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1. 気絶心筋または冬眠心筋の病態生理 pathophysiology of stunned or hibernating myocardium
2. もやもや病：治療および予後 moyamoya disease treatment and prognosis
3. 小児における胸壁損傷 chest wall injuries in children
4. 急性虚血脳卒中の神経画像 neuroimaging of acute ischemic stroke
5. 慢性血栓塞栓性肺高血圧症の臨床症状および診断 clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension

English Journal

Triptolide reverses hypoxia-induced epithelial-mesenchymal transition and stem-like features in pancreatic cancer by NF-κB downregulation.

Liu L, Salnikov AV, Bauer N, Aleksandrowicz E, Labsch S, Nwaeburu C, Mattern J, Gladkich J, Schemmer P, Werner J, Herr I.AbstractPancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignancies characterized by an intense tumor stroma with hypoperfused regions, a significant inflammatory response and pronounced therapy resistance. New therapeutic agents are urgently needed. The plant-derived agent triptolide also known as "thunder god vine" has a long history in traditional Chinese medicine for treatment of rheumatoid arthritis and cancer and is now in a clinical phase II trial for establishing the efficacy against a placebo. The authors mimicked the situation in patient tumors by induction of hypoxia in experimental models of pancreatic cancer stem cells (CSCs) and evaluated the therapeutic effect of triptolide. Hypoxia led to induction of colony and spheroid formation, aldehyde dehydrogenase 1 (ALDH1) and NF-κB activity, migratory potential and a switch in morphology to a fibroblastoid phenotype, as well as stem cell- and epithelial-mesenchymal transition-associated protein expression. Triptolide efficiently inhibited hypoxia-induced transcriptional signaling and downregulated epithelial-mesenchymal transition (EMT) and CSC features in established highly malignant cell lines, whereas sensitive cancer cells or nonmalignant cells were less affected. In vivo triptolide inhibited tumor take and tumor growth. In primary CSCs isolated from patient tumors, triptolide downregulated markers of CSCs, proliferation and mesenchymal cells along with upregulation of markers for apoptosis and epithelial cells. This study is the first to show that triptolide reverses EMT and CSC characteristics and therefore may be superior to current chemotherapeutics for treatment of PDA.
International journal of cancer. Journal international du cancer.Int J Cancer.2014 May 15;134(10):2489-503.
Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignancies characterized by an intense tumor stroma with hypoperfused regions, a significant inflammatory response and pronounced therapy resistance. New therapeutic agents are urgently needed. The plant-derived agent triptolide also
PMID 24615157

Endothelial Kruppel-like Factor 4 Regulates Angiogenesis and the Notch Signaling Pathway.

Hale AT1, Tian H, Anih E, Recio FO 3rd, Shatat MA, Johnson T, Liao X, Ramirez-Bergeron DL, Proweller A, Ishikawa M, Hamik A.Author information 1From the Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute and.AbstractRegulation of endothelial cell biology by the Notch signaling pathway (Notch) is essential to vascular development, homeostasis, and sprouting angiogenesis. Although Notch determines cell fate and differentiation in a wide variety of cells, the molecular basis of upstream regulation of Notch remains poorly understood. Our group and others have implicated the Krüppel-like factor family of transcription factors as critical regulators of endothelial function. Here, we show that Krüppel-like factor 4 (KLF4) is a central regulator of sprouting angiogenesis via regulating Notch. Using a murine model in which KLF4 is overexpressed exclusively in the endothelium, we found that sustained expression of KLF4 promotes ineffective angiogenesis leading to diminished tumor growth independent of endothelial cell proliferation or cell cycling effects. These tumors feature increased vessel density yet are hypoperfused, leading to tumor hypoxia. Mechanistically, we show that KLF4 differentially regulates expression of Notch receptors, ligands, and target genes. We also demonstrate that KLF4 limits cleavage-mediated activation of Notch1. Finally, we rescue Notch target gene expression and the KLF4 sprouting angiogenesis phenotype by supplementation of DLL4 recombinant protein. Identification of this hitherto undiscovered role of KLF4 implicates this transcription factor as a critical regulator of Notch, tumor angiogenesis, and sprouting angiogenesis.
The Journal of biological chemistry.J Biol Chem.2014 Apr 25;289(17):12016-28. doi: 10.1074/jbc.M113.530956. Epub 2014 Mar 5.
Regulation of endothelial cell biology by the Notch signaling pathway (Notch) is essential to vascular development, homeostasis, and sprouting angiogenesis. Although Notch determines cell fate and differentiation in a wide variety of cells, the molecular basis of upstream regulation of Notch remains
PMID 24599951

Taxanes: impact on pancreatic cancer.

Chiorean EG1, Von Hoff DD.Author information 1aDepartment of Medicine, University of Washington, Seattle, Washington bTranslational Genomics Research Institute (TGen)/Virginia Piper Cancer Center, Scottsdale, Arizona, USA.AbstractTaxanes are core therapeutic components for several advanced malignancies, and have been studied extensively in pancreatic adenocarcinomas with mixed results. Although the triplet combination FOLFIRINOX improves outcomes for patients with metastatic disease, it is compounded by significant toxicity, and novel regimens, rationally designed and based on thorough mechanistic activity on the tumor targets, are clearly needed. Solvent-based taxanes, docetaxel and paclitaxel, have little activity as single agents, but combinations with fluoropyrimidines and gemcitabine show efficacy, albeit they have not undergone testing in phase III trials. Pancreatic cancer is characterized by an abundant desmoplastic, fibroinflammatory and hypoperfused stroma, which has been blamed for its overall chemoresistance. Nanoparticle bound paclitaxel (nab-paclitaxel) has been pharmacologically designed as a novel water-soluble agent, with improved therapeutic index compared with the cremophor-based formulation, capable of achieving higher systemic exposure. In preclinical systems, when combined with gemcitabine, nab-paclitaxel increased intratumoral gemcitabine delivery, possibly due to inducing stromal 'collapse' and through inhibition of the gemcitabine-catabolizing enzyme cytidine deaminase. Most recently, the combination of nab-paclitaxel and gemcitabine demonstrated significant survival benefit with good tolerability in metastatic pancreatic cancer in the phase III trial MPACT, and now represents one of the gold-standard regimens for this disease. Although taxanes are overall potent chemotherapeutics for various cancers, it is clear that for meaningful results in pancreatic adenocarcinomas, rationally designed combinations and novel technologies for drug delivery are likely to be most successful.
Anti-cancer drugs.Anticancer Drugs.2014 Apr;25(4):584-92. doi: 10.1097/CAD.0000000000000073.
Taxanes are core therapeutic components for several advanced malignancies, and have been studied extensively in pancreatic adenocarcinomas with mixed results. Although the triplet combination FOLFIRINOX improves outcomes for patients with metastatic disease, it is compounded by significant toxicity,
PMID 24463484

Japanese Journal

Impaired Subendocardial Wall Thickening and Post-Systolic Shortening Are Signs of Critical Myocardial Ischemia in Patients With Flow-Limiting Coronary Stenosis

ISHIZU Tomoko,SEO Yoshihiro,BABA Masako,MACHINO Tomoko,HIGUCHI Haruhiko,SHIOTSUKA Junji,NOGUCHI Yuichi,AONUMA Kazutaka
Circulation journal : official journal of the Japanese Circulation Society 75(8), 1934-1941, 2011-07-25
… Myocardial strain was measured using layer-by-layer analysis in severely hypoperfused segments. …
NAID 10029128048

Development of Computer-aided Classification of Alzheimer's Disease Based on Cerebral Blood Flow map by MR imaging

山下泰生,有村秀孝,吉浦敬,徳永千晶,桑水流純平,馬込大貴,門司晃,小林幸次,古閑省一,中村泰彦,大屋信義,本田浩,大喜雅文,豊福不可依
医用画像情報学会雑誌 28(3), 72-78, 2011
… In the second step, a support vector machine was trained by the average CBFs in 6 cortical functional regions which are known as hypoperfused regions(decreasing regions of blood flow)in AD, and then was employed to distinguish patients with AD from control subjects. …
NAID 130001206625

Myocardial Transfection of Hypoxia Inducible Factor-1α via an Adenoviral Vector During Coronary Artery Bypass Grafting : A Multicenter Phase I and Safety Study

KILIAN Eckehard Gerd,SADONI Sebastian,VICOL Calin,KELLY Ralph,VAN HULST Karen,SCHWAIGER Markus,KUPATT Christian,BOEKSTEGERS Peter,PILLAI Ravi,CHANNON Keith,HETZER Roland,REICHART Bruno
Circulation journal : official journal of the Japanese Circulation Society 74(5), 916-924, 2010-04-25
… The 13 patients were included under the following criteria: 1 hypoperfused area of viable ventricular muscle without options for revascularization and left ventricular ejection fraction ≥30%. …
NAID 10026473576

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