RESUMO
The central objectives of this paper are to enhance the understanding of how consumers in developed economies value credence attributes and to understand their preferences for red-pulp kiwifruit. To achieve this, we utilised the choice experiment method through surveys conducted in Italy, Spain, France, and Germany, targeting kiwifruit consumers through specific questionnaires. Regarding red kiwifruit, a significant percentage of those who are already familiar with them either purchase or intend to purchase them. What is equally interesting is the high percentage of those who declared themselves to be undecided about making a purchase. Specific marketing actions can be directed towards the following two categories: converting the intention to purchase into an actual purchase and shifting the current inclination towards an intention or act of purchase, for example, by improving the knowledge about this relatively unknown fruit. This paper contributes to the market chain by assessing consumers' choice and willingness to pay for red kiwifruit, while also comparing developed economy markets.
RESUMO
A 24-amino acid leader peptide of a new human recombinant manganese superoxide dismutase can enter cells and carry molecules. Here, we demonstrated that six of the 24 amino acids penetrate cells through a particular gate represented by a specific amino acid sequence of the oestrogen receptor (ER). We analysed the internalization of the synthetic hexapeptide and the cytotoxic activity of the hexapeptide conjugated to cisplatin on a cell line panel. In most cell lines, the hexapeptide delivered an amount of cisplatin that was 2 to 8 times greater than that released by cisplatin when the drug was used alone. This increased delivery increases the therapeutic index of cisplatin and reduces side effects caused by a high dosage or long-term treatment times. We may consider this hexapeptide a new molecular carrier to deliver molecules with therapeutic activity into ER(+) cells for diagnostic purposes and clinical or immune therapy.
Assuntos
Portadores de Fármacos/química , Fragmentos de Peptídeos/química , Sequência de Aminoácidos , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/química , Cisplatino/metabolismo , Cisplatino/farmacologia , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Retículo Endoplasmático/metabolismo , Fluoresceína/química , Fluoresceína/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Humanos , Concentração Inibidora 50 , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Sinais Direcionadores de Proteínas , Receptores de Estrogênio/metabolismo , Proteínas Recombinantes/química , Superóxido Dismutase/químicaRESUMO
The leader peptide of a recombinant manganese superoxide dismutase (rMnSOD-Lp) acts as a molecular carrier. Clonogenic tests on normal (MRC-5) and endometrial adenocarcinoma cells (HTB-112) were carried out in the presence of rMnSOD-Lp, cisplatin alone (CC) or cisplatin conjugated to the rMnSOD-Lp (rMnSOD-Lp-CC). The platinum delivered into the cells was measured by atomic spectrophotometric absorbance. The treatments on tumor and normal cells were finally evaluated by LM and TM microscopy. Tumor cell death in the case of 0.5 µM cisplatin on its own was minimal, while in the presence of 0.5 µM rMnSOD-Lp-CC, no tumor cells survived. Atomic absorbance analysis showed that rMnSOD-Lp-CC delivered approximately four times more cisplatin into HTB-112 cells than the amount delivered using cisplatin alone. By LM observation, the cells treated with rMnSOD-Lp-CC showed signs of nuclear and cytoplasmic fragmentation, that is, apoptosis induced by the treatment. The therapeutic effect of rMnSOD-Lp-CC on endometrial cancer cells was significant, while on the normal cells it showed only a minimal toxicity. We believe that rMnSOD-Lp deserves to be considered as a molecular carrier to deliver cisplatin directly into tumor cells, thus transforming its antireplicative activity into a specific and selective antitumor agent.
Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/uso terapêutico , Portadores de Fármacos/química , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Espectrofotometria Atômica , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
The leader peptide of a recombinant MnSOD (rMnSOD-Lp) constitutes the carrier that allows rMnSOD to penetrate tumor cells. A synthetic preparation of rMnSOD-Lp was 68Ga labeled (rMnSOD-Lp- 68Ga) and injected into animals bearing spontaneous mammary cancers, followed by PET examinations, which demonstrated unambiguously the tumor sites in all the animals, suggesting that if rMnSOD-Lp was able to transport the radioisotope into tumor cells, it would also be able to deliver cytotoxic molecules. The rMnSOD-Lp was, therefore, conjugated to cisplatin (rMnSOD-Lp-CC) and added to cultured tumor cells. Equal concentrations of cisplatin were used for the tests. After treating the ovarian cancer cells with 11.1 µg of cisplatin alone, analysis by atomic absorbance spectrophotometry was able to detect only 6 ng of platinum, whereas when the same cells were treated with the same amount of cisplatin conjugated to leader peptide rMnSOD, 387 ng of platinum were detected, i.e., an amount 80 times greater. Only the tumor cells died following treatment with rMnSOD-Lp-CC; molecular analysis revealed that its addition generated an increasing expression of Erk-2 and Bax products, which could be inhibited only by a selective MAP/ERK kinase inhibitor (PD98059), revealing that rMnSOD-Lp-CC has an apoptotic function, exactly as occurs when using the cisplatin alone. Data are statistically significant and indicate that by using rMnSOD-Lp-CC, the cisplatin can be transformed from an agent with antireplicative activity into a specific and selective antitumor molecule, increasing its therapeutic index. We think that rMnSOD-Lp-CC deserves to be considered as a new antitumor agent.