Extracorporeal Photopheresis with 5-Aminolevulinic Acid in Crohn's Disease-A First-in-Human Phase I/II Study.

With the increasing prevalence of Crohn's disease (CD), treatment options for patients who fail conventional and advanced therapy are highly needed. Therefore, we explored the safety and efficacy of extracorporeal photopheresis (ECP) using 5-aminolevulinic acid (ALA) and blue light (405 nm). Patients with active CD who failed or were intolerant to biological therapy were eligible.

Photodynamic Effects with 5-Aminolevulinic Acid on Cytokines and Exosomes in Human Peripheral Blood Mononuclear Cells from Patients with Crohn's Disease.

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) which is the precursor of the photosensitizer protoporphyrin IX (PpIX) is an available treatment for several diseases. ALA-PDT induces the apoptosis and necrosis of target lesions. We have recently reported the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs).

Amphiphilic Protoporphyrin IX Derivatives as New Photosensitizing Agents for the Improvement of Photodynamic Therapy.

Photodynamic therapy (PDT) is a non-invasive therapeutic modality based on the interaction between a photosensitive molecule called photosensitizer (PS) and visible light irradiation in the presence of oxygen molecule. Protoporphyrin IX (PpIX), an efficient and widely used PS, is hampered in clinical PDT by its poor water-solubility and tendency to self-aggregate. These features are strongly related to the PS hydrophilic-lipophilic balance.

Photodynamic Effects with 5-Aminolevulinic Acid on Cytokines and Exosomes in Human Peripheral Blood Mononuclear Cells.

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor to the potent photosensitizer, protoporphyrin IX (PpIX), is an established modality for several malignant and premalignant diseases. This treatment is based on the light-activated PpIX in targeted lesions. Although numerous studies have confirmed the necrosis and apoptosis involved in the mechanism of action of this modality, little information is available for the change of exosome levels after treatment.

Correction: Sioud et al. Evaluation of In Vitro Phototoxicity of a Minibody-IR700 Conjugate Using Monolayer and Multicellular Tumor Spheroid Models. 2021, , 3356.

The authors wish to make the following corrections to this paper [...

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Patients with Chronic Graft-versus-Host Disease: A First-in-Human Study.

Extracorporeal photopheresis (ECP), an immunomodulatory therapy for the treatment of chronic graft-versus-host disease (cGvHD), exposes isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light to induce the apoptosis of T-cells and, hence, to modulate immune responses. However, 8-MOP-ECP kills diseased and healthy cells with no selectivity and has limited efficacy in many cases. The use of 5-aminolevulinic acid (ALA) and light (ALA-based photodynamic therapy) may be an alternative, as ex vivo investigations show that ALA-ECP kills T-cells from cGvHD patients more selectively and efficiently than those treated with 8-MOP-ECP.

Evaluation of In Vitro Phototoxicity of a Minibody-IR700 Conjugate Using Cell Monolayer and Multicellular Tumor Spheroid Models.

Photodynamic therapy (PDT) is a treatment strategy that utilizes photosensitizers (PSs) and light of a specific wavelength to kill cancer cells. However, limited tumor specificity is still a drawback for the clinical application of PDT. To increase the therapeutic efficacy and specificity of PDT, a novel human minibody (MS5) that recognizes a cell surface receptor expressed on various cancer cells was labeled with the hydrophilic phthalocyanine PS IR700 to generate an MS5-IR700 conjugate that is activated by near-infrared (NIR) light.

Evaluation of the PSMA-Binding Ligand Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer.

Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer.

Predictive biomarkers for 5-ALA-PDT can lead to personalized treatments and overcome tumor-specific resistances.

Background: Photodynamic therapy (PDT) is a minimally invasive, clinically approved therapy with numerous advantages over other mainstream cancer therapies. 5-aminolevulinic acid (5-ALA)-PDT is of particular interest, as it uses the photosensitiser PpIX, naturally produced in the heme pathway, following 5-ALA administration. Even though 5-ALA-PDT shows high specificity to cancers, differences in treatment outcomes call for predictive biomarkers to better stratify patients and to also diversify 5-ALA-PDT based on each cancer's phenotypic and genotypic individualities.

Selective Killing of Activated T Cells by 5-Aminolevulinic Acid Mediated Photodynamic Effect: Potential Improvement of Extracorporeal Photopheresis.

Extracorporeal photopheresis (ECP), a modality that exposes isolated leukocytes to the photosensitizer 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) light, is used to treat conditions such as cutaneous T-cell lymphoma and graft-versus-host disease. However, the current procedure of ECP has limited selectivity and efficiency; and produces only partial response in the majority of treated patients. Additionally, the treatment is expensive and time-consuming, so the improvement for this modality is needed.

The Akt pathway in oncology therapy and beyond (Review).

Protein kinase B (Akt), similar to many other protein kinases, is at the crossroads of cell death and survival, playing a pivotal role in multiple interconnected cell signaling mechanisms implicated in cell metabolism, growth and division, apoptosis suppression and angiogenesis. Akt protein kinase displays important metabolic effects, among which are glucose uptake in muscle and fat cells or the suppression of neuronal cell death. Disruptions in the Akt‑regulated pathways are associated with cancer, diabetes, cardiovascular and neurological diseases.

Combined inhibition of Wee1 and Chk1 gives synergistic DNA damage in S-phase due to distinct regulation of CDK activity and CDC45 loading.

Recent studies have shown synergistic cytotoxic effects of simultaneous Chk1- and Wee1-inhibition. However, the mechanisms behind this synergy are not known. Here, we present a flow cytometry-based screen for compounds that cause increased DNA damage in S-phase when combined with the Wee1-inhibitor MK1775.

Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review).

Targeted cancer therapies are used to inhibit the growth, progression, and metastasis of the tumor by interfering with specific molecular targets and are currently the focus of anticancer drug development. Protein kinase B, also known as Akt, plays a central role in many types of cancer and has been validated as a therapeutic target nearly two decades ago. This review summarizes the intracellular functions of Akt as a pivotal point of converging signaling pathways involved in cell growth, proliferation, apoptotis and neo‑angiogenesis, and focuses on the drug design strategies to develop potent anticancer agents targeting Akt.

Supramolecular nanoscale assemblies for cancer diagnosis and therapy.

Nanocarriers based on polymers, metals and lipids have been extensively developed for cancer therapy and diagnosis due to their ability to enhance drug accumulation in cancer cells and decrease undesired drug toxicity in healthy tissues. Overcoming multidrug resistance by designing proper drug nanocarriers will improve outcome of existing oncologic treatments such as chemotherapy and radiotherapy. In this article the relation between physicochemical properties and capacity of a nanosystem to deliver therapeutic agents into pathological sites is discussed.

Radiosensitizing effect of zinc oxide and silica nanocomposites on cancer cells.

Nanoparticulates responsive to X-rays offer increased efficacy of radiation therapy. However, successful demonstrations of such nanoparticle use are limited so far due to lack of significant radiosensitizing effects or poor nanoparticle stability in a biological system. Zinc oxide (ZnO) is the most promising biocompatible material for medicinal applications.

Enhancing proteasome-lnhibitor effect by functionalized gold nanoparticles.

Colloidal gold nanoparticles intensify the anticancer response of the drug bortezomib, a proteasome inhibitor. Polyethylene glycol-coated gold nanoparticles and the drug show a synergistic effect in reducing the cell viability of prostate cancer cell line Du145. It was observed a significant cell viability reduction with bortezomib concentrations as low as 4 nM.

X-ray-induced nanoparticle-based photodynamic therapy of cancer.

Aim: In this study, Ce(3+)-doped lanthanum(III) fluoride (LaF3:Ce(3+)) nanoparticles were synthesized by a wet-chemistry method in dimethyl sulfoxide (DMSO) and their application as an intracellular light source for photodynamic activation was demonstrated.

Materials & Methods: The LaF3:Ce(3+)/DMSO nanoparticles have a strong green emission with a peak at approximately 520 nm, which is effectively overlapped with the absorption of protoporphyrin IX (PPIX). The nanoparticles were encapsulated into poly(D,L-lactide-co-glycolide (PLGA) microspheres along with PPIX.

Gold nanoparticle delivery-enhanced proteasome inhibitor effect in adenocarcinoma cells.

Background: Proteasome inhibition is a current therapeutic strategy used in the treatment of multiple myeloma. Drugs controlling proteasome activity are ideally suited for unidirectional manipulation of cellular pathways such as apoptosis. The first proteasome inhibitor approved in clinics was bortezomib.

Carbon-core silver-shell nanodots as sensitizers for phototherapy and radiotherapy.

Spherical carbon nanoparticles (carbon nanodots) with a silver shell were investigated as potential sensitizing agents. The cytotoxicity of the combination of ultraviolet radiation or x-rays with the nanodots was examined in cancer cells in vitro. The cell viability decreased following the exposure to the radiation.

Blebbistatin, a myosin inhibitor, is phototoxic to human cancer cells under exposure to blue light.

Background: Blebbistatin is a new inhibitor of cell motility. It is used to study dynamics of cytokinesis machinery in cells. However, the potential of this inhibitor as an anticancer agent has not been studied so far.

Carbon dots as antioxidants and prooxidants.

In this study we report the effect of classical CdSe/ZnS quantum dots and novel spherical carbon dots on generation of singlet oxygen and other reactive oxygen species (ROS) in aqueous solutions in vitro. Free radicals were initiated either chemically using 2,2'-azodiisobutyramidine dihydrochloride (AAPH) or by radiation with a blue light source emitting 390-470 nm (peak 420 nm). Two reagents, dihydrorhodamine 123 (Dhr123) and singlet oxygen sensor green (SOSG), were used as radical probes.

Quantum dots affect expression of CD133 surface antigen in melanoma cells.

Background: In novel treatment approaches, therapeutics should be designed to target cancer stem cells (CSCs). Quantum dots (QDs) are a promising new tool in fighting against cancer. However, little is known about accumulation and cytotoxicity of QDs in CSCs.

Entrapment in phospholipid vesicles quenches photoactivity of quantum dots.

Quantum dots have emerged with great promise for biological applications as fluorescent markers for immunostaining, labels for intracellular trafficking, and photosensitizers for photodynamic therapy. However, upon entry into a cell, quantum dots are trapped and their fluorescence is quenched in endocytic vesicles such as endosomes and lysosomes. In this study, the photophysical properties of quantum dots were investigated in liposomes as an in vitro vesicle model.

Epigallocatechin gallate-loaded polysaccharide nanoparticles for prostate cancer chemoprevention.

Aims: Polysaccharide nanoparticles were studied as drug delivery vehicles for chemopreventive agents.

Materials & Methods: Green tea polyphenol epigallocatechin-3-gallate (EGCG) was incorporated into a carbohydrate matrix of gum arabic and maltodextrin with an encapsulation efficiency of approximately 85%.

Results: Encapsulated EGCG retained its biological activity, reducing the cell viability and inducing apoptosis of Du145 prostate cancer cells.