Compared with traditional two-dimensional culture, a three-dimensional (3D) culture platform can not only provide more reliable prediction results, but also provide a simple, inexpensive and less time-consuming method compared with animal models. A direct in vitro model of the patient’s tumor can help to achieve individualized and precise treatment. However, the existing 3D culture system based on microwell arrays has disadvantages, such as poor controllability, an uneven spheroid size, a long spheroid formation time, low-throughput and complicated operation, resulting in the need for considerable labor, etc. Here, we developed a new type of microdevice based on a 384-well plate/96-well plate microarray design. With our design, cells can quickly aggregate into clusters to form cell spheroids with better roundness. This design has the advantage of high throughput; the throughput is 33 times that of a 384-well plate. This novel microdevice is simple to process and convenient to detect without transferring the cell spheroid. The results show that the new microdevice can aggregate cells into spheroids within 24 h and can support drug and radiation sensitivity analyses in situ in approximately one week. In summary, our microdevices are fast, efficient, high-throughput, simple to process and easy to detect, providing a feasible tool for the clinical validation of individualized drug/radiation responses in patients.
Previous studies have confirmed that the gap junction protein Connexin26 (Cx26) is specifically expressed in human skin tissue. Cx26 can transmit radiation-induced damage signals. However, no study has yet reported whether Cx26 expression affects the radiosensitivity of human skin squamous cancer cells or the mechanism by which this occurs. In this study, we found that human skin squamous cell carcinoma cells (A431 cells) expressed significantly more Cx26 and were more sensitive to radiation compared to normal human keratinocytes (HaCaT cells). Knockdown of Cx26 in A431 cells (A431Cx26–/–) decreased radiosensitivity relative to control cells and altered the expression of key proteins in the MAPK and NF-κB signaling pathways. These results demonstrate that Cx26 expression might play an important role in mediating radiation damage in A431 cells and could serve as a potential target for clinical radiotherapy for cutaneous squamous cell carcinoma.
Presently 4T-1 luc cells were irradiated with proton under ultra-high dose rate FLASH or with gamma-ray with conventional dose rate, and then subcutaneous vaccination with or without Mn immuno-enhancing adjuvant into the mice for three times. One week later, we injected untreated 4T-1 luc cells on the other side of the vaccinated mice, and found that the untreated 4T-1 luc cells injected later nearly totally did not grow tumor (1/17) while controls without previous vaccination all grow tumors (18/18). The result is very interesting and the findings may help to explore in situ tumor vaccination as well as new combined radiotherapy strategies to effectively ablate primary and disseminated tumors. To our limited knowledge, this is the first paper reporting the high efficiency induction of systemic vaccination suppressing the metastasized/disseminated tumor progression.