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Biomedical subjects

H Inohara

Publications and source records attributed to H Inohara.

At least 19 recordsLinked to original sources
PubMed2004

Expression level of valosin-containing protein (VCP) as a prognostic marker for gingival squamous cell carcinoma.

BACKGROUND: Valosin-containing protein (VCP) is associated with anti-apoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In the present study, association of VCP expression with prognosis of gingival squamous cell carcinoma (GSCC) was examined. PATIENTS AND METHODS: VCP expression in 74 patients with GSCC (34 males and 40 females) with ages ranging from 42 to 85 (median 66) years was evaluated by immunohistochemistry, in which staining intensity in tumor cells was categorized as either weaker (level 1) or equal to/stronger (level 2) than that in the endothelial cells. RESULTS: Twenty-four (32.4%) cases showed level 1 and 50 (67.6%) level 2 VCP expression. Patients with level 1 GSCC showed a significantly better 5-year survival rate than those with level 2 GSCC (5-year overall survival: 100% versus 84.9%, P < 0.05). Multivariate analysis revealed VCP expression level, lymph node metastasis and pT(TNM) to be independent factors for overall survival. Patients with GSCC at stages I and II showed favorable prognosis regardless of VCP expression status, whereas at stages III and IV, patients with level 1 VCP expression showed better survival rates than those with level 2 expression. CONCLUSION: Prognostic significance of VCP expression level in GSCC was demonstrated.

Adenosine Triphosphatases↗
PubMed2001

Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions.

BACKGROUND: Thyroid cancer is the most common endocrine malignant disease, but preoperative diagnosis remains a challenge. Fine-needle aspiration cytology has greatly improved the clinical management of thyroid nodules, but the preoperative characterisation of follicular lesions is very difficult. Many patients are thus referred to surgery more for diagnosis than for therapeutic necessity. We undertook an international multicentre study to assess the usefulness of immunohistocytochemical staining for two potential markers of malignant thyrocytes. METHODS: Expression of galectin-3 and CD44v6 was tested on 1009 thyroid lesions (tissue specimens and cytological cell-blocks) and 226 fresh cytological samples obtained preoperatively by ultrasound-guided fine-needle aspiration of thyroid nodules (prospective analysis). The test used monoclonal antibodies specific for CD44v6 and galectin-3, the indirect avidin-biotin complex immunoperoxidase method, and 3-amino-9-ethyl-carbazole as substrate. FINDINGS: The sensitivity, specificity, positive predictive value, and diagnostic accuracy of this test method (for coexpression of the two markers) in the prospective analysis were 88%, 98%, 91%, and 97%, respectively. The sensitivity and specificity of galectin-3 immunodetection alone in discriminating benign from malignant thyroid lesions were more than 99% and 98% respectively, and the positive predictive value and diagnostic accuracy were 92% and 99%. INTERPRETATION: The integration of galectin-3 immunostaining with conventional cytomorphological and clinical diagnostic procedures represents a sensitive and reliable diagnostic approach for preoperative identification of thyroid carcinomas. This test method improves the diagnostic accuracy of conventional cytology and provides the molecular basis for a new nosological assignation of the not yet classified thyroid neoplasms of indeterminate malignant behaviour.

Antigens, Differentiation↗
PubMed2001

2',4'-BNA bearing unnatural nucleobases: toward the expansion of the target sequence of double-stranded DNA in triplex formation.

It is absolutely necessary for practical application of antigene strategy to create nucleoside analogues recognizing pyrimidine.purine interruption in dsDNA. To develop a nucleoside analogue to interact with T.A interruption, we designed and synthesized a novel 2',4'-BNA monomer (HBB), 2-(2'-O,4'-C-methyleneribofuranosyl)phenol, and it was introduced into a triplex-forming oligonucleotide (TFO). On melting temperature (Tm) measurements, HBB was found to interact with T.A interruption with moderate binding affinity, and unprecedented dU.A base pair recognition ability of HBB was also observed.

Base Sequence↗
PubMed2001

Galectin-3 maintains the transformed phenotype of thyroid papillary carcinoma cells.

Galectin-3, a beta-galactoside-binding protein, is highly expressed in thyroid papillary carcinomas, while functional relevance of galectin-3 overexpression to the malignant phenotype remains elusive. In the present study we transfected galectin-3 antisense cDNA into the human thyroid papillary carcinoma cell line NPA which expresses an innately high level of galectin-3, and examined the effect of antisense inhibition of galectin-3 expression on the transformed phenotype. There was no difference in anchorage-dependent growth between the antisense clones and either the control or parental clones. In contrast, anchorage-independent growth and saturation density of the antisense clones were significantly suppressed compared to those of either the control or parental clones. These results demonstrate that overexpression of galectin-3 in thyroid papillary carcinoma cells is necessary for the maintenance of transformed phenotype, and suggest galectin-3 as a potential target for therapeutic interventions in the future.

Antigens, Differentiation↗
PubMed2001

Down-regulation of galectin-3 suppresses tumorigenicity of human breast carcinoma cells.

Galectin-3 is an endogenous beta-galactoside-binding protein with specificity for type I and II ABH blood group epitopes and poly-N-acetyllactosamine glycan-containing cell surface glycoproteins and is the major nonintegrin cellular laminin-binding protein. Galectin-3 is expressed at an elevated level in a wide range of neoplasms, and expression was shown to be associated in some tumor cell systems with metastases. Here we determined the functional consequence of blocking galectin-3 expression in highly malignant human breast carcinoma MDA-MB-435 cells. Inhibition of galectin-3 expression led to reversion of the transformed phenotype as determined by altered morphology, loss of serum-independent growth, acquisition of growth inhibition properties by cell contact, and abrogation of anchorage-independent growth. The blockage of galectin-3 expression led to a significant suppression of tumor growth in nude mice. These results provide direct evidence that galectin-3 expression is necessary for the maintenance of the transformed and tumorigenic phenotype of MDA-MB-435 breast carcinoma cells.

Animals↗
PubMed2000

Association of p53 expression with second primary tumour development in hypopharyngeal carcinoma.

Abnormalities of p53 tumour suppressor gene are detected in a diversity of malignancies and play an important role in their pathogenesis. Hypopharyngeal carcinoma is the most morbid among head and neck squamous cell carcinomas because of the high incidence of treatment failures and because a biological marker predictive of the treatment failures remains elusive. The expression of p53 protein in 46 hypopharyngeal squamous cell carcinomas was examined histochemically and p53 immunoreactivity was found in 19 of 46 cases (41.3 per cent). The rate of second primary tumour development was significantly higher in the p53-positive group than in the p53-negative group (p = 0.039), whereas that of tumour recurrence was not significantly different between the two. Moreover, there was no statistically significant difference in either overall or disease-free survival between the p53-positive and -negative groups. These results indicate that although p53 expression significantly correlates with second primary tumour development in patients with hypopharyngeal squamous cell carcinomas, it is not predictive of the clinical outcome.

Biomarkers, Tumor↗
PubMed2000

Expression of cytoplasmic galectin-3 as a prognostic marker in tongue carcinoma.

Galectin-3 is a member of the beta-galactoside-binding mammalian lectin family with affinity to ABH group epitopes, cell surface and extracellular polylactosamine glycans. It has been shown to be involved in differentiation, morphogenesis, tumor progression, and metastasis. Here we questioned the possible involvement of galectin-3 in the neoplastic progression of the tongue epithelium and evaluated its prognostic value in tongue cancer patients. Galectin-3 expression was analyzed by the immunohistochemical method in 77 tongue specimens (54 squamous cell carcinomas and 23 specimens of distinct normal mucosa). Levels of nuclear expression of galectin-3 markedly decreased during the progression from normal to cancerous states (P < 0.0001), while cytoplasmic expression increased (P < 0.0001). Enhanced expression of galectin-3 in the cytoplasm was associated with a reduced disease-free survival of tongue cancer patients. Multivariate analysis identified enhanced expression of cytoplasmic galectin-3 as an independent predictor of disease recurrence (P = 0.0120). These results suggest that the observed translocation of galectin-3 from the nucleus to the cytoplasm during neoplastic progression may serve as a prognostic factor for tongue cancer patients.

Adult↗
PubMed1999

Expression of galectin-3 in fine-needle aspirates as a diagnostic marker differentiating benign from malignant thyroid neoplasms.

BACKGROUND: Galectin-3 is a beta-galactoside-binding protein that has been reported to be expressed preferentially in thyroid malignancies. The current study was designed to substantiate this finding further and to establish a presurgical diagnostic modality of differentiating between benign and malignant thyroid neoplasms by analyzing galectin-3 expression in fine-needle aspirates. METHODS: The expression of galectin-3 was examined immunohistochemically in total of 172 specimens: 45 primary and 20 metastatic papillary carcinomas, 8 primary and 2 metastatic follicular carcinomas, 5 primary and 3 metastatic anaplastic carcinomas, 3 primary medullary carcinomas, 25 follicular adenomas, 3 goiters, and 58 adjacent normal thyroid tissue. Alternatively, epithelial cells were isolated from the fine- needle aspirates of 14 thyroid nodules and subjected to immunoblotting analysis of galectin-3. RESULTS: Immunohistochemical analysis revealed that all thyroid malignancies of follicular cell origin (including papillary, follicular, and anaplastic carcinomas) showed high and diffuse expression of galectin-3, whereas one of the three medullary carcinomas of parafollicular cell origin displayed weaker and focal expression of galectin-3. In contrast, neither benign thyroid adenomas, goiters, nor normal thyroid tissues expressed galectin-3. Immunoblot analysis of the isolated epithelial cells detected galectin-3 in nine thyroid nodules that were proven histologically to be malignant ( eight papillary carcinomas and one follicular carcinoma) after surgical intervention, whereas galectin-3 was not detected in five nodules proven to be benign follicular adenomas. CONCLUSIONS: Galectin-3 serves as a marker of thyroid malignancy of follicular cell origin. Analysis of galectin-3 expression in fine-needle aspirates enhances the differential diagnostic accuracy between benign and malignant thyroid neoplasms.

Antigens, Differentiation↗
PubMed1999

Chronological changes in incidences of polymorphic reticulosis in Korea and Japan.

Lethal midline granuloma (LMG) is a clinical term, which describes a group of diseases histologically comprising Wegener's granulomatosis, polymorphic reticulosis (PR), and malignant lymphoma of the ordinary type (ML). PR is a variant of ML, and is considered to be a type of NK/T cell lymphoma. Our previous study revealed the clustering of patients with PR in East Asia including China, Korea and Japan. However, the frequency rate of PR varied even among these countries, with that of Korea being approximately 5 times higher than that of Japan. In the present study, we examined the incidences of each type of LMG, especially PR, in Korea (Yonsei University) and Japan (59 university hospitals) over time. A total of 102 cases and 655 cases of LMG admitted to Yonsei University, Korea from 1977 to 1996 and 59 university hospitals in Japan between 1965 and 1996, respectively, were examined. The frequency rate of PR per 100,000 outpatients of ears, nose and throat (ENT) clinics in Korea decreased from 40 to 20 between the periods of 1977-1989 and 1990-1996. However, there were no significant changes in Japan during the period studied.

Adolescent↗
PubMed1998

Galectin-3 stimulates cell proliferation.

Galectin-3, a beta-galactoside-binding protein, has been shown to be involved in multiple biological processes through interaction with its complementary glycoconjugates. Here we provide the first evidence of galectin-3 as a mitogen. Incubation of quiescent cultures of normal human lung fibroblast IMR-90 cells with recombinant galectin-3 (rgalectin-3) stimulated DNA synthesis as well as cell proliferation in a dose-dependent manner. This mitogenic activity was dependent on the lectin property of galectin-3, as it could be significantly inhibited by lactose, a disaccharide competitive for carbohydrate-binding by galectin-3. Chemical cross-linking and affinity-purification experiments identified binding of rgalectin-3 to cell surface glycoproteins, which were not recognized by antibodies directed against lysosome-associated membrane proteins (LAMPs), putative cellular ligands for galectin-3. Moreover, pulse-chase analysis revealed no secretion of galectin-3 by IMR-90 cells. These results indicate that galectin-3 is a mitogen capable of stimulating fibroblast cell proliferation in a paracrine fashion through interaction with cell surface glycoconjugates different from LAMPs and suggest a possible involvement of galectin-3 in tissue remodeling.

Antigens, CD↗
PubMed1997

Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family.

Galectin-3, a beta-galactoside-binding protein, has been shown to be involved in tumor progression and metastasis. Here, we demonstrate that expression of galectin-3 in human breast carcinoma BT549 cells inhibits cis-diamminedichloroplatinum (cisplatin)-induced poly(ADP-ribose) polymerase degradation and apoptosis, without altering Bcl-2, Bcl-X(L), or Bax expressions. Galectin-3 contains the NWGR amino acid sequence highly conserved in the BH1 domain of the bcl-2 gene family, and a substitution of glycine to alanine in this motif abrogated its antiapoptotic activity. Our findings demonstrate that galectin-3 inhibits apoptosis through a cysteine protease pathway and highlight the functional significance of the NWGR motif in apoptosis resistance of a non-Bcl-2 protein.

Amino Acid Sequence↗
PubMed1996

Interactions between galectin-3 and Mac-2-binding protein mediate cell-cell adhesion.

Galectin-3 is a beta-galactoside-specific lectin implicated in diverse processes involved in cellular interactions. Recently, the Mac-2-binding protein, a heavily N-glycosylated secreted protein with a subunit Mr of 97,000, was identified as its ligand. The present study characterizes the interaction between galectin-3 and Mac-2-binding protein in whole cells and measures their relative expression levels. Incubation of A375 cells with affinity-purified Mac-2-binding protein resulted in its binding to galectin-3 on the cell surface in a specific carbohydrate-dependent manner. Mac-2-binding protein also induced homotypic cell aggregation, which was inhibited by lactose or Fab' fragments of an anti-galectin-3 antibody. Northern blotting analysis revealed differences in the transcriptional regulation of galectin-3 and Mac-2-binding protein. These results provide the first direct evidence for a Mac-2-binding protein function and suggest that it may play a role in tumor cell embolization during metastasis through interaction with galectin-3.

Antigens, Differentiation↗
PubMed1995

Galectin-3 is a nuclear matrix protein which binds RNA.

The endogenous galectin-3 is a carbohydrate-binding protein of M(r) approximately 30,000 serving in the cytoplasm and on the cell surface as a receptor for ligands containing poly-N-acetyllactosamine sequences. In addition, galectin-3 has been demonstrated to be associated in the nucleus with ribonucleoprotein complexes and to act as a pre-mRNA splicing factor and to be involved in spliceosome assembly. However, little is known about either its nuclear localization or its ligand(s), respectively. We demonstrate directly here that galectin-3 is associated with the RNA protein skeleton of the nucleus, i.e., the nuclear matrix, and binds with single-stranded DNA (ssDNA) and with RNA. The affinity of binding was determined to be 2.3 microM. Lactose, which inhibits galectin-3 binding to glycoconjugates, failed to inhibit either galectin-3-ssDNA or galectin-3-RNA binding. Galectin-3 exhibited the highest affinity to poly(A) ribonucleotide homopolymers. The results presented here shows that galectin-3 may act as a RNA-binding protein in the nuclear matrix in a non-carbohydrate-dependent manner.

Animals↗
PubMed1995

Functional evidence that cell surface galectin-3 mediates homotypic cell adhesion.

Galectin-3 (Gal-3) is a beta-galactoside-binding protein with M(r) approximately 30,000. Cell surface Gal-3 is postulated to be involved in homotypic aggregation of tumor cells in the circulation during metastasis through attachment to a complementary serum glycoprotein(s), which serves as a cross-linking bridge between adjacent cells. To test this hypothesis a recombinant strain of baculovirus encoding Gal-3 was used to infect Sf9 insect cells, which lack endogenous Gal-3. Immunoblotting and indirect immunofluorescence studies revealed that the infection with recombinant virus conferred Gal-3 expression on Sf9 cells, and the Gal-3 was localized on the cell surface as well as in the cytoplasm. Sf9 cells infected with recombinant virus underwent homotypic aggregation in the presence of exogenous glycoprotein (i.e., asialofetuin), whereas control cells uninfected or infected with wild-type virus did not. Lactose and Fab' fragments of anti-Gal-3 antibodies markedly inhibited the cell-cell aggregation. Moreover, cosuspension of Sf9 cells infected with the recombinant virus with uninfected cells in the presence of asialofetuin resulted in a preferential cell-cell adhesion of the Gal-3-expressing cells. These results directly demonstrate the ability of cell surface Gal-3 molecules to mediate homotypic cell adhesion by bridging through branched, soluble complementary glycoconjugates.

Animals↗
PubMed1994

Identification of human melanoma cellular and secreted ligands for galectin-3.

The endogenous human tumor-associated galectin-3 (hL-31) is a functional molecule which acts as a receptor for ligands containing poly-N-acetyllactosamine sequences. However, little is known about its native ligand(s). In order to identify the ligand(s), the human melanoma cell line A375 was metabolically labeled with [3H]glucosamine, and total cell extracts and serum-free conditioned medium of the labeled cells were affinity-purified on immobilized recombinant hL-31 followed by elution with lactose, the specific sugar inhibitor of the lectin. Cellular ligands for hL-31 were found to be composed of the two lysosome-associated membrane proteins, LAMP-1 and LAMP-2, while secreted ligands consisted of two glycoproteins of 98 and 70 kDa. N-terminal protein microsequencing revealed that the 98 kDa and 70 kDa species share the same N-terminal sequence. The functional relevance of these secreted ligands was demonstrated by their ability to inhibit lectin-mediated hemagglutination in a manner similar to the specific sugar inhibitor lactose. Computer-assisted sequence library searches have identified the 98 kDa human melanoma secreted ligand to be the Mac-2-binding protein (Mac-2-BP), also known as the human lung tumor L3 antigen.

Amino Acid Sequence↗