-
[show abstract]
[hide abstract]
ABSTRACT: To determine the prevalence of hepatitis C virus (HCV) infection in B-cell lymphoma in Japan. HCV infection and type II (monoclonal IgM) cryoglobulinaemia (CG) may be involved in the pathogenesis of low-grade B-cell lymphoma (ML) in southern Europe.
Forty-five (11.3%) of 400 B-cell ML cases were HCV antibody (Ab) positive, which was significantly (P < 0.01) higher than the blood donors (2.5%). Among them, 28 diffuse large B-cell lymphoma (DLBCL) cases were included. In the primary sites, 10 (47.6%) of 21 splenic DLBCL and seven (23.3%) of 30 gastric DLBCL were HCV Ab positive, which were significantly (P < 0.05) higher than the myeloma cases (4.9%). HCV infection was rarely (4.2%) detected in 24 lymphoplasmacytic and salivary gland low-grade B-cell ML cases. Type II CG was detected in one myeloma case (3.5%) of 29 HCV+ B-cell ML. By real-time polymerase chain reaction, HCV RNA was detected in fresh tumour tissues of all 11 B-cell ML cases examined. Lymphoma cells were positive for the envelope HCV non-structural (NS)3 and envelope (E2) proteins in six of eight examined B-cell ML cases.
The rare incidence of type II CG is characteristic of Japanese HCV+ ML patients and may influence the low incidence of low-grade B-cell ML. HCV infection may play a role in lymphomagenesis of splenic and gastric DLBCL.
Histopathology 01/2006; 48(2):189-98. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In order to clarify angiogenic mechanism in biliary tract carcinoma, expressions and functions of basic fibroblast growth factor (bFGF) and its receptors (FGFR-1-4), and vascular endothelial growth factor (VEGF) and its receptors were investigated by using human biliary tract carcinoma cell lines (KMC-1, KMC-2, KMBC and KMG-C). Expression of bFGF was confirmed in KMC-1 and KMC-2, and that of FGFR-1-4 in all the cell lines except no FGFR-2 in KMC-2. Expression of VEGF was detected in all the cell lines, whereas the cell lines did not express VEGF receptors. Addition of anti-bFGF neutralizing antibody to the medium did not suppress cell proliferation, whereas exogenous bFGF with or without heparin accelerated cell proliferation in all cell lines. Addition of anti-bFGF neutralizing antibody or anti-VEGF neutralizing antibody to the co-culture of human umbilical vascular endothelial cells (HUVEC) and KMC-2 suppressed the proliferation of HUVEC. Surgically obtained cholangiocarcinoma tissues (n=7) were immunohistochemically negative to bFGF, while six of the seven were positive to VEGF. These findings suggested that human biliary tract carcinoma cells express both bFGF and VEGF not as autocrine growth factors but as angiogenic factors. On the other hand, expression of VEGF was found at a higher frequency than bFGF both in the cell lines and tissues.
Hepatology Research 06/2001; 20(1):97-113. · 2.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Expression and functions of interleukin (IL)-8, a pro-inflammatory cytokine with angiogenesis action, was examined in 23 surgically resected hepatocellular carcinoma (HCC) specimens and 7 HCC cell lines. In all HCC tissues, IL-8 expression was confirmed with reverse-transcription polymerase chain reaction method and enzyme-linked immunosorbent assay, and immunohistochemistry showed HCC cells were the major producer of IL-8 in the tissues. Microvessel density was measured by the double immunohistochemical staining of muscular vessels in HCC tissues, but the density was not related to the level of IL-8 in the HCC tissues. On the other hand, in the co-culture of human umbilical vein endothelial cells (HUVEC) and a HCC cell line (KIM-1), IL-8 produced by KIM-1 significantly accelerated the proliferation of HUVEC. In addition, cases with a high IL-8 level in cancerous tissue had a significantly higher frequency of portal vein invasion, venous invasion and bile duct invasion (p<0.05). In the cultures of 7 HCC cell lines IL-8 secretion into culture medium increased with the treatment of IL-1beta or tumor necrosis factor-alpha. This showed IL-8 expression is regulated by inflammatory cytokines. IL-8 produced by HCC is an angiogenesis factor of HCC, but it could have a much more important role in the invasion and metastasis of HCC.
International Journal of Oncology 02/2001; 18(2):257-64. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Type I interferon (IFN) receptor consists of two chains (Hu-IFN-alphaR1 and Hu-IFN-alphaR2), and Hu-IFN-alphaR2 takes a soluble, short, or long form (Hu-IFN-alphaR2a, Hu-IFN-alphaR2b, or Hu-IFN-alphaR2c, respectively). We examined Hu-IFN-alphaR2 expression in hepatocellular carcinoma (HCC) tissues and their corresponding non-cancerous (non-HCC) tissues. Immunohistochemically, Hu-IFN-alphaR2 expression was positive in 53 (77%) of 69 HCC tissues and in 61 (88%) of 69 non-HCC tissues. Hu-IFN-alphaR2 protein in tissue homogenates of HCC and non-HCC tissues obtained from 29 patients was measured by using ELISA kits, and the amount was 12.7+/-10.9 pg/mg protein in HCC tissue and 10.5+/-5.0 pg/mg protein in non-HCC tissue. Number of specimens in which Hu-IFN-alphaR2 level was 3 pg/mg protein or lower, or 20 pg/mg protein or higher, was one each for non-HCC, while it was 7 (24%) and 6 (21%) for HCC. RT-PCR analysis was done in 7 of the 29 HCC cases. It revealed both Hu-IFN-alphaR2a and Hu-IFN-alphaR2c were expressed in all HCC tissues and in 6 of the 7 non-HCC tissues, and Hu-IFN-alphaR2b was expressed in all HCC tissues and in 4 of the 7 non-HCC tissues. Because immunostaining intensity of Hu-IFN-alphaR2 tended to be higher in the areas with active inflammation, effects of inflammatory cytokines (IL-1alpha, IL-1beta, and TNF-alpha) on Hu-IFN-alphaR2 expression were examined on 11 HCC cell lines. As a result, TNF-alpha up-regulated Hu-IFN-alphaR2 expression in 7 of the 11 cell lines. In 3 of the 7 cell lines, up-regulation of Hu-IFN-alphaR2 on cell surface, as well as of the soluble form of Hu-IFN-alphaR2, was induced not only by TNF-alpha, but also by IL-1alpha or IL-1beta. In conclusion, both HCC and non-HCC tissues frequently express Hu-IFN-alphaR2c that is necessary for Type I IFN response. Hu-IFN-alphaR2 expression in HCC tissues is often attenuated or enhanced, and may be regulated by inflammatory cytokines.
International Journal of Molecular Medicine 01/2001; 6(6):621-7. · 1.98 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: True splenic cyst is a relatively rare disease, and the majority of the cases are classified as epidermoid cysts. Three cases of epidermoid cysts in the spleen or accessory spleen were studied using an immunohistochemical technique and staining for mucin. In case 1, serum carcinoembryonic antigen (CEA) and CA19-9, and in cases 2 and 3, serum CA19-9, before surgery were markedly elevated, and these levels decreased postoperatively. This strongly indicates the relationship between the increase of tumor marker levels and the presence of the epidermoid cyst. In addition, stratified squamous epithelium in the resected tissues of cases 1 and 2 was positive for anti-CEA antibody and anti-CA19-9 antibody, and that of case 3 was positive for anti-CA19-9 antibody. This strongly supports CEA or CA19-9 production in the squamous epithelium.
American Journal of Surgical Pathology 07/1998; 22(6):704-8. · 4.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Fas transduces apoptotic signals upon cross-linking with the Fas ligand, which is experimentally replaced by anti-Fas antibodies. Because little is known about Fas expression and function in hepatocellular carcinoma, these issues are addressed in the current article.
We examined Fas expressions at protein and mRNA levels, and susceptibility to anti-Fas-mediated apoptosis, on six hepatocellular carcinoma cell lines.
Two cell lines constitutively expressed high levels of Fas both on their cell surface and in their cytoplasm, whereas the other four cell lines expressed Fas mainly in their cytoplasm. Fas mRNA of normal size was detected in all cell lines in reverse transcriptase-polymerase chain reaction analyses. Although a Fas mRNA variant, suggesting a soluble Fas molecule, was detected in the two cell lines expressing high levels of Fas, its amount was very small compared to that of normal-sized Fas transcript. Anti-Fas dose-dependently induced apoptosis exclusively in the two cell lines which constitutively express high levels of cell surface Fas. However, after preincubation with interferon-gamma, one cell line with low surface Fas expression became anti-Fas sensitive equivalent to the two cell lines expressing surface Fas at high levels. Studies of two clonally related cell lines showed that dedifferentiated clones had lower Fas expression and resistance to anti-Fas, suggesting deterioration of Fas system after clonal cell dedifferentiation.
These findings suggest sensitivity to anti-Fas is virtually relevant to cell surface Fas, but not to cytoplasmic Fas expression. However, its expression level does not correlate to sensitivity to anti-Fas.
Journal of Hepatology 11/1996; 25(4):454-64. · 9.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Apoptosis, a programmed cell death, can be observed in the tissues of viral or autoimmune hepatitis and of hepatocellular carcinoma. Fas antigen (Fas) was proposed as a protein that triggers apoptosis. To elucidate the relationship between Fas expression and its location in hepatocellular carcinoma cells, we histochemically examined Fas expression by using 25 hepatocellular carcinoma tissues and their corresponding noncancerous tissues, which were surgically obtained from the same patients. In addition, the relationship between Fas expression and apoptotic cell numbers was examined in the hematoxylin-and-eosin-stained specimens obtained from 23 of the 25 patients. Hepatocellular carcinoma tissues expressed Fas less frequently and more weakly than noncancerous tissues. The majority of noncancerous specimens expressed Fas both on the surface and in the cytoplasm, whereas the majority of hepatocellular carcinoma expressed Fas only in the cytoplasm. Apoptotic cell counts were significantly higher in Fas-expressing tissues than in Fas-negative tissues. Among Fas-expressing tissues, the counts were higher in surface Fas-expressing tissues than in tissues that expressed only cytoplasmic Fas (P < 0.01 to 0.05). Our findings indicate that the development of apoptosis in hepatocellular carcinoma tissues relates to not only Fas expression but also its location.
American Journal Of Pathology 09/1996; 149(2):429-37. · 4.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Combined hepatocellular and cholangiocarcinoma is a rare tumor of the liver, and its histogenesis remains unclear. The authors addressed this issue in the current article.
A specimen aseptically obtained from the surgically resected combined hepatocellular and cholangiocarcinoma was processed for primary culture. The morphologic features of the established cell line cultured on a plastic dish and in type I collagen gel matrix, and transplanted in nude mice were examined.
The authors established a new human combined hepatocellular and cholangiocarcinoma cell line, designated KMCH-2, from a 40-year-old Japanese man. KMCH-2 cells on a plastic dish proliferated in a monolayered sheet with a population doubling time of 32 to 44 h. KMCH-2 expressed functional characteristics of hepatocellular carcinoma, such as albumin synthesis at protein and mRNA levels, but were poorly differentiated in morphology, showing an overlap of features with cholangiocarcinoma. KMCH-2 cells cultured within type I collagen gel matrix proliferated, forming compact to vaguely trabecular and pseudoglandular arrangements, and differentiated to show morphological characteristics of hepatocellular carcinoma unlike the cells on a plastic dish. Mucin production was not detected in KMCH-2 cells in vitro. Subcutaneous tumors which developed in nude mice injected with KMCH-2 cells represented features of adenocarcinoma with mucin production.
The present results revealed the presence of an albumin-producing human hepatic neoplastic cell, such as KMCH-2, that can differentiate to show not only the features of hepatocellular carcinoma but also those of cholangiocarcinoma under certain growth conditions.
Journal of Hepatology 05/1996; 24(4):413-22. · 9.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We investigated the expression of intercellular adhesion molecule 1 (ICAM-1) in ex vivo human hepatocellular carcinoma (HCC) cells and in vitro in eight liver cancer cell lines, including six HCC cell lines and two combined hepatocholangiocarcinoma (CHC) cell lines. Immunohistochemistry showed the expression of ICAM-1 on the HCC cell surface with honeycomblike appearance in most cases (96.2%). On the other hand, hepatocytes in noncancerous areas did not express ICAM-1, except those hepatocytes in the periportal and intra-acinar areas with inflammation. Immunohistochemical study on cultured cells revealed that four cultured HCC cell lines and one CHC cell line constitutively expressed ICAM-1 on the cell surface and in the cytoplasm. Flow cytometric analysis revealed that immunostain-positive cells expressed surface ICAM-1 with more than a 90% positive cell rate, and their expressions were upregulated by incubation of cells with inflammatory cytokines, such as interferon alfa, interferon gamma, tumor necrosis factor-alpha, and interleukin 1 beta. Soluble ICAM-1 was detected in supernatants of cell lines expressing cell surface ICAM-1 expression, and was increased in amounts 2- to 20-fold by inflammatory cytokines. These findings suggest that liver cancer cells in ex vivo may express not only surface but also a soluble form of ICAM-1, differently from normal hepatocytes, and that both expressions are upregulated by inflammatory cytokines.
Hepatology 01/1996; 22(6):1708-13. · 11.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The authors evaluated the efficacy of extended radical (three-field) lymphadenectomy for esophageal cancer compared with less radical (two-field) lymphadenectomy. STUDY SUBJECTS AND ANALYTIC METHODS: The mortality and morbidity rates, postoperative courses, and survival rates were compared between 63 patients who underwent three-field lymph node dissection and 65 who underwent two-field lymph node dissection at Kurume University Hospital from 1986 to 1991. Long-term quality of life after surgery was compared between 37 patients who underwent three-field dissection and 35 who underwent two-field dissection from 1980 to 1991.
Three-field dissection resulted in better survival for patients with positive lymph node metastasis from a carcinoma in the upper thoracic or midthoracic esophagus compared with two-field dissection. The mortality rates, postoperative courses and quality of life were the same for both procedures.
Three-field dissection is preferred for upper thoracic or midthoracic esophageal cancer because of improved survival, acceptable mortality and morbidity rates, and good postoperative course and quality of life.
Annals of Surgery 12/1995; 222(5):654-62. · 7.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although the incidence of pulmonary tuberculosis had been rapidly decreased in Japan, it is pointed out that the rate of decrease in annual incidence became smaller in recent years. This slowing down of the rate of decrease is considered to be resulted from an increase in number of individuals who are more susceptible to tuberculous infection; such as the elderly, young people who are not exposed to TB bacilli previously and therefore not immunized, patients with malignant disease or with organ transplantation and HIV-infected persons. Pulmonary tuberculosis still remained as a pulmonary infectious disease of highly ranked importance. Especially, miliary tuberculosis is life-threatening and occasionally fatal unless early intensive antituberculosis chemotherapy was started on the basis of a rapid and definite diagnosis. We made a retrospective survey to clarify the characteristic clinical features of miliary tuberculosis. For this purpose, we compared the characteristics and clinical features of 10 patients with miliary tuberculosis and those of 18 patients with severe pulmonary tuberculosis, not due to hematogenous dissemination. The mean ages of miliary tuberculosis group and that of severe pulmonary tuberculosis group were 62.6 and 63.8 years old, respectively, with no significant difference. Nine out of ten patients with miliary tuberculosis had fever as one of initial symptoms, whereas, all the patients with severe pulmonary tuberculosis had cough and sputa but they seldom developed fever (high fever) at the initial stage of their diseases. Duration from onset of symptom to the admission was 1.2 months on average in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Kekkaku: [Tuberculosis] 03/1995; 70(2):87-91.
-
[show abstract]
[hide abstract]
ABSTRACT: We produced two types of murine monoclonal antibodies, KYSM-1 and KIS-1, against human squamous cell carcinoma of the esophagus for quantitative diagnosis and optimum therapy. The isotypes of KYSM-1 and KIS-1 were IgM and IgG1, respectively. Immunohistochemical staining demonstrated that both antibodies strongly reacted with human carcinoma cell lines of the esophagus, lung and oral cavity. Fluorescence activated cell sorter analysis demonstrated that each antigen of KYSM-1 and KIS-1 exposed to cellular membrane of squamous carcinoma cells and molecular weights of these antigens detected by KYSM-1 and KIS-1 were 60 kDa and 90 kDa, respectively, in non-reduced condition. These 2 monoclonal antibodies were labeled with 125I by the Iodogen method, and each antibody was injected into nude mice with human squamous cell carcinoma of the esophagus. Regarding in vivo accumulation of 125I-labeled antibodies, however, KIS-1 alone showed significantly high values in the tumor at 5 and 7 days after the injection. From this result, KIS-1 was labeled with 131I and injected into the tumor-bearing mice with a dose of 200 microCi. Moderately effective results were found in the tumor by 14 days after the injection. Furthermore, KIS-1 was also conjugated to peplomycin (PEP). In in vitro and in vivo effects of targeting chemotherapy, the conjugates killed human squamous carcinoma cells and tumor-implanted nude mice. These results suggest that the 131I-labeled KIS-1 and/or KIS-1-PEP conjugate may provide a targeting therapy in patients with squamous cell carcinoma of the esophagus.
Gan to kagaku ryoho. Cancer & chemotherapy 06/1994; 21(6):755-60.
-
[show abstract]
[hide abstract]
ABSTRACT: A 68-year-old woman presented a one-month history of lower abdominal pain and weight loss, and was admitted to our hospital. On physical examination, a large hard mass was palpated in her right lower abdomen. An ultrasonograph and computed tomographic (CT) scan revealed a right ovarian tumor that measured 6.9 x 4.9 cm in size. A total hysterectomy and bilateral salpingo-oophorectomy were performed. The postoperative diagnosis of the tumor was squamous cell carcinoma (SCC) of the ovary. She died of infection and disseminated intravascular coagulation 5 months after surgery. The clinical and autopsy examinations did not show the primary lesions of SCC except in the right ovary. Mature cystic teratoma, Brenner tumor and endometriosis, which are ordinary regarded as the histogenesis of ovarian SCC, were not found, but a few surface epithelial inclusion cysts with squamous metaplasia were observed in non-cancerous area of the right ovary, and the contiguous transition from the metaplastic cyst wall to SCC was confirmed by stepwise serial sections. The present case suggests that the surface epithelium of ovary could be the fourth possibility in the histogenesis of the ovarian SCC.
The Kurume Medical Journal 02/1994; 41(4):177-82.
-
[show abstract]
[hide abstract]
ABSTRACT: Flt-1 (VEGF receptor-1) and KDR/Flk-1 (VEGF receptor-2) are the high-affinity receptors for the angiogenesis factor, vascular endothelial growth factor (VEGF). VEGF expression has been confirmed in human hepatocellular carcinoma (HCC), and VEGF is thought to be involved in the angiogenesis within HCC tissues. However, expressions of VEGF receptors in HCC have not been reported. We immunohistochemically examined expressions and localizations of Flt-1 and KDR in 28 surgically resected HCC tissues. In non-cancerous area, Flt-1 and KDR were mainly found in macrophages including Kupffer cells; both receptors were found in vascular endothelial cells in the portal veins and arteries within portal tracts; and KDR was also found in some sinusoidal endothelial cells. In cancerous area, Flt-1 and KDR were found in some macrophages, and also in the endothelial cells of intratumoral blood vessels. In 25 moderately and/or poorly differentiated HCCs, KDR expression in the blood space endothelial cells was clear and continuous in 20 cases, and focal in 5 cases. These results suggest that there would be an angiogenesis mechanism via VEGF/Flt-1 or VEGF/KDR in HCC, and the VEGF/KDR system would take a more important role.
Oncology Reports 7(4):725-9. · 1.84 Impact Factor
