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Biomedical subjects

A Aicher

Publications and source records attributed to A Aicher.

16 recordsLinked to original sources
PubMed2001

Vitamin C inhibits endothelial cell apoptosis in congestive heart failure.

BACKGROUND: Proinflammatory cytokines like tumor necrosis factor-alpha and oxidative stress induce apoptotic cell death in endothelial cells (ECs). Systemic inflammation and increased oxidative stress in congestive heart failure (CHF) coincide with enhanced EC apoptosis and the development of endothelial dysfunction. Therefore, we investigated the effects of antioxidative vitamin C therapy on EC apoptosis in CHF patients. METHODS AND RESULTS: Vitamin C dose dependently suppressed the induction of EC apoptosis by tumor necrosis factor-alpha and angiotensin II in vitro as assessed by DNA fragmentation, DAPI nuclear staining, and MTT viability assay. The antiapoptotic effect of vitamin C was associated with reduced cytochrome C release from mitochondria and the inhibition of caspase-9 activity. To assess EC protection by vitamin C in CHF patients, we prospectively randomized CHF patients in a double-blind trial to vitamin C treatment versus placebo. Vitamin C administration to CHF patients markedly reduced plasma levels of circulating apoptotic microparticles to 32+/-8% of baseline levels, whereas placebo had no effect (87+/-14%, P<0.005). In addition, vitamin C administration suppressed the proapoptotic activity on EC of the serum of CHF patients (P<0.001). CONCLUSIONS: Administration of vitamin C to CHF patients suppresses EC apoptosis in vivo, which might contribute to the established functional benefit of vitamin C supplementation on endothelial function.

Administration, Oral↗
PubMed2001

Aging enhances the sensitivity of endothelial cells toward apoptotic stimuli: important role of nitric oxide.

Advanced aging leads to impaired endothelial NO synthesis and enhanced endothelial cell apoptosis; therefore, we investigated the sensitivity of aged endothelial cells toward apoptotic stimuli and determined the role of NO. Human umbilical vein endothelial cells (HUVECs) were cultured until 14th passage. In aged cells, oxLDL and tumor necrosis factor-alpha-induced apoptosis and caspase-3-like activity were significantly enhanced more than 3-fold compared with young cells (passage 3). Because NO contributes to protection against endothelial cell death via S-nitrosylation of caspases, we determined endothelial NO synthase (eNOS) protein expression and the content of S-nitrosylated proteins. Aged HUVECs showed significantly reduced eNOS expression (35+/-10%) and a decrease in the overall S-NO content (33+/-3%), suggesting that eNOS downregulation may be involved in age-dependent increase of apoptosis sensitivity. Indeed, eNOS knockout endothelial cells showed a significantly enhanced apoptosis induction. Exogenous NO donors abolished increased apoptosis and caspase-3-like activity. In contrast, the application of shear stress, which exerts a profound apoptosis inhibitory effect via upregulation of NO synthesis in young cells, failed to inhibit apoptosis in aged cells. Moreover, no upregulation of eNOS protein expression and S-NO content in response to shear stress was detected in aged cells. Overexpression of wild-type eNOS completely restored the antiapoptotic effect of shear stress, whereas only a partial inhibitory effect was detected under steady conditions. Strikingly, transfection of constitutively active phosphomimetic eNOS (S1177D) further abrogated apoptosis in aged HUVECs. Thus, aging of endothelial cells is associated with decreased NO synthesis and concomitantly increased sensitivity of apoptosis, which may contribute to functional impairment of the endothelial monolayer.

Aging↗
PubMed2001

Tumor necrosis factor-alpha regulates the expression of inducible costimulator receptor ligand on CD34(+) progenitor cells during differentiation into antigen presenting cells.

The inducible costimulator receptor (ICOS) is a third member of the CD28 receptor family that regulates T cell activation and function. ICOS binds to a newly identified ligand on antigen presenting cells different from the CD152 ligands CD80 and CD86. We used soluble ICOSIg and a newly developed murine anti-human ICOS ligand (ICOSL) monoclonal antibody to further characterize the ICOSL during ontogeny of antigen presenting cells. In a previous study, we found that ICOSL is expressed on monocytes, dendritic cells, and B cells. To define when ICOSL is first expressed on myeloid antigen presenting cells, we examined ICOSL expression on CD34(+) cells in bone marrow. We found that CD34(bright) cells regardless of their myeloid commitment were ICOSL(-), whereas ICOSL was first expressed when CD34 expression diminished and the myeloid marker CD33 appeared. However, acute myeloid leukemia cells were ICOSL-negative, whereas among B-cell malignancies only some cases of the most mature tumors such as prolymphocytic leukemia and hairy cell leukemia were positive. Next, we investigated purified CD34(+) hematopoietic progenitor cells that did not constitutively express ICOSL but were induced to express ICOSL within 12 h after granulocyte/macrophage colony-stimulating factor/tumor necrosis factor alpha (TNF-alpha) stimulation. Interestingly, ICOSL was induced prior to CD80/CD86 induction on CD34(+) cells so that ICOSL was expressed in the absence of CD80/CD86. This suggests that ICOSL is an early differentiation marker along the monocytic/dendritic maturation pathway. Induction of ICOSL was dependent on TNF-alpha and was regulated via NF-kappa B as revealed by use of inhibitors specific for I kappa B alpha phosphorylation such as BAY 11-7082 and BAY 11-7085. The antigen presenting capacity of TNF-alpha stimulated CD34(+) cells was strongly inhibited by ICOSIg fusion proteins or by NF-kappa B inhibition. Thus, TNF-alpha-induced ICOSL expression seemed to be functionally important for the costimulatory capacity of CD34(+) hematopoietic progenitor cells.

Antigens, CD34↗
PubMed2001

Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease.

Recent studies provide increasing evidence that postnatal neovascularization involves bone marrow-derived circulating endothelial progenitor cells (EPCs). The regulation of EPCs in patients with coronary artery disease (CAD) is unclear at present. Therefore, we determined the number and functional activity of EPCs in 45 patients with CAD and 15 healthy volunteers. The numbers of isolated EPCs and circulating CD34/kinase insert domain receptor (KDR)-positive precursor cells were significantly reduced in patients with CAD by approximately 40% and 48%, respectively. To determine the influence of atherosclerotic risk factors, a risk factor score including age, sex, hypertension, diabetes, smoking, positive family history of CAD, and LDL cholesterol levels was used. The number of risk factors was significantly correlated with a reduction of EPC levels (R=-0.394, P=0.002) and CD34-/KDR-positive cells (R=-0.537, P<0.001). Analysis of the individual risk factors demonstrated that smokers had significantly reduced levels of EPCs (P<0.001) and CD34-/KDR-positive cells (P=0.003). Moreover, a positive family history of CAD was associated with reduced CD34-/KDR-positive cells (P=0.011). Most importantly, EPCs isolated from patients with CAD also revealed an impaired migratory response, which was inversely correlated with the number of risk factors (R=-0.484, P=0.002). By multivariate analysis, hypertension was identified as a major independent predictor for impaired EPC migration (P=0.043). The present study demonstrates that patients with CAD revealed reduced levels and functional impairment of EPCs, which correlated with risk factors for CAD. Given the important role of EPCs for neovascularization of ischemic tissue, the decrease of EPC numbers and activity may contribute to impaired vascularization in patients with CAD. The full text of this article is available at http://www.circresaha.org.

AC133 Antigen↗
PubMed2001

Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease.

BACKGROUND: Therapeutic neovascularization may constitute an important strategy to salvage tissue from critical ischemia. Circulating bone marrow-derived endothelial progenitor cells (EPCs) were shown to augment the neovascularization of ischemic tissue. In addition to lipid-lowering activity, hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) reportedly promote the neovascularization of ischemic tissue in normocholesterolemic animals. Methods and Results-Fifteen patients with angiographically documented stable coronary artery disease (CAD) were prospectively treated with 40 mg of atorvastatin per day for 4 weeks. Before and weekly after the initiation of statin therapy, EPCs were isolated from peripheral blood and counted. In addition, the number of hematopoietic precursor cells positive for CD34, CD133, and CD34/kinase insert domain receptor was analyzed. Statin treatment of patients with stable CAD was associated with an approximately 1.5-fold increase in the number of circulating EPCs by 1 week after initiation of treatment; this was followed by sustained increased levels to approximately 3-fold throughout the 4-week study period. Moreover, the number of CD34/kinase insert domain receptor-positive hematopoietic progenitor cells was significantly augmented after 4 weeks of therapy. Atorvastatin treatment increased the further functional activity of EPCs, as assessed by their migratory capacity. CONCLUSION: The results of the present study define a novel mechanism of action of statin treatment in patients with stable CAD: the augmentation of circulating EPCs with enhanced functional activity. Given the well-established role of EPCs of participating in repair after ischemic injury, stimulation of EPCs by statins may contribute to the clinical benefit of statin therapy in patients with CAD.

Adult↗
PubMed2001

The role of toll-like receptors (TLRs) in bacteria-induced maturation of murine dendritic cells (DCS). Peptidoglycan and lipoteichoic acid are inducers of DC maturation and require TLR2.

Toll-like receptors (TLRs) have been found to be key elements in pathogen recognition by the host immune system. Dendritic cells (DCs) are crucial for both innate immune responses and initiation of acquired immunity. Here we focus on the potential involvement of TLR ligand interaction in DC maturation. TLR2 knockout mice and mice carrying a TLR4 mutation (C3H/HeJ) were investigated for DC maturation induced by peptidoglycan (PGN), lipopolysaccharide (LPS), or lipoteichoic acids (LTAs). All stimuli induced maturation of murine bone marrow-derived DCs in control mice. TLR2(-)/- mice lacked maturation upon stimulation with PGN, as assessed by expression of major histocompatibility complex class II, CD86, cytokine, and chemokine production, fluorescein isothiocyanate-dextran uptake, and mixed lymphocyte reactions, while being completely responsive to LPS. A similar lack of maturation was observed in C3H/HeJ mice upon stimulation with LPS. DC maturation induced by LTAs from two different types of bacteria was severely impaired in TLR2(-)/-, whereas C3H/HeJ mice responded to LTAs in a manner similar to wild-type mice. We demonstrate that DC maturation is induced by stimuli from Gram-positive microorganisms, such as PGN and LTA, with similar efficiency as by LPS. Finally, we provide evidence that TLR2 and TLR4 interaction with the appropriate ligand is essential for bacteria-induced maturation of DCs.

Animals↗
PubMed2001

Osteoprotegerin, a crucial regulator of bone metabolism, also regulates B cell development and function.

Osteoprotegerin (OPG) is a CD40-regulated gene in B cells and dendritic cells (DCs). We investigated the role of OPG in the immune system by generating opg(-/-) mice. Like its role as a regulator of bone metabolism, OPG also influences processes in the immune system, notably in B cell development. Ex vivo, opg(-/-) pro-B cells have enhanced proliferation to IL-7, and in opg(-/-) spleen, there is an accumulation of type 1 transitional B cells. Furthermore, opg(-/-) bone marrow-derived DCs are more effective in stimulating allogeneic T cells than control DCs. When challenged with a T-dependent Ag, opg(-/-) mice had a compromised ability to sustain an IgG3 Ag-specific response. Thus, in the immune system, OPG regulates B cell maturation and development of efficient Ab responses.

Animals↗
PubMed2001

HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway.

HMG-CoA reductase inhibitors (statins) have been developed as lipid-lowering drugs and are well established to reduce morbidity and mortality from coronary artery disease. Here we demonstrate that statins potently augment endothelial progenitor cell differentiation in mononuclear cells and CD34-positive hematopoietic stem cells isolated from peripheral blood. Moreover, treatment of mice with statins increased c-kit(+)/Sca-1(+)--positive hematopoietic stem cells in the bone marrow and further elevated the number of differentiated endothelial progenitor cells (EPCs). Statins induce EPC differentiation via the PI 3-kinase/Akt (PI3K/Akt) pathway as demonstrated by the inhibitory effect of pharmacological PI3K blockers or overexpression of a dominant negative Akt construct. Similarly, the potent angiogenic growth factor VEGF requires Akt to augment EPC numbers, suggesting an essential role for Akt in regulating hematopoietic progenitor cell differentiation. Given that statins are at least as potent as VEGF in increasing EPC differentiation, augmentation of circulating EPC might importantly contribute to the well-established beneficial effects of statins in patients with coronary artery disease.

Animals↗
PubMed2000

Characterization of human inducible costimulator ligand expression and function.

The inducible costimulator (ICOS) is the newest member of the CD28/CD152 receptor family involved in regulating T cell activation. We constructed a soluble-Ig fusion protein of the extracellular domain of human ICOS and used it as a probe to characterize expression patterns of the ICOS ligand (ICOSL). ICOSIg did not bind to CD80- or CD86-transfected Chinese hamster ovary cell lines, demonstrating that ICOSL is distinct from those ligands identified for CD28/CD152. ICOSIg showed selective binding to monocytic and B cell lines, whereas binding was undetectable on unstimulated monocytes and peripheral blood T and B cells. Expression of ICOSL was induced on monocytes after integrin-dependent plastic adhesion. Pretreatment of monocytes with mAb to the beta2-integrin subunit CD18 decreased adhesion and abolished ICOSL up-regulation but had no effect on CD80/86 (CD152 ligand (CD152L)) expression. Both ICOSL and CD152L were up-regulated on monocytes by IFN-gamma but by distinct signaling pathways. Unlike CD152L expression, ICOSL expression did not change when monocytes were differentiated into dendritic cells (DCs) or after DCs were induced to mature by LPS, TNF-alpha, or CD40 ligation. Addition of ICOSIg to allogeneic MLRs between DCs and T cells reduced T cell proliferative responses but did so less efficiently than CTLA4Ig (CD152Ig) did. Similarly, ICOSIg also blocked Ag-specific T cell proliferation to tetanus toxoid. Thus, ICOSL, like CD80/86, is expressed on activated monocytes and dendritic cells but is regulated differently and delivers distinct signals to T cells that can be specifically inhibited by ICOSIg.

Abatacept↗
PubMed1999

Differential role for p38 mitogen-activated protein kinase in regulating CD40-induced gene expression in dendritic cells and B cells.

We investigated whether human monocyte-derived dendritic cells (DCs) differed from tonsillar B cells in the set of cell fate genes they express constitutively and in the way these genes are affected after CD40 ligation. In particular, Bcl-2, TNF receptor-associated factor-2 (TRAF2), and TRAF4 were clearly inducible via CD40 in B cells but not in DCs. DCs, unlike B cells, were induced to increase expression of IL-1beta, IL-1Ra, IL-8, IL-12 p40, RANTES, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1 after CD40 ligation. We next tested whether CD40-induced signaling pathways were different in DCs vs B cells. In DCs, as in B cells, CD40 ligation activated p38 mitogen-activated protein kinase (MAPK), its downstream target, MAPKAPK-2, and the c-Jun N-terminal kinase. The p38 MAPK-specific inhibitor, SB203580, blocked CD40-induced MAPKAPK-2 activation, but did not affect activation of c-Jun N-terminal kinase. Furthermore, unlike in B cells, extracellular signal-regulated kinase-1 and -2 were activated after CD40 ligation in DCs. SB203580 strongly blocked CD40-induced IL-12 p40 production in DCs at both mRNA and protein levels, while having minimal effect on CD40-induced expression of the chemokine RANTES. In contrast, no detectable IL-12 p40 protein was secreted in CD40-stimulated B cells. Furthermore, CD40-induced mRNA expression of cellular inhibitor of apoptosis protein-2 was also dependent on the p38 MAPK pathway in DCs and differed compared with that in B cells. In conclusion, CD40 induces distinct programs in DCs and B cells, and the set of p38 MAPK-dependent genes in DCs (IL-12 p40 and cellular inhibitor of apoptosis protein-2) is different from that in B cells (IL-10 and IL-1beta).

Apoptosis↗
PubMed1998

Retroviral interleukin-7 gene transfer into human dendritic cells enhances T cell activation.

Tumor vaccination with dendritic cells (DC) presenting tumor antigens to T cells is a promising approach in immunotherapy. The aim of this study was to enhance T cell stimulatory ability of human DC by retroviral expression of the interleukin-7 (IL-7) gene. IL-7 has been shown to provide a potent costimulatory signal for the proliferation of T cells and the generation of cytotoxic T cells (CTL). DC were generated from human peripheral blood mononuclear cells (PBMC). DC were analyzed by light- and electron-microscopy, immunophenotype (CD1a+, CD14-, CD80+, CD86+, HLA-DR+) and functional assays. According to these criteria, 75-85% of the cells were DC. The cells did not produce measurable amounts of IL-7 spontaneously nor did they express the IL-7 receptor. A retroviral IL-7 expression vector was constructed. Retroviral infection was performed with either the LXSN-hIL-7 vector of its variant LXSN. Using the LXSN-hIL-7 vector, IL-7 production of 2296 pg/10(6) cells/24 h could be achieved on average. Transduction of DC was confirmed by RT-PCR in a CD1a-enriched cell fraction. Transduction efficiency by a control virus coding for beta-galactosidase was about 30%. In autologous mixed lymphocyte reaction (MLR), IL-7 transduced DC augmented T cell proliferation by a factor of two compared with unmodified or mock-transfected DC, and in allogeneic MLR there was a 2.7-fold increase in T cell proliferation. The increase in T cell proliferation could be correlated to IL-7 secretion by DC. Dendritic cells that have been simultaneously peptide-loaded and gene-modified to secrete IL-7 are a potential tool to amplify activation of tumor-specific T cells.

Cells, Cultured↗
PubMed1997

Lack of correlation between rejection of tumor cells co-expressing interleukin-2 and B7.1 and vaccine efficiency.

Genetically modifying tumor cells to express a variety of cytokines such as interleukin-2 (IL-2) or the co-stimulatory molecule B7.1 leads to increased immunogenicity and reduced tumorigenicity of tumors in several models with T cells involved in the process. We have previously reported decreased tumorigenicity of the murine plasmacytoma J558L [major histocompatibility complex (MHC) class I+ and class II-] expressing IL-2 or B7.1. When systemic immunity was analyzed, immunization with either J558-IL2 or J558-B7.1 cells generated moderate protection against unmodified J558L tumor cells, comparable to immunization with a tumor cells/adjuvant Corynebacterium parvum mixture. In this study, we asked whether the co-expression of IL-2 and B7.1 in tumor cells would augment vaccine potency, cytotoxic T lymphocyte (CTL) activity and protective immunity. Rejection of single IL-2 or B7.1 or co-transfected IL-2/B7.1 cells occurred in most syngeneic animals but not in T cell-deficient nude mice, thus confirming that T cells were required for tumor rejection. We knew from previous experiments that CD8+ T cells were responsible for rejection. Surprisingly, immunization with J558-IL2/B7.1 cells followed by challenge with parental J558L caused a reduction in systemic protection as compared to J558-B7.1 or J558-IL2 alone. We examined the mechanism underlying this unexpected result: 6 days after injection of J558-IL2/B7.1 cells, tumor were nearly completely destroyed and were almost devoid of CD8+ cells, while CD8+ cells were increased in both IL-2- and B7.1-transfected tumors. In addition, immunization with J558-IL2/B7.1 tumors had an adverse effect on the generation of CTL. Mice immunized with J558-B7.1 and to a lesser extent J558-IL2 cells mounted a CTL response against J558L cells while, in contrast, no CTL activity could be detected in mice immunized with J558-IL2/B7.1, thus showing a correlation between the absence of CTL activity and the lack of in vivo protection. We demonstrate that "hyperstimulation" of the immune response by genetically modified cancer vaccines can have adverse effects on tumor immunity, even though the mechanism is not yet completely understood.

Animals↗
PubMed1997

Successful retroviral mediated transduction of a reporter gene in human dendritic cells: feasibility of therapy with gene-modified antigen presenting cells.

In this study we have analyzed the feasibility of gene transfer in human dendritic cells (DCs). DCs were generated from T and B cell-depleted peripheral blood mononuclear cells cultured for 7 days in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The cells showed morphologic and immunophenotypical features typical of DCs, including expression of major histocompatibility complex (MHC) class I and II molecules, CD1a, CD80, CD86, CD13, CD33, CD40, and CD54. The cells showed high stimulatory activity in both allogeneic and autologous mixed lymphocyte reaction (MLR). The bacterial reporter gene lacZ coding for beta-galactosidase (beta-gal) was introduced in DCs by three sequential cycles of infection using a MFG retroviral vector system. After 7 days of culture 35-67% of the cells showed high expression of beta-gal activity, proving successful gene transfer. Stable integration of the lacZ gene was demonstrated by genomic DNA-polymerase chain reaction (PCR) up to 20 days after gene transfer. The percentage of transduction was similar when DCs were further purified by immunomagnetic separation according to CD1a-expression. We conclude that human DCs can be efficiently gene modified, further broadening the spectrum of possible DC-based clinical applications.

Antigen Presentation↗
PubMed1995

Tumor cells cotransfected with interleukin-7 and B7.1 genes induce CD25 and CD28 on tumor-infiltrating T lymphocytes and are strong vaccines.

Interleukin-7 (IL-7) and the membrane molecule B7 are both able to provide proliferation and activation signals for T cells. However, tumor cells transfected to express either molecule alone are not reliably rejected in syngeneic hosts or are not sufficiently immunogenic to serve as potent tumor vaccines. Since IL-7 and B7 have shown synergistically to induce activation and proliferation of T cells in vitro, we have expressed B7.1 by means of a retrovirus in the mammary adenocarcinoma TS/A which arose spontaneously in a BALB/c mouse and in the plasmacytoma J558L and their IL-7-transfected sublines to improve vaccine efficacy. Expression of IL-7 or B7.1 alone in tumor cells decreased tumorigenicity, but nevertheless tumors grew in a substantial number of mice. In contrast, IL-7/B7.1 cotransfected cells did not grow as tumor in a single case. This inhibition of tumor growth was completely T cell dependent, because TS/A-IL-7/B7.1 cells retained their full tumorigenic potential in T cell-deficient mice. Analysis of tumor-infiltrating T lymphocytes revealed increased numbers of T cells in B7, IL-7 and IL-7/B7 transfected compared to parental tumors. In IL-7/B7 transfected tumors, T cell numbers were not further increased compared to that in single-gene-transfected tumors. However, T cells in B7 and IL-7 transfected tumors differed phenotypically with respect to activation markers. In B7 transfected tumors, T cells were predominantly CD28+ and CD25-, while in IL-7 transfected tumors, T cells were mainly CD28- and CD25+. In IL-7/B7 cotransfected tumors, the majority of T cells was CD28+ and CD25+. Thus, IL-7 and B7 induced an anti-tumor immune response by complementary T cell directed pathways in a cooperative fashion. Importantly, immunization of mice with the transfected cells and subsequent contralateral challenge with parental tumor cells showed that IL-7/B7 co-expressing cells induced the most strongly protective immunity, which is superior to that induced by single-gene transfectants and to the adjuvant Corynebacterium parvum. Vaccine efficacy was abrogated when irradiated cells were used for vaccination. Together, our results show that IL-7 and B7.1 transfected tumor cells induce strong T cell activation and tumor immunity.

Animals↗
PubMed1994

Photodynamic therapy of human bladder carcinoma cells in vitro with pH-sensitive liposomes as carriers for 9-acetoxy-tetra-n-propylporphycene.

In vitro experiments were performed on human bladder carcinoma cells to evaluate the efficiency of the recently synthesized photosensitizer 9-acetoxy-tetra-n-propylporphycene (ATPPn) for photodynamic therapy. To improve cytoplasmic delivery of this hydrophobic compound, we prepared pH-sensitive liposomes composed of phosphatidylethanolamine (PE) and cholesteryl hemisuccinate (CHEMS) in comparison with pH-insensitive liposomes consisting of phosphatidylcholine (PC) and CHEMS. Dynamic light scattering measurements were used to monitor the acid-induced liposome destabilization. After incubation with liposome-bound ATPPn, bladder carcinoma cells were irradiated by a dye laser with increasing light fluence rates from 1 to 48 J/cm2. The photodynamic effects were then assessed from cell survival curves. No dark or phospholipid toxicity was measured for 2 micrograms ATPPn/1.5 ml medium. Qualitative cellular uptake of ATPPn was determined by fluorescence microscopy, while photodamage was elucidated by transmission and scanning electron microscopy. Absorption spectra performed up to 42 days revealed changes in shape for the pH-sensitive liposomes after storage at room temperature. ATPPn was proved to be an encouraging photosensitizer, capable of reducing cell survival to 0.1% after short-term incubation of 60 min with a drug dose of 2 micrograms ATPPn/1.5 ml medium. Although pH-sensitive PE/CHEMS liposomes showed significantly (P < 0.05) more photokilling effects at 24 J/cm2 and 48 J/cm2, no further advantages over non-pH-sensitive PC/CHEMS liposomes were found.

Carcinoma↗