Orally administered low-molecular weight agaro-oligosaccharides are absorbed into the plasma of healthy humans

Agaro-oligosaccharides (AOSs) are known to have biological activities, such as anti-inflammatory, anti-tumor, and anti-obesity effects. Although existing evidence suggests the presence of AOSs in peripheral tissues after oral administration, whether AOSs permeate into the blood circulation remains unknown. Thus, we hypothesized that AOSs with low-molecular weight can permeate the human gastrointestinal tract. To test this hypothesis, the time course of absorption was examined by analyzing plasma samples before and 1, 2, and 4 h after ingestion. Analysis was performed using liquid chromatography/mass spectrometry after labeling with p-aminobenzoic ethyl ester. Our results showed that the plasma concentration of agarobiose (Abi) was higher than that of agarotetraose (Ate); however, agarohexaose was not detected. Additionally, plasma levels of Abi and Ate were proportional to the dose. These results suggest that permeation efficiency is dependent on the molecular weight and that the systemic absorption of Abi via the gastrointestinal tract is better than that of Ate. These findings will contribute to a better understanding of the bioactivity of orally administered AOSs in peripheral tissues

FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m2, P = 1.9 × 10−105), and all participants (0.30 [0.30, 0.35] kg/m2, P = 3.6 × 10−107). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10−16), and relative weak associations with lower total energy intake (−6.4 [−10.1, −2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (−0.07 [−0.11, −0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10−9) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposit

Carbon Ion Radiotherapy for Lymph Node Recurrence

Purpose/Objective(s): To evaluate the effectiveness and usefulness ofcarbon ion radiation therapy (CIRT) in patients with lymph node recur-rence, we analyzed our treatment results with various primary sites.\nMaterials/Methods: Patient\u27s eligibility of CIRT for lymph node recur-rence in principle were, 1) lymph node recurrence after primary treatment,2) no other metastasis has been observed, 3) ECOG PS 0-2, 4) at least 5-mm gap between the recurrent lesion and radiosensitive organs, includinggastrointestinal tract and bladder, and 5) Irradiated field not exceeding 15cm. In some cases, Gore-Tex made spacer had been inserted surgicallybefore CIRT to make a gap between surrounding radiosensitive tissue. AsCIRTtechnique, all sites were irradiated using 3-D conformal planningsystem with 2 to 4 portals, withrespiratory gating if necessary. In targetdelineation, involved node was defined as GTV, prophylactic lymph nodearea was defined as CTV, and CTV + 5 mm (excluding GI) was defined as PTV. Treatment was performed 4 times a week, up to a total dose of 48GyE / 12 fractions / 3 weeks in principle.\nResults: From December 1996 to February 2012, 189 cases with 233 siteswere treated. Patient\u27 age ranged from 32 to 87 with a median of 65, with141 males and 92 females. The primary sites were lung in 68, rectum in 44,pancreas in 12, uterine cervix and body in 11, colon in 8, stomach and esophagus in 5, renal pelvis in 4 and others in 21. The tumors were histologically classified as follows: 160 with adenocarcinoma, 37 squa-mous cell carcinoma, 12 with transitional cell carcinoma, and 24 withothers. The sites of recurrent lymph nodes were 92 in chest, 69 in abdomen, 59 in pelvis and 13 in neck. The radiation doses were 30-38.4GyE in 10, 40-45.6GyE in 18, 48GyE in 106, 50.2-57.6GyE in 84, 60-64GyE in 9 and 70.4-73.6GyE in 6 cases. Among them, 23 sites were previously irradiated. The follow up period ranged from 1 month to 9 years7 months with a median of 1 year 6 months. No acute grade 3 or higheradverse toxicities have been observed. Late adverse events were observed in 1 case, who developed duodenum bleeding at re-irradiate site. Tumorprogressions were recognized at irradiated sites in 18 (8%), regional in 34(15%), whereas distant sites in 128 (55%). At the time of analysis. 115patients had died, including 99 of the malignancies and 16 of intercurrent diseases. Survival rates were calculated at 204 sites followed for more than6 months from the completion of the treatment or followed to the death.The overall survival rates of entire group were 77.3% in 1 year, 52.8% in 2year, 42.5% in 3 year and 29.0% in 4 year, respectively (median survivaltime: 2 year and 2 months). The overall 2 year survival rates of lung and rectal cancer were 45.4% and 42.6%, respectively.\nConclusions: CIRT for lymph node recurrence from various malignanciesmight be promising to have favorable local control with acceptable toxicities, although not affecting to reduce distant metastases.ASTRO\u27s 54th Annual Meetin

Data_Sheet_1_Orally administered low-molecular weight agaro-oligosaccharides are absorbed into the plasma of healthy humans.docx

Agaro-oligosaccharides (AOSs) are known to have biological activities, such as anti-inflammatory, anti-tumor, and anti-obesity effects. Although existing evidence suggests the presence of AOSs in peripheral tissues after oral administration, whether AOSs permeate into the blood circulation remains unknown. Thus, we hypothesized that AOSs with low-molecular weight can permeate the human gastrointestinal tract. To test this hypothesis, the time course of absorption was examined by analyzing plasma samples before and 1, 2, and 4 h after ingestion. Analysis was performed using liquid chromatography/mass spectrometry after labeling with p-aminobenzoic ethyl ester. Our results showed that the plasma concentration of agarobiose (Abi) was higher than that of agarotetraose (Ate); however, agarohexaose was not detected. Additionally, plasma levels of Abi and Ate were proportional to the dose. These results suggest that permeation efficiency is dependent on the molecular weight and that the systemic absorption of Abi via the gastrointestinal tract is better than that of Ate. These findings will contribute to a better understanding of the bioactivity of orally administered AOSs in peripheral tissues.</p

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