Alpha<sub>1</sub>Fetoglobulin in the Diagnosis of Human Hepatoma

Alpert, M.E.; Uriel, J; Néchaud, Béatrice de

doi:10.1056/nejm196805022781804

Cited by 244 publications

(53 citation statements)

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“…However, most hepatoma cells re-express the AFP gene. 12 There has been a great deal of progress in characterization of cis-and trans-acting elements regulating the human AFP gene. [13][14][15][16][17] The AFP gene silencer elements existing between its enhancer and promoter regions play a major role in repressing the AFP gene expression in the low AFP-producing hepatoma cells.…”

Section: Discussionmentioning

confidence: 99%

Utilization of variant-type of human α-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma

et al. 1999

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We previously reported that the retroviral vector intermediate AFP-producing cells (PLC/PRF/5). By the (LNAFW0.3TK) expressing the herpes simplex thymidine reporter gene transfection assay, the activity of the variantkinase (HSVtk) gene under the control of the 0.3 kb human type of the promoter was much higher than that of the wild-␣-fetoprotein (AFP) promoter provided the ganciclovir type of the promoter in both HuH-7 and huH-1/cl.2 cells. (GCV)-mediated cytotoxicity in the high AFP-producing Consistent with this, LNAFM0.3TK infection could sensitize (HuH-7) but not in the low AFP-producing (huH-1/cl.2) huH-1/cl.2 cells, as well as HuH-7 and PLC/PRF/5 cells to human hepatoma cells. In the present study, we con-GCV, but did not affect cell growth of nonhepatoma cells structed the retroviral vector (LNAFM0.3TK) in which the (HeLa). In addition, the bystander effect was achieved HSVtk gene expression is regulated by the variant-type of more efficiently by LNAFM0.3TK infection than the 0.3 kb human AFP promoter with a G-to-A substitution LNAFW0.3TK infection in HuH-7 cells. These results sugat nucleotide −119, a point mutation responsible for heredigest that the variant-type of the human AFP promoter tary persistence of human AFP and the vector was applied ensures the therapeutic gene expression in gene therapy to three human hepatoma cell lines, HuH-7, huH-1/cl.2 and particularly for the low AFP-producing hepatoma cells.

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Section: Discussionmentioning

confidence: 99%

Utilization of variant-type of human α-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma

et al. 1999

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“…In this case sera were examined for the presence of the fetoprotein (Alpert et al 1971) which when found essentially always signifies the diagnosis of hepatoma (Alpert et al 1968). Fetoglobulin was found in the preoperative sample.…”

Section: Liver Transplantation For Hepatomamentioning

confidence: 99%

Iatrogenic Alterations of Immunologic Surveillance in Man and Their Influence on Malignancy

Starzl

Penn

Putnam

et al. 1971

Immunological Reviews

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The surveillance hypothesis of the immunologic control of malignancy has far-reaching clinical implications, of which two major and essentially opposite ones will be considered in this communication. The first concerns the growth of tumors in patients with surveillance failure. From the premise of Burnet (1957Burnet ( , 1963Burnet ( , 1967Burnet ( , 1970 and Thomas (1959), it could have been predicted and was (Thomas 1959, Starzl 1964b, Schwartz et al. 1966) that an increased incidence of de novo tumors would develop in people with naturally occurring immunologic deficiency diseases or in patients whose immune reactivity was deliberately depressed in order to permit their acceptance of organ homografts. The hazard of malignancy consequent to spontaneous deficiency is so well known (Page et al. 1963, Green et al. 1966, Dent et al. 1968, Huber 1968) that it will not be reviewed here. However, the analogous data in iatrogenically immunosuppressed transplant recipients that have accumulated since 1968 will be brought up to date. In addition, some comments will be made about the accidental transplantation of tumors to immunologically depressed humans and about the growth of metastases or residual tumor under these same conditions.The second general topic of this report, and a far more interesting one from a therapeutic point of view, is the expectation that the artificial endowment of immunologic surveillance in a patient whose natural defense system had failed to prevent neoplasia might then have an inhibitory or even destructive effect upon the established growth. Of course, a necessary condition to evaluate this latter possibility is the successful transplantation of immunologically competent tissue such as spleen or bone marrow while at the same time avoiding the kind of fatal graft-versus-host reaction that has defeated essentially all efforts at bone marrow grafting for whatever purpose except between a few HL-A identical siblings. As a first step toward this previously unattainable goal, suggestions will be made for the application to the bone marrow problem of immunosuppressive regimens that have been evolved in the successful transplantation of whole organs such as the kidney, liver, and heart. IMMUNOSUPPRESSION AND DE NOVO MALIGNANCIESAlthough it was hardly surprising when it occurred, a convincing association between immunosuppression and new malignant neoplasms was not claimed until European and American meetings held respectively in March and April 1968. Prior to the first of these conferences, two reticulum cell sarcomas had been observed in our own patients and an anaplastic neoplasm (later judged to be a carcinoma) had been contributed to us by Dr. Claude Hitchcock of Minneapolis; in discussion of the paper from the floor, Woodruff added another reticulum cell sarcoma from his Edinburgh experience. By the time of the second meeting in Boston less than a month later, a third lymphoma had been encountered in our series. The five cases were discussed again at a Dundee, Scotland, cancer NIH Public Access ...

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“…In 1963, alpha-fetoprotein (AFP) was first found in the serum of mice suffering from liver cancer; Soon afterwards it was detected in the serum of hepatocellular carcinoma patients in 1964 (Alpert et al, 1968;Abelev et al, 1971). From then on, AFP, as a generally accepted tumor marker, especially used for diagnosis of HCC, was gradually concerned by us.…”

Section: Introductionmentioning

confidence: 99%

Distinctions Between Clinicopathological Factors and Prognosis of Alpha-fetoprotein Negative and Positive Hepatocelluar Carcinoma Patients

Xu¹,

Liu²,

Zhou³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Serum alpha-fetoprotein (AFP) is a significant marker for clinical diagnosis and prognosis evaluation in hepatocellular carcinoma (HCC) patients. However, some proportion of liver cancer patients are AFP-negative (AFP ≤20ng/ml). In order to study the differences between clinicopathological factors and prognosis of alphafetoprotein negative and positive patients, a total of 114 cases (41 AFP-negative and 73 AFP-positive) were selected for our research. By systematically statistical analysis, the results demonstrated that compared with AFPnegative patients, AFP-positive examples were more likely to feature cirrhosis nodules, non-complete neoplasm capsules, and a poor Edmondson-steiner grade. Furthermore, AFP-negative patients demonstrated a favorable long-term prognosis. By univariate analysis and multivariate analysis with Cox's proportional hazards model, multiple tumors were found to be independent risk factors for worse survival of AFP negative patients; however, less tumor-free margins, multiple tumors and Edmondson-steiner grades Ⅲ/Ⅳ, proved to be independent risk factors leading to a poor prognosis of AFP positive cases. Finally, we can infer that high levels of AFP signify a highly malignant tumor and unfavorable prognosis.

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Alpha₁Fetoglobulin in the Diagnosis of Human Hepatoma

Cited by 244 publications

References 9 publications

Utilization of variant-type of human α-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma

Utilization of variant-type of human α-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma

Iatrogenic Alterations of Immunologic Surveillance in Man and Their Influence on Malignancy

Distinctions Between Clinicopathological Factors and Prognosis of Alpha-fetoprotein Negative and Positive Hepatocelluar Carcinoma Patients

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Alpha1Fetoglobulin in the Diagnosis of Human Hepatoma

Cited by 244 publications

References 9 publications

Utilization of variant-type of human α-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma

Utilization of variant-type of human α-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma

Iatrogenic Alterations of Immunologic Surveillance in Man and Their Influence on Malignancy

Distinctions Between Clinicopathological Factors and Prognosis of Alpha-fetoprotein Negative and Positive Hepatocelluar Carcinoma Patients

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Alpha₁Fetoglobulin in the Diagnosis of Human Hepatoma