Drug Targeting in Human Cancer Chemotherapy

Schneider, Y.‐J.; Abarca, Jorge; Aboud-Pirak, Esther; Baurain, R.; Ceulemans, F.; Campeneere, D. Deprez-De; Lesur, Brigitte; Masquelier, Michèle; Otteslachmuylder, C.; Swieten, D. Rolin-Van; Trouet, André

doi:10.1007/978-1-4684-4862-7_1

Cited by 19 publications

(14 citation statements)

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“…The conjugates selectively enter hepatocytes, where the lysosomal enzymes split the bond between the carrier and the drug, which becomes concentrated in liver cells. A similar strategy was suggested in order to increase the chemotherapeutic index of drugs inhibiting DNA synthesis in the treatment of human hepatocellular carcinoma (HCC) (Schneider et al, 1984;O'Hare et al, 1989;Di Stefano et al, 1998). This approach obviously requires the presence of the receptor in the neoplastic tissue and maintenance of its expression on DNA synthesizing cells.…”

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confidence: 99%

The asialoglycoprotein receptor in human hepatocellular carcinomas: its expression on proliferating cells

et al. 1999

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The asialoglycoprotein receptor (ASGP-R) is a glycoprotein present in large amount only on hepatocytes where it is expressed on the sinusoidal and lateral plasma membrane (Morell et al, 1968;Geffen and Spiess, 1992). ASGP-R binds and internalizes a broad range of molecules exposing galactose or N-acetyl-galactosamine residues. Following internalization the fate of ligand is lysosomal degradation (Morell et al, 1968;Geffen and Spiess, 1992).Taking advantage of this receptor a chemotherapeutic approach has been developed to reduce the extrahepatic side-effects of nucleoside analogues (NAs) used in chronic viral hepatitis (Fiume et al, 1979(Fiume et al, , 1997 Torriani et al, 1996). These drugs are coupled to galactosyl-terminating peptides. The conjugates selectively enter hepatocytes, where the lysosomal enzymes split the bond between the carrier and the drug, which becomes concentrated in liver cells. A similar strategy was suggested in order to increase the chemotherapeutic index of drugs inhibiting DNA synthesis in the treatment of human hepatocellular carcinoma (HCC) (Schneider et al, 1984;O'Hare et al, 1989;Di Stefano et al, 1998). This approach obviously requires the presence of the receptor in the neoplastic tissue and maintenance of its expression on DNA synthesizing cells.Few and conflicting data are available on the distribution of ASGP-R in human neoplastic hepatocytes. In a study in which the receptor was measured by a biochemical procedure, it was not found in HCC samples (Sawamura et al, 1984), whereas in an immunohistochemical investigation carried out on ten cases of HCC the presence of the receptor was demonstrated in the more differentiated forms (Hyodo et al, 1993). In the present study we have first assessed the frequency of ASGP-R expression in a large number of human HCCs. For this purpose, needle biopsy samples of sixty consecutive HCCs were analysed. Visualization of the receptor was obtained using an anti-ASGP-R monoclonal antibody applied after antigen retrieval procedure to routinely formalinfixed, paraffin-embedded liver samples. Since we found that the ASGP-R was present in 33 HCCs we also investigated whether the ASGP-R was maintained on the plasma membrane of DNA synthesizing cancer cells. For this purpose we incubated HCC tissue samples with bromodeoxyuridine (BrdU). The presence of ASGP-R on DNA-synthesizing cancer cells was immunohistochemically assessed using anti-BrdU and anti-ASGP-R antibodies on the same tissue section. Summary The expression of the asialoglycoprotein receptor (ASGP-R) on human hepatocellular carcinoma (HCC) cells might be exploited to reduce the extrahepatic toxicity of DNA synthesis inhibitors by their conjugation with galactosyl-terminating peptides. In the present study we first assessed the frequency of ASGP-R expression in 60 HCCs. Secondly, we investigated whether the receptor was maintained on the plasma membranes of DNA synthesizing cancer cells. Needle biopsies of HCC were evaluated. Diagnosis and grading of HCC were performed on routine haematoxyli...

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confidence: 99%

The asialoglycoprotein receptor in human hepatocellular carcinomas: its expression on proliferating cells

et al. 1999

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“…T AAs are present on the surface of embryonic cells and reappear in the course of malignant transformations or exist in small amounts on normal cells and in large amounts on tumor cells. Tumor specific antigens may be expressed during malignant transformations and are expressed at the surface of tumor cells (SCHNEIDER et al 1984). Monoclonal antibodies have been produced which react with a wide range of human cancers, including carcinomas of the colon, rectum, breast, ovary, lung, pancreas, and bladder, malignant melanomas, bone and soft tissue sarcomas, and leukemias.…”

Section: Antibodiesmentioning

confidence: 99%

“…(For informative reviews on polymeric antitumor drugs see DORN et al 1985, FERRum and TANZI 1986, SEZAKI et aI, 1989and HOES and FEUEN 1989.) The main criteria to be followed in designing these targetable polymer conjugates are (SCHNEIDER et al 1984):…”

Section: E Targeting I Principles Of Targetingmentioning

confidence: 99%

Soluble Polymers as Targetable Drug Carriers

Krinick¹,

Kopeček²

1991

Targeted Drug Delivery

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“…In addition to organ-specific drug delivery, targeting to the galactose receptor may also permit tumour-selective therapy since some human primary hepatomas are known to retain the galactose receptor (Schneider et al, 1984 (Figure 6). …”

Section: Assessment Of Release Of Liver Enzymesmentioning

confidence: 99%

“…Indeed, the hepatocyte galactose receptor itself is retained by some human primary hepatomas (Schneider et al, 1984) and may represent a useful target for the treatment of this disease.…”

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confidence: 99%