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Shigeki Morita,
Akihiko Yoshida, Akiteru Goto,
Satoshi Ota,
Koji Tsuta,
Karin Yokozawa,
Hisao Asamura,
Jun Nakajima,
Daiya Takai,
Masaya Mori,
Teruaki Oka,
Junichi Tamaru,
Shinji Itoyama,
Koh Furuta,
Masashi Fukayama,
Hitoshi Tsuda
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ABSTRACT: Low-grade lung adenocarcinoma of fetal lung type, which is well characterized by its unique clinicopathologic and molecular features, is recognized as a distinct variant of lung cancer. In contrast, high-grade lung adenocarcinoma with fetal lung-like morphology (HG-LAFM) has not been studied widely. To characterize this subset better, we analyzed 17 high-grade adenocarcinomas with at least focal component resembling a developing epithelium in the pseudoglandular phase of the fetal lung. These rare (ca. 0.4%) carcinomas occurred predominantly in elderly men with a heavy smoking history, who showed elevated serum α-fetoprotein in 4 of 5 cases tested. Histologic examination revealed a fetal lung-like component as a focal finding accounting for 5% to 60% of the total tumor volume. It was invariably admixed with tissues having a morphology not resembling that of a fetal lung. A coexisting non-fetal lung-like element was quite heterogenous in appearance, showing various growth patterns. However, clear-cell (88%), hepatoid (29%), and large cell neuroendocrine carcinoma (24%) histology seemed overrepresented. HG-LAFM was characterized immunohistochemically by frequent expression of α-fetoprotein (41%), glypican-3 (88%), SALL-4 (59%), neuroendocrine markers (82%), CDX-2 (35%), and p53 (65%). HG-LAFM was molecularly heterogenous in that EGFR or KRAS mutation was observed in 22% of cases tested for both. Our data indicate that HG-LAFMs might form a coherent subgroup of lung adenocarcinomas. However, the uniformly focal nature of the fetal lung-like element, widely diverse coexisting non-fetal lung-like histology, and inhomogenous molecular profiles lead us to believe that HG-LAFM is best regarded as a morphologic pattern showing characteristic association with several clinicopathologic parameters rather than a specific tumor entity.
The American journal of surgical pathology 04/2013; · 4.06 Impact Factor
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Kumi Shoji,
Takashi Murayama,
Imari Mimura,
Takehiko Wada,
Haruki Kume, Akiteru Goto,
Takamoto Ohse,
Tetsuhiro Tanaka,
Reiko Inagi,
Frans A van der Hoorn,
Ichiro Manabe,
Yukio Homma,
Masashi Fukayama,
Takashi Sakurai,
Takeshi Hasegawa,
Hiroyuki Aburatani,
Tatsuhiko Kodama,
Masaomi Nangaku
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ABSTRACT: Hypoxia plays a crucial role in many pathophysiological conditions, including cancer biology, and hypoxia-inducible factor (HIF) regulates transcriptional responses under hypoxia. To elucidate the cellular responses to hypoxia, we performed chromatin immunoprecipitation with deep sequencing in combination with microarray analysis and identified HIF-1 targets. We focused on one of the novel targets, sperm-associated antigen 4 (SPAG4), whose function was unknown. SPAG4, an HIF-1-specific target, is up-regulated in various cultured cells under hypoxia. Examination of SPAG4 expression using a tissue microarray consisting of 190 human renal cell carcinoma (RCC) samples revealed that SPAG4 is an independent prognostic factor of cancer-specific mortality. Live-cell imaging revealed localization of SPAG4 at the intercellular bridge in telophase. We also studied cells in which SPAG4 was knocked down. Hypoxia enhances tetraploidy, which disturbs cell proliferation, and knockdown of SPAG4 increased tetraploid formation and decreased cell proliferation under both normoxic and hypoxic conditions. Studies using deletion mutants of SPAG4 also suggested the involvement of SPAG4 in cytokinesis. Microarray analysis confirmed dysregulation of cytokinesis-related genes by knockdown of SPAG4. In conclusion, SPAG4 is an independent prognostic factor in RCC and plays a crucial role in cytokinesis to defend against hypoxia-induced tetraploid formation. This defensive mechanism may promote survival of cancer cells under hypoxic conditions, thus leading to poor prognosis.
American Journal Of Pathology 04/2013; · 4.89 Impact Factor
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ABSTRACT: Merkel cell polyomavirus (MCPyV) has recently been identified in Merkel cell carcinoma (MCC), an aggressive cancer that occurs in sun-exposed skin. Conventional technologies, such as polymerase chain reaction (PCR) and immunohistochemistry, have produced conflicting results for MCPyV infections in non-MCC tumors. Therefore, we performed quantitative analyses of the MCPyV copy number in various skin tumor tissues, including MCC (n = 9) and other sun exposure-related skin tumors (basal cell carcinoma [BCC, n = 45], actinic keratosis [AK, n = 52], Bowen's disease [n = 34], seborrheic keratosis [n = 5], primary cutaneous anaplastic large-cell lymphoma [n = 5], malignant melanoma [n = 5], and melanocytic nevus [n = 6]). In a conventional PCR analysis, MCPyV DNA was detected in MCC (9 cases; 100%), BCC (1 case; 2%), and AK (3 cases; 6%). We then used digital PCR technology to estimate the absolute viral copy number per haploid human genome in these tissues. The viral copy number per haploid genome was estimated to be around 1 in most MCC tissues, and there were marked differences between the MCC (0.119-42.8) and AK (0.02-0.07) groups. PCR-positive BCC tissue showed a similar viral load as MCC tissue (0.662). Immunohistochemistry with a monoclonal antibody against the MCPyV T antigen (CM2B4) demonstrated positive nuclear localization in most of the high-viral-load tumor groups (8 of 9 MCC and 1 BCC), but not in the low-viral-load or PCR-negative tumor groups. These results demonstrated that MCPyV infection is possibly involved in a minority of sun-exposed skin tumors, including BCC and AK, and that these tumors display different modes of infection.
PLoS ONE 01/2012; 7(6):e39954. · 4.09 Impact Factor
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ABSTRACT: Lymph node (LN) structure is remodeled during immune responses, a process which is considered to play an important role in the regulation of immune function. To date, little attention has been paid to the remodeling of the medullary region, despite its proposed role as a niche for antibody-producing plasma cells. Here, we show that B cells mediate medullary remodeling of antigen-draining LNs during inflammation. This process occurs with kinetics similar to changes in plasma cell number and is accompanied by stromal renetworking which manifests as the segregation of B cells and plasma cells. Medullary remodeling depends on signaling via the lymphotoxin-β receptor and the presence of B cells but occurs independently of T-dependent humoral responses or other immune cell subsets including T cells, monocytes and neutrophils. Moreover, reconstitution of non-cognate polyclonal B cells in B cell-deficient mice restores not only the medullary remodeling but also the antibody response by separately transferred cognate B cells, suggesting that non-cognate B cells contribute to antibody responses through medullary remodeling. We propose that non-cognate B cells mediate the expansion of the plasma cell niche in LN through medullary remodeling, thereby regulating the size of the LN plasma cell pool.
International Immunology 01/2012; 24(1):17-27. · 3.41 Impact Factor
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Kentaro Kitano,
Kousuke Watanabe,
Noriko Emoto,
Hidenori Kage,
Emi Hamano,
Takahide Nagase,
Atsushi Sano,
Tomohiro Murakawa,
Jun Nakajima, Akiteru Goto,
Masashi Fukayama,
Yutaka Yatomi,
Nobuya Ohishi,
Daiya Takai
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ABSTRACT: We investigated whether the CpG island methylation of certain microRNAs was associated with the clinicopathological features and the prognosis of non-small-cell lung cancer. The methylation of mir-152, -9-3, -124-1, -124-2, and -124-3 was analyzed in 96 non-small-cell lung cancer specimens using a combined bisulfite restriction analysis. The median observation period was 49.5 months. The methylation of mir-9-3, -124-2, and -124-3 was individually associated with an advanced T factor independent of age, sex, and smoking habit. Moreover, the methylation of multiple microRNA loci was associated with a poorer progression-free survival in a univariate analysis. Our result enlightens the accumulation of aberrant DNA methylation which occurs in concordance with the tumor progression. (Cancer Sci 2011; 102: 2126–2131)
Cancer Science 10/2011; 102(12):2126 - 2131. · 3.33 Impact Factor
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ABSTRACT: Zygomycosis is a life-threatening fungal infection, and its successful treatment requires early diagnosis. To establish radiologic and clinical criteria for early diagnosis, we reviewed 3 post-mortem cases with zygomycosis secondary to hematological diseases. In all cases, an irregular dilatation of pulmonary veins on computed tomography suggested venous invasion by fungal hyphae, which was confirmed at autopsy. In addition, serum samples tested negative for the Aspergillus galactomannan antigen in all cases. These distinguishing radiologic and clinical features may contribute to an earlier diagnosis; more radical treatments, such as amphotericin-B or pulmonary resection; and a more successful outcome for patients with zygomycosis.
Journal of thoracic imaging 09/2011; 27(4):W97-9. · 1.42 Impact Factor
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Akiteru Goto,
Chih-Ping Li,
Satoshi Ota,
Toshiro Niki,
Yuji Ohtsuki,
Shinichi Kitajima,
Suguru Yonezawa,
Chihaya Koriyama,
Suminori Akiba,
Hisataka Uchima,
Yueh-Min Lin,
Kun-Tu Yeh,
Jae-Soo Koh,
Chul-Woo Kim,
Kun-Yong Kwon,
Min En Nga,
Masashi Fukayama
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ABSTRACT: The role of human papillomavirus (HPV) in the development of lung and esophageal cancer remains inconclusive, which is in contrast to the established role HPV plays in the development of uterine cervical cancer. One of the reasons for this is the difference among reported HPV infection rates in these cancers. An analysis of 485 lung and esophageal cancers (176 lung squamous cell carcinoma, 128 lung adenocarcinoma, 181 esophageal carcinoma) in eight institutions in Asia (Tokyo, Kochi, Kagoshima, and Okinawa, Japan; Seoul and Daegu, Korea; Changhua, Republic of China (Taiwan); Singapore, Singapore) was carried out in order to clarify infection rates with HPV. Samples were examined in one laboratory of the Department of Pathology, the University of Tokyo, Japan in order to avoid inter-laboratory variation using a combination of polymerase chain reaction and in situ hybridization (ISH). HPV was found in 6.3%, 7%, and 9.4% of patients with lung squamous cell carcinoma, lung adenocarcinoma, and esophageal cancer, respectively. Among the geographic areas surveyed, Kagoshima exhibited a significantly higher prevalence of HPV infection in cases of esophageal carcinoma (24.1%). There was no geographical difference in the infection rates of HPV in lung carcinomas. Subtype-specific ISH was also performed, which identified the high-risk HPV types 16/18 in the majority (75.7%) of the patients with lung and esophageal cancer positive for HPV.
Journal of Medical Virology 08/2011; 83(8):1383-90. · 2.82 Impact Factor
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Kousuke Watanabe,
Noriko Emoto,
Emi Hamano,
Mitsuhiro Sunohara,
Masanori Kawakami,
Hidenori Kage,
Kentaro Kitano,
Jun Nakajima, Akiteru Goto,
Masashi Fukayama,
Takahide Nagase,
Yutaka Yatomi,
Nobuya Ohishi,
Daiya Takai
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ABSTRACT: MicroRNA (miRNA) expression is frequently altered in human cancers. To search for epigenetically silenced miRNAs in non-small-cell lung cancer (NSCLC), we mapped human miRNAs on autosomal chromosomes and selected 55 miRNAs in silico. We treated six NSCLC cell lines with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) and determined the expressions of the 55 miRNAs. Fourteen miRNAs were decreased in the cancer cell lines and were induced after 5-aza-CdR treatment. After a detailed DNA methylation analysis, we found that mir-34b and mir-126 were silenced by DNA methylation. Mir-34b was silenced by the DNA methylation of its own promoter, whereas mir-126 was silenced by the DNA methylation of its host gene, EGFL7. A chromatin immunoprecipitation assay revealed H3K9me2 and H3K9me3 in mir-34b and EGFL7, and H3K27me3 in EGFL7. The overexpression of mir-34b and mir-126 decreased the expression of c-Met and Crk, respectively. The 5-aza-CdR treatment of lung cancer cell line resulted in increased mir-34b expression and decreased c-Met protein. We next analyzed the DNA methylation status of these miRNAs using 99 primary NSCLCs. Mir-34b and mir-126 were methylated in 41 and 7% of all the cases, respectively. The DNA methylation of mir-34b was not associated with c-Met expression determined by immunohistochemistry, but both mir-34b methylation (p = 0.007) and c-Met expression (p = 0.005) were significantly associated with lymphatic invasion in a multivariate analysis. The DNA methylation of mir-34b can be used as a biomarker for an invasive phenotype of lung cancer.
International Journal of Cancer 06/2011; 130(11):2580-90. · 5.44 Impact Factor
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Masayoshi Nagata,
Mika Sakurai-Yageta,
Daisuke Yamada, Akiteru Goto,
Akihiko Ito,
Hiroshi Fukuhara,
Haruki Kume,
Teppei Morikawa,
Masashi Fukayama,
Yukio Homma,
Yoshinori Murakami
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ABSTRACT: Renal clear cell carcinoma (RCCC) is the most frequent subpopulation of renal cell carcinoma and is derived from the proximal uriniferous tubules. We have previously reported that an actin-binding protein, 4.1B/DAL-1, is expressed in renal proximal tubules, whereas it is inactivated in 45% of RCCC by promoter methylation. In the lung and several epithelial tissues, 4.1B is shown to associate with a tumor suppressor protein, CADM1, belonging to the immunoglobulin-superfamily cell adhesion molecules. Here, we demonstrate by immunohistochemistry that another member of the CADM-family protein, CADM4, as well as 4.1B is expressed specifically in human proximal tubules, while CADM1 and 4.1N, another member of the 4.1 proteins, are expressed in the distal tubules. Immunoprecipitation analysis coupled with Western blotting revealed that CADM4 associated with 4.1B, while CADM1 associated with 4.1N in the lysate from normal human kidney, implicating that a cascade of CADM4 and 4.1B plays an important role in normal cell adhesion of the proximal tubules. On the other hand, CADM4 expression was lost or markedly reduced in 7 of 10 (70%) RCC cell lines and 28 of 40 (70%) surgically resected RCCC, including 10 of 16 (63%) tumors with T1a. CADM4 expression was more preferentially lost in RCCC with vascular infiltration (p = 0.04), suggesting that loss of CADM4 is involved in tumor invasion. Finally, introduction of CADM4 into an RCC cell line, 786-O, dramatically suppressed tumor formation in nude mice. These findings suggest that CADM4 is a novel tumor suppressor candidate in RCCC acting with its binding partner 4.1B.
International Journal of Cancer 05/2011; 130(6):1329-37. · 5.44 Impact Factor
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ABSTRACT: Multicystic mesothelioma is a well recognized but rare serosal tumor which mainly arises from the peritoneum in women and is considered as a benign lesion. This is the second case report of pericardial multicystic mesothelioma, which took a fatal clinical course. A 63-year-old man presented with pitting edema, shortness of breath, and hoarseness. Radiological investigations revealed solid and cystic tumor of the pericardium which was continuously extending into the mediastinum and the liver. Pericardial biopsy showed micro-cystic tumor lined by single layer of mesothelial cells without atypia, and the diagnosis was multicystic mesothelioma. Curative surgery could not be performed, and three years and four months later, the patient died because of the direct compression of the heart by the tumor. At autopsy, the tumor was found to be directly extending into the right pleural cavity and the right lung, besides the mediastinum and the liver. Neither malignant transformation nor metastatic tumor was identified.
Pathology International 05/2011; 61(5):319-21. · 1.62 Impact Factor
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Yuka Takahashi,
Miwako Iwai,
Taketo Kawai,
Atsushi Arakawa,
Takeshi Ito,
Mika Sakurai-Yageta,
Akihiko Ito, Akiteru Goto,
Mitsue Saito,
Fujio Kasumi,
Yoshinori Murakami
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ABSTRACT: The tumor suppressor genes CADM1/TSLC1 and DAL-1/4.1B are frequently inactivated by promoter methylation in non-small cell lung cancer. The proteins they encode, CADM1 and 4.1B, form a complex in human epithelial cells and are involved in cell-cell adhesion.
Expression of CADM1 and 4.1B proteins was examined by immunohistochemistry in 67 primary breast cancer and adjacent noncancerous tissues. CADM1 and 4.1B messenger RNA (mRNA) was detected by reverse-transcription polymerase chain reaction (RT-PCR). The methylation status of the CADM1 and 4.1B promoters was determined quantitatively by bisulfite treatment followed by pyrosequencing.
CADM1 and 4.1B protein signals were detected along the cell membrane in normal mammary epithelia. By contrast, 47 (70%) and 49 (73%) of 67 primary breast cancers showed aberrant CADM1 and 4.1B staining, respectively. Aberrant CADM1 staining was more frequently observed in pT2 and pT3 tumors and for stages II and III (P = 0.045 and P = 0.020, respectively), while aberrant 4.1B staining was more often observed in tumors with lymph node metastasis, for pT2 and pT3 tumors, and for stages II and III (P = 0.0058, P = 0.0098, and P = 0.0007, respectively). Furthermore, aberrant CADM1 and 4.1B expression was preferentially observed in invasive relative to noninvasive lesions from the same specimen (P = 0.036 and P = 0.0009, respectively). Finally, hypermethylation of CADM1 and 4.1B genes was detected in 46% and 42% of primary breast cancers, respectively.
Our findings suggest that aberrant CADM1 and 4.1B expression is involved in progression of breast cancer, especially in invasion into the stroma and metastasis.
Breast Cancer 04/2011; 19(3):242-52. · 1.36 Impact Factor
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ABSTRACT: A 52-year-old man received a left pneumonectomy for pulmonary squamous cell carcinoma without signs of recurrence after surgery. At age 68 years, a capsulated huge mass developed in the left pleural cavity, which was diagnosed as chronic expanding hematoma. Two years and 8 months after detection, the lesion began to invade the chest wall, and 10 months later, the patient died of active bleeding and direct compression of the heart by the lesion. At autopsy, the left thoracic cavity was occupied by a cystic and hemorrhagic mass infiltrating into the surrounding structures. In addition, scattered tumorous nodules were observed in the right lung. Histologically, angiosarcoma with irregularly anastomosing vessels lined with atypical endothelial cells was noted in the chronic expanding hematoma. The final diagnosis was pleural cavity angiosarcoma arising in chronic expanding hematoma and its metastases to the right lung.
Human pathology 04/2011; 42(10):1576-9. · 3.03 Impact Factor
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ABSTRACT: We report an extremely rare case of small intestinal cancer metastasized to the urinary bladder, presenting a urologic symptom. A 41-year-old man first presented with nausea, vomiting and abdominal pain. Based on the clinical diagnosis of jejunal cancer, he underwent a partial resection of the jejunum with lymph node dissection. The pathological diagnosis was moderately differentiated adenocarcinoma of the jejunum, pT4N0. Seventeen months after surgery, he presented with a gross hematuria. Computed tomographic scan showed wall thickening of the posterior wall of the urinary bladder. No tumor was found in other organs or lymph nodes. Based on histological and immunohistochemical analysis, the diagnosis of urinary bladder metastasis from jejunal adenocarcinoma was made. This is the first report of urinary bladder metastasis from small intestinal cancer. Although very rare, the possibility of metastatic small intestinal cancer should be considered in differential diagnosis in patients with adenocarcinoma involving the urinary bladder.
Case Reports in Oncology 01/2010; 3(3):334-338.
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ABSTRACT: Imaging findings of low-grade fibromyxoid sarcoma (LGFMS) are reported in three thoracic cases, two in the mediastinum and one in the chest wall. The multinodular intralesional structure with strongly enhancing components in the periphery and components with abrupt transition may be suggestive of LGFMS. Strongly enhancing areas correlated with the hypercellular zone, and weakly enhancing areas correlated with the myxoid zone with less cellularity, or hyalinization. No differences in vasculature densities between the myxoid and fibrous zones were demonstrated.
Japanese journal of radiology 11/2009; 27(9):375-80. · 0.65 Impact Factor
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ABSTRACT: We report here the presence of subepithelial myofibroblasts in pure bronchioloalveolar carcinoma and a subset of invasive lung adenocarcinoma. The subepithelial myofibroblasts we describe were observed in a peculiar location beneath the cancer cells in the alveolar septa. Immunohistochemically, they were positive for alpha-smooth muscle actin and calponin, but negative for desmin and h-caldesmon. To gain insight into their biological significance, we examined 116 surgically resected lung adenocarcinomas. The resected tumors included 13 bronchioloalveolar carcinomas, 20 mixed type adenocarcinomas with bronchioloalveolar carcinoma components, 57 papillary adenocarcinomas, 22 solid adenocarcinomas with mucin, and 4 acinar adenocarcinomas. All specimens were immunostained for alpha-smooth muscle actin to visualize the myofibroblasts. In all of the pure bronchioloalveolar carcinomas observed, the subepithelial myofibroblasts were completely preserved adjacent to the cancer cells. In mixed adenocarcinomas with bronchioloalveolar carcinoma components, subepithelial myofibroblasts were present in the bronchioloalveolar carcinoma components, but scanty in the invasive areas, where stromal myofibroblasts emerged between the cancer cell nests. Subepithelial myofibroblasts were retained, however, in the invasive areas of a subset of invasive adenocarcinomas. Survival analysis showed that the retention of subepithelial myofibroblasts in these invasive tumors was associated with low rates of lymphatic and vascular invasion, a low rate of lymph node involvement, and an excellent patient survival. These results suggest that subepithelial myofibroblasts increase in bronchioloalveolar carcinomas, but are gradually replaced by typical stromal myofibroblasts during progression into invasive cancer. A subset of invasive adenocarcinomas retains subepithelial myofibroblasts. Analysis of subepithelial myofibroblasts may be helpful in identifying a subset of lung adenocarcinoma with excellent prognosis.
Modern Pathology 04/2009; 22(6):776-85. · 4.79 Impact Factor
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ABSTRACT: The gene for the human orthologue of mouse epiglycanin, a mucin expressed on mammary carcinoma TA3-Ha cells but not TA3-St cells, was identified by homology search to a mouse epiglycanin cDNA fragment identified by representational difference analysis between TA3-Ha and TA3-St cells. The open reading frame of this gene was cloned from human cervical carcinoma ME-180 cells. It consists of a mucin domain with 28 nonidentical tandem repeats of 45 nucleotides each corresponding to a threonine/serine-rich peptide, a stem domain, a transmembrane domain, and a cytoplasmic tail. The cloned cDNA with a FLAG sequence was expressed in K562 cells. A combination of immunoprecipitation with a polyclonal antibody specific for the cytoplasmic tail and Western blotting analysis with an anti-FLAG antibody and lectins revealed a mucin-like component as the gene product. Analysis by the use of tissue cDNA libraries indicated that the gene is expressed in lung, large intestine, thymus, and testis among 16 normal tissues tested. The polyclonal antibody specific for a synthetic peptide from the cytoplasmic tail, when tested for its reactivity with normal lung tissues, reacted with epithelia of bronchi and bronchioli but not with alveoli. All of 24 lung adenocarcinomas specimens tested were reactive with the antibody, whereas reactivity was observed with only 2 out of 24 squamous and none out of 24 small cell lung carcinomas. This is a novel transmembrane mucin and designated as MUC21.
Glycobiology 02/2008; 18(1):74-83. · 3.58 Impact Factor
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ABSTRACT: The incidence of lung cancer (LC) is markedly increased among patients with usual interstitial pneumonia (UIP), and tobacco smoking is its superimposed risk factor. AKR1B10 (aldo-keto reductase 1B10) is frequently overexpressed in pulmonary squamous cell carcinoma and adenocarcinoma in smokers. To investigate the role of AKR1B10 in the pulmonary carcinogenesis in UIP with correlation to tobacco smoking, we examined 13 UIP cases with LC, 13 UIP cases without LC, and 30 cases of non-UIP LC using AKR1B10 immunohistochemistry. AKR1B10 immunoreactivity was confined to squamous metaplasia in honeycomb lesions of UIP and neoplastic cells of LC. Squamous metaplastic foci showed AKR1B10 immunoreactivity more frequently in UIP with LC (24/36 foci, 67%) than in UIP without LC (16/44 foci, 37%) (P<0.01). AKR1B10 expression in UIP was also more frequent in squamous metaplastic foci in smokers (38/67 foci, 57%) than in non-smokers (2/13 foci, 15%) (P<0.01). AKR1B10 expression was frequently observed in both UIP-associated LC (10/13 foci, 77%) and non-UIP LC (18/30 foci, 60%). Ki-67 labeling index was significantly higher in AKR1B10-positive squamous metaplasia of UIP than in AKR1B10-negative squamous metaplasia of UIP. Our results demonstrate that AKR1B10 is involved in the development of LC in UIP in association with smoking. AKR1B10 might be useful as a new marker for identification of high LC risk patients in UIP.
Pathology - Research and Practice 01/2008; 204(5):295-304. · 1.21 Impact Factor
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ABSTRACT: The progression of olfactory neuroblastoma showed a biphasic pattern. As well as Hyams' histopathological grading and neck metastasis at presentation, early phase recurrence should be regarded as an important prognosticator. A high local failure rate suggests that craniofacial resection followed by postoperative radiotherapy should still be the standard treatment for olfactory neuroblastoma.
The aim of this study was to evaluate factors associated with survival and local control of olfactory neuroblastoma in the long run and to estimate treatment strategies.
Twelve patients (seven men and five women) who had undergone initial curative treatment for olfactory neuroblastoma were retrospectively analyzed.
Cause-specific 10-year survival was 64.8%, while disease-free 10-year survival remained 28.6%. Local failure was found in half of the patients. All of the three patients who did not receive radiotherapy developed local failure. A biphasic pattern of recurrence was observed. The early phase recurrence group showed a significantly poorer survival than the late phase recurrence group. Hyams' histopathological grading and neck metastasis at presentation were also correlated with survival.
Acta oto-laryngologica. Supplementum 01/2008;
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ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is the most common lung disease predisposing lung cancer. To clarify the early phase of epithelial abnormalities in IPF, we used an in vitro squamous metaplasia model, transforming growth factor beta1 (TGF beta1)-treated airway epithelial cells (BEAS-2B). The model repeated the expression of squamous epithelial character, such as involucrin, and keratin 6 and 14. DNA microarray analysis disclosed a unique expression signature in TGF beta1-treated airway epithelial cells, 20 specifically up-regulated genes including p63, jagged 1 (jag1) and the genes of structure proteins. Western blotting and RT-PCR analysis revealed that DeltaNp63alpha was the dominant isoform of p63 in our experimental model. Immunohistochemical analysis demonstrated the expression of p63 and jag1 in lung tissues of IPF. Inhibition of p63 with siRNA caused the down-regulation of jag1 expression, but not of involucrin, or keratin 6 and 14. Interestingly, the up-regulation of p63 was totally suppressed by N-acetyl-l-cysteine (NAC), but not by dexamethasone or pirfenidone. Thus, the p63-jag1 pathway may be up-regulated at an early phase of epithelial abnormalities in IPF, which can be overcome by NAC even in the TGF beta1-rich milieu.
Experimental and Molecular Pathology 01/2008; 83(3):367-76. · 2.42 Impact Factor
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ABSTRACT: In this study we explored the mechanisms of constitutive activation of c-Met in lung adenocarcinoma cell lines. First, we examined levels of c-Met and phospho-c-Met (Y1234/Y1235) in a panel of lung adenocarcinoma cell lines by Western blot analysis. c-Met expression was found in 12 of 14 cell lines and an overall correlation between the expressions of c-Met and phospho-c-Met was noted. c-Met was constitutively activated particularly at high levels in five cell lines (PC3, LC-2/ad, L27, H1648, and H2009). c-Met amplification was identified in L27 and H1648 by single nucleotide polymorphism array analysis, but no mutations were identified in the Sema domain or in any part of the cytoplasmic domain of c-Met. Experiments with neutralizing anti-hepatocyte growth factor (HGF) antibody, scatter assay using Madin–Darby canine kidney cells, and Western blotting on conditioned media of the cell lines revealed that the constitutive phosphorylation of c-Met was largely ligand-independent. The inhibition of cell–matrix adhesion induced the dephosphorylation of c-Met in the five cell lines tested. This was accompanied by downregulation of c-Met in three of the five cell lines. In contrast, the inhibition of cell–cell adhesion by neutralizing E-cadherin antibody had a minimal effect on the expression and phosphorylation of c-Met. These results reveal three features of the constitutive activation of c-Met in our panel of lung adenocarcinoma cell lines: (i) it correlates with c-Met overexpression, either with or without gene amplification; (ii) it is largely ligand-independent; and (iii) it depends on cell–matrix adhesion. (Cancer Sci 2008; 99: 14–22)
Cancer Science 10/2007; 99(1):14 - 22. · 3.33 Impact Factor
