Search

Abstract Purpose It is still technically difficult to collect high purity cancer cells from tumor tissues, which contain noncancerous cells. We hypothesized that xenograft models of NOG mice expressing enhanced green fluorescent protein (eGFP), referred to as NOG-EGFP mice, may be useful for obtaining such high purity cancer cells for detailed molecular and cellular analyses. Methods Pancreato-biliary cancer cell lines were implanted subcutaneously to compare the tumorigenicity between NOG-EGFP mice and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. To obtain high purity cancer cells, the subcutaneous tumors were harvested from the mice and enzymatically dissociated into single-cell suspensions. Then, the cells were sorted by fluorescence-activated cell sorting (FACS) for separation of the host cells and the cancer cells. Thereafter, the contamination rate of host cells in collected cancer cells was quantified by using FACS analysis. The viability of cancer cells after FACS sorting was evaluated by cell culture and subsequent subcutaneous reimplantation in NOG-EGFP mice. Results The tumorigenicity of NOG-EGFP mice was significantly better than that of NOD/SCID mice in all of the analyzed cell lines (p Conclusions This method provides a novel cancer sampling system for molecular and cellular analysis with high accuracy and should contribute to the development of personalized medicine.

In this paper, we give an overview of some applications of combinatorics and permutations in music through the centuries. The concepts of permutation and tonnetz (spatial representation of voice leading and modulation) can be joined together in a physical device, the CubeHarmonic, a musical version of the Rubik's cube. We finally describe a prototype of the CubeHarmonic that uses the magnetic tracking technology developed at the Tohoku University.

Abstract Background Parkinson's disease (PD) and cerebral ischemia are chronic and acute neurodegenerative diseases, respectively, and onsets of these diseases are thought to be induced at least by oxidative stress. PD is caused by decreased dopamine levels in the substantia nigra and striatum, and cerebral ischemia occurs as a result of local reduction or arrest of blood supply. Although a precursor of dopamine and inhibitors of dopamine degradation have been used for PD therapy and an anti-oxidant have been used for cerebral ischemia therapy, cell death progresses during treatment. Reagents that prevent oxidative stress-induced cell death are therefore necessary for fundamental therapies for PD and cerebral ischemia. DJ-1, a causative gene product of a familial form of PD, PARK7, plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106) of DJ-1 renders DJ-1 inactive, and such oxidized DJ-1 has been observed in patients with the sporadic form of PD. Results In this study, a compound, comp-23, that binds to DJ-1 was isolated by virtual screening. Comp-23 prevented oxidative stress-induced death of SH-SY5Y cells and primary neuronal cells of the ventral mesencephalon but not that of DJ-1-knockdown SH-SY5Y cells, indicating that the effect of the compound is specific to DJ-1. Comp-23 inhibited the production of reactive oxygen species (ROS) induced by oxidative stress and prevented excess oxidation of DJ-1. Furthermore, comp-23 prevented dopaminergic cell death in the substantia nigra and restored movement abnormality in 6-hydroxyldopamine-injected and rotenone-treated PD model rats and mice. Comp-23 also reduced infarct size of cerebral ischemia in rats that had been induced by middle cerebral artery occlusion. Protective activity of comp-23 seemed to be stronger than that of previously identified compound B. Conclusions The results indicate that comp-23 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that comp-23 becomes a lead compound for PD and ischemic neurodegeneration therapies.

Abstract Background Deterioration of peroxisomal β-oxidation activity causes an accumulation of very long chain saturated fatty acids (VLCSFA) in various organs. We have recently reported that the levels of VLCSFA in the plasma and/or membranes of blood cells were significantly higher in patients with metabolic syndrome and in patients with coronary artery disease than the controls. The aim of the present study is to investigate the effect of VLCSFA accumulation on inflammatory and oxidative responses in VLCSFA-accumulated macrophages derived from X-linked adrenoleukodystrophy (X-ALD) protein (ALDP)-deficient mice. Results Elevated levels of VLCSFA were confirmed in macrophages from ALDP-deficient mice. The levels of nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ), intracellular reactive oxygen species (ROS), and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interluekin-6 (IL-6), and interleukin-12p70 (IL-12p70), were significantly higher in macrophages from ALDP-deficient mice than in those from wild-type mice. The inducible NO synthase (iNOS) mRNA expression also showed an increase in macrophages from ALDP-deficient mice. Conclusion These results suggested that VLCSFA accumulation in macrophages may contribute to the pathogenesis of inflammatory diseases through the enhancement of inflammatory and oxidative responses.

Purpose: The incidence and etiology of primary osteoarthritis (OA) of the scaphotrapeziotrapezoid joint (STTJ), radiocarpal joint (RCJ), and distal radioulnar joint (DRUJ) remains unknown. The purpose of this study was to evaluate the prevalence and factors associated with primary wrist OA in a cross-sectional study of a basic resident registry., Methods: A total of 1,297 residents between the ages of 50 and 89 years were randomly sampled from the registry of a Japanese town. A questionnaire was administered to all subjects, and each of them underwent radiographs of the bilateral hands, wrists, and elbows. STTJ, RCJ, and DRUJ radiographic osteoarthritis (ROA) were evaluated according to a previously described method. Associated factors for STTJ and DRUJ ROA were recorded. Associations between the incidence of ROA of the DRUJ, ulnar variance, and severity of elbow ROA were investigated., Results: A total of 676 wrists (162 men and 176 women; mean age of 69.0 years) were investigated. The prevalence of STTJ, RCJ, and DRUJ ROA was 5.3%, 1.5%, and 21.2%, respectively. Factors associated with STTJ ROA were thumb carpometacarpal joint ROA, female sex, and increasing age. Factors associated with DRUJ ROA were elbow ROA, use of vibrating tools, increasing age, and positive ulnar variance. Prevalence of DRUJ ROA was 54.4% in wrists with severe-grade elbow ROA. Ulnar variance of the wrist in severe-grade elbow ROA was significantly larger than that in mild-grade or nonelbow ROA., Conclusions: The prevalence of ROA was highest in the DRUJ, followed by the STTJ, and lowest in the RCJ. The occurrence of ROA of the STTJ and DRUJ was affected by the presence of ROA of the adjacent joint., Clinical Relevance: Primary DRUJ ROA occurs at a moderate frequency, similar to primary ROA of other extremity joints; however, primary STTJ and RCJ ROA is rare., (Copyright © 2023 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background : In the conservative management of distal radial fractures (DRFs), the optimal dorsi-volar angulation of the wrist at cast immobilization and proper cast molding to minimize the risk of redisplacement are unclear. This study identified the predictors of fracture redisplacement during cast immobilization for adult DRFs. Methods : We examined for dorsi-volar angulation, gap index, volar tilt (VT), radial inclination (RI), and radial length (RL) in lateral or posteroanterior radiographs of 90 DRFs. We investigated possible predisposition factors for redisplacement including patient age, sex, extra- or intra-articular fracture, metaphyseal comminution, original displacements, dorsi-volar angulation of the wrist at cast immobilization, restoration of the volar cortex at cast immobilization, and gap index of the cast. Results : Neither dorsi-volar angulation nor gap index had significant association with an unacceptable alignment nor decrease of VT, RI, and RL. In multivariate analysis, patient age, original displacement, and intra-articular fracture were the significant predictors of an unacceptable alignment or decrease of VT and RI. Conclusions : Our findings indicate dorsi-volar angulation and cast molding quality have no clinical effect on preventing fracture redisplacement. The predictive factors of the displacement were patient age, original displacement, and intra-articular fracture.

Background/aims: Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of gastric cancer remains unknown., Methodology: Methylation status of the WNT5A gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the WNT5A gene was detected in 7 out of the 38 (18%) primary gastric carcinomas, suggesting that the methylation of WNT5A is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0226). Moreover, a trend was shown towards early TNM stages in methylated tumors (p=0.209)., Conclusions: WNT5A was more frequently methylated in early gastric carcinomas.

Background/aims: Gemcitabine is widely used as a first-line therapy for biliary tract cancer (BTC). However, few studies have been conducted to analyze second- line therapies., Methodology: From 33 patients who had been administered gemcitabine following resection between May 2005 and August 2007, we retrospectively analyzed the safety and efficacy of S-1 in 11 cases who received S-1 as second-line therapy due to recurrence or relapse of the primary disease., Results: Among the adverse events (AEs) observed during S-1 administration, the most common was a decrease in the concentration of hemoglobin, followed by thrombocytopenia. No Grade 4 AEs or worse were detected. In addition, the AEs and their respective severity strongly resembled those of gemcitabine used as a first-line therapy. There were 7 cases that could be evaluated according to RECIST criteria, of which 1 was considered in the partial response and 3 as stable disease. The medians of time to progression after S-1 administration and survival after S-1 administration were 5.6 months and 31 months, respectively., Conclusions: S-1 could be taken safely as a second-line therapy without provoking severe AEs. By preventing the cessation of S-1 administration due to its AEs, more continued S-1 administration could lead to a better prognosis for BTC.

A 45-year-old man underwent a low anterior resection for rectal cancer [T3, N1, M0, Stage IIa: UICC]. He received a postoperative systemic chemotherapy with 5-FU and LV. Five months after the operation, multiple liver metastases were detected in the right hepatic lobe (S5, 6, 8). Right hepatectomy was performed. Seventeen courses of postoperative hepatic arterial infusion (HAI) chemotherapy (weekly high-dose 5-FU regimen) were performed without severe adverse events. He was still alive with no sign of recurrence for 69 months after hepatectomy. After liver resection for metastases of colorectal cancer, although a systemic chemotherapy has been mainly performed, HAI chemotherapy is one of the important options for prevention of local recurrence.

Background: Recently, Glockner et al. identified the methylation of TFPI2 as a frequent event in human colorectal cancer using a gene expression array-based strategy., Materials and Methods: Methylation status of the TFPI2 gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the TFPI2 gene was detected in 7 out of 38 (18%) primary gastric carcinomas, suggesting that the methylation of TFPI2 is frequently observed in gastric carcinomas. The clinicopathological data were correlated with the methylation results. A significant difference was observed in maximal tumour size (p=0.0084), extent of tumour (p=0.0068), and TNM stage (p=0.0392)., Conclusion: TFPI2 is frequently methylated in advanced gastric carcinomas.

Background: A tumor suppressor gene, p16, was found to harbor promoter methylation associated with the loss of protein expression in cancer cells, suggesting that p16 inactivation due to promoter methylation may be important for gastric tumorigenesis., Patients and Methods: The methylation status of the p16 gene was examined in primary carcinomas and the corresponding normal tissues derived from 49 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the p16 gene was detected in 17 out of the 49 (34%) primary gastric carcinomas, suggesting that the aberrant methylation of p16 is frequently observed in gastric carcinomas. The clinicopathological data were then correlated with these results. Significant differences were observed with lymphatic invasion (p=0.046) and tumor site (p=0.010)., Conclusion: p16 might act as a tumor suppressor in gastric carcinomas and appears to be more frequently methylated in lymphatic-invasive gastric carcinomas.

Background: Recently, it has been reported that TFPI2 (tissue factor pathway inhibitor-2), a Kunitz-type serine proteinase inhibitor, is frequently methylated in human colorectal cancer using a gene expression array-based strategy. The aim of this study therefore was to examine whether the TFPI2 methylation in surgically removed colorectal cancers was correlated to the clinicopathological features., Materials and Methods: The methylation status of the TFPI2 gene was examined in primary carcinomas and corresponding normal tissues derived from 50 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP), and the correlation between the methylation status and the clinicopathological findings was evaluated. Results. Methylation of the TFPI2 gene was detected in 31 out of the 50 (62%) primary colon carcinomas, suggesting that the methylation of TFPI2 is frequently observed in colorectal cancer. The clinicopathological data were compared with these results. Significant differences were observed between methylation of TFPI2 and histology (p=0.0053) or lymph node metastasis (p=0.0396). These results indicated that TFPI2 was more frequently methylated in well-differentiated advanced colorectal carcinomas., Conclusion: TFPI2 may act as a tumour suppressor in colorectal carcinomas and TFPI2 methylation may present a potential risk of malignancy in colorectal cancer.

Background: Recently, it has been reported that colorectal carcinoma is created and propagated by a small number of undifferentiated tumorigenic CD133(+) cells. Furthermore, it has been reported that CD133 expression is directly regulated by epigenetic modifications. Therefore, it is possible that CD133 expression by gene demethylation is related to colorectal and gastric carcinogenesis., Materials and Methods: The methylation status of the CD133 gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Demethylation of the CD133 gene was detected in 14 out of the 36 (39%) primary gastric carcinomas, suggesting that the demethylation of CD133 is frequently observed in gastric carcinomas. The clinicopathological data were correlated with the demethylation results. A significant decrease of CD133 methylation was observed in the extent of tumor (p=0.0421). Moreover, a trend was shown toward smaller maximal tumor size in tumors with demethylated CD133 (p=0.0556)., Conclusion: CD133 appears to be frequently demethylated in early gastric carcinomas.

Background: Deleted in colorectal carcinoma (DCC), one of the Netrin-1 receptors, belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Recently, we examined the methylation status of the DCC gene in colorectal carcinomas and found that aberrant methylation of the DCC gene was detected in 28 out of the 50 (56%) primary colon carcinomas. This result prompted us to examine the methylation status of the DCC gene in gastric carcinoma., Materials and Methods: The methylation status of the DCC gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the DCC gene was detected in 16 out of the 36 (44%) primary gastric carcinomas. A significant difference was observed in regard to the TNM stage (p=0.0093)., Conclusion: DCC methylation was observed in the course of gastric carcinogenesis and disappeared in advanced gastric carcinoma.

Background: Recently, Herfarth et al. reported that a subset of colorectal tumors was characterized by a specific methylation pattern in the MGMT promoter associated with reduced MGMT expression., Materials and Methods: Methylation status of the MGMT gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the MGMT gene was detected in 4 out of the 38 (11%) primary gastric carcinomas, suggesting that the methylation of MGMT is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0470), lymph node metastasis (p=0.0470), and TNM stage (p=0.0377) (Table I). Moreover, a trend was shown toward large maximal tumor size in methylated tumors (p=0.134)., Conclusion: MGMT was more frequently methylated in advanced gastric carcinomas.

Background: UNC5C, one of the netrin-1 receptors, belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Recently, aberrant methylation of the UNC5C gene was found in 34 out of 49 (69%) primary colon carcinomas., Materials and Methods: The methylation status of the UNC5C gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction, and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the UNC5C gene was detected in 9 out of the 36 (25%) primary gastric carcinomas. A significant difference was observed in regard to the TNM stage (p=0.0455)., Conclusion: UNC5C methylation was observed in the course of gastric carcinogenesis and disappeared in highly advanced gastric carcinomas.

Background: Recently, it was shown that the loss of human Tip60 leads to an accumulation of double-strand DNA breaks and is linked to a growing number of cancer types., Patients and Methods: Tip60 expression levels were in examined in 38 colorectal cancer samples using a quantitative real-time polymerase chain reaction. Subsequently, clinicopathological data were correlated with the Tip60 expression score., Results: A down-regulation of the Tip60 gene was observed 5 out of 38 (13%) specimens of primary colorectal cancer. Tip60 down-regulation showed significant correlation with larger tumor size (p=0.0005), poorly differentiated type (p=0.0394), peritoneal dissemination (p=0.0053), distant metastasis (p=0.0394), and higher stage of TNM classification (p=0.0226)., Conclusion: These results suggested that Tip60 was more frequently down-regulated in advanced colorectal carcinoma.

Background: We recently found that CDH3 was frequently demethylated in advanced colorectal carcinomas. This prompted us to examine the demethylation status of the CDH3 gene in gastric carcinomas., Materials and Methods: The demethylation status of the CDH3 gene was examined in primary tumors derived from 36 patients with gastric carcinoma using a quantitative methylation-specific PCR (qMSP) and was evaluated the correlation between the demethylation status and the clinicopathological findings., Results: Demethylation of the CDH3 gene was detected in 25 out of the 36 (69%) primary gastric carcinomas, suggesting that the aberrant demethylation of CDH3 is a frequent event in gastric carcinomas. Demethylation of CDH3 was significantly associated with increasing TNM stage (p=0.0261). Moreover, a trend was shown toward infiltration beyond the serosa being associated with demethylation of CDH3 (p=0.0733)., Conclusion: CDH3 was frequently demethylated in advanced gastric carcinomas.

Background: We recently examined the methylation status of the HACE1 gene in primary carcinomas derived from 32 patients with colorectal cancer. A significant increase was observed in the maximal tumor size of the tumors with methylated HACE1 (p=0.0304). Moreover, a trend was shown toward preferentially developing lymph node metastasis in the carcinomas with methylated HACE1 (p=0.0612), suggesting that HACE1 might present a malignant potential in colorectal cancer. These results prompted us to examine the methylation status of the HACE1 gene in gastric carcinomas., Materials and Methods: The methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 34 patients with gastric carcinoma using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: An aberrant methylation of the HACE1 gene was detected in 9 out of 34 (26%) primary gastric carcinomas. Subsequently, clinicopathological data were tested for correlation with the methylation score. A significant difference was observed in patient gender (p=0.0429)., Conclusion: HACE1 was frequently methylated in gastric carcinoma derived from male patients.

Background: Recently, it has been proven that the CDH3 promoter was hypomethylated in colonic aberrant foci and colorectal cancer. The hypomethylation was also associated with induction of CDH3 expression in colorectal cancer. These results indicated that epigenetic demethylation of the CDH3 promoter in the human intestine permits its ectopic expression in colorectal cancer., Materials and Methods: The demethylation status of the CDH3 gene was examined in primary carcinomas and the corresponding normal tissues derived from 53 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the demethylation status and the clinicopathological findings was evaluated., Results: Aberrant demethylation of the CDH3 gene was detected in 41 out of the 53 (77%) primary colon carcinomas. The clinicopathological data were correlated with the demethylation results. A significant difference was observed in the tumor site and Dukes' stage (p=0.0187 and p=0.0192, respectively). Moreover, a trend was shown toward preferentially developing tumor size (p=0.140)., Conclusion: These results indicated that CDH3 was more frequently demethylated in advanced colorectal carcinomas.

Background: Recently, it was shown that the vimentin gene, usually activated in mesenchymal cells, was highly methylated in colorectal carcinoma., Materials and Methods: The methylation status of the vimentin gene was examined in primary carcinomas and the corresponding normal tissues derived from 37 patients with gastric carcinoma using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the vimentin gene was detected in 14 out of 37 (38%) primary gastric carcinomas. This result suggested that the aberrant methylation of the vimentin gene was frequent in gastric carcinomas. Subsequently, clinicopathological data were correlated with the methylation score. A significant difference was observed in histology (p=0.0429). In addition, a trend was shown toward advancement of gastric carcinomas with vimentin methylation (p=0.0588)., Conclusion: In gastric carcinomas, well-differentiated adenocarcinoma was significantly methylated compared to poorly differentiated.