Hypoxic Jumbo Spheroids On-A-Chip (HOnAChip): Insights into Treatment Efficacy.

Hypoxia is a key characteristic of the tumor microenvironment, too rarely considered during drug development due to the lack of a user-friendly method to culture naturally hypoxic 3D tumor models. In this study, we used soft lithography to engineer a microfluidic platform allowing the culture of up to 240 naturally hypoxic tumor spheroids within an 80 mm by 82.5 mm chip.

Synergy between Non-Thermal Plasma with Radiation Therapy and Olaparib in a Panel of Breast Cancer Cell Lines.

Cancer therapy has evolved to a more targeted approach and often involves drug combinations to achieve better response rates. Non-thermal plasma (NTP), a technology rapidly expanding its application in the medical field, is a near room temperature ionized gas capable of producing reactive species, and can induce cancer cell death both in vitro and in vivo. Here, we used proliferation assay to characterize the plasma sensitivity of fourteen breast cancer cell lines.

Heat shock induces the cellular antioxidant defenses peroxiredoxin, glutathione and glucose 6-phosphate dehydrogenase through Nrf2.

Hyperthermia is a promising anticancer treatment used in combination with radiotherapy and/or chemotherapy. Heat (42-45 °C) can kill cancer cells. Low doses of heat at milder temperatures (39-41 °C) induce thermotolerance, an adaptive survival response that upregulates defense molecules to protect cells against subsequent exposure to toxic stress.

On-chip combined radiotherapy and chemotherapy testing on soft-tissue sarcoma spheroids to study cell death using flow cytometry and clonogenic assay.

Radiotherapy (RT) and chemotherapy (CT) are the major therapeutics to treat cancer patients. Conventional in vitro 2D models are insufficient to study the combined effects of RT and CT towards optimized dose selection or drug screening. Soft-tissue sarcomas (STS) are rare cancers with profound social impacts as they affect patients of all ages.

The antioxidant transcription factor Nrf2 contributes to the protective effect of mild thermotolerance (40°C) against heat shock-induced apoptosis.

The exposure of cells to low doses of stress induces adaptive survival responses that protect cells against subsequent exposure to toxic stress. The ability of cells to resist subsequent toxic stress following exposure to low dose heat stress at 40°C is known as mild thermotolerance. Mild thermotolerance involves increased expression of heat shock proteins and antioxidants, but the initiating factors in this response are not understood.

Mild thermotolerance induced at 40 °C protects cells against hyperthermia-induced pro-apoptotic changes in Bcl-2 family proteins.

Purpose: Despite clinical progress, mechanisms involved in cellular responses to low and high doses of hyperthermia are not entirely clear. This study investigates the role of Bcl-2 family proteins in control of the mitochondrial pathway of apoptosis during hyperthermia at 42-43 °C and the protective effect of a low dose adaptive survival response, mild thermotolerance induced at 40 °C.

Materials And Methods: Levels of Bcl-2 family proteins were detected in HeLa cells by western blotting, caspase activation by spectrofluorimetry and apoptosis by chromatin condensation.