Extremely Shallow Valence Band in Lanthanum Trihydride.

Hydride ions (H-) in solvents are chemically active anions with strong electron-donating ability and are used as reducing agents in organic chemistry. Here, we evaluate the energy level of 1s-electrons in H- accommodated in solid lanthanum hydrides, LaHx (2 ≤ x ≤ 3), by photoemission (ultraviolet photoelectron and photoelectron yield spectroscopies) measurements and density functional theory calculations. We show that a very shallow valance band maximum with an ionization potential of 3.8 eV is attained in LaH3 and that the primary cause is attributed to the small electronegativity of hydrogen and the significant bonding-antibonding interaction between neighboring H-s with a close separation originating from the H-stuffed fluorite-related structure. These results encourage the challenge for p-type conduction in hydride semiconductors and provide a clue to the chemical understanding of polyhydride superconductors.

Real-world assessment of comprehensive genome profiling impact on clinical outcomes: A single-institution study in Japan.

INTRODUCTION: Comprehensive genome profiling (CGP) has revolutionized healthcare by offering personalized medicine opportunities. However, its real-world utility and impact remain incompletely understood. This study examined the extent to which CGP leads to genomically matched therapy and its effectiveness. METHODS: We analyzed data from advanced solid tumor patients who underwent CGP panel between December 2019 and May 2023 at the Osaka International Cancer Institute. Patient demographics, specimen details, and expert panel assessments were collected. Turnaround time (TAT) and genomically matched therapy outcomes were analyzed. Gene alterations and their co-occurrence patterns were also assessed. RESULTS: Among 1437 patients, 1096 results were available for analysis. The median TAT was 63 [28-182] days. There were 667 (60.9%) cases wherein recommended clinical trials were presented and there were 12 (1.1%) cases that could be enrolled in the trial and 25 (2.3%) cases that could lead to therapies under insurance reimbursement. The median progression free survival of the trial treatment was 1.58 months (95% CI: 0.66-4.37) in clinical trials and 3.66 months (95% CI: 2.14-7.13) in treatment under insurance. Pathologic germline variants were confirmed in 15 patients (1.3%). Co-alteration of CDKN2A, CDKN2B, and MTAP was significantly observed in overall population. CONCLUSION: The effectiveness of the genomically matched therapy based on the CGP panel was unsatisfactory. Expansion of clinical trials and utilization of remote clinical trials are required to ensure that the results of the CGP panel can be fully returned to patients.

Utility of Comprehensive Genomic Profiling Tests for Patients with Incurable Pancreatic Cancer in Clinical Practice.

Although comprehensive genomic profiling (CGP) tests have been covered under the Japanese national health insurance program since 2018, the utility and issues of CGP tests have not been clarified. We retrospectively reviewed 115 patients with incurable pancreatic cancer (IPC) who underwent CGP tests in a Japanese cancer referral center from November 2019 to August 2021. We evaluated the results of CGP tests, treatments based on CGP tests, and survival time. Eight cases (6.9%) were diagnosed as tumor mutation burden-high (TMB-H) and/or microsatellite instability-high (MSI-H). The gene mutation rates of KRAS/TP53/CDKN2A/SMAD4 were 93.0/83.0/53.0/25.2%, respectively. Twenty-five patients (21.7%) had homologous recombination deficiency (HRD)-related genetic mutations. Four patients (3.5%) having TMB-H and/or MSI-H were treated with pembrolizumab, and only two patients (1.7%) participated in the clinical trials. Patient characteristics were not significantly different between patients with and without HRD-related gene mutations. The median OS was significantly longer in the HRD (+) group than in the HRD (-) group (749 days vs. 519 days, p = 0.047). In multivariate analysis, HRD-related gene mutation was an independent prognostic factor associated with favorable OS. CGP tests for patients with IPC have the potential utility of detecting HRD-related gene mutations as prognostic factors as well as a therapeutic search.

Characteristic Resistive Switching of Rare-Earth Oxyhydrides by Hydride Ion Insertion and Extraction.

Resistive switching induced by ion migration is promising for applications such as random-access memory (ReRAM) and neuromorphic transistors. Hydride ions (H-) are an interesting candidate as the migration ion for resistive switching devices because they have fast diffusion in several compounds at room temperature and doping/dedoping can be used effectively to achieve significant changes in the electronic conductivity. Here, we report reversible resistive switching characteristics in rare-earth oxyhydrides (REHxO(3-x)/2) induced by field insertion/extraction of H-. The current-voltage measurements revealed that the resistive switching response, hysteresis, and switching voltage vary greatly with the H-/O2- ratio in the films. We fabricated a ReRAM device using Ti/YH1.3O0.85/MoOx structure and confirmed the bipolar-type operation with the resistance switching ratio of 1 order of magnitude over 1000 cycles. The composition gradient of H-/O2- in YHxO(3-x)/2 films, in addition to the hydrogen-absorbing ability of the top electrode, is essential for effective device operation. Our findings show that hydride-conducting solid-state electrolytes are suitable for resistive switching device development.

Utility of p16/Ki67 double immunocytochemistry for detection of cervical adenocarcinoma.

BACKGROUND: Although the incidence of cervical adenocarcinoma has consistently increased, especially among young women, there is no established best means for screening. This study evaluated the screening efficacy of CINtec PLUS (CINtec; p16/Ki67 double immunocytochemistry) expression in cervical glandular cells. METHODS: Cervical cytology was examined using abnormal glandular cells. The CINtec status of 100 samples with corresponding surgically resected specimens and 11 samples that exhibited negative results for intraepithelial lesion or malignancy at follow-up was analyzed. Additionally, 31 negative samples containing benign glandular cells were included. RESULTS: Of the 142 samples, CINtec status was diffusely positive in 74, focally positive in 24, and negative in 44. The 74 diffusely positive samples included 70 adenocarcinomas (62 cervical, seven uterine, and one ovarian) and four cases of high-grade cervical intraepithelial neoplasia. The 24 focally positive samples included 15 adenocarcinomas (seven cervical, seven uterine, and one fallopian tube) and nine without malignancy. The 44 negative samples included nine adenocarcinomas (five uterine and four cervical) and 35 without malignancy. The sensitivity, specificity, positive predictive value, and negative predictive value of the CINtec diffusely or focally positive cases for cervical adenocarcinomas were 94.5%, 58.0%, 70.4%, and 90.9%, respectively. In CINtec diffusely positive cases, the respective values were 84.9%, 82.6%, 83.8%, and 83.8%, and in women aged ≤39 years the values were 90.6%, 89.5%, 93.5%, and 85.0%, respectively. CONCLUSIONS: CINtec may support efficient detection of cervical adenocarcinomas.

Clinical application of comprehensive genomic profiling panel to thoracic malignancies: A single-center retrospective study.

BACKGROUND: The usefulness of comprehensive genomic profiling (CGP) panels for thoracic malignancies after completion of the standard treatment is unclear. METHODS: The results of CGP panels for malignant thoracic diseases performed at our hospital between December 2019 and June 2022 were collected. We examined whether CGP panel results led to new treatment, correlated with the effectiveness of immune checkpoint inhibitors (ICIs), or revealed secondary findings related to hereditary tumors. RESULTS: A total of 60 patients were enrolled, of which 52 (86.6%) had lung cancer. In six (10%) patients, the panel results led to treatment with insurance-listed molecular-targeted agents; four patients had EGFR mutations not detected by the real-time polymerase chain reaction assay and two had MET ex.14 skipping mutations. In small-cell lung cancer, the tumor mutation burden was high in 4/6 (66.7%) patients and pembrolizumab was available. Another MET ex.14 skipping mutation was detected in two cases with EGFR-tyrosine kinase inhibitor resistance. ICI efficacy was ≤1 year in patients with STK-11, KEAP1, and NEF2L2 mutations. A BRCA2 mutation with a high probability of germline mutation was detected in one patient. A thymic carcinoma with no detectable oncogenic mutation responded to second-line treatment with Tegafur-Gimeracil-Oteracil Potassium (TS-1) for ≥9 years. CONCLUSIONS: CGP panels are useful in thoracic malignancies, especially lung cancer, because they can detect overlooked driver mutations and genetic alterations. We believe that the significance of conducting a CGP panel prior to treatment may also exist, as it may lead to the prediction of ICI treatment efficacy.

Establishment of preanalytical conditions for microRNA profile analysis of clinical plasma samples.

The relationship between the expression of microRNAs (miRNAs) in blood and a variety of diseases has been investigated. MiRNA-based liquid biopsy has attracted much attention, and cancer-specific miRNAs have been reported. However, the results of analyses of the expression of these miRNAs vary among studies. The reproduction of results regarding miRNA expression levels could be difficult if there are differences in the data acquisition process. Previous studies have shown that the anticoagulant type used during plasma preparation and sample storage conditions could contribute to differences in measured miRNA levels. Thus, the impact of these preanalytical conditions on comprehensive miRNA expression profiles was examined. First, the miRNA expression profiles of samples obtained from healthy volunteers were analyzed using next-generation sequencing. Based on an analysis of the library concentration, human genome identification rate, ratio of unique sequences and expression profiles, the optimal preanalytical conditions for obtaining highly reproducible miRNA expression profiles were established. The optimal preanalytical conditions were as follows: ethylenediaminetetraacetic acid (EDTA) as the anticoagulant, whole-blood storage at room temperature within 6 hours, and plasma storage at 4°C or -20°C within 30 days. Next, plasma samples were collected from 60 cancer patients (3 facilities × 20 patients/facility), and miRNA expression profiles were analyzed. There were no significant differences in measurements except in the expression of erythrocyte-derived hsa-miR-451a. However, the variation in hsa-miR-451a levels was smaller among facilities than among individuals. This finding suggests that samples obtained from the same facility could show significantly different degrees of hemolysis across individuals. We found that the standardization of anticoagulant use and storage conditions contributed to reducing the variation in sample quality across facilities. The findings from this study could be useful in developing protocols for collecting samples from multiple facilities for cancer screening tests.

Conventional Direct Smear Yields Diagnostic Indicators of Gastric-Type Mucinous Carcinoma Compared with Cytomorphological Features Identified by Liquid-Based Cervical Cytology.

INTRODUCTION: Gastric-type mucinous carcinoma (GAS) of the uterine cervix is an adenocarcinoma subtype with a gastric phenotype that poses diagnostic pitfalls in cervical screening cytology because of its blunt morphologic atypia and the limited utility of human papillomavirus testing and ancillary immunochemical staining. Despite the recent widespread uptake of liquid-based cytology (LBC) systems, the cytomorphological features of GAS in LBC samples and the differential features between GAS and usual-type endocervical adenocarcinoma (UEA) remain unclear. METHODS: Eight GAS cases, all of which were surgically treated following histological confirmation, were examined. Direct Papanicolaou-stained smears and LBC samples were reviewed and compared with 10 UEA cases as controls. Featured cytomorphological findings were as follows: background (mucinous, inflammatory, or necrotic), cell crowding (size of neoplastic cell clusters), cytoplasm (golden mucin and cell border), and nuclei (nuclear chromatin and nucleoli). RESULTS: Of 18 adenocarcinomas, 16 were detected against a non-mucinous background in LBC samples, most of which were accompanied by mild to moderate inflammation. Clusters comprising >300 neoplastic cells were identified in both GAS and UEA in conventional smears (CSs), while no LBC samples harboured clusters as large as these. Cell borders of GAS were more distinct than those of UEA in CSs (p < 0.001), although fewer populations of neoplastic clusters revealed distinct cell borders in both GAS and UEA in LBC samples. Three of 8 and 2 of 8 GAS cases had golden mucin in CSs and in LBC samples, respectively, which was not detected in UEA at all. Nucleoli against fine nuclear chromatin were more pronounced in GAS than in UEA on CS (p = 0.03), although the difference between GAS and UEA was not apparent in LBC samples. DISCUSSION/CONCLUSION: This study demonstrated that the diagnostic clues to detect GAS using the conventional approach, namely distinct cell borders and prominent nucleoli, are not useful for excluding UEA in LBC samples. Conventional cervical smears may indicate a diagnosis of GAS; however, specific high-risk HPV detection approaches, such as HPV test or immunocytochemical p16/Ki-67 dual staining, are desirable to differentiate GAS from UEA in the setting of LBC with ambiguous cytomorphological features.

Late recurrence of lung adenocarcinoma harboring EGFR exon 20 insertion (A763_Y764insFQEA) mutation successfully treated with osimertinib.

The EGFR-A763_Y764insFQEA is a unique mutation among EGFR exon 20 insertion mutations in that it is associated with sensitivity to conventional EGFR-tyrosine kinase inhibitors. This mutation, which was not initially covered by conventional reverse transcription polymerase chain reaction (RT-PCR) genotyping method, has only been detected in clinical practice when a next-generation sequencing (NGS)-based cancer panel is implemented. We present the case of a female patient with recurrent lung adenocarcinoma from a lung tumor resected 10 years earlier. Sequential single-gene investigations and the OncomineTM Comprehensive Assay (ver.3) analysis of the recurrent tumor did not reveal any targetable driver mutations. However, the second NGS analysis with the OncoGuideTM NCC oncopanel found the EGFR-A763_Y764insFQEA mutation after tumor progression with carcinomatous lymphangiomatosis and multiple brain metastases. Osimertinib treatment improved her condition immediately. The identical EGFR-A763_Y764insFQEA mutation was detected in the tumor resected 10 years earlier. Based on this common mutation the patient was diagnosed with late recurrence of lung cancer harboring the EGFR-A763_Y764insFQEA mutation. The OncoGuideTM NCC oncopanel covered whole exons of the EGFR gene and was able to detect this mutation. In the present clinical practice, the EGFR-A763_Y764insFQEA mutation is the only treatable mutation among EGFR Ex.20 insertion mutations. We need to understand the gene mutation profile identified by each panel and consider reexamining them for this mutation.

CEA-antigen and SCC-antigen mRNA expression in peripheral blood predict hematogenous recurrence after resection in patients with esophageal cancer.

BACKGROUND: Although several studies have suggested an association between circulating tumor cells (CTC) and prognosis after esophageal cancer surgery, large-scale studies are lacking. The aim of this study was to prospectively examine the correlation between CTC and outcome in a large number of patients who underwent esophagectomy. MATERIALS AND METHODS: A cohort of 244 patients with squamous cell carcinoma of the esophagus who underwent curative surgery between 2002 and 2007 were prospectively analyzed for CTC before surgery and after the thoracic procedure. Reverse transcription-polymerase chain reaction for CEA and SCC antigen mRNA was used to detect cancer cells in the peripheral blood. CTC was defined as positive when at least 1 tumor marker mRNA was detected. RESULTS: CTC was positive in 34 patients (13.9%) before surgery and in 41 patients (16.8%) after the thoracic procedure. Multivariate analysis identified tumor depth (hazard ratio [HR], 0.439; 95% confidence interval [95% CI], 0.268-0.722; P = 0.0012), lymph node metastasis (HR, 2.467; 95% CI, 1.436-4.237; P = 0.0011), venous invasion (HR, 1.802; 95% CI, 1.082-3.002; P = 0.0236), and CTC status after the thoracic procedure (HR, 1.647; 95% CI, 1.032-2.629; P = 0.0365) as independent prognostic factors of disease-free survival. The rates of hematogenous (P = 0.0222) and local (P = 0.0464) recurrences were significantly higher in patients with CTC(+) after the thoracic procedure than those with CTC(-) after the thoracic procedure. Responders to neoadjuvant chemotherapy showed less lymphatic invasion and a decreased positive CTC rate after the thoracic procedure than nonresponders. CONCLUSIONS: CTC status after the thoracic procedure is a useful predictor for hematogenous and local recurrences in patients with esophageal cancer.

Different Immune Reconstitution between Cord Blood and Unrelated Bone Marrow Transplantation with Relation to Chronic Graft-versus-Host Disease.

Background: Advances of allogeneic hematopoietic cell transplantation (allo-HCT) have brought long-term survival to the patients with hematologic malignancies. Chronic graft-versus-host disease (GVHD) is one of major problems for the long- term survivors after allo-HCT. Dysregulation of immune reconstitution has been reported to be involved in the pathogenesis of chronic GVHD. Differences of immune reconstitution between cord blood transplantation (CBT) and unrelated bone marrow transplantation (UBMT) remain unclear in long-term survivors. We investigated immune reconstitution in patients surviving for more than 2 years after CBT (n=21) or UBMT (n=20) without relapse of underlying disease. Materials and Methods: Using flow cytometric analysis of peripheral blood, we investigated immune reconstitution of T cells, B cells, and NK cells between CBT and UBMT patients. We collected clinical data regarding allo-HCT and examined the relation of immune reconstitution to the development of chronic GVHD. Results: Between CBT and UBMT patients, we found significant differences in absolute cell number of CD8+ as well as CD19+ cell and CD4/CD8 ratio even more than 2 years after allo-HCT. Among UBMT patients, absolute cell number of naive CD4+ cell was significantly lower in patients with chronic GVHD. In addition, we found significant differences in absolute cell number of CD19+ cell, especially naive B cell between patients with and without chronic GVHD in both CBT and UBMT patients. Conclusion: These results suggest that differences of immune recovery between CBT and UBMT patients may exist even in patients surviving for more than 2 years and might be related to the development of chronic GVHD.

Analysis of Dietary Factors Affecting Body Mass Index in Elderly Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Body mass index (BMI) is correlated with the outcomes of various metabolic and pathological conditions. To elucidate the factors affecting BMI in elderly persons, we studied elderly persons with and without diabetes mellitus for BMI management target values using receiver operating characteristic (ROC) analysis. METHODS: We conducted a dietary survey targeting 60 elderly outpatients with type 2 diabetes mellitus (diabetes group, 70.1 ± 7.8 years) and 66 elderly persons who participated in a health class offered by the municipality (health class group, 72.5 ± 5.7 years). RESULTS: In the diabetes group, positive correlations were observed between BMI and several variables including blood glucose levels (all P < 0.05), whereas BMI had negative correlations with the third principal component (positive weight for oils and fats). In addition, BMI was negatively correlated with the intake of oils and fats. In the health class group, BMI was positively correlated (all P < 0.05) with grip strength/sixth principal component (positive weight for sweets)/condiments. An analysis of dietary patterns revealed that dietary factors correlated with BMI in each group. The cutoff value of BMI was suggested to be near the normal upper limit or slightly higher in the subject group. CONCLUSION: We considered that BMI management was useful as an indicator for maintaining grip and muscle strength in elderly persons and as an indicator for diabetes care management. From the present study, we may propose the utility of a careful dietary survey as one of the approaches for these aims.

Detection of pagetoid urothelial intraepithelial neoplasia extending to the vagina by cervical screening cytology: a case report with renewed immunochemical summary.

BACKGROUND: Pagetoid spread of urothelial carcinoma (UC) to the lower genital tract is quite a rare and diagnostically challenging condition. Pagetoid urothelial intraepithelial neoplasia extending to the vagina is difficult to diagnose, especially in remote recurrences without symptomatic or macroscopic lesions typical to Paget disease. However, its identification by cervical screening cytology is important because UC is often characterized by a long history of relapse. CASE PRESENTATION: A 68-year-old Japanese postmenopausal woman developed brown vaginal discharge after radical cystectomy for bladder cancer (high-grade UC, pT2a pN0 cM0 [Union for International Cancer Control, 8th edition]) concomitant with focal in-situ UC in the urethra. She had a history of left renal pelvis UC, which was surgically removed 9 months before the radical cystectomy. Gynecologic examination of the lower genital tract was unremarkable although cervical screening cytology demonstrated severely atypical cells with pleomorphism repeatedly. Cervical colposcopy and diagnostic conization revealed no cervical neoplasm. In retrospect, immunocytochemical p16/Ki-67 dual staining for the previous cervical screening was negative for p16 labeling, and the neoplastic cells were positive for cytokeratins 7 and 20, p63, and GATA binding protein 3. No high-risk human papillomavirus genotype was identified by an automated DNA chip system using liquid-based cytology samples. Eleven months post-cystectomy, punch biopsy of the vulva and vagina confirmed intraepithelial UC in the juxtaposed squamous epithelium with pagetoid spread demonstrating positivity for specific urothelial markers: uroplakins II and III and thrombomodulin. Concurrent invasive malignancy was ruled out, and CO2 laser vaporization of the vulvar and vaginal lesion was performed. The patient remained alive without evidence of invasive malignancy for 14 months after the radical cystectomy for bladder cancer. CONCLUSIONS: To detect recurrent pagetoid urothelial intraepithelial neoplasia with pagetoid spread in the lower genital tract, pathologists should recognize the history of prior UC with special attention to absence of p16 labeling in cervical cytology as a pointer to the diagnosis of urothelial cancer. Using further biopsy and immunohistochemical confirmation of UC relapse, investigation to rule out invasive malignancies and careful follow-up throughout the patient's lifetime is recommended.

The utility of nutritional supportive care with an eicosapentaenoic acid (EPA)-enriched nutrition agent during pre-operative chemoradiotherapy for pancreatic cancer: Prospective randomized control study.

BACKGROUND & AIMS: Neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer (PC) is potentially associated with various toxicities, which can lead to impaired nutritional status. Eicosapentaenoic acid (EPA) can reduce proinflammatory cytokines and positively influence cancer cachexia syndrome. The aim of this study is to clarify the utility of EPA enriched nutrition support during NACRT for PC. METHODS: We randomly assigned 62 patients with PC that received NACRT to either a nutrition intervention (NI) or a normal diet (ND). Patients in the NI group received 2 bottles/day (550 kcal/day) of an EPA-enriched nutrition supplement during NACRT. The primary endpoints were the before-to-after NACRT ratios (post/pre ratios) of skeletal muscle mass and psoas major muscle area (PMA). The secondary endpoints were the post/pre ratios of other nutritional parameters and treatment-related toxicities. RESULTS: Only 14 patients (45.2%) in the NI group consumed more than 50% of the EPA-enriched supplement provided. The post/pre ratio of skeletal muscle mass in the NI group (0.99 ± 0.060) was not significantly different from that of the ND group (0.96 ± 0.079, p = 0.102). However, patients that consumed ≥50% of the EPA-enriched supplement (the good intake group) had significantly higher skeletal muscle mass ratios than patients in the ND group (p = 0.042). The PMA ratio was significantly higher in the NI group (0.96 ± 0.081) than in the ND group (0.89 ± 0.072, p = 0.001). The NI and ND groups were not significantly different in other nutritional parameters or in NACRT-related toxicity. CONCLUSIONS: We found that EPA-enriched intake could potentially improve the nutritional status of patients with PC that received NACRT, but it was difficult for many patients to drink, due to its disagreeable taste. University Hospital Medical Information Network (http://www.umin.ac.jp), registration number UMIN000033589, https://upload.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000038300.

Evaluation of the lateral sentinel node by indocyanine green for rectal cancer based on micrometastasis determined by reverse transcriptase-polymerase chain reaction.

The significance of dissecting the lateral pelvic lymph node (LN) for lower rectal cancer remains controversial. We detected the lateral sentinel node (SN) by indocyanine green (ICG) and micrometastases using carcinoembryonic antigen (CEA)-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Twenty-five patients who underwent curative surgery with a dissection of the lateral pelvic LNs between 2003 and 2005 were examined. We investigated the existence of lateral SNs and any associations between pathological metastases and micrometastases by RT-PCR. Lateral SNs were detected in 7 (28%) of the 25 patients. The number of lateral SNs was 13 LNs, or 1.9 nodes per case. Of the 25 cases, 7 had lateral LN metastases based on pathological examinations in dissected lateral LNs. Three cases had massive lateral LN swelling by pre-operative pelvic CT and the SNs were not detected in them. The SNs were detected in two cases and were negative based on pathological examinations and positive according to a genetic diagnosis. SNs were detected in one case, which was positive based on pathological examinations and a genetic diagnosis. SN was not detected in one case. There were five SNs in which CEA was positive by RT-PCR, though only one of them was positive based on pathological examinations. No SNs were observed that were negative based on a genetic diagnosis, but were positive according to the pathological diagnosis. We detected the lateral SNs using ICG. The sensitivity of identifying lateral LN metastasis was improved by the use of a genetic diagnosis. However, the detection rate was still low, therefore we need to develop a new method for detecting SNs.

[Relationship between hyperuricemia and metabolic syndrome].

Metabolic syndrome is a cluster of cardiovascular risk factors such as hypertriglyceridemia, hypertension, insulin resistance, based on visceral fat accumulation. Hyperuricemia is also thought as a one of the complications of metabolic syndrome. Hyperinsulinemia caused by insulin resistance induces the low excretion type hyperuricemia. In contrast visceral fat accumulation itself causes the hypersynthetic type hyperuricemia through increased fatty acid influx into the liver. Recently hyperuricemia is suggested to play a causal role for the metabolic syndrome. Xanthine oxido-reductase, a key enzyme of uric acid metabolism was indicated as one of regulatory factors in adipocyte differentiation. These studies may shed a new light on the understanding of the relationship between hyperuricemia and metabolic syndrome.

Relationship between Food-Intake Trends and Estimated Glomerular Filtration Rate in Elderly Patients with Type 2 Diabetes Mellitus.

The aim of this study is to investigate how vegetable and fruit intake trends affect the estimated glomerular filtration rate (eGFR) by analyzing therapeutic diet status in elderly type 2 diabetes mellitus patients. The study included 59 elderly patients with type 2 diabetes mellitus (mean age: 70.1±7.8 y) who had previously received therapeutic education for type 2 diabetes mellitus from a clinical team and were subsequently receiving outpatient treatment. Blood examination data were retrospectively collected from medical records and diet status was investigated using a simplified self-administered diet history questionnaire. Dietary patterns were extracted using principal component analysis, and the relationships with each blood examination data were investigated. Linear regression analysis was then used to examine the intake food groups related to eGFR. Energy intake was 27±9 kcal/kg. Overall, these results were in line with the Guidelines for the Treatment of Diabetes in Japan 2016. As a result of principal component analysis, seven dietary patterns were extracted, and the cumulative contribution ratio of the seven components was 74.0%. Among the dietary patterns, the 6th factor (positive weighting with fruit) for eGFR was a negative prognostic factor (p=0.010). Analysis of food group intake and eGFR indicated that green and yellow vegetables were positive prognostic factors, whereas fruits were negative prognostic factors (both p<0.05). The dietary patterns dependent on green and yellow vegetables and fruit intake appeared to influence eGFR positively and negatively, respectively.

Subclinical cancer cell dissemination in peritoneal lavage fluid detected by reverse-transcription polymerase chain reaction identifies patients at high risk for peritoneal recurrence and consequent impaired survival in the setting of preoperative chemoradiation therapy for pancreatic cancer.

BACKGROUND: Preoperative chemoradiation therapy is a promising strategy for pancreatic cancer. Peritoneal recurrence is a major recurrence pattern after surgery for pancreatic cancer following preoperative chemoradiation therapy, even in patients with negative peritoneal lavage fluid cytology. Previous reports have indicated that the detection of carcinoembryonic antigen mRNA by reverse transcription polymerase chain reaction is useful for evaluating subclinical tumor cell dissemination in peritoneal lavage fluid. METHODS: Patients with resectable and borderline resectable pancreatic cancer treated with preoperative gemcitabine-based chemoradiation therapy and subsequent surgery were enrolled in this study. In all patients, a conventional cytologic examination of peritoneal lavage fluid from laparotomy confirmed the negative peritoneal cytology status. Carcinoembryonic antigen mRNA was detected in the peritoneal lavage fluid at laparotomy using reverse transcription polymerase chain reaction. Recurrence patterns and survival were evaluated in association with the carcinoembryonic antigen mRNA status in the peritoneal lavage fluid. RESULTS: The peritoneal lavage fluid from 57 of the 237 patients (24%) was carcinoembryonic antigen mRNA(+). The carcinoembryonic antigen mRNA(+) patients had a significantly higher incidence of peritoneal recurrence than the carcinoembryonic antigen mRNA(-) patients (36% vs. 15%, P < .001). The 5-year survival rates of the carcinoembryonic antigen mRNA(+) and carcinoembryonic antigen mRNA(-) patients were 31% and 51%, respectively (P = .037). A multivariable analysis for survival revealed that borderline resectability, positive nodal status, and positive carcinoembryonic antigen mRNA status were independent variables for impaired survival. CONCLUSION: Carcinoembryonic antigen mRNA(+) status was associated with a significantly increased incidence of peritoneal recurrence in patients with pancreatic cancer treated with preoperative chemoradiation therapy, resulting in impaired survival.

Phosphofructokinase deficiency; past, present and future.

Phosphofructokinase deficiency (Tarui disease, glycogen storage disease VII, GSD VII) stands out among all the GSDs. PFK deficiency was the first recognized disorder that directly affects glycolysis. Ever since the discovery of the disease in 1965, a wide range of biochemical, physiological and molecular studies of the disorder have greatly expanded our understanding of the function of normal muscle, general control of glycolysis and glycogen metabolism. The studies of PFK deficiency vastly enriched the field of glycogen storage diseases, as well as the field of metabolic and neuromuscular disorders. This article cites a historical overview of this clinical entity and the progress that has been made in molecular genetic area. We will also present the results of a search in-silico, which allowed us to identify a previously unknown sequence of the human platelet PFK gene (PFK-P). In addition, we will describe phylogenetic analysis of evolution of PFK genes.

Cloning and reporter analysis of human mitochondrial phosphoenolpyruvate carboxykinase gene promoter.

Phosphoenolpyruvate carboxykinase (PEPCK) is one of the key regulatory enzymes in gluconeogenesis. In human liver, PEPCK is about equally distributed in both cytosol (PEPCK-1) and mitochondria (PEPCK-2). The human pepck2 gene and cDNA have been reported, but the cloning of the promoter region of the pepck2 gene has not been elucidated yet. We isolated and characterized human genomic P1-artificial chromosome (PAC) clones carrying the human pepck2 gene promoter. The oligocapping method revealed that the transcriptional start point (tsp) of the human pepck2 gene is located at 97 bp upstream of the first adenine residue of the translation start site. We also determined the nucleotide sequence to 1819 bp upstream of tsp. Sequence analysis of this region revealed that it contained several potential regulatory elements, including five GC boxes and three CCAAT boxes. Reporter analysis using transient transfection with firefly luciferase synthetic gene indicated 5' flanking region up to 822 bp, and 317 bp upstream of tsp had transcriptional activity. These results suggest that these regions of the human pepck2 gene play an important role for its expression.