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Mitsuhiro Takenoyama

Publications and source records attributed to Mitsuhiro Takenoyama.

10 recordsLinked to original sources
PubMed2003

Survival and prognostic factors of surgically resected T4 non-small cell lung cancer.

BACKGROUND: Category T4 nonsmall cell lung cancer (NSCLC) encompasses heterogenous subgroups. We retrospectively analyzed the survival of patients with surgically resected T4 NSCLC to evaluate the evidence for prognostic implications according to the subgroups of T4 category, nodal status, and resection completeness. METHODS: Seventy-six patients with T4N0-2M0 NSCLC were divided into three subgroups within the T4 category: 24 patients with the tumor invading the mediastinal organs (mediastinal group), 16 with a malignant pleural effusion or dissemination (pleural group), and 36 with satellite tumor nodules within the ipsilateral primary tumor lobe (satellite group). Complete resection was possible in 47 patients (61.8%). The pathologic N statuses were N0 in 28, N1 in 13, and N2 in 35 patients. RESULTS: The overall survival of the 76 patients was 19.1% at 5 years. The overall 5-year survivals according to the three subgroups of the T4 category were as follows: mediastinal group, 18.2%; pleural group, 0%; and satellite group, 26.7% (mediastinal/satellite versus pleural, p = 0.037). Factors significantly influencing the overall 5-year survival were the pathologic N status (N2 versus N0-1, p = 0.022) and the completeness of resection (complete versus incomplete, p = 0.0001). A multivariate survival analysis demonstrated that the pathologic N status and the completeness of resection were significant independent predictors of a poorer prognosis even after adjusting for the subgroup of the T4 category. CONCLUSIONS: Resectable T4N0-1 NSCLC that is not due to pleural disease deserves consideration of aggressive surgical resection with expected 5-year survival of about 20%.

Adult↗
PubMed2003

Genetic alteration in carcinoid tumors of the lung.

Surgically resected specimens of 13 carcinoid tumors of the lung including nine typical carcinoids and four atypical carcinoids, and eight salivary gland type carcinomas (six mucoepidermoid carcinomas and two adenoid cystic carcinomas) were analyzed regarding p53 expression, loss of heterozygosity (LOH) in chromosome 3p, 9p, and K-ras mutation. The overexpression of p53 was identified in four atypical carcinoid tumors, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma, however, none of typical carcinoids showed p53 immunoreactivity. LOH in 3p14 was demonstrated in three of seven informative cases in all tumors. LOH in 9p was demonstrated in two of five informative cases in all tumors. Two of three cases with LOH at 3p14 had a poor prognosis, one of which also had LOH at 9p. No mutation of the K-ras gene was observed in any of these tumors. These data thus indicate that p53 overexpression might distinguish atypical carcinoid tumors from typical tumors and might therefore be useful as an adjunct modality in the differential diagnosis of pulmonary carcinoid tumors. The presence of LOH at 3p14 or 9p may thus help to identify lung cancer patients with a poor prognosis.

Carcinoid Tumor↗
PubMed2002

Prognostic impact of micrometastatic tumor cells in the lymph nodes and bone marrow of patients with completely resected stage I non-small-cell lung cancer.

PURPOSE: This study was designed to substantiate the prognostic impact of occult micrometastatic tumor cells in the lymph nodes (LNs) and bone marrow (BM) in stage I non-small-cell lung cancer (NSCLC) patients using cytokeratin (CK) as a micrometastatic marker and the relationship between the micrometastases in the LNs and BM. PATIENTS AND METHODS: A total of 2,432 hilar and mediastinal LNs were removed during surgery from 115 patients with completely resected stage I NSCLC. The LNs were analyzed for micrometastasis using immunohistochemistry with the biclonal anti-CK antibody AE1/AE3. BM aspirates from 115 patients were immunocytochemically stained with the monoclonal anti-CK antibody CK2. RESULTS: CK-positive (CK+) cells were detected in 42 (1.7%) of 2,432 LNs, in 32 (27.8%) of 115 patients, and in 32 (27.8%) of 115 BM aspirates. There was no relationship between the frequencies of CK+ cells in the LNs and in the BM. The patients with CK+ cells in the LNs had a poor prognosis by both univariate (P =.008) and multivariate analyses (P =.01), whereas the presence of CK+ cells in the BM did not allow prediction of survival (P =.32). The prognostic impact of LNs micrometastasis was independent even after adjusting for the status of BM micrometastasis. CONCLUSION: The detection of lymph nodal micrometastatic tumor cells provides an accurate assessment of tumor staging and has powerful prognostic implications for completely resected stage I NSCLC patients.

Aged↗
PubMed2002

[Pulmonary resection for metastatic colorectal cancer].

We analyzed the outcome of 30 patients who underwent surgery (40 operations) for pulmonary metastases of colorectal cancer. Overall 5-year survival rate was 56%. There were no significant differences in survivals 5 years after the first surgery on the basis of potential prognostic factors: disease free interval, number of pulmonary metastases and size of metastatic lesion. Three patients with recurrent pulmonary metastases after the first resection underwent repeated resections and are alive 23, 58 and 62 months after the first pulmonary metastasectomy, respectively. Pulmonary resection for metastases from colorectal cancer prolonged the survival of patients, even those with bilateral lesions or recurrent metastases. These results confirm that pulmonary resection for metastatic colorectal cancer is a potentially curative therapy.

Adult↗
PubMed2002

Tumor-infiltrating B lymphocytes as a potential source of identifying tumor antigen in human lung cancer.

Functional studies using freshly isolated tumor-infiltrating B lymphocytes(TIB) are difficult to perform and interpret. Here we document a novel function of TIB using fresh human lung cancer tissues engrafted in SCID mice; they are at activated state and produce tumor-specific antibodies in tumor microenvironment: (a) TIB engrafted in SCID mice produced human IgG; (b) IgG derived from TIB highly bound intracellular and membrane-bound antigens of autologous cancer cells; and (c) less recognition of autoantigens expressed on normal lymphocytes by IgG derived from TIB compared with IgG from the serum of the patient. On the basis of the novel findings presented in this study, we modified the original serological analysis of antigens by recombinant cDNA expression cloning design in a patient with lung cancer who expressed unusually favorable clinical evolution and analyzed humoral immunity against identified mutated p53 antigen. This study provides the first demonstration that antibodies derived from TIB recognize tumor antigens by serological analysis of antigens by recombinant cDNA expression cloning methodology and circulating anti-p53 antibodies in sera derived from TIB in tumor microenvironment. Our approach using TIB may allow the identification of key antigens in the humoral cancer-related immune system.

Animals↗
PubMed2002

Feasibility of induction chemotherapy using bronchial arterial infusion for locally advanced non-small cell lung cancer: a pilot study.

PURPOSE: We examined the feasibility and effectiveness of bronchial arterial infusion (BAI) as induction chemotherapy before surgery for locally advanced non-small cell lung cancer (NSCLC). METHODS: Eighteen patients with locally advanced NSCLC were given BAI consisting of cis-diamminedichloroplatinum (CDDP) (50-100 mg/m(2)) as induction chemotherapy before surgery (induction BAI). Six patients with clinical stage IIIA cancer had bulky N2 metastatic lymph nodes, and 12 patients with clinical stage IIIB cancer had T4 disease. RESULTS: Of the 18 patients, 12 (67%) showed a partial response to the BAI therapy. Standard pulmonary resection was performed in 5 patients, pulmonary resection with the combined resection of adjacent organs was performed in 10 patients, and pulmonary resection with carinal resection and reconstruction was performed in 3 patients. Complete resection was possible in 14 patients (78%). There were no serious BAI therapy-related complications or postoperative deaths. The 5-year survival rate of the 18 patients was 35.7% and the median survival time (MST) was 19.4 months. Survival was better when complete resection was achieved after the induction BAI, especially in patients with stage IIIB (T4) disease. CONCLUSION: Based on our preliminary findings, BAI with CDDP as induction chemotherapy is feasible and may be an effective therapeutic modality for locally advanced NSCLC.

Adult↗
PubMed2002

Establishment of an immortalized T-cell line from lung cancer tissue: phenotypic and functional analyses.

BACKGROUND: In order to investigate host defense against solid tumors, valuable information could be provided by ex-vivo analyses of functional immune cells in tumor tissues. However, available sources of fresh tumor-infiltrating T cells (TIL) are usually very limited, and it is often difficult to establish TIL lines. In this study, we analyzed the phenotypic and functional characteristics of TIL, using an immortalized cell line prepared by cotransfection of human c-myc and c-Ha-ras. METHODS: A human T-cell line was established by cotransfecting c-Ha-ras and c-myc oncogenes to T lymphocytes freshly isolated from human lung large-cell carcinoma tissue. The phenotypes were assessed by flow cytometry. T-cell receptor (TCR) V alpha- and beta-usage was analyzed by polymerase chain reaction (PCR) and Southern blot. Cytotoxic activity against autologous and allogeneic tumor cell lines was examined by standard 51Cr-release cytotoxicity assays. Cytokine production by the established T-cell line, 904-T1, in response to stimulation by autologous tumor cells was assayed by using an enzyme-linked immunosorbent assay. RESULTS: 904-T1 (CD3+, CD8+, CD56+, CD16-, CD161-, TCR V alpha 9, 13, and V beta 1, 5) displayed a broad range of MHC-nonrestricted tumoricidal activity against various human tumor cell lines, but did not lyse autologous B cells transformed by Epstein-Barr virus. The cytotoxicity of 904-T1 was not mediated by a T-cell antigen receptor or by Fas-ligand, but by perforin-based cytolytic pathways, and was enhanced by interleukin (IL)-12. 904-T1 cells produced large amounts of interferon (IFN)-gamma, but not tumor necrosis factor (TNF)-alpha or IL-4 in response to autologous tumor cells, and produced high levels of IFN-gamma and TNF-alpha, and a substantial level of IL-4 following stimulation with anti-CD3 monoclonal antibody. CONCLUSIONS: Our results suggest that 904-T1 cells were natural killer T (NKT)-like cells with regard to their non-specific killing, cytokine repertoire, and sensitivity to IL-12, although the repertoire of the TCR variable region was not compatible with that of NKT cells.

Adenocarcinoma↗
PubMed2002

Establishment of 15 cancer cell lines from patients with lung cancer and the potential tools for immunotherapy.

BACKGROUND: Since lung cancer is the major cause of death not only in Japan but in many other industrialized countries, the development of new therapeutic modalities is quite important. In patients with melanoma, immunotherapy with some tumor antigens has been shown to result in tumor regression. However, little is known about specific immune responses and tumor antigens in lung cancer, due to difficulty in establishing appropriate lung cancer cell lines. In order to resolve these difficulties, we tried to establish and characterize lung cancer cell lines as useful tools for the analysis of tumor-specific immune responses in patients with lung cancer. MATERIALS AND METHODS: We tried to establish lung cancer cell lines from 549 patients with resectable lung cancer and from 21 patients with pleural and pericardial effusions or lymph node metastasis. We characterized the established cell lines after the induction of tumor-specific cytotoxic T lymphocytes (CTLs), and analyzed both the major histocompatibility complex (MHC) class I and class II molecules on their surfaces. RESULTS: We succeeded in establishing 15 lung cancer cell lines from 570 specimens (2.6%). The success rate of the establishment of lung cancer cell lines was significantly higher in patients at such advanced stages as MHC III and IV than in those at MHC stages I and II (p = 0.004). MHC class I molecules were expressed in 12 of 15 cell lines (80%), while MHC class II molecules were found in 3 of 15 cell lines (20%) on their cell surfaces by flow cytometry. A haplotype loss of MHC class I antigens was found in 6 of 15 cell lines (40%). Although CTLs were induced in only two of eight cell lines tried by stimulation with nontransduced autologous tumor cell lines, CTLs were successfully induced in all of eight cell lines tested by stimulation with CD80-transfected autologous tumor cells. CONCLUSIONS: These results suggested that the tumor antigens recognized by CTLs could thus exist in the tumor cells derived from many lung cancer patients. It is, therefore, possible that antigen-specific immunotherapies may be potentially effective for patients with lung cancer by adoptive transfer of CTLs, as well as by vaccine therapy using tumor-specific antigens.

Aged↗
PubMedDate not supplied

A case-case study comparing the usefulness of serum trace elements (Cu, Zn and Se) and tumor markers (CEA, SCC and SLX) in non-small cell lung cancer patients.

UNLABELLED: Serum copper (Cu), zinc (Zn) the Cu/Zn ratio (Cu/Zn) and selenium (Se) were evaluated in 84 patients with non-small cell lung cancer (NSCLC) before surgery. Serum carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and sialyl Lewis X-i antigen (SLX) levels were also determined in the same cases. The cut-off values of Cu, Zn and Se were established to create two categories with equal numbers of patients. We investigated the clinical and prognostic usefulness of assays of serum trace elements (Cu, Zn, Cu/Zn and Se) and compared levels of serum trace elements and serum tumor markers (CEA, SCC and SLX) in NSCLC patients. Furthermore, we evaluated the usefulness of serum trace elements, when compared with tumor markers, in assessing prognosis for NSCLC. IN CONCLUSION: (1) a preoperative increase in Cu/Zn level predicted tumor progression more effectively than changes in Cu or Zn levels; (2) Se levels seemed to vary with age, but there was no relationship between Se level and disease stage; (3) the measurement of Cu/Zn was useful for assessing both prognosis and extent of the disease in NSCLC patients, similar to the measurement of serum tumor markers such as CEA; and (4) the measurement of the Cu/Zn had prognostic significance, but was inferior to disease stage in predicting outcome. Cu and Zn in serum are storable and the determination of Cu/Zn level is so simple and inexpensive that it can be helpful in determining clinical stages and predicting the prognoses of NSCLC patients.

Adult↗