Biomedical subjects

A Hiraki

Publications and source records attributed to A Hiraki.

At least 19 recordsLinked to original sources

PubMed2003

Simultaneous measurement of T-helper 1 cytokines in tuberculous pleural effusion.

OBJECTIVE: Tuberculosis, the leading cause of death among infectious diseases worldwide, is a major cause of lymphocytic exudative pleural effusion. T-helper 1 cytokines, including interferon-gamma (IFN-gamma), interleukin (IL)-12p40 and IL-18 are predominantly associated with cell-mediated immune responses, and play an important role in immunity to Mycobacterium tuberculosis. DESIGN: We studied 55 patients presenting with pleural effusion at the National Sanyo Hospital between April 2000 and September 2001 (42 men and 13 women; mean age 67 years). Twenty patients (36%) had tuberculous pleurisy, while 18 (33%) had malignant effusions and 17 (31%) had an effusion with another aetiology. Pleural fluid concentrations of IL-12p40 and IL-18 as well as IFN-gamma measured by enzyme-immunoassays. RESULTS: Concentrations of all three cytokines were significantly higher in tuberculous than other pleural effusions. Significant correlations were evident between IFN-gamma and IL-12. We found particularly high concentrations of IL-12p40 and IFN-gamma in tuberculous patients with high fever. CONCLUSION: The results indicate that T-helper 1 cytokines are involved in intrapulmonary cellular immune responses to M. tuberculosis, and suggest that the interactions between them may play an important role in the pathogenesis and severity of the pleural effusion. Understanding the development of this response may enhance our understanding of the pathogenesis of tuberculous pleural effusion and suggest new therapies.

Adult↗

PubMed2001

Tumor-specific cytotoxic T lymphocyte responses against chondrosarcoma with HLA haplotype loss restricted by the remaining HLA class I allele.

Although loss of HLA expression by malignant cells has also been demonstrated, it has not been clarified how the loss of HLA expression observed in vitro actually results in immune escape. We demonstrated two major findings: (i) a part of chromosome 6 coding for HLA haplotypes was deleted from the genome of chondrosarcoma cell line, OUMS-27; furthermore, immunohistostaining for HLA-A11 showed that the original chondrosarcoma tissue lost the expression of HLA-A11, implicating that HLA haplotype loss was already present in the original tumor tissue and (2) HLA class I-restricted and autologous tumor-specific cytotoxic T cells (CTL) were generated from peripheral blood lymphocytes of the patient with chondrosarcoma, from whom OUMS-27 originated. This CTL line was maintained by weekly stimulation with OUMS-27, and lysed OUMS-27 in an HLA-A24 dependent manner but did not either K562 or autologous (EBV)-transformed B cells. These observations indicated that OUMS-27 and its original tumor are still immunogenic and can present antigen peptides with the remaining HLA-A24, even if HLA expression is partially lost. Tumor specific immunotherapy can be applied to the treatment of malignancies, even if HLA expression is partially lost.

Aged↗

PubMed2001

Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen.

Serological expression cloning of antigens eliciting a humoral immune response to a syngeneic mouse sarcoma identified pem (mouse placenta and embryonic expression gene) as a new member of the cancer/testis family. To identify the human homologue of pem, mouse pem sequences and pem-related expressed sequence tags from human testis were used as PCR primers for amplification using human testis cDNA. However, rather than pem, another gene, designated OY-TES-1, was isolated and found to be the human homologue of proacrosin binding protein sp32 precursor originally identified in mouse, guinea pig, and pig. OY-TES-1 maps to chromosome 12p12-p13 and contains 10 exons. Southern blot analysis suggests the presence of two OY-TES-1-related genes in the human genome. In normal tissues, OY-TES-1 mRNA was expressed only in testis, whereas in malignant tissues, a variable proportion of a wide array of cancers, including bladder, breast, lung, liver, and colon cancers, expressed OY-TES-1. Serological survey of 362 cancer patients with a range of different cancers showed antibody to OY-TES-1 in 25 patients. No OY-TES-1 sera reactivity was found in 20 normal individuals. These findings indicate that OY-TES-1 is an additional member of the cancer/testis family of antigens and that OY-TES-1 is immunogenic in humans.

Amino Acid Sequence↗

PubMed2001

Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias : combination analysis with cDNA expression array and tissue microarray.

To investigate the lymphomagenesis of NK/T lymphoma, we comprehensively and systematically analyzed the expression pattern of the human NK/T cell line (NK-YS) genome by cDNA expression array and tissue microarray. We detected significant changes in the gene expression of NK-YS cell line: an increase in 18 and a decrease in 20 genes compared to normal NK cells or peripheral blood mononuclear cells. Among these genes, we found a strong decrease in hematopoietic cell specific protein-tyrosine-phosphatase SH-PTP1 (SHP1) mRNA by cDNA expression array and reverse transcriptase-polymerase chain reaction. Further analysis with standard immunohistochemistry and tissue microarray, which used 207 paraffin-embedded specimens of various kinds of malignant lymphomas, showed that 100% of NK/T lymphoma specimens and more than 95% of various types of malignant lymphoma were negative for SHP1 protein expression. On the other hand, SHP1 protein was strongly expressed in the mantle zone and interfollicular zone lymphocytes in reactive lymphoid hyperplasia specimens. In addition, various kinds of hematopoietic cell lines, particularly the highly aggressive lymphoma/leukemia lines, lacked SHP1 expression in vitro, suggesting that loss of SHP1 expression may be related to not only malignant transformation, but also tumor cell aggressiveness. SHP1 expression could not be induced in either of two NK/T cell lines by phorbol ester, suggesting that genetic impairment or modification with methylation of SHP1 DNA could be one of the critical events in the pathogenesis of NK/T lymphoma. This evidence strongly suggests that loss of SHP1 gene expression plays an important role in multistep tumorigenesis, possibly as an anti-oncogene in the wide range of lymphomas/leukemias as well as NK/T lymphomas.

DNA, Complementary↗

PubMed2001

Metastasis to the penis in a patient with squamous cell carcinoma of the lung with a review of reported cases.

Metastasis to the penis is very rare in lung cancer. We describe a patient with squamous cell carcinoma of the lung who developed a metastatic lesion in the penis. A 75-year-old Japanese male visited a local hospital complaining cough and bloody sputum. A chest plain radiograph and computed tomographic (CT) scans of the chest demonstrated a right hilar mass. He was diagnosed with squamous cell carcinoma of the lung at stage IIIB (T4N2M0). Then he was treated with concurrent chemoradiotherapy consisting of cisplatin, docetaxel, and thoracic irradiation, and after the chemoradiotherapy, he achieved a partial response. However, 6 months later, he visited an urologist complaining of firm mass in the penis with slight pain. A biopsy of the corpus cavernosum penis was performed, which provided a histological diagnosis of squamous cell carcinoma. The histology of the specimen was consistent with that of previous lung cancer, so he was considered to have penile metastasis from squamous cell carcinoma of the lung. Radiotherapy was given to the metastatic tumor in the penis. The penile tumor was diminished and the pain was completely relieved. In addition, we review reported cases to investigate the clinical characteristics and appropriate management of this rare involvement.

Aged↗

PubMed2001

A case-control study of lung cancer screening in Okayama Prefecture, Japan.

The effectiveness of lung cancer screening in reducing mortality still remains uncertain. In order to evaluate the efficacy of lung cancer screening, a case-control study was conducted in Okayama Prefecture, Japan. The study area consisted of 34 municipalities where a population-based lung cancer screening had been conducted. Chest X-ray examinations for all participants and sputum cytology for high-risk participants were offered annually. The cases analyzed in this study consisted of 412 individuals aged between 40 and 79 who died of lung cancer. A total of 3490 controls, two to ten for each case matched by gender, year of birth, and living district were randomly collected. Screening histories of cases were compared with those of and matched controls for the identical calendar period prio to diagnosis of the case. Smoking adjusted odds ratio (OR) of death from lung cancer for screened individuals versus unscreened, within 12 months before diagnosis, was calculated as 0.59 (95% confidence interval: 0.46-0.74; P=0.0001). The OR for women (0.39, 95% confidence interval: 0.24-0.64) was lower than that for men (0.67, 95% confidence interval: 0.51-0.87), although both were statistically significant. These results suggest that lung cancer screening contributes to reducing lung cancer mortality by 41%.

Adult↗

PubMed2001

Genetics of Epstein-Barr virus infection.

Epstein-Barr (EBV) virus is a member of the human herpesvirus family. EBV is the etiologic agent of acute infectious mononucleosis and is closely associated with the genesis of Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma. EBV is also implicated in a variety of other diseases, such as X-linked lymphoproliferative syndrome, T-cell non-Hodgkin's lymphoma, Hodgkin's disease, and NK-cell granular lymphoproliferative disorder. Recently, lymphoepithelial carcinoma of the stomach, gastric carcinoma, pyothorax-associated lymphoma, and smooth muscle tumors were also recognized as EBV-associated diseases. It is therefore important to review the genetics and immunological response of EBV infection. In this review we summarize the genetics of EBV, immunological responses and clinical findings of EBV-associated diseases, which would help us to understand the pathophysiology of EBV-associated disease and develop specific treatments.

Epstein-Barr Virus Infections↗

PubMed2000

Intramedullary spinal cord recurrence after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation for limited-disease small cell lung cancer.

Intramedullary spinal cord metastasis is very rare in small-cell lung cancer (SCLC), and develops in only 2% of neurological disorders associated with SCLC according to previous reports. We describe here a patient with SCLC who developed intramedullary spinal cord recurrence after high-dose chemotherapy (HDCT) followed by autologous blood progenitor cell transplantation (ABPCT). A 59-year-old Japanese male was referred to us for diagnosis and treatment of an abnormal shadow on a chest radiograph. Based on transbronchial biopsy and staging procedures, he was diagnosed with limited-disease (LD)-SCLC. He received concurrent chemoradiotherapy followed by late intensification with HDCT supported by ABPCT. He achieved complete response and was discharged after receiving prophylactic cranial irradiation (PCI). However 6 months later, he noticed rapidly progressive weakness of the left lower extremity and bowel/bladder dysfunction. Magnetic resonance imaging (MRI) of the spinal cord disclosed an intramedullary tumor exhibiting an enhancement effect with Gd-DTPA at the 11-12th level of the thoracic vertebra. Immediately, radiotherapy to the spinal cord metastasis was given at a dose of 30 Gy, and his neurological disorders were completely resolved. At this time of reporting, he is doing well without recurrence. This case indicates that intramedullary spinal cord is one of the recurrence sites implicated after HDCT and PCI in LD-SCLC.

Carcinoma, Small Cell↗

PubMed2000

Allogeneic peripheral blood stem cell transplantation for the treatment of chronic active Epstein-Barr virus infection.

The prognosis of chronic active Epstein-Barr virus infection (CAEBV) is very poor. We describe a 24-year-old male with severe CAEBV who was treated with allogeneic peripheral blood stem cell transplantation (allo-PBSCT). On admission, EBER-1 in lymphocytes infiltrating the liver, EBV-DNA in peripheral blood mononuclear cells (PBMC) and monoclonal NK cell proliferation were confirmed. After unsuccessful chemotherapy, he received an allo-PBSCT from his HLA-identical sister. Although he died of pulmonary hemorrhage on day +19, EBV-DNA was undetectable by PCR in PBMC, and the post-mortem liver showed no EBER-1-positive lymphocytes. This experience suggests that EBV-positive lymphocytes in CAEBV may be eradicated by allo-PBSCT, thereby raising the possibility of a new treatment modality. Bone Marrow Transplantation (2000) 26, 805-808.

Adult↗

PubMed2000

Prognostic factors in advanced non-small cell lung cancer: elevated serum levels of neuron specific enolase indicate poor prognosis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is resistant to chemotherapy and prognosis of advanced NSCLC patients is considered to be dependent on various prognostic factors. METHODS: We analyzed prognostic factors in patients with advanced NSCLC who had been enrolled in clinical trials conducted by the Okayama Lung Cancer Study Group between 1978 and 1992 using two kinds of multivariate analysis, Cox's multivariate analysis and recursive partitioning and amalgamation (RPA) analysis. RESULTS: The first analysis was performed on 261 patients using 28 variables. Performance status (PS), clinical stage, liver metastasis or serum albumin level was an independent prognostic factor by Cox's analysis. In the second analysis performed on 128 patients having data on neuron specific enolase (NSE), NSE was the most important prognostic factor. Using the RPA method, three subgroups with significantly different survival potentials were defined. Among them, patients with normal serum NSE levels and good PS were found to obtain a markedly favorable prognosis [median survival time (MST) 22.1 months, 3-year survival rate 42.9%], whereas the survival of patients with elevated serum NSE levels and bone metastasis was extremely short (MST 4.7 months, 3-year survival rate 0%). CONCLUSIONS: These results indicate that analysis of prognostic factors including serum levels of NSE is useful for predicting the survival of patients with advanced NSCLC.

Adult↗

PubMed2000

Antiviral substance from silkworm faeces: characterization of its antiviral activity.

The antiviral activity of a substance (L4-1) purified from silkworm faeces was examined in an HVJ (Sendai virus)-LLC-MK2 cell system. Its antiviral effect depended on the period of light irradiation and was inhibited by sodium sulfite and anaerobic conditions. These results indicate that the antiviral activity of L4-1 is associated with active oxygen species produced from the substance. SDS-polyacrylamide gel electrophoretic analysis showed that viral proteins were damaged by this substance under light irradiation. The results suggest that the antiviral activity is due to damage to viral protein(s) caused by active oxygen species produced from L4-1.

Animals↗

PubMed1999

Immunohistochemical study of sialyl Le(a) and sialyl Le(x) antigen in oral squamous cell carcinoma: the association of sialyl Le(a) expression with the metastatic potential.

BACKGROUND: Carbohydrate antigens in cancer cells are considered to be involved in the binding of cancer cells to the endothelium during metastasis. METHODS: Seventy cases of primary oral squamous cell carcinoma (SCC) were obtained from biopsy specimens and were analyzed immunohistochemically using an antibody against sialyl Lewis (Le)a or sialyl Le(x). Flow cytometry was performed to detect the sialyl Le(a) or sialyl Le(x) expressed on oral SCC cell lines. RESULTS: The expressions of sialyl Le(a), but not sialyl Le(x), of primary tumors significantly correlated to nodal metastasis; 71% of the metastatic cases express sialyl Le(a) and the cases with positive sialyl Le(a) and no sialyl Le(x) demonstrated a high incidence of metastasis (80%). A flow cytometric study demonstrated the oral SCC cell line, which can metastasize in nude mice, to express a high level of sialyl Le(a). CONCLUSION: The high expression of sialyl Le(a) in primary tumors may thus be involved in nodal metastasis and therefore predict a poor prognosis in oral SCC.

Animals↗

PubMed1999

Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis.

BACKGROUND: Matrix metalloproteinases (MMPs) that degrade the extracellular matrices (ECMs) have been thought to play an important role in both the invasion and metastasis of tumors. However, the detailed role of MMPs and TIMPs (tissue inhibitors of MMP) on the biological behavior of tumor cells has yet to be elucidated in vivo. The aim of the present study was thus to determine whether expression of MMPs on tumor cells is associated with such clinicopathological features as the invasive and metastatic potential. MATERIALS AND METHODS: This study included 96 cases of primary oral squamous cell carcinoma (OSCC), of which 38 cases showed lymph node metastases. The relationship between the expression of MMPs and the staining of ECMs, the mode of tumor invasion, nodal involvement, and expression of TIMPs was immunohistochemically examined. RESULTS: First of all, a decrease in the staining of ECMs was observed in cases with an increased expression of MMP-1, -2, and -9. The association between the expression of MMPs and the loss of ECMs was thus found to be statistically significant. Secondly, in both invasive and metastatic cases, a marked expression of MMP-1, -2, -3, -9 and MT1-MMP was frequently observed. The association of the expression of MMPs both with the mode of tumor invasion and nodal involvement was thus found to be statistically significant. Thirdly, TIMP-2 was thus found not to significantly decrease in metastatic cases, while TIMP-1 expression significantly increased in metastatic cases. CONCLUSION: These results suggest that tumor progression is dependent on the ability of tumor cells to degrade ECMs, while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis than the production of TIMPs in vivo.

Adult↗

PubMed1999

Double high-dose chemotherapy supported by autologous transplantation of peripheral blood stem cells for treatment of an elderly patient with small-cell lung cancer.

We report a 62-year-old male with extensive disease small-cell lung cancer (SCLC) who was successfully treated with double high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT). This patient achieved a partial response with 3 cycles of induction chemotherapy. After the peripheral blood stem cell mobilization, two cycles of high-dose ICE regimen (ifosfamide 3,000 mg/m2 at days 1 to 5, carboplatin 400 mg/m2 at days 1, 3, 5, and etoposide 500 mg/m2 at days 1, 3, 5) could be given with further regression of the tumor and acceptable toxicities. This successful case suggests the feasibility of double high-dose ICE with auto-PBSCT in elderly patients with SCLC.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Loss of HLA haplotype in lung cancer cell lines: implications for immunosurveillance of altered HLA class I/II phenotypes in lung cancer.

Loss of expression of HLA class I antigens has been demonstrated in a wide variety of tumors and is considered to be one of the mechanisms whereby tumors escape T-cell surveillance. Genomic DNA of MHC class I/II molecules in seven lung cancer cell lines was investigated and compared with that in peripheral blood mononuclear cells. In three cell lines, OU-LC-A1, OU-LC-A2, and OU-LC-AS1, a loss of HLA haplotype was observed. Aberrations of HLA class I/II in tumor cell lines should be considered when MHC-restricted phenomena in vitro models are assessed and clinical use of tumor vaccination in vivo is considered.

Carcinoma, Non-Small-Cell Lung↗

PubMed1998

Characterization of a novel human natural killer-cell line (NK-YS) established from natural killer cell lymphoma/leukemia associated with Epstein-Barr virus infection.

A novel cell line was established from a patient with a leukemic-state nasal angiocentric natural killer (NK) cell lymphoma with systemic skin infiltration. The morphology of the leukemic cells was large-granular-lymphocyte (LGL), and their immunophenotype was CD2+, CD3-, CD5+, CD7+, CD16-, CD56+, and CD57-. The presence of Epstein-Barr viral (EBV) genome was shown in specimens from the patient's nose, skin, and peripheral blood by in situ hybridization using an EBV-encoded small RNA-1 probe or by Southern blotting using a terminal-repeat probe of the EBV genome. Leukemic cells were cocultured with a mouse stromal cell line (SPY3-2) in the presence of 100 U/mL recombinant human interleukin-2 and a novel stromal cell-independent cell line, NK-YS, was established. The NK-YS cells showed LGL morphology and expressed surface CD2, CD5, CD7, CD25, CD56, and CD95. The NK-YS cells retained cytotoxicity against K562 and Jurkat cells. A Southern blotting using a terminal-repeat probe of EBV showed that NK-YS and fresh leukemic cells had a clonal EBV genome, whereas the T-cell receptor beta and gamma chain genes of NK-YS were not rearranged. In an immunocytochemical analysis, the NK-YS cells showed a type-II latent infection of EBV. The NK-YS cells preserved the original characteristics of NK cell lymphoma/leukemia and will be a useful tool for the study of biological characteristics of EBV-associated nasal angiocentric NK cell lymphoma/leukemia.

Adult↗

PubMed1998

Immunohistochemical study of desmosomes in oral squamous cell carcinoma: correlation with cytokeratin and E-cadherin staining, and with tumour behaviour.

Reduction or loss of the intercellular junctions known as desmosomes may contribute to the invasive and metastatic behaviour of various carcinomas. Previous studies have shown that metastasis of oral squamous cell carcinomas of the head and neck correlates with a reduction in immunohistochemical staining for desmoplakin and desmoglein at the invasion front. The primary aim of the present study was to extend these observations to include a third component of desmosomes, the glycoprotein desmocollin. An additional aim was to determine whether the differentiation status of tumours is reflected in their staining for cytokeratins 1, 13, and 19, and, if so, whether these parameters correlate with desmosomal staining and/or metastasis. The study included 54 primary tumours of which 28 showed lymph node metastases. The results of this investigation show that tumours can be divided into three groups according to whether they have lost staining for no, one or more than one desmosomal component. A statistically significant correlation was found between the number of desmosomal components lost and metastasis. Tumours could also be divided into five groups according to their staining for different combinations of cytokeratins. Furthermore, differentiation status as indicated both histologically and by cytokeratin staining correlated with reduced desmosomal staining and metastasis. Tumours were also examined for intensity of staining for the adhesion molecule E-cadherin. Reduction in E-cadherin staining was correlated with mode of invasion and with reduction in desmosomal staining, but not with poor differentiation as indicated by cytokeratin staining. The results of this extensive study reinforce the view that adhesive junctions and adhesion molecules contribute to the suppression of tumour invasion and metastasis.

Adult↗

PubMed1998

Spontaneous biloma as a complication of small cell lung cancer.

Biloma is an extraductular collection of bile within a defined capsular space. Prior reports have documented an association between biloma and abdominal trauma, and between biloma and iatrogenic injury resulting from abdominal surgery, percutaneous catheter drainage, or transhepatic cholangiogram. To our knowledge, bilomas have not previously been associated with lung cancer. We report a case of spontaneous biloma that developed as a complication of small cell lung cancer.

Aged↗