Ferrofluid for radiofrequency capacitive hyperthermia: In-vitro study

The current work deals with preparation and characterization of electrically lossy ferrofluid which can be used as a mediator for radio frequency (RF) - capacitive hyperthermia method. To this end, ferrofluid that can absorb the energy of alternating electrical field at the frequencies commonly employed in RF-capacitive hyperthermia (13.56 and 27.12 MHz) has been prepared by co-precipitation method. This ferrofluid comprises of electrically conductive component with core-shell structure, i.e. magnetite nanoparticles (NPs) coated by dextran, organized in chain-like structure. The effect of RF - capacitive hyperthermia in the presence of mediator was studied on the series of tests performed on HaCaT and HepG2 cell lines using MMT test. The RF-electrical field (13.56 MHz) with controllable power output was applied using the EHY-110 SA (Oncotherm group) to increase the temperature of samples from 37°C up to target temperature of 44°C. The results of in-vitro test clearly indicate that the usage of capacitive heating of obtained ferrofluid substantially contribute to cytotoxic effect of hyperthermia treatment.Ministry of Education, Youth and Sports of the Czech Republic Program NPU I [LO1504

Bratislava Statement: consensus recommendations for improving pancreatic cancer care

Pancreatic cancer is one of the most lethal tumours, and it is the fourth cause of cancer death in Europe. Despite its important public health impact, no effective treatments exist, nor are there high-visibility research efforts to improve care. This alarming situation is emblematic of a larger group of cancer diseases, known as neglected cancers. To address the impact of these diseases, the European Commission-supported Innovative Partnership for Action Against Cancer launched a multi-stakeholder initiative to determine key steps that healthcare systems can rapidly implement to improve their response. A working group comprising 20 representatives from European medical societies, patient associations, cancer plan organisations and other relevant European healthcare stakeholders was organised. A consensus process based on the results of different studies, discussion of research outcomes, and development and endorsement of draft statements resulted in 22 consensus recommendations (the Bratislava Statement). The statement argues that substantial improvements can be achieved in patient outcomes by centralising pancreatic cancer care around state-of-the-art reference centres, staffed by expert multidisciplinary teams capable of providing high-quality care. This organisational model requires a specific care framework encompassing primary, palliative and survivorship care, and a policy environment prioritising the use of quality criteria and performance assessments as well as research investments dedicated to prevention, risk prediction, early detection and diagnosis. In order to address the challenges posed by neglected cancers in general and pancreatic cancer in particular, a specific control strategy tailored to this reality is required

DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death

The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan-Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06-1.90) for overall mortality, and 1.94 (1.04-3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases

ALDH1A inhibition sensitizes colon cancer cells to chemotherapy

Abstract Background Recent evidence in cancer research, developed the notion that malignant tumors consist of different subpopulations of cells, one of them, known as cancer stem cells, being attributed many important properties such as enhanced tumorigenicity, proliferation potential and profound multidrug resistance to chemotherapy. Several key stem cells markers were identified in colon cancer. In our study we focused on the aldehyde dehydrogenase type 1 (ALDH1) expression in colon cancer-derived cell lines HT-29/eGFP, HCT-116/eGFP and LS-180/eGFP, and its role in the chemoresistance and tumorigenic potential. Methods The effect of pharmacological inhibition of ALDH activity by diethylaminobenzaldehyde (DEAB) and also effect of molecular inhibition by specific siRNA was evaluated in vitro in cultures of human colorectal cell lines. The expression level of different isoenzymes of aldehyde dehydrogenase was determined using qPCR. Changes in cell biology were evaluated by expression analysis, western blot and apoptosis assay. The efficiency of cytotoxic treatment in the presence of different chemotherapeutic drugs was analyzed by fluorimetric assay. Tumorigenicity of cells with specific ALDH1A1 siRNA was tested in xenograft model in vivo. Results Treatment by DEAB partially sensitized the tested cell lines to chemotherapeutics. Subsequently the molecular inhibition of specific isoforms of ALDH by ALDH1A1 or ALDH1A3 siRNA led to sensitizing of cell lines HT-29/eGFP, HCT-116/eGFP to capecitabine and 5-FU. On the model of athymic mice we observed the effect of molecular inhibition of ALDH1A1 in HT-29/eGFP cells by siRNA. We observed inhibition of proliferation of subcutaneous xenografts in comparison to control cells. Conclusion This research, verifies the significance of the ALDH1A isoforms in multidrug resistance of human colorectal cancer cells and its potential as a cancer stem cell marker. This provides the basis for the development of new approaches regarding the treatment of patients with colorectal adenocarcinoma and potentially the treatment of other tumor malignancies