Self-regulation of type I collagen degradation by collagen-induced production of matrix metalloproteinase-1 on cholangiocarcinoma and hepatocellular carcinoma cells.
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Animals↗
Biomedical subjects
M Enjoji
Publications and source records attributed to M Enjoji.
Reversibility of serum NH3 level in a case of sudden onset and rapidly progressive case of type 2 citrullinemia.
A 48-year-old male presented with an acute change in mental status due to a marked elevation of plasma NH3 and was diagnosed with citrullinemia with amino acid analysis of blood. Hemodialysis and hemodiafiltration were performed, but serum chemical analysis did not show any improvement which led us to terminate dialysis following intensive care for 3 days. Surprisingly, NH3 level had decreased by 6 days after admission, coinciding with normalization of the size of the pupils. Since spontaneous remission had never been discussed, we discuss this relatively rare, but clinically significant entity with regard to its acute phase management and its potential reversibility.
Ammonia↗
Hammerhead ribozyme cleavage of apolipoprotein B mRNA generates a truncated protein.
Target substrate-specific hammerhead ribozyme cleaves the specific mRNA and results in the inhibition of gene expression. In humans, overproduction of apolipoprotein B (apoB) is positively associated with premature coronary artery diseases. To modulate apoB gene expression, we designed hammerhead ribozymes targeted at AUA(6665) and GUA(6679) of apoB mRNA, designated RB16 and RB15, respectively, and investigated their effects on apoB mRNA in HepG2 cells. The results demonstrated that RB15 and RB16 ribozyme RNAs cleaved apoB RNA efficiently in vitro. Both ribozymes, RB15 and RB16, were used to construct recombinant adenoviral vectors, designated AvRB15 and AvRB16, respectively, for in vivo gene transfer. HepG2 cells were infected with 2 x 10(5) plaque-forming units of AvRB15 for 5, 10, 15, and 24 h. An RNase protection assay showed that the expression of the RB15 transcript was time-dependent; it increased approximately 300-fold from 5 to 24 h. Using reverse ligation-mediated polymerase chain reaction, the 3' cleavage product of apoB mRNA was detected, and the exact cleavage site of apoB mRNA was confirmed by sequencing. Importantly, the levels of apoB mRNA in HepG2 cells decreased approximately 80% after AvRB15 infection. Pulse/chase experiments on HepG2 cells treated with AvRB15 and AvRB16 demonstrated that ribozyme cleavage produced a truncated protein that was secreted at a density of 1. 063-1.210 g/ml. The cleavage activity of RB15 on apoB mRNA was more efficient than that of RB16. Moreover, pulse/chase experiments in HepG2 cells treated with AvRB15 revealed that most of the truncated apoB protein was degraded intracellularly. We conclude that hammerhead ribozyme targeted at GUA(6679) of apoB mRNA cleaves apoB mRNA, results in decreased apoB mRNA levels, and generates a truncated apoB of the expected size in vivo. Thus, the therapeutic application of ribozyme in regulating apoB production holds promise.
Adenoviridae↗
Serum level of interleukin-4 is a possible marker of therapeutic response to interferon treatment in patients with chronic hepatitis C.
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Antiviral Agents↗
Integrins: utility as cell type- and stage-specific markers for hepatocellular carcinoma and cholangiocarcinoma.
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Biomarkers, Tumor↗
Hepatocytic phenotypes induced in sarcomatous cholangiocarcinoma cells treated with 5-azacytidine.
The sarcomatoid cells found in cholangiocarcinoma (CC) or hepatocellular carcinoma (HCC) are not well characterized. In this study, a human sarcomatoid CC cell line, ETK-1, was established from a patient, and then morphological and phenotypical characteristics of the ETK-1 cells were evaluated before and after treatment with differentiation-inducing 5-azacytidine (5-azaCR). Phenotypically, the ETK-1 cells appeared immature. Exposure to 5-azaCR induced morphological transformation; a converted cell line, MEK, was successfully established. The MEK cells expressed such hepatocyte-specific proteins as alpha-fetoprotein, albumin, integrin alpha1, and thrombopoietin, but lost such bile duct-specific proteins as integrin alpha3 and integrin beta4. The histopathology of MEK xenografts resembled that of HCC. The ETK-1 cells appeared to be converted into hepatocytes by exposure to 5-azaCR. On the other hand, ETK-1 xenografts were diagnosed as tubular adenocarcinoma, and the tumor cells had a ductal phenotype. This suggests the possibility that ETK-1 cells can differentiate along a biliary epithelial cell lineage. ETK-1 and MEK will be useful in studying hepatocytic differentiation and the transformation from a biliary epithelial cell to a hepatocytic lineage.
Animals↗
Sarcomatous and adenocarcinoma cell lines from the same nodule of cholangiocarcinoma.
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Adenocarcinoma↗
Establishment and characterization of choroid plexus carcinoma cell lines: connection between choroid plexus and immune systems.
Murine choroid plexus cell lines were produced from choroid plexus carcinoma generated in transgenic mice harboring the viral oncogene simian virus 40 large tumor antigen under transcriptional control of an intronic enhancer region from the human immunoglobulin heavy chain (IgH) gene. Two morphologically distinct cell lines have been cloned. These established cell lines retained the characteristics of choroid plexus cells in that they expressed such choroid plexus cell marker or related proteins as transthyretin and alpha2-macroglobulin. They were tumorigenic in nude mice. In the cell lines, the muA and muB (HE2) motifs within the IgH intronic enhancer were active and we also demonstrated the existence of the proteins binding to these motifs, suggesting a potential link between the choroid plexus and immune systems. It is considered that these binding proteins act as trans-activators for the enhancer and may belong to the class of ETS-related proteins. These cell lines and xenografts should be useful materials for analyses of choroid plexus functions.
Animals↗
Case report: intrahepatic cholangiocarcinoma with rhabdoid transformation.
Sarcomatous transformation is found in approximately 5% of patients with intrahepatic cholangiocarcinoma. According to previous reports, sarcomatous cholangiocarcinomas are composed of spindle-shaped cells and/or multinucleated giant cells. Usually, vimentin is expressed by these sarcomatoid cells. We report a case of intrahepatic cholangiocarcinoma with an element of rhabdoid cells that occurred in a 61-year-old woman admitted for back pain. Various imaging techniques demonstrated multiple liver masses. Histologically, these tumours formed in both sarcomatous and ordinary tubular adenocarcinomatous areas. The sarcomatoid areas were occupied mainly by loosely arranged, eosinophilic rhabdoid cells, which expressed both keratin and vimentin. These findings suggest that rhabdoid cells may occur in an undifferentiated stage of cholangiocarcinoma and possess a strong tendency to metastasize.
Bile Duct Neoplasms↗
IgH intronic enhancer element HE2 (mu B) functions as a cis-activator in choroid plexus cells at the cellular level as well as in transgenic mice.
Immunoglobulin heavy-chain (IgH) gene expression is regulated largely by the IgH gene intronic enhancer (ENHiH), which is composed of multiple protein-binding motifs. These motifs are DNA elements that are important for the regulation of IgH gene transcription. It has been reported that the HE2 (mu B) and mu A motifs within the ENHiH affect B cell-specific gene expression. To examine the function of the HE2 and mu A elements in vivo, we established transgenic mouse lines. A deletion mutant of the human ENHiH that contains the HE2 and mu A motifs, but lacks the motifs corresponding to murine E5, E3, and octamer, functioned not only in B lymphocytes but also in choroid plexus cells, which secrete CSF. As a result, we obtained choroid plexus tumor-bearing transgenic mice and could establish choroid plexus carcinoma cell lines. In addition, using the luciferase assay, we confirmed at the cellular level that the HE2 motif shows a fair degree of enhancer activity in cultured choroid plexus carcinoma cells. These results suggest the existence of a trans-acting factor for the HE2 motif in choroid plexus cells. Actually, in this cultured cell line, the existence of a protein binding to the HE2 motif was demonstrated by a gel retardation assay. Due to the sequence homology between the HE2 motif and the Ets-binding sites, an Ets-related protein is a highly probable candidate for being the binding factor.
Animals↗
Establishment of a melanoma cell line with metastatic characteristics.
We report here the establishment and characterization of a human melanoma cell line derived from the ascitic fluid of a patient with metastatic malignant melanoma with peritonitis carcinomatosa. This cell line was easily transplanted into nude mice. Flow cytometry and immunocytochemical analyses demonstrated that the cells expressed melanotransferrin and S-100 protein. Expression of cell adhesion and HLA molecules on the cells was also investigated. The results indicate that the cell line possesses some metastatic characteristics.
Aged↗
Human HE2 (microB) and microA motifs show the same function as whole IgH intronic enhancer in transgenic mice.
In the murine IgH gene intronic enhancer (ENHiH), two major functional domains were reported. One is the E4/octomer region and another includes the microA and microB motifs. In the human ENHiH, it was reported that the HE2, which corresponds to the murine microB, and E6 motifs play an important role in an enhancer activity and a tissue-specificity at cellular level. Here we examined the in vivo function of the E6, microA and HE2 motifs within the human ENHiH by using the transgenic mice technique. The microA and HE2 motifs together revealed almost the same enhancer function as the whole human ENHiH, but the E6 motif had lesser enhancer activity and tissue-specificity.
Animals↗
Transitional cell carcinoma pattern in primary carcinoma of the fallopian tube.
BACKGROUND: A broad papillary proliferation resembling that in transitional cell carcinoma (TCC) of the urinary bladder was seen in 12 of 21 primary carcinomas of the Fallopian tube (PCFT). METHODS: According to their predominant histologic pattern (more than 50%), PCFT were classified into 9 TCC-predominant and 12 non-TCC-predominant tumors. The two groups were compared by clinicopathologic, histochemical, and immunohistochemical means. RESULTS: TCC-predominant tumors were grossly solid and microscopically demonstrated more frequent tumor necrosis and spindled tumor cells than non-TCC-predominant tumors. Mucin histochemistry revealed a correlation between TCC-predominant tumor and sulfomucin-predominant secretion and between non-TCC-predominant tumor and sialomucin-predominant secretion. Immunohistochemical studies for cytokeratins, vimentin, epithelial membrane antigen (EMA), Leu-M1, carcinoembryonic antigen (CEA), and CA 125 were not useful for discrimination between the two groups. Both groups showed similar features in patient age, clinical stage, cytology of ascites or peritoneal washing, and serum CA 125 level. Despite the similarity in treatment (surgery and postoperative chemotherapy) between the two groups, TCC-predominant tumors tended to relapse later (mean, 31.2 months after diagnosis) than non-TCC-predominant tumors (mean, 14.4 months after diagnosis), resulting in a significant difference in the 2-year disease-free survival rate. CONCLUSIONS: TCC pattern and non-TCC pattern are considered to be worthy of distinction in PCFT.
Adult↗
Prognostic factors of malignant fibrous histiocytoma of bone. A clinical and histopathologic analysis of 34 cases.
BACKGROUND: Malignant fibrous histiocytoma (MFH) of bone is a rare bone tumor, and its prognosis has been controversial. METHODS: Thirty-four patients with MFH of bone were examined clinicopathologically for prognostic factors. RESULTS: The most common skeletal site of the tumor was the femur (15 cases), followed by the pelvic bones (6 cases), tibia (5 cases), and fibula (5 cases). Of 29 patients available for follow-up, the 5-year survival rate of 17 who underwent adequate surgical treatment was 63%. The 5-year survival rate of the remaining 12 patients, including 5 with MFH of the pelvic bone who received inadequate or palliative surgery, was 17%. All six patients who received intensive chemotherapy combined with adequate surgical treatment were alive and well 5 years after the initial treatment. Histologically, the presence of desmoplasia and chronic inflammatory infiltration in the tumor tended to be prognostic indicators, although not to a statistically significant extent. Patients whose tumors contained wide areas of desmoplasia had a worse prognosis (5-year survival rate, 20%). In contrast, those with a prominent chronic inflammatory infiltrate had a 5-year survival rate of 78%. CONCLUSIONS: These histologic variables would be helpful for predicting the prognosis of MFH of bone. Adjuvant intensive chemotherapy combined with adequate initial surgery may effect a clinical cure.
Adolescent↗
Microvascular architecture of early gastric carcinoma. Microvascular-histopathologic correlates.
BACKGROUND: Gastric carcinoma is clinicopathologically divided into differentiated and undifferentiated types. The former is grossly protuberant and often causes hematogenous metastasis to the liver or lung, whereas the latter is mostly depressed or ulcerated from its early stage and rarely causes blood-borne metastasis. The purpose of this study is to clarify the microvascular architecture of early gastric carcinoma with reference to the histologic subtypes. METHODS: A silicone rubber compound (Microfil) injection method with a methyl salicylate clearing technique was used in 32 resected early gastric carcinomas. The microvascular architecture was observed both in the carcinoma and its surrounding noncancerous tissue in each specimen under a stereomicroscope and light microscope. RESULTS: Compared to the surrounding normal mucosa, the differentiated carcinomas (DC) mostly were hypervascular (24%) or normovascular (65%), whereas the undifferentiated carcinomas (UC) often were hypovascular (60%). Irregularity of tumor vessels (67%) and an arcade-like appearance (33%) was encountered frequently in UC, whereas hypervascularity of the surrounding noncancerous mucosa (29%) often was noticed in DC. Quantitative analysis, including vascular volume, mean vascular diameter, and cut section area, supported these differences between DC and UC. CONCLUSIONS: The results suggest that vascular structures of gastric carcinomas are characteristic with regard to their histologic subtypes; DC is normovascular or hypervascular, whereas UC is hypovascular.
Carcinoma↗
Benign schwannoma in the hepatoduodenal ligament: report of a case.
A 62-year-old woman with a large mass in the hepatic hilus underwent surgery. Histologically the tumor was predominantly composed of spindle-shaped cells with nuclear palisading and cells that stained positively for S-100 protein. The diagnosis was benign schwannoma (neurilemoma). The presence of lymphoid cuffing with lymphoid follicles in the capsule and xanthomatous change differed from conventional soft parts schwannoma and closely resembled benign schwannoma in the gastrointestinal tract.
Bile Duct Neoplasms↗
Malignant oncocytoma of the parotid gland: a case report with an immunohistochemical and ultrastructural study.
A rare case of a 71-year-old man with malignant oncocytoma is presented. The tumour was found in the left parotid region with enlarged lymph nodes in the neck. The resected parotid mass consisted of three discrete nodules, each histologically characterized by a uniform proliferation of oncocytic tumour cells. The patient underwent repeated operations for recurrences and metastases, and eventually died of acute pneumonia 18 months after the first admission. Metastases to the lymph nodes, ribs, spine and liver had been clinically pointed out. Immunohistochemically, the tumour cells were positive for alpha-1-antitrypsin, alpha-1-antichymotrypsin, lactoferrin, secretory component and carcinoembryonic antigen (CEA), while they were negative for S-100 protein and HHF35 (muscle specific actin). Ultrastructural pictures disclosed numerous mitochondria in the cytoplasm of the tumour cells, revealing neither myofibrils nor secretory granules. These findings therefore support the concept that this tumour is of a glandular epithelial origin.
Adenoma↗
Prognostic significance of histologic parameters of soft tissue sarcomas.
BACKGROUND AND METHODS: A univariate and multivariate analysis for the correlation between histomorphologic factors and prognosis was made using data from 1116 patients with soft tissue sarcoma, including 1005 cases available with complete histologic and follow-up data. RESULTS: The overall 5-year survival rate was 43.6%. The univariate analysis using Kaplan-Meier survival curves showed that tumor differentiation, cellularity, nuclear atypia, cellular pleomorphism, mitotic activity, amount of fibrous stroma, extent of myxoid areas, extent of tumor necrosis, and histologic grading (determined by the estimated range of malignancy for each type of sarcoma using a reported guideline) were all significant prognostic factors in the overall soft tissue sarcoma group. By a multivariate analysis using a procedure based on the Weibull model to failure data, the histologic grading and extent of tumor necrosis were proved to be prognostically significant in the overall sarcoma group. However, after additional analysis on each histologic type of sarcoma, it was determined that both tumor necrosis and histologic grading were applicable in only two types: malignant fibrous histiocytoma and leiomyosarcoma. Liposarcoma, synovial sarcoma, and malignant schwannoma each also showed some determinable factor of prognostic significance. CONCLUSIONS: It was concluded that there seemed to be no single universal prognostic parameter that could be applied to each soft tissue sarcoma type. These results suggest that the predictive significance of the various histologic parameters should be based on each specific type of sarcoma.
Adolescent↗