The Synergistic Antitumor Effect of Combined Anti-Human Epidermal Growth Factor Receptor 2 Antibody and Gamma Interferon Therapy on Antibody-resistant Breast Cancer Cells

The anti-human epidermal growth factor receptor 2 （HER2） antibody （Ab） is a molecularly targeted Ab for cancer therapy. In the field of breast cancer, approximately 20％ overexpress HER2 protein. However, the recurrence rate is 30％ and the metastasis rate is 18％ one year after treatment of anti-HER2 Ab for HER2 positive breast cancer. The resistance to Ab treatment is a major problem for patients. We previously reported that anti-HER2 Ab and Gamma Interferon （IFN-γ） combined therapy show a higher anti-tumor effect than typical therapy in in vitro and in vivo mouse experiments. In this study, we evaluated whether anti-HER2 Ab and IFN-γ combined therapy shows a good synergistic effect against drug-resistant HER2 positive breast cancer cells and a higher antitumor effect than chemotherapy as a conventional clinical treatment. Further, we evaluated a synergy effect with the PD-L1 as a new check point inhibitor. The resistant cell lines were made under the continuous presence of Ab until cell growth was not affected by the drug. The resistant cells were divided into the appropriate number of groups, and then treated with anti-cancer therapy. We evaluated the antitumor effect for both the in vitro study and in vivo mouse xenograft model prepared with the same immunogenicity. The differences of immunofluorescence staining of CD8, Gr-1 and PDL-1 in tissues were investigated, especially in relation to the immune system. The combined therapy showed a significantly higher anti-tumor effect than other groups in in vitro and in vivo experiments. The combined therapy affected anti-tumor immunity in this immunofluorescence experiment. Taken together, we showed the possibility that combined therapy could be an effective treatment option for anti-HER2 Ab resistant breast cancer, thus helping patients suffering from cancer progression after developing treatment resistance

Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy

Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy

The circadian clock is disrupted in mice with adenine-induced tubulointerstitial nephropathy.

Chronic Kidney Disease (CKD) is increasing in incidence and has become a worldwide health problem. Sleep disorders are prevalent in patients with CKD raising the possibility that these patients have a disorganized circadian timing system. Here, we examined the effect of adenine-induced tubulointerstitial nephropathy on the circadian system in mice. Compared to controls, adenine-treated mice showed serum biochemistry evidence of CKD as well as increased kidney expression of inflammation and fibrosis markers. Mice with CKD exhibited fragmented sleep behavior and locomotor activity, with lower degrees of cage activity compared to mice without CKD. On a molecular level, mice with CKD exhibited low amplitude rhythms in their central circadian clock as measured by bioluminescence in slices of the suprachiasmatic nucleus of PERIOD 2::LUCIFERASE mice. Whole animal imaging indicated that adenine treated mice also exhibited dampened oscillations in intact kidney, liver, and submandibular gland. Consistently, dampened circadian oscillations were observed in several circadian clock genes and clock-controlled genes in the kidney of the mice with CKD. Finally, mice with a genetically disrupted circadian clock (Clock mutants) were treated with adenine and compared to wild type control mice. The treatment evoked worse kidney damage as indicated by higher deposition of gelatinases (matrix metalloproteinase-2 and 9) and adenine metabolites in the kidney. Adenine also caused non-dipping hypertension and lower heart rate. Thus, our data indicate that central and peripheral circadian clocks are disrupted in the adenine-treated mice, and suggest that the disruption of the circadian clock accelerates CKD progression

災害時避難に資する携帯端末を用いた避難共助支援システムの開発および小規模避難実験

金沢大学総合メディア基盤センターEmbargo Period 12 monthsThe 41st Symposium on Computer Technology of Information, Systems and Applications, Architectural Institute of Japa