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71.
72.
Twee Tsao Yuexi Shi Steven Kornblau Hongbo Lu Sergej Konoplev Ansu Antony Vivian Ruvolo Yi Hua Qiu Ninaxiang Zhang Kevin R. Coombes Michael Andreeff Kensuke Kojima Marina Konopleva 《Annals of hematology》2012,91(12):1861-1870
DNA methylation and BLC-2 are potential therapeutic targets in acute myeloid leukemia (AML). We investigated pharmacologic interaction between the DNA methyltransferase inhibitor 5-azacytidine (5-AZA) and the BCL-2 inhibitor ABT-737. Increased BCL-2 expression determined by reverse phase protein analysis was associated with poor survival in AML patients with unfavorable cytogenetics (n?=?195). We found that 5-AZA, which itself has modest apoptotic activity, acts synergistically with ABT-737 to induce apoptosis. The 5-AZA/ABT-737 combination enhanced mitochondrial outer membrane permeabilization, as evidenced by effective conformational activation of BAX and ?ψm loss. Although absence of p53 limited apoptotic activities of 5-AZA and ABT-737 as single agents, the combination synergistically induced apoptosis independent of p53 expression. 5-AZA down-regulated MCL-1, known to mediate resistance to ABT-737, in a p53-independent manner. The 5-AZA/ABT-737 combination synergistically induced apoptosis in AML cells in seven of eight patients. 5-AZA significantly reduced MCL-1 levels in two of three samples examined. Our data provide a molecular rationale for this combination strategy in AML therapy. 相似文献
73.
Takuma K Kamisawa T Gopalakrishna R Hara S Tabata T Inaba Y Egawa N Igarashi Y 《World journal of gastroenterology : WJG》2012,18(10):1015-1020
Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organs of AIP patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease". Clinically, AIP patients and patients with pancreatic cancer share many features, such as preponderance of elderly males, frequent initial symptom of painless jaundice, development of new-onset diabetes mellitus, and elevated levels of serum tumor markers. It is of uppermost importance not to misdiagnose AIP as pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, and approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological, and histopathological features. Findings suggesting AIP rather than pancreatic cancer include: fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed enhancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography, presence of other organ involvement such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis; negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection. 相似文献
74.
Snábel V Taira K Cavallero S D'Amelio S Rudohradská P Saitoh Y 《Japanese journal of infectious diseases》2012,65(2):179-183
Ascaris roundworm isolates from Japan and central Europe were examined by sequencing analyses to better understand geographically induced nucleotide variation and genotype distribution according to host. Three well-supported clusters (denoted as A, B, C) were identified by generating cox1 sequences of mtDNA from these regions. Among 5 pig isolates collected in eastern Honshu, Japan, in 2010, 3 carried DNA characteristics for cluster A and 2 corresponded with the characteristics of cluster B. The sequence of the human isolate JH1 from north-central Honshu, fixed in formalin since 1972, conformed to the characteristics of cluster A. Differential analysis of ribosomal ITS1 region revealed the JH1 isolate sequence profile of Ascaris lumbricoides. Cluster C, which was the most distinguish cluster, was formed by reference Slovak isolates and has been so far found almost exclusively in European pigs. A fluctuating prevailing distribution of A and B lineages in human and pig hosts in different territories of the world and the global distribution of several haplotypes indicate their establishment before secondary differentiation in a given region due to host affiliation. The protocol established for DNA isolation from formalin-fixed specimens using the modified procedure with the Qiagen extraction set can be used as a tool for retrospective studies in ascarid helminths when only archival specimens are available. 相似文献
75.
Matsui S Taki H Shinoda K Suzuki K Hayashi R Tobe K Tokimitsu Y Ishida M Fushiki H Seto H Fukuoka J Ishizawa S 《Modern rheumatology / the Japan Rheumatism Association》2012,22(1):31-39
'Immunoglobulin G4 (IgG4)-related disease' is a new clinical concept of multi-organ diseases, with Mikulicz's disease (MD) being a clinical phenotype of IgG4-related disease. To clarify the clinical characteristics of respiratory involvement associated with IgG4-related MD, we retrospectively assessed 25 patients with MD, 11 (44%) of whom had allergic symptoms, and 7 (28%) of whom complained of respiratory problems. Thirteen patients (52%) presented with pulmonary and/or mediastinal lesions (P-MD) on chest computed tomography (CT), and 11 (44%) had lesions limited to the lacrimal and/or salivary glands (L-MD). Mean serum total protein, IgG, and IgG4 concentrations were significantly higher and CH50 was significantly lower in the P-MD than in the L-MD group. Immune complex was present only in the P-MD group. Chest CT images showed bronchial wall thickening, consolidation, nodule(s), interlobular thickening, ground glass opacity, pleural thickening/effusion, and mediastinal lymphadenopathy. Five of seven patients who underwent histological examination of the lungs had abundant IgG4-positive plasma cell infiltrates (IgG4/IgG-positive plasma cells >40%), but the other two did not. These findings suggest that respiratory lesions are not rare in patients with IgG4-related MD, and that they present with various manifestations. IgG4-related MD should be differentiated from similar diseases, such as sarcoidosis, bronchial asthma, Sj?gren's syndrome, and malignant lymphoma. 相似文献
76.
77.
Yukihiko Hiroshima Fumio Nakamura Hiroshi Miyamoto Ryutaro Mori Koichi Taniguchi Ryusei Matsuyama Hirotoshi Akiyama Kuniya Tanaka Yasushi Ichikawa Shingo Kato Noritoshi Kobayashi Kensuke Kubota Yoji Nagashima Yoshio Goshima Itaru Endo 《Annals of surgical oncology》2013,20(3):369-378
Background
Pancreatic cancer is an aggressive malignancy with one of the worst mortality rates of all cancers. Recently, collapsin response mediator proteins (CRMPs) were reported to be associated with proliferation, apoptosis, differentiation, and invasion in several cancers. However, CRMP expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer.Methods
Expression of crmp genes in 11 pairs of pancreatic cancer and corresponding noncancerous pancreas tissues were examined by real-time RT-PCR. Knockdown of CRMP4 expression using siRNA was examined in pancreatic cancer cell lines to determine whether CRMP4 regulates cell proliferation and invasion in vitro. Furthermore, CRMP4 protein levels in primary tumors of pancreatic cancer (n = 53) were examined by immunohistochemistry and compared with the clinicopathological features of the tumors.Results
Of all the CRMPs, only CRMP4 was differentially expressed in pancreatic cancer tissues (p = 0.008). CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. The expression of CRMP4 was detected immunohistochemically in 34 (64.2 %) of the 53 pancreatic cancer samples, and CRMP4 expression was correlated with severe venous invasion (p = 0.044), stage (p = 0.019), and liver metastasis (p = 0.021). Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival.Conclusions
Our results suggested that CRMP4 is significantly associated with poor prognosis by promoting liver metastasis and can serve as a novel therapeutic target for pancreatic cancer.78.
Kensuke K. Kiyokawa Yoshiaki Tai Yojiro Inoue Hiroko Yanaga Tanabe Koji Hayakawa Kazunori Mori Minoru Hirano Minoru Shigemori Takashi Tokutomi 《Journal of plastic surgery and hand surgery》2013,47(1):43-53
The skeletal stability of Le Fort I osteotomy was evaluated cephalometrically in 40 consecutive patients with unilateral cleft lip and palate (UCLP) (27 male and 13 female) who were operated on between 1987-1995. Their mean age at the time of operation was 23.7 years (range 16.3-40.4). The onepiece Le Fort I osteotomy was fixed with titanium plates and the osteotomy line was bone-grafted. Neither intermaxillary fixation nor occlusal splints were used postoperatively. Skeletal stability was analysed both horizontally and vertically on cephalograms taken shortly before operation, immediately afterwards, and at six months and at one year postoperatively. The mean maxillary advancement (point A) during the Le Fort I was 3.9 mm (range 0- 8.9) and mean vertical lengthening 4.5 mm (range -0.6-10.5). One year postoperatively the mean maxillary horizontal relapse was 20.5% (0.8 mm, range 0-3.7) whereas the mean vertical relapse was 22.2% (1 mm, range 0-5.7). The vertical relapse reduced from 38% to 8.3% between 1987 and 1995, and there was a positive correlation between the amount of maxillary advancement and relapse both horizontally and vertically. 相似文献
79.
Local delivery of mutant CCL2 protein‐reduced orthopaedic implant wear particle‐induced osteolysis and inflammation in vivo 下载免费PDF全文
Xinyi Jiang Taishi Sato Zhenyu Yao Michael Keeney Jukka Pajarinen Tzu‐hua Lin Florence Loi Kensuke Egashira Stuart Goodman Fan Yang 《Journal of orthopaedic research》2016,34(1):58-64
Total joint replacement (TJR) has been widely used as a standard treatment for late‐stage arthritis. One challenge for long‐term efficacy of TJR is the generation of ultra‐high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle‐induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle‐induced osteolysis and the effects of 7ND treatment were evaluated using micro‐CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle‐induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle‐induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:58–64, 2016. 相似文献
80.
Junko?KishikawaEmail author Shinsuke?Kazama Koji?Oba Kiyoshi?Hasegawa Hiroyuki?Anzai Yuzo?Harada Hiroyuki?Abe Keisuke?Matsusaka Kumiko?Hongo Masaru?Oba Koji?Yasuda Kensuke?Otani Takeshi?Nishikawa Toshiaki?Tanaka Junichiro?Tanaka Tomomichi?Kiyomatsu Keisuke?Hata Kazushige?Kawai Hiroaki?Nozawa Hironori?Yamaguchi Soichiro?Ishihara Eiji?Sunami Tetsuo?Ushiku Joji?Kitayama Masashi?Fukayama Norihiro?Kokudo Toshiaki?Watanabe 《Annals of surgical oncology》2016,23(6):1916-1923