Indirect detection of photosensitizer ex vivo

Bourré, Ludovic; Thibaut, Sonia; Briffaud, Amélie; Rousset, Nathalie; Eléouet, Sabine; Lajat, Y.; Patrice, Thierry

doi:10.1016/s1011-1344(02)00279-8

Cited by 111 publications

(93 citation statements)

References 27 publications

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“…The second-generation photosensitizer m-THPC has already been used as an exogenous photoactive agent for PDT in a wide field of cancer treatments. [16][17][18][19][20] In this study, several formulations of liposomes formed by m-THPC/DMPC/G1 surfactant were used to assess the extent of photosensitizer delivery into human and murine glioblastoma cells, and the relative cytotoxicity before and after irradiation with laser light at 652 nm. In addition, the uptake and intracellular distribution of cationic liposomes were analyzed using flow cytometry and laser scanning confocal microscopy, respectively.…”

Section: Resultsmentioning

confidence: 99%

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m‐THPC‐mediated photodynamic therapy of malignant gliomas: Assessment of a new transfection strategy

Molinari

Bombelli²,

Mannino

et al. 2007

Intl Journal of Cancer

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Malignant gliomas represent the most common primary brain tumor: more than 50% of them are glioblastoma multiforme (GBM). Photodynamic therapy may offer a very good chance of targeted destruction of infiltrating GBM cells, thus increasing the survival time and recurrence-free interval of GBM patients. Among photosensitizing agents, meta-tetrahydroxyphenylchlorin (m-THPC) is promising for the treatment of brain tumors. In previous studies, we investigated the transfection activity of dimyristoyl-sn-glycero-phosphatidylcholine (DMPC) liposomes, containing a cationic gemini surfactant, loaded with m-THPC on human colon adenocarcinoma and glioblastoma cell lines. In this paper, the uptake and the intracellular distribution of m-THPC, loaded in several formulations of cationic liposomes, were analyzed, by making a comparison with those obtained using the same chlorin in the pharmaceutical form (Foscan 1 ). Moreover, by cloning efficiency assay the potential therapeutic efficiency of chlorin delivered by liposome formulations was compared with that of the pharmaceutical compound, before and after irradiation with laser light at 652 nm. The obtained results indicated that cationic liposomes (i) transferred m-THPC in glioblastoma cells more efficiently than pharmaceutical formulation; (ii) significantly (p < 0.001) increased the m-THPC cytotoxic effect after laser irradiation; (iii) seemed to exert their cytotoxic action in the early phase of interaction with the cells, during adhesion to the plasma membrane. ' 2007 Wiley-Liss, Inc.Key words: cationic liposomes; photodynamic therapy; m-THPC; glioblastoma Malignant gliomas represent the most common primary brain tumor. With an incidence of 5 cases per 100,000 population per year, they are the fourth most common cause of cancer-related deaths and are among the most lethal cancers, with an overall survival length of less than 2 years. Moreover, more than 50% of them are glioblastoma multiforme (GBM; the most malignant brain tumor) that has a 30% survival rate at 1 year and less than 3% at 3 years. The great technical advances of diagnostic tools and operative technical management have reduced postoperative mortality and morbidity in patients with malignant gliomas, but the long-term prognosis is still poor. On this basis, many different adjuvant therapies have been developed. Among them, one the most promising is photodynamic therapy (PDT). 1-4Initiated by Diamond et al. 5 in 1972 and Signorelli et al. 6 in 1978, PDT is based on photochemical reactions between light and tumoral tissue selectively labeled with exogenous photosensitizing agents. Such reactions produce, at intracellular level, vast amounts of free radicals (singlet oxygen, superoxide), which determine tumor cell destruction. 7,8 PDT may offer a very good chance of targeted destruction of infiltrating GBM cells; this could increase survival time and recurrence-free interval of GBM patients. 9Among photosensitizing agents, meta-tetrahydroxyphenylchlorin (m-THPC) is promising for the treatment of brain tumor...

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Section: Resultsmentioning

confidence: 99%

“…16 At least 10,000 events were analyzed. The photosensitizer content was evaluated as fluorescence intensity, expressed as mean fluorescence channel (MFC).…”

Section: Flow Cytometrymentioning

confidence: 99%

m‐THPC‐mediated photodynamic therapy of malignant gliomas: Assessment of a new transfection strategy

Molinari

Bombelli²,

Mannino

et al. 2007

Intl Journal of Cancer

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“…Hence, post-treatment management should be considerably simplified for a patient receiving Tookad-PDT. It has been recently demonstrated that there is little uptake of Tookad ® by tumor but a gradual accumulation of Tookad ® in the liver of a mouse model [27]. The uptake of Tookad, in the prostate gland and prostatic urethral mucosa needs to be investigated in further studies.…”

Section: Discussionmentioning

confidence: 99%

Studies of a vascular‐acting photosensitizer, Pd‐bacteriopheophorbide (Tookad), in normal canine prostate and spontaneous canine prostate cancer

et al. 2005

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“…The cells were washed once in phosphate-buffered saline (pH 7.4) and immediately examined under a confocal microscope (LSM510; Zeiss) (1). Measurement was done fluorometrically with excitation at 506 nm and emission at 526 nm (1,4). The mean fluorescent intensity was analyzed using a Beckman Coulter (Cytomix FC 500) flow cytometer at 530 Ϯ 30 nm.…”

Section: Methodsmentioning

confidence: 99%

The 29-Kilodalton Thiol-Dependent Peroxidase of Entamoeba histolytica Is a Factor Involved in Pathogenesis and Survival of the Parasite during Oxidative Stress

et al. 2007

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The 29-kDa surface antigen (thiol-dependent peroxidase; Eh29) of Entamoeba histolytica exhibits peroxidative and protective antioxidant activities. During tissue invasion, the trophozoites are exposed to oxidative stress and need to deal with highly toxic reactive oxygen species (ROS). In this investigation, attempts have been made to understand the role of the 29-kDa peroxidase gene in parasite survival and pathogenesis. Inhibition of eh29 gene expression by antisense RNA technology has shown approximately 55% inhibition in eh29 expression, maximum ROS accumulation, and significantly lower viability in 29-kDa downregulated trophozoites during oxidative stress. The cytopathic and cytotoxic activities were also found to decrease effectively in the 29-kDa downregulated trophozoites. Size of liver abscesses was substantially lower in hamsters inoculated with 29-kDa downregulated trophozoites compared to the normal HM1:IMSS. These findings clearly suggest that the 29-kDa protein of E. histolytica has a role in both survival of trophozoites in the presence of ROS and pathogenesis of amoebiasis.Entamoeba histolytica, the enteric protozoa, is a well-established causative agent of amoebic dysentery and liver abscesses in humans (37). E. histolytica is well known for its high potential for invading and destroying human tissue, leading to diseases such as hemorrhagic colitis and extraintestinal abscesses (30). The parasite usually lives and multiplies within the human gut, which constitutes an environment of reduced oxygen pressure. During tissue invasion, E. histolytica is exposed to elevated amounts of exogenous reactive oxygen species (ROS), such as superoxide radical anions (O 2 ⅐ Ϫ ) and hydrogen peroxide (H 2 O 2 ) (14, 26). These highly toxic molecules cause severe damage to biological macromolecules, leading to metabolic malfunctions. In addition, E. histolytica has to inactivate the ROS produced by endogenous enzymes for its survival. Several defense mechanisms exist in which a wide array of enzymatic and nonenzymatic antioxidants, including superoxide dismutase (SOD), glutathione peroxidase, catalase, and glutathione, play an active role in cell survival during oxidative stress. E. histolytica produces an iron-containing SOD that is induced by superoxide anions to produce H 2 O 2 (9). Hydroperoxides produced during oxidative stress could be detoxified by a bifunctional NADPH:flavin oxidoreductase containing NADPH-dependent disulfide reductase and a H 2 O 2 -forming NADPH oxidase activity (10, 12). Catalase and glutathione reductase systems are absent in E. histolytica, but it encodes a 29-kDa cysteine-rich antigen (thiol-dependent peroxiredoxin) located on the surface of the trophozoites (8). The 29-kDa thiol-dependent peroxiredoxin of E. histolytica (Eh29) is homologous to AhpC (alkyl hydroperoxide C-22 protein) of Salmonella enterica serovar Typhimurium and Saccharomyces cerevisiae thiol-specific antioxidant protein (17). In our previous study it was clearly demonstrated that the enzymes SOD and Eh29 increased...

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Indirect detection of photosensitizer ex vivo

Cited by 111 publications

References 27 publications

m‐THPC‐mediated photodynamic therapy of malignant gliomas: Assessment of a new transfection strategy

m‐THPC‐mediated photodynamic therapy of malignant gliomas: Assessment of a new transfection strategy

Studies of a vascular‐acting photosensitizer, Pd‐bacteriopheophorbide (Tookad), in normal canine prostate and spontaneous canine prostate cancer

The 29-Kilodalton Thiol-Dependent Peroxidase of Entamoeba histolytica Is a Factor Involved in Pathogenesis and Survival of the Parasite during Oxidative Stress

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