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Tatsuo Iijima

Publications and source records attributed to Tatsuo Iijima.

At least 19 recordsLinked to original sources
PubMed2007

OCIA domain containing 2 is highly expressed in adenocarcinoma mixed subtype with bronchioloalveolar carcinoma component and is associated with better prognosis.

Although lung adenocarcinoma is a major cause of cancer death worldwide, details of its molecular carcinogenesis and stepwise progression are still unclear. To characterize the sequential progression from bronchioloalveolar adenocarcinoma of the lung (BAC, in situ carcinoma) to adenocarcinoma mixed subtype with BAC component polymerase chain reaction-based cDNA suppression subtractive hybridization (SSH) was carried out using two representative cases of BAC (non-invasive tumors) and adenocarcinoma mixed subtype with BAC (invasive tumors). Through differential screening, virtual reverse northern hybridization and quantitative real-time reverse-transcription-polymerase chain reaction (qRT-PCR) we selected five genes (TncRNA, OCIAD2, ANXA2, TMED4 and LGALS4) that were expressed at significantly higher levels in invasive adenocarcinoma mixed subtype with BAC than in BAC. After in situ hybridization and qRT-PCR analyses, we confirmed that only the OCIAD2 gene showed significantly higher expression in the tumor cells of invasive adenocarcinoma mixed subtype with BAC than in BAC (P = 0.026). We then carried out in situ hybridization of OCIAD2 in 56 adenocarcinoma mixed subtype with BAC component and assessed the correlation between OCIAD2 expression and clinicopathological features. In contrast to our expectation, the patients with OCIAD2 expression showed a better clinical outcome than those without OCIAD2 expression, and OCIAD2 expression showed an inverse correlation with lymphatic invasion, blood vessel invasion and lymph node metastasis. These results suggest that OCIAD2 begins to express at the progression from in situ to invasive carcinoma, and is associated with the favorable prognosis of adenocarcinoma mixed subtype with BAC component.

Adenocarcinoma↗
PubMed2006

Basaloid squamous cell carcinoma of the maxillary sinus: a report of two cases.

Basaloid squamous cell carcinoma (BSCC) is a highly aggressive neoplasm and a histologically distinctive variant of squamous cell carcinoma. Since the first description by Wain et al. in 1986, only 18 cases with BSCC in the nasal cavity or in the paranasal cavity have been reported in the English literature. We report herein two cases of BSCC of the maxillary sinus. Case 1 was 78-year-old man, who received preoperative radiotherapy and operation. He was alive without disease for 25 months after the operation. Case 2 was a 60-year-old man who received radiotherapy without operation. He died of lung metastasis 6 months after the initial diagnosis. We reviewed the clinical features of BSCC from the literature.

Aged↗
PubMed2006

Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma.

BACKGROUND: The regulation of programmed cell death, or apoptosis, is crucial for normal development and for the maintenance of homeostasis. It has been shown that the novel antiapoptotic protein Bax inhibitor-1 (BI-1) represents a new type of regulator of cell death pathways controlled by Bcl-2 and Bax. METHODS: Surgically resected lung specimens were obtained from 32 patients with peripheral adenocarcinomas, and BI-1 gene expression was examined and compared with expression of the p53, bcl-2 and Bax genes. RESULTS: Fourteen of 32 tumors (43.8%) were positive for BI-1 gene expression by in situ hybridization. BI-1 gene expression in tumor specimens was significantly higher in adenocarcinomas with bronchioloalveolar carcinoma (BAC) and in adenocarcinomas of mixed subtypes with bronchioloalveolar spreading (14 of 17 tumors; 82.4%) than in carcinomas without it spreading. Patients who had BI-1-positive adenocarcinoma showed a relatively favorable prognosis compared with patients who had BI-1-negative adenocarcinoma. Eleven of 32 tumors (34.4%) were positive for the p53 protein, only 1 of 32 tumors (3.1%) was positive for the Bcl-2 protein, and 26 of 32 tumors (81.3%) were positive for the Bax protein. Protein expressions of p53, Bcl-2, and Bax, as detected by immunohistochemistry, were not associated with BI-1 gene expression. CONCLUSIONS: BI-1 gene expression was restricted to tumor cells with lepidic growth and was a prognostic factor for peripheral-type adenocarcinoma. It is believed that BI-1 gene expression is conserved evolutionarily and may act as a key regulator of the apoptotic pathway in BAC.

Adenocarcinoma↗
PubMed2006

Characteristics of loss of heterozygosity in large cell neuroendocrine carcinomas of the lung and small cell lung carcinomas.

Large cell neuroendocrine carcinoma (LCNEC) of the lung is a new entity. Besides morphological characteristics, its molecular biological features have been investigated by many researchers and compared to those of other neuroendocrine carcinomas, small cell lung carcinoma (SCLC) and carcinoid tumor (CT). However, there are few reports that show the significantly different genetic characteristics between them. The purpose of the present paper was to study the frequency of loss of heterozygosity (LOH) at chromosome 3p (3p14.2) in 38 neuroendocrine carcinomas of the lung (13 LCNEC, 11 SCLC and 14 CT) and 10 large cell carcinomas (LCC). The frequencies of LOH at 3p14.2 were 69.2% in LCNEC, 81.8% in SCLC, 50.0% in LCC and 7.14% in CT. Those at 22q13.3 were 30.8% in LCNEC, 72.7% in SCLC, 45.5% in LCC and 7.14% in CT. In particular, the frequency of SCLC with LOH at both 3p14.2 and 22q13.3 (63.6%) was significantly higher than that of LCNEC (15.4%). LCNEC and SCLC had different characteristics of LOH patterns at 3p14.2 and 22q13.3. The combined analysis of the LOH at 3p14.2 and 22q13.3 is thought to be useful for differential diagnosis between LCNEC and SCLC.

Biomarkers, Tumor↗
PubMed2005

Loss of function of p16 gene and prognosis of pulmonary adenocarcinoma.

BACKGROUND: Stepwise progression of peripheral-type lung adenocarcinoma was characterized morphologically and was related to prognosis. Expression of the tumor suppressor gene p16 in pulmonary adenocarcinoma decreased, mainly as a result of aberrant methylation of the CpG islands of the promoter region. METHODS: Aberrant methylation status of the p16 promoter region, the expression of its product, and loss of heterozygosity (LOH) on 9p21 were examined in surgically resected lung specimens from 57 patients (28 males and 29 females) with peripheral-type lung adenocarcinoma measuring </= 2 cm in diameter. RESULTS: Aberrant methylation of the p16 promoter region, negative p16 protein expression, and LOH of the 9p21 region were detected in 40.4%, 50.9%, and 40.4% of tumor samples, respectively. The alterations of the p16 gene were associated with poor prognosis, and in particular the prognosis of patients with aberrant p16 methylation was significantly worse than that of patients without aberrant methylation. These alterations also were associated with morphologic classification into bronchioloalveolar carcinoma (BAC) and non-BAC adenocarcinoma. Both aberrant methylation and LOH of 9p21 were associated with negative protein expression, but the former was correlated more closely with loss of function than was the latter. Cases with both alterations were completely negative for expression of the p16 gene product. CONCLUSIONS: Aberrant methylation of the promoter region of the p16 gene and loss of expression of its product were in accord with the multistep progression of peripheral-type lung adenocarcinoma, and these alterations were associated closely with poor prognosis of the disease.

Adenocarcinoma↗
PubMed2005

Prognostication of small-sized primary pulmonary adenocarcinomas by histopathological and karyometric analysis.

To reveal useful prognostic factors in cases of small-sized pulmonary adenocarcinoma, we conducted a histological and karyometric analysis of 116 small-sized pulmonary adenocarcinomas measuring less than 2 cm in maximum diameter and four specimens of atypical adenomatous hyperplasia (AAH). The small-sized pulmonary adenocarcinomas were classified by using criteria described previously [Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Lung Cancer 1995:75;2844-52]. There were 99 tumors of replacement-type adenocarcinoma, comprising 11 type A, localized bronchioloalveolar adenocarcinoma (LBAC); 6 type B, LBAC with alveolar collapse; and 82 type C, LBAC with foci of fibroblastic proliferation. The 17 remaining tumors were non-replacement-type adenocarcinomas. Among the potential prognostic factors examined, histological subtype was the most closely correlated with 5-year relapse-free survival rate. Furthermore, in patients with type C adenocarcinomas, a small fibroblastic proliferation (F) to fibrosis area (f) ratio (F-f ratio) (<10%) of the tumor and a small maximum nuclear diameter (Max ND; <13.50 microm) of tumor cells were closely associated with an excellent prognosis. Histological subtypes of type A and B adenocarcinomas, a small F-f ratio, and a small Max ND of type C adenocarcinomas were closely correlated with an excellent prognosis in small-sized adenocarcinoma.

Adenocarcinoma↗
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

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↗
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

Association of non-alcoholic steatohepatitis (NASH) with chronic neutrophilic leukemia.

A 54-yr-old female having chronic neutrophilic leukemia (CNL) associated with severe liver injury is presented. Physical examination on admission showed severe jaundice, hepatosplenomegaly, massive ascites, and pretibial edema. Complete blood count showed a hemoglobin level of 9.1 g/dL, platelet count of 25.8 x 10(4)/microL, and white blood cell count of 36.6 x 10(3)/microL with 89.7% neutrophils. Blood chemistry showed hyperbilirubinemia (21.9 mg/dL) with normal transaminase levels. There was no abnormality in serum cholesterol, triglyceride, or glucose levels. Neutrophil alkaline phosphatase activity was significantly elevated. Bone marrow aspiration showed myeloid hyperplasia with normal karyotype. Rearrangement of the bcr/abl was not detected by either polymerase chain reaction or fluorescence in situ hybridization. Human androgen receptor gene assay (HUMARA) of the bone marrow cells showed clonal proliferation of neutrophils. The patient was diagnosed as having CNL. To evaluate the pathogenesis of the liver injury, a needle biopsy was performed, which showed steatohepatitis with infiltration of neutrophils. As the patient had no history of alcohol abuse, a diagnosis of non-alcoholic steatohepatitis (NASH) was made. Assuming that the infiltration of abnormal neutrophils into the liver contributed to the development of NASH, she was treated with cytoreductive chemotherapy (cytosine arabinoside: 100 mg/d, 1-3 doses/wk). With decreases in white blood cell counts, serum bilirubin levels decreased gradually to 1.5 mg/mL. A postchemotherapy liver biopsy specimen showed marked improvement of the fatty degenerative change. To our knowledge, this is the first report describing the development of NASH in a myeloproliferative disorder. We believe that the infiltration of leukemic cells contributed to the development of NASH in this patient.

Antimetabolites, Antineoplastic↗
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↗
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

Early acquisition of gelatinolytic activity in carcinogenesis of the uterine cervix.

Film in situ zymography is a newly developed technique for detecting in situ gelatinolytic activity. Using the film in situ zymography method to stamp preparations, we evaluated the gelatinolytic activity in early stage cervical neoplasia and invasive squamous cell carcinoma. To determine the sensitivity of film in situ zymography for detecting gelatinase expression, slides made from stamps of 50 specimens resected from the uterine cervix, including early invasive carcinoma (FIGO Ia1 and Ib1) and cervical intraepithelial neoplasia (CIN) were examined by film in situ zymography. The specimens were also examined immunohistochemically with regard to mitotic activity and gelatinase expression. Gelatinolytic activity was subdivided into two patterns, the homogeneous pattern and the heterogeneous pattern. The homogeneous pattern consisted of circumscribed areas around atypical cell clusters; these areas were composed of homogenously digested full-thickness collagen, whereas the heterogeneous pattern consisted of spottily digested areas of superficial collagen around atypical cell clusters. All invasive carcinomas (8/8 cases) and carcinoma in situ (14/14 cases) were positive for gelatinolytic activity, and 33.3%(5/15 cases) of the specimens of CIN-1, CIN-2, and severe dysplasia were also positive. All invasive carcinomas and 6 of 14 carcinoma in situ (43%) showed homogenous pattern, and the other positive specimens showed heterogenous pattern. The MIB-1 index was 33.8% in invasive carcinoma, increasing stepwise from dysplasia to carcinoma. Matrix metalloproteinase-2 immunostaining was positive in 4 of 8 cases of invasive carcinoma and generally stained the stromal area around the tumor nest. These results indicated that matrix metalloproteinases are functionally activated even in carcinoma in situ and in cervical intraepithelial neoplasia of the uterine cervix not showing invasive growth histologically. Film in situ zymography can detect with sensitivity the invasive potential of carcinoma in situ and cervical intraepithelial neoplasia. An analysis combining cytological examination and film in situ zymography is a potentially useful tool for estimating invasive activity.

Carcinoma↗
PubMed2003

The implication of background anthracosis in the development and progression of pulmonary adenocarcinoma.

In order to characterize the relationship between background anthracosis and pulmonary adenocarcinogenesis, surgically resected tissues of 66 cases of stage I pulmonary adenocarcinoma, 4 cm or less at their greatest dimension, were examined. These cases were diagnosed based on the classification of small-sized adenocarcinoma of the lung (Noguchi et al., Cancer 75, 1995). Thirteen cases were diagnosed as types A (localized bronchioloalveolar adenocarcinoma, LBAC) and B (LBAC with alveolar collapse), 40 cases as type C (LBAC with a focus of fibroblastic proliferation), 8 as type D (poorly differentiated adenocarcinoma) and 5 as types E (bronchial gland type adenocarcinoma) and F (true papillary adenocarcinoma). The 5-year survival rate of types A and B cases was 100%, while those of type C, type D and types E and F were 52%, 48% and 39%, respectively. Nuclear accumulation of abnormal p53 protein in non-replacement type adenocarcinomas (types D, E and F) was detected more frequently than that in replacement type adenocarcinomas (types A, B and C) (P < 0.05). In each case, black dusty material was extracted from tumorous lesions and non-tumorous regions and blotted onto a nitrocellulose membrane. The anthracotic index (AI) was calculated with a densitometer. AIs of non-tumorous regions in early and replacement type adenocarcinomas (types A and B) were significantly less than in relatively advanced (type C) and poorly differentiated (type D) adenocarcinomas (P < 0.05). These results indicated that adenocarcinoma developing in heavily anthracotic lungs readily progresses to an advanced stage, or that adenocarcinoma with a less favorable prognosis tends to develop in severely anthracotic lungs.

Adenocarcinoma↗