Fukuoka Cancer General Clinic

Fukuoka-shi, Japan

Fukuoka Cancer General Clinic

Fukuoka-shi, Japan
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Kuroki M.,Fukuoka University | Miyamoto S.,Fukuoka University | Morisaki T.,Fukuoka Cancer General Clinic | Yotsumoto F.,Fukuoka University | And 3 more authors.
Anticancer Research | Year: 2012

Biotherapy is a form of treatment that uses the natural immune system to protect the body against infection, cancer, and other diseases, and can fortify the body against some side-effects of other treatments. Biotherapy employs substances called biological response modifiers (BRMs), which include vaccines, monoclonal antibodies, cytokines, and adjuvants. BRMs are used alone or in combination with each other. Several BRMs are widely accepted in the treatment of certain types of cancer, while others are being tried in research studies. Side-effects of biotherapy vary among agents and patients. However, these side-effects usually disappear after the end of treatment.

Onishi H.,Kyushu University | Morisaki T.,Fukuoka Cancer General Clinic | Nakafusa Y.,Red Cross | Nakashima Y.,Red Cross | And 2 more authors.
International Journal of Clinical Oncology | Year: 2011

A 45-year-old woman with HER2(-)/HER1(-) breast cancer underwent radical mastectomy, followed by radiation and chemotherapy. However, her symptoms progressed rapidly owing to meningitis carcinomatosa and she was fitted with a urethral catheter. She also had difficulty in walking. However, immediately after treatment with lapatinib, her symptoms almost completely disappeared. The catheter was removed and she no longer needed a wheelchair. Unfortunately, after treatment was stopped, the bilateral upper limb skin metastases reappeared, the brain metastases relapsed, and she again experienced symptoms of meningitis carcinomatosa. Lapatinib was restarted, resulting in an immediate improvement in the symptoms and a reduction in the skin and brain metastases. Immunohistochemical staining of the lapatinib-sensitive metastatic skin tumor showed it to be HER2(2+), FISH(-)/HER1(-). This result suggested that the lapatinib-sensitive lesions in the brain and meninges were also HER2-positive. Carcinomatosa meningitis has a very poor prognosis and no effective treatment has yet been developed. Here, we report the first case in which lapatinib has been used to effectively treat meningitis carcinomatosa in HER2(-)/HER1(-) relapsed breast cancer. © 2011 Japan Society of Clinical Oncology.

Onishi H.,Kyushu University | Morisaki T.,Fukuoka Cancer General Clinic | Katano M.,Kyushu University
Anticancer Research | Year: 2012

The immune system prevents establishment and progression of cancer through innate and adaptive surveillance. However, some cancerous cells successfully evade the immune system. Regulatory T-cells (Tregs) facilitate such evasion. Tregs may be the factor responsible for the limited success of human tumor immunotherapy to date. To improve immunotherapy, it is thought that the number of Tregs and their functions should be inhibited in patients with advanced cancer. In this review, we focus on recent immunotherapy efforts targeting Tregs.

Wada J.,Kyushu University | Onishi H.,Kyushu University | Suzuki H.,Kyushu University | Yamasaki A.,Kyushu University | And 3 more authors.
Anticancer Research | Year: 2010

Background: This study analysed the contribution of malignant-effusion derived exosomes (Eff-Ex) to the number and function of regulatory T-cells (Treg) in malignant effusions. Patients and Methods: Eff-Ex were collected from the malignant effusions of 24 cancer patients. Peripheral blood mononuclear cells (PBMCs) were co-cultured with different concentrations of Eff-Ex. FOXP3+ CD4+ T-cells were defined as Treg. Expression of molecules on Eff-Ex was determined by flow cytometric analysis. Results: The number of Treg decreased daily in parallel with the FOXP3 expression level. Purified Eff-Ex prevented the decreases in both Treg number and FOXP3 expression levels in a dose-dependent manner. Pre-treatment of Eff-Ex with a neutralizing mAb against TGF-β1 significantly reduced these effects and the suppressive function of Treg. Conclusion: Elimination of Eff-Ex or control of Eff-Ex expressing TGF-β1 may be new therapeutic strategies in immunotherapy for advanced cancer patients with malignant effusions.

Yamasaki A.,Kyushu University | Onishi H.,Kyushu University | Morisaki T.,Fukuoka Cancer General Clinic | Katano M.,Kyushu University
Anticancer Research | Year: 2011

Cytotoxic γδ T-cells recognize antigens directly without the need for antigen processing and presentation. Recently, it was reported that they can also present antigens and proliferate in vitro. In this study, we examined whether γδ T-cells isolated from patients with advanced cancer can be used for immunotherapy. Twenty-two inoperable patients with multiple cancer metastases were enrolled in the study. There was no significant difference in the ratio of γδ T-cells within the peripheral blood mononuclear cell population isolated from healthy volunteers and cancer patients. γδ T-Cells isolated from cancer patients were expanded 2- to 5-fold using zoledronic acid or 2-methyl-3butenyl-1-pyrophosphate and IL-2. Autologous CD8+ T-cells cocultured with expanded CEA peptide-pulsed γδ T-cells from cancer patients with HLA-A24 killed more CEA-positive HLA-A24-matched gastric cancer cells and secreted higher levels of interferon-γ. These results suggest that γδ T-cells from cancer patients may be ideal candidates for adoptive immunotherapy.

Suzuki H.,Kyushu University | Onishi H.,Kyushu University | Wada J.,Kyushu University | Yamasaki A.,Kyushu University | And 4 more authors.
European Journal of Immunology | Year: 2010

CD25+ FOXP3+CD4+ T cells (Treg) have been considered to play an important role in immune tolerance against several tumor antigens. It has also been indicated that high-level expression of FOXP3 (FOXP3high) is sufficient to confer suppressive activity to normal non-Treg. Here, we showed for the first time that vascular endothelial growth factor receptor 2 (VEGFR2) is selectively expressed by FOXP3high but not FOXP3low Treg. Such VEGFR2+ Treg exist in several tissues including PBMC and malignant effusion-derived lymphocytes. In conclusion, VEGFR2 may be a novel target for controlling Treg with highly suppressive function. © 2009 WILEY-VCH Verlag GmbH & Co. KGaA.

Onishi H.,Kyushu University | Koya N.,Fukuoka Cancer General Clinic | Kiyota A.,Fukuoka Cancer General Clinic | Tanaka H.,Fukuoka Cancer General Clinic | And 3 more authors.
Anticancer Research | Year: 2012

Immunotherapy using cytotoxic T-lymphocytes (CTLs) still has limited success. An increase in the frequency of CTL administration is one method to improve immunotherapy using CTLs. The conventional method (C-method) that generates CTLs after the induction of dendritic cells requires a long time period. If CTLs can be more rapidly and simply induced, the frequency of immunotherapy could be increased and unexpected contamination could be avoided. In this study, in order to more rapidly induce functional CTLs, we investigated a new method (N-method) that uses a cytokine cocktail, including interleukin (IL)-2, IL- 4, granulocyte macrophage colony-stimulating factor, tumour necrosis factor-α and interferon-α, together with a tumour lysate. CTLs induced by the N-method had equivalent functions, such as proliferation, surface antigen expression and cytotoxicity, compared with those induced by the C-method. These results suggest that the N-method can substitute the C-method in order to improve the effect of immunotherapy using CTLs.

Ogino T.,Kyushu University | Onishi H.,Kyushu University | Suzuki H.,Kyushu University | Morisaki T.,Fukuoka Cancer General Clinic | And 2 more authors.
Cancer Immunology, Immunotherapy | Year: 2012

Dendritic cells (DCs) generated from monocytes under 20% O 2 are now used as therapeutic tools for cancer patients. However, the O 2 concentration is between 3 and 0.5% in most tissues. We evaluated these complicated functions of DCs under oxygen tensions mimicking in vivo situations. Immature DCs (imDCs) were generated from monocytes using IL-4 and GM-CSF under normoxia (20% O 2; N-imDCs) or hypoxia (1% O 2; H-imDCs). Mature DCs (mDCs) were induced with LPS. DCs were further exposed to normoxia (N/N-DCs) or hypoxia (N/H-DCs and H/H-DCs) conditions. Using a 2-D culture system, H-DCs were smaller in size than N-DCs, and H/HDCs exhibited higher allo-T cell stimulation ability than N/N-DCs and N/H-DCs. On the other hand, motility and phagocytic ability of H/H-DCs were significantly lower than those of N/H-DCs and N/N-DCs. In a 3-D culture system, however, maturation of H/H-imDCs and N/H-im- DCs was suppressed compared with N/N-imDCs as a result of their decreased motility and phagocytosis. Interestingly, silencing of HIF-1α by RNA interference decreased CD83 expression without affecting any antigen presentation abilities except for the ability to stimulate the allo-T cell population. Our data could help our understanding of DCs, especially therapeutic DCs, in vivo. © Springer-Verlag 2011.

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