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1.
Proc Natl Acad Sci U S A ; 102(36): 12962-7, 2005 Sep 06.
Article in English | MEDLINE | ID: mdl-16123131

ABSTRACT

The central problem in cancer chemotherapy is the severe toxic side effects of anticancer drugs on healthy tissues. Invariably the side effects impose dose reduction, treatment delay, or discontinuance of therapy. To limit the adverse side effects of cancer chemotherapy on healthy organs, we proposed a drug delivery system (DDS) with specific targeting ligands for cancer cells. The proposed DDS minimizes the uptake of the drug by normal cells and enhances the influx and retention of the drug in cancer cells. This delivery system includes three main components: (i) an apoptosis-inducing agent (anticancer drug), (ii) a targeting moiety-penetration enhancer, and (iii) a carrier. We describe one of the variants of such a system, which utilizes camptothecin as an apoptosis-inducing agent and poly(ethylene glycol) as a carrier. Luteinizing hormone-releasing hormone (LHRH) was used as a targeting moiety (ligand) to LHRH receptors that are overexpressed in the plasma membrane of several types of cancer cells and are not expressed detectably in normal visceral organs. The results showed that the use of LHRH peptide as a targeting moiety in the anticancer DDS substantially enhanced the efficacy of chemotherapy, led to amplified apoptosis induction in the tumor, and minimized the side effects of the anticancer drug on healthy organs. The LHRH receptor targeting DDS did not show in vivo pituitary toxicity and did not significantly influence the time course or the plasma concentration of luteinizing hormone and its physiological effects on the reproductive functions of mice.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Drug Delivery Systems/methods , Gonadotropin-Releasing Hormone/pharmacokinetics , Neoplasms/drug therapy , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor , Disease Models, Animal , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , Mice, Nude , Molecular Structure , Neoplasms/genetics , Neoplasms/pathology , Organ Specificity , Receptors, LHRH/genetics , Receptors, LHRH/metabolism , Xenograft Model Antitumor Assays
2.
Genet Anal ; 15(3-5): 107-13, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10596748

ABSTRACT

Improvements in modern commercial aquaculture are linked to the utilization of biotechnological methods and processes. The most visible approach has been the use of growth hormone (GH) and/or insulin-like growth factor I and II (IGF-I and II), to accelerate the growth of fish. Previously we have reported that the injection of bovine GH, (bGH) in striped bass hybrids increased the specific growth rate and food conversion efficiency without significant alteration of food consumption rate. In this paper we present the results of experiments in which growth, food consumption, conversion efficiency, ammonia excretion, and amino acid absorption were monitored for individual fish after bGH injection. The specific growth rate was stimulated by 50% without significant change in relative food consumption rate. Food conversion efficiency increased by 51%. Intestinal L-leucine absorption was increased by 25-40% at various concentrations tested. The relative N-retention was stimulated by 20% when computed raw. When a correction factor derived from the elevated amino acid absorption was introduced into the computations. the calculated relative N-retention was increased by 56%. Muscle amino acid profile was appreciably altered. We conclude GH supplementation or over-expression in aquaculture profoundly alters the physiological and nutritional conditions of fish. Nutritional profiles of fish food must be altered relative to these physiological changes in order to maximize growth.


Subject(s)
Amino Acids, Essential/pharmacokinetics , Bass/physiology , Growth Hormone/pharmacology , Muscle, Skeletal/chemistry , Nitrogen/metabolism , Amino Acids/analysis , Ammonia/metabolism , Animals , Bass/growth & development , Bass/metabolism , Cattle , Energy Metabolism/drug effects , Feeding Behavior/drug effects , Female , Growth/drug effects , Growth Hormone/administration & dosage , Hybridization, Genetic , Injections, Intramuscular , Intestinal Absorption/drug effects , Male , Nutritional Requirements , Species Specificity
3.
Science ; 171(3972): 672-5, 1971 Feb 19.
Article in English | MEDLINE | ID: mdl-5540306

ABSTRACT

Food materials from the sunken and recovered research submarine Alvin were found to be in a strikingly well-preserved state after exposure for more than 10 months to deep-sea conditions. Subsequent experiments substantiated this observation and indicated that rates of microbial degradation were 10 to 100 times slower in the deep sea than in controls under comparable temperatures.


Subject(s)
Bacteria/metabolism , Food Microbiology , Oceanography , Water Microbiology , Acetates/metabolism , Albumins/metabolism , Amino Acids/metabolism , Carbon Dioxide/metabolism , Carbon Isotopes , Cold Temperature , Galactose/metabolism , Glutamates/metabolism , Mannitol/metabolism , Massachusetts , Peptones/metabolism , Pressure , Seawater , Starch/metabolism
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