Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. Our study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intravesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17 mM) on days 3 to 11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group, compared to sham-treated mice. Tumor markers Ki-67, Cyclin D1 and VEGF were inhibited in a dose-dependent manner, as was the expression of cancer-related genes. Remarkably, toxicity for healthy tissue was not detected in alpha1-oleate-treated, tumor-bearing mice or healthy mice or rabbits, challenged with increasing doses of the active complex. The results define a dose-dependent therapeutic effect of alpha1-oleate in a murine bladder cancer model.
- MeSH
- antitumorózní látky aplikace a dávkování chemie toxicita MeSH
- aplikace intravezikální MeSH
- králíci MeSH
- kyselina olejová aplikace a dávkování chemie toxicita MeSH
- laktalbumin aplikace a dávkování chemie toxicita MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- močový měchýř účinky léků patologie MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádorové buněčné linie transplantace MeSH
- nádory močového měchýře farmakoterapie patologie MeSH
- testy subchronické toxicity MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: The aim of this study was to demonstrate suitability and safety of an infant formula enriched with α-lactalbumin with a reduced protein content of 1.89 g protein/100 kcal. METHODS: This was a randomized, double-blind controlled trial with 80 healthy newborn infants who were assigned to receive either an isocaloric low- or high-protein content formula (1.89 versus 2.1 g/100 kcal). The low-protein content formula was enriched with α-lactalbumin. A breast-fed reference group of 40 infants was studied concurrently. Anthropometric measures were taken at inclusion, after 6 and 12 wk as well as after 6 and 12 mo of follow-up. Primary outcome was weight gain in g/d between study inclusion to 12 wk. Secondary outcomes included anthropometric measures expressed in Z-scores, mean formula consumption, and caloric intake as well as food tolerance. RESULTS: Fifty-two infants in the formula group (low protein: 26, high protein: 26) and 32 in the breast-fed reference group completed the 3-mo intervention period. There was no difference in weight gain among feeding groups at the end of the intervention period. Mean weight gain in g/d was 32 in the low-protein, 31 in the high-protein, and 33 in the breast-fed reference group. No significant difference was found between study groups in Z-scores for weight, length, head circumference, weight-for-length, or body mass index nor for fat percentage at end of intervention and after follow-up. CONCLUSION: α-lactalbumin-enriched formula with a protein content of 1.89 g protein/100 kcal is safe and supports adequate growth.
- MeSH
- dietní proteiny MeSH
- fyziologie výživy kojenců MeSH
- kojenec MeSH
- kojení MeSH
- laktalbumin * MeSH
- lidé MeSH
- náhražky mateřského mléka * MeSH
- nízkoproteinová dieta MeSH
- novorozenec MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Understanding the interaction between graphene oxide (GO) and the biomolecules is fundamentally essential, especially for disease- and drug-related peptides and proteins. In this study, the interaction between GO and albumins (bovine serum albumin, human serum albumin, and bovine alpha-lactalbumin) has been performed by fluorescence and UV-Vis spectroscopic techniques. The fluorescence quenching mechanism between GO and aromatic acids residues with intrinsic fluorescence was determined as mainly static quenching in combination with dynamic quenching. The optimal conditions for the most effective affinity between albumins and GO have been estimated at neutral pH and room temperature. The strong impact of the size of graphene oxide on the interaction between proteins and graphene oxide has been confirmed, as well. The interaction between GO and albumins has been examined as electrostatic and hydrophobic. The electrostatic interaction was confirmed by pH effect, while the hydrophobic interaction was proved by the presence of Poloxamer188. The CD spectra of albumins exhibit decreasing helicity in the secondary structure of albumins upon the addition of GO. However, no significant changes in position and shape of characteristic negative bands have been noted. Mentioned changes indicate the successful interaction between GO and proteins, the predominantly α-helical structure of albumins has been preserved.
- MeSH
- cirkulární dichroismus MeSH
- grafit chemie MeSH
- koncentrace vodíkových iontů MeSH
- laktalbumin chemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- oxidy chemie MeSH
- sérový albumin hovězí chemie MeSH
- sérový albumin chemie MeSH
- skot MeSH
- teplota MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- apoptóza imunologie účinky léků MeSH
- cytochromy c farmakologie fyziologie účinky léků MeSH
- kaspasy farmakologie fyziologie MeSH
- klinické zkoušky jako téma MeSH
- laktalbumin farmakologie imunologie terapeutické užití MeSH
- lékařská onkologie dějiny metody trendy MeSH
- lidé MeSH
- mateřské mléko imunologie MeSH
- mitochondriální membrány fyziologie imunologie MeSH
- molekulární biologie metody trendy MeSH
- nenasycené mastné kyseliny izolace a purifikace metabolismus MeSH
- papilom farmakoterapie MeSH
- permeabilita buněčné membrány fyziologie účinky léků MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Švédsko MeSH
