Biomedical subjects

F Tanaka

Publications and source records attributed to F Tanaka.

At least 19 recordsLinked to original sources

PubMed2001

Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas.

Cancer-testis antigens (CTAs) such as MAGE are selectively expressed in various types of human neoplasms but not in normal tissues other than testis. This characteristic feature of CTAs makes them promising antigens for cancer-specific immunotherapy. A critical requirement for this therapy is identification of promising antigens. In this study, we investigated the expression of 6 genes recently identified by serological analysis of antigens by recombinant expression (SEREX) libraries: NY-ESO-1, LAGE-1, SCP-1, SSX-1, SSX-2, and SSX-4, in many surgical samples of gastrointestinal and breast carcinomas using reverse transcription-polymerase chain reaction. We found relatively high expression of SCP-1 (23.5%) and SSX-4 (20.6%) in gastric carcinoma, LAGE-1 (39.1%) and NY-ESO-1 (23.9%) in oesophageal carcinoma, and SCP-1 (34.1%) in breast carcinoma. We also found frequent synchronous expression with MAGE, including LAGE-1 (46.2%) in oesophageal carcinoma, SSX-4 (46.7%) in gastric carcinoma, and SCP-1 (38.3%) in breast carcinoma. Immunohistochemical analysis of the tumour samples expressing both MAGE-4 and NY-ESO-1 genes demonstrated differences in distribution between MAGE-4 and NY-ESO-1 in serial sections. We concluded that NY-ESO-1, LAGE-1, SCP-1 and SSX-4 genes may be promising candidates for cancer-specific immunotherapy in addition to MAGE, and that polyvalent cancer vaccines may be useful in cases of heterogeneous expressions of CTA genes in gastrointestinal and breast carcinomas.

Antigens, Neoplasm↗

PubMed2001

Prognostic significance of polysialic acid expression in resected non-small cell lung cancer.

Polysialic acid (PSA) is a carbohydrate attached mainly to the neural cell adhesion molecule. Because PSA is composed of a linear homopolymer of alpha-2-8-linked sialic acid residues and has a large negative charge, the presence of PSA attenuates the adhesive property of neural cell adhesion molecule and increases cellular motility. In an earlier study, we demonstrated that PSA and STX, a polysialyltransferase, were associated with tumor progression in non-small cell lung cancer (NSCLC) (F. Tanaka et al., Cancer Res., 60: 3072-3080, 2000). Therefore, in the present study, to assess the prognostic significance of PSA in resected NSCLC, a total of 236 patients who underwent complete resection for pathological (p)-stage I-IIIa disease were reviewed retrospectively. PSA was expressed in 44 of 236 (18.6%) patients, and the expression was correlated with p-stage disease. For all p-stage patients, 5-year survival rates for those with PSA-positive and PSA-negative tumors were 52.1% and 71.3%, respectively, demonstrating a significantly worse prognosis for the PSA-positive patients (P = 0.012). Analysis for only p-stage I patients also demonstrated a significantly worse prognosis for the PSA-positive patients; 5-year survival rates of the PSA-positive and the PSA-negative patients were 45.1% and 83.5%, respectively, (P < 0.001). In addition, there proved to be no difference in the postoperative survival among p-stage I, II, and IIIa patients when PSA expression was positive. Multivariate analysis confirmed that PSA expression was an independent factor to predict poor prognosis in resected NSCLC. These results suggested that PSA could be an important clinical marker and that preoperative induction and/or postoperative adjuvant therapies should be performed for PSA-positive NSCLC, even if the disease is classified as p-stage I.

Biomarkers, Tumor↗

PubMed2001

Expression of neural cell adhesion molecules (polysialylated form of neural cell adhesion molecule and L1-cell adhesion molecule) on resected small cell lung cancer specimens: in relation to proliferation state.

BACKGROUND AND OBJECTIVES: Alteration of homotypic cell-cell adhesion has been suggested to play an important role in tumor progression. The present study examined the relationship between neural cell adhesion molecules and state of proliferation of small cell lung cancer (SCLC) cells. METHODS: Seventeen surgically resected specimens of SCLC were immunohistochemically examined, by using monoclonal antibodies against neural cell adhesion molecule (NCAM) and its polysialic acid side chains, and L1 cell adhesion molecule (L1-CAM). Ki-67 labeling indices were also determined immunohistochemically. RESULTS: All patients were positive for L1-CAM. Fifteen patients (88.2%) were positive for NCAM. Among the fifteen patients, nine (60.0%) were positive for NCAM PSA side chain. The probability of survival of the NCAM without PSA side chain group was significantly higher than that of the NCAM with PSA side chain group (log-rank test; P = 0.500). CONCLUSIONS: The expression of NCAM with PSA side chains might be a prognostic factor and NCAM a marker for SCLC. L1-CAM may be synthesized independent of state of proliferation of individual tumor cell and may affect clinical feature of SCLC.

Adolescent↗

PubMed2001

The prognostic significance of malignant pleural effusion at the time of thoracotomy in patients with non-small cell lung cancer.

Surgery is usually not indicated for malignant pleural effusion (PE) due to its poor prognosis. However, PE is first detected at thoracotomy, and it is difficult to judge an appropriate mode of resection. Forty-nine patients with lung cancer were first diagnosed as PE and/or pleural dissemination (PD) at thoracotomy. The histological types were 36 adenocarcinoma, ten squamous cell carcinoma and three large cell carcinoma. Sixteen patients had only PE, 17 had only PD, and 16 had both PE and PD. Ten patients underwent only exploratory thoracotomy, seven partial resection, 27 lobectomy and five panpleuropneumonectomy. The overall survival rate was 26.7% at 3 years. The patients with PE and/or PD seemed to have a poorer survival compared to our previous study. The patients with only PE showed a significantly better prognosis than the patients with only PD (P=0.0001) or with PD+PE (P=0.019). The patients who underwent exploratory thoracotomy showed poor survival. There were significant differences in the survival in relation to the extent of the primary tumor. In conclusion, the patients with T1-2 of primary tumor and only a small amount of PE without PD can be expected to show long-term survival after tumor resection.

Aged↗

PubMed2001

Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC).

OBJECTIVES: To clarify prognostic factors in resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC). METHODS: A total of 95 consecutive patients who underwent complete tumor resection and mediastinal dissection for pT1-2N1M0 NSCLC between 1976 and 1997 were retrospectively reviewed. p53 status and proliferative activity were evaluated immunohistochemically. RESULTS: The extent of N1 stations and p53 status proved to be significant prognostic factors. The 5-year survival rate for tumor without hilar node (#10) involvement was 66%, significantly higher than that for tumor with #10 involvement (39%, P<0.01). The 5-year survival rate for tumor with aberrant p53 expression was 37%, significantly lower than that for tumor without aberrant p53 expression (74%, P<0.01). There proved to be no significant difference in the prognosis between pT1 disease and pT2 disease; the 5-year survival rates for pT1 and pT2 diseases were 62 and 56%, respectively. Age, gender, performance status, grade of tumor differentiation, histological type, or proliferative activity were not significant factors. Multivariate analysis of prognostic factors using Cox's proportional hazard model confirmed these results. CONCLUSIONS: Involvement of the hilar node and aberrant p53 expression were significant factors to predict a worse prognosis in resected T1-2N1M0 NSCLC.

Biomarkers, Tumor↗

PubMed2001

Apoptosis and p53 status predict the efficacy of postoperative administration of UFT in non-small cell lung cancer.

To examine whether efficacy of postoperative oral administration of UFT, a 5-fluorouracil derivative chemotherapeutic agent, may be influenced by incidence of apoptosis (apoptosis index) or apoptosis-related gene status (p53 and bcl-2) of the tumour, a total of 162 patients with pathologic stage I non-small cell lung cancer were retrospectively reviewed. UFT was administrated postoperatively to 44 patients (UFT group), and not to the other 118 patients (Control group). For all patients, 5-year survival rate of the UFT group (79.9%) seemed higher than that of the Control group (69.8%), although without significant difference (P = 0.054). For patients with higher apoptotic index, 5-year survival rate of the UFT group (83.3%) was significantly higher than that of the Control group (67.6%, P = 0.039); for patients with lower apoptotic index, however, there was no difference in the prognosis between these two groups. Similarly, UFT was effective for patients without p53 aberrant expression (5-year survival rates: 95.2% for the UFT group and 74.3% for the Control group, P = 0.022), whereas not effective for patients with p53 aberrant expression. Bcl-2 status did not influence the efficacy of UFT. In conclusion, apoptotic index and p53 status are useful factors to predict the efficacy of postoperative adjuvant therapy using UFT.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Isolation and characterization of an N-linked oligosaccharide that is significantly increased in sera from patients with non-small cell lung cancer.

The structures of N-linked oligosaccharides present in human sera from 12 healthy volunteers and from 14 patients with non-small cell lung cancer (NSCLC) were analyzed by our recently developed partially automated systematic method. Thirty different structures of oligosaccharides were deduced, and these accounted for 84.1% of the total N-linked oligosaccharides present in human sera. All of the quantified oligosaccharide levels in healthy human sera were within twice the standard deviation. The amount of a triantennary trigalactosylated structure with one outer arm fucosylation (A3G3Fo) was found to be markedly increased in NSCLC patients in comparison to that in healthy volunteers (p < 0.01). No significant positive correlation with other clinical data was found. Serum A3G3Fo levels can thus be a novel marker for the diagnosis of NSCLC.

Adult↗

PubMed2001

[A case of orbital MALT lymphoma in which 67Ga scintigraphy was useful for evaluating the radiation therapy response].

A 67-year-old man was hospitalized at our institution complaining with epiphora and exophthalmos on the left side. Magnetic resonance imaging (MRI) showed an ill demarcated retrobulbar mass in the left orbit. 67Ga scintigraphy revealed avid uptake in the left orbital region. The patient was treated with radiation therapy. One month after the radiation therapy, the size of the mass decreased remarkably on MRI. 67Ga planar imaging after treatment showed no uptake, but 67Ga SPECT showed slightly increased uptake in the left orbital region. One year after the radiation therapy, MRI showed residual mass in the left orbital region. Both 67Ga planar imaging and SPECT showed no uptake in the left orbital region. 1.8 years after the radiation therapy, MRI showed the residual mass with no interval change in size. Both 67Ga planar imaging and SPECT showed no uptake in the left orbital region. The patient remains well with no evidence of local recurrence. 67Ga scintigraphy is useful in assessing the response to radiation therapy of MALT lymphoma in this case.

Aged↗

PubMed2001

Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinomas.

The MAGE gene is selectively expressed in cancer tissues such as melanoma or gastrointestinal carcinomas, whereas no expression is observed in normal tissues except testis. There are several reports of successful induction of HLA class I-restricted antitumor CTLs using MAGE peptides, and some clinical trials with these immunogenic peptides were reported as effective for some patients with malignant melanoma. However, there are no similar studies in gastrointestinal carcinomas, which are important neoplasms. Autologous dendritic cells (DCs) were generated ex vivo and were pulsed with MAGE-3 peptide, depending on the patient's HLA haplotype (HLA-A2 or A24). Patients were immunized with DC pulsed with MAGE-3 peptide every 3 weeks at four times. Twelve patients with advanced gastrointestinal carcinoma (six stomach, three esophagus, and three colon) were treated, and no toxic side effects were observed. Peptide-specific CTL responses after vaccination were observed in four of eight patients. Improvement in performance status was recognized in four patients. Tumor markers decreased in seven patients. In addition, minor tumor regressions evidenced by imaging studies were seen in three patients. These results suggested that DC vaccination with MAGE-3 peptide is a safe and promising approach in the treatment of gastrointestinal carcinomas.

Aged↗

PubMed2001

[Preoperative induction therapy in non-small cell lung cancer].

The clinical significance of preoperative induction therapy for non-small cell lung cancer (NSCLC) is reviewed. As the survival rate in locally advanced NSCLC patients remains poor, preoperative therapy has been attempted in order to improve survival. Whereas some prospective phase II and phase III studies have demonstrated that preoperative cisplatin-based chemotherapy with or without concurrent radiation may improve the prognosis, the efficacy has not been established. Recently, some new chemotherapeutic agents such as paclitaxel and gemcitabine have been introduced, and it has been suggested that preoperative therapy using these new drugs may be more effective. To establish effective preoperative therapy regimens, more sophisticated, prospective, randomized studies in sufficient numbers of homogenous populations such as mediastinoscopy-proven stage IIIA, T1-2N2 patients should be conducted.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Detection of triplet repeat expansion in the human genome by use of hybridization signal intensity.

Triplet repeat disease is a group of hereditary neurodegenerative disorders caused by expansion of trinucleotide repeats such as CAG/CTG, CGG/CCG, and GAA/TTC. Direct detection of the expansion in the patient's genome shortcuts the tedious process needed for identification of disease genes by conventional approaches. Here we describe a method to detect triplet repeat expansion from the hybridization signal intensity. Using a digoxigenin-labeled (CTG)9 probe, the hybridization intensity and number of repeats showed a good linear correlation. The technique detected expansion in genomic DNA in all cases with moderate or large expansion. Even in the case of a small expansion, this method could detect the mutant fragment. The technique has advantages over related techniques because it is more sensitive and can be applied to cases where a small repeat expansion is involved.

Alleles↗

PubMed2000

Rapid generation of potent and tumor-specific cytotoxic T lymphocytes by interleukin 18 using dendritic cells and natural killer cells.

We hypothesized that antitumor-specific immunity, which is induced by interleukin (IL) 18 treatment in murine tumor models, is promoted by enhancing natural killer (NK)-mediated destruction of tumor and delivery to dendritic cells (DCs). These activated and antigen-pulsed DCs then critically and optimally induce an adoptive immune response, positioning IL-18 as an important bridge between the innate and adoptive immune response. The effect of IL-18 added to cultures of live tumor cells (MCA205, a mouse sarcoma cell line), NK cells, DCs, and T cells was assessed. When recombinant (r) mIL-18 protein was added to this culture, potent NK cytolytic activity with subsequent generation of CTLs was observed in a dose-dependent manner. Without introduction of either rmIL-18 or NK cells into this culture, systemic cytolytic activity was significantly decreased. Following the absence of direct contact of either NK cells or DCs with other cells in this cooperative coculture system using transwell, the systemic cytolytic activity of both NK cells and CTLs was greatly suppressed. The cytolysis mediated by effector cells harvested after completion of the culture was primarily restricted to MHC class I and highly specific for the tumor cells used in the coculture. Furthermore, we examined the efficiency in the induction of cytolytic T cells of other established IFN-gamma inducing T-cell growth factors, IL-2, and IL-12 in this culture system and compared them with that mediated by IL-18. Neither IL-2 nor IL-12 induced tumor-specific cytolytic T cells to the same degree as that mediated by IL-18. Efficacy of this system in induction of tumor-specific CTLs was also observed in the system using MC38 adenocarcinoma cells. These results are consistent with the notion that IL-18 induces tumor-specific immunity through enhancing NK activity, which in turn mediates tumor cell death and activates and primes DCs.

Adenocarcinoma↗

PubMed2000

Expression of polysialic acid and STX, a human polysialyltransferase, is correlated with tumor progression in non-small cell lung cancer.

Polysialic acid (PSA) is a carbohydrate composed of a linear homopolymer of alpha-2-8-linked sialic acid residues and is mainly attached to the neural cell adhesion molecule (NCAM). Because of the large negative charge of PSA, presence of PSA attenuates the adhesive property of NCAM and increases the cellular motility. PSA expression on NCAM is developmentally regulated, and PSA plays important roles in formation and remodeling of the neural system through regulation of the adhesive property of NCAM. Expression of the polysialated form of NCAM has been also demonstrated in some malignant tumors, such as Wilms' tumor and small cell lung cancer. Despite the possible importance as an onco-developmental antigen, however, significance of PSA expression in most malignant tumors has not been revealed. Therefore, PSA expression in non-small cell lung cancer was assessed in the present study. PSA was expressed only in 5 (20.8%) of 24 pathological stage I cases, whereas it was expressed in most stage IV cases (76.8%, 11 of 14 cases). PSA expression was correlated with nodal metastasis and distant metastasis, but not with local extent of the primary tumor. Next, expression of polysialyltransferase genes (PST and STX genes) which controlled formation of PSA, was examined. The PST gene was constantly expressed in both normal lung tissue and tumor tissue of all cases. In contrast, the STX gene was not expressed in normal lung tissue of any case, and STX gene expression in tumor tissue was closely correlated with tumor progression. The STX gene was expressed only in 1 (4.2%) of 24 stage I cases, whereas it was expressed in most stage IV cases (85.7%, 12 of 14 cases). These results suggested that the PSA and STX genes could be new targets of cancer therapy as well as important clinical markers.

Adult↗

PubMed2000

Using antibody catalysis to study the outcome of multiple evolutionary trials of a chemical task.

Catalytic aldolase antibodies generated by immunization with two different, but structurally related, beta-diketone haptens were cloned and sequenced to study similarities and differences between independently evolved catalysts. Kinetic and sequence analysis coupled with mutagenesis, structural, and modeling studies reveal that the defining event in the evolution of these catalysts was a somatic mutation that placed a lysine residue in a deep, yet otherwise unrefined, hydrophobic pocket. We suggest that covalent chemistries may be as readily selected from the immune repertoire as the traditional noncovalent interactions that have formed the basis of immunochemistry until this time. Further, we believe that these experiments recapitulate the defining events in the evolution of nature's enzymes, particularly as they relate to chemical mechanism, catalytic promiscuity, and gene duplication.

Amino Acid Sequence↗

PubMed2000

Association of osteopontin with ischemic axonal death in periventricular leukomalacia.

Osteopontin (OPN) is a bone matrix protein expressed my macrophages and related to the process of tissue calcification, and is also known to protect ischemic cells. To understand how OPN is involved in the process of ischemic axonal death in periventricular leukomalacia (PVL), we examined the immunoreactivity of OPN and ionized calcium binding adaptor molecule 1 (Iba1; microglia/macrophage marker) at various stages of PVL. OPN immunoreactivity paralleled the number of Iba1-positive foam cells; a finding which suggests the production of OPN protein by foam cells. OPN immunoreactivity was not found in either normal white matter or acute PVL lesions, but was detected at the subacute and chronic stages in swollen and calcified axons bordering the ischemic zone. These findings suggest that OPN is closely associated with death of swollen axons at the periphery of the ischemic zone, regulating the presence or absence of calcification.

Axons↗

PubMed2000

Differential somatic CAG repeat instability in variable brain cell lineage in dentatorubral pallidoluysian atrophy (DRPLA): a laser-captured microdissection (LCM)-based analysis.

Employing a laser-captured microdissection (LCM), we have investigated the somatic instability of CAG repeats in the variable brain cell lineage in three patients with dentatorubral pallidoluysian atrophy (DRPLA). LCM enables the isolation of single lineage brain cells for subsequent molecular analysis. We have found that CAG repeat size and the range of CAG repeats in the cerebellar granular cells is smaller than those in cerebellar glial cells. Similarly, those in the cerebral neuronal cells are significantly shorter than those in cerebral glial cells. These data directly indicate that the CAG repeat is relatively more stable in neuronal cells than in glial cells. Furthermore, cerebellar granular cells show significantly smaller main CAG repeat size and CAG repeat range than either Purkinje cells or cerebral neuronal cells, suggesting that somatic instability in the CAG repeat is markedly variable even among the different types of neuronal populations. The cell-specific CAG repeat instability may thus be more complex than has previously been considered. LCM is a powerful tool for elucidating the mechanism of the triplet repeat instability of each cell type.

Adult↗

PubMed2000

Biological features and preoperative evaluation of mediastinal nodal status in non-small cell lung cancer.

BACKGROUND: To examine whether biological features of primary tumor can help preoperative evaluation of mediastinal nodal status in non-small cell lung cancer. METHODS: A total of 450 patients who underwent tumor resection and mediastinal dissection were reviewed. p53 status and proliferative fraction (PI) were evaluated immunohistochemically. RESULTS: The accuracy of preoperative evaluation of mediastinal nodal status with computed tomography (CT) was 72.2%; mediastinal nodal metastases had not been revealed until operation in 59 patients (13.1%) (false-negative), and no metastasis was revealed in 66 patients (14.7%) although mediastinal nodal enlargement had been demonstrated by CT (false-positive). The number of false-negative patients was significantly larger when p53 aberrant expression was positive or when PI was higher. Combined with p53 status and PI, there were 27 false-negatives (24.1%) among patients with aberrant p53 expression and higher PI, whereas only two false-negatives (1.5%) among those with negative p53 expression and lower PI. CONCLUSIONS: Mediastinoscopy may be recommended for tumor showing aberrant p53 expression and higher PI, even when CT demonstrates no mediastinal nodal enlargement.

Aged↗

PubMed2000

Evaluation of tracheo-bronchial wall invasion using transbronchial ultrasonography (TBUS).

BACKGROUND: Whereas accurate evaluation of tumor invasion into the tracheo-bronchial wall is a critical factor in decision-making of therapy for intra-thoracic malignancies, it is sometimes difficult with usual thoracic imaging techniques such as computed tomography. As recent progress in technology of ultrasonography is marked, usefulness of transbronchial ultrasonography (TBUS) in evaluation of tracheo-bronchial wall invasion was assessed. METHODS: Following routine fiberoptic bronchoscopy, an ultrasound probe (20 MHz) covered with a balloon sheath was inserted through the bronchoscope. After air present between the ultrasound probe and the tracheo-bronchial wall was eliminated with filling the balloon with distilled water, TBUS imaging was taken. RESULTS: With TBUS, normal tracheo-bronchial wall was represented as a five-layer structure at the cartilagenous portion and a three-layer structure at the membranous portion. Based on this normal TBUS imaging, tumor extent was judged in 35 patients with intra-thoracic malignancies. Among 25 patients with extra-wall tumor including esophageal cancer (n=15) and metastatic lymph nodes (n=7), tracheo-bronchial wall invasion was clearly demonstrated in nine patients, and no invasion was demonstrated in the other 16 patients. Among ten patients with tumor originating from the tracheo-bronchial wall, tumor extent beyond outer border of the wall was demonstrated with TBUS in five patients. These diagnoses were examined pathologically in 15 patients who underwent the operation, and the accuracy was 93.3%. CONCLUSIONS: It is suggested TBUS can be a useful diagnostic tool in evaluation of tumor invasion to the tracheo-bronchial wall.

Adult↗