Targeting Receptor Tyrosine Kinases for Chemoprevention by Green Tea Catechin, EGCG

Tea is one of the most popular beverages consumed worldwide. Epidemiologic studies show an inverse relationship between consumption of tea, especially green tea, and development of cancers. Numerous in vivo and in vitro studies indicate strong chemopreventive effects for green tea and its constituents against cancers of various organs. (–)-Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, appears to be the most biologically active constituent in tea with respect to inhibiting cell proliferation and inducing apoptosis in cancer cells. Recent studies indicate that the receptor tyrosine kinases (RTKs) are one of the critical targets of EGCG to inhibit cancer cell growth. EGCG inhibits the activation of EGFR (erbB1), HER2 (neu/erbB2) and also HER3 (neu/erbB3), which belong to subclass I of the RTK superfamily, in various types of human cancer cells. The activation of IGF-1 and VEGF receptors, the other members of RTK family, is also inhibited by EGCG. In addition, EGCG alters membrane lipid organization and thus inhibits the dimerization and activation of EGFR. Therefore, EGCG inhibits the Ras/MAPK and PI3K/Akt signaling pathways, which are RTK-related cell signaling pathways, as well as the activation of AP-1 and NF-κB, thereby modulating the expression of target genes which are associated with induction of apoptosis and cell cycle arrest in cancer cells. These findings are significant because abnormalities in the expression and function of RTKs and their downstream effectors play a critical role in the development of several types of human malignancies. In this paper we review evidence indicating that EGCG exerts anticancer effects, at least in part, through inhibition of activation of the specific RTKs and conclude that targeting RTKs and related signaling pathway by tea catechins might be a promising strategy for the prevention of human cancers

トクシマケン ノ トウニョウビョウ ニオケル ケンコウ ホジ ゾウシン タイセイ : キカン ビョウイン カラ ノ トウニョウビョウ チイキ レンケイ ノ ジッシレイ トウニョウビョウ レンケイ テチョウ ノ カツヨウ

Patients with diabetes are increasing in Japan. In２００７,８．９million persons were estimated to have diabetes in Japan. Forty four ％ of them were not treated, and only３０％ achieved good glycemic controls. On the other hand, there are only３７diabetes specialists in Tokushima（January２０１１）. To break away the worst mortality rate, we needed to use limited medical resources, effectively. From April２００８, we created a critical pathway to regional medical network for diabetes. Unfortunately, this critical pathway adapted very limited patients, because it was inconvenient to carry to several hospitals. Next, we used diabetes network notebook published by Japan Association for Diabetes Education and Care. To evaluate its usefulness as a tool for regional network,３５patients who were treated by general practitioner and diabetes specialist, introduced this diabetes network notebooks. Thirty two patients（９１．４％）carried the notebooks at their second visit. HbA１c levels did not change between before and after. Therefore we suggest this notebook may be useful to promote diabetes regional network

Development of High Specific Speed Mixed Flow Compressors

Special PaperPg. 139-148The results of a study on the aerodynamic performance of a high specific speed, mixed flow compressor are presented. The specific speed was N. = 450 to 550 (m³/min) ½ (rpm) (m⁻¾ ), with approximately a 2.0 pressure ratio per stage. The flow path from the outlet of the mixed flow impeller was inclined in the axial direction and entered into a curved diffuser. A theoretical flow analysis and a performance test were performed. The slip factor for this type of compressor should be predicted by a different formula from that used for centrifugal compressors. Distributions of the flow velocity, temperature and pressure were measured, using a highly sensitive pressure transducer and a total temperature probe. The flow field, including the end wall boundary layer, was surveyed. The losses and the flow condition of the unsteady flow were analyzed. The compressor of N (Subscript s) = 450 to 500 showed high efficiency and handled a flowrate of about twice as much as a conventional centrifugal compressor. This development contributes tremendously in reducing the compressor size

The Association between Preoperative Blood Pressure Elevations and Postoperative Adverse Outcomes after Non-cardiac Surgery: A Single-center Retrospective Observational Study

Blood pressure (BP) often rises before surgery. This study investigated whether BP elevation immediately before surgery was associated with adverse outcomes. Medical records of 11,732 patients (average age: 61 years; male: 47.4%) who underwent non-cardiac elective inpatient surgery under general anesthesia at Kagawa University Hospital between January 2011 and June 2019 were reviewed. Differences between the first BP values measured on the day before surgery and the first BP values in the operating room were defined as Δ systolic BP (ΔSBP) and Δ diastolic BP (ΔDBP). The relationships between ΔSBP/ΔDBP and 30-day mortality, 30-day readmission, and over-the-standard length of hospital stay (OSLOS) were assessed. OSLOS was defined as a hospital stay longer than mean+2 standard deviations and was calculated using the Japanese Diagnosis Procedure Combination data. In univariate analysis, the differences in ΔSBP and ΔDBP between the OSLOS and standard LOS groups were both 2 mmHg. In multivariate logistic regression analysis, only ΔDBP was associated with OSLOS. The adjusted odds ratio (95% confidence interval) for the largest quartile was 1.31 (1.02-1.69) (p<0.05). ΔDBP was associated with OSLOS; however, there may be little need to worry about large ΔSBPs and ΔDBPs in clinical practice

Serum and urinary ferritin levels in patients with rheumatoid arthritis

The serum and urinary ferritin levels in 52 RA patients were measured by the 2-site immunoradiometric assay method. Serum ferritin levels in RA patients correlated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) but not with serum iron levels and hemoglobin concentrations, although they were within the normal range. High serum ferritin levels were associated with sera with hyper gamma-globulin and rheumatoid factors. In sequential studies, serum ferritin changed in parallel with ESR, CRP and disease activity in a majority of the patients. The urinary ferritin levels and u/s ratios in some RA patients were higher than control values. Higher values were found particularly in the group of patients under gold therapy but not in groups under other treatments.</p

A Case of Obstetrical DIC Probably Due to Uterine Type of Amniotic Fluid Embolism during Cesarean Section

A 42-year-old woman diagnosed as marginal placenta previa underwent cesarean section and bilateral tubal ligation under general anesthesia in 37th gestational week. Uterine contraction after delivery was good, but atonic bleeding progressed during tubal ligation. Oxytocic drugs were ineffective. We suspected obstetrical DIC and started treatment for DIC immediately, but the bleeding lasted. After total hysterectomy, she had stable vital signs. She broke away from DIC immediately after surgery. Intraoperative findings were satisfied the criteria for clinical uterine type amniotic fluid embolism (AFE). Although AFE indicates a bad prognosis, we saved her without any sequelae

ドウジキ ニ 1ガタ トウニョウビョウ オ ハッショウシ タセンセイ ジコ メンエキ ショウコウグン IIIガタ ト シンダンシ エタ コウキ コウレイシャ ノ ドウホウ ショウレイ

We herein presented a case of a ７９-year-old woman who was referred to our hospital with dry mouth and polyuria that had persisted for three months prior to her admission. She developed Hashimoto disease at ７３ years old and pernicious anemia at ７８ years old. Her blood glucose level was ６８２ mg/dl, HbA１c １４．６％, and urinary ketone was positive ; therefore, she was diagnosed with diabetic ketosis. Acute-onset autoimmune type １ diabetes mellitus was diagnosed based on the diagnostic criteria for acute-onset type １ diabetes mellitus （２０１２） by the committee of the Japan Diabetes Society. Autoimmune polyglandular syndrome was subsequently diagnosed based on the complications of type １ diabetes and Hashimoto’s thyroiditis. Her ８７-year-old brother had developed acute-onset autoimmune type １ diabetes ２ months before his sister was hospitalized. Autoimmune polyglandular syndrome type III was also diagnosed because he had autoimmune thyroid disease. No epidemiological data are currently available for late elderly with acute-onset type １ diabetes in Japan. To the best of our knowledge, this is the first case of acute-onset autoimmune type １ diabetes mellitus that developed around the same time period in an elderly brother and sister who were diagnosed with autoimmune polyglandular syndrome type III. Common genetic and environmental factors were etiologically implicated in the almost simultaneous onset between these siblings

ヒトウニョウビョウセイ ジンフゼン デ イジ トウセキチュウ ニ キュウセイ ハッショウ 1ガタ トウニョウビョウ オ ハッショウ シタ コウキ コウレイシャ ノ 1レイ

We herein presented a case of a ７５-year-old man who was referred to our hospital for hyperglycemia in a drowsy state following a convulsive seizure after receiving hemodialysis at another clinic. He had been receiving maintenance hemodialysis for non-diabetic renal failure from the age of ７３ years. He was diagnosed with diabetic ketosis because his blood glucose level was ７０７mg/dl, HbA１c ８．３％, glycoalbumin ４０．５％, serum osmolality ３２３mosm/kg, and ３-hydroxybutyric acid ５．８ mmol/l. Continuous intravenous insulin infusion therapy was immediately initiated and was changed to intensive insulin therapy on the ７th day after his admission. He did not have metabolic acidosis or serious dehydration associated with the acute metabolic derangement observed on arrival because fluid corrections for acid-base and electrolyte imbalances in the blood had been achieved by hemodialysis prior to his referral to our hospital. ΔCPR at six minutes in the glucagon loading test was hardly affected, indicating that his endogenous insulin secretory capacity was markedly reduced. The GAD antibody was negative. He had the haplotype of HLA DR４, which is considered to reflect disease susceptibility for type１diabetes in Japanese individuals. Acuteonset type １ diabetes mellitus was diagnosed based on the diagnostic criteria for acute-onset type１ diabetes mellitus （２０１２） by the Committee of the Japan Diabetes Society. At the time of his discharge, ８ units of insulin lispro were being administered prior to each meal in addition to ２ units of insulin glargine before sleeping. He was transferred to a local clinic on the ２３rd day after his admission. Although glycoalbumin had been measured every six months in the present case, it was not useful for detecting new onset diabetes. Therefore, blood glucose measurements before dialysis need to be regularly performed, even in dialysis patients with non-diabetic renal failure, in order to detect the new onset of diabetes at an early stage