I graduated from Kyushu Univ Med School in 1969.I was the assistant prof at Med School Kyushu university in 1984 and became Prof at Univ ofOccupational and Environmental Health, Kitakyushu,Dept of General Thoracic Surg. I retired from UOEH in 2010 and became Emeritus Prof of UOEH.
Two hundred and seventy-one sera from patients with lung cancer were checked to determine whether... more Two hundred and seventy-one sera from patients with lung cancer were checked to determine whether they exerted a blocking or potentiating effect on normal lymphocyte-cytotoxicity against lung cancer targets using a microcytotoxicity assay. A blocking effect was observed in 15 of 49 untreated patients (30.6%), but a potentiating effect was detected in 10 of 49 (20.4%). Such effects were not correlated with stages of the disease or the clinical status of patients. Such a blocking effect was also detected in patients with pneumonia, pulmonary tuberculosis, benign mediastinal tumor and malignancies other than lung cancer, but the potentiating effect could not detected in such patients. Using an indirect membrane immunofluorescence test, IgG antibodies against QG-56 of a lung cancer cell line were detected in 54.3% of potentiating sera and in 20.5% of blocking sera. Such antibodies were cross-reactive with 2 other lung cancer cell lines and one of 4 uterine cancer lines, however, no cros...
The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer‐sp... more The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer‐specific CTLs to establish forceful cancer‐specific adoptive immunotherapy. We cloned the TCRαβ genes from CTLs showing HLA‐B15 restricted recognition of Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαβ and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL‐2. The KK‐LC‐1‐specific TCRαβ‐CD8 γδT cells showed cytotoxic activity against the KK‐LC‐1 positive lung cancer cell line F1121L and produced IFN‐γ against F1121L and KK‐LC‐1 peptide‐pulsed F1121 EBV‐B cells. These responses were blocked by HLA class I and HLA‐B/C antibodies. An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells (TCRαβ‐CD8 γδT cells) were intravenously injected. Growth inhibition of ...
18081 Background: Somatically acquired mutations in the EGFR gene in non-small cell lung cancer a... more 18081 Background: Somatically acquired mutations in the EGFR gene in non-small cell lung cancer are associated with a significant clinical response to gefitinib, a tyrosine kinase inhibitor that targets EGFR, especially in patients with adenocarcinoma, females, and/or never/light smokers. In our retrospective study, cases with EGFR mutations (exon19del or L858R) showed a high sensitivity to gefitinib, and the patients with sensitive EGFR mutations also tended to have a more favorable prognosis than those with wild-type after gefitinib treatment (Uramoto, et al. Lung Cancer 2006;51:71). In the present study, we prospectively assessed the efficacy of gefitinib and the survival benefit for patients with EGFR mutations. Methods: Patients with either recurrent disease after undergoing surgery or advanced disease (IIIB or IV) of NSCLC which demonstrated EGFR mutations were eligible for this study. EGFR mutations in exons 19–21 were examined by our previously described screening method (Su...
Lung cancer tissues are often infiltrated by B lymphocytes, but it is not clear whether these inf... more Lung cancer tissues are often infiltrated by B lymphocytes, but it is not clear whether these infiltrations represent tumor-specific immune response or a nonspecific reaction. The serological analysis of recombinant cDNA expression libraries (SEREX) were previously modified using a severe combined immunodeficient (SCID) mice model engrafted with fresh human lung cancer. Here, a panel of antigens recognized by tumor-infiltrating B lymphocytes (TIB) in human lung cancer were characterized. The modified SEREX analysis identified 22 distinct antigens in a large cell carcinoma of the lung. Sequence analysis and real time-PCR analysis showed that 55% of isolated antigens were overexpressed in tumor tissues and 9% had mutation. The results of this study indicate that the humoral immune response of TIB in lung cancer patients can be detected in the xenotransplanted SCID mouse model and our modification shows high sensitivity and specificity for identification of tumor antigens.
Not only serum tumor markers, such as carcinoembryonic antigen (CEA), squamous cell carcinoma ant... more Not only serum tumor markers, such as carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and carbohydrate antigen (CA) 125, but also serum growth factors have been examined to evaluate tumor stages and to predict the recurrence and metastasis in patients with non-small cell lung cancer (NSCLC) (1-5). In recent years, the analysis of the genome and proteome has advanced remarkably. An array of molecular genetic tumor markers (MGTMs) have been identified based on the biological characterization of tumors, such as tumor development, growth, invasion and metastasis. Molecular genetic tumor marker research has also entered a new era, since comprehensive gene profile analysis using cDNA microarrays and comprehensive protein expression analysis using proteomics technology have been developed. On the other hand, the frequency of lung cancer patients with which various tumor markers are associated is increasing in Japan (6-8). This paper reviews MGTMs characteristic of lun...
Clinical cancer research : an official journal of the American Association for Cancer Research, 1996
We examined 110 patients with non-small cell lung cancer who underwent consecutive pulmonary rese... more We examined 110 patients with non-small cell lung cancer who underwent consecutive pulmonary resection for loss of heterozygosity (LOH) at the short arm of chromosome 3 (3p). We performed a PCR-based microsatellite polymorphism analysis for detection of LOH. The microsatellite markers used were D3S966 (3p21.3), D3S1007 (3p21. 3-22), and D3S1228 (3p14.1-14.3). Of 98 informative cases, 3p LOH was found in 45 (46%). 3p LOH was more prevalent in squamous cell carcinoma (24/35, 69%) than in adenocarcinoma (18/52, 35%; P = 0.0019). There was no significant association between 3p LOH and sex, disease stage, or grade of differentiation. However, patients with 3p LOH tended to survive for a shorter period of time (P = 0.0631, log rank test). There was no such tendency in squamous cell carcinoma (P = 0.7513), but in adenocarcinoma, the difference of survival was significant (P = 0.0015). Cox's proportional hazards model also predicted that 3p LOH was an independent poor prognostic marker ...
We examined argyrophil nuclear organizer regions (AgNOR) and proliferating cell nuclear antigen (... more We examined argyrophil nuclear organizer regions (AgNOR) and proliferating cell nuclear antigen (PCNA) in 41 patients with surgically-treated thymic disease. AgNOR count and PCNA labeling index (LI) in thymic carcinoma were significantly higher than those in thymoma and thymic hyperplasia. A positive correlation was observed between the PCNA LI and argyrophilic nucleolar organizer region (AgNOR) counts within all thymic disease (r=0.31, P=0.002). The PCNA LI in invasive thymoma was lower than that in non-invasive thymoma. In survival analysis, the cut-off values for the PCNA LI and AgNOR count were chosen to produce two categories with equal numbers of 26 thymoma patients. There were no significant difference in the survival rate between the lower and higher group patients in relation with AgNOR count and PCNA LI. We conclude that combining AgNOR and PCNA may discriminate the biological activity of thymic disease. These staining methods can be performed with ease and, applied in a clinical laboratory on a routine basis to help predict cytological malignancy of thymic disease.
Purpose: ΔNp73 is an isoform of the p53 homologue p73, which lacks an NH2-terminal transactivatio... more Purpose: ΔNp73 is an isoform of the p53 homologue p73, which lacks an NH2-terminal transactivation domain and antagonizes the induction of gene expression by p53/p73. The aim of this study was to detect ΔNp73 expression in lung cancer and to evaluate the relationship between the ΔNp73 expression level and the prognosis of patients with resected lung cancer. Experimental Design: We used immunohistochemistry to analyze the protein expression of ΔNp73 in paraffin-embedded tumor samples from 132 well-characterized lung cancer patients and compared the expression level of ΔNp73, clinical variables, and survival outcome. Results: Positive expression of ΔNp73 was detected mainly in the cytoplasm of tumor cells in 77 of 132 patients (58.3%) with lung cancer. The incidence of positive expression of ΔNp73 was 52.2, 50.0, and 70.2% in patients with stage I, II, and III, respectively (P = 0.04). Positive expression of ΔNp73 was associated with gender but not associated with age, histologic type...
Clinical evaluation of micrometastases in the lymph nodes of lung cancer patients is not currentl... more Clinical evaluation of micrometastases in the lymph nodes of lung cancer patients is not currently recommended in guidelines because of several different results concerning their prevalence and prognostic implications. However, a recent large, prospective, multicenter clinical study has shown a significant prognostic impact of micrometasteses in the lymph nodes of patients with resectable lung cancer; therefore, the clinical significance of micrometastases as predictive markers of recurrence and prognosis has begun to be clarified. From the viewpoint of surgery for lung cancer, sentinel node navigation surgery, segmentectomy, and individualized therapies such as adjuvant chemotherapy are expected to be developed. In the near future, standardization and improvement of the efficiency of diagnostic procedures will be necessary in common clinical practice. Recently, minimal residual cancer cell research, such as circulating tumor cells in the peripheral blood and disseminated tumor cell...
Two hundred and seventy-one sera from patients with lung cancer were checked to determine whether... more Two hundred and seventy-one sera from patients with lung cancer were checked to determine whether they exerted a blocking or potentiating effect on normal lymphocyte-cytotoxicity against lung cancer targets using a microcytotoxicity assay. A blocking effect was observed in 15 of 49 untreated patients (30.6%), but a potentiating effect was detected in 10 of 49 (20.4%). Such effects were not correlated with stages of the disease or the clinical status of patients. Such a blocking effect was also detected in patients with pneumonia, pulmonary tuberculosis, benign mediastinal tumor and malignancies other than lung cancer, but the potentiating effect could not detected in such patients. Using an indirect membrane immunofluorescence test, IgG antibodies against QG-56 of a lung cancer cell line were detected in 54.3% of potentiating sera and in 20.5% of blocking sera. Such antibodies were cross-reactive with 2 other lung cancer cell lines and one of 4 uterine cancer lines, however, no cros...
The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer‐sp... more The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer‐specific CTLs to establish forceful cancer‐specific adoptive immunotherapy. We cloned the TCRαβ genes from CTLs showing HLA‐B15 restricted recognition of Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαβ and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL‐2. The KK‐LC‐1‐specific TCRαβ‐CD8 γδT cells showed cytotoxic activity against the KK‐LC‐1 positive lung cancer cell line F1121L and produced IFN‐γ against F1121L and KK‐LC‐1 peptide‐pulsed F1121 EBV‐B cells. These responses were blocked by HLA class I and HLA‐B/C antibodies. An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells (TCRαβ‐CD8 γδT cells) were intravenously injected. Growth inhibition of ...
18081 Background: Somatically acquired mutations in the EGFR gene in non-small cell lung cancer a... more 18081 Background: Somatically acquired mutations in the EGFR gene in non-small cell lung cancer are associated with a significant clinical response to gefitinib, a tyrosine kinase inhibitor that targets EGFR, especially in patients with adenocarcinoma, females, and/or never/light smokers. In our retrospective study, cases with EGFR mutations (exon19del or L858R) showed a high sensitivity to gefitinib, and the patients with sensitive EGFR mutations also tended to have a more favorable prognosis than those with wild-type after gefitinib treatment (Uramoto, et al. Lung Cancer 2006;51:71). In the present study, we prospectively assessed the efficacy of gefitinib and the survival benefit for patients with EGFR mutations. Methods: Patients with either recurrent disease after undergoing surgery or advanced disease (IIIB or IV) of NSCLC which demonstrated EGFR mutations were eligible for this study. EGFR mutations in exons 19–21 were examined by our previously described screening method (Su...
Lung cancer tissues are often infiltrated by B lymphocytes, but it is not clear whether these inf... more Lung cancer tissues are often infiltrated by B lymphocytes, but it is not clear whether these infiltrations represent tumor-specific immune response or a nonspecific reaction. The serological analysis of recombinant cDNA expression libraries (SEREX) were previously modified using a severe combined immunodeficient (SCID) mice model engrafted with fresh human lung cancer. Here, a panel of antigens recognized by tumor-infiltrating B lymphocytes (TIB) in human lung cancer were characterized. The modified SEREX analysis identified 22 distinct antigens in a large cell carcinoma of the lung. Sequence analysis and real time-PCR analysis showed that 55% of isolated antigens were overexpressed in tumor tissues and 9% had mutation. The results of this study indicate that the humoral immune response of TIB in lung cancer patients can be detected in the xenotransplanted SCID mouse model and our modification shows high sensitivity and specificity for identification of tumor antigens.
Not only serum tumor markers, such as carcinoembryonic antigen (CEA), squamous cell carcinoma ant... more Not only serum tumor markers, such as carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and carbohydrate antigen (CA) 125, but also serum growth factors have been examined to evaluate tumor stages and to predict the recurrence and metastasis in patients with non-small cell lung cancer (NSCLC) (1-5). In recent years, the analysis of the genome and proteome has advanced remarkably. An array of molecular genetic tumor markers (MGTMs) have been identified based on the biological characterization of tumors, such as tumor development, growth, invasion and metastasis. Molecular genetic tumor marker research has also entered a new era, since comprehensive gene profile analysis using cDNA microarrays and comprehensive protein expression analysis using proteomics technology have been developed. On the other hand, the frequency of lung cancer patients with which various tumor markers are associated is increasing in Japan (6-8). This paper reviews MGTMs characteristic of lun...
Clinical cancer research : an official journal of the American Association for Cancer Research, 1996
We examined 110 patients with non-small cell lung cancer who underwent consecutive pulmonary rese... more We examined 110 patients with non-small cell lung cancer who underwent consecutive pulmonary resection for loss of heterozygosity (LOH) at the short arm of chromosome 3 (3p). We performed a PCR-based microsatellite polymorphism analysis for detection of LOH. The microsatellite markers used were D3S966 (3p21.3), D3S1007 (3p21. 3-22), and D3S1228 (3p14.1-14.3). Of 98 informative cases, 3p LOH was found in 45 (46%). 3p LOH was more prevalent in squamous cell carcinoma (24/35, 69%) than in adenocarcinoma (18/52, 35%; P = 0.0019). There was no significant association between 3p LOH and sex, disease stage, or grade of differentiation. However, patients with 3p LOH tended to survive for a shorter period of time (P = 0.0631, log rank test). There was no such tendency in squamous cell carcinoma (P = 0.7513), but in adenocarcinoma, the difference of survival was significant (P = 0.0015). Cox's proportional hazards model also predicted that 3p LOH was an independent poor prognostic marker ...
We examined argyrophil nuclear organizer regions (AgNOR) and proliferating cell nuclear antigen (... more We examined argyrophil nuclear organizer regions (AgNOR) and proliferating cell nuclear antigen (PCNA) in 41 patients with surgically-treated thymic disease. AgNOR count and PCNA labeling index (LI) in thymic carcinoma were significantly higher than those in thymoma and thymic hyperplasia. A positive correlation was observed between the PCNA LI and argyrophilic nucleolar organizer region (AgNOR) counts within all thymic disease (r=0.31, P=0.002). The PCNA LI in invasive thymoma was lower than that in non-invasive thymoma. In survival analysis, the cut-off values for the PCNA LI and AgNOR count were chosen to produce two categories with equal numbers of 26 thymoma patients. There were no significant difference in the survival rate between the lower and higher group patients in relation with AgNOR count and PCNA LI. We conclude that combining AgNOR and PCNA may discriminate the biological activity of thymic disease. These staining methods can be performed with ease and, applied in a clinical laboratory on a routine basis to help predict cytological malignancy of thymic disease.
Purpose: ΔNp73 is an isoform of the p53 homologue p73, which lacks an NH2-terminal transactivatio... more Purpose: ΔNp73 is an isoform of the p53 homologue p73, which lacks an NH2-terminal transactivation domain and antagonizes the induction of gene expression by p53/p73. The aim of this study was to detect ΔNp73 expression in lung cancer and to evaluate the relationship between the ΔNp73 expression level and the prognosis of patients with resected lung cancer. Experimental Design: We used immunohistochemistry to analyze the protein expression of ΔNp73 in paraffin-embedded tumor samples from 132 well-characterized lung cancer patients and compared the expression level of ΔNp73, clinical variables, and survival outcome. Results: Positive expression of ΔNp73 was detected mainly in the cytoplasm of tumor cells in 77 of 132 patients (58.3%) with lung cancer. The incidence of positive expression of ΔNp73 was 52.2, 50.0, and 70.2% in patients with stage I, II, and III, respectively (P = 0.04). Positive expression of ΔNp73 was associated with gender but not associated with age, histologic type...
Clinical evaluation of micrometastases in the lymph nodes of lung cancer patients is not currentl... more Clinical evaluation of micrometastases in the lymph nodes of lung cancer patients is not currently recommended in guidelines because of several different results concerning their prevalence and prognostic implications. However, a recent large, prospective, multicenter clinical study has shown a significant prognostic impact of micrometasteses in the lymph nodes of patients with resectable lung cancer; therefore, the clinical significance of micrometastases as predictive markers of recurrence and prognosis has begun to be clarified. From the viewpoint of surgery for lung cancer, sentinel node navigation surgery, segmentectomy, and individualized therapies such as adjuvant chemotherapy are expected to be developed. In the near future, standardization and improvement of the efficiency of diagnostic procedures will be necessary in common clinical practice. Recently, minimal residual cancer cell research, such as circulating tumor cells in the peripheral blood and disseminated tumor cell...
Uploads