Increase in cell motility by carbon ion irradiation via the Rho signaling pathway and its inhibition by the ROCK inhibitor Y-27632 in lung adenocarcinoma A549 cells

学位記番号：医博甲147

Day-to-Day Variation in the Hoffmann Reflex in Females

The present study aimed to investigate changes in the Hoffmann reflex (H-reflex) at the same time on different days and to compare the findings between genders. Four males and five females in healthy subjects agreed to participate in the study and provided informed consent. All subjects were nonsmokers, and none of the females were consuming any oral contraceptives. The H-reflex was elicited in the right soleus muscle by constant current stimulation of the tibial nerve in the popliteal fossa with the subjects in the prone position. As a reference, the maximal amplitude of the H-wave relative to that of the M-wave (Hmax/Mmax) was measured to determine changes in α-motoneuron excitability. Hmax/Mmax of 6 to 9 trials and was represented by the coefficient of variation (CV). The CV of Hmax/Mmax in females was significantly higher than that in males. The level of Hmax/Mmax for males was highly reproducible, suggesting that fewer factors alter α-motoneuron excitability in males compared with those in females. Several female subjects experienced symptoms of depression and suffered from body and menstrual pain. Variations in Hmax/Mmax values were considerably greater for females than for males, suggesting that the α-motoneuron might be influenced by the menstrual cycle phase as well as by individual differences

Prospective Study of Isolated Recurrent Tumor Re-irradiation With Carbon-Ion Beams

Purpose: To perform a prospective study to evaluate the efficacy and safety of isolated recurrent tumor re-irradiation with carbon-ion radiotherapy (RT).Methods and Materials: The inclusion criteria were clinically proven recurrent tumors, measurable by computed tomography or magnetic resonance imaging, patients ≥ 16 years old, performance status scores between 0 and 2, isolated tumor at a previously irradiated site, and a life expectancy > 6 months. The exclusion criteria were tumor invasion into the gastrointestinal tract or a major blood vessel, uncontrolled infection, early recurrence (<3 months), and severe concomitant diseases. The primary end-point was the local control rate, the secondary end-points including the overall survival rate, and adverse events.Results: Between December 2013 and March 2016, 22 patients were enrolled in this prospective study. All patients were re-irradiated with carbon-ion RT with radical intent. Five patients had rectal cancer, 4 had sarcoma, 4 had lung cancer, 3 had hepatic cell carcinoma, and 6 had other tumors. The median follow-up time was 26 months. Eight patients developed local recurrence, and the 1- and 2-year local control rates were 71 and 60%, respectively. Eight patients died of their cancers and 2 died of other diseases. The 1- and 2-year overall survival rates were 76 and 67%, respectively. There were no grade 2 or higher acute adverse events and 4 patients (18%) developed grade 3 late adverse events. The group with the longer interval (>16 months) between the first RT and re-irradiation had significantly better outcomes than the shorter interval group (≤ 16 months).Conclusions: Re-irradiation, using carbon-ion RT with radical intent, had favorable local control and overall survival rates without severe toxicities for selected patients. Re-irradiation has the potential to improve clinical outcomes for isolated, local, recurrent tumors; further investigations are required to confirm the therapeutic efficacy

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

Activation of Mammalian Unfolded Protein Response Is Compatible with the Quality Control System Operating in the Endoplasmic Reticulum

Newly synthesized secretory and transmembrane proteins are folded and assembled in the endoplasmic reticulum (ER) where an efficient quality control system operates so that only correctly folded molecules are allowed to move along the secretory pathway. The productive folding process in the ER has been thought to be supported by the unfolded protein response (UPR), which is activated by the accumulation of unfolded proteins in the ER. However, a dilemma has emerged; activation of ATF6, a key regulator of mammalian UPR, requires intracellular transport from the ER to the Golgi apparatus. This suggests that unfolded proteins might be leaked from the ER together with ATF6 in response to ER stress, exhibiting proteotoxicity in the secretory pathway. We show here that ATF6 and correctly folded proteins are transported to the Golgi apparatus via the same route and by the same mechanism under conditions of ER stress, whereas unfolded proteins are retained in the ER. Thus, activation of the UPR is compatible with the quality control in the ER and the ER possesses a remarkable ability to select proteins to be transported in mammalian cells in marked contrast to yeast cells, which actively utilize intracellular traffic to deal with unfolded proteins accumulated in the ER

Secondary cancers after carbon-ion radiotherapy and photon beam radiotherapy for uterine cervical cancer: A comparative study.

Background: There are limited studies on the risk of secondary cancers after carbon-ion radiotherapy (CIRT). We assessed the incidence of secondary cancers in patients treated with CIRT for cervical cancer. We also evaluated the incidence of secondary cancers in patients who received standard photon radiotherapy (RT) throughout the same period.Methods: This retrospective study included patients with cervical cancer who underwent curative RT at our hospital. All cancers discovered for the first time after RT were classified as secondary cancers. To compare the risk of secondary cancers among cervical cancer survivors to the general population, standardized incidence ratios (SIRs) were calculated.Results: The analysis included a total of 197 and 417 patients in the CIRT and photon RT groups, respectively. The total person-years during the observation period were 1052.4 in the CIRT group and 2481.5 in the photon RT group. The SIR for all secondary cancers was 1.1 (95% confidence interval [CI], 0.6-2.1) in the CIRT group and 1.4 (95% CI, 1.0-2.1) in the photon RT group. The 10-year cumulative incidence of all secondary cancers was 9.5% (95% CI, 4.0-21.5) in the CIRT group and 9.4% (95% CI, 6.2-14.1) in the photon RT group. The CIRT and photon RT groups were not significantly different in incidence (p = 0.268).Conclusions: The incidence of secondary cancers after CIRT for cervical cancer was similar to that after photon RT. Validation of our findings after long-term observation is warranted