Bulk evidence of anisotropic s-wave pairing with no sign change in the kagome superconductor CsV3Sb5.

The recently discovered kagome superconductors AV3Sb5 (A = K, Rb, Cs) exhibit unusual charge-density-wave (CDW) orders with time-reversal and rotational symmetry breaking. One of the most crucial unresolved issues is identifying the symmetry of the superconductivity that develops inside the CDW phase. Theory predicts a variety of unconventional superconducting symmetries with sign-changing and chiral order parameters. Experimentally, however, superconducting phase information in AV3Sb5 is still lacking. Here we report the impurity effects in CsV3Sb5 using electron irradiation as a phase-sensitive probe of superconductivity. Our magnetic penetration depth measurements reveal that with increasing impurities, an anisotropic fully-gapped state changes to an isotropic full-gap state without passing through a nodal state. Furthermore, transport measurements under pressure show that the double superconducting dome in the pressure-temperature phase diagram survives against sufficient impurities. These results support that CsV3Sb5 is a non-chiral, anisotropic s-wave superconductor with no sign change both at ambient and under pressure.

Influence of lower extremity rotation on knee kinematics in single-leg landing.

OBJECTIVES: Although the rotation of lower extremities has gained increasing recognition as a risk factor for anterior cruciate ligament (ACL) injury. This study clarified the influence of lower extremity rotation on the knee during single-leg landing. DESIGN AND SETTING: We recruited 30 students to perform single-leg landing from a height of 30 cm with their lower extremities in neutral, and externally and internally rotated. The knee abduction, flexion angles, and abduction angular velocity were measured. Furthermore, the abduction angle was analyzed at knee flexion angles of 15°, 20°, 25°, and 30° and compared among the three conditions using a repeated measures analysis of variance with Bonferroni post hoc tests. RESULTS: The maximum abduction angle was significantly greater when internally rotated than in the neutral. The maximum abduction angular velocity was significantly greater in the internally rotated compared to in the neutral. Finally, the abduction angle at a knee flexion angle of 30° was significantly greater when internally rotated compared to in the neutral. CONCLUSION: Rotation of the lower extremities affects knee kinematics, and landing on a knee that is internally rotated may increase the risk of ACL injury.

Dietary salt with nitric oxide deficiency induces nocturnal polyuria in mice via hyperactivation of intrarenal angiotensin II-SPAK-NCC pathway.

Nocturnal polyuria is the most frequent cause of nocturia, a common disease associated with a compromised quality of life and increased mortality. Its pathogenesis is complex, and the detailed underlying mechanism remains unknown. Herein, we report that concomitant intake of a high-salt diet and reduced nitric oxide (NO) production achieved through Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) administration in mice resulted in nocturnal polyuria recapitulating the clinical features in humans. High salt intake under reduced NO production overactivated the angiotensin II-SPAK (STE20/SPS1-related proline-alanine-rich protein kinase)-NCC (sodium chloride co-transporter) pathway in the kidney, resulting in the insufficient excretion of sodium during the day and its excessive excretion at night. Excessive Na excretion at night in turn leads to nocturnal polyuria due to osmotic diuresis. Our study identified a central role for the intrarenal angiotensin II-SPAK-NCC pathway in the pathophysiology of nocturnal polyuria, highlighting its potential as a promising therapeutic target.

Dietary Patterns and Muscle Mass, Muscle Strength, and Physical Performance in the Elderly: A 3-Year Cohort Study.

OBJECTIVES: Nutritional support effectively prevents and treats sarcopenia; however, the influence of overall dietary patterns on sarcopenia parameters is less investigated. This study aimed to determine the association between adherence to Mediterranean-style diet (MD), Dietary Approaches to Stop Hypertension (DASH), Japanese Food Guide Spinning Top (JFG-ST), and modified JFG-ST (mJFG-ST) and muscle mass, muscle strength, and physical performance in community-dwelling Japanese elderly. DESIGN AND SETTINGS: This prospective cohort study recruited individuals aged over 60 years from a community college in Nagoya, Japan. PARTICIPANTS AND MEASUREMENTS: A total of 666 participants were followed up annually from 2014 to 2017. Demographic data, anthropometric measurements, and sarcopenia parameters including walking speed (WS), hand grip strength in the dominant hand (HGS), and skeletal mass index (SMI) were recorded. Self-recall dietary intake was assessed using a validated food frequency questionnaire comprising 29 food groups. Adherence to MD, DASH, JFG-ST, and mJFG-ST was determined by tertiles. RESULTS: At baseline, the mean age of all participants (56.5% women) was 69.4±4.4 years. WS, HGS, and SMI were 1.4±0.2 (m/s), 28.9±8.1 (kg), and 6.7±1.0 (kg/m2), respectively. In longitudinal analysis, participants with higher JFG-ST adherence scores were more likely to have higher SMI (Q3 vs. Q1: mean difference, 0.048; p=0.04) after adjustment, and its benefits were more evident in men (Q2 vs. Q1: mean difference, 0.098; p=0.047; Q3 vs. Q1: mean difference, 0.091; p=0.017) than in women. WS and HGS were not associated with any type of dietary pattern. CONCLUSIONS: Adherence to JFG-ST was positively associated with SMI in Japanese community-dwelling elderly adults aged over 60 years, specifically in men. The country-specific dietary recommendations are required to be developed for sarcopenia prevention.

Fibronectin plays a major role in hypoxia-induced lenvatinib resistance in hepatocellular carcinoma PLC/PRF/5 cells.

Resistance to lenvatinib mesylate (LEN), a systemic chemotherapy that can be administered orally, has been a major issue for treatment of hepatocellular carcinoma (HCC). Although HCC is the tumor that most exhibits intratumoral hypoxia, which has been shown to be involved in the development of treatment resistance, there are no reports of LEN resistance in HCC treatment under hypoxia. The purpose of our study was to elucidate the mechanism of treatment resistance to LEN under hypoxia using HCC cell lines. We confirmed LEN resistance under hypoxic conditions in HCC cell lines. There was a significant increase in the IC50 value of PLC/PRF/5 cells from 13.0±0.8 µM in normoxia to 21.3±1.1 µM in hypoxia, but in HepG2 cells, the increase was not significant. To elucidate the LEN resistance mechanism of PLC/PRF/5 cells under hypoxia, we performed microarray analysis and extracted genes that are thought to be related to this mechanism. Furthermore, in-silico analysis confirmed significant changes in the extracellular matrix, and among them, FN1 encoding fibronectin was determined as the hub of the gene cluster. The expression of fibronectin in PLC/PRF/5 cells examined with immunofluorescence staining was significantly elevated in and outside of cells under hypoxia, and tended to decrease when cells were exposed to LEN under normoxia. Furthermore, the fibronectin concentration in the culture solution of PLC/PRF/5 cells examined by ELISA was 2.3 times higher under hypoxia than under normoxia under LEN(-) conditions, and 1.6 times higher under hypoxia than under normoxia under LEN(+) conditions. It is assumed that in PLC/PRF/5 cells, fibronectin is probably suppressed as an indirect effect of LEN under normoxia, but transcription factors such as HIF-1α are induced under hypoxia, thus enhancing the production of fibronectin and attenuating the effect of LEN, resulting in drug resistance. This behavior of fibronectin with LEN exposure under hypoxia is probably specific to PLC/PRF/5 cells. Further studies should verify the combined effective inhibition of fibronectin and the MAPK pathway as a promising therapeutic strategy to enhance the value of LEN in HCC treatment.

Multicenter prospective trial of total gastrectomy versus proximal gastrectomy for upper third cT1 gastric cancer.

BACKGROUND: The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient population. METHODS: A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures. RESULTS: Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (n = 159) or TG (n = 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (- 12.8% versus - 16.9%; p = 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min; p < 0.0001), but there were no group-dependent differences in blood loss and postoperative complications. For long-term outcomes, incidence of reflux esophagitis in the PG group was significantly higher than that of the TG group (14.5% versus 5.4%; p = 0.02), while there were no differences in the incidence of anastomotic stenosis between the two (5.7% versus 5.4%; p = 0.92). Overall patient survival rates were similar between the two groups (3-year survival rates: 96% versus 92% in the PG and TG groups, respectively; p = 0.49). CONCLUSIONS: Patients who underwent PG were better able to control weight loss without worsening the prognosis, relative to those in the TG group. Optimization of a reconstruction method to reduce reflux in PG patients will be important.

Short communication: Detection of mastication speed during rumination in cattle using 3-axis, neck-mounted accelerometers and fast Fourier transfer algorithm.

There have been limited reports on mastication speed during cattle rumination. The objective of this study was to establish a method to detect mastication speed based on data obtained during rumination through the use of a 3-axis accelerometer attached to the neck. A 3-axis accelerometer was attached to 6 dry Holstein cattle. When rumination behavior was observed, the accelerometer and the high-speed camera simultaneously recorded acceleration at the neck and moving image of the head movement. Based on the number of mastication movements recorded on video, mastication speed A was calculated. Data obtained from the 3-axis accelerometer were analyzed with fast Fourier transfer algorithm and identified as mastication speed B. The vibration of the neck recorded in the accelerometer during rumination was considered as mastication movement. Using Bland-Altman plot analysis, the mean difference between mastication speed A and mastication speed B was 0.041 s/bite, and the 95% limits of agreement ranged from -0.080 to 0.161. Since mastication movement occurred periodically, it was possible to detect the movement using spectrum analysis, as mastication speed B. Although there were some differences between calculated speeds and speeds obtained from spectrum analysis, there was clinical compatibility between mastication speed A and B. This study showed the feasibility of establishing a detection method for mastication speed during rumination, which might provide a basic procedure for studying the purpose of mastication and the variable factors involved.

Utility of synthetic MRI in predicting the Ki-67 status of oestrogen receptor-positive breast cancer: a feasibility study.

AIM: To evaluate the utility of synthetic magnetic resonance imaging (MRI) of the breast in predicting the Ki-67 status in patients with oestrogen receptor (ER)-positive breast cancer. MATERIALS AND METHODS: Forty-nine patients with 50 histopathologically proven breast cancers who underwent additional synthetic MRI were enrolled in the present study. Using synthetic MRI images, T1 and T2 relaxation times and their standard deviations (SD) in the breast lesions before (T1-Pre, T2-Pre, PD-Pre, SD of T1-Pre, SD of T2-Pre, SD of PD-Pre) and after (T1-Gd, T2-Gd, PD-Gd, SD of T1-Gd, SD of T2-Gd, SD of PD-Gd) contrast agent injection were obtained. These quantitative values were compared between the low Ki-67 expression (<14%) lesions (low-proliferation group: n=23) and high Ki-67 expression (≥14%) lesions (high-proliferation group: n=27). RESULTS: The univariate analysis showed that the SD of T1-Gd (p<0.001) and T2-Gd (p=0.042) were significantly higher in the high-proliferation group than in the low-proliferation group. Multivariate analysis further showed that the SD of T1-Gd was a significant and independent predictor of Ki-67 expression, with an area under the receiver operating characteristic (AUROC) curve of 0.885. The sensitivity, specificity, and accuracy of the SD of T1-Gd with an optimal cut-off value of 98.5 were 77.8%, 87%, and 82%, respectively. CONCLUSION: The SD of T1-Gd obtained from synthetic MRI was useful to predict Ki-67 status.

Visualization and quantification of anastomotic perfusion in colorectal surgery using near-infrared fluorescence.

BACKGROUND: Anastomotic leakage (AL) is one of the most troublesome complications in colorectal surgery. Recently, near-infrared fluorescence (NIRF) imaging has been used intraoperatively to detect sentinel lymph nodes and visualize the blood supply at the region of interest (ROI). The aim of this study was to evaluate the role of visualization and quantification of bowel perfusion around the anastomosis using NIRF system in predicting AL. METHODS: A prospective study was conducted on patients who had laparoscopic surgery for colorectal cancer at our institution. Perfusion of the anastomosis was evaluated with NIRF imaging after intravenous injection of indocyanine green (ICG). The time course of fluorescence intensity was recorded by an imaging analyzer We measured the time from ICG injection to the beginning of fluorescence (T0), maximum intensity (Imax), time to reach Imax (Tmax), time to reach Imax 50% ([Formula: see text]) and slope (S) after the anastomosis. RESULTS: Tumor locations were as follows; cecum: 2, ascending colon: 2, transverse colon: 7, descending colon: 1, sigmoid colon: 2, rectosigmoid colon: 3 and rectum: 6 (one case with synchronous cancer). All operations were performed laparoscopically. Four patients were diagnosed with or suspected to have AL (2 patients with grade B anastomotic leakage after low anterior resection, 1 patient with minor leakage in transverse colon resection and 1 patient needing re-anastomosis intraoperatively in transverse colon resection). T0 was significantly longer in the AL group than in patients without AL (64.3 ± 27.6 and 18.2 ± 6.6 s, p = 2.2 × 10-3). CONCLUSIONS: Perfusion of the anastomosis could be successfully visualized and quantified using NIRF imaging with ICG. T0 might be a useful parameter for prediction of AL.

First Measurement of a Long-Lived π

The adapted DIRAC experiment at the CERN PS accelerator observed for the first time long-lived hydrogenlike π^{+}π^{-} atoms, produced by protons hitting a beryllium target. A part of these atoms crossed the gap of 96 mm between the target and a 2.1 µm thick platinum foil, in which most of them dissociated. Analyzing the observed number of atomic pairs, n_{A}^{L}=436_{-61}^{+157}|_{tot}, the lifetime of the 2p state is found to be τ_{2p}=(0.45_{-0.30}^{+1.08}|_{tot})×10^{-11} s, not contradicting the corresponding QED 2p state lifetime τ_{2p}^{QED}=1.17×10^{-11} s. This lifetime value is three orders of magnitude larger than our previously measured value of the π^{+}π^{-} atom ground state lifetime τ=(3.15_{-0.26}^{+0.28}|_{tot})×10^{-15} s. Further studies of long-lived π^{+}π^{-} atoms will allow us to measure energy differences between p and s atomic states and so to discriminate between the isoscalar and isotensor ππ scattering lengths with the aim to check QCD predictions.

PCR-based clonality analysis of antigen receptor gene rearrangements in canine cutaneous plasmacytoma.

Plasmacytomas are discrete, B cell-derived, round cell tumours that sometimes are difficult to distinguish from canine cutaneous histiocytomas or T cell lymphosarcomas (lymphomas). Diagnosis of plasmacytomas relies on morphological observations and immunohistochemistry for multiple myeloma oncogene-1 (MUM-1) and cluster of differentiation 3 (CD3). Clonality testing often is used as an adjunct diagnostic tool to examine lymphoproliferative diseases. In this study, the sensitivity of PCR-based clonality analysis of antigen receptor gene rearrangements in canine cutaneous plasmacytomas was determined. Formalin-fixed paraffin-embedded sections of 29 canine plasmacytomas, 23 diffuse large B cell lymphomas (DLBCLs) and 23 lymph nodes without lymphoma were used for clonality analysis. New oligonucleotide primers for the framework (FR)2 and FR3 regions of the immunoglobulin heavy chain (IGH) V gene subgroup 3 were designed and used with previously reported FR3 primers. Although plasma cells are of B cell lineage, the detected frequency of IGH clonality in plasmacytoma was 0-34.5% with the seven primers used, whereas in DLBCLs it was 8.7-78.3%. In 23 lymph nodes without lymphoma, IGH clonality was detected in only one case with two out of the seven primers used. Sequence analysis of PCR products from plasmacytomas revealed mismatches in the annealing region of the FR3 primers. The sensitivity of detecting IGH clonality in canine plasmacytomas was lower than in DLBCLs. The low detection rate of IGH clonality in canine plasmacytoma may be due to somatic hypermutation of the variable region.

First Direct Mass Measurements of Nuclides around Z=100 with a Multireflection Time-of-Flight Mass Spectrograph.

The masses of ^{246}Es, ^{251}Fm, and the transfermium nuclei ^{249-252}Md and ^{254}No, produced by hot- and cold-fusion reactions, in the vicinity of the deformed N=152 neutron shell closure, have been directly measured using a multireflection time-of-flight mass spectrograph. The masses of ^{246}Es and ^{249,250,252}Md were measured for the first time. Using the masses of ^{249,250}Md as anchor points for α decay chains, the masses of heavier nuclei, up to ^{261}Bh and ^{266}Mt, were determined. These new masses were compared with theoretical global mass models and demonstrated to be in good agreement with macroscopic-microscopic models in this region. The empirical shell gap parameter δ_{2n} derived from three isotopic masses was updated with the new masses and corroborates the existence of the deformed N=152 neutron shell closure for Md and Lr.

Evaluation of the safety of ramucirumab in Japanese patients with advanced gastric cancer.

As a result of the RAINBOW trial, ramucirumab plus paclitaxel was established as a second-line treatment of advanced gastric cancer. Regarding the safety of ramucirumab plus paclitaxel in the Japanese, a subgroup analysis of the RAINBOW trial was conducted. The incidence of neutropenia was higher in Japanese patients. However, information is lacking concerning the safety of ramucirumab after marketing in Japanese patients. Therefore, the aim of this study was to evaluate the safety of ramucirumab in Japanese patients with advanced gastric cancer. The inclusion criteria were patients diagnosed with advanced gastric cancer who had commenced treatment with ramucirumab plus paclitaxel or paclitaxel only at Ogaki Municipal Hospital (Gifu, Japan) between January 2015 and December 2016. There were 26 patients in the ramucirumab plus paclitaxel group and 22 patients in the paclitaxel only group. Treatment-related adverse events were documented in 100.0% of the patients in the ramucirumab plus paclitaxel group (Grade 3-4, 73.1%) and 90.9 % of the patients in the paclitaxel only group (Grade 3-4, 45.5 %). The most frequently observed adverse event in both treatment groups was anemia. The second common adverse event was neutropenia. The incidence of neutropenia of Grade ≥3 was significantly higher in the ramucirumab plus paclitaxel group than in the paclitaxel only group. In conclusion, the incidence of neutropenia is high. However, we believe that ramucirumab plus paclitaxel can be safely administered.

Thoracic aortic aneurysm is an independent factor associated with diffuse idiopathic skeletal hyperostosis.

Aims: Although we often encounter patients with an aortic aneurysm who also have diffuse idiopathic skeletal hyperostosis (DISH), there are no reports to date of an association between these two conditions and the pathogenesis of DISH remains unknown. This study therefore evaluated the prevalence of DISH in patients with a thoracic aortic aneurysm (AA). Patients and Methods: The medical records of 298 patients who underwent CT scans for a diagnosis of an AA or following high-energy trauma were retrospectively examined. A total of 204 patients underwent surgery for an AA and 94 had a high-energy injury and formed the non-AA group. The prevalence of DISH was assessed on CT scans of the chest and abdomen and the relationship between DISH and AA by comparison between the AA and non-AA groups. Results: The prevalence of DISH in the AA group (114/204; 55.9%) was higher than that in the non-AA group (31/94; 33.0%). On multivariate analysis, the factors of AA, male gender, and ageing were independent predictors of the existence of DISH, with odds ratios of 2.9, 1.9, and 1.03, respectively. Conclusion: This study revealed that the prevalence of DISH is higher in patients with an AA than in those without an AA, and that the presence of an AA significantly influenced the prevalence of DISH. Cite this article: Bone Joint J 2018;100-B:617-21.

Simultaneous detection of ABL1 mutation and IKZF1 deletion in Philadelphia chromosome-positive acute lymphoblastic leukemia using a customized target enrichment system panel.

INTRODUCTION: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary. METHODS: We evaluated a next-generation sequencing (NGS)-based customized HaloPlex target enrichment system panel to simultaneously detect coding mutations, indel and CNVs. We analysed approximately 160 known genes associated with hematological disorders in 5 pediatric Ph+ALL patients. RESULTS: Mono-allelic IKZF1 deletions were found in 4 patients at diagnosis. Furthermore, the mono-allelic deletions were found in exons of RB1, EBF1, PAX5 and ETV6 genes. Bi-allelic deletions were detected in CDKN2A and CDKN2B genes in 1 patient. ABL1 mutation was also detected in 1 patient at relapse. These results were almost comparable with the results of the multiplex ligation-dependent probe amplification (MLPA) method or Sanger sequence. CONCLUSION: Next-generation sequencing-based custom HaloPlex target enrichment system panel allows us to detect the coding mutations, indel, and CNVs in pediatric Ph+ALL simultaneously, and its results seem comparable with those of other methods.

Key factors for school health policy implementation in Thailand.

Thailand formulated a National School Health Policy (NSHP) in 1998, and it has been widely implemented but has not been evaluated. This case study aimed to identify factors that have influenced the implementation of NSHP in Thailand. For this purpose, we conducted a document review and key informant interviews. We selected key interviewees, from NSHP implementers at national, provincial and school levels in four geographical areas. We adopted a content analysis method, using a framework of 12 influential components of successful policy implementation and triangular policy framework. This study showed that NSHP was well-disseminated and implemented at whole country. We identified seven positive factors influencing NSHP implementation, namely matching with ongoing educational strategy, competition and encouragement by an awarding system, sustainable human capacity building at school level, participation of multiple stakeholders, sufficient understanding and acceptance of school health concepts, sharing information and collaboration among schools in the same clusters and functional fund raising activities. In addition, we identified three negative factors, namely lack of institutional sustainability, vague role of provincial officers and diverse health problems among Thai children. The government should clarify the role of provincial level and set up institutionalized capacity-building system as measures to strengthen monitoring and evaluation activities.

High rate capability by sulfur-doping into LiFePO4 matrix.

Enhanced electrochemical performance of LiFePO4 for Li-ion batteries has been anticipated by anion doping at the O-site rather than cation doping at the Fe-site. We report on the electrochemical performance of S-doped LiFePO4 nanoparticles synthesized by a solvothermal method using thioacetamide as a sulfur source. S-doping into the LiFePO4 matrix expands the lattice due to the larger ionic radius of S2- than that of O2-. The lattice parameters a and b increase by around 0.2% with sulfur content, while that of c remains almost unchanged with only 0.03% increase. The S-doping also contributes to the suppression of antisite defects (Fe occupying Li sites), which facilitates the easy migration of Li in the diffusion channels without blockage. Owing to these effects of S-doping, the S-doped LiFePO4 nanoparticles show enhanced electrochemical properties with a high discharge capacity of ∼113 mA h g-1 even at a high rate of 10C.

Short communication: Neonatal calves coagulate first-milking colostrum and produce a large curd for efficient absorption of immunoglobulins after first ingestion.

Calves are fed milk and milk replacer for their growth until approximately 2 mo after birth. During this period, their abomasa produce curd and whey from milk. It has been thought that curd formation is important for digestion and absorption of milk nutrients and immune substances in calves. However, no study has been done observing abomasal contents in neonatal calves after first ingestion of first milking colostrum. Here we report curd formation in neonatal calves and its physiological function with a focus on immunoglobulin absorption. We first examined curd formation by ultrasonography in 3 neonatal calves after first ingestion of first-milking colostrum. Between 0.5 and 8 h after colostrum ingestion, a curd was visualized as a large echogenic image with a clear outline, which was surrounded by an anechoic image corresponding to whey. We next compared serum IgG and IgA concentrations in 10 calves fed the pooled colostrum and 7 calves fed the whey solution that did not coagulate into curds. Serum from 1 calf in the pooled colostrum sample set was excluded due to incomplete curd formation in that the whole colostrum did not coagulate into a large mass of curd and a portion of the colostrum remained as its residue caseins detectable from the abomasal fluid. Serum IgG and IgA concentrations were significantly higher in the 9 calves fed the colostrum than the 7 calves fed the whey solution. One calf exhibiting incomplete curd formation showed low levels of serum IgG and IgA after ingestion, similar to the calves fed the whey solution. These results indicate that curd formation is associated with IgG and IgA absorption in neonatal calves after first ingestion of colostrum.

Gene expression levels of gamma-glutamyl hydrolase in tumor tissues may be a useful biomarker for the proper use of S-1 and tegafur-uracil/leucovorin in preoperative chemoradiotherapy for patients with rectal cancer.

PURPOSE: Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based chemotherapy is the standard of care for rectal cancer. The effect of additional chemotherapy during the period between the completion of radiotherapy and surgery remains unclear. Predictive factors for CRT may differ between combination chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV). METHODS: The subjects were 54 patients with locally advanced rectal cancer who received preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed according to the tumor regression grade (TRG). The expression levels of 18 CRT-related genes were determined using RT-PCR assay. RESULTS: A pathological response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate logistic regression analysis for pathological response, the overall expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the accuracy rate of the predictive model was 83.3%. The effects of the gene expression levels of GGH on the response differed significantly according to the treatment regimen. The total pathological response rate of both high-GGH patients in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%. CONCLUSION: Additional treatment with 5-FU-based chemotherapy during the interval between radiotherapy and surgery is not beneficial in patients who have received 5-FU-based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in tumor tissues can predict the response to preoperative CRT including either S-1 or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.