Yuichiro Honjo

Galectin-3 induces endothelial cell morphogenesis and angiogenesis

Increasing evidence suggests that carbohydrate-binding proteins play an essential role in tumor growth and metastasis. However, conflicting results on their function in the regulation of cell proliferation and differentiation during angiogenesis have been reported. We have examined the role of galectin-3 in the regulation of human umbilical vein endothelial cell proliferation, differentiation, migration, and neovascularization. Galectin-3, a carbohydrate-binding protein, with specificity for type 1 and 11 ABH blood group epitopes and polylactosamine glycan containing cell surface glycoproteins, is the major nonintegrin cellular laminin-binding protein. Because galectin-3 expression was shown to be associated in some tumor systems with metastasis, we questioned whether it induces endothelial cell morphogenesis. Here we show that galectin-3 affects chemotaxis and morphology and stimulates capillary tube formation of HUV-EC-C in vitro and angiogenesis in vivo. Endothelial cell morphogenesis is a carbohydrate-dependent process, as it is neutralized by specific sugars and antibodies. These findings demonstrate that endothelial cell surface carbohydrate recognition event(s) can induce a signaling cascade leading to the differentiation and angiogenesis of endothelial cells.

Malignant transformation of thyroid follicular cells by galectin-3

Galectin-3, a beta-galactoside binding lectin, is highly expressed in thyroid carcinomas of follicular cell origin, whereas neither benign thyroid adenomas nor normal thyroid tissues express galectin-3. We previously showed that antisense inhibition of galectin-3 expression markedly reduced the malignant phenotype of thyroid papillary carcinoma cells. In the present study we transfected galectin-3 cDNA into TAD-2 normal thyroid follicular cells. Stable transfectants expressing galectin-3 acquired the phenotype of serum-independent growth, clonogenicity in soft agar, as well as loss of contact inhibition. We also compared the gene expression profile of the galectin-3 transfectants to that of the vehicle control, which revealed that a series of genes were differentially expressed between the two. They include proliferating cell nuclear antigen, replication factor C, and retinoblastoma genes that participate in G1-S transition. These results indicate the transformation of thyroid follicular cells by galectin-3 and possible involvement of galectin-3 in cell cycle.

Granulocyte colony stimulating factor‐producing tongue carcinoma

Leukocytosis without infection in patients with malignancies is known as the leukemoid reaction. The mechanisms involved in this phenomenon remain uncertain.

DNA ploidy, proliferative activities, and immunophenotype of malignant lymphoma: Application of flow cytometry

To explore the flow cytometric diagnosis of malignant lymphoma, we examined the deoxyribonucleic acid (DNA) ploidy, proliferative activities, and immunophenotype of surgical biopsy‐ and fine‐needle aspiration (FNA)–derived materials. Our goal was to determine the possibility of making a diagnosis of malignant lymphoma by flow cytometric analysis of FNA‐derived materials.

Pre-operative assessment of metastatic parotid tumors

Metastatic disease to the parotid gland is rare and its diagnosing procedures are not established. We assessed several parameters, including the prior history of malignancy, fine needle aspiration cytology (FNAC) and magnetic resonance (MR) imaging and determined the most useful combinations for diagnosing metastatic parotid tumors. The primary tumors were squamous cell carcinomas of the eyelid, larynx, tonsil and of unknown origin, malignant melanoma of the auricle and small cell lung carcinoma. In three of four patients with parotid lymph node metastasis who underwent MR imaging, rim enhancement of the tumor was observed on gadolinium (Gd)-enhanced fat-suppressed T1-weighted MR images (sensitivity 75%). In the histopathologic examinations, the tumor was encapsulated and massive infiltration of normal lymphocytes was found peripheral to the capsule. These were not seen in the patients with metastasis to the parotid parenchyma via hematogeneous dissemination or with advanced-stage parotid node metastasis. The FNAC diagnosis accorded with the tumor histology in five of six patients (sensitivity 83%). Three of the six patients had a prior history of malignancy in other sites (sensitivity 50%). The triad of FNAC, prior history of malignancy and enhanced MR images was identified as the combination most useful in the diagnosis of metastatic parotid tumors (sensitivity 100%).

Accessory parotid gland tumor: a case report

We report a case of pleomorphic adenoma which was assessed pre-operatively as arising from the accessory parotid gland. Computed tomography (CT)-sialography provided information about the relationship between the tumor and the remaining normal accessory parotid tissue, and fine-needle aspiration of the tumor provided additional information as to the histologic features of the tumor, i.e. it was identified as of salivary origin. Zygomatic and buccal branches of the facial nerve extended over the accessory parotid gland tumor and the parotid duct was located just beneath the tumor. Therefore, pre-operative assessment of the tumors nature was important for prevention of facial nerve damage and salivary fistula. The normal accessory parotid gland tissue associated with the accessory parotid tumor was histologically different from that of normal parotid gland tissue dissected in other patients with pleomorphic adenoma of the parotid gland. It is suggested that the difference in cell composition between these glands affects the development of the associated tumors.

Ki-67 Positive Fractions in Benign and Malignant Thyroid Tumours: Application of Flow Cytometry

We investigated the DNA ploidy pattern, cell cycle and the percentage of Ki-67 positive fractions in fresh surgical material from 17 benign and 33 malignant thyroid tumours using flow cytometry. DNA aneuploidy was not seen at all in benign tumours, but was seen in 3 out of 33 malignant tumours, suggesting that detection of DNA aneuploidy indicates malignancy, although the detection sensitivity was low. Regarding the cell cycle, there was no difference in the percentage of S-phase fractions (SPF) or G2 plus M phase fractions (G2M) between benign and malignant tumours. However, the percentage of Ki-67 positive fractions in malignant tumours (39.9 +/- 3.9%) was significantly higher than that in benign tumours (9.4 +/- 2.1%), indicating that malignant thyroid tumours contained a large population of G phase cells. When a cut-off value of 20%, was used for Ki-67 positive fractions, sensitivity was 82%, specificity was 88% and accuracy was 84% for the diagnosis of malignant tumours. Although this study was carried out on surgically derived materials, it is possible that flow cytometric analysis of fine needle aspiration-derived materials may have a place in preoperative histopathological assessment of thyroid tumours.

Primary thyroid lymphoma associated with metastatic thyroid tumor : Discrimination with US

We surgically treated a 75-year-old man who suffered from metastatic adenocarcinoma from the colon associated with primary thyroid lymphoma measuring 1 cm maximum in diameter. Radiologic findings were correlated with histopathology of excised specimens. Ultrasonography could discriminate between these two tumors based on the margin characteristics and the lesion echogenicity: the metastatic tumor was shown as an ill-defined hypo to iso echoic mass, while the malignant lymphoma was detected as a well-defined markedly hypoechoic mass. In addition, we could confirm that early-stage primary thyroid lymphoma even as small as 1 cm shows the same radiologic appearance as that of a bulky lymphoma.

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.

A clinical study of 104 patients with tongue cancer and the relationship between DNA ploidy and prognosis in 41 cases

One-hundred and four patients with previously untreated tongue cancer seen in our department between 1986 and 1998 were enrolled in a clinical study. The DNA ploidy patterns observed in fresh frozen specimens obtained from 41 patients were analyzed, and prognostic factors were investigated. According to the TNM classification (UICC 1997), 43 patients had stage I tumors, 29 had stage II tumors, 17 had stage III tumors, and 15 had stage IV tumors. The 5-year cause-specific survival rates for each stage were 94.7%, 64.4%, 50.0% and 45.7%, respectively. The most frequent cause of death associated with the original disease was the recurrence of the disease in cervical lymph nodes (19/27, 70.4%). The occurrence of late cervical metastasis was high among patients with a T2N0 disease. Patients with stage II disease should undergo elective neck dissection or be carefully monitored using ultrasonography. Among the 41 cases in which the DNA ploidy pattern was analyzed, diploid patterns were found in 30 cases and aneuploid patterns were found in 11. The 5-year cause-specific survival rate and the 5-year locoregional control rate were significantly lower for the aneuploid cases (18.2%, 38.9%) than for the diploid cases (66.5%, 69.8%) (p = 0.0003, p = 0.0339). The incidence of distant metastasis was significantly higher among the aneuploid cases (6/11, 54.5%) than among the diploid cases (3/30, 10.0%) (p = 0.0058). The ploidy pattern, as determined by flow cytometric DNA analysis, may reflect the malignancy grade of tongue cancers.