排序方式: 共有90条查询结果,搜索用时 15 毫秒
51.
Sadarangani A Kato S Espinoza N Lange S Llados C Espinosa M Villalón M Lipkowitz S Cuello M Owen GI 《Apoptosis : an international journal on programmed cell death》2007,12(1):73-85
Cancer of the reproductive tract encompasses malignancies of the uterine corpus, cervix, ovary, Fallopian tube, among others
and accounts for 15% of female cancer mortalities. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates
apoptosis by binding to death receptors and offers a promising cancer treatment.
The goal of this study was to investigate and characterize the effect of TRAIL in endometrial cancer cell lines and normal
(non-cancerous) epithelial cells of endometrial origin. We also examined the effect of TRAIL in other primary cultured cancers
and normal cells of the human female reproductive tract and evaluated if TRAIL mediated apoptosis correlated with death receptors
and decoy receptors 1 and 2.
Herein, we demonstrate that TRAIL at concentrations which kill cancerous cells, does not mediate apoptosis or alter cell viability
in normal human endometrium, ovary, cervix or Fallopian tube. The partial inhibition by a caspase 9 inhibitor and the total
inhibition by a caspase 8 inhibitor demonstrates the dependency on the extrinsic apoptotic pathway. The selective mortality
does not correlate with the presence of death or decoy receptors. These results suggest that TRAIL may be an effective treatment
for endometrial cancer and other female reproductive cancers, with minimal secondary effects on healthy tissue.
This work was supported by a grant from the Wellcome Trust GR071469 (GIO) and the Chilean national science grants FONDECYT
1060495 (GIO) and 1020675 (MC).
An erratum to this article is available at . 相似文献
52.
53.
Hiroshi Kawamoto Kazuhiko Ito Saburo Kashii Sumie Monden Masahiro Fujita Mihoko Norioka Yoshiki Sasai Minoru Okuma 《Journal of cellular biochemistry》1993,51(3):322-325
An adenosine deaminase (ADA;EC 3.5.4.4)-deficient B lymphoblastoid cell line BAD05 derived from a Japanese patient with severe combined immunodeficiency was characterized. As previously reported, one allele of BAD05 expresses undetectable ADA mRNA, and the other allele produces an aberrant mRNA without exon 7. Genomic ADA DNA of BAD05 spanning from a portion of exon 6 to a portion of exon 8 was amplified by PCR. The amplified fragments were cloned into a vector, and 8 clones were isolated and sequenced. The analytical result showed a single base change of G to A at the invariant 5′ GT of intron 7 of ADA gene in one allele of BAD05, which accounts for the elimination of exon 7 during splicing. © 1993 Wiley-Liss, Inc. 相似文献
54.
55.
Adachi Y Hiramatsu S Tokuda N Sharifi K Ebrahimi M Islam A Kagawa Y Koshy Vaidyan L Sawada T Hamano K Owada Y 《Histochemistry and cell biology》2012,138(3):397-406
Thymic stromal cells, including cortical thymic epithelial cells (cTEC) produce many humoral factors, such as cytokines and eicosanoids to modulate thymocyte homeostasis, thereby regulating the peripheral immune responses. In this study, we identified fatty acid-binding protein (FABP4), an intracellular fatty acid chaperone, in the mouse thymus, and examined its role in the control of cytokine production in comparison with FABP5. By immunofluorescent staining, FABP4(+) cells enclosing the thymocytes were scattered throughout the thymic cortex with a spatial difference from the FABP5(+) cell that were distributed widely throughout the cTEC. The FABP4(+) cells were immunopositive for MHC class II, NLDC145 and cytokeratin 8, and were identified as part of cTEC. The FABP4(+) cells were identified as thymic nurse cells (TNC), a subpopulation of cTEC, by their active phagocytosis of apoptotic thymocytes. Furthermore, FABP4 expression was confirmed in the isolated TNC at the gene and protein levels. To explore the function of FABP in TNC, TSt-4/DLL1 cells stably expressing either FABP4 or FABP5 were established and the gene expressions of various cytokines were examined. The gene expression of interleukin (IL)-7 and IL-18 was increased both in FABP4 and FABP5 over-expressing cells compared with controls, and moreover, the increase in their expressions by adding of stearic acids was significantly enhanced in the FABP4 over-expressing cells. These data suggest that both FABPs are involved in the maintenance of T lymphocyte homeostasis through the modulation of cytokine production, which is possibly regulated by cellular fatty acid-mediated signaling in TEC, including TNC. 相似文献
56.
Tomohiro Yoshida Fumihiko Akahoshi Hiroshi Sakashita Hiroshi Kitajima Mitsuharu Nakamura Shuji Sonda Masahiro Takeuchi Yoshihito Tanaka Naoko Ueda Sumie Sekiguchi Takayuki Ishige Kyoko Shima Mika Nabeno Yuji Abe Jun Anabuki Aki Soejima Kumiko Yoshida Yoko Takashina Shinichi Ishii Satoko Kiuchi Yoshiharu Hayashi 《Bioorganic & medicinal chemistry》2012,20(19):5705-5719
Dipeptidyl peptidase IV (DPP-4) inhibition is suitable mechanism for once daily oral dosing regimen because of its low risk of hypoglycemia. We explored linked bicyclic heteroarylpiperazines substituted at the γ-position of the proline structure in the course of the investigation of l-prolylthiazolidines. The efforts led to the discovery of a highly potent, selective, long-lasting and orally active DPP-4 inhibitor, 3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine (8g), which has a unique structure characterized by five consecutive rings. An X-ray co-crystal structure of 8g in DPP-4 demonstrated that the key interaction between the phenyl ring on the pyrazole and the S2 extensive subsite of DPP-4 not only boosted potency, but also increased selectivity. Compound 8g, at 0.03 mg/kg or higher doses, significantly inhibited the increase of plasma glucose levels after an oral glucose load in Zucker fatty rats. Compound 8g (teneligliptin) has been approved for the treatment of type 2 diabetes in Japan. 相似文献
57.
Sasangka P Matsuno A Tanaka A Akasaka Y Suyama S Kano S Miyazaki M Akao T Kato M Kobayashi T Tsukagoshi N 《Microbiological research》2002,157(4):337-344
A maltose binding protein, p78, was purified to homogeneity from Aspergillus nidulans by a single column chromatography step on cross-linked amylose. The partial amino acid sequence was highly homologous to the glycogen branching enzymes (GBEs) of human and yeast, and p78 did show branching enzyme activity. The genomic gene and its cDNA encoding GBE (p78) were isolated from the A. nidulans genomic and cDNA libraries. Furthermore, a cDNA encoding A. oryzae GBE was entirely sequenced. A. nidulans GBE shared overall and significant amino acid sequence identity with GBEs from A. oryzae (83.9%), Saccharomyces cerevisiae (61.1%) and human (63.0%), and with starch branching enzymes from green plants (55–56%). 相似文献
58.
Martins JA de Freitas Figueiredo R Yoshizaki CS Paneto GG Cicarelli RM 《Molecular biology reports》2011,38(8):5397-5403
The genetic markers most commonly utilized to determine identity and in paternity testing are autosomal short tandem repeats (STRs); to interpret the DNA analysis, the results of a case have to be compared with a pertinent reference population. Thus, the aim of this work was to characterize the genetic profile of the population of Araraquara (São Paulo, Brazil) by analyzing 15 STR loci included in the PowerPlex® 16 System and to correlate these data with the migration history of the population. No deviations from the Hardy–Weinberg equilibrium were observed for any of the loci, after Bonferroni’s correction. Forensic parameters exhibited high values, the most polymorphic loci being Penta E, D18S51 and FGA. An unweighted pair-group method with arithmetic mean (UPGMA) tree based on genetic distances showed that the current population of Araraquara is grouped with populations of the southeastern region of Brazil, which are close to the European group but distant from African and Amerindian populations. Estimates of admixture components revealed that the contributions to the population of Araraquara were 76% European, 18% African, and 6% Amerindian. 相似文献
59.
60.
Mizuho Sato Kazuma Murakami Mayumi Uno Yu Nakagawa Sumie Katayama Ken-ichi Akagi Yuichi Masuda Kiyonori Takegoshi Kazuhiro Irie 《The Journal of biological chemistry》2013,288(32):23212-23224
The aggregation of the 42-residue amyloid β-protein (Aβ42) is involved in the pathogenesis of Alzheimer disease (AD). Numerous flavonoids exhibit inhibitory activity against Aβ42 aggregation, but their mechanism remains unclear in the molecular level. Here we propose the site-specific inhibitory mechanism of (+)-taxifolin, a catechol-type flavonoid, whose 3′,4′-dihydroxyl groups of the B-ring plays a critical role. Addition of sodium periodate, an oxidant, strengthened suppression of Aβ42 aggregation by (+)-taxifolin, whereas no inhibition was observed under anaerobic conditions, suggesting the inhibition to be associated with the oxidation to form o-quinone. Because formation of the Aβ42-taxifolin adduct was suggested by mass spectrometry, Aβ42 mutants substituted at Arg5, Lys16, and/or Lys28 with norleucine (Nle) were prepared to identify the residues involved in the conjugate formation. (+)-Taxifolin did not suppress the aggregation of Aβ42 mutants at Lys16 and/or Lys28 except for the mutant at Arg5. In addition, the aggregation of Aβ42 was inhibited by other catechol-type flavonoids, whereas that of K16Nle-Aβ42 was not. In contrast, some non-catechol-type flavonoids suppressed the aggregation of K16Nle-Aβ42 as well as Aβ42. Furthermore, interaction of (+)-taxifolin with the β-sheet region in Aβ42 was not observed using solid-state NMR unlike curcumin of the non-catechol-type. These results demonstrate that catechol-type flavonoids could specifically suppress Aβ42 aggregation by targeting Lys residues. Although the anti-AD activity of flavonoids has been ascribed to their antioxidative activity, the mechanism that the o-quinone reacts with Lys residues of Aβ42 might be more intrinsic. The Lys residues could be targets for Alzheimer disease therapy. 相似文献