排序方式: 共有19条查询结果,搜索用时 15 毫秒
1.
Yosuke Shikama Yasusei Kudo Naozumi Ishimaru Makoto Funaki 《Journal of cellular physiology》2015,230(12):2981-2989
2.
Nguyen PT Kudo Y Yoshida M Kamata N Ogawa I Takata T 《Histology and histopathology》2011,26(2):147-156
The loss of E-cadherin and the gain of N-cadherin expression are known as "cadherin switching". Cadherin switching is a major hallmark of epithelial-mesenchymal transition (EMT). EMT is a crucial process in cancer progression, providing cancer cells with the ability to escape from the primary focus, to invade stromal tissues and to migrate to distant regions. Although down-regulation of E-cadherin is well known in various cancers, there are a few studies on N-cadherin expression in cancer. Here, therefore, we investigated whether N-cadherin expression was associated with the progression of head and neck squamous cell carcinoma (HNSCC). First, we examined the expression of N-cadherin by immunohistochemistry and its correlation with clinico-pathological findings. High expression of N-cadherin was observed in 52 of 80 HNSCC cases and was significantly correlated with malignant behaviors. Next, we examined the correlation between N-cadherin and E-cadherin. Cadherin switching (high expression of N-cadherin and low expression of E-cadherin) was found in 30 of 80 HNSCC cases and was well correlated with histological differentiation, pattern of invasion and lymph node metastasis in HNSCC cases. Moreover, we examined the expression of N-cadherin and E-cadherin by RT-PCR in 16 HNSCC cell lines to confirm the immunohistochemical findings. N-cadherin expression was observed in 7 of 16 HNSCC cells, and cadherin switching was observed in 2 HNSCC cells. Interestingly, HNSCC cells with cadherin switching have EMT features. In conclusion, we suggest that i) N-cadherin may play an important role in malignant behaviors of HNSCC, and ii) cadherin switching might be considered as a discrete critical event in EMT and metastatic potential of HNSCC. 相似文献
3.
Miyauchi M Kitagawa S Hiraoka M Saito A Sato S Kudo Y Ogawa I Takata T 《Histochemistry and cell biology》2004,121(4):291-297
This study investigated the recruitment of polymorphonuclear leukocytes (PMNs) and the immunolocalization of CXC chemokines, including macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant-2 (CINC-2) in rat periodontal tissue after topical application of lipopolysaccharide (LPS; 5 mg/ml) from Escherichia coli into the rat molar gingival sulcus. In normal periodontal tissues, a small number of MIP-2- and CINC-2-positive cells were seen in junctional epithelium (JE), especially in its coronal half. After topical application of LPS, a prominent increase of MIP-2- and CINC-2-positive JE cells was observed. Almost all JE cells strongly expressed them at day 1 and day 2, and then the number of chemokine-positive cells returned to normal at day 7. Corresponding to these chemokine expressions, LPS application induced a significant increase in the number of PMNs in the sub-JE area from 1 h to 2 days and a significant increase in JE area from 3 h to 5 days, indicating a dynamic flow of PMNs from the sub-JE area into JE. These findings indicated that JE cells produced MIP-2 and CINC-2 in response to LPS stimulation and suggested that MIP-2 and CINC-2 may be responsible for PMN migration toward the periodontal pathogen and may play an important role in the initiation of inflammation and subsequent periodontal tissue destruction. 相似文献
4.
DesRochers TM Shamis Y Alt-Holland A Kudo Y Takata T Wang G Jackson-Grusby L Garlick JA 《Epigenetics》2012,7(1):34-46
The microenvironment plays a significant role in human cancer progression. However, the role of the tumor microenvironment in the epigenetic control of genes critical to cancer progression remains unclear. As transient E-cadherin expression is central to many stages of neoplasia and is sensitive to regulation by the microenvironment, we have studied if microenvironmental control of E-cadherin expression is linked to transient epigenetic regulation of its promoter, contributing to the unstable and reversible expression of E-cadherin seen during tumor progression. We used 3D, bioengineered human tissue constructs that mimic the complexity of their in vivo counterparts, to show that the tumor microenvironment can direct the re-expression of E-cadherin through the reversal of methylation-mediated silencing of its promoter. This loss of DNA methylation results from the induction of homotypic cell-cell interactions as cells undergo tissue organization. E-cadherin re-expression is associated with multiple epigenetic changes including altered methylation of a small number of CpGs, specific histone modifications, and control of miR-148a expression. These epigenetic changes may drive the plasticity of E-cadherin-mediated adhesion in different tissue microenvironments during tumor cell invasion and metastasis. Thus, we suggest that epigenetic regulation is a mechanism through which tumor cell colonization of metastatic sites occurs as E-cadherin-expressing cells arise from E-cadherin-deficient cells. 相似文献
5.
Natsumi Shimizu Nakako Izumi Nakajima Takaaki Tsunematsu Ikuko Ogawa Hidehiko Kawai Ryoichi Hirayama Akira Fujimori Akiko Yamada Ryuichi Okayasu Naozumi Ishimaru Takashi Takata Yasusei Kudo 《The Journal of biological chemistry》2013,288(24):17238-17252
Chemotherapy and radiation in addition to surgery has proven useful in a number of different cancer types, but the effectiveness in normal tissue cannot be avoided in these therapies. To improve the effectiveness of these therapies selectively in cancer tissue is important for avoiding side effects. Early mitotic inhibitor 1 (Emi1) is known to have the function to inhibit anaphase-promoting complex/cyclosome ubiquitin ligase complex, which ubiquitylates the cell cycle-related proteins. It recently has been shown that Emi1 knockdown prevents transition from S to G2 phase by down-regulating geminin via anaphase-promoting complex/cyclosome activation. At present, anticancer drugs for targeting DNA synthesis to interfere with rapidly dividing cells commonly are used. As Emi1 depletion interferes with completion of DNA synthesis in cancer cells, we thought that Emi1 knockdown might enhance the sensitivity for anticancer agents. Here, we confirmed that Emi1 siRNA induced polyploidy for preventing transition from S to G2 phase in several cancer cell lines. Then, we treated Emi1 depleted cells with doxorubicin. Interestingly, increased apoptotic cells were observed after doxorubicin treatment in Emi1 siRNA-treated cancer cells. In addition, Emi1 depletion enhanced the sensitivity of x-ray irradiation in cancer cells. Importantly, synergistic effect of Emi1 knockdown in these combination therapies was not observed in normal cells. These results suggest that Emi1 siRNA can be a useful tool for enhancing of sensitivity of cancer cells to anticancer reagents and radiation. 相似文献
6.
Xu D Takeshita F Hino Y Fukunaga S Kudo Y Tamaki A Matsunaga J Takahashi RU Takata T Shimamoto A Ochiya T Tahara H 《The Journal of cell biology》2011,193(2):409-424
Cellular senescence acts as a barrier to cancer progression, and microRNAs (miRNAs) are thought to be potential senescence regulators. However, whether senescence-associated miRNAs (SA-miRNAs) contribute to tumor suppression remains unknown. Here, we report that miR-22, a novel SA-miRNA, has an impact on tumorigenesis. miR-22 is up-regulated in human senescent fibroblasts and epithelial cells but down-regulated in various cancer cell lines. miR-22 overexpression induces growth suppression and acquisition of a senescent phenotype in human normal and cancer cells. miR-22 knockdown in presenescent fibroblasts decreased cell size, and cells became more compact. miR-22-induced senescence also decreases cell motility and inhibits cell invasion in vitro. Synthetic miR-22 delivery suppresses tumor growth and metastasis in vivo by inducing cellular senescence in a mouse model of breast carcinoma. We confirmed that CDK6, SIRT1, and Sp1, genes involved in the senescence program, are direct targets of miR-22. Our study provides the first evidence that miR-22 restores the cellular senescence program in cancer cells and acts as a tumor suppressor. 相似文献
7.
Rieko Arakaki Hiroshi Eguchi Akiko Yamada Yasusei Kudo Akihiko Iwasa Tserennadmid Enkhmaa Fumika Hotta Sayaka Mitamura-Aizawa Yoshinori Mitamura Yoshio Hayashi Naozumi Ishimaru 《PloS one》2014,9(5)
Background
Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren''s syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown.Methods and Finding
Reb eyedrops were administered to the murine model of SS aged 4–8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment.Conclusion
Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces. 相似文献8.
Y Kudo S Iizuka M Yoshida PT Nguyen SB Siriwardena T Tsunematsu M Ohbayashi T Ando D Hatakeyama T Shibata K Koizumi M Maeda N Ishimaru I Ogawa T Takata 《PloS one》2012,7(8):e44488
Background
Metastasis to regional lymph nodes via lymphatic vessels plays a key role in cancer progression. Tumor lymphangiogenesis is known to promote lymphatic metastasis, and vascular endothelial growth factor C (VEGF-C) is a critical activator of tumor lymphangiogenesis during the process of metastasis. We previously identified periostin as an invasion- and angiogenesis-promoting factor in head and neck squamous cell carcinoma (HNSCC). In this study, we discovered a novel role for periostin in tumor lymphangiogenesis.Methods and Findings
Periostin overexpression upregulated VEGF-C mRNA expression in HNSCC cells. By using conditioned media from periostin-overexpressing HNSCC cells, we examined tube formation of lymphatic endothelial cells. Conditioned media from periostin-overexpressing cells promoted tube formation. To know the correlation between periostin and VEGF-C, we compared Periostin expression with VEGF-C expression in 54 HNSCC cases by immunohistochemistry. Periostin expression was correlated well with VEGF-C expression in HNSCC cases. Moreover, correlation between periostin and VEGF-C secretion was observed in serum from HNSCC patients. Interestingly, periostin itself promoted tube formation of lymphatic endothelial cells independently of VEGF-C. Periostin-promoted lymphangiogenesis was mediated by Src and Akt activity. Indeed possible correlation between periostin and lymphatic status in periostin-overexpressing xenograft tumors and HNSCC cases was observed.Conclusions
Our findings suggest that periostin itself as well as periostin-induced upregulation of VEGF-C may promote lymphangiogenesis. We suggest that periostin may be a marker for prediction of malignant behaviors in HNSCC and a potential target for future therapeutic intervention to obstruct tumoral lymphatic invasion and lymphangiogenesis in HNSCC patients. 相似文献9.
Yasusei Kudo Shinji Iizuka Maki Yoshida Takaaki Tsunematsu Tomoyuki Kondo Ajiravudh Subarnbhesaj Elsayed M. Deraz Samadarani B. S. M. Siriwardena Hidetoshi Tahara Naozumi Ishimaru Ikuko Ogawa Takashi Takata 《The Journal of biological chemistry》2012,287(46):38716-38728
Matrix metalloproteinases (MMPs) are extracellular zinc-dependent endopeptidases involved in the degradation and remodeling of extracellular matrix in physiological and pathological processes. MMPs also have a role in cell proliferation, migration, differentiation, angiogenesis, and apoptosis. We previously identified cancer invasion-related factors by comparing the gene expression profiles between parent and the highly invasive clone of cancer cells. Matrix metalloproteinase-13 (MMP-13) was identified as a common up-regulated gene by cancer invasion-related factors. Although MMP-13 slightly promoted tumor invasion, we found that MMP-13 was involved in tumor angiogenesis. Conditioned medium from MMP-13-overexpressing cells promoted capillary formation of immortalized human umbilical vein endothelial cells. Furthermore, treatment with recombinant MMP-13 protein enhanced capillary tube formation both in vitro and in vivo. MMP-13-promoted capillary tube formation was mediated by activation of focal adhesion kinase and ERK. Interestingly, MMP-13 promoted the secretion of VEGF-A from fibroblasts and endothelial cells. By immunohistochemical analysis, we found a possible correlation between MMP-13 expression and the number of blood vessels in human cancer cases. In summary, these findings suggest that MMP-13 may directly and indirectly promote tumor angiogenesis. 相似文献
10.
D'Angiolella V Donato V Forrester FM Jeong YT Pellacani C Kudo Y Saraf A Florens L Washburn MP Pagano M 《Cell》2012,149(5):1023-1034
F-box proteins are the substrate binding subunits of SCF (Skp1-Cul1-F-box protein) ubiquitin ligase complexes. Using affinity purifications and mass spectrometry, we identified RRM2 (the ribonucleotide reductase family member 2) as an interactor of the F-box protein cyclin F. Ribonucleotide reductase (RNR) catalyzes the conversion of ribonucleotides to deoxyribonucleotides (dNTPs), which are necessary for both replicative and repair DNA synthesis. We?found that, during G2, following CDK-mediated phosphorylation of Thr33, RRM2 is degraded via SCF(cyclin F) to maintain balanced dNTP pools and genome stability. After DNA damage, cyclin F is downregulated in an ATR-dependent manner to allow accumulation of RRM2. Defective elimination of cyclin F delays DNA repair and sensitizes cells to DNA damage, a phenotype that is reverted by expressing a nondegradable RRM2 mutant. In summary, we have identified a biochemical pathway that controls the abundance of dNTPs and ensures efficient DNA repair in response to genotoxic stress. 相似文献