Simultaneous Time-Resolved Photoluminescence and X-Ray Absorption Fine Structure Operando Measurement during Ag Cluster Formation in Ag Zeolite X

We use operando X-ray absorption fine structure (XAFS) to analyze the relation between the properties of photoluminescence (PL) and the structures of Ag clusters and Ag ions. The Ag clusters are generated by evacuation in the cavity of Ag-type zeolite-X. The Ag clusters in the zeolite cavity collapse when exposed to the atmosphere. The results reported herein indicate that the collapsing Ag cluster plays an important role in generating strong PL bands and that Ag clusters might not be a direct species of PL. Results of XAFS analysis show that the Ag cluster formed in the zeolite cavity by evacuation can be tetrahedral with four atoms. By evacuation, 9 or 10 Ag tetrahedral are formed, two of which are expected to be responsible for strong PL. This result suggests that the Ag ion position after cluster collapse plays an important role in PL band generation and that Ag clusters are not direct luminescent species of PL

Infrequent RAS mutation is not associated with specific histological phenotype in gliomas

BACKGROUND: Mutations in driver genes such as IDH and BRAF have been identified in gliomas. Meanwhile, dysregulations in the p53, RB1, and MAPK and/or PI3K pathways are involved in the molecular pathogenesis of glioblastoma. RAS family genes activate MAPK through activation of RAF and PI3K to promote cell proliferation. RAS mutations are a well-known driver of mutation in many types of cancers, but knowledge of their significance for glioma is insufficient. The purpose of this study was to reveal the frequency and the clinical phenotype of RAS mutant in gliomas. METHODS: This study analysed RAS mutations and their clinical significance in 242 gliomas that were stored as unfixed or cryopreserved specimens removed at Kyoto University and Osaka National Hospital between May 2006 and October 2017. The hot spots mutation of IDH1/2, H3F3A, HIST1H3B, and TERT promoter and exon 2 and exon 3 of KRAS, HRAS, and NRAS were analysed with Sanger sequencing method, and 1p/19q codeletion was analysed with multiplex ligation-dependent probe amplification. DNA methylation array was performed in some RAS mutant tumours to improve accuracy of diagnosis. RESULTS: RAS mutations were identified in four gliomas with three KRAS mutations and one NRAS mutation in one anaplastic oligodendroglioma, two anaplastic astrocytomas (IDH wild-type in each), and one ganglioglioma. RAS-mutant gliomas were identified with various types of glioma histology. CONCLUSION: RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma

Circulating miR-203 derived from metastatic tissues promotes myopenia in colorectal cancer patients

Sarcopenia frequently occurs in metastatic cancer patients. Emerging evidence has revealed that various secretory products from metastatic tumours can influence host organs and promote sarcopenia in patients with malignancies. Furthermore, the biological functions of microRNAs in cell-to-cell communication by incorporating into neighbouring or distal cells, which have been gradually elucidated in various diseases, including sarcopenia, have been elucidated. We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using pre-operative computed tomography imaging in 183 colorectal cancer (CRC) patients. miR-203 expression levels in CRC tissues and pre-operative serum were evaluated using quantitative polymerase chain reaction. Functional analysis of miR-203 overexpression was investigated in human skeletal muscle cells (SkMCs), and cells were analysed for proliferation and apoptosis. Expressions of several putative miR-203 target genes (CASP3, CASP10, BIRC5, BMI1, BIRC2, and BIRC3) in SKMCs were validated. A total of 183 patients (108 men and 75 women) were included. The median age of enrolled patients at diagnosis was 68.0 years (range 35-89 years). High IMAC status significantly correlated with female gender (P = 0.004) and older age (P = 0.0003); however, no other clinicopathological factors correlated with IMAC status in CRC patients. In contrast, decreased PMI significantly correlated with female gender (P = 0.006) and all well-established disease development factors, including advanced T stage (P = 0.035), presence of venous invasion (P = 0.034), lymphovascular invasion (P = 0.012), lymph node (P = 0.001), distant metastasis (P = 0.002), and advanced Union for International Cancer Control tumour-node-metastasis stage classification (P = 0.0004). Although both high IMAC status and low PMI status significantly correlated with poor overall survival (IMAC: P = 0.0002; PMI: P < 0.0001; log-rank test) and disease-free survival (IMAC: P = 0.0003; PMI: P = 0.0002; log-rank test), multivariate Cox's regression analysis revealed that low PMI was an independent prognostic factor for both overall survival (hazard ratio: 4.69, 95% confidence interval (CI): 2.19-10, P = 0.0001) and disease-free survival (hazard ratio: 2.33, 95% CI: 1.14-4.77, P = 0.021) in CRC patients. Serum miR-203 expression negatively correlated with pre-operative PMI level (P = 0.0001, ρ = -0.25), and multivariate logistic regression analysis revealed that elevated serum miR-203 was an independent risk factor for myopenia (low PMI) in CRC patients (odds ratio: 5.16, 95% CI: 1.8-14.8, P = 0.002). Overexpression of miR-203 inhibited cell proliferation and induced apoptosis via down-regulation of BIRC5 (survivin) expression in human SkMC line. Assessment of serum miR-203 expression could be used for risk assessment of myopenia, and miR-203 might be a novel therapeutic target for inhibition of myopenia in CRC

Fusobacterium nucleatum Infection in Colorectal Cancer: Linking Inflammation, DNA Mismatch Repair and Genetic and Epigenetic Alterations

It has been recently reported that the population of Fusobacterium, particularly Fusobacteriumnucleatum (Fn), is overrepresented in colorectal cancers (CRCs) and adenomas. The promoting effects of Fn infection on adenoma and/or carcinoma formation have been shown in ApcMin/+mice. Characteristics of Fn-associated CRC were identified through studies using human CRC cohorts and include right-sided colon location, CpG island methylation phenotype (CIMP)-high, high level of microsatellite instability (MSI-H), and poor patient prognosis. A subset of Fn-associated CRC exhibits a low level of microsatellite instability (MSI-L) and elevated microsatellite alterations in selected tetra-nucleotide repeats (EMAST) induced by translocation of MSH3 from the nucleus to the cytoplasm in response to oxidative DNA damage or inflammatory signals. The association between CIMP/MSI-H and Fn infection can be explained by the role of the mismatch repair protein complex formed between MSH2 and MSH6 (MutSα) to repair aberrant bases generated by reactive oxygen species (ROS) to form 7,8-dihydro-8-oxo-guanine (8-oxoG). Clustered 8-oxoGs formed at CpG-rich regions including promoters by ROS is refractory to base excision repair. Under these conditions, MutSα initiates repair in cooperation with DNA methyltransferases (DNMTs) and the polycomb repressive complex 4. DNMTs at damaged sites methylate CpG islands to repress transcription of target genes and promote repair reactions. Thus, continuous generation of ROS through chronic Fn infection may initiate (1) CIMP-positive adenoma and carcinoma in an MSH2/MSH6-dependent manner and/or (2) MSI-L/EMAST CRC in an MSH3-dependent manner. The poor prognosis of Fn-associated CRC can be explained by Fn-induced immune-evasion and/or chemoresistance

Double inferior vena cava, an uncommon but relevant anatomical anomaly in surgery for lower rectal cancer: a report of two cases

Abstract Background Double inferior vena cava (DIVC) is rare and usually detected incidentally. DIVC may be associated with several anatomical variants of the retroperitoneal and pelvic veins. These variants can pose a clinical problem during colorectal surgery. We present two patients with lower rectal cancer who also had a DIVC. Case presentation Case 1 was a 72-year-old man with advanced lower rectal cancer (T3N0M0) who underwent robot-assisted low anterior resection after neoadjuvant therapy. A DIVC was detected on preoperative computed tomography (CT). During the operation, a presacral vein was injured while mobilizing the rectum and hemostasis could not be achieved. We converted to open surgery and packed the pelvic cavity for hemostasis. Retrospective analysis suggested the injured vein arose from an interiliac vein of the presacral pelvic venous plexus. Case 2 was a 50-year-old woman with lower rectal cancer (T3N0M0), immune thrombocytopenic purpura, and a DIVC. Although preoperative three-dimensional CT angiography showed no obvious pelvic vein abnormalities, a short course of preoperative radiotherapy was delivered to avoid lateral pelvic lymph node dissection. Chemotherapy was deferred owing to her thrombocytopenic disease. Laparoscopic abdominoperineal resection was performed meticulously to minimize bleeding and achieve rapid hemostasis. No intraoperative complications occurred. Conclusion DIVC is often accompanied by venous malformations that may pose a problem when mobilizing the mesorectum from the retroperitoneum. Preoperative assessment of pelvic vessel anatomy using three-dimensional CT is essential in patients with a DIVC who undergo rectal surgery

Supplementary Table S3 from <i>Fusobacterium nucleatum</i> Load Correlates with <i>KRAS</i> Mutation and Sessile Serrated Pathogenesis in Colorectal Adenocarcinoma

Table S3 shows relationship between Fn copy number and genetic pathway in colorectal cancers</p

TABLE 2 from <i>Fusobacterium nucleatum</i> Load Correlates with <i>KRAS</i> Mutation and Sessile Serrated Pathogenesis in Colorectal Adenocarcinoma

Association of Fn infection with genomic/clinicopathologic factors (multivariate analysis)</p

Supplementary Table S1 from <i>Fusobacterium nucleatum</i> Load Correlates with <i>KRAS</i> Mutation and Sessile Serrated Pathogenesis in Colorectal Adenocarcinoma

Table S1 lists data for 306 cases of colorectal cancers</p

Supplementary Table S2 from <i>Fusobacterium nucleatum</i> Load Correlates with <i>KRAS</i> Mutation and Sessile Serrated Pathogenesis in Colorectal Adenocarcinoma

Table S2 lists data for 32 cases of adenomas</p