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K Notohara

Publications and source records attributed to K Notohara.

At least 19 recordsLinked to original sources
PubMed2006

Oesophageal squamous cell carcinoma may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa.

BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) often arises from preceding dysplastic lesions in the oesophageal epithelium. However, the molecular changes occurring in premalignant lesions are not well understood. An epigenetic change is an example of OSCC that may occur within the epithelium. AIM: To investigate the methylation status of multiple promoters in cancer-derived DNA, as well as in the background epithelium of OSCC, including dysplastic lesions and non-neoplastic mucosa. The normal epithelium from patients without cancer was also examined. The findings were correlated with the mutational status of p53. PATIENTS AND METHODS: 56 patients with advanced OSCC, 21 patients with intraepithelial neoplasia (IEN), 56 patients with a background of non-neoplastic epithelium, adjacent to the OSCC, and 42 normal control epithelia from healthy volunteers were studied. The promoter methylation status of SFRP1, SFRP2, DCC, APC, p16(INK4a), p14(ARF), MINT1, MINT2, MINT31, CACNA1G, COX2, DAPK, hMLH1 and MGMT was examined by methylation-specific single polymerase chain reaction or combined bisulphite restriction analysis. The mutation of p53 by direct sequencing was assessed. RESULTS: DNA methylation was observed in OSCC and in its background epithelium. The frequency of CpG island methylation increased from a baseline level in the background non-neoplastic epithelium, through IEN, to advanced OSCC. However, mutations in p53 were almost exclusively observed in IEN and OSCC. More extensive DNA methylation was seen in the neoplastic lesions (OSCC or IEN) having a p53 mutation than in those with wild-type p53. CONCLUSION: DNA methylation is present at low levels in the non-neoplastic oesophageal epithelium and appears to contribute to the progression of the dysplasia-carcinoma sequence in OSCC carcinogenesis.

Adult↗
PubMed2003

Hepatosplenic T cell lymphoma with no expression of cytotoxic molecules.

Hepatosplenic T cell lymphoma is defined as an extranodal and systemic neoplasm derived from cytotoxic T cells. This report describes a postmortem case of T cell lymphoma that showed histological features of hepatosplenic T cell lymphoma but did not express cytotoxic molecules. The patient was a 57 year old man who presented with severe icterus and hepatosplenomegaly, followed by an aggressive clinical course. The liver and spleen were enlarged, weighing 2000 g and 360 g, respectively. Histologically, the liver, spleen, and bone marrow were entirely affected by lymphoma, comprising pleomorphic small and large cells, which displayed sinusoidal infiltration in the liver, diffuse infiltration in the splenic cord, and interstitial/diffuse infiltration with fibrosis in the bone marrow. Lymphoma cells showed positivity for CD3 epsilon, CD8, and CD45RO and clonal rearrangement of the TCRgamma gene by the polymerase chain reaction on paraffin wax embedded sections. However, they were negative for TIA-1 and granzyme B, in addition to betaF1, CD4, and CD56. Few neoplastic cells were stained for Epstein-Barr virus encoded mRNA 1. These findings indicate that this case might represent a variant of hepatosplenic T cell lymphoma despite the absence of cytotoxic molecules.

Biomarkers, Tumor↗
PubMed2001

Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm.

Significance of Wnt signaling with beta-catenin mutations on solid-pseudopapillary neoplasm (SPN) of the pancreas was studied by immunohistochemistry and molecular analysis. On immunohistochemistry, all 18 SPNs tested showed diffuse cytoplasmic/nuclear positivity for beta-catenin. Upon direct DNA sequencing of exon 3 of the beta-catenin gene, 15 (83%) of the 18 SPNs showed 1-bp missense mutation in codons 32 (5 cases), 33 (3 cases), 34 (3 cases), 37 (3 cases), and 41 (1 case). Immunoreactivity for cyclin D1, one of the intranuclear targets of beta-catenin complexes, was found in tumor cells of more than half the tumor cells of all of the 18 SPNs. The present study strongly suggested a significant role of Wnt signaling, mostly associated with beta-catenin mutations in the tumorigenesis of SPN.

Adolescent↗
PubMed2001

High frequency of low-level microsatellite instability in early colorectal cancer.

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

Aged↗
PubMed2001

Leiomyosarcoma arising in a remnant esophagus after esophagectomy: a case report.

We report an extremely rare case of leiomyosarcoma arising from a remnant esophagus. A 52-year-old Japanese man was referred to our hospital for treatment of a tumor arising from the remnant esophagus. Four years earlier, he underwent a subtotal esophagectomy for esophageal squamous cell carcinoma (well differentiated squamous cell carcinoma, T1N0M0 Stage I) located in the lower esophagus. After preoperative studies, partial esophagectomy with laryngeal preservation and reconstruction using a free graft from the jejunum were performed. Histopathological and immunohistochemical examination revealed leiomyosarcoma without metastasis. Immunohistochemical examination showed that most tumor cells were positive for smooth muscle actin and vimentin, but were negative for cytokeratin and S100. The deeply biopsied specimens are helpful for preoperative histological diagnosis. Mitotic activity has been considered an important criterion of malignancy. However, some cases with minimal mitosis in the tumor grow rapidly and were associated with poor prognosis. Therefore, we advocate that the clinical behavior is the only true indication of malignancy. We also provide a review of 64 cases of esophageal leiomyosarcoma reported in the Japanese literature with available data between 1969 and 1999, including the present case, and discuss their clinicopathological features. Asynchronous occurrence of leiomyosarcoma and squamous cell carcinoma in the esophagus is most unusual and has never been reported. Patients with infiltrating type leiomyosarcoma measuring more than 5 cm in diameter tend to have a poor prognosis. Chemotherapy did not exhibit any survival benefits. In the present patient, no recurrence has been noted for 23 months after surgery.

Carcinoma, Squamous Cell↗
PubMed2001

Successful resection of rectal carcinoma in an Evans' syndrome patient followed by predonisolone and high-dose immunoglobulin: report of a case.

A 69-year-old woman was admitted to our hospital because of anal bleeding and fatigue. The patient was previously diagnosed as having Evans' syndrome on the basis of hematological examination and had been treated with predonisolone for 8 years. On admission, severe anemia and thrombocytopenia were noted. Colonoscopy and Barium enema studies demonstrated an irregular tumor with hemorrhagic ulceration in the rectum, which was histopathologically confirmed as an adenocarcinoma. After red blood cells and platelets were transfused, and the patient was treated with high-dose gammaglobulin, predonisolone, and camostat mesylate, the platelet count gradually increased and hemolysis was well controlled. The patient then underwent Hartmann's operation and splenectomy without any postoperative complications. Predonisolone and high-dose immunoglobulin therapy in a rectal cancer burdened patient with Evans' syndrome is considered useful in combination with surgical treatment. This is the first case report of rectal carcinoma resection in a patient with Evans' syndrome.

Adenocarcinoma↗
PubMed2001

Reduced expression of hMLH1 and hMSH2 gene products in high-grade hepatocellular carcinoma.

We performed an immunohistochemical analysis of 2 major DNA mismatch repair proteins, human Mut L homologue-1 (hMLH1) and human Mut S homologue-2 (hMSH2), in hepatocellular carcinoma (HCC) using 33 biopsied and 58 surgically resected specimens, as well as 30 samples from non-cancerous livers. In well-differentiated HCCs, the immunoreactivity for these antigens was well preserved, and the staining intensity was stronger compared to the surrounding liver tissues. However, among 41 moderately-differentiated and 9 poorly-differentiated HCCs of the resected cases, hMLH1- and hMSH2-positive cells were significantly reduced in 19 (38%) and 9 (18%) cases, respectively. In 9 resected tumors, the expression of both of these antigens was reduced. Moreover, in 41 tumors of differing histological grades, 10 and 5 tumors for hMLH1 and hMSH2, respectively, contained a less-differentiated area with a reduced number of immunoreactive cells. The samples from non-cancerous biopsied liver and fetal autopsy tissue were well immunostained for both hMLH1 and hMSH2. We confirmed in this series that the hMLH1 and hMSH2 defect did commonly occur in high-grade HCCs, and that it might play a role in tumor progression.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Endogenous amoebic endophthalmitis.

A 42-year-old man experienced abrupt reduction of vision in the left eye and had vitreous opacity and hypopyon on initial examination. He underwent an emergency vitrectomy and phacoemulsification with posterior capsulectomy, followed by a 2-week course of intravenous fluconazole and antibiotics. The final visual acuity was 20/20 OS. Amoebas, together with polymorphonuclear cells, were observed on examination of specimens of the aqueous humor and vitreous fluid obtained during the surgery. Staphylococcus epidermidis was also cultured from the vitreous fluid. The amoebas had a crescent-shaped periphery of the cytoplasm and ambiguous nuclei. Ultrastructurally, the cytoplasm was surrounded by a thick electron-dense coating. The early vitrectomy and combined use of antibiotics and antifungals might have led to the good visual outcome in this patient.

Adult↗
PubMed2000

Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10.

To clarify the neuroendocrine differentiation and CD10 expression in solid-pseudopapillary tumors (SPTs) of the pancreas, we performed immunohistochemical analysis in 19 such tumors, including one solid-pseudopapillary carcinoma (SPC), along with 20 pancreatic neuroendocrine tumors (PNTs), six acinar cell carcinomas (ACCs), and one pancreatoblastoma (PB). We used antisera directed against CD56, synaptophysin, protein gene product 9.5, the alpha-subunit of Go protein, chromogranin A, CD10, trypsin, chymotrypsin, various cytokeratins (CKs), CA19-9, vimentin, and alpha-1-antitrypsin (AAT). All SPTs exhibited immunoreactivity for CD56 and CD10, and 15 expressed other neuroendocrine markers focally with the exception of chromogranin A. Frequent clustering of synaptophysin-positive cells was noted. Two cases contained a peculiar nodule that cytomorphologically and immunohistochemically resembled PNT. CD10-positive cells were scarce in one SPC. PNTs were CD56-positive, but often with faint intensity, and staining for other neuroendocrine markers, including chromogranin A, was diffusely positive. CD10 was detected, mostly in a focal pattern, in five PNTs. Pan-CK, CK8, CK18, and CK19 were more frequently demonstrated in PNT than SPT. Vimentin and AAT were often identified in PNT as well and were not specific for SPT. ACCs were CD56-negative, with the exception of one case designated as a mixed acinar-endocrine carcinoma. PB was focally positive for CD56 at the periphery of the tumor nests. Four ACCs and one PB exhibited focal CD10 reactivity. This study demonstrated the unique immunohistochemical features of SPT. Our results also suggest that SPT exhibits, at least focally, neuroendocrine differentiation, and that these neuroendocrine markers and CD10 are diagnostically useful.

Adolescent↗
PubMed2000

Suppression of tumor growth and downregulation of platelet-derived endothelial cell growth factor / thymidine phosphorylase in tumor cells by angiogenesis inhibitor TNP-470.

We investigated the effects of the angiogenesis inhibitor TNP-470 on human lung squamous cell carcinoma cell lines H226B and H226Br both in vivo and in vitro. H226B was established from human lung squamous cell carcinoma and H226Br was established from a brain metastatic lesion of H226B in nude mice. Nude mice inoculated with these cells were treated with 30 mg / kg of TNP-470 subcutaneously every other day. At this dose, TNP-470 only significantly suppressed the growth of H226Br tumor, but not H226B tumor. Attempts to use a high dose of TNP-470 (100 mg / kg) resulted in a severe loss of body weight. Immunohistochemical studies showed marked tumor vascularization in H226Br tumor, but the formation of new blood vessels was suppressed by 30 mg / kg of TNP-470. Investigation of the mechanism of anti-angiogenic effects of TNP-470 in vivo showed that the expression and the activity of platelet-derived endothelial cell growth factor / thymidine phosphorylase (PD-ECGF / dThdPase) in H226Br tumor was significantly suppressed by 30 mg / kg of TNP-470. Furthermore, TNP-470 inhibited cell growth of cultured H226Br dose-dependently at concentrations of 1 microg / ml. Immunoblot analysis revealed H226Br cells gave a stronger PD-ECGF signal than H226B cells, and the expression of PD-ECGF / dThdPase in H226Br was also suppressed by treatment with TNP-470 at 0.1 microg / ml. No change in basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) was noted in these cell lines. Our results suggested that TNP-470 acts, at least in part, by downregulation of PD-ECGF / dThdPase in this cell line.

Angiogenesis Inhibitors↗
PubMed2000

Choroidal schwannoma: immunohistochemical and electron-microscopic study.

Schwannoma (neurilemoma) arising from the ciliary body and choroid is a rare form of intraocular tumor and usually misdiagnosed clinically as amelanotic melanoma. This case report describes a 73-year-old woman who developed a large nonpigmented intraocular tumor of the choroid in the left eye and underwent enucleation with a clinical diagnosis of malignant melanoma. The tumor consisted of spindle-shaped cells with an indefinite cytoplasm and twisted nuclei, which had positive immunoreactivity for S-100 protein, vimentin, glial fibrillary acidic protein and neural cell adhesion molecule. A continuous basal lamina encompassing the tumor cells was demonstrated by immunostaining for laminin and type IV collagen. Ultrastructurally, tumor cells with scant organelles had delicate cytoplasmic processes apposing each other, all indicative of Schwann cell origin. In reexamination of fluorescein angiograms, ultrasonograms and magnetic resonance images, no findings were incompatible with a diagnosis of choroidal melanoma. Histopathological studies showed that the tumor was a schwannoma. At present, we do not have a benchmark for the clinical diagnosis of intraocular schwannoma.

Actins↗
PubMed1999

Dermoid cyst of the spleen: report of a case.

A rare splenic dermoid cyst in an 11-year-old girl is reported herein. The patient was referred to us with the chief complaint of acute-onset abdominal pain. The lesion was demonstrated by ultrasonography, computed tomography, and magnetic resonance imaging to be a cystic lesion containing serous fluid. A splenectomy was performed. Both histopathological and immunohistochemical findings demonstrated the cyst to be a dermoid cyst of the spleen. To avoid the risk of infection following splenectomy, polyvalent pneumococcus vaccine was administered. The patient recovered uneventfully. We performed immunohistochemical studies with cytokeratin and electron microscopy to determine the origin of the cyst.

Abdominal Pain↗
PubMed1999

Very young patient with peculiar squamous cell carcinoma of the lung.

A 20-year-old man with squamous cell carcinoma of the lung is described. Histology of the open lung biopsy specimen revealed squamous cell carcinoma with definite keratinization. Interestingly, the tumor cells were characterized by partial expression of CD34 antigen and neuroendocrine differentiation. The diagnosis was delayed in this case because of his young age. This delayed diagnosis resulted in rapid progression and short survival time. In our review of 667 cases of lung cancers at Okayama University Hospital, only 3 (0.4%) of them were under 30 years of age and also showed advanced stage and very poor prognosis. It is important to take note of lung cancer as a differential diagnosis to detect early-stage lung cancer in young patients when they present with abnormal shadow on chest radiograph.

Adult↗
PubMed1998

Bone marrow necrosis in a patient with acute myeloblastic leukemia during administration of G-CSF and rapid hematologic recovery after allotransplantation of peripheral blood stem cells.

Allogeneic peripheral blood stem cell transplantation from an HLA-identical sibling was performed for a 38-year-old male with refractory acute myeloblastic leukemia. The patient was conditioned with total body irradiation (TBI) and high-dose cytosine arabinoside (Ara-C). G-CSF (300 microg/body) was started for priming of residual leukemic cells 24 hr before the beginning of TBI (day -9). However, intolerable generalized bone pain appeared shortly after the start of first dose of G-CSF, and persisted for 3 days in spite of the cessation of G-CSF. Posttransplant hematopoietic engraftment was very rapid. Bone marrow biopsy specimens on day 14 and 30 showed typical bone marrow necrosis histologically. This is the first case of bone marrow necrosis during administration of G-CSF, and our experience suggests that PBSC could repopulate hematopoiesis in spite of severe bone marrow necrosis.

Adult↗
PubMed1991

t(11;14) (q13;q32) in B-cell lymphomas (intermediately differentiated lymphocytic and follicular). A report of four cases.

The association of recurrent chromosomal abnormalities with certain types of non-Hodgkin's lymphomas (NHLs) provides important clues to their classification and pathogenesis. The t(11;14), an uncommon abnormality, has been reported in a variety of B-cell lymphomas, including the intermediately differentiated lymphocytic lymphoma (IDLL). The authors report here the histologic, immunophenotypic, and cytogenetic findings in four additional patients with such translocation. They represent 8% of 51 patients with NHL studied by cytogenetics in a provincial hospital of Western mainland Japan. Three of the patients had IDLL and one a follicular lymphoma of large cell type. These findings strengthen the association between t(11;14) and IDLL. Furthermore, the occurrence of t(11;14) in a follicular lymphoma, as the sole abnormality, along with histogenetic considerations, suggests the possible existence of a rarer subset of follicular lymphoma, not associated with the t(14;18) and histogenetically related to IDLL.

Aged↗
PubMed1990

Chromosome abnormalities in malignant lymphoma in patients from Kurashiki: histological and immunophenotypic correlations.

Clonal chromosomal abnormalities were found in tumor tissue of 43 (84%) of 51 patients with non-Hodgkin's lymphoma (B-cell, 32; T-cell, 15) from an adult T-cell leukemia/lymphoma-nonendemic area in western mainland Japan. Four tumors were tetraploid, and the other 39 had a chromosome number in the diploid range. Trisomies 3, 5, 7, 18, and X, monosomy 13, and loss of an X in female and a Y in male were found in more than three patients each. Structural abnormalities in arms 1p, 1q, 2q, 3q, 13q, 14q, and 18q were found in eight or more patients each. Clustering of breaks occurred in 3q25-29 (ten patients, nine of whom with a B-cell tumor), 11q13 (five patients), dir dup(12)(q13-15----q21-24) (four patients), 14q32 (12 patients), and 18q21 (seven patients). The 14q32 translocations were all associated with B-cell tumors. t(8;14) was seen in a small noncleaved cell lymphoma, t(11;14)(q13;q32) in one follicular and three intermediately differentiated lymphocytic lymphomas, and t(14;18)(q32;q21) in two follicular lymphomas and one diffuse small cleaved cell tumor. The translocation partner of 14q could not be determined in the other four patients, three of whom had der(18)t(18;?)(q21;?). The seven 18q21 abnormalities, including a novel translocation t(2;18)(p11;q21.3), all occurred in B-cell tumors; even in the absence of t(14;18), they were closely associated with lymphomas of follicular center cell origin (six of seven).

Adolescent↗
PubMed1990

Glial fibrillary acidic protein immunoreactivity of chondrocytes in immature and mature teratomas.

The immunoreactivity of chondrocytes for glial fibrillary acidic protein (GFAP), other intermediate filament proteins and S-100 protein was studied in formalin-fixed paraffin-embedded sections. A total of 95 cartilage specimens were examined from five immature teratomas, 12 mature teratomas, and a teratocarcinoma. GFAP-immunoreactive chondrocytes were abundant in immature cartilages, and as the cartilages maturated, these chondrocytes decreased and became distributed peripherally. Elastic cartilage had more GFAP-immunoreactive chondrocytes than non-elastic cartilage. GFAP-immunoreactive cartilage was often located close to central nervous tissue. Immunostaining for vimentin and S-100 protein revealed extensive distribution of immunoreactive chondrocytes in immature and mature cartilages, but in mature cartilage, chondrocytes at the center had less vimentin immunoreactivity. GFAP-immunoreactive chondrocytes also showed apparent immunostaining for vimentin. There was no difference in immunohistochemical staining for the alpha and beta subunits of S-100 protein. The immunoreactivities of teratoma cartilage specimens were quite similar to those of respiratory tract cartilage.

Cartilage↗