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Masayuki Noguchi

Publications and source records attributed to Masayuki Noguchi.

At least 37 records · Page 2Linked to original sources
PubMed2005

Phenotypic characteristics of mouse lung adenoma induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

The expression profile of adenoma induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice was compared with that of normal lung tissue by suppression subtractive hybridization (SSH). The mRNAs of surfactant-associated protein A (SP-A) and lysozyme showed characteristically higher transcription in the adenoma tissue than in normal lung. High expression of both SP-A and lysozyme in tumor cells was confirmed by in situ hybridization (ISH). In normal lung, alveolar type II pneumocytes were positive for both SP-A and lysozyme, indicating that tumor cells retained the phenotypic characteristics of the murine alveolar type II pneumocytes. Previous studies of human adenocarcinomas have shown that the two proteins are expressed reciprocally; SP-A and lysozyme are differential markers of atypical adenomatous hyperplasia (AAH) and non-goblet cell type adenocarcinoma, and of goblet cell type adenocarcinoma, respectively. Thus, the present results indicate that the phenotype of NNK-induced A/J mouse adenoma differs from that of AAH, which is thought to be a preinvasive lesion of human adenocarcinoma.

Adenoma↗
PubMed2005

A direct measurement of serum amylase levels produced by lung cancer.

The production of amylase by lung cancer has been previously diagnosed pathologically or immunohistochemically, or it has been confirmed by a decrease in serum levels after resection. It is possible to directly probe the continuous production of amylase by collecting samples from the inflow and outflow vessels of lung cancer. We herein describe an intraoperative measurement in which the amylase level in the pulmonary lobar vein was 3 times greater than that in the superior vena cava which was 6 times greater than the normal range. The venous level of amylase returned to a normal range after resection.

Amylases↗
PubMed2005

Diffuse pulmonary hamartoma: a case report.

Pulmonary hamartoma usually occurs as a benign, well-circumscribed single nodule in the lung parenchyma. We report on a unique case of hamartoma that extended along the bronchial tree, formed endobronchial polypoid lesions, and expanded into the lung parenchyma. The patient, a 48-year-old man, was admitted with dyspnea and chest pain. A transbronchial biopsy was performed on a tumorous lesion that was diagnosed histologically as a hamartoma. As this lesion was found to be growing diffusely along the bronchial tree, a left pneumonectomy was performed. Gross examination showed that yellowish soft tissue had surrounded the bronchial tree and extended into the lung parenchyma. Histologically, the lesion contained mainly mature adipose tissue, cartilage, and muscle tissue with a minor component of short spindle cells in a myxomatous matrix. The patient was diagnosed as having diffuse pulmonary hamartoma.

Cell Nucleus↗
PubMed2005

Establishment of an immortalized cell line from a precancerous lesion of lung adenocarcinoma, and genes highly expressed in the early stages of lung adenocarcinoma development.

Atypical adenomatous hyperplasia (AAH) is classified as a precancerous lesion of lung adenocarcinoma. We established an immortalized AAH cell line (PL16T) and a human non-neoplastic bronchial epithelial cell line (PL16B) from the same patient by transfection with the gene for SV40 large T antigen. The expression profile of PL16T was compared with that of PL16B by the suppression subtractive hybridization method. From 704 selectively hybridized clones, we finally selected 25 fragments of mRNA that showed transcription levels more than three times higher in PL16T than in PL16B. Thirteen (52%) and eight (32%) of them encoded tumor-associated calcium signal transducer 2 (TACSTD2) and S100 calcium binding protein A2 (S100A2), respectively. The high transcription of TACSTD2 and S100A2 in PL16T was confirmed by in situ hybridization. In normal lung tissue, both TACSTD2 and S100A2 were expressed at very low levels, but seven and five of 14 AAH were positive for TACSTD2 and S100A2, respectively. The frequency of TACSTD2 positivity was increased in 16 of 22 bronchioloalveolar carcinomas (BAC) and adenocarcinoma with mixed subtype with BAC component (mixed BAC). Positivity for S100A2 occurred in four of 22 BAC and mixed BAC. The abnormal transcription of TACSTD2 and S100A2 are thought to be unique molecular markers of the preinvasive stage of lung adenocarcinoma.

Adenocarcinoma↗
PubMed2005

Reproducibility of the diagnosis of small adenocarcinoma of the lung and usefulness of an educational program for the diagnostic criteria.

Using 32 small adenocarcinomas of the lung including bronchioloalveolar carcinoma (BAC), the reproducibility of diagnosis by the modified diagnostic criteria for small adenocarcinoma (Cancer 75; 2844, 1995) and the effectiveness of an educational program for 27 volunteer general pathologists were examined. The average coincidence rate of the diagnosis before and after the program was 42.4% and 56.6%, respectively. The coincidence rate after the program was significantly higher than that before the program (P < 0.05). In contrast, the average coincidence rate of six lung cancer specialists was 71.4%, and this was significantly higher than that for general pathologists after the program (P < 0.05). When the cases were divided into two groups (in situ adenocarcinoma (BAC and BAC with alveolar collapse) and early invasive adenocarcinoma), the average coincidence rate for the general pathologists after the program increased to 85.3%, which was significantly higher than that before the program (80.3%; P < 0.05). The rate for the specialists was 89%, which was higher than that for the general pathologists after the program but not significantly so. This trial was thought to provide a theoretical background for the histological diagnosis of peripheral type adenocarcinoma of the lung and to justify the existing diagnostic criteria.

Adenocarcinoma↗
PubMed2005

Retroperitoneal extragonadal germ cell tumor in a patient with Klinefelter's syndrome.

A 22-year-old man was diagnosed with retroperitoneal seminoma associated with Klinefelter's syndrome. The tumor was 14 x 12 cm in size and surrounded the superior mesenteric artery. He received induction chemotherapy with bleomycin, etoposide and cisplatin (BEP) followed by salvage chemotherapy with paclitaxel, ifosfamide and cisplatin (TIP). The tumor considerably decreased in size and remains as a poorly defined plaque. At the time of writing, he is being followed closely and is free from progression.

Adult↗
PubMed2004

Anthracotic index and DNA methylation status of sputum contents can be used for identifying the population at risk of lung carcinoma.

BACKGROUND: Sputum cytology for the mass screening of lung carcinoma is a noninvasive, repeatable, and useful examination, but the detection rate is usually < 0.05% and the reliability is not high. METHODS: The anthracotic index (AI) and methylation status of the promoter regions of the p16, adenomatous polyposis coli (APC), and retinoic acid receptor-beta (RARbeta) genes were examined in 356 sputum specimens after routine cytologic examination. RESULTS: The mean AI of specimens from males was significantly higher than that from females. AI increased with increasing age and smoking index. The mean AI of patients with lung carcinoma was significantly higher than that of the nonaffected population. Furthermore, the mean AI of the specimens with or without cancer cells from patients with cancer was significantly higher than that of the nonaffected population. Abnormal methylation of the p16, APC, and RARbeta genes was detected in 21.7%, 28.2%, and 26.9% of specimens from patients with cancer, respectively. These ratios were significantly higher than those of the nonaffected populations (0%, 3.9%, and 7.6%, respectively). The incidences of abnormal methylation of the three genes were not associated with histologic classification, smoking index, gender, age, or occupation. CONCLUSIONS: These findings suggested that the AI and abnormal methylation status were useful for identifying a population at risk of lung carcinoma using mass screening of cytology specimens.

Aged↗
PubMed2004

Inhibition of Akt kinase activity by a peptide spanning the betaA strand of the proto-oncogene TCL1.

Akt plays a central role in the regulation of cellular anti-apoptosis underlying various human neoplastic diseases. We have demonstrated previously that TCL1 (a proto-oncogene underlying human T cell prolymphocytic leukemia) interacts with Akt and functions as an Akt kinase co-activator. With the aim to develop an Akt kinase inhibitor, we hypothesized that a peptide, which spans the Akt-binding site, binds to Akt and modulates Akt kinase activity and its downstream biological responses. Indeed, we demonstrated that a peptide, named "Akt-in" (Akt inhibitor, NH(2)-AVTDHPDRLWAWEKF-COOH, encompassing the betaA strand of human TCL1), interacted with Akt and specifically inhibited its kinase activity. Nuclear magnetic resonance studies suggested that interaction of Akt-in with the pleckstrin homology domain (PH) of Akt caused conformational changes on the variable loop 1 of Akt, the locus mediating phosphoinositide binding. Consistently, interaction of Akt-in with the Akt PH domain prevented phosphoinositide binding and hence inhibited membrane translocation and activation of Akt. Moreover, Akt-in inhibited not only cellular proliferation and anti-apoptosis in vitro but also in vivo tumor growth without any adverse effect. The roles of Akt, which possesses a PH domain, in intracellular signaling were well established. Hence, Akt inhibitors create an attractive target for anticancer therapy. However, no effective inhibitors specific for Akt have been developed. Akt-in, which inhibits association of phosphatidylinositol with Akt, is the first molecule to demonstrate specific Akt kinase inhibition potency. This observation will facilitate the design of specific inhibitors for Akt, a core intracellular survival factor underlying various human neoplastic diseases.

Amino Acid Sequence↗
PubMed2004

Structural basis for the co-activation of protein kinase B by T-cell leukemia-1 (TCL1) family proto-oncoproteins.

Chromosomal translocations leading to overexpression of p14(TCL1) and its homologue p13(MTCP1) are hallmarks of several human T-cell malignancies (1). p14(TCL1)/p13(MTCP1) co-activate protein kinase B (PKB, also named Akt) by binding to its pleckstrin homology (PH) domain, suggesting that p14(TCL1)/p13(MTCP1) induce T-cell leukemia by promoting anti-apoptotic signals via PKB (2, 3). Here we combined fluorescence anisotropy, NMR, and small angle x-ray-scattering measurements to determine the affinities, molecular interfaces, and low resolution structure of the complex formed between PKBbeta-PH and p14(TCL1)/p13(MTCP1). We show that p14(TCL1)/p13(MTCP1) target PKB-PH at a site that has not yet been observed in PH-protein interactions. Located opposite the phospholipid binding pocket and distal from known protein-protein interaction sites on PH domains, the binding of dimeric TCL1 proteins to this site would allow the crosslinking of two PKB molecules at the cellular membrane in a preactivated conformation without disrupting certain PH-ligand interactions. Thus this interaction could serve to strengthen membrane association, promote trans-phosphorylation, hinder deactivation of PKB, and involve PKB in a multi-protein complex, explaining the array of known effects of TCL1. The binding sites on both proteins present attractive drug targets against leukemia caused by TCL1 proteins.

Amino Acid Sequence↗
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↗
PubMed2004

Diagnosis of intra-oral MALT lymphoma using seminested polymerase chain reaction.

Diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma based on histological examination alone is difficult. We report three patients with histologically suspected MALT lymphoma who developed lymphoproliferative lesions of the sublingual gland. Seminested polymerase chain reaction (PCR) analysis applied to formalin-fixed and paraffin-embedded specimens showed clonal rearrangement of immunoglobulin heavy chain genes in two patients and a polyclonal characteristic in one. The clinical findings and Southern blot analysis confirmed the accuracy of the diagnosis. The molecular method described can be applied routinely to processed specimens to obtain helpful information for the diagnosis of low-grade malignancies of lymphoproliferative disorders, such as MALT lymphoma.

Aged↗
PubMed2004

Solution structure and backbone dynamics of the pleckstrin homology domain of the human protein kinase B (PKB/Akt). Interaction with inositol phosphates.

The programmed cell death occurs as part of normal mammalian development. The induction of developmental cell death is a highly regulated process and can be suppressed by a variety of extracellular stimuli. Recently, the ability of trophic factors to promote survival have been attributed, at least in part, to the phosphatidylinositide 3'-OH kinase (PI3K)/Protein Kinase B (PKB, also named Akt) cascade. Several targets of the PI3K/PKB signaling pathway have been identified that may underlie the ability of this regulatory cascade to promote cell survival. PKB possesses a N-terminal Pleckstrin Homology (PH) domain that binds specifically and with high affinity to PtIns(3,4,5)P(3) and PtIns(3,4)P(2), the PI3K second messengers. PKB is then recruited to the plasma membrane by virtue of its interaction with 3'-OH phosphatidylinositides and activated. Recent evidence indicates that PKB is active in various types of human cancer; constitutive PKB signaling activation is believed to promote proliferation and increased cell survival, thereby contributing to cancer progression. Thus, it has been shown that induction of PKB activity is augmented by the TCL1/MTCP1 oncoproteins through a physical association requiring the PKB PH domain. Here we present the three-dimensional solution structure of the PH domain of the human protein PKB (isoform beta). PKBbeta-PH is an electrostatically polarized molecule that adopts the same fold and topology as other PH-domains, consisting of a beta-sandwich of seven strands capped on one top by an alpha-helix. The opposite face presents three variable loops that appear poorly defined in the NMR structure. Measurements of (15)N spin relaxation times and heteronuclear (15)N[(1)H]NOEs showed that this poor definition is due to intrinsic flexibility, involving complex motions on different time scales. Chemical shift mapping studies correctly defined the binding site of Ins(1,3,4,5)P(4) (the head group of PtIns(3,4,5)P(3)), as was previously proposed from a crystallographic study. More interestingly, these studies allowed us to define a putative alternative low-affinity binding site for Ins(1,4,5)P(3). The binding of this sugar to PKBbeta-PH might also involve non-specific association that could explain the stabilization of the protein in solution in the presence of Ins(1,4,5)P(3).

Apoptosis↗
PubMed2004

Phenotypic differences of proliferating fibroblasts in the stroma of lung adenocarcinoma and normal bronchus tissue.

Fibroblasts in tumor tissue are thought to interact with tumor cells directly and/or indirectly and to have important roles in tumor invasion and metastasis. To characterize the phenotype of proliferating fibroblasts in pulmonary adenocarcinoma, we established short-term fibroblast cell lines from both normal bronchus and adenocarcinoma tissues obtained from the same patients and compared the gene expression profiles. Four sets of fibroblast cell lines (eight cell lines in total) were used in the analysis. Total RNA was extracted from each cell line and hybridized with 550 cancer-related RNAs blotted on a cDNA filter array. Five up-regulated genes and 12 down-regulated genes (total of 17 genes) were detected in the fibroblast cell lines from the tumor tissues compared with those from normal bronchus. Using real-time quantitative RT-PCR methods, the expression profile of each gene was examined; five genes, one up-regulated (MLH1) and four down-regulated (Cox1, FGFR4, p120, and Smad3), were confirmed. Furthermore, the protein expression levels of the five genes in the cancerous and normal tissues were examined immunohistochemically, and the up-regulation of MLH1 and the down-regulation of Cox1 in cancerous tissue were confirmed in vivo. These results indicate that the proliferating fibroblasts in pulmonary adenocarcinomas are phenotypically different from fibroblasts in normal bronchus tissues.

Adenocarcinoma↗
PubMed2004

MMP-2 activation and stepwise progression of pulmonary adenocarcinoma: analysis of MMP-2 and MMP-9 with gelatin zymography.

Small pulmonary adenocarcinomas can be classified on the basis of their histological characteristics and prognosis, and when classified as such, the prognosis of replacing-type adenocarcinoma with active fibroblast proliferation is significantly worse than adenocarcinoma without fibroblast proliferation. In order to clarify the biological mechanisms of the key to the morphological changes associated with active fibroblast proliferation, we examined the activities of matrix metalloproteinase (MMP)-2 and MMP-9, which are important enzymes in the stromal invasion by cancers. The active MMP-2 and MMP-9 content of 40 pulmonary adenocarcinomas that were less than 20 mm in diameter was measured by the gelatin zymography method. The quantity of active MMP-2 in the pulmonary adenocarcinomas with active fibroblast proliferation was higher than in the pulmonary adenocarcinomas without proliferation (P < 0.001), but there were no correlations between the histological features and the activation of MMP-9. The presence of active fibroblast proliferation in small pulmonary adenocarcinomas suggests that the cancer cells have acquired the ability to invade through the action of active MMP-2, and this is thought to be one of the reasons for the worse prognosis of pulmonary adenocarcinoma with active fibroblast proliferation.

Adenocarcinoma↗
PubMed2004

[A case of Williams syndrome who exhibited fetishism].

Williams syndrome is a rare congenital disease in which the etiological locus is a micro-deletion in chromosome 7. Here, we describe the case of a 22-year-old male who was diagnosed with Williams syndrome at the age of 3 years. As a child, the patient exhibited patterns of behavior characteristic of this syndrome including hyperactivity, attention deficit, and over-friendliness. He also showed persistent interest in construction vehicles, playgrounds, and gloves. He became interested in gloves after watching a television program in which the heroine fought her enemies while wearing gloves. Watching pornographic movies allowed him to attach strong sexual significance to gloves when he was 19 years old. Since that time, he has assaulted women wearing gloves four times to rob them of the gloves. The current paper discusses both the role of the cognitive profile unique to Williams syndrome and that of environmental factors in the development of fetishism in this case.

Adolescent↗
PubMed2003

Pulmonary adenocarcinoma with massive lymphocyte infiltration: report of three cases.

We report on three cases of pulmonary adenocarcinoma with lymphoid stroma. In these cases the lesions were small pulmonary adenocarcinomas, less than 2 cm in diameter, and histologically diagnosed as poorly or moderately differentiated adenocarcinomas. Histologically, the tumors were characterized by a small number of cancer cells and numerous infiltrating lymphoid cells, especially CD8 positive T-cell lymphocytes. No Epstein-Barr virus (EBV) genomes were demonstrated by in situ hybridization in the tumor cells of any of the tumors. Lobectomy and regional lymph node dissection were performed and intrapulmonary and mediastinal lymph node metastases were demonstrated in one of these cases (pT4N0M0, pT1N2M0 and pT1N0M0). Two patients are alive and the other died of pneumonia 26 months after the operation. None of the patients experienced recurrence of carcinoma. This unique type of adenocarcinoma characterized by massive lymphocyte infiltration could be referred to as "pulmonary adenocarcinoma with lymphoid stroma".

Adenocarcinoma↗
PubMed2003

Volumetric and histologic responses to radiotherapy or radiochemotherapy of metastatic cervical lymph nodes of oral squamous cell carcinoma.

PURPOSE: The relationship between the volumetric and histologic responses of metastatic cervical nodes to radiotherapy or chemotherapy in the oral and maxillofacial region is unclear. In this study, we evaluated the correlation between the initial volume and regression rate of metastatic nodes with their histologic response to preoperative radiotherapy or radiochemotherapy. PATIENTS AND METHODS: The volume of 54 metastatic nodes in 32 patients with squamous cell carcinoma in the oral and maxillofacial region was measured by ultrasonography before and after preoperative therapy, and the rate of the volume change was calculated. All surgically removed nodes were histologically classified as poor, good, or complete response according to their histologic features. RESULTS: There was no significant difference in initial volume among the 3 response groups. Good and complete response nodes showed a significant increase in regression rate compared with poor response nodes. All 11 nodes showing no regression were poor response nodes, and 7 with a regression rate of more than 90% were good or complete response nodes. The remaining 36 nodes (regression rate, 0% to 90%) represented all 3 types of histologic response. Of these, 7 of 9 complete response nodes were found in 5 patients who received combination chemotherapy consisting of 5-fluorouracil, leucovorin, and cisplatin. CONCLUSIONS: The initial nodal volume before therapy is not a good indicator for the response to radiotherapy and/or chemotherapy. A regression rate of more than 90% may be a useful predictor of the effectiveness of preoperative treatments, but it was difficult to define the cutoff values in regression rates for differentiating types of histologic response.

Adult↗