Photofrin II as an efficient radiosensitizing agent in an experimental tumor

Background and Objective: The use of ionizing irradiation as radiation therapy (RT) for tumor treatment represents a well-established method. The use of photodynamic therapy (PDT), especially with Photofrin II, for tumor treatment is also known. Chemical modifiers enhancing the action of radiation therapy are well known and widely used in medicine. None of these compounds, however, is a selective radiosensitizer. Materials and Methods: Several series of animal experiments were performed, The highly differentiated human bladder cancer cell line RT4 was implanted subcutaneously in nude mice. The mice were injected 10 mg/kg Photofrin II and irradiated with 5 Gy. Results: Photofrin II has proved to be a chemical modifier of ionizing irradiation, enhancing the tumor doubling time (tumor growth) from 6.2 to 10.9 days in the control group with the use of irradiation and injection of porphyrin. Conclusion: Photofrin II shows a high activity as radiosensitizer and, in the future, can be used as a selective radiosensitizer for tumor treatment with ionizing radiation

Métodos de captura, contenção e fixação de transmissores VHF em caititus (Tayassu tajacu).

O objetivo do trabalho foi descrever metodologias para a captura, contenção e marcação de caititus. A captura foi realizada de duas formas: com laço e com armadilhas; os métodos de contenção considerados foram: físico e químico; transmissores de VHF foram afixados aos animais para monitoramento após captura utilizando colar de couro, colar de aço revestido ou brinco. As armadilhas medindo 1,5m x 0,8m x 0,6m, foram instaladas em locais com indícios da presença da espécie, durante a estação seca no Pantanal da Nhecolândia. Água em reservatórios plásticos nivelados à superfície do solo (25 litros) e pequenas quantidades de mandioca foram utilizadas como atrativo. As armadilhas instaladas nas condições descritas mostraram-se eficientes para atração e captura de animais da espécie. Embora o método do laço tenha se mostrado eficiente, seu uso certamente compromete o bem estar dos animais manejados, devido à presença de cães. Quando houve apenas a contenção física dos animais a mortalidade pós-captura foi menor. Dentre as opções testadas para anexar transmissores aos animais, o colar confeccionado manualmente utilizando sola de couro foi a mais viável

Controlled targeting of different subcellular sites by porphyrins in tumour-bearing mice.

Unilamellar liposomes of dipalmitoyl-phosphatidylcholine can incorporate various porphyrins in either the phospholipid bilayer or the internal aqueous compartment depending on the water-/lipo-solubility of the drug. Intraperitoneal injection of the liposome-bound porphyrins to mice bearing a MS-2 fibrosarcoma results in remarkably more efficient tumour targeting than that obtained by administration of the same porphyrins dissolved in homogeneous aqueous solution. Moreover, also water-insoluble porphyrins can be transported to the tumour via liposomes. Fractionation of liver and neoplastic cells indicates that the subcellular distribution of liposome-delivered porphyrins is also dependent on their solubility properties: thus, relatively polar porphyrins, such as tetra(4-sulfonatophenyl)porphine and uroporphyrin, are mainly recovered from the soluble fraction, whereas hydrophobic porphyrins, such as haematoporphyrin or porphyrin esters, preferentially partition in the cytoplasmic membrane. As a consequence, different subcellular sites can be targeted by porphyrins and possibly photodamaged through a suitable choice of the drug-carrier system

Liposome- or LDL-administered Zn (II)-phthalocyanine as a photodynamic agent for tumours. I. Pharmacokinetic properties and phototherapeutic efficiency.

The pharmacokinetics of Zn-phthalocyanine (Zn-Pc) in mice bearing a transplanted MS-2 fibrosarcoma has been studied using dipalmitoyl-phosphatidylcholine (DPPC) liposomes and low density lipoproteins (LDL) as drug delivery systems. LDL induce a higher Zn-Pc uptake by the tumour and improve the selectivity of tumour targeting as compared to DPPC liposomes. Experimental photodynamic therapy (PDT) of the MS-2 fibrosarcoma has been performed using liposome-delivered Zn-Pc and the efficiency of tumour necrosis has been measured following four different irradiation protocols. We found that Zn-Pc doses as low as 0.07-0.35 mg kg-1 are sufficient for inducing an efficient tumour response that is linearly dependent on the injected dose. The amount of Zn-Pc in the tumour decreases very slowly as a function of time, hence PDT gives satisfactory results even if performed at relatively long time intervals after administration