Alternating Electric Fields (Tumor-Treating Fields Therapy) Can Improve Chemotherapy Treatment Efficacy in Non-Small Cell Lung Cancer Both In Vitro and In Vivo

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Common treatment modalities for NSCLC include surgery, radiotherapy, chemotherapy, and, in recent years, the clinical management paradigm has evolved with the advent of targeted therapies. Despite such advances, the impact of systemic therapies for advanced disease remains modest, and as such, the prognosis for patients with NSCLC remains poor. Standard modalities are not without their respective toxicities and there is a clear need to improve both efficacy and safety for current management approaches. Tumor-treating fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that disrupt proper spindle microtubule arrangement, thereby leading to mitotic arrest and ultimately to cell death. We evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. We investigated the response of Lewis lung carcinoma and KLN205 squamous cell carcinoma in mice treated with TTFields in combination with pemetrexed, cisplatin, or paclitaxel and compared these to the efficacy observed in mice exposed only to the single agents. Combining TTFields with these therapeutic agents enhanced treatment efficacy in comparison with the respective single agents and control groups in all animal models. Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC

Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs

Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot clinical trials in patients with advanced stage solid tumors. TTFields were tested for their potential to inhibit metastatic spread of solid tumors to the lungs in two animal models: (1) Mice injected with malignant melanoma cells (B16F10) into the tail vein, (2) New Zealand White rabbits implanted with VX-2 tumors within the kidney capsule. Mice and rabbits were treated using two-directional TTFields at 100–200 kHz. Animals were either monitored for survival, or sacrificed for pathological and histological analysis of the lungs. The total number of lung surface metastases and the absolute weight of the lungs were both significantly lower in TTFields treated mice then in sham control mice. TTFields treated rabbits survived longer than sham control animals. This extension in survival was found to be due to an inhibition of metastatic spread, seeding or growth in the lungs of TTFields treated rabbits compared to controls. Histologically, extensive peri- and intra-tumoral immune cell infiltration was seen in TTFields treated rabbits only. These results raise the possibility that in addition to their proven inhibitory effect on the growth of solid tumors, TTFields may also have clinical benefit in the prevention of metastatic spread from primary tumors

Field sensitivity action spectra of cone photoreceptors in the turtle retina

The Stiles two-colour increment threshold technique was applied to turtle cone photoreceptors in order to derive their field sensitivity action spectra.Photoresponses of cone photoreceptors were recorded intracellularly. Flash sensitivities were calculated from small amplitude (< 1 mV) responses. The desensitizing effects of backgrounds of different wavelengths were measured and the background irradiance needed to desensitize the cone by a factor of 10 (1 log unit) was defined as threshold. The reciprocals of these thresholds were used to construct the field sensitivity action spectrum.The field sensitivity action spectra of long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cones depended upon the wavelength of the test flash used to measure them. This excludes the possibility that turtle cones can function as single-colour mechanisms in the Stiles sense.In fourteen L-cones, the average wavelength of peak sensitivity of the field sensitivity action spectrum was 613.7 ± 7.7 nm for the 500 nm test and 635.6 ± 9.6 nm for the 700 nm test. For six M-cones, these values were 558.5 ± 6.8 and 628.8 ± 10.6 nm for the 500 and 700 nm tests, respectively.Two physiological mechanisms are suggested as contributing to the dependency of the field sensitivity action spectrum upon test wavelength. One is based upon the transmissivity properties of the coloured oil droplets, while the other hypothesizes excitatory interactions between cones of different spectral type.Computer simulations of the field sensitivity action spectra indicate that both mechanisms are needed in order to account for the dependency of the field sensitivity action spectrum upon the wavelength of the test flash