Tumor microenvironment plays a key role for tumor development and progression. Although adipose tissue is a predominant component of stroma in mammary tissues and secretes various cytokines, chemokines and growth factors, roles of adipocytes in breast cancers remain to be elucidated. In this study, we found that adipsin, an adipokine secreted from mammary adipose tissues, enhanced proliferation and cancer stem cell (CSC)-like properties of human breast cancer patient-derived xenograft (PDX) cells. Adipsin was predominantly expressed in both adipose tissues of the surgical specimens of breast cancer patients and adipose-derived stem cells (ADSCs) isolated from them, and its expression level was significantly higher in obese patients. ADSCs significantly enhanced the sphere-forming ability of breast cancer PDX cells derived from both estrogen receptor-positive and -negative breast cancer PDX cells. Suppression of adipsin-mediated signaling by a specific inhibitor or adipsin knockdown in ADSCs significantly decreased the sphere-forming ability and the expression of CSC markers in co-cultured breast cancer PDX cells. Growth of breast cancer PDX tumors was significantly enhanced by co-transplantation with ADSCs in vivo, and it was weakened when co-transplanted with the adipsin knocked-down ADSCs. These results suggest that adipsin is an important adipokine secreted from mammary adipose tissue that functions as a component of tumor microenvironment and a CSC niche in breast cancers.

The ~30-km-long surface ruptures associated with the M w 7.0 (M j 7.3) earthquake at 01:25 JST on April 16 in Kumamoto Prefecture appeared along the previously mapped ~100-km-long active fault called the Futagawa-Hinagu fault zone (FHFZ). The surface ruptures appeared to have extended further west out of the main FHFZ into the Kumamoto Plain. Although InSAR analysis by Geospatial Information Authority of Japan (GSI) indicated coseismic surface deformation in and around the downtown of Kumamoto City, the surface ruptures have not been clearly mapped in the central part of the Kumamoto Plain, and whether there are other active faults other than the Futagawa fault in the Kumamoto Plain remained unclear. We produced topographical stereo images (anaglyph) from 5-m-mesh digital elevation model of GSI, which was generated from light detection and ranging data. We interpreted them and identified that several SW-sloping river terraces formed after the deposition of the pyroclastic flow deposits related to the latest large eruption of the Aso caldera (86.8-87.3 ka) are cut and deformed by several NW-trending flexure scarps down to the southwest. These 5.4-km-long scarps that cut across downtown Kumamoto were identified for the first time, and we name them as the Suizenji fault zone. Surface deformation such as continuous cracks, tilts, and monoclinal folding associated with the main shock of the 2016 Kumamoto earthquake was observed in the field along the fault zone. The amount of vertical deformation (~0.1 m) along this fault associated with the 2016 Kumamoto earthquake was quite small compared to the empirically calculated coseismic slip (0.5 m) based on the fault length. We thus suggest that the slip on this fault zone was triggered by the Kumamoto earthquake, but the fault zone has potential to generate an earthquake with larger slip that poses a high seismic risk in downtown Kumamoto area.

Background Multitarget kinase inhibitors (m‐TKI), including lenvatinib, are now available as treatment options for radioiodine‐refractory differentiated thyroid cancer (RR‐DTC). However, the optimal timing of treatment initiation with m‐TKI in these patients remains to be defined. Methods We retrospectively reviewed the clinical records of 30 consecutive patients with RR‐DTC. The relationship between clinical characteristics was evaluated, including tumor growth parameters at pretreatment/post‐treatment and efficacy of lenvatinib. Results A total of 26 patients with RR‐DTC treated with lenvatinib were evaluable for response and eligible for analysis. From the results of multivariate analysis, baseline tumor size and tumor‐related symptoms were independent negative prognostic factors for overall survival (OS) and progression‐free survival (PFS). Pretreatment tumor growth parameters were not prognostic for either PFS or OS. Conclusions Patients with RR‐DTC with a high tumor burden and tumor‐related symptoms had significantly worse prognosis. Greater tumor reduction after starting lenvatinib may lead to better prognosis, irrespective of pretreatment high tumor growth rate.

BackgroundVitamin C is a well-documented antioxidant that reduces oxidative stress and fluid infusion in high doses; however, the association between high-dose vitamin C and reduced mortality remains unclear. This study evaluates the effect of high-dose vitamin C in severe burn patients under two varying thresholds.MethodsWe enrolled adult patients with severe burns (burn index ≥ 15) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2016. Propensity score matching was performed between patients who received high-dose vitamin C within 1 day of admission (vitamin C group) and those who did not (control group). High-dose vitamin C was defined as a dosage in excess of 10 g or 24 g within 2 days of admission. The primary outcome was in-hospital mortality.ResultsEligible patients (n = 2713) were categorized into the vitamin C group (n = 157) or control group (n = 2556). After 1:4 propensity score matching, we compared 157 and 628 patients who were administered high-dose vitamin C (> 10-g threshold) and controls, respectively. Under this particular threshold, high-dose vitamin C therapy was associated with reduced in-hospital mortality (risk ratio, 0.79; 95% confidence interval, 0.66–0.95; p = 0.006). In contrast, in-hospital mortality did not differ between the control and high-dose vitamin C group under the > 24-g threshold (risk ratio, 0.83; 95% confidence interval, 0.68–1.02; p = 0.068).ConclusionsHigh-dose vitamin C therapy was associated with reduced mortality in patients with severe burns when used under a minimum threshold of 10 g within the first 2 days of admission. While “high-dose” vitamin C therapy lacks a universal definition, the present study reveals that different “high-dose” regimens may yield improved outcomes.

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