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Chemotherapy using a lymphatic drug delivery system (LDDS) targeting lymph nodes (LNs) in the early stage of metastasis has a superior antitumor effect to systemic chemotherapy. An LDDS produces a higher drug retention rate and tissue selectivity in LNs. To expand the therapeutic coverage of LDDS from local treatment of metastatic LNs to prevention of distant metastases, the combination of treatment with therapies that enhance systemic tumor immune effects is an important therapeutic strategy. Recently, total body irradiation (TBI) has been shown to activate immune responses and alter the tumor microenvironment. Here we show that combination therapy with TBI and LDDS improves the antitumor effect of metastatic LNs and lung metastasis. Tumor cells were inoculated into the subiliac LN (SiLN) to induce metastasis into the proper axillary LN (PALN) and lung in a mouse model. TBI was carried out on day 4 after inoculation using a gamma irradiator. Lymphatic drug delivery into the accessory axillary LN was used to treat PALN. In vivo bioluminescence imaging, high-frequency ultrasound, and histology showed that combination therapy using TBI (total dose 1.0 Gy once) and the LDDS suppressed tumor growth in LNs and lung metastases and was more effective than using LDDS or TBI alone. Quantitative RT-PCR of spleens after combination therapy revealed increased expression of CD4, CD8, and IL-12b, indicating an activated immune response. The results show that combination therapy with TBI and LDDS is a method to improve the efficacy of LN metastases and distant metastases therapy and is a promising novel approach to treat cancer patients.

Malignant neoplasms (Cancers) are the most causes of the death in Japan. Especially, the lung cancer is the most severe factor of all kinds of cancers. it is mainly removed by video assisted thoracic surgery. However, the lung cancer is estimated visually in the surgery. So, the surgery needs a lot of time and the advance techniques to estimate the cancerous tissue. In this paper, the flat-types of the electrodes have been proposed in order to improve the accuracy of the estimation of the lung position; decrease the burden of the surgery; shorten the surgery time. Our results indicate the possibility of the estimation of the cancer. Using the proposed method, the cancer would be estimated easily. And we will miniaturize the structure of the flat-types of the electrodes and improve the estimation sensibility.