The use of tumor-treating fields (TTFields) has revolutionized the treatment of recurrent and newly diagnosed glioblastoma (GBM). TTFields are low-intensity, intermediate frequency, alternating electric fields that are applied to tumor regions and cells using non-invasive arrays. The predominant mechanism by which TTFields are thought to kill tumor cells is the disruption of mitosis. Using five non-small cell lung cancer (NSCLC) cell lines we found that there is a variable response in cell proliferation and cell killing between these NSCLC cell lines that was independent of p53 status. TTFields treatment increased the G2/M population, with a concomitant reduction in S-phase cells followed by the appearance of a sub-G1 population indicative of apoptosis. Temporal changes in gene expression during TTFields exposure was evaluated to identify molecular signaling changes underlying the differential TTFields response. The most differentially expressed genes were associated with the cell cycle and cell proliferation pathways. However, the expression of genes found within the BRCA1 DNA-damage response were significantly downregulated (Po0.05) during TTFields treatment. DNA double-strand break (DSB) repair foci increased when cells were exposed to TTFields as did the appearance of chromatid-type aberrations, suggesting an interphase mechanism responsible for cell death involving DNA repair. Exposing cells to TTFields immediately following ionizing radiation resulted in increased chromatid aberrations and a reduced capacity to repair DNA DSBs, which were likely responsible for at least a portion of the enhanced cell killing seen with the combination. These findings suggest that TTFields induce a state of 'BRCAness' leading to a conditional susceptibility resulting in enhanced sensitivity to ionizing radiation and provides a strong rationale for the use of TTFields as a combined modality therapy with radiation or other DNA-damaging agents. Lung cancer is the second most prevalent cancer and the leading cause of cancer-related death in the United States. 1 Non-small cell lung cancer (NSCLC) is the most prevalent type, accounting for~80% of new cases. 2,3 A plethora of treatment options exist including surgical resection, chemotherapy, radiation therapy and immunotherapy. 4,5 Fiveyear survival rates for patients with stage I and II NSCLC arẽ 50% and 30%, respectively. However, despite this myriad of options, 5-year survival rates for patients with late stage IIIA, IIIB and IV are 14%, 5% and 1%, respectively (www.cancer. net), highlighting the need for novel treatment modalities that can be utilized alone or in combination with conventional therapies to increase survival rates.The advent of Tumor-Treating Fields (TTFields), a novel physical treatment modality, has been effective for the treatment of solid, therapy-resistant primary and recurrent tumors. 6-9 TTFields electrodes are non-invasive and deliver a low-intensity (1-3 V/cm) intermediate frequency (100-300 kHz) alternating electric field across the tumor bed. 10 TTFie...

Layered double hydroxides (LDHs) with the hydrotalcite-like structure have been prepared containing different amounts of Ni 2z , Cu 2z and Al 3z in the brucite-like layers by a coprecipitation method. The samples have been characterized by elemental chemical analysis, powder X-ray diffraction, differential thermal analysis and thermogravimetric analysis, FT-IR and UV±VIS diffuse re¯ectance spectroscopies, temperature-programmed reduction, and speci®c surface area and porosity assessment by N 2 adsorption at 2196 ³C. The nature of the phase obtained, crystallinity of the HT-like phase and thermal behaviour of these materials were in¯uenced by M II /Al atomic composition and concentration of bivalent metal ion. Calcination at 500 ³C leads to mostly amorphous solids containing NiO, and also CuO (tenorite) for large Cu 2z contents (Cu/Ni molar ratio equal to 4). When the calcination temperature is increased to 850 ³C, crystallization of well de®ned phases (NiO, CuO and NiAl 2 O 4 , depending on the relative amounts of Ni, Cu and Al) takes place. Reduction of Cu 2z species in these samples takes place at a lower temperature than that for Ni 2z , while the temperature of reduction of nickel is increased with an increase in aluminium and copper content of the samples.

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RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage. In the absence of RAD51, the unprotected newly replicated genome is degraded by the exonuclease activity of MRE11, and the fragmented nascent DNA accumulates in the cytosol, initiating an innate immune response. Our data suggest that in addition to playing roles in homologous recombination-mediated DNA double-strand break repair and replication fork processing, RAD51 is also implicated in the suppression of innate immunity. Thus, our study reveals a previously uncharacterized role of RAD51 in initiating immune signaling, placing it at the hub of new interconnections between DNA replication, DNA repair, and immunity.

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