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Boron Neutron Capture Therapy (BNCT) has recently been used in clinical oncology thanks to recent developments of accelerator-based BNCT systems. Although there are some specific processes for BNCT, they have not yet been discussed in detail.The aim of this study is to provide comprehensive data on the risk of accelerator-based BNCT system to institutions planning to implement an accelerator-based BNCT system.In this study, failure mode and effects analysis (FMEA) was performed based on a treatment process map prepared for the accelerator-based BNCT system. A multidisciplinary team consisting of a medical doctor (MD), a registered nurse (RN), two medical physicists (MP), and three radiologic technologists (RT) identified the failure modes (FMs). Occurrence (O), severity (S), and detectability (D) were scored on a scale of 10, respectively. For each failure mode (FM), risk priority number (RPN) was calculated by multiplying the values of O, S, and D, and it was then categorized as high risk, very high risk, and other. Additionally, FMs were statistically compared in terms of countermeasures, associated occupations, and whether or not they were the patient-derived.The identified FMs for BNCT were 165 in which 30 and 17 FMs were classified as high risk and very high risk, respectively. Additionally, 71 FMs were accelerator-based BNCT-specific FMs in which 18 and 5 FMs were classified as high risk and very high risk, respectively. The FMs for which countermeasures were "Education" or "Confirmation" were statistically significantly higher for S than the others (p = 0.019). As the number of BNCT facilities is expected to increase, staff education is even more important. Comparing patient-derived and other FMs, O tended to be higher in patient-derived FMs. This could be because the non-patient-derived FMs included events that could be controlled by software, whereas the patient-derived FMs were impossible to prevent and might also depend on the patient's condition. Alternatively, there were non-patient-derived FMs with higher D, which were difficult to detect mechanically and were classified as more than high risk. In O, significantly higher values (p = 0.096) were found for FMs from MD and RN associated with much patient intervention compared to FMs from MP and RT less patient intervention. Comparing conventional radiotherapy and accelerator-based BNCT, although there were events with comparable risk in same FMs, there were also events with different risk in same FMs. They could be related to differences in the physical characteristics of the two modalities.This study is the first report for conducting a risk analysis for BNCT using FMEA. Thus, this study provides comprehensive data needed for quality assurance/quality control (QA/QC) in the treatment process for facilities considering the implementation of accelerator-based BNCT in the future. Because many BNCT-specific risks were discussed, it is important to understand the characteristics of BNCT and to take adequate measures in advance. If the effects of all FMs and countermeasures are discussed by multidisciplinary team, it will be possible to take countermeasures against individual FMs from many perspectives and provide BNCT more safely and effectively.

Deficiencies in mitochondrial protein import are associated with a number of diseases. However, although nonimported mitochondrial proteins are at great risk of aggregation, it remains largely unclear how their accumulation causes cell dysfunction. Here, we show that nonimported citrate synthase is targeted for proteasomal degradation by the ubiquitin ligase SCF Ucc1 . Unexpectedly, our structural and genetic analyses revealed that nonimported citrate synthase appears to form an enzymatically active conformation in the cytosol. Its excess accumulation caused ectopic citrate synthesis, which, in turn, led to an imbalance in carbon flux of sugar, a reduction of the pool of amino acids and nucleotides, and a growth defect. Under these conditions, translation repression is induced and acts as a protective mechanism that mitigates the growth defect. We propose that the consequence of mitochondrial import failure is not limited to proteotoxic insults, but that the accumulation of a nonimported metabolic enzyme elicits ectopic metabolic stress.

Misfolded luminal and membrane proteins in the endoplasmic reticulum (ER) are recognized and retrotranslocated to the cytosol for proteasomal degradation, a process referred to as ER-associated degradation (ERAD). InSaccharomyces cerevisiae, ERAD substrates with luminal lesions are targeted for proteasomal degradation by the Hrd1 ubiquitin ligase complex (ERAD-L pathway). Membrane proteins containing lesions within their membrane-spanning regions are also targeted for degradation by the Hrd1 complex (ERAD-M pathway), while those containing lesions within their cytosolic regions are targeted for degradation mainly by the Doa10 ubiquitin ligase complex (ERAD-C pathway). Here, we demonstrate that hydroxyurea (HU), which is widely used to arrest cells in S-phase and is also used to manage several diseases including sickle cell anemia and chronic myeloproliferative disorders, inhibited ERAD-L, but not ERAD-M or -C. HU-mediated inhibition of ERAD-L occurred independently of S-phase arrest. In HU-treated cells, the integrity of the Hrd1 ubiquitin ligase complex remained intact and substrate recognition was unaffected. Moreover, induction of the unfolded protein response was undetectable in cells in which ERAD-L was inhibited by HU. These results suggest an unexpected action of HU, which modulates protein quality control in the secretory pathway, and also suggest the existence of an additional regulatory step in ERAD.

In recent years, drug therapy for esophageal cancer has seen rapid progress, including immune checkpoint inhibitors. Guidelines for the treatment of esophageal cancer recommend nivolumab as second-line therapy. We report the results of nivolumab for unresectable advanced or recurrent esophageal cancer in our institution, including the cases that responded to the therapy. We analyzed 12 patients (male: female = 10:2, median age: 67 years) treated with nivolumab for unresectable advanced or recurrent esophageal cancer between March 2020 and March 2022. The status of treatment, response rate, adverse effects, and conversion rate to next line were analyzed for these patients. The median follow-up period was 4.2 months, and the median number of treatment cycles was 5 (2-41). Response rate was 17%, and disease control rate was 42%. Adverse effects included one case (8%) of severe diarrhea, considered ir-AE. The patient was treated with steroids. The rate of conversion to next-line treatment was 17% (2 cases). Nivolumab for esophageal cancer has a good prognosis in patients who respond to it. In addition, it is important to pay attention to ir-AE, perform imaging and physical examinations, and evaluate accurately and treat quickly.

In this study, gallium oxide (Ga2O3) nanoparticles were synthesized by sonochemical techniques at room temperature. We investigate the ultrasound irradiation conditions and the solvent type to synthesize Ga2O3 nanoparticles. γ-Ga2O3 nanoparticles were synthesized by irradiating gallium metal with ultrasound in hydrazine monohydrate solvent. The irradiation of hydrazine with ultasound suppresses the generation of ·OH, and GaOOH was not formed, and gallium metal directly oxidized. When the synthesized γ-Ga2O3 nanoparticles were heat-treated, a transition to β-Ga2O3 was observed. The heat-treated Ga2O3 nanoparticles showed excellent photocatalytic activity for the decomposition of RhB under UV irradiation.

ObjectivesFlow diverter or stent implantation to intracranial target lesion requires large inner diameter microcatheter navigation. The exchange method using stiff long wire is often necessary if it is difficult to navigate over the regular guidewire. However, this method has an intrinsic risk of vessel damage and may cause severe complications. We investigated the safety and efficacy of a new device, the Stabilizer device for navigation in a first-in-human clinical trial under the Certified Review Board agreement.Materials and methodsThe Stabilizer is a 320cm length exchange wire with a stent for anchoring and is compatible with a 0.0165" microcatheter. The trial design is a prospective single-arm open-label registry. Inclusion criteria are elective flow diverter treatment or stent-assisted coiling, expected to be difficult to navigate a microcatheter with a regular micro guidewire, and obtained documented consent. The primary endpoint of the study was a hemorrhagic complication.ResultsFive patients were enrolled in this trial. The median age is 52 years, ranges from 41 to 70, and all patients were female. Three aneurysms were located on the internal carotid artery, one on the vertebral artery, and one on the basilar artery. Basilar artery aneurysm was treated by stent-assisted coiling and others were treated by flow diverter deployment. All cases successfully navigate microcatheter for the treatment by the trial method using Stabilizer device without any adverse event.ConclusionsThe results from this first-in-human consecutive five cases show the safety of the Stabilizer device in neuro-endovascular therapy for navigation of devices to the intracranial target lesion.

The stable water isotopes (SWIs) (δ18O and δD) are used as an indicator of the intensity of the atmospheric hydrological cycle due to their large variability in time and space. SWIs are used for investigating the model’s bias and uncertainty. In this study, we developed a new global storm-resolving model equipped with SWIs (NICAM-WISO). We applied the new model to conduct three current climate simulations using a single-moment cloud microphysics scheme, without any convection parameterization scheme: CTRL, LRES, and HRES. These simulations used the same physical process but at a different horizontal resolution (LRES, 224 km; CTRL, 56 km; HRES, 14 km). We conducted the simulations on the supercomputer Fugaku. CTRL reproduced the seasonal means of the atmospheric hydrological cycle, as well as precipitation isotopic ratios. However, all simulation results have three types of biases. First, in tropical ocean regions, the model had a negative bias in precipitation isotopic ratios; this was caused by a negative bias in vapor isotopic ratios for the middle troposphere, which resulted from excess condensation biases during upward transportation and high-frequency deep convection. Second, all simulations overestimated precipitation isotopic ratios in the East Asia summer monsoon region due to low precipitation in the region caused by a shift in the moisture convergence zone from eastern China to the western Pacific Ocean. Third, in cold continental regions such as Siberia, Greenland, and Antarctica, the model had a positive bias in precipitation isotopic ratios due to a moisture bias and a low temperature effect; these regions also had a large positive bias in terms of precipitation deuterium excess. A particularly large bias was observed in ice clouds with low ice water content, indicating uncertainties in the vapor deposition process. Together, these results suggest that stable water isotopes are helpful for identifying biases associated with cloud microphysics and the atmospheric hydrological cycle. The unique constraints of stable water isotopes revealed cloud microphysics uncertainty and biases in the hydrological simulations.

[Purpose] Most exercise therapy procedures induce hemodynamic changes and could be a cardiovascular risk. This pilot study investigated factors that induce an exaggerated increase in blood pressure during exercise therapy. [Participants and Methods] We measured the blood pressure and pulse rate before and after exercise therapy for ambulation on days 1, 2, and 7 of the exercise therapy in patients (n=23; age, 69 ± 11 years) who were hospitalized for a stroke or an orthopedic surgery. [Results] Each participant’s blood pressure and pulse rate were significantly increased after the exercise therapy. Regression analysis demonstrated that the increase in systolic blood pressure was independently predicted by body weight and pulse rate before the exercise therapy. In the logistic regression analysis, age and body weight were independent predictors of the exaggerated increase in systolic blood pressure (fourth quartile). [Conclusion] A significant increase in blood pressure was induced by exercise therapy. There was a correlation between systolic blood pressure increase and pulse rate before the exercise therapy. Old age or increased body weight predicts exaggerated increase in blood pressure during exercise therapy.

We propose a boron–rhodamine-containing carboxylic acid (BRhoC) substance as a new sugar chemosensor. BRhoC was obtained by the Friedel–Crafts reaction of 4-formylbenzoic acid and N,N-dimethylphenylboronic acid, followed by chloranil oxidation. In an aqueous buffer solution at pH 7.4, BRhoC exhibited an absorption maximum (Absmax) at 621 nm. Its molar absorption coefficient at Absmax was calculated to be 1.4 × 105 M−1 cm−1, and it exhibited an emission maximum (Emmax) at 644 nm for the excitation at 621 nm. The quantum yield of BRhoC in CH3OH was calculated to be 0.16. The borinate group of BRhoC reacted with a diol moiety of sugar to form a cyclic ester, which induced a change in the absorbance and fluorescence spectra. An increase in the D-fructose (Fru) concentration resulted in the red shift of the Absmax (621 nm without sugar and 637 nm with 100 mM Fru) and Emmax (644 nm without sugar and 658 nm with 100 mM Fru) peaks. From the curve fitting of the plots of the fluorescence intensity ratio at 644 nm and 658 nm, the binding constants (K) were determined to be 2.3 × 102 M−1 and 3.1 M−1 for Fru and D-glucose, respectively. The sugar-binding ability and presence of a carboxyl group render BRhoC a suitable building block for the fabrication of highly advanced chemosensors.

Background Whole-layer laparoscopic cholecystectomy (W-LC) has recently been advocated as a total biopsy for potentially malignant neoplasms of the gallbladder; however, it is not an injury-proof procedure. This study reports W-LC using the segment IV approach (technique for securing the whole-layer gallbladder at the medial origin of the cystic plate).MethodsTwenty among twenty-five patients diagnosed with potentially malignant gallbladder polyps underwent this technique.ResultsMostly, W-LC was performed successfully (median operative time 135 min) without intraoperative and postoperative complications. Pathological findings indicated that cholesteric polyps was the most common type (n=13), followed by adenomatous polyps (25%) and carcinoma in situ (5%).ConclusionsWe conclude that the segment IV approach is appropriate for performing total biopsy in patients diagnosed with potentially malignant gallbladder polyps.

Misfolded proteins in the endoplasmic reticulum (ER) are retrotranslocated to the cytosol for ubiquitination and degradation by the proteasome. During this process, known as ER-associated degradation (ERAD), the ER-embedded Hrd1 ubiquitin ligase plays a central role in recognizing, ubiquitinating, and retrotranslocating scores of lumenal and integral membrane proteins. To better define the mechanisms underlying Hrd1 function in Saccharomyces cerevisiae, several model substrates have been developed. One substrate is Sec61–2, a temperature sensitive allele of the Sec61 translocation channel. Cells expressing Sec61–2 grow at 25 °C because the protein is stable, but sec61–2 yeast are inviable at 38 °C because the mutated protein is degraded in a Hrd1-dependent manner. Therefore, deleting HRD1 stabilizes Sec61–2 and hence sec61–2hrd1△ double mutants are viable at 38 °C. This unique phenotype allowed us to perform a non-biased screen for loss-of-function alleles in HRD1. Based on its importance in mediating substrate retrotranslocation, the screen was also developed to focus on mutations in sequences encoding Hrd1’s transmembrane-rich domain. Ultimately, a group of recessive mutations was identified in HRD1, including an ensemble of destabilizing mutations that resulted in the delivery of Hrd1 to the ERAD pathway. A more stable mutant resided in a buried transmembrane domain, yet the Hrd1 complex was disrupted in yeast expressing this mutant. Together, these data confirm the importance of Hrd1 complex integrity during ERAD, suggest that allosteric interactions between transmembrane domains regulate Hrd1 complex formation, and provide the field with new tools to define the dynamic interactions between ERAD components during substrate retrotranslocation.

The stable water isotopes (SWIs) (δ18O and δD) are used as an indicator of the intensity of the atmospheric hydrological cycle due to their large variability in time and space. Although data about vapor isotope ratio with high frequency and high resolution are now available by satellite observations and spectroscopic analyses, there is some room for discussion on the variability of isotope ratios in vapor and precipitation related to cloud microphysical processes.Here, we incorporated SWI tracer into the latest version of a global cloud system resolving model (the Nonhydrostatic Icosahedral Atmospheric Model (NICAM)), iso-NICAM, and investigated the contribution of cloud microphysical processes to the variability of isotope ratios in precipitation and vapor. One of the merits used NICAM is that its physical process can cover from low spatial resolution to high spatial resolution. We conducted two mode simulations (GCM and CRM). The GCM mode simulation is based on the Arakawa-Schubert scheme as convective parameterization and a large-scale condensation scheme as the cloud physical process. In contrast, the CRM mode simulation is based on the a single-moment bulk cloud microphysics scheme with 6 water categories as cloud microphysical scheme, convective parameterization scheme was not used. These simulations are set to about 223 km of horizontal mesh resolution and 78 vertical layers. We conducted an AMIP-type climate experiment for one year from 1979.The simulated precipitation δ18O showed the latitude effect pattern (high δ18O in low latitude region, low δ18O in high latitude region), but those values in the CRM mode was slightly lower than that in the GCM mode . The simulated precipitation δ18O in the CRM mode was lower in high altitude or inland regions compared with those in the GCM mode . Besides, the precipitation d-excess in the CRM mode shows large spatial variability compared with the GCM mode. Although the low spatial resolution was set in this study, these simulations indicated cloud microphysical processes are important for understanding the variability of isotope physics. We will conduct these simulations with finer spatial resolution and a more extended simulation period.

This study was aimed at evaluating the oncologic outcomes of our preoperative treatment strategies for cStage Ⅱ/Ⅲ lower rectal cancer. At our hospital, neoadjuvant chemotherapy is administered for patients with bulky mesenteric lymph nodes on pretreatment imaging, and neoadjuvant chemoradiotherapy is administered for patients whose circumferential radial or distal margin cannot be secured because of strong local extension.Thirty patients who underwent preoperative therapy followed by total mesorectal excision for cStage Ⅱ/Ⅲ lower rectal cancer were retrospectively analyzed from October 2010 to October 2015.Twenty-five patients underwent neoadjuvant chemotherapy, and 5 patients underwent neoadjuvant chemotherapy. Tumor recurrence occurred in 10 patients at local(5 patients)and distant(5 patients)sites. The 5-year recurrence-free survival(5RFS)was 63.9%.We performed preoperative therapy in poor-risk locally advanced lower rectal cancer and obtained good results.

The standard treatment in Japan for advanced lower rectal cancer is total mesorectal excision(TME)plus lateral lymph node dissection(LLND). However, the standard treatment in Western countries is preoperative treatment plus TME. There have been some discussions on preoperative chemotherapy and chemoradiation therapy. This study was aimed at identifying the prognostic factors of recurrence after curative surgery for advanced lower rectal cancer.A total of 54 patients with advanced lower rectal cancer who had undergone curative operation at our department from 2010 to 2015 were retrospectively analyzed, excluding patients with both LLND and preoperative therapy. The primary endpoint of this study was the 5-year recurrence-free survival(5RFS).The overall 5RFS was 57.6%. The univariate analysis demonstrated that lymph node metastasis(p=0.038)and radial margin(RM, p=0.015)were significant risk factors, with a 5RFS of 39.7% and 0%, respectively. The multivariate analysis revealed that only RM significantly affected 5RFS(p= 0.009).Our results suggest that securing an adequate circumferential resection margin together with proper surgical technique and preoperative therapy are important for decreasing postoperative recurrence rates of advanced lower rectal cancer.

A 49-year-old man was preoperatively diagnosed with rectosigmoid carcinoma, c-T4a, N3, M1b, Stage Ⅳb. On CT, lymph node swelling outside that area, including lesser-curvature lymph nodes(LNS), and liver metastases were seen. Laparoscopic high anterior resection was performed with the aim of local control. Additionally, D3 dissection and LNS sampling were performed. The tumor had invaded the bladder wall, and removed LNS were positive for metastasis. The final diagnosis was f-T4b, N3, M1b, Stage Ⅳb. One month after surgery, a CV port was implanted, and chemotherapy was initiated for unresectable cancer. The regimen was capecitabine and oxaliplatin(CAPOX)plus bevacizumab(BEV). After 5 courses, the patient was hospitalized for a CV thrombus that had occurred, and his chemotherapy was withdrawn for approximately 1 month while he was receiving antithrombotic therapy. After discharge, BEV was discontinued, and he received CAPOX alone. Bleeding from a pituitary adenoma was seen after a total of 19 courses. He was hospitalized for 2 months for the treatment, including surgery. A clinical complete response was determined based on CT and PET-CT performed after chemotherapy had been withdrawn for approximately 3 months. For approximately 1 year since the chemotherapy was discontinued, progression-free survival has been maintained.

Aim The optimal method for pancreatic stump closure to prevent postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP), remains controversial though DP is still the only curative treatment for pancreatic cancer and other malignancies located on pancreatic body or tail. Patients and methods A total of 44 patients who consecutively underwent open DP were retrospectively analyzed, dividing them into two groups: group H (hand-sewn; n=24) and group S (stapler closure; n=20). Results POPFs were encountered in 5 (21%) and 11 (55%) patients in groups H and S, respectively (p=0.02). POPFs of Clavien-Dindo grade IIIa or above were observed in two (8%) and seven (35%) patients in groups H and S, respectively (p=0.03). Conclusion When indicating stapler closure, caution should be exercised for pancreatic consistency and thickness, device and cartridge type, and pancreatic duct ligation to more effectively control POPF rates.

A cage compound was synthesized in order to investigate the structure and cation-π interactions of the metal ion complex. The multi-step synthesis was achieved starting from trimesic acid triethyl ester. In solution, a completely symmetrical structure that was anticipated by the molecular design was observed by 1H and 13C NMR spectroscopy. However, in the solid state, X-ray crystallographic analysis revealed that the compound had a collapsed structure.

Introduction Accidental gallbladder perforation frequently occurs during laparoscopic cholecystectomy and may increase the risk of infection. However, the necessity of antimicrobial prophylaxis for these patients is unclear. The aim of this study was to examine the clinical outcomes and necessity of antimicrobial prophylaxis after laparoscopic cholecystectomy with gallbladder perforation. Methods One hundred patients who underwent laparoscopic cholecystectomy were divided into two groups: patients with gallbladder perforation (Group A, n = 37) and patients without perforation (Group B, n = 63). We compared the white blood cell count and C-reactive protein level the day after the operation, the complication rates of systemic inflammatory response syndrome and surgical-site infection, and postoperative hospital stay between the two groups. All patients received antimicrobial prophylaxis only once before the operation. Results There were significant differences in every variable with the exception of postoperative hospital stay. Group A had a higher risk of infection, but the postoperative clinical course of Group A was not inferior to that of Group B. Conclusion The clinical outcomes of patients with accidental gallbladder perforation were acceptable, and the use of antimicrobial prophylaxis once before the operation was sufficient.

Sudden oculomotor palsy with severe headache is known to suggest a ruptured ipsilateral internal carotid artery aneurysm. We encountered a case of contralateral oculomotor nerve palsy due to internal carotid artery-anterior choroidal artery ruptured aneurysm. A 63-year-old woman presented with severe headache and sudden right oculomotor palsy. Computed tomography(CT)showed subarachnoid hemorrhage, and three-dimensional CT showed a left internal carotid artery-anterior choroidal artery aneurysm. We performed neck clipping via a left pterional approach. After the surgery, right oculomotor palsy was not observed. We think the causes of oculomotor nerve palsy in this case were hematoma and elevated intracranial pressure. Once these factors were removed, we think that oculomotor nerve palsy was not observed.

The plastin3 (PLS3) gene, which encodes an actin bundling protein known to inhibit cofilin-mediated depolymerization of actin fiber, has been previously reported to serve an important role in the epithelial-mesenchymal transition (EMT) in cancer. The aim of the present study was to determine the clinical significance of PLS3 and its role in regulating EMT, as well as in promoting cell invasion and migration in gastric cancer. The expression of plastin3 mRNA was measured in 163 resected gastric cancer specimens, in order to determine the clinicopathological significance. Furthermore, in vitro invasion and migration assays were performed on gastric cancer cells, which revealed that PLS3 expression was suppressed. The high PLS3 expression group had a higher incidence of advanced tumour stage, cancer differentiation, tumour invasion depth and distant metastases compared with the low PLS3 expression group (P

Recent studies have indicated that increased ribosomal activity contributes to cancer progression. Transcription termination factor, RNA polymerase I (TTF1) acts as a transcription factor for RNA polymerase I. However, the role which TTF1 plays in cancer progression still remains unknown. The present study aimed to determine whether TTF1 plays a critical role in the progression of human liver hepatocellular carcinoma (HCC). In the present study, quantitative real-time reverse transcription polymerase chain reaction was conducted to evaluate TTF1 mRNA expression in 60 HCC tissue samples in order to determine the clinicopathological significance of TTF1. To investigate whether the expression levels of TTF1 were associated known gene signatures which represented ribosomal activity, we applied gene set enrichment analysis (GSEA) to HCC cases in The Cancer Genome Atlas (TCGA) a. We also performed in vitro proliferation assays using TTF1‑overexpressing HCC cells. TTF1 expression was significantly higher in HCC tumor tissues than in adjacent liver tissues (P

Background: Insertion of an external ventricular drain (EVD) is an important neurosurgical technique. There is a minor risk of misplacement, and complications including infections or hemorrhages have been reported. Transient neurological complications are, however, very rare, especially when EVD is placed under endoscope assistance. We report a case of unilateral transient oculomotor palsy after an EVD procedure. Case presentation: An 11-year-old boy with past medical history of moyamoya disease suffered from intraventricular hemorrhage and acute hydrocephalus. Insertion of EVD and hematoma removal was performed with endoscope assistance. After the surgery, transient oculomotor palsy occurred by the direct compression of the brain stem by the drainage tube. Conclusion: Transient unilateral oculomotor palsy due to the direct compression of the midbrain by an EVD tube is a very rare, but possible complication, even under endoscopic assistance. Attention through the procedure is required until skin closure to avoid tube dislocation.

Background/aim Omega-3 fatty acids may improve cancer cachexia, but only in patients with pancreatic and bile duct cancer. Patients with pancreatic cancer commonly suffer from exocrine pancreatic insufficiency, and the ingestion of digestive enzyme supplements may improve absorption. Patients and methods Racol®, an enteral nutrient formulated with omega-3 fatty acids, was administered to patients with unresectable pancreatic and bile duct cancer. The skeletal muscle mass and blood test data were taken pre-administration and at 4 and 8 weeks after. Patients with pancreatic cancer were given the digestive enzyme supplement LipaCreon® from the fifth week after the start of administration. Results In all 27 patients, skeletal muscle mass was significantly increased at both 4 and 8 weeks after the start of administration versus pre-administration (p=0.006, p=0.002, respectively). Conclusion Omega-3 fatty acid supplementation in patients with unresectable pancreatic and bile duct cancer may improve cancer cachexia.

Nematic liquid crystals (NLCs) absorbed in a nonwoven of surface-treated silica nanofibres (SiO2-NFs) orient the director along the nonwoven thickness direction if the NLCs prefer homeotropic anchoring onto the fibre surface. The nonwoven has vacant spaces with the dimensions of 0.3 and 0.6 μm in the thickness and cross directions, respectively, bordered with SiO2-NFs with 93 nm in diameter. The SiO2-NF surface was treated with a silane-coupling agent to induce the homeotropic anchoring of NLC mesogens onto the surface. The nematic director is arranged radially from the fibres although it is more severely constrained by the proximity between fibre surfaces along the thickness direction. Consequently, the NLCs can align along the nonwoven thickness direction involving −1/2 wedge disclinations on both sides of the fibres.

RNA polymerase 1 transcription termination factor (TTF1) mediates the transcription of ribosomal RNA (rRNA). In the current study, we investigated the clinical and biological significance of the TTF1 gene in colorectal cancer (CRC). The expression of TTF1 messenger RNA (mRNA) in tumor and normal tissues from 136 patients with CRC was examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). We also performed in vitro cell proliferation and migration assays in TTF1-expressing CRC cells. The biological role of TTF1 in CRC was further elucidated using gene set enrichment analysis (GSEA) with CRC samples. TTF1 expression was significantly higher in tumor tissues than in corresponding normal tissues (p = 0.016). In clinicopathological analysis, the high-TTF1 expression group showed a higher incidence of liver metastasis and lymphatic invasion than the low-TTF1 expression group (p

MicroRNAs have roles in the regulation of the epithelial–mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer. In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3′ untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines. Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P

Downregulation of paired related homeobox 1 (PRRX1) is associated with the acquisition of cancer stem cell (CSC)-like properties and poor prognosis in cancers. The purpose of this study is to clarify the role of PRRX1 expression in predicting prognosis and mediating CSC-like properties in hepatocellular carcinoma (HCC). The association between PRRX1 expression and overall survival (OS) of patients with HCC was analyzed in three independent datasets: 62 resected primary cases, 242 cases from GSE14520, and 162 cases from The Cancer Genome Atlas (TCGA). A cell line expressing PRRX1 (HuH7) was established for the functional analyses. The ability to form spheres, the expression levels of the hepatic CSC surface markers (CD13, CD133, and EpCAM), in vitro chemosensitivity to 5-fluorouracil (FU), and radiosensitivity were evaluated. Univariate and multivariate analyses showed that the 5-year OS of the low PRRX1 expression group was significantly poorer than that of the high PRRX1 expression group (P = 0.024 and P = 0.045, respectively). Consistent with this, the low PRRX1 expression group in GSE14520 and TCGA datasets showed significantly shorter OS (P = 0.027 and P = 0.010, respectively). Gene set enrichment analysis on GSE14520 and TCGA datasets indicated that downregulation of PRRX1 was correlated with the stemness signature. The number of spheres and the expression levels of CSC markers were significantly decreased when PRRX1 was expressed. Moreover, PRRX1 impaired resistance to 5-FU and radiation. Downregulation of PRRX1 expression contributes to the poor prognosis of patients with HCC through acquisition of CSC-like properties.

// Yuki Takano 1, 2, * , Takaaki Masuda 1, * , Hisae Iinuma 3 , Rui Yamaguchi 4 , Kuniaki Sato 1 , Taro Tobo 5 , Hidenari Hirata 1 , Yosuke Kuroda 1 , Sho Nambara 1 , Naoki Hayashi 1 , Tomohiro Iguchi 1 , Shuhei Ito 1 , Hidetoshi Eguchi 1 , Takahiro Ochiya 6 , Katsuhiko Yanaga 2 , Satoru Miyano 4 and Koshi Mimori 1 1 Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan 2 Department of Surgery, Jikei University School of Medicine, Tokyo, Japan 3 Department of Surgery, Teikyo University, Tokyo, Japan 4 Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan 5 Department of Pathology, Kyushu University Beppu Hospital, Beppu, Japan 6 Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan * These authors have contributed equally to this work Correspondence to: Koshi Mimori, email: kmimori@beppu.kyushu-u.ac.jp Keywords: miR-203, exosome, tumor-host interaction, tumor-associated macrophage, colorectal cancer Received: March 06, 2017 Accepted: June 26, 2017 Published: August 07, 2017 ABSTRACT A primary tumor can create a premetastatic niche in distant organs to facilitate the development of metastasis. The mechanism by which tumor cells communicate with host cells to develop premetastatic niches is unclear. We focused on the role of microRNA (miR) signaling in promoting metastasis. Here, we identified miR-203 as a signaling molecule between tumors and monocytes in metastatic colorectal cancer (CRC) patients. Notably, high expression of serum exosomal miR-203 , a major form in circulation, was associated with distant metastasis and an independent poor prognostic factor, whereas low expression in tumor tissues was a poor prognostic factor in CRC patients. We also found that exosomes carrying miR-203 from CRC cells were incorporated into monocytes and miR-203 could promote the expression of M2 markers in vitro , suggesting miR-203 promoted the differentiation of monocytes to M2-tumor-associated macrophages (TAMs). In a xenograft mouse model, miR-203 -transfected CRC cells developed more liver metastasis compared to control cells. In conclusion, serum exosomal miR-203 expression is a novel biomarker for predicting metastasis, possibly via promoting the differentiation of monocytes to M2-TAMs in CRC. Furthermore, we propose the concept of site-dependent functions for miR-203 in tumor progression.

The optimal method for pancreatic stump closure to prevent postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP), remains controversial though DP is still the only curative treatment for pancreatic cancer and other malignancies located on pancreatic body or tail.A total of 44 patients who consecutively underwent open DP were retrospectively analyzed, dividing them into two groups: group H (hand-sewn; n=24) and group S (stapler closure; n=20).POPFs were encountered in 5 (21%) and 11 (55%) patients in groups H and S, respectively (p=0.02). POPFs of Clavien-Dindo grade IIIa or above were observed in two (8%) and seven (35%) patients in groups H and S, respectively (p=0.03).When indicating stapler closure, caution should be exercised for pancreatic consistency and thickness, device and cartridge type, and pancreatic duct ligation to more effectively control POPF rates.

Recent studies indicated that the scaffolding adaptor protein GAB2 (GRB2-associated binding protein 2) plays a critical role in the proliferation and migration of various cancers. This study aimed to determine the role of aberrant GAB2 expression in human colorectal cancer (CRC). Quantitative real-time reverse transcription polymerase chain reaction was used to evaluate GAB2 mRNA expression in 152 CRC tissues samples to determine the clinicopathological significance of GAB2 expression. We also performed in vitro proliferation assays using siGAB2-transfected CRC cells. GAB2 expression in tumor colorectal tissues was significantly higher than in normal colorectal tissues (p = 0.0212). High GAB2 expression levels were associated with malignant clinicopathologic potential factors, including lymphatic invasion (p = 0.0003), venous invasion (p = 0.0170), and liver metastasis (p = 0.0144). The survival rate of patients with high GAB2 expression levels was significantly lower than that of patients with low GAB2 expression (p = 0.0074). Multivariate analysis indicated that GAB2 expression was a factor affecting lymph node metastasis. Cell proliferation was significantly suppressed by siGAB2 expression in CRC cells in vitro. GAB2 expression was associated with lymph node metastasis and may play a role in the growth and metastasis of CRC. These results suggest that GAB2 is a potential therapeutic target in CRC.

A novel method using metastatic breast cancer cell lines was established for producing monoclonal antibodies (mAbs) against multi-span membrane proteins. Grafting of metastatic cells (MCF7-14) into the mammary gland of BALB/cJ/nu/nu mice induced splenic hypertrophy (1.6-3.0×10(8)cells/spleen [n=6]). More than half of the mAbs against MCF7-14 cells reacted with the cell membrane. Inducing production of antibodies against the extracellular domain of multi-pass membrane proteins is difficult. Because the protein structure becomes more complex as the number of transmembrane domains increases, preparing antigens for immunization in which the original structure is maintained is challenging. Using highly metastatic MDA-MB231 cells as the host cell line, we produced mAbs against a 12 transmembrane protein, solute carrier family 6 member 6 (SLC6A6), as a model antigen. When SLC6A6-overexpressing MDA-MB231 cells were grafted into nude mice, the number of splenocytes increased to 2.7-11.4×10(8)cells/spleen (n=10). Seven mAb-producing clones that not only recognized the extracellular domain of SLC6A6 but also were of the IgG subclass were obtained. Immunocytochemistry and flow cytometry analyses revealed that these mAbs recognized the native form of the extracellular domain of SLC6A6 on the cell surface. Our novel immunization method involving highly metastatic cells could be used to develop therapeutic mAbs against other multi-pass membrane proteins.

Depressed and flat surface lesions are not easy to identify with routine colonoscopies during screening for colorectal cancer (CRC). Identifying clinically relevant genes that influence tumor shape could be useful when screening for the presence of depressed lesions. Total RNA was extracted from tumor cells collected by laser microdissection from the primary lesions of 146 CRC cases. Microarray analysis was performed to identify genes that were differentially expressed between depressed and elevated tumors. Single nucleotide polymorphism (SNP) analysis of genomic DNA from the peripheral blood of 67 CRC patients was then used to associate polymorphisms with the occurrence of depressed tumors. Microarray analysis revealed significantly higher expression of the fibronectin 1 (FN1) gene in 129 depressed-type tumors and lesions compared to 17 elevated-type tumors. FN1-abundant CRC tumors were large with a significantly higher incidence of lymphatic permeation. SNP analysis indicated that 44 tumors with a GG genotype at SNP rs6707530 showed significantly higher FN1 expression than did 23 tumors with GT/TT genotypes (p

We herein describe the first known case of diffuse alveolar hemorrhage (DAH) associated with the administration of Makyo-kanseki-to, a Chinese herbal drug. A 64-year-old man with bronchial asthma presented with persistent cough. Makyo-kanseki-to was prescribed as an adjunctive treatment for bronchial asthma. Immediately after drug ingestion, the patient expectorated bloody sputum. DAH was diagnosed based on the presence of bilateral ground-glass opacity which was identified on chest computed tomography and bloody bronchoalveolar lavage fluid. We diagnosed that the administration of Makyo-kanseki-to was the responsible medication because the hemorrhage developed immediately after drug ingestion and resolved after the cessation of such medication with no subsequent recurrence.

NIMA-related kinase 2 (NEK2), an enzyme involved in the development and progression of cancer, is abnormally expressed in a wide variety of human cancers, including colorectal cancer (CRC), and is known to have roles in cell division and mitotic regulation through centrosome splitting. We investigated the clinical significance of NEK2 in CRC. In particular, we examined miR-128 expression, which is thought to target NEK2. We measured NEK2 mRNA and miR-128 levels in clinical samples by quantitative reverse transcription real-time PCR and analyzed the associations between NEK2 levels, miR-128 levels, clinicopathological factors, and prognoses. Furthermore, we performed in vitro assays using a pre-miR-128 precursor and conducted miR-128 methylation analyses. MiR-128 inhibited NEK2 expression and cancer cell proliferation via cell cycle arrest. Moreover, miR-128 was silenced by DNA methylation. Increased NEK2 expression was associated with serosal invasion, lymphatic invasion, and peritoneal dissemination. Patients with high NEK2 expression also had significantly poorer prognoses. Multivariate analysis indicated that high NEK2 expression was an independent prognostic factor for survival. Patients with high miR-128 expression had significantly lower NEK2 expression and lower recurrence rates than those with low miR-128 expression. NEK2 may be an independent prognostic factor for CRC and was regulated by miR-128, a microRNA that was subjected to epigenetic regulation. Thus, this miR-128/NEK2 pathway may be a prospective therapeutic target for patients with CRC.

The prognosis for individuals that are diagnosed with gastric cancer remains poor due to the high frequency of metastatic disease. In response to tumor-derived secreted factors, the bone marrow generates a suitable microenvironment for the development of metastasis. However, it is largely unknown whether secreted factors in bone marrow associated with metastatic disease of patients with gastric cancer are present. Secreted factors from the bone marrow of patients with metastatic gastric cancer were identified using a DNA microarray analysis and the mRNA expression levels were investigated in 355 bone marrow, 295 peripheral blood and 144 primary site samples using quantitative PCR (qPCR). Using DNA microarray analysis, the present study identified bone morphogenetic protein 8B (BMP8B) as a secreted signaling molecule in the bone marrow that was associated with the metastatic disease of human gastric cancer. The expression levels of BMP8B in the bone marrow of 355 gastric cancer patients were increased with metastatic disease. A significant correlation was demonstrated between BMP8B mRNA expression in the bone marrow and in the peripheral blood. High BMP8B expression in the bone marrow was associated with the diffuse type of gastric cancer (P=0.009), lymph node metastasis (P=0.009), liver metastasis (P=0.044) and peritoneal dissemination (P

TP53 is one of the most widely known cancer suppressor genes. Mutations in TP53 are ubiquitously observed in almost all cancers. Incidences of mutations range from ~15–70 % in patients with hepatocellular carcinoma (HCC). Moreover, patients with mutated TP53 have poorer prognoses than those with wild-type TP53; therefore, it would be beneficial to predict the prognosis of HCC patients with wild-type TP53. We previously reported that PICT1, coding a nucleolus protein, regulates TP53 through indirect association. In this study, we examined PICT1 expression levels and the status of TP53 in 51 primary HCC tissues in order to determine the clinical significance of PICT1 expression and the function of PICT1 in HCC cells. We detected 6 mutations in the 51 samples. In 45 patients with wild-type TP53, those with high PICT1 expression (n = 11) had poorer prognoses than those with low PICT1 expression (n = 34), and there were no significant associations with other clinicopathological factors. According to gene set enrichment analysis, PICT1 expression was inversely correlated with the gene set of TP53. In vitro assays indicated that suppression of PICT1 expression caused an increase in TP53 expression, reduction in cell proliferation, and arrest at the G1 phase of the cell cycle in HCC cells expressing wild-type TP53. PICT1 should be a useful prognostic marker in HCC patients having wild-type TP53. Furthermore, PICT1 may become a promising therapeutic target because of its ability to increase the expression and activation of TP53.

Accidental gallbladder perforation frequently occurs during laparoscopic cholecystectomy and may increase the risk of infection. However, the necessity of antimicrobial prophylaxis for these patients is unclear. The aim of this study was to examine the clinical outcomes and necessity of antimicrobial prophylaxis after laparoscopic cholecystectomy with gallbladder perforation.One hundred patients who underwent laparoscopic cholecystectomy were divided into two groups: patients with gallbladder perforation (Group A, n = 37) and patients without perforation (Group B, n = 63). We compared the white blood cell count and C-reactive protein level the day after the operation, the complication rates of systemic inflammatory response syndrome and surgical-site infection, and postoperative hospital stay between the two groups. All patients received antimicrobial prophylaxis only once before the operation.There were significant differences in every variable with the exception of postoperative hospital stay. Group A had a higher risk of infection, but the postoperative clinical course of Group A was not inferior to that of Group B.The clinical outcomes of patients with accidental gallbladder perforation were acceptable, and the use of antimicrobial prophylaxis once before the operation was sufficient.