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Biomedical subjects

M Kojiro

Publications and source records attributed to M Kojiro.

At least 73 records · Page 4Linked to original sources
PubMed1996

Biliary hamartomas simulating multiple hepatic metastasis on imaging findings.

We encountered a 62-year-old female with advanced gastric cancer, in whom multiple nodular lesions in the liver, which were depicted as small low density areas, less than 5 mm in diameter, on computed tomography and demonstrated as a heterogenic pattern on ultrasonograms. This patient was suspected to have multiple liver metastases of gastric cancer. She deteriorated gradually and died of respiratory failure due to lung metastasis. At autopsy these hepatic nodular lesions were biliary hamartomas. Biliary hamartoma is a lesion usually identified microscopically, and there have been only 8 cases including ours, which were depicted on images. Along with a remarkable advance in imagings, it should become more important to differentiate biliary hamartoma from malignant hepatic neoplasms on images.

Bile Duct Diseases↗
PubMed1996

[Pathomorphologic characteristics and differential diagnosis of small hepatocellular carcinoma].

Recent advances in various diagnostic imagings have made possible early diagnosis of hepatocellular carcinoma (HCC). Grossly, small HCCs of the early stage up to around 1.5 cm in diameter are vaguely demarcated from surrounding liver tissue. Such minute tumors are classified as small HCC with indistinct margins. Histologically, these tumors consist of uniform distribution of well-differentiated cancerous tissues, which are characterized by increased cell density with increased nuclear/cytoplasmic ratio, irregular thin-trabecular pattern with occasional pseudoglandular structure, and frequent fatty and/or clear cell change. In all small HCCs with indistinct margins, varying numbers of portal tracts are contained within the cancerous tissues. None of them represents invasion of the portal vein or intrahepatic metastasis. Thus, small HCC with indistinct margins is considered to be HCC of the earliest stage that can be clinically detected at this moment. Along with the increase of resected small HCCs, hyperplastic lesions such as adenomatous hyperplasia (AH) and atypical AH, which are difficult to differentiate from well-differentiated HCC have also been found. Atypical AH is considered a borderline malignancy. Some focal nodular hyperplasias and liver cell adenomas are also difficult to differentiate from well-differentiated HCC. It should be recalled that some metastatic tumors such as carcinoid tumor, renal cell carcinoma and hepatoid adenocarcinoma also resemble HCC.

Adenocarcinoma, Clear Cell↗
PubMed1996

Fas antigen expression and its relationship with apoptosis in human hepatocellular carcinoma and noncancerous tissues.

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.

Adult↗
PubMed1995

Nodules of less-differentiated tumor within or adjacent to hepatocellular carcinoma: relative expression of transforming growth factor-alpha and its receptor in the different areas of tumor.

Expression of transforming growth factor-alpha (TGF-alpha) and its receptor, the epidermal growth factor receptor (EGFR), in hepatocellular carcinomas (HCCs) and adjacent nontumorous livers from 25 Japanese patients were examined using immunoperoxidase staining of paraffin-embedded sections. TGF-alpha was detected in 24 of 25 (96%) HCCs and 23 of 24 (96%) available adjacent nontumorous livers. EGFR was detected in 16 of 25 (64%) HCCs and 17 of 24 (71%) adjacent nontumorous livers. TGF-alpha and EGFR were not detected by immunohistochemical staining in normal livers. Fifteen of 25 HCCs contained an apparent area of a second tumor (two of the 15 also contained a third tumor) that had a less-differentiated histological grade developing within or adjacent to the first tumor. In those cases, staining in the less-differentiated area of tumor was usually less intense than in the more highly differentiated area (80% of cases for TGF-alpha; 91% for EGFR). These data confirm that increased expression of TGF-alpha and EGFR occur frequently in human HCC. Furthermore, the detection of greater staining in more highly differentiated portions of the tumors suggests that increased expression of TGF-alpha and EGFR may be events of the early stages of human hepatocarcinogenesis.

Adult↗
PubMed1995

Effects of nine active ingredients in Chinese herbal medicine sho-saiko-to on 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide mutagenicity.

The antimutagenic effects of nine active compounds in the Chinese herbal medicine "sho-saiko-to" on mutagenesis induced by a direct-acting mutagen, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) were investigated in Salmonella typhimurium, strain TA100. The active compounds examined were classified into two major groups, saponins and flavonoids, the former comprising glycyrrhizin, saikosaponins a, c, and d, and ginsenosides Rb1 and Rg1, and the latter, baicalin, baicalein and wogonin. Saikosaponin a and ginsenoside Rb1 were found to reduce the mutagenicity of AF-2 significantly when applied post-AF-2-treatment in the Salmonella mutagenicity assay. Ginsenoside Rb1 also decreased the mutagenic activity of AF-2 in a simultaneous treatment protocol. The results indicate that saikosaponin a and ginsenoside Rb1 may enhance DNA repair, and ginsenoside Rb1 may also have the ability to inactivate the mutagenic activity of AF-2 directly. On the other hand, saikosaponin d and baicalin showed a slight enhancing effect. None of the compounds, except baicalein, showed any toxic effect on the test strain. These findings may be useful for the development of chemopreventive agents.

Animals↗
PubMed1995

Establishment of a human hepatic adenosquamous carcinoma cell line (KMC-2) and its response to cytokines.

A human hepatic adenosquamous carcinoma cell line (KMC-2) was established from a serially transplanted tumor in nude mice (nuKMC-2), which originated from human cholangio-cellular carcinoma and showed histological alteration from adenocarcinoma to squamous cell carcinoma (SCC) along with serial transplantation. KMC-2 cells in monolayer culture proliferated in a sheet-like arrangement with a population doubling time of 29.5 h, whereas the cells in 0.1% collagen gel embedded culture formed a compact and tubular structure with the population doubling time of 35.4 h. The cells secreted carbohydrate antigen 19-9 (CA19-9), tissue polypeptide antigen and SCC-related antigen. The back-transplanted nude mouse tumor exhibited morphologic features of adenosquamous carcinoma resembling those in the original nude mouse tumor. IFN-alpha, IFN-gamma and TNF-alpha suppressed cell proliferation significantly. Functionally, IFN-gamma significantly suppressed CA19-9 secretion, and conversely promoted SCC-related antigen secretion. These findings suggest that KMC-2 is the first human hepatic adenosquamous carcinoma cell line primarily originated from adenocarcinoma; the environmental factors, such as the presence of extracellular matrix and the cytokines influenced the growth, morphology and function of KMC-2.

Animals↗
PubMed1995

Expression of intercellular adhesion molecule 1 in human hepatocellular carcinoma.

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.

Blotting, Western↗
PubMed1995

Expression of CD44 in human hepatocellular carcinoma cell lines.

CD44 is a glycosylated cell surface adhesion molecule expressed on a diverse range of cells and has several variant forms, some of which are involved in metastasis of cancer cells. Because little is known about CD44 in human hepatocellular carcinoma (HCC), we investigated its expression in tissue specimens from primary lesions (12 cases), in smear specimens from peritoneal effusions (2 cases), and in cell lines (HCC cell lines, KIM-1, KYN-1, KYN-2, KYN-3, HAK-1A, and HAK-1B; combined hepatocholangiocarcinoma cell lines, KMCH-1 and KMCH-2; and bile duct carcinoma cell lines, KMC-1 and KMBC). Immunohistochemical studies using monoclonal antibody recognizing epitope Group 1 of human CD44 molecule showed that HCC cells in all tissue specimens, including the original tumors of one smear specimen and HAK-1A, were negative for CD44; whereas, HCC cells in two-smear specimens, KIM-1, KYN-2, KYN-3, HAK-1A, HAK-1B, KMCH-1, KMC-1, and KMBC, showed positive reactions on the cell membrane. Immunostain-positive cell lines showed a positive cell rate of 51.9% to 99.8% by flow cytometric analysis. Western blotting detected CD44 protein of hemopoietic type in KIM-1, KYN-3, HAK-1A, and HAK-B and epithelial type in KMC-1 and KMBC. Southern blotting of complementary DNA amplified after reverse transcriptase-polymerase chain reaction (RT-PCR) detected hemopoietic type and some variant forms with longer insertion in all cell lines but KMCH-2, whereas hemopoietic type and variants with minor insertion were only detectable in tissue specimens. These findings suggest that HCC cells in ascites and in culture often express CD44, but those in tissue do not at protein level.

Base Sequence↗
PubMed1995

Pathomorphologic characteristics of small hepatocellular carcinoma: a special reference to small hepatocellular carcinoma with indistinct margins.

Some surgically resected small hepatocellular carcinoma (HCC) up to 2 cm in diameter have indistinct margins, and it is sometimes difficult to identify the margins of the cancer nodule in the resected specimen. We classified such tumors as small HCC with indistinct margins and carried out a morphological study to define their characteristics in comparison with small HCC with distinct margins as a control group. We have encountered 27 examples among 86 tumors smaller than 2.0 cm in diameter. The tumors of this type indistinctly retained the basic architecture of the background and were vaguely demarcated. Most tumors were uniformly composed of well-differentiated cancer tissue, which is characterized by increased cell density with increased nuclear/cytoplasm ratio, increased cytoplasmic eosinophilia, and irregular thin-trabecular pattern with occasional pseudoglandular pattern. Portal tracts were included within the cancerous tissue. There was a "replacing" growth pattern at the tumor/nontumor boundary. Four of the 27 lesions had a nodule-in-nodule appearance, and the inner nodules consisted of moderately differentiated HCC without portal tracts. In all of the small HCC with indistinct margins, tumor invasion into the portal vein and intrahepatic metastasis were not found. In a control group, the tumors were well-demarcated, and 53% of them were encapsulated. They were well-differentiated in 9, moderately differentiated in 38 and mixed well and moderately in 12. Tumor invasion into the portal vein and intrahepatic metastasis was found in 16 (27.1%) and 6 (10.2%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Pathomorphologic comparison of hepatitis C virus-related and hepatitis B virus-related cirrhosis bearing hepatocellular carcinoma.

A morphologic comparison between hepatitis C virus-related cirrhosis (HCV cirrhosis) and hepatitis B virus-related cirrhosis (HBV cirrhosis) was performed. The materials consisted of 37 surgical specimens obtained from patients with hepatocellular carcinoma (HCC) positive for antibodies to HCV (anti-HCV) and negative for HBV serologic markers, and 21 specimens from patients positive only for hepatitis B surface antigen (HBsAg). In addition, the evolution of the type of cirrhosis associated with HCC was studied in 43 autopsy cases from 1970 to 1975 and 44 cases from 1989 to 1994. The histological features of HCV cirrhosis are characterized by broadly expanded fibrous septa, small regenerative nodules, and a relatively strong inflammatory reaction with prominent lymphoid aggregation and mild regenerative activity of the hepatocytes. HBV cirrhosis is characterized by larger regenerative nodules, a weak inflammatory reaction, and marked regenerative activity of the hepatocytes. In a comparison of the types of cirrhosis associated with HCC during the six-year period from 1970 to 1975 with the six-year period from 1989 to 1994 at Kurume University School of Medicine, macronodular cirrhosis (which was mostly HBsAg-positive) declined from 38.8% to 13.6%; by 1989-1994, most of the associated cirrhosis was mixed macronodular and micronodular type with anti-HCV in serum (in 84%). The morphologic type of cirrhosis associated with HCC reflected the proportion of viral hepatitis due to HBV or HCV involved.

Carcinoma, Hepatocellular↗
PubMed1994

The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase.

Water-soluble ingredients of the herbal medicine sho-saiko-to dose-dependently inhibited the proliferation of a human hepatocellular carcinoma cell line (KIM-1) and a cholangiocarcinoma cell line (KMC-1). Fifty % effective doses on day 3 of exposure to sho-saiko-to were 353.5 +/- 32.4 micrograms/ml for KIM-1 and 236.3 +/- 26.5 micrograms/ml for KMC-1. However, almost no suppressive effects were detected in normal human peripheral blood lymphocytes or normal rat hepatocytes. Sho-saiko-to suppressed the proliferation of the carcinoma cell lines significantly more strongly than did each of its major ingredients, i.e., saikosaponin a, c, and d, ginsenoside Rb1 and Rg1, glycyrrhizin, baicalin, baicalein, and wogonin, or another herbal medicine, juzen-taiho-to (P < 0.05 or 0.005). Because such ingredients are barely soluble in water, there could be synergistic or additive effects of the ingredients in sho-saiko-to. Morphological, DNA, and cell cycle analyses revealed two possible modes of action of sho-saiko-to to suppress the proliferation of carcinoma cells; (a) it induces apoptosis in the early period of exposure and (b) it induces arrest at the G0/G1 phase in the late period of exposure.

Bile Duct Neoplasms↗
PubMed1994

Differential regulation of tissue transglutaminase in rat hepatoma cell lines McA-RH7777 and McA-RH8994: relation to growth rate and cell death.

Close correlation between tissue transglutaminase (tTG) induction and growth regulation and/or cell death processes has been suggested in many cell lineages. In this study, the regulation of the tTG levels by various growth and differentiation factors and its relation to growth rate and cell death processes were investigated in two rat hepatoma cell lines, McA-RH7777 and McA-RH8994, using a monoclonal antibody against liver tTG. Transforming growth factor-beta 1 (TGF-beta 1) and retinoic acid (RA) each increased tTG to the level of 8- to 32-fold above that of control cultures in both cell lines after 72-h treatment. Dexamethasone (DEX) induced a 16- to 32-fold of tTG in McA-RH8994 cells while it did not change the enzyme level in McA-RH7777 cells. Simultaneous addition of DEX and RA increased the tTG level to more than 50-fold in McA-RH7777 cells as well as McA-RH8994 cells. Other factors, such as TGF-alpha, hepatocyte growth factor, dimethyl sulfoxide, and protein kinase C activator, did not show significant increases of the tTG levels. Although tTG induction by TGF-beta 1 or DEX appeared to be correlated with their growth suppressive effects, RA increased the tTG level without suppressing the growth rate of hepatoma cells. TGF-beta 1 was also shown to induce cell death in both cell lines. Our results demonstrate that RA and DEX are capable of modulating the TGF-beta 1-induced cell death processes independent of the tTG levels. We present evidence here that tTG induction by itself is not the direct cause of growth suppression and cell death in these hepatoma cells.

Animals↗
PubMed1994

A patient with hepatic granuloma formation and angiotensin-converting enzyme production by granuloma cells during clinical relapse of hepatitis A.

Elevation of the serum angiotensin-converting enzyme (sACE) level and hepatic granulomas were found during a clinical relapse in a 22 year old patient with acute viral hepatitis type A (AVH-A). The serum transaminase level and sACE level remained high for more than 6 months. In the biopsied specimen of the liver, fibrous rings of granulomas composed of collagen types I, III, and V were observed. Furthermore, the localization of ACE was visible in the rough endoplasmic reticulum of epithelioid cells of granulomas in the liver under electron microscopy using the indirect immunoperoxidase method. These results suggest that granuloma cells in the liver caused by hepatitis A may be involved in ACE production. In addition, other diseases associated with the presence of granulomas in the liver, such as lymphoma, cytomegalovirus infection, visceral leishmaniasis, and lupoid hepatitis, were ruled out. However, the hepatic granulomas disappeared with the healing of AVH-A. In this regard, the present case is considered to be one of the very few cases of hepatic sarcoidosis.

Adult↗
PubMed1994

Squamous cell carcinoma of the ovary--a case report.

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.

Aged↗
PubMed1994

[Clinicopathological significance of adenomatous hyperplasia of the liver].

Adenomatous hyperplasia (AH) is defined as a discrete nodular lesion showing varying degrees of hepatocyte hyperplasia in chronic liver disease, particularly in liver cirrhosis. Recently, AH has attracted the attention of both clinician and pathologist regarding the possibility of the precursor lesion of hepatocellular carcinoma (HCC) because AH is frequently coexistent with HCC and occasionally contains foci of well-differentiated HCC within a nodule. Of the 60 resected HCCs, smaller than 2 cm in diameter, in case of liver cirrhosis in our hospital, AH was found in the vicinity of HCC of 7 cases (12%). Of the 8 autopsy cases of HCCs, smaller than 2 cm in diameter with liver cirrhosis, AH was found in the vicinity of HCC of 3 cases (37.5%). On the other hand, there was no association of AH in 94 resected HCCs with chronic hepatitis. Furthermore, among 51 autopsy cases of liver cirrhosis, 41 nodular lesions, smaller than 2 cm in diameter, were found and 23 large regenerative nodules (56.1%), 6 AHs (14.6%), 4 AHs containing cancerous foci (9.8%) and 8 HCCs (19.5%). Accordingly, if AH could be a precursor of HCC, it could be said that approximately 12-37.5% of HCC would be multicentric origin and the association of liver cirrhosis would be inevitable for the multicentric occurrence of HCC from the view point of morphologic observation. Together with frequent association of HCC and AH, and the presence of AH containing HCC foci, AH may have a high potency of a precursor lesion, and it is important to conduct a meticulous follow-up for AH.

Carcinoma, Hepatocellular↗