Low-density lipoprotein as a potential vehicle for chemotherapeutic agents and radionucleotides in the management of gynecologic neoplasms.
Identifieur interne : 003756 ( Main/Exploration ); précédent : 003755; suivant : 003757Low-density lipoprotein as a potential vehicle for chemotherapeutic agents and radionucleotides in the management of gynecologic neoplasms.
Auteurs : D. Gal ; M. Ohashi ; P C Macdonald ; H J Buchsbaum ; E R SimpsonSource :
- American journal of obstetrics and gynecology [ 0002-9378 ] ; 1981.
Descripteurs français
- KwdFr :
- ADN (métabolisme), Adénocarcinome (métabolisme), Animaux, Antinéoplasiques (administration et posologie), Carcinome épidermoïde (métabolisme), Cellules cultivées, Cholestérol (biosynthèse), Femelle, Humains, Lipoprotéines LDL (métabolisme), Lipoprotéines LDL (usage thérapeutique), Radio-isotopes de l'iode (administration et posologie), Souris, Souris nude, Techniques de culture d'organes, Tumeurs de l'utérus (), Tumeurs de l'utérus (métabolisme), Tumeurs du col de l'utérus (métabolisme), Véhicules pharmaceutiques.
- MESH :
- administration et posologie : Antinéoplasiques, Radio-isotopes de l'iode.
- biosynthèse : Cholestérol.
- métabolisme : ADN, Adénocarcinome, Carcinome épidermoïde, Lipoprotéines LDL, Tumeurs de l'utérus, Tumeurs du col de l'utérus.
- usage thérapeutique : Lipoprotéines LDL.
- Animaux, Cellules cultivées, Femelle, Humains, Souris, Souris nude, Techniques de culture d'organes, Tumeurs de l'utérus, Véhicules pharmaceutiques.
English descriptors
- KwdEn :
- Adenocarcinoma (metabolism), Animals, Antineoplastic Agents (administration & dosage), Carcinoma, Squamous Cell (metabolism), Cells, Cultured, Cholesterol (biosynthesis), DNA (metabolism), Female, Humans, Iodine Radioisotopes (administration & dosage), Lipoproteins, LDL (metabolism), Lipoproteins, LDL (therapeutic use), Mice, Mice, Nude, Organ Culture Techniques, Pharmaceutical Vehicles, Uterine Cervical Neoplasms (metabolism), Uterine Neoplasms (metabolism), Uterine Neoplasms (therapy).
- MESH :
- chemical , administration & dosage : Antineoplastic Agents, Iodine Radioisotopes.
- chemical , biosynthesis : Cholesterol.
- metabolism : Adenocarcinoma, Carcinoma, Squamous Cell, DNA, Lipoproteins, LDL, Uterine Cervical Neoplasms, Uterine Neoplasms.
- chemical , therapeutic use : Lipoproteins, LDL.
- therapy : Uterine Neoplasms.
- Animals, Cells, Cultured, Female, Humans, Mice, Mice, Nude, Organ Culture Techniques, Pharmaceutical Vehicles.
Abstract
Cholesterol metabolism was studied in cells from two established gynecologic cancer cell lines which were maintained in monolayer cultures. The cell lines were derived and established from poorly differentiated epidermoid cervical carcinoma (EC-50) and endometrial adenocarcinoma (AC-258). The specific activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme of cholesterol de novo synthesis, in AC-258 cells (1,700 pmoles x mg-1 microsomal protein x min-1) was three times higher than that found in EC-50 cells (550 pmoles x mg-1 microsomal protein x min-1). However, epidermoid cervical cancer cells (EC-50) metabolized low-density lipoprotein (LDL), the major transport vehicle for cholesterol in plasma, at a very high rate (14,000 ng x mg-1 cell protein x 6 hours). This rate is fifteen times greater than the rate observed in fetal adrenal tissue and fifty times greater than the rate observed in nonneoplastic gynecologic tissue, each in organ culture. Both cancer cells (EC-50 and AC-258) in monolayer culture were shown to have specific receptors for LDL. These cancer cells demonstrate no defect in LDL metabolism, and lysosomal degradation of LDL was blocked by chloroquine. From the results of studies of specific binding of LDL in tissues obtained from nude mice it was demonstrated that membrane fractions prepared from EC-50 cells, after propagation in the mice, contained fifteen to thirty times more specific binding capacity for [125I]iodo-LDL than vital organs of the mouse, such as the liver, heart, lung, kidney, or brain. The results of these studies are suggestive that certain tumor cells might have a higher affinity for LDL than normal tissues and cytotoxic drugs or radionucleotides ligated to the LDL macromolecule may be utilized for the specific delivery of these agents.
DOI: 10.1016/0002-9378(81)90952-2
PubMed: 7223790
Affiliations:
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Le document en format XML
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Ohashi</name></author><author><name sortKey="Macdonald, P C" sort="Macdonald, P C" uniqKey="Macdonald P" first="P C" last="Macdonald">P C Macdonald</name></author><author><name sortKey="Buchsbaum, H J" sort="Buchsbaum, H J" uniqKey="Buchsbaum H" first="H J" last="Buchsbaum">H J Buchsbaum</name></author><author><name sortKey="Simpson, E R" sort="Simpson, E R" uniqKey="Simpson E" first="E R" last="Simpson">E R Simpson</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1981">1981</date><idno type="RBID">pubmed:7223790</idno><idno type="pmid">7223790</idno><idno type="doi">10.1016/0002-9378(81)90952-2</idno><idno type="wicri:Area/PubMed/Corpus">000608</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000608</idno><idno type="wicri:Area/PubMed/Curation">000608</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000608</idno><idno type="wicri:Area/PubMed/Checkpoint">000579</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000579</idno><idno type="wicri:Area/Ncbi/Merge">001137</idno><idno type="wicri:Area/Ncbi/Curation">001137</idno><idno type="wicri:Area/Ncbi/Checkpoint">001137</idno><idno type="wicri:doubleKey">0002-9378:1981:Gal D:low:density:lipoprotein</idno><idno type="wicri:Area/Main/Merge">003835</idno><idno type="wicri:Area/Main/Curation">003756</idno><idno type="wicri:Area/Main/Exploration">003756</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Low-density lipoprotein as a potential vehicle for chemotherapeutic agents and radionucleotides in the management of gynecologic neoplasms.</title><author><name sortKey="Gal, D" sort="Gal, D" uniqKey="Gal D" first="D" last="Gal">D. Gal</name></author><author><name sortKey="Ohashi, M" sort="Ohashi, M" uniqKey="Ohashi M" first="M" last="Ohashi">M. Ohashi</name></author><author><name sortKey="Macdonald, P C" sort="Macdonald, P C" uniqKey="Macdonald P" first="P C" last="Macdonald">P C Macdonald</name></author><author><name sortKey="Buchsbaum, H J" sort="Buchsbaum, H J" uniqKey="Buchsbaum H" first="H J" last="Buchsbaum">H J Buchsbaum</name></author><author><name sortKey="Simpson, E R" sort="Simpson, E R" uniqKey="Simpson E" first="E R" last="Simpson">E R Simpson</name></author></analytic><series><title level="j">American journal of obstetrics and gynecology</title><idno type="ISSN">0002-9378</idno><imprint><date when="1981" type="published">1981</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenocarcinoma (metabolism)</term><term>Animals</term><term>Antineoplastic Agents (administration & dosage)</term><term>Carcinoma, Squamous Cell (metabolism)</term><term>Cells, Cultured</term><term>Cholesterol (biosynthesis)</term><term>DNA (metabolism)</term><term>Female</term><term>Humans</term><term>Iodine Radioisotopes (administration & dosage)</term><term>Lipoproteins, LDL (metabolism)</term><term>Lipoproteins, LDL (therapeutic use)</term><term>Mice</term><term>Mice, Nude</term><term>Organ Culture Techniques</term><term>Pharmaceutical Vehicles</term><term>Uterine Cervical Neoplasms (metabolism)</term><term>Uterine Neoplasms (metabolism)</term><term>Uterine Neoplasms (therapy)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN (métabolisme)</term><term>Adénocarcinome (métabolisme)</term><term>Animaux</term><term>Antinéoplasiques (administration et posologie)</term><term>Carcinome épidermoïde (métabolisme)</term><term>Cellules cultivées</term><term>Cholestérol (biosynthèse)</term><term>Femelle</term><term>Humains</term><term>Lipoprotéines LDL (métabolisme)</term><term>Lipoprotéines LDL (usage thérapeutique)</term><term>Radio-isotopes de l'iode (administration et posologie)</term><term>Souris</term><term>Souris nude</term><term>Techniques de culture d'organes</term><term>Tumeurs de l'utérus ()</term><term>Tumeurs de l'utérus (métabolisme)</term><term>Tumeurs du col de l'utérus (métabolisme)</term><term>Véhicules pharmaceutiques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antineoplastic Agents</term><term>Iodine Radioisotopes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cholesterol</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Antinéoplasiques</term><term>Radio-isotopes de l'iode</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Cholestérol</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Adenocarcinoma</term><term>Carcinoma, Squamous Cell</term><term>DNA</term><term>Lipoproteins, LDL</term><term>Uterine Cervical Neoplasms</term><term>Uterine Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ADN</term><term>Adénocarcinome</term><term>Carcinome épidermoïde</term><term>Lipoprotéines LDL</term><term>Tumeurs de l'utérus</term><term>Tumeurs du col de l'utérus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Lipoproteins, LDL</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Uterine Neoplasms</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Lipoprotéines LDL</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Nude</term><term>Organ Culture Techniques</term><term>Pharmaceutical Vehicles</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Femelle</term><term>Humains</term><term>Souris</term><term>Souris nude</term><term>Techniques de culture d'organes</term><term>Tumeurs de l'utérus</term><term>Véhicules pharmaceutiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cholesterol metabolism was studied in cells from two established gynecologic cancer cell lines which were maintained in monolayer cultures. The cell lines were derived and established from poorly differentiated epidermoid cervical carcinoma (EC-50) and endometrial adenocarcinoma (AC-258). The specific activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme of cholesterol de novo synthesis, in AC-258 cells (1,700 pmoles x mg-1 microsomal protein x min-1) was three times higher than that found in EC-50 cells (550 pmoles x mg-1 microsomal protein x min-1). However, epidermoid cervical cancer cells (EC-50) metabolized low-density lipoprotein (LDL), the major transport vehicle for cholesterol in plasma, at a very high rate (14,000 ng x mg-1 cell protein x 6 hours). This rate is fifteen times greater than the rate observed in fetal adrenal tissue and fifty times greater than the rate observed in nonneoplastic gynecologic tissue, each in organ culture. Both cancer cells (EC-50 and AC-258) in monolayer culture were shown to have specific receptors for LDL. These cancer cells demonstrate no defect in LDL metabolism, and lysosomal degradation of LDL was blocked by chloroquine. From the results of studies of specific binding of LDL in tissues obtained from nude mice it was demonstrated that membrane fractions prepared from EC-50 cells, after propagation in the mice, contained fifteen to thirty times more specific binding capacity for [125I]iodo-LDL than vital organs of the mouse, such as the liver, heart, lung, kidney, or brain. The results of these studies are suggestive that certain tumor cells might have a higher affinity for LDL than normal tissues and cytotoxic drugs or radionucleotides ligated to the LDL macromolecule may be utilized for the specific delivery of these agents.</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Buchsbaum, H J" sort="Buchsbaum, H J" uniqKey="Buchsbaum H" first="H J" last="Buchsbaum">H J Buchsbaum</name><name sortKey="Gal, D" sort="Gal, D" uniqKey="Gal D" first="D" last="Gal">D. Gal</name><name sortKey="Macdonald, P C" sort="Macdonald, P C" uniqKey="Macdonald P" first="P C" last="Macdonald">P C Macdonald</name><name sortKey="Ohashi, M" sort="Ohashi, M" uniqKey="Ohashi M" first="M" last="Ohashi">M. Ohashi</name><name sortKey="Simpson, E R" sort="Simpson, E R" uniqKey="Simpson E" first="E R" last="Simpson">E R Simpson</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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