Analysis of the cell culture fluid from two new human hepatoma-derived cell lines reveals that 17 of the major human plasma proteins are synthesized and secreted by these cells. One of these cell lines, Hep 3B, also produces the two major polypeptides of the hepatitis B virus surface antigen. When Hep 3B in injected into athymic mice, metastatic hepatocellular carcinomas appear. These cell lines provide experimental models for investigation of plasma protein biosynthesis and the relation of the hepatitis B viru genome to tumorigenicity.

https://science.sciencemag.org/content/sci/209/4455/497.full.pdf

Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen.

Free radicals, antioxidant enzymes, and carcinogenesis

Cellular and molecular diversities of mammalian skeletal muscle fibers

HPMA copolymer-anticancer drug conjugates: design, activity, and mechanism of action.

Targeted drug delivery by thermally responsive polymers.

A patient with primary gastric adenocarcinoma with extremely high serum alpha-fetoprotein (AFP) levels (12,000 ng/ml) is described. Histologically, foci strongly resembling hepatocellular carcinoma with hyaline globules were noted. Within tumor cells, AFP was identified with both light and electron microscopy, showing the production of AFP by tumor cells themselves. Furthermore, 88% of serum AFP combined with Concanavalin A (ConA), revealing that it was hepatic-type AFP and not germ-cell-type. Localization of alpha-1-antitrypsin within tumor cells was also noted. Ultrastructural study showed that there were two types of structures corresponding to periodic acid-Schiff (PAS)-positive globules, one of which, the proteinaceous material in intracytoplasmic lumina, was found to contain AFP. Among gastric adenocarcinomas with a high serum AFP level (several thousand or more ng/ml of AFP), foci resembling hepatocellular carcinomas have been reported by several investigators. Those gastric carcinomas, together with the current case, may constitute a clinicopathologic entity, hepatoid adenocarcinoma of the stomach.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819850815%2956%3A4%3C840%3A%3AAID-CNCR2820560423%3E3.0.CO%3B2-E

An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report

We have analyzed collagenous components produced by an albumin-producing rat liver parenchymal cell clone (BB) in culture. The cells secreted over 90% of the [3H]proline-labeled collagenous components into the medium after 18 h of incubation in vitro. Analysis of the components by sodium dodecyl sulfate-polyacrylamide gell electrophoresis and by carboxymethylcellulose chromatography of cyanogen bromide peptides after separation of individual collagen chains showed that the cells produced type I, type I trimer, and type II collagens in the ration 59:29:4. These components account for over 90% of the collagen isolated. Type I and type I trimer collagens were present in both the medium and cell layer fractions, but type III collagen was found solely in the medium. The cells also produced other minor collagenous components, one of which was quite similar to type V collagen. Analysis of collagen components produced by another liver parenchymal cell clone (BC) and by three subclones derived from BB cells showed that these cloned cells synthesized similar types of collagen. These results support the idea that parenchymal cells play an essential role in the heaptic connective tissue metabolism under normal and pathological conditions.

Biosynthesis of interstitial types of collagen by albumin-producing rat liver parenchymal cell (hepatocyte) clones in culture

Biochemical and immunohistochemical analyses were done on five cases of gastric carcinoma with excessive production of alpha-fetoprotein (AFP). Histologic and ultrastructural examination of these cases showed conventional poorly differentiated adenocarcinoma of cuboidal or polygonal tumor cells in the medullary area with scattered AFP-positive cancer cells. Comparative studies on serum AFP between these cases and in hepatocellular carcinoma (HCC) or in testicular yolk sac tumor cases using concanavalin A (ConA)-affinity and lens culinalis agglutinin A (LCA)-affinity sepharose columns revealed that the AFP derived from four cases had a high ConA nonadsorping rate and high LCA-reactive fraction similar to that of yolk sac tumor. The AFP from one case had a small LCA-reactive fraction similar to that of HCC. Further immunohistochemical study using several markers for liver cells or germ cell tumor did not show additional evidence of these tumor cells to differentiate into liver cells or yolk sac tumor cells. Thus, this study indicates that AFP-producing gastric carcinomas are not always derived from hepatoid differentiation of the foregut. These gastric carcinomas might be categorized into medullary tumor with gastrointestinal tract-specific AFP.

Alpha-fetoprotein (AFP)-producing gastric carcinoma. Is it hepatoid differentiation?

Using the indirect immunoperoxidase method, we studied the localization of carbonic anhydrase-III (CA-III) in frozen sections of biopsies of human skeletal muscle which had no definite pathology. CA-III was found to be localized in Type-I muscle fibers when compared with serial sections stained with myosin ATPase and other reactions. Our finding was in accordance with the biochemical data so far reported. It was thought that CA-III could be used as a marker for abnormal Type-I muscle fibers in several neuromuscular diseases.

Carbonic anhydrase-III immunohistochemical localization in human skeletal muscle

Ubiquitin, which can conjugate with cellular proteins, is classified into two forms: free ubiquitin and multiubiquitin chains. The latter is active as a signal for degradation of the targeted proteins. We found both forms in human serum and, using two immunoassays, quantitated them in sera from healthy subjects and patients with some diseases. Because of putative leakage of erythrocyte ubiquitin, hemolytic serum and serum obtained after long incubation (> 1-2 h) of blood at room temperature were excluded. Serum concentrations of multiubiquitin chains and free ubiquitin were substantially higher in rheumatoid arthritis and hemodialysis patients, respectively, than healthy subjects. Additionally, in acute viral hepatitis, serum multiubiquitin chain concentrations were increased in the acute phase, decreased in the recovery phase, and correlated with alanine and aspartate aminotransferase activities (r = 0.676 and 0.610, P < 0.0001 and < 0.001, respectively). Therefore, serum ubiquitin may have prognostic value.

/pdf/serum-concentrations-of-free-ubiquitin-and-multiubiquitin-1oss0d7oj6.pdf

Yutaka Tsukada

Papers

An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report

Biosynthesis of interstitial types of collagen by albumin-producing rat liver parenchymal cell (hepatocyte) clones in culture

Alpha-fetoprotein (AFP)-producing gastric carcinoma. Is it hepatoid differentiation?

Carbonic anhydrase-III immunohistochemical localization in human skeletal muscle

Serum concentrations of free ubiquitin and multiubiquitin chains