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N Akakura

Publications and source records attributed to N Akakura.

7 recordsLinked to original sources
PubMed2002

Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells.

The incidence of distant metastases is higher in the tumours with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumour cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumour cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. Autocrine motility factor inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1alpha, we established hypoxia-inducible factor-1alpha-transfectants and dominant negative hypoxia-inducible factor-1alpha-transfectants. Transfection with hypoxia-inducible factor-1alpha and dominant-negative hypoxia-inducible factor-1alpha enhanced and suppressed the expression of autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA expression and that the disruption of the hypoxia-inducible factor-1 pathway may be an effective treatment for metastasis.

Blotting, Northern↗
PubMed2001

Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation.

Hypovasculature is an outstanding characteristic of pancreatic cancers in imaging diagnosis, suggesting that blood supply is poor in pancreatic cancer tissues. Despite poor blood supply, pancreatic cancer cells survive and proliferate in severe hypoxia and nutrient deprivation. To demonstrate how pancreatic cancer cells adapt themselves to hypoxia and nutrient deprivation, we investigated the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) protein and HIF-1-inducible genes in human pancreatic cancer cell lines in comparison with other cancer cell lines. We found that HIF-1alpha protein was constitutively expressed in 15 of 20 pancreatic cancer cell lines (75%) but in none of other cancer cell lines tested in this study. The cells with constitutive expression of HIF-1alpha were more resistant to apoptosis induced by hypoxia and glucose deprivation than those without constitutive expression of HIF-1alpha. Transfection with HIF-1alpha transformed the latter cells resistant to apoptosis and increased in vivo tumorigenicity. Furthermore, anaerobic metabolism-associated genes, Glut1 and aldolase A, were more highly expressed in the cells with constitutive expression of HIF-1alpha than in the cells without it. These results suggest that constitutive expression of HIF-1alpha contributes to the survival and proliferation of pancreatic cancer cells in hypoxia and glucose deprivation through the activation of anaerobic metabolism.

Animals↗
PubMed2000

Successful treatment of IBL-like T-cell lymphoma with cyclosporin A: two case reports with special reference to serum cytokine levels.

The prognosis of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is grave, and its effective treatments have not been established. We applied oral cyclosporin A (CsA) treatment to two cases of IBL-like T-cell lymphoma, and succeeded in achieving complete remissions. CsA is known to have a suppressive effect on the immune system, most notably T-cells, but it also has a direct cytotoxic/apoptosis-inducing effect on lymphocytes. Its combined effects on neoplastic T-cells might have played an important role in achieving remission. In both cases, serum levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) were elevated and decreased or returned to normal after achieving remissions. Considering that both cytokines represent monokines, it seems that a macrophage system is also involved in the pathogenesis of this disorder. Our two cases indicate that administration of CsA may be an effective therapy for IBL-like T-cell lymphoma.

Administration, Oral↗
PubMed1999

Successful treatment of immunoblastic lymphadenopathy-like T-cell lymphoma with cyclosporin A.

Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is considered to belong to peripheral T-cell lymphoma. Its prognosis is grave and effective treatments have not been established. Recently, we gave oral cyclosporin A (CsA) to a patient with IBL-like T-cell lymphoma, and succeeded in achieving dramatic remission. In this case, serum levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF alpha) were elevated and decreased or returned to normal after achieving remission. Since CsA is a potent suppressor of the immune system and most notably T-cells, the immunosuppression of T-cell function might have played an important role in achieving remission in this case, although the precise mechanism still remains to be elucidated. The present case indicates that administration of CsA may be a very effective and safe selection of therapy for IBL-like T-cell lymphoma, as well as analogous disorders such as IBL and angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), thereby will contribute to improving the prognosis of patients with these diseases.

Administration, Oral↗
PubMed1993

Topographical corneal edema. An update.

Measurement of the topographical corneal edema response has been previously restricted by the use of optical pachometry and small sample sizes. This study uses ultrasound pachometry to measure changes in the corneal thickness of 23 subjects at 9 locations during 2 hours' wear of a thick soft contact lens. The data are analysed using both averaged and individual location data. The averaged location analysis supports the current paradigm that less edema occurs in the peripheral cornea than in the central cornea during contact lens wear. However, the individual location analysis reveals a more complex corneal edema response in which the greatest amount of edema following 2 hours' contact lens wear occurred in the central and mid-peripheral temporal cornea, in comparison with the peripheral nasal and peripheral inferior cornea which showed the least edema. The edema measured in the peripheral temporal and peripheral superior cornea following 2 hours' contact lens wear was not significantly different from that measured in the central cornea. The edema measured in the central cornea following 2 hours' contact lens wear was not significantly different from that found at any mid-peripheral location. This study demonstrates that the corneal edema response associated with 2 hours' wear of a thick soft contact lens is a complex dynamic topographical process and cannot be simply modelled using averaged data from small samples.

Adult↗