New Strategy of Adult T-cell Leukemia Treatment Targeted for Anti-tumor Immunity and a Longevity Gene-encoded Protein

Kozako, Tomohiro

doi:10.1248/yakushi.131.1061

Cited by 9 publications

(11 citation statements)

References 62 publications

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“…New strategies for the therapy and prophylaxis of ATL ( e.g. , vaccines and novel molecular target agents) are still required 5, 8–10…”

mentioning

confidence: 99%

“…6,7 New strategies for the therapy and prophylaxis of ATL (e.g., vaccines and novel molecular target agents) are still required. 5,[8][9][10] Histone deacetylase (HDAC) inhibitors are a new class of antitumor agent that is currently undergoing intensive pre-clinical and clinical testing. 11 Depsipeptides (FR901228, FK228), a member of the cyclic peptide class of HDAC class I/II inhibitors, have shown cytotoxic effects on several malignant lymphoid cell lines, 12 including HTLV-1-infected T-cell lines.…”

mentioning

confidence: 99%

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High expression of the longevity gene product SIRT1 and apoptosis induction by sirtinol in adult T‐cell leukemia cells

Kozako

Aikawa

Shoji

et al. 2012

Intl Journal of Cancer

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Adult T-cell leukemia-lymphoma (ATL) is an aggressive peripheral T-cell neoplasm that develops after long-term infection with human T-cell leukemia virus (HTLV-1). SIRT1, a nicotinamide adenine dinucleotide 1 -dependent histone/protein deacetylase, plays a crucial role in various physiological processes, such as aging, metabolism, neurogenesis and apoptosis, owing to its ability to deacetylate numerous substrates, such as histone and NF-jB, which is implicated as an exacerbation factor in ATL.Here, we assessed how SIRT1 is regulated in primary ATL cells and leukemic cell lines. SIRT1 expression in ATL patients was significantly higher than that in healthy controls, especially in the acute type. Sirtinol, a SIRT1 inhibitor, induced significant growth inhibition or apoptosis in cells from ATL patients and leukemic cell lines, especially HTLV-1-related cell lines. Sirtinolinduced apoptosis was mediated by activation of the caspase family and degradation of SIRT1 in the nucleus. Furthermore, SIRT1 knockdown by SIRT1-specific small interfering RNA caused apoptosis via activation of caspase-3 and PARP in MT-2 cells, HTLV-1-related cell line. These results suggest that SIRT1 is a crucial antiapoptotic molecule in ATL cells and that SIRT1 inhibitors may be useful therapeutic agents for leukemia, especially in patients with ATL.

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“…New strategies for the therapy and prophylaxis of ATL ( e.g. , vaccines and novel molecular target agents) are still required 5, 8–10…”

mentioning

confidence: 99%

mentioning

confidence: 99%

High expression of the longevity gene product SIRT1 and apoptosis induction by sirtinol in adult T‐cell leukemia cells

Kozako

Aikawa

Shoji

et al. 2012

Intl Journal of Cancer

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“…A study by Herth et al (18) previously concluded that thalidomide maintenance therapy drives the maturation of T cells toward a memory phenotype, however, compromises antigen-specific immunity. Additionally, the decreased frequency and function of CD8 + T cells has been previously described for T-cell lymphoma (19). It was hypothesized that the cause of IgA pemphigus in the present patient may have been a combination of the immunological imbalance, which was caused by the blood-lymphatic system cancer, and thalidomide-induced immunomodulatory effects.…”

Section: Discussionmentioning

confidence: 65%

Peripheral T-cell lymphoma complicated by immunoglobulin A pemphigus: A case report and literature review

et al. 2014

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Peripheral T-cell lymphomas (PTCLs) account for 12% of non-Hodgkin’s lymphomas (NHLs). Immunoglobulin (Ig) A pemphigus is an autoimmune blistering disease characterized by tissue-bound and circulating IgA antibodies that target epidermal cell surface components. Malignant lymphomas are often linked with autoimmune disease and the autoimmune blistering disease, paraneoplastic pemphigus, has been associated with NHL. However, cases of PTCLs that are complicated by IgA pemphigus are particularly rare. The current study presents the first known case of PTCL complicated by IgA pemphigus. A 43-year-old male was admitted to the Union Hospital (Wuhan, China) in March 2012 with multiple swollen lymph nodes. Pathology examinations revealed PTCL. Immunohistochemical staining was positive for cluster of differentiation (CD)2, CD3, CD5, CD7 and CD47, and negative for CD20. Ki-67 was ~40% positive. The patient was treated with four cycles of cyclophosphamide, Adriamycin, vincristine and prednisone, and two cycles of gemcitabine, cisplatin and dexamethasone; in addition, the patient received radiation of the retroperitoneal region (total dose, 36 Gy). The patient underwent thalidomide maintenance therapy for 20 days before flaccid blisters appeared on the trunk and limbs. Histopathology and immunofluorescence indicated IgA pemphigus, and intravenous methylprednisolone was administered, followed by treatment with prednisone. Subsequently, no evidence of recurrent lymphoma or pemphigus has been observed.

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“…[2][3][4] Cluster of differentiation (CD) molecules are expressed on most normal cells. However, CD molecules are often overexpressed on tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Liposomes and nanotechnology in drug development: focus on oncotargets

Kozako¹,

Arima²,

Yoshimitsu³

et al. 2012

IJN

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Nanotechnology is the development of an engineered device at the atomic, molecular, and macromolecular level in the nanometer range. Advances in nanotechnology have proven beneficial in therapeutic fields such as drug-delivery and gene/protein delivery. Antigen delivery systems are important for inducing and modifying immune responses. In cellular immunity, cytotoxic T lymphocytes (CTLs) are important in the host defense against tumors. Key to the development of CTL-inducible vaccines is the ability to deliver antigens to antigen-presenting cells efficiently and to induce the subsequent activation of T cell-mediated immunity without adjuvants, as they can induce excessive inflammation leading to systemic febrile disease. Since expression and cloning methods for tumor-associated antigens have been reported, cancer vaccines that induce effective cell immunity may be promising therapeutic candidates, but Th2 cells are undesirable for use in cancer immunotherapy. Peptide vaccines have immunological and economic advantages as cancer vaccines because CTL epitope peptides from tumorassociated antigens have high antigen-specificity. However, cancer vaccines have had limited effectiveness in clinical responses due to the ability of cancer cells to "escape" from cancer immunity and a low efficiency of antigen-specific CTL induction due to immunogenic-free synthetic peptides. In contrast, carbohydrate-decorated particles such as carbohydrate-coated liposomes with encapsulated antigens might be more suitable as antigen delivery vehicles to antigen-presenting cells. Oligomannose-coated liposomes (OML) can eliminate established tumors in mouse cancer models. In addition, OMLs with an encased antigen can induce antigenspecific CTLs from peripheral blood mononuclear cells obtained from patients. Feasibility studies of OML-based vaccines have revealed their potential for clinical use as vaccines for diseases where CTLs act as effector cells. Furthermore, use of the hepatitis B core particle, in which tumor-antigen epitopes are set, has consistently been shown to induce strong CTL responses without the use of an adjuvant. Thus, nanoparticles may provide a new prophylactic strategy for infectious disease and therapeutic approaches for cancer via the induction of T-cell immunity.

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New Strategy of Adult T-cell Leukemia Treatment Targeted for Anti-tumor Immunity and a Longevity Gene-encoded Protein

Cited by 9 publications

References 62 publications

High expression of the longevity gene product SIRT1 and apoptosis induction by sirtinol in adult T‐cell leukemia cells

High expression of the longevity gene product SIRT1 and apoptosis induction by sirtinol in adult T‐cell leukemia cells

Peripheral T-cell lymphoma complicated by immunoglobulin A pemphigus: A case report and literature review

Liposomes and nanotechnology in drug development: focus on oncotargets

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