Biomedical subjects

Naoki Oyaizu

Publications and source records attributed to Naoki Oyaizu.

10 recordsLinked to original sources

PubMed2006

Decrease in Epstein-Barr virus-positive AIDS-related lymphoma in the era of highly active antiretroviral therapy.

Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced the incidence of lymphoma among HIV-infected individuals. A clinicopathological study was performed on 86 AIDS-related lymphoma patients who were treated in Tokyo area from 1987 to 2005. The incidence of lymphoma detected by autopsy was 27% (53 cases/198 autopsies). Diffuse large B cell lymphoma was the most predominant histological subtype throughout the period (78%). Burkitt's lymphoma (BL) increased from 2% in the pre-HAART era (before end-1997) to 13% in the HAART era, whereas incidence of BL did not vary between HAART users and non-users. Epstein-Barr virus (EBV)-positive lymphoma decreased from 88% in the pre-HAART era to 58% in the HAART era, but did not differ significantly between HAART users (73%) and non-users (74%). Nodal involvement of lymphoma increased from 14% in the pre-HAART era to 50% in the HAART era; however, central nervous system involvement decreased from 62 to 38%. Kaposi's sarcoma-associated herpesvirus infection was rare (4%) among all cases. These data suggest that HAART might play a partial role in these changes, and the alteration in immunological backgrounds, such as EBV prevalence, is suggested as another leading cause of these changes in Japanese AIDS-related lymphoma.

Adolescent↗

PubMed2005

Carbonic anhydrase II is a tumor vessel endothelium-associated antigen targeted by dendritic cell therapy.

Tumor-associated antigens are promising candidates as target molecules for immunotherapy and a wide variety of tumor-associated antigens have been discovered through the presence of serum antibodies in cancer patients. We previously conducted dendritic cell therapy on 10 malignant melanoma patients and shrinkage or disappearance of metastatic tumors with massive necrosis occurred in two patients. In this study, we found a 29-kDa protein against which antibody was elicited by dendritic cell therapy in one of the two patients. Matrix-assisted laser desorption ionization-time of flight/mass spectrometry analysis of the protein isolated by two-dimensional electrophoresis combined with Western blots revealed that the 29-kDa protein was carbonic anhydrase II (CA-II). Immunohistochemistry of the tumors and normal tissues showed that CA-II was expressed in the tumor vessel but not in normal vessel endothelium. CA-II expression in tumor endothelium was observed as well in other cancers including esophageal, renal, and lung cancers. In an in vitro angiogenesis model, CA-II expression of normal human vein endothelial cells was significantly up-regulated when cells were cultured in the acidic and hypoxic conditions indicative of a tumor environment. These findings suggest that CA-II is a tumor vessel endothelium-associated antigen in melanoma and other cancers, and elicitation of serum anti-CA-II antibody by dendritic cell therapy may be associated with good clinical outcome including tumor reduction.

Adult↗

PubMed2005

Therapeutic potential of antibodies against FZD 10, a cell-surface protein, for synovial sarcomas.

Genome-wide expression profiling revealed overexpression of the gene encoding frizzled homologue 10 (FZD 10), a cell-surface receptor for molecules in the Wnt pathway, as a potential contributor to synovial sarcomas (SS). Northern blotting and immunohistochemical staining confirmed that expression levels of FZD 10 were very high in nearly all SS tumors and cell lines examined but absent in most normal organs or in some cancers arising in other tissues. Treatment of human SS cells with small-interfering RNA (siRNA) to FZD 10 decreased the amount of its product and suppressed growth of SS cells. Moreover, a polyclonal antibody specifically recognizing the extracellular domain (ECD) of FZD 10 was markedly effective in mediating ADCC against FZD 10-overexpressing synovial sarcoma cells in vitro. Injection of the antibody into SS xenografts in nude mice attenuated tumor growth, and TUNEL assays revealed clusters of apoptotic cells in antibody-treated xenografts. Taken together, these findings suggest that a humanized antibody against FZD 10 might be a promising treatment for patients with tumors that overexpress FZD 10; minimal or no adverse reactions would be expected because FZD 10 protein is not abundant in vital organs.

Amino Acid Sequence↗

PubMed2005

A case of pure red cell aplasia complicated with diffuse large B cell lymphoma, T-cell-rich/histiocyte-rich variant: effectiveness of rituximab and implications for a common immunopathogenic role of B lymphocytes.

Diffuse large B cell lymphoma, T-cell-rich/histiocyte-rich variant (DLBL-TH), is characterized by the presence of neoplastic B cells set in a background containing numerous non-neoplastic T lymphocytes and histiocytes. We report here the case of a patient with DLBL-TH who developed overt pure red cell aplasia (PRCA) following chemotherapy and autologous peripheral blood stem cell transplantation. Posttransplantation bone marrow biopsies revealed the absence of erythroid precursors associated with lymphoid aggregates composed of B cells mixed with numerous T cells and histiocytes. Administration of rituximab has led to complete recovery of erythropoiesis, which was associated not only with B cell depletion but also with a marked reduction in bone marrow T cells and histiocytes. These observations strongly suggest the particular pathogenetic role of the patient's B cells in inducing PRCA and recruiting T cells and histiocytes in situ.

Antibodies, Monoclonal↗

PubMed2005

Atypical hypersensitivity to mosquito bites without natural killer cell proliferative disease in an adult patient.

Hypersensitivity to mosquito bites (HMB) is a rare disorder that occurs in the first 2 decades of life and is considered to be associated with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukemia/lymphoma. EBV-encoded small nuclear RNA (EBER)-positive NK cells infiltrate the skin lesion at the site of the mosquito bite. In this report, we present the case of an adult patient with mantle cell lymphoma complicated by atypical HMB. The anti-EBV antibody titer of the patient indicated reactivation of chronic infection with this virus, and EBV DNA in the peripheral blood mononuclear cells was detected after chemotherapy by quantitative polymerase chain reaction analysis. However, an in situ hybridization analysis did not detect EBER-positive cells in the skin lesion at the bite site or in the lymph node. Peripheral NK cell lymphocytosis and EBV-associated lymphoproliferative disease did not develop. These findings suggest that some patients with chronic EBV infection may develop HMB without NK cell proliferative disease.

Animals↗

PubMed2004

The destruction box of human Geminin is critical for proliferation and tumor growth in human colon cancer cells.

A domain-specific disruption was performed on the destruction box sequence of endogenous Geminin gene, an inhibitor of the DNA replication initiation complex, in a human cancer cell line HCT116 resulting in the formation of a protein that was stable in the G1 phase of the cell cycle. Although the total amount of Geminin in asynchronous cultures was not elevated, the G1-specific stabilization of Geminin, diminished chromatin loading of minichromosome maintenance complex, inhibited DNA replication, and resulted in the accumulation of cells in G1. The mutated Geminin suppressed in vivo tumorigenicity and in vitro cell growth. Cells carrying this mutation failed to support the replication of a plasmid bearing the oriP replicator of Epstein-Barr virus. The DNA damage checkpoint pathway was activated in the mutated cells with increased levels of p53 protein and its target, the p21 protein. All these deficits were rescued by overexpression of Cdt1, a replication initiator protein that binds to Geminin. Therefore, alteration of the cell cycle-dependent regulation of endogenous Geminin in human cells without increasing total protein level inhibits DNA replication and suppresses tumor growth.

Alleles↗

PubMed2004

Phase I study of autologous tumor vaccines transduced with the GM-CSF gene in four patients with stage IV renal cell cancer in Japan: clinical and immunological findings.

We produced lethally irradiated retrovirally GM-CSF-transduced autologous renal tumor cell vaccines (GVAX) from six Japanese patients with stage IV renal cell cancer (RCC). Four patients received GVAX ranging from 1.4 x 10(8) to 3.7 x 10(8) cells on 6-17 occasions. Throughout a total of 48 vaccinations, there were no severe adverse events. After vaccination, DTH skin tests became positive to autologous RCC (auto-RCC) in all patients. The vaccination sites showed significant infiltration by CD4(+) T cells, eosinophils, and HLA-DR-positive cells. The kinetic analyses of cellular immune responses using peripheral blood lymphocytes revealed an enhanced proliferative response against auto-RCC in four patients, and cytotoxicity against auto-RCC was augmented in three patients. T cell receptor beta-chain analysis revealed oligoclonal expansion of T cells in the peripheral blood, skin biopsy specimens from DTH sites, and tumors. Western blot analysis demonstrated the induction of a humoral immune response against auto-RCC. Two of the four patients are currently alive 58 and 40 months after the initial vaccination with low-dose interleukin-2. Our results suggest that GVAX substantially enhanced the antitumor cellular and humoral immune responses, which might have contributed to the relatively long survival times of our patients in the present study.

Aged↗

PubMed2003

Results of a phase I clinical study using autologous tumour lysate-pulsed monocyte-derived mature dendritic cell vaccinations for stage IV malignant melanoma patients combined with low dose interleukin-2.

We conducted a pilot study to assess the feasibility and efficacy of immunotherapy for stage IV malignant melanoma patients resistant to conventional therapies involving vaccination with mature dendritic cells (mDCs) combined with administration of low dose interleukin-2. Autologous monocytes were harvested from a single apheresis and cultured for 7 days with granulocyte-macrophage colony-stimulating factor and interleukin-4, yielding immature dendritic cells (iDCs), which were then cryopreserved until use. For 4 days prior to vaccination, iDCs were exposed to autologous tumour lysate combined with tumour necrosis factor-alpha to induce terminal differentiation into mDCs. Patients were then vaccinated weekly with 107 mDCs for 10 weeks and given 350-700 kIU of interleukin-2 three times per week. Of the 10 patients in the study, one showed stable disease, seven showed progressive disease, and two showed mixed responses, including partial tumour regression, and were therefore given 20 additional injections. Only minimal adverse events were noted, including localized skin reactions and mild fever (NIH-CTC grade 0-1). Median survival from the first vaccination was 240 days (range 31-735 days). In vitro, melanoma patient-derived dendritic cells (DCs) showed reduced cell surface expression of CD1a antigen on iDCs and reduced CD86 and HLA-DR expression on mDCs. In addition, antigen uptake, chemotaxis and antigen presentation were all attenuated in DCs from the patients. In summary, although improvement of clinical efficacy will require further research, autologous tumour lysate-pulsed monocyte-derived mDCs could be safely harvested, cryopreserved and administrated to patients without obvious complications.

Adult↗

PubMed2002

The first isolation of Nocardia nova from an HIV-1 infected individual in Japan.

Nocardia species are opportunistic pathogens of immunocompromised patients. We report a case of Nocardia nova infection complicating Pneumocystis carinii pneumonia (PCP) in an HIV-1 infected individual. A 27-year-old man with hemophilia A was admitted on October 17, 2000, with fever and dyspnea. CD4 cell counts were 5/microl on admission. Prophylaxis against PCP was administered by inhalation of pentamidine isethionate because he was allergic to sulfamethoxazole-trimethoprim (SMZ-TMP). He was diagnosed with PCP from chest X-ray and bronchoalveolar lavage. The sputum obtained for culture on admission was positive for Gram-positive branching rods; the organism was later identified as Nocardia nova. He died from respiratory failure on November 7, 2000. Although PCP might be a principal factor in respiratory failure, this case shows the need to consider pulmonary nocardiosis as a cause of respiratory illness in patients with advanced HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Disseminated coccidioidomycosis with intra- and paravertebral abscesses.

We report a case of paravertebral and intravertebral abscesses caused by Coccidioides immitis in a Japanese man. The patient had lived in Arizona, United States, for 5 years, and suffered from overt disease after coming back to Japan. Culture of pus from the paravertebral abscess revealed Coccidioides immitis, and a diagnosis of disseminated coccidioidomycosis was made. Fluconazole (600 mg/day), taken orally, was started, and the abscesses surrounding the vertebral bodies disappeared after 2 years of treatment. The abscess in the vertebral bodies also responded to treatment, but a small lesion was still left in the 10th vertebral body after 2 years of treatment. Coccidioidomycosis is a fungal infection that is endemic in the southwestern United States and in Central and South America. Although coccidioidomycosis causes self-limiting flu-like illness or pneumonia, a small proportion of the infections progress to disseminated diseases. Because the incidence of coccidioidomycosis is increasing year by year, physicians not only in endemic but also in nonendemic areas have to consider coccidioidomycosis as one of the differential diagnoses when they examine patients from endemic areas.

Abscess↗