Know Anything About That": Sexual and Reproductive Health of Migrant and Refugee Women.

PURPOSE: Migrant and refugee women are at risk of negative sexual and reproductive health (SRH) outcomes due to low utilisation of SRH services. SRH is shaped by socio-cultural factors which can act as barriers to knowledge and influence access to healthcare. Research is needed to examine constructions and experiences of SRH in non-English-speaking migrant and refugee women, across a range of cultural groups. METHOD: This qualitative study examined the constructions and experiences of SRH among recent migrant and refugee women living in Sydney, Australia, and Vancouver, Canada. A total of 169 women from Afghanistan, Iraq, Somalia, South Sudan, Sudan, India, Sri Lanka and South America participated in the study, through 84 individual interviews, and 16 focus groups comprised of 85 participants. Thematic analysis was used to analyse the data. RESULTS: Three themes were identified: "women's assessments of inadequate knowledge of sexual and reproductive health and preventative screening practices", "barriers to sexual and reproductive health" and "negative sexual and reproductive health outcomes". Across all cultural groups, many women had inadequate knowledge of SRH, due to taboos associated with constructions and experiences of menstruation and sexuality. This has implications for migrant and refugee women's ability to access SRH education and information, including contraception, and sexual health screening, making them vulnerable to SRH difficulties, such as sexually transmissible infections and unplanned pregnancies. CONCLUSION: It is essential for researchers and health service providers to understand socio-cultural constraints which may impede SRH knowledge and behaviour of recent migrant and refugee women, in order to provide culturally safe SRH education and services that are accessible to all women at resettlement irrespective of ethnicity or migration category.