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Biomedical subjects

François Guillemin

Publications and source records attributed to François Guillemin.

At least 19 recordsLinked to original sources

Gap junctional intercellular communication capacity by gap-FRAP technique: a comparative study.

Gap junctions play an important role in vital functions, including the regulation of cell growth and cell differentiation. Connexins 43 (Cx43) are the most widely expressed gap junction proteins. Cellular localization of phosphorylated Cx43 has been implicated in the capacity of gap junctional intercellular communication (GJIC). To follow the functionality of GJIC of different cell types, in monolayer cultures, characterized by different patterns of phosphorylated Cx43, we used a fluorescence recovery after photobleaching (FRAP) technique, and compared two tracers, 5(6)-carboxyfluorescein diacetate (CFDA) and calcein acetoxymethylester (AM). The GJIC capacity was quantified by estimating fluorescence redistribution parameters. The functionality of GJIC was in relation with the staining localization of phosphorylated Cx43 to the cell-cell contact areas, corresponding to gap junctions between contacting cells. GJIC involvement in fluorescence restitution after photobleaching was checked by a gap junction channel inhibition assay. We demonstrated that the choice of the dye did not significantly influence the fluorescence recovery percentages despite a cell line-dependent CFDA release, whereas it had an important impact on fluorescence kinetic profiles. This study reinforces the interest of the gap-FRAP approach to quantify modifications in the functionality of gap junctions and, above all, argues about the limits of CFDA for 3-D future approaches.

Cell Communication↗

Interest of RGD-containing linear or cyclic peptide targeted tetraphenylchlorin as novel photosensitizers for selective photodynamic activity.

Destruction of the neovasculature is essential for tumor eradication by photodynamic therapy. Since the over-expression of integrins is correlated with tumor angiogenesis, we conjugated a photosensitizer (5-(4-carboxyphenyl)-10,15,20-triphenylchlorin or porphyrin) to the alpha(v)beta(3) integrin specific peptide RGD (H-Arg-Gly-Asp-OH) motif as a common sequence. We reported an efficient solid-phase synthesis of a new family of peptidic photosensitizers with linear or cyclic[RGDfK] RGD motif and compared conjugates in vitro selectivity and photodynamic activity. The conjugates were characterized by (1)H NMR, MALDI, UV-visible spectroscopy and singlet oxygen formation was performed. Chlorins containing linear and constrained RGD motif were incorporated up to 98- and 80-fold more, respectively, than the unconjugated photosensitizer over a 24-h exposure in human umbilical vein endothelial cells (HUVEC) over-expressing alpha(v)beta(3) integrin. Peptidic moiety also led to a non-specific increased cellular uptake by murine mammary carcinoma cells (EMT-6), lacking RGD binding receptors. Survival measurements demonstrated that HUVEC were greatly sensitive to conjugates-mediated photodynamic therapy.

Animals↗

A novel orthotopic bladder tumor model with predictable localization of a solitary tumor.

An ideal bladder tumor model consists in an orthotopic solitary tumor with a well-defined localization and stage, as well as unaltered normal mucosa. None of the existing models covers all these requirements. We have created a new model, suitable for diagnostic and therapeutic purposes. Female Fisher rats were divided into different groups according to bladder preconditioning and tumor cell (AY27) administration. Generalized desepithelialization was obtained by an intravesical instillation of HCl, neutralized by NaOH. Localized desepithelialization of the bladder fundus was the result of application of a micro-swab, imbibed with the same chemicals. Tumor cells administration was either generalized (intravesical instillation) or focal (micro swab). No bladder perforations were observed. Generalized desquamation always produced multifocal tumors, whereas focal application of HCl/NaOH resulted in solitary tumors of the bladder fundus, irrespective of the method of tumor cell administration. Only hyperplasia could be detected at day 3. AY27 cells were covered by umbrella cells at day 5 and subepithelial AY 27 tumor nests, covered by full thickness epithelium were observed day 7.

Animals↗

Redistribution of Foscan from plasma proteins to model membranes.

Photodynamic therapy is a comparatively novel modality of tumours treatment that includes simultaneous action of photosensitizers, light and oxygen. Photosensitizer redistribution between plasma proteins and biomembranes define photosensitizers interaction with cells, their intracellular localization and kinetics of sensitizers accumulation in the tumour. Present study investigates the kinetics of Foscan release from plasma proteins to model membranes using fluorescence resonance energy transfer (FRET) from label, covalently bound to protein, to sensitizer. We have demonstrated very slow kinetics of Foscan release from protein complexes with rate constants of (1.7 +/- 0.1) x 10(-3) s(-1) for albumin and (1.6 +/- 0.3) x 10(-4) s(-1) for high-density lipoproteins (HDL). Foscan redistributes by both collision and diffusion-mediated transfer from complexes with HDL, with bimolecular rate constant k(out) = (8.8 +/- 1.4) x 10(-2) M(-1) s(-1). Thermodynamic considerations proposed that sensitizer release from HDL into the aqueous medium is unfavourable and collision mechanism appeared to be a preferred mode of transfer in biological environment. Slow rates of Foscan redistribution from plasma proteins should be considered while planning dosimetry protocol of Foscan-PDT.

Binding Sites↗

Establishment of a reliable method for direct proteome characterization of human articular cartilage.

Articular cartilage consists mainly of extracellular matrix, mostly made of collagens and proteoglycans. These macromolecules have so far impaired the detailed two-dimensional electrophoresis-based proteomic analysis of articular cartilage. Here we describe a method for selective protein extraction from cartilage, which excludes proteoglycans and collagen species, thus allowing direct profiling of the protein content of cartilage by two-dimensional electrophoresis. Consistent electrophoretic patterns of more than 600 protein states were reproducibly obtained after silver staining from 500 mg of human articular cartilage from joints with diverse pathologies. The extraction yield increased when the method was applied to a chondrosarcoma sample, consistent with selective extraction of cellular components. Nearly 200 of the most intensely stained protein spots were analyzed by MALDI-TOF mass spectrometry after trypsin digestion. They represented 127 different proteins with diverse functions. Our method provides a rapid, efficient, and pertinent alternative to previously proposed approaches for proteomic characterization of cartilage phenotypes. It will be useful for detecting protein expression patterns that relate pathophysiological processes of cartilaginous tissues such as osteoarthritis and chondrosarcoma.

Adult↗

Eradication of p53-mutated head and neck squamous cell carcinoma xenografts using nonviral p53 gene therapy and photochemical internalization.

Photochemical internalization (PCI) technology has been used for PEI-mediated p53 gene transfer in mice bearing head and neck squamous cell carcinoma (HNSCC) xenografts. Using luciferase as a reporter gene, PCI led to a 20-fold increase in transgene expression 48 h after transfection and sustained transgene expression for 7 days. Therefore, iterative p53 gene transfer was performed by means of a weekly single injection of PEIGlu4/p53 complexes alone or with PCI for 5 (group A) or 7 (group B) weeks. The efficiency of p53 gene therapy was evaluated by following tumor growth and expression of P53-related downstream proteins (P21, MDM2, Bcl2, Bax). Apoptosis induction was evidenced through caspase-3 activation and PARP cleavage. Using PCI, tumor growth inhibition was observed in all transfected animals. Further, successful tumor cure was achieved in 17% (group A) and 83% (group B) of animals. PCI-mediated p53 gene transfer led to higher P53 protein expression that was correlated with induction of Bax and P21 proapoptotic proteins, repression of Bcl2 as well as activation of caspase-3, and cleavage of PARP. The present study demonstrates that PCI enhances the in vivo efficiency of PEI-mediated p53 gene transfer and can be proposed for p53 gene therapy in HNSCC.

Animals↗

A peptide competing with VEGF165 binding on neuropilin-1 mediates targeting of a chlorin-type photosensitizer and potentiates its photodynamic activity in human endothelial cells.

Destruction of the neovasculature is essential for efficient tumor eradication by photodynamic therapy (PDT). Since the over-expression of receptors for vascular endothelial growth factor (VEGF) is correlated with tumor angiogenesis and subsequent growth, we conjugated a photosensitizer (5-(4-carboxyphenyl)-10,15,20-triphenyl-chlorin, TPC), via a spacer (6-aminohexanoic acid, Ahx), to a VEGF receptor-specific heptapeptide (ATWLPPR). ATWLPPR and TPC-Ahx-ATWLPPR bound exclusively to neuropilin-1 (NRP-1) recombinant chimeric protein (IC50=19 and 171 microM, respectively) but were devoid of affinity for VEGF receptor type 2 (VEGFR-2, KDR), to which ATWLPPR was initially thought to bind. TPC-Ahx-ATWLPPR was incorporated up to 25-fold more in human umbilical vein endothelial cells (HUVEC) than TPC over a 24-h period, and the addition of 8 mM ATWLPPR induced a significant decrease of this uptake (P<0.05), corroborating a receptor-mediated incorporation. Slightly less cytotoxic in the dark, TPC-Ahx-ATWLPPR exhibited enhanced in vitro photodynamic activity (10.4-fold), compared to TPC. Pharmacokinetic analysis in nude mice xenografted with U87 human malignant glioma cells revealed relevant tumor levels as soon as 1 h after intravenous injection of TPC-Ahx-ATWLPPR, and a rapid elimination from the blood compartment. Moreover, TPC-Ahx-ATWLPPR was not degraded in vivo up to 2 h after intravenous injection. Taken together, our results demonstrate that TPC-Ahx-ATWLPPR is a much more potent photosensitizer in vitro than TPC, in NRP-1-expressing cells. Thus, it may efficiently potentiate the vascular effect of PDT in vivo.

Animals↗

Results of preoperative lymphoscintigraphy for breast cancer are predictive of identification of axillary sentinel lymph nodes.

The aim of this study was to identify the variables associated with successful peroperative sentinel lymph node (SLN) localization. We studied 201 patients with T1, T2, N0 invasive breast cancer who underwent a SLN procedure from 1999 to 2003. Of these 201 patients, 55 underwent peritumoral and 146 underwent periareolar radioisotope injection before the blue dye injection. All patients were operated on by breast conservative surgery and axillary dissection after SLN biopsy. Age, weight, menopausal status, previous biopsy, localization of the tumor, results of lymphoscintigraphy, site of radiotracer injection, tumor size, tumor grade, experience of surgeons, and the number of invaded axillary nodes were analyzed to determine whether they had any significant correlation with successful identification of SLN. Variables found to have a statistically significant influence on the SLN identification rate and on preoperative lymphoscintigraphy identification were introduced into a univariate and multivariate logistic regression model. In multivariate analysis, successful lymphoscintigraphy (P < 0.0001) and the absence of metastatic axillary nodes (P < 0.005) were associated with successful identification of SLNs. The peritumoral injection of radiotracer (P < 0.001), patient age > 60 years (P < 0.003), and localization of the tumor in the upper outer quadrant (P < 0.004) were associated with failure of lymphoscintigraphic visualization of SLN. The technique of SLN detection thus appears to be better for patients with low risk of invaded axillary lymph nodes.

Adult↗

Prevention of biliary lesions that may occur during radiofrequency ablation of the liver: study on the pig.

OBJECTIVE: To prevent bile duct injury by using a cold 5% glucose isotonic solution cooling in the bile ducts when radiofrequency (RF) is performed in a porcine model. SUMMARY BACKGROUND DATA: Complications that may arise during liver RF ablation include biliary stenosis and abscesses. METHODS: The RITA 1500 generator was used for the experiments. Two lesions were performed in the left liver. The pigs were killed 1 or 3 weeks after the procedure. An ex vivo cholangiogram was obtained by direct injection into the main bile duct. Samples of RF lesions, of liver parenchyma near and at a distance from the RF lesions, underwent pathologic studies. Two groups of 20 pigs each were treated: one without perfusion of the bile ducts and the other with perfusion of cold 5% glucose isotonic solution into the bile ducts. The Pringle maneuver was used in 50% of the RF procedures. Radiologic lesions were classified as biliary stenosis, complete interruption of the bile duct, or extravasation of the radiologic contrast liquid. RESULTS: Histologic lesions of the bile ducts were observed near the ablated RF lesion site and at a distance from the RF lesions when a Pringle maneuver was performed. Radiologic and histologic lesions of the bile ducts were significantly reduced (P < 0.0001) when the bile ducts were cooled. CONCLUSIONS: Cooling of the bile ducts with a cold 5% glucose isotonic solution significantly protects the intrahepatic bile ducts from damages caused by the heat generated by RF when performed close to the bile ducts.

Abdominal Injuries↗

Recent improvements in the use of synthetic peptides for a selective photodynamic therapy.

Photodynamic therapy (PDT) is a relatively new cytotoxic treatment, predominantly used in anti-cancer approaches, that depends on the retention of photosensitizers in tumor and their activation after light exposure. Photosensitizers are photoactive compounds such as porphyrins and chlorins that upon photoactivation, effect strongly localized oxidative damage within the target cells. The ability to confine activation of the photosensitizer by restricting illumination to the tumor allows for a certain degree of selectivity. Nevertheless, the targeted delivery of photosensitizers to defined cells is a major problem in PDT of cancer, and one area of importance is photosensitizer targeting. Alterations or increased levels in receptor expression of specific cellular type occur in the diseased tissues. Therefore, photosensitizers can be covalently attached to molecules such as peptides, leading to a receptor-mediated targeting strategy. These active-targeting approaches may be particularly useful for anti-vascular PDT. Moreover, it has been shown that the photocytotoxicity of photodynamic drugs could be enhanced by delivering high amounts of a photosensitizer into subcellular organelles such as the nucleus where nucleic acids represent target molecules sensitive to photodamage. The recent progresses in the use of active-targeting strategy with synthetic peptides and the interest of using an active-targeting strategy in PDT, which could allow efficient cellular internalization of photosensitizers, are described in this review.

Amino Acid Sequence↗

Investigation of Foscan interactions with plasma proteins.

The present study investigates the interaction of the second generation photosensitizer Foscan with plasma albumin and lipoproteins. Spectroscopic studies indicated the presence of monomeric and aggregated Foscan species upon addition to plasma protein solutions. Kinetics of Foscan disaggregation in albumin-enriched solutions were very sensitive to the protein concentration and incubation temperature. Kinetic analysis demonstrated that two types of Foscan aggregated species could be involved in disaggregation: dimers with a rate constant of k1 = (2.30+/-0.15) x 10(-3) s(-1) and higher aggregates with rate constants varying from (0.55+/-0.04) x 10(-3) s(-1) for the lowest to the (0.17+/-0.02) x 10(-3) s(-1) for the highest albumin concentration. Disaggregation considerably increased with the temperature rise from 15 degrees C to 37 degrees C. Compared to albumin, Foscan disaggregation kinetics in the presence of lipoproteins displayed poorer dependency on lipoprotein concentrations and smaller variations in disaggregation rate constants. Gel-filtration chromatography analysis of Foscan in albumin solutions demonstrated the presence of aggregated fraction of free, non-bound to protein Foscan and monomeric Foscan, bound to protein.

Animals↗

The 2-aminoglucosamide motif improves cellular uptake and photodynamic activity of tetraphenylporphyrin.

Several strategies have been proposed to improve the efficiency of photosensitizers used in photodynamic therapy (PDT). In this context, the synthesis of mono- (1) and di-glucosylated (2) porphyrins, and mono-glucosylated chlorin (3) was performed. HT29 human adenocarcinoma cells were significantly more sensitive to asymmetric and less hydrophobic glucosylated photosensitizers-mediated PDT (1, 3), compared to tetraphenylporphyrin (TPP). The lowest photosensitivity observed for TPP was consistent with the lowest uptake. Moreover, the most pronounced photodynamic activity measured for 3 was in relation with the improvement of cellular uptake, the singlet oxygen quantum yield and the high extinction coefficient value at 650 nm compared to porphyrins. Cellular localization analysis showed that 1 and 3 accumulated mainly inside the endoplasmic reticulum.

Cell Proliferation↗

Necrotic and apoptotic features of cell death in response to Foscan photosensitization of HT29 monolayer and multicell spheroids.

Photodynamic therapy (PDT) is an approved anticancer treatment modality that eliminates unwanted cells by the photochemical generation of reactive oxygen species following absorption of visible light by a photosensitizer, which is selectively taken up by tumor cells. Present study reports the modalities of cell death after photosensitization of human adenocarcinoma HT29 monolayer and spheroid cells with a second generation photosensitizer Foscan. Kinetics of apoptosis and necrosis after Foscan-PDT in monolayer cells determined by flow cytometry using labeling of cleaved poly(ADP-ribose) polymerase (PARP) and staining with propidium iodide (PI) demonstrated that Foscan was not a strong inducer of apoptosis and necrosis was a prevailing mode of cell death. Cytochrome c release (cyt c) and mitochondrial membrane potential (Deltapsim) addressed by flow cytometry technique at different time points post-Foscan-PDT demonstrated that cell photoinactivation was governed by these mitochondrial events. Foscan-loaded HT29 multicell spheroids, subjected to irradiation with different fluence rates and equivalent light doses, displayed much better tumoricidal activity at the lowest fluence rate used. Apoptosis, measured by caspase-3 activation was evidenced only in spheroids irradiated with the lowest fluence rate and moderate fluence inducing 65% of cell death. Application of higher fluence rates for the same level of photocytotoxicity did not result in caspase-3 activation. The observation of the fluence rate-dependent modulation of caspase-3 activity in spheroids offers the possibility of regulating the mechanism of direct cell photodamage and could be of great potential in the clinical context.

Apoptosis↗

Design, synthesis, and biological evaluation of folic acid targeted tetraphenylporphyrin as novel photosensitizers for selective photodynamic therapy.

Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate light wavelength, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Targeted PDT offers the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. Two new conjugates of three components, folic acid/hexane-1,6-diamine/4-carboxyphenylporphyrine 1 and folic acid/2,2'-(ethylenedioxy)-bis-ethylamine/4-carboxyphenylporphyrine 2 were synthesized. The conjugates were characterized by 1H NMR, MALDI, UV-visible spectroscopy, and fluorescence quantum yield. The targeted delivery of these photoactive compounds to KB nasopharyngeal cell line, which is one of the numerous tumor cell types that overexpress folate receptors was studied. It was found that after 24 h incubation, conjugates 1 and 2 cellular uptake was on average 7-fold higher than tetraphenylporphyrin (TPP) used as reference and that 1 and 2 cellular uptake kinetics increased steadily over the 24 h period, suggesting an active transport via receptor-mediated endocytosis. In corresponding results, conjugates 1 and 2 accumulation displayed a reduction of 70% in the presence of a competitive concentration of folic acid. Survival measurements demonstrated that KB cells were significantly more sensitive to conjugated porphyrins-mediated PDT. Under the same experimental conditions and the same photosensitizer concentration, TPP displayed no photocytotoxicity while conjugates 1 and 2 showed photodynamic activity with light dose values yielding 50% growth inhibition of 22.6 and 6.7 J/cm2, respectively.

Binding, Competitive↗

MALDI-TOF mass spectrometric analysis for the characterization of the 5,10,15,20-tetrakis- (m-hydroxyphenyl)bacteriochlorin (m-THPBC) photoproducts in biological environment.

Photoproducts formation upon irradiation (739 nm) of 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (m-THPBC) in phosphate buffer saline (PBS) supplemented with human serum albumin (HSA) were studied by means of absorption spectroscopy and MALDI-TOF mass spectrometry. The experiments were performed with a freshly prepared PBS-HSA solution of m-THPBC and with a PBS-HSA m-THPBC solution incubated for 6 h at 37 degrees C. The incubation of m-THPBC solution leads to the dye monomerisation, whereas in the freshly prepared solution, m-THPBC is under an aggregated form. Regardless of the incubation condition, photobleaching experiments carried out by absorption spectroscopy demonstrate the degradation of the photosensitizer and its phototransformation in m-THPC. Moreover, m-THPC was the sole photoproduct detected using absorption spectroscopy. Together with a degradation of m-THPBC and formation of m-THPC, MALDI-TOF mass spectrometry evidenced several other photoinduced modifications. Photoproducts such as dihydroxy m-THPBC and dihydroxy m-THPC were detected in both conditions; however, the formation of hydroxylated photoproducts was significantly greater in incubated solution. In addition, small molecules arising from the degradation of the photosensitizer and identified as dipyrin derivatives and dipyrrolic synthon were observed.

Environmental Monitoring↗

[Clinical Practice Guidelines 2004. Standards, Options and Recommendations for the management of patient with adenocarcinoma of the stomach: radiotherapy (therapeutic evaluation)].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French regional cancer centers, and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To elaborate clinical practice guidelines for patients with stomach adenocarcinoma. These recommendations cover the diagnosis, treatment and follow-up of these tumors. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. The Standards, Options and Recommendations are thus based on the best available evidence and expert agreement. RESULTS: This guidelines presents the synthesis of the data concerning the evaluation of the therapeutic ones. The main questions concern the type of gastrectomy to realize (Total Gastrectomy or gastrectomy subtotal), the extent of the lymphadenectomy (D2, D3 versus D1, D3, D2 versus D4) and the role of postoperative chemotherapy and adjuvant concomitant chemoradiotherapy.

Adenocarcinoma↗

Development of an HT29 liver metastases model in nude rats.

The liver is the most frequent and fatal site of distant spreading of colorectal cancer. Most liver metastases animal models involve nude mice and an injection of tumour cells through the spleen or portal vein, or orthotopic implantation of tumour cells in the colon wall. The aim of this study was to develop a reliable rat model of liver metastases with human colorectal HT29 cells. Seventy male athymic Rowett nude rats weighing 300+/-30 g were separated into three groups. The first group (n=20) consisted of untreated rats, rats in the second group (n=20) were immunosuppressed by cyclosporin A, and those in the third group (n=30) were irradiated the day before cell grafting. Tumour cells (2 x 10(7)) were subcapsulary injected into the liver, and rats were sacrificed after 60 days. The livers were excised, and tumours were serially sectioned to determine size and volume, then fixed for histological studies. The take-rate was 55% in the first group, 35% in the second and 74% in the third group. The mean volume of tumours in the first group was 537+/-162 mm(3), 613+/-232 mm(3) in the second group and 2949+/-629 mm(3) in the third group. In conclusion, subcapsular injection of the human colonic HT29 cancer cells into the liver of preoperatively irradiated nude rats is a reliable, reproducible and easily obtained model, which should be useful for preclinical studies.

Animals↗

Photodegradation and phototransformation of 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (m-THPBC) in solution.

The kinetics of photobleaching and formation of photoproducts upon irradiation (735 nm) of 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (m-THPBC) in phosphate buffer saline (PBS) supplemented with human serum albumin (HSA) were studied by means of absorption and steady-state fluorescence spectroscopy. Measurements were performed either immediately after the dye was dissolved in the HSA solution (0 h) or after six hours incubation in the HSA solution (6 h). Spectroscopic studies indicated that the dye was mainly present as aggregates in freshly prepared solutions, whereas incubation favored monomerisation. Irrespective to incubation time, the rates of photobleaching obtained by fluorescence measurements were higher than those obtained from absorbance measurements. Photobleaching of freshly prepared m-THPBC can be described by a single exponential decay, while the absorbance and fluorescence decays of the incubated dye solutions better fit a bi-exponential decay. Two photobleaching rates probably reflect differences in the photosensitivity of monomer (bound to proteins) and aggregated (non-bound) forms. Irradiation of the freshly prepared m-THPBC solution led to phototransformation of 50% of the bleached m-THPBC into 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (m-THPC), a clinically used second generation photosensitizer. For irradiation 6 h after dissolving m-THPBC, different kinetics of m-THPC formation were found. A rapid decrease in concentration of m-THPBC was accompanied by a slow formation of m-THPC. The quantum yield of this process was small since only 5% of m-THPBC was transformed to m-THPC. The kinetics characteristics of m-THPBC photobleaching reported in the present study, together with the different kinetics of photoproduct formation during m-THPBC photobleaching, may provide important indications in the m-THPBC-based PDT dosimetry.

Humans↗