Biomedical subjects

Naoki Yamanaka

Publications and source records attributed to Naoki Yamanaka.

At least 19 recordsLinked to original sources

PubMed2007

Hedgehog signaling pathway is a possible therapeutic target for gastric cancer.

BACKGROUND AND OBJECTIVES: It has been shown that the hedgehog (Hh) signaling pathway is activated in gastric cancer. To investigate the viability of the Hh pathway as a therapeutic target, we analyzed activation of the Hh pathway in gastric cancer. METHODS: Surgically resected gastric carcinoma specimens and lymph nodes were analyzed immunohistochemically. We used the percentage of cancer cells with nuclear translocation of Gli1 as a marker of Hh pathway activation. RESULTS: Nuclear localization of Gli1 was higher in 28 undifferentiated-type tumors than in 30 differentiated-type tumors. Eighteen of the fifty-eight cancer specimens consisted of a mixture of a histologically predominant part and a small area with different histology. In these 18 tumors, the percentage of cells showing nuclear staining of Gli1 was higher in the undifferentiated-type part than in the differentiated-type part. Nuclear staining of Gli1 in primary tumors was positively correlated with lymph node metastasis. The Gli1 nuclear staining percentage of metastatic lymph nodes correlated closely with that of each primary carcinoma. Cyclopamine, a Hh pathway inhibitor, suppressed the growth of gastric cancer cells in vitro. CONCLUSIONS: The Hh pathway may be a useful therapeutic target for such as undifferentiated-type gastric cancer with lymph node metastasis.

Adenocarcinoma↗

PubMed2006

Nuclear factor-kappaB contributes to hedgehog signaling pathway activation through sonic hedgehog induction in pancreatic cancer.

The hedgehog (Hh) signaling pathway, which functions as an organizer in embryonic development, is implicated in the development of various tumors. In pancreatic cancer, pathway activation is reported to result from aberrant expression of the ligand, sonic Hh (Shh). However, the details of the mechanisms regulating Shh expression are not yet known. We hypothesized that nuclear factor-kappaB (NF-kappaB), a hallmark transcription factor in inflammatory responses, contributes to the overexpression of Shh in pancreatic cancer. In the present study, we found a close positive correlation between NF-kappaB p65 and Shh expression in surgically resected pancreas specimens, including specimens of chronic pancreatitis and pancreatic adenocarcinoma. We showed that blockade of NF-kappaB suppressed constitutive expression of Shh mRNA in pancreatic cancer cells. Further activation of NF-kappaB by inflammatory stimuli, including interleukin-1beta, tumor necrosis factor-alpha, and lipopolysaccharide, induced overexpression of Shh, resulting in activation of the Hh pathway. Overexpression of Shh induced by these stimuli was also suppressed by blockade of NF-kappaB. NF-kappaB-induced Shh expression actually activated the Hh pathway in a ligand-dependent manner and enhanced cell proliferation in pancreatic cancer cells. In addition, inhibition of the Hh pathway as well as NF-kappaB suppressed the enhanced cell proliferation. Our data suggest that NF-kappaB activation is one of the mechanisms underlying Shh overexpression in pancreatic cancer and that proliferation of pancreatic cancer cells is accelerated by NF-kappaB activation in part through Shh overexpression.

Animals↗

PubMed2006

Regulation of insect steroid hormone biosynthesis by innervating peptidergic neurons.

In insects, steroid hormones named ecdysteroids elicit molting and metamorphosis. The prothoracic gland (PG) is a predominant source of ecdysteroids, where their biosynthesis (ecdysteroidogenesis) is regulated by several neuropeptides. Here, we report that FMRFamide-related peptides (FaRPs) regulate ecdysteroidogenesis through direct innervation of the PG in the silkworm Bombyx mori. We purified a previously uncharacterized Bombyx FaRP, DPSFIRFamide, and identified the corresponding Bombyx FMRFamide gene (Bommo-FMRFamide, BRFa), which encodes three additional FaRPs. All BRFa peptides suppressed ecdysteroidogenesis in the PG by reducing cAMP production by means of the receptor for Bommo-myosuppressin, another FaRP we have previously shown to act as a prothoracicostatic factor. BRFa is predominantly expressed in neurosecretory cells of thoracic ganglia, and the neurons in the prothoracic ganglion innervate the PG to supply all four peptides to the gland surface. Electrophysiological recordings during development confirmed the increased firing activity of BRFa neurons in stages with low PG activity and decreased ecdysteroid levels in the hemolymph. To our knowledge, this study provides the first report of peptides controlling ecdysteroidogenesis by direct innervation.

Amino Acid Sequence↗

PubMed2006

Oncocytic non-functioning endocrine tumor of the pancreas.

Herein is presented the case of a malignant non-functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65-year-old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon-like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non-functioning endocrine tumors among them, most of which are malignant.

Adenoma, Oxyphilic↗

PubMed2005

Identification of a novel prothoracicostatic hormone and its receptor in the silkworm Bombyx mori.

The insect brain regulates the activity of the prothoracic glands to secrete ecdysteroids, which affect growth, molting, and metamorphosis. Here we report the identification of a novel prothoracicostatic factor and its receptor in the silkworm Bombyx mori. The prothoracicostatic factor purified from pupal brains of B. mori is a decapeptide with the conserved structure of an insect myosuppressin and thus named Bommo-myosuppressin. Bommo-myosuppressin dose dependently suppressed the cAMP level and inhibited ecdysteroidogenesis in the larval prothoracic glands at much lower concentrations than the prothoracicostatic peptide, the other prothoracicostatic factor reported previously. In vitro analyses using a prothoracic gland incubation method revealed that Bommo-myosuppressin and prothoracicostatic peptide regulate the prothoracic gland activity via different receptors. In situ hybridization and immunohistochemistry revealed the existence of Bommo-myosuppressin in the brain neurosecretory cells projecting to neurohemal organs in which it is stored. We also identified and functionally characterized a specific receptor for Bommo-myosuppressin and showed its high expression in the prothoracic glands. All these results suggest that Bommo-myosuppressin functions as a prothoracicostatic hormone and plays an important role in controlling insect development.

Amino Acid Sequence↗

PubMed2005

Fine mapping of the FT1 locus for soybean flowering time using a residual heterozygous line derived from a recombinant inbred line.

Fine-mapping of loci related to complex quantitative traits is essential for map-based cloning. A residual heterozygous line (RHL) of soybean (Glycine max) derived from a recombinant inbred line (RIL) was used for fine-mapping FT1, which is a major quantitative trait locus (QTL) responsible for soybean flowering time. The residual heterozygous line RHL1-156 was selected from the RILs that were derived from two distantly related varieties, Misuzudaizu and Moshidou Gong 503. The genome of RHL1-156 contains a heterozygous segment (approximately 17 cM) surrounding the FT1 locus but is homozygous in other regions, including three other loci affecting flowering time. A large segregating population of 1,006 individuals derived by selfing of RHL1-156 included two homozygous genotypes for the nearest marker of FT1 whose flowering time differed by 26 days. No continuous range of phenotypes was observed, in contrast to the F2 population, suggesting that a single FT1 locus affected the flowering time in the RHL1-156 line. Linkage analysis revealed that the FT1 locus mapped as a single Mendelian factor between two tightly linked DNA markers, Satt365 and GM169, at distances of approximately 0.1 cM and 0.4 cM, respectively. Our results show that a RHL derived from RILs can be used to fine-map a QTL and that RHLs can be an efficient tool for a systematic fine-mapping of QTLs.

Breeding↗

PubMed2004

Paclitaxel probably enhances cytotoxicity of natural killer cells against breast carcinoma cells by increasing perforin production.

Paclitaxel, a semisynthetic taxane, is one of the most active chemotherapeutic agents for the treatment of patients with breast cancer. We focused on the effect of paclitaxel on the cytotoxicity of natural killer (NK) cells. NK cells were purified by negative selection with magnetic beads from peripheral blood mononuclear cells of healthy volunteers. A human breast carcinoma cell line BT-474 and an NK cell-sensitive erythroleukemia cell line K562 were used as targets. Cytotoxicity of NK cells was determined by 51Cr-release assay with labeled target cells. Paclitaxel (1-100 nM) did not affect cellular viability, and significantly enhanced cytotoxicity of NK cells in a dose-dependent manner. Although paclitaxel did not affect Fas-ligand expression of NK cells, paclitaxel induced mRNA and protein production of perforin, an effector molecule in NK cell-mediated cytotoxicity. Concanamycin A, a potent inhibitor of the perforin-mediated cytotoxic pathway, inhibited paclitaxel-dependent NK cell-mediated cytotoxicity. Furthermore, paclitaxel induced activation of nuclear factor kappa B (NF-kappa B) in NK cells. NF-kappa B inhibitor pyrrolidine dithiocarbamate significantly suppressed both paclitaxel-induced perforin expression and NK cell cytotoxicity. Our results show for the first time that paclitaxel enhances in vitro cytotoxicity of human NK cells. Moreover, our results suggest a significant association between enhanced NK cell cytotoxicity, increased perforin production, and NF-kappa B activation.

Adenocarcinoma↗

PubMed2004

Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer.

The Hedgehog (Hh) signaling pathway functions as an organizer in embryonic development. Genetic analysis has demonstrated a critical role for the Hh pathway in mammary gland morphogenesis. Disruption of Patched1, a component of the Hh pathway, results in abnormal growth of mammary duct. Recent studies have shown constitutive activation of the Hh pathway in various types of malignancies. However, it remains unclear whether this pathway is activated in human breast cancer. Here, we determined the expression of the components, including Sonic Hh, Patched1, and Gli1, of the Hh pathway by immunohistochemical staining in a series of 52 human breast carcinomas. All of 52 tumors display staining of high intensity for Gli1 when compared with adjacent normal tissue. The nuclear staining ratio of Gli1 correlates with expression of estrogen receptor and histologic type. Exposure to cyclopamine, a steroidal alkaloid that blocks the Hh pathway, suppresses expression of Gli1 and the growth of the Hh pathway-activated breast carcinoma cells. These data indicate that the Hh pathway is a new candidate for therapeutic target of breast cancer.

Adult↗

PubMed2004

Interleukin 1beta enhances invasive ability of gastric carcinoma through nuclear factor-kappaB activation.

PURPOSE: We examined the role of interleukin (IL)-1beta in activation of nuclear factor kappaB (NF-kappaB) and the biological function of activated NF-kappaB in gastric carcinoma cells. EXPERIMENTAL DESIGN: Human gastric carcinoma cell line GCTM-1 was used to examine NF-kappaB activation by immunostaining and electrophoretic mobility shift assay. Matrix metalloproteinase (MMP)-9 expression, which plays an important role in tumor invasion, was assessed by semiquantitative reverse transcription-PCR, Western blotting, and immunostaining. The invasive ability of GCTM-1 cells was measured by Matrigel invasion assay. In vivo expression of IL-1beta and MMP-9 and activation of NF-kappaB in 10 surgically resected gastric carcinoma specimens were examined immunohistochemically. RESULTS: IL-1beta enhanced NF-kappaB activation, MMP-9 expression, and the invasive ability of GCTM-1. A NF-kappaB inhibitor, pyrrolidine dithiocarbamate, suppressed both MMP-9 expression and invasiveness of IL-1beta-treated GCTM-1 cells. IL-1beta did not increase the invasive ability of GCTM-1 cells transfected with MMP-9 antisense oligonucleotide. Concomitant expression of IL-1beta and nuclear NF-kappaB was observed in 3 of 10 gastric carcinoma specimens. Cells producing IL-1beta were tumor-infiltrating macrophages in two specimens and gastric carcinoma cells in one specimen. CONCLUSIONS: One of the molecules that may play a role in NF-kappaB activation in some gastric carcinomas is IL-1beta. The present results suggest that IL-1beta increases the invasive ability of carcinoma cells through activation of NF-kappaB and the resulting MMP-9 expression.

Base Sequence↗

PubMed2004

Three-dimensional two-layer collagen matrix gel culture model for evaluating complex biological functions of monocyte-derived dendritic cells.

Dendritic cell-like cells (Mo-DCs) generated from peripheral blood monocytes with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used as tools to treat cancer patients (DC-vaccines). Because Mo-DCs have multiple antigen presentation-related functions, including phagocytosis, migration, cytokine production, and T cell stimulation, establishment of a method for simultaneously evaluating the various functions of Mo-DCs is important. We developed a new in vitro three-dimensional two-layer collagen matrix culture model that consists of a collagen gel containing Mo-DCs as the lower layer and a collagen gel containing necrotic GCTM-1 tumor cells and/or T cells as the upper layer. We used this system to observe simultaneously multiple functions of Mo-DCs by phase-contrast or fluorescence microscopy and to assess IL-12 secretion during more than 2 weeks of culture. We also observed interactions between Mo-DCs and necrotic GCTM-1 or T cells on an individual cell basis by time-lapse videomicroscopy. In addition, we collected Mo-DCs from the collagen gels by collagenase treatment and analyzed the expression of antigen presentation-related molecules such as HLA-DR, CD80, CD83, and CD86 on Mo-DCs. This model may be a useful tool for evaluation of the various functions of Mo-DCs used as DC vaccines and for studies of the complex behaviors of Mo-DCs in vivo.

Antigen Presentation↗

PubMed2003

Cyclosporin-A enhances docetaxel-induced apoptosis through inhibition of nuclear factor-kappaB activation in human gastric carcinoma cells.

PURPOSE: We sought to determine whether cyclosporin-A (CsA) enhances docetaxel [Taxotere (TXT)]- induced apoptosis in human gastric carcinoma cells, and, if so, to determine the relation between this apoptosis and nuclear factor-kappaB (NF-kappaB) activation. EXPERIMENTAL DESIGN: Two human gastric carcinoma cell lines (GCTM-1 and MK-1), a human embryonic pulmonary fibroblast cell line, and human umbilical vein endothelial cells were used as drug targets. Apoptotic cell death was verified morphologically by nuclear fragmentation assay with Hoechst staining. Electrophoretic mobility shift assays were performed to check for nuclear translocation of NF-kappaB. The therapeutic effects of a combination of TXT and CsA were assessed in a mouse peritoneal dissemination model. RESULTS: A combination of CsA (5 micro M) and TXT (10 nM) significantly enhanced apoptotic cell death in both carcinoma cell lines but not in nonmalignant cell lines in comparison with the single-agent treatment alone. This effect was not related to drug uptake, efflux, or MDR1 expression. These effects were also observed in freshly obtained TXT-resistant gastric carcinoma cells isolated from a patient with malignant ascites. TXT alone induced NF-kappaB activation in both carcinoma cell types, and this activation was suppressed by CsA. A combination of TXT and NF-kappaB decoy, a well-known NF-kappaB inhibitor, also enhanced apoptotic cell death in the carcinoma cells. A combination of CsA and TXT significantly suppressed peritoneal dissemination in vivo relative to the single-agent effect. CONCLUSIONS: Treatment with CsA and TXT in combination may be an effective therapeutic strategy for patients with gastric carcinoma.

Adenocarcinoma↗

PubMed2003

Squamous cell carcinoma of the anal margin with pruritus ani of long duration.

BACKGROUND: Anal margin is an unusual location for squamous cell carcinoma (SCC). On rare occasions, anal margin carcinoma is the cause of pruritus ani. OBJECTIVE: To describe a case of SCC of the anal margin with pruritus ani of long duration. RESULTS: A 52-year-old man had been aware of perianal itching for over 10 years. Examination of the perianal area revealed a reddish, eroded, hard nodule that was 2.0 x 1.5 x 0.3 cm in size located in the 3 o'clock position. The histopathologic diagnosis was well-differentiated SCC. The nodule was totally excised with a 1-cm margin. No recurrence or metastases were observed for 7 months. CONCLUSION: When pruritus ani does not respond to conservative therapy and when symptoms have existed for a long time, we should suspect the presence of malignancy.

Anus Neoplasms↗

PubMed2003

Large ulcerated perianal hidradenoma papilliferum in a young female.

BACKGROUND: Hidradenoma papilliferum is an uncommon benign tumor that is located almost exclusively in the vulvar and anal areas. It is usually very small and asymptomatic, and to make a correct diagnosis is clinically very difficult. Occasionally the tumor becomes elevated to form a reddish brown papillary mass, and the surface ulcerates, which may erroneously suggest malignancy. OBJECTIVE: We report a case of a large, perianal hidradenoma papilliferum with suspected malignancy in a young Japanese female. RESULTS: A 22-year-old female had been aware of a perianal nodule for approximately 1 year. Examination of the perianal area revealed a wide pedunculated, reddish nodule with several white maculae. It was ulcerated and bleeding, 2.0 x 1.2 x 0.8 cm in size, and located in the 3 o'clock position. The nodule was totally excised with a narrow margin. The histopathologic diagnosis was hidradenoma papilliferum. No recurrence was observed for 23 months. CONCLUSION: When dermatologists encounter tumors of the anogenital area of adult females, it is important to keep hidradenoma papilliferum in mind as the differential diagnosis. Dermatologists should recognize that the tumor is benign, eliminating the need for wide resection.

Adenoma, Sweat Gland↗

PubMed2002

Evidence-based infection control in thoracic surgery.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) continues to pose a major threat to the lung and cardiovascular surgery patients. We propose evidence-based infection control (EBIC) against MRSA. METHODS: We conducted a basic study comparing genotyping to cluster analysis using minimal inhibition concentration on 17 drugs for 21 MRSA strains. With or without EBIC using cluster analysis and global evidence, we compared the incidence of postoperative MRSA infection. Notably, we eliminated tweezers stands and emesis basins. RESULTS: Cluster analysis showed a typing sensitivity of 72%. The use of EBIC decreased MRSA cross-infection in the recovery room. A lung surgery series showed an MRSA incidence of 1/190 before and 0/200 after EBIC was introduced. For a cardiovascular surgery series, the MRSA incidence was 2/169 before and 0/84 after EBIC was introduced. Across wards, MRSA among Staphylococcus aureus in patient fell from 68% in 1999 to 57% in 2000. CONCLUSIONS: EBIC consisting of global guidelines and cluster analysis was useful in controlling MRSA in lung and cardiovascular surgery patients.

Cluster Analysis↗

PubMed2002

A single-base deletion in soybean flavonoid 3'-hydroxylase gene is associated with gray pubescence color.

The T locus of soybean (Glycine max (L.) Merr.) controls pubescence and seed coat color and is presumed to encode flavonoid 3'-hydroxylase (F3'H). The dominant T and the recessive t allele of the locus produce brown and gray pubescence, respectively. PCR primers were constructed based on the sequence of a soybean EST clone homologous to the F3'H gene. A putative full-length cDNA, sf3'h1 was isolated by 3' and 5' RACE. Sequence analysis revealed that sf3'h1 consists of 1690 nucleotides encoding 513 amino acids. It had 68% and 66% homology with corresponding F3'H protein sequences of petunia and Arabidopsis, respectively. A conserved amino acid sequence of F3'H proteins, GGEK, was found in the deduced polypeptide. Sequence analysis of the gene from a pair of near-isogenic lines for T, To7B (TT, brown) and To7G (tt, gray) revealed that they differed by a single C deletion in the coding region of To7G. The deletion changed the subsequent reading frame resulting in a truncated polypeptide lacking the GGEK consensus sequence and the heme-binding domain. Genomic Southern analysis probed by sf3'h1 revealed restriction fragment length polymorphisms between cultivars with different pubescence color. Further, sf3'h1 was mapped at the same position with T locus on LG3(c2). PCR-RFLP analysis was performed to detect the single-base deletion. To7B and three cultivars with brown pubescence exhibited shorter fragments, while To7G and three cultivars with gray pubescence had longer fragments due to the single-base deletion. The PCR-RFLP marker co-segregated with genotypes at the T locus in a F2 population segregating for the T locus. The above results strongly suggest that sJ3'h1 represents the T gene of soybean responsible for pubescence color and that the single-base deletion may be responsible for gray pubescence color.

Alleles↗

PubMedDate not supplied

Combination of adoptive immunotherapy with Herceptin for patients with HER2-expressing breast cancer.

Clinical use of Herceptin (trastuzumab), which is a humanized monoclonal antibody against HER2, started for patients with HER2-overexpressing breast cancer. To potentiate the efficacy of the Herceptin therapy, this study focused on the combination of Herceptin with activated immune lymphocytes. We used peripheral blood mononuclear cells (PBMCs) as effector cells and used HER2-unexpressing K562 cells, HER2-weakly-expressing breast carcinoma cells (Breast-M), or HER2-strongly-expressing breast carcinoma cells (BT-474) as target cells. Interleukin-2 (IL-2)-activated PBMCs, IL-2/OKT-3-activated PBMCs and a streptococcal preparation OK-432-activated PBMCs were generated and used as effector cells. Cytotoxic activity was determined with 4-hour 51Cr release assay. Both fresh PBMCs and activated PBMCs exhibited Herceptin-dependent cytotoxicity. Importantly, Herceptin-dependent cytotoxicity was found even at a lower effector to target cell ratio (E/T ratio) than that of Herceptin-independent cytotoxicity. In addition, Herceptin-dependent cytotoxicity by these activated PBMCs was observed even in HER2-weakly-expressing Breast-M cells. Since gamma-globulin or anti-CD16 antibody abrogated Herceptin-dependent cytotoxicity, it seems likely that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in the Herceptin-dependent cytotoxicity. We present a recurrent breast cancer patient with malignant pleural effusion, in which HER2-strongly-expressing tumor cells were present, who was undergoing Herceptin therapy. Cluster formation between tumor cells and intrapleural mononuclear cells was induced 24 hours after intravenous injection of Herceptin (4 mg/kg). Mononuclear cells bound specifically to HER2-strongly-expressing tumor cells but not to other cells, such as mesothelial cells, suggested a Herceptin-mediated binding like ADCC in vivo. Taken together, these findings suggest that the combination of Herceptin with various types of activated lymphocytes may be a new therapeutic strategy, not only for HER2-strongly-expressing breast cancer but also for HER2-weakly-expressing cancer.

Adenocarcinoma↗

PubMedDate not supplied

Nuclear factor-kappaB p65 is a prognostic indicator in gastric carcinoma.

BACKGROUND: In common with other investigators, we have reported the constitutive activation of transcription factor nuclear factor-kappaB (NF-kappaB) in a variety of carcinomas, but there is no definite information on its clinical significance. MATERIALS AND METHODS: NF-kappaB p65 activation was determined by immunohistochemical analysis of surgically resected specimens from 63 gastric carcinomas. The 63 patients were divided into a high NF-kappaB group (21 patients) and a low NF-kappaB group (42 patients). Forty-seven of the 63 patients underwent curative resection. The 47 patients consisted of 13 high NF-kappaB patients and 34 low NF-kappaB patients. RESULTS: The high NF-kappaB group demonstrated a shorter overall survival rate compared with the low NF-kappaB group (p=0.015). In the 47 patients who underwent curative resection, the high NF-kappaB group also showed a poor survival prognosis (p=0.032). Multivariate analysis indicated that NF-kappaB activation is a potential prognostic factor in gastric carcinoma. CONCLUSION: Constitutive activation of NF-kappaB p65 may be a new prognostic parameter in gastric carcinoma.

Aged↗

PubMedDate not supplied

Immunohistochemical staining of hedgehog pathway-related proteins in human thymomas.

The thymus plays an essential role in the maturing of progenitor cells to functional T cells. Recent studies suggest that the Hedgehog (Hh) signaling pathway contributes to this differentiation process. However, there is limited information concerning the expression of Hh pathway-related proteins (Hh proteins) in the human thymus. The staining of Hh proteins in the thymic epithelium of 26 surgically resected thymoma tissues was examined by immunohistochemistry. The staining of sonic Hh (Shh) correlated relatively well with the World Health Organization histological classification of thymoma. The higher the grade, the fainter the staining. However, no significant difference in Shh staining was found between normal and neoplastic epithelia. Interestingly, Gli1 staining in thymomas was significantly greater than that in normal thymus (p < 0.0001). Thus, some members of the Hh signaling pathway may contribute to the development of thymoma.

Adult↗