Johan Emelian Moan

Bio: Johan Emelian Moan is an academic researcher from Oslo University Hospital. The author has contributed to research in topics: Protoporphyrin IX & Photodynamic therapy. The author has an hindex of 72, co-authored 389 publications receiving 18378 citations. Previous affiliations of Johan Emelian Moan include University of Oslo & Rikshospitalet–Radiumhospitalet.

5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges.

Abstract: BACKGROUND Photodynamic therapy (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25 years PDT involves administration of a tumor-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light Although several photosensitizers other than ALA-derived protoporphyrin IX (PpIX) have been used in clinical PDT, ALA-based PDT has been the most active area of clinical PDT research during the past 5 years Studies have shown that a higher accumulation of ALA-derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALA-based PDT and diagnosis However, no review updating the clinical data has appeared so far METHODS A review of recently published data on clinical ALA-based PDT and diagnosis was conducted RESULTS Several individual studies in which patients with primary nonmelanoma cutaneous tumors received topical ALA-based PDT have reported promising results, including outstanding cosmetic results However, the modality with present protocols does not, in general, appear to be superior to conventional therapies with respect to initial complete response rates and long term recurrence rates, particularly in the treatment of nodular skin tumors Topical ALA-PDT does have the following advantages over conventional treatments: it is noninvasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse surgery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity Topical ALA-PDT also has potential as a treatment for nonneoplastic skin diseases Systemic administration of ALA does not seem to be severely toxic, but the advantage of using this approach for PDT of superficial lesions of internal hollow organs is still uncertain The ALA-derived porphyrin fluorescence technique would be useful in the diagnosis of superficial lesions of internal hollow organs CONCLUSIONS Promising results of ALA-based clinical PDT and diagnosis have been obtained The modality has advantages over conventional treatments However, some improvements need to be made, such as optimization of parameters of ALA-based PDT and diagnosis; increased tumor selectivity of ALA-derived PpIX; better understanding of light distribution in tissue; improvement of light dosimetry procedure; and development of simpler, cheaper, and more efficient light delivery systems Cancer 1997; 79:2282-308 © 1997 American Cancer Society

The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen

Abstract: NHIK 3025 cells were incubated with Photofrin II (PII) and/or tetra (3-hydroxyphenyl)porphyrin (3THPP) and exposed to light at either 400 or 420 nm, i.e. at the wavelengths of the maxima of the fluorescence excitation spectra of the two dyes. The kinetics of the photodegradation of the dyes were studied. When present separately in the cells the two dyes are photodegraded with a similar quantum yield. 3THPP is degraded 3-6 times more efficiently by light quanta absorbed by the fluorescent fraction of 3THPP than by light quanta absorbed by the fluorescent fraction of PII present in the same cells. The distance diffused by the reactive intermediate, supposedly mainly 1O2, causing the photodegradation was estimated to be on the order of 0.01-0.02 micron, which corresponds to a lifetime of 0.01-0.04 microsecond of the intermediate in the cells. PII has binding sites at proteins in the cells as shown by an energy transfer band in the fluorescence excitation spectrum at 290 nm. During light exposure this band decays faster than the Soret band of PII under the present conditions. Photoproducts (1O2 etc.) generated at one binding site contribute significantly in the destruction of remote binding sites.

5‐Aminolevulinic Acid‐Based Photodynamic Therapy: Principles and Experimental Research

Abstract: The iron(I1) complex of protoporphyrin IX (PpIX)? (heme) is bound to different proteins to form key biomolecules (hemoproteins) such as hemoglobin, myoglobin, cytochromes, catalase, peroxidase and tryptophan pyrrolase. The lives of the cells and of the body as a whole is therefore crucially dependent upon the biosynthesis and metabolism of porphyrins. Almost all types of cells of the human body, with the exception of mature red blood cells, are equipped with a machinery to synthesize heme. In the first step of the heme biosynthetic pathway 5-aminolevulinic acid (ALA) is formed from glycine and succinyl CoA. The synthesis of ALA is regulated by the amount of heme in the cell. The last step in the formation of heme is the incorporation of iron into PpIX and takes place in the mitochondria under the action of the enzyme, ferrochelatase. By adding exogenous ALA, PpIX may accumulate because of the limited capacity of ferrochelatase. Porphobilinogen deaminase (PBGD) is another enzyme that is active in the heme synthesis pathway (catalyzing the formation of uroporphyrinogen from porphobilinogen [PBG]). The activity of this enzyme is higher in some tumors (1-3), while that of ferrochelatase is lower (2-7), so that PpIX accumulates with some degree of selectivity in tumors. Because PpIX is an efficient photosensitizer, ALA has been introduced as a drug for clinical photodynamic therapy (PDT) of cancer (8,9). Photodynamic therapy involves systemic administration of a tumor-localizing photosensitizer and its subsequent activation by light of an appropriate wavelength to create a pho-

Photochemical internalization: a novel technology for delivery of macromolecules into cytosol.

Abstract: The therapeutic usefulness of macromolecules, such as in gene therapy, is often limited by an inefficient transfer of the macromolecule to the cytosol and a lack of tissue-specific targeting. The possibility of photochemically releasing macromolecules from endosomes and lysosomes into the cytosol was examined. Endocytosed macromolecules and photosensitizer were exposed to light and intracellular localization and the expression of macomolecules in the cytosol was analyzed. This novel technology, named photochemical internalization (PCI), was found to efficiently deliver type I ribosome-inactivating proteins, horseradish peroxidase, a p21ras-derived peptide, and a plasmid encoding green fluorescent protein into cytosol in a light-dependent manner. The results presented here show that PCI can induce efficient light-directed delivery of macromolecules into the cytosol, indicating that PCI may have a variety of useful applications for site-specific drug delivery, e.g., in gene therapy, vaccination, and cancer treatment.

The dependency of vitamin D status on body mass index, gender, age and season

Abstract: Background: Obesity is a rapidly growing health problem in most developed countries. Excess body weight is a risk factor for many somatic and even psychological disorders, including cardiovascular disease, type 2 diabetes mellitus, osteoarthritis and several cancer types. Recently, overweight and obesity have been shown to be related to low vitamin D status. Materials and Methods: The 25(OH)D 3 status was analyzed in a population of 2,126 patients registered in a Metabolic and Medical Lifestyle Management Clinic in Oslo, Norway. Seasonal variation and prevalence of vitamin D deficiency were assessed in different body mass index (BMI), sex and age categories. Results: For both sexes and both age groups (<50 years and ≥50 years) there was a significant decrease of serum 25(OH)D 3 levels with increasing BMI. Surprisingly, not only were the 25(OH)D 3 levels negatively correlated with BMI, but the serum 1,25(OH) 2 D 3 levels were also. The seasonal variation of serum 25(OH)D 3 was highest in young (<50 years) non-obese men. The prevalence of vitamin D deficiency was highest in individuals with BMI ≥40, being as high as 32% among women and 46% among men. Conclusion: The 25(OH)D 3 level, as well as its seasonal variation and the prevalence of vitamin D deficiency, are all dependent on BMI, and age separately. The results of the study suggest that 1 in 3 women and 1 in 2 men with BMI ≥40 are vitamin D deficient.

Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline

Abstract: Objective: The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. Participants: The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Conclusions: Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recomme...

Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline (Journal of Clinical Endocrinology and Metabolism (2011) 96, (1911-1930))

Abstract: OBJECTIVE The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. PARTICIPANTS The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. CONSENSUS PROCESS Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. CONCLUSIONS Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.

Photodynamic therapy for cancer

Abstract: The therapeutic properties of light have been known for thousands of years, but it was only in the last century that photodynamic therapy (PDT) was developed. At present, PDT is being tested in the clinic for use in oncology--to treat cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate and skin. How does PDT work, and how can it be used to treat cancer and other diseases?

Role of free radicals and catalytic metal ions in human disease: an overview.

Abstract: Publisher Summary This chapter discusses the role of free radicals and catalytic metal ions in human disease. The importance of transition metal ions in mediating oxidant damage naturally leads to the question as to what forms of such ions might be available to catalyze radical reactions in vivo . The chapter discusses the metabolism of transition metals, such as iron and copper. It also discusses the chelation therapy that is an approach to site-specific antioxidant protection. The detection and measurement of lipid peroxidation is the evidence most frequently cited to support the involvement of free radical reactions in toxicology and in human disease. A wide range of techniques is available to measure the rate of this process, but none is applicable to all circumstances. The two most popular are the measurement of diene conjugation and the thiobarbituric acid (TBA) test, but they are both subject to pitfalls, especially when applied to human samples. The chapter also discusses the essential principles of the peroxidation process. When discussing lipid peroxidation, it is essential to use clear terminology for the sequence of events involved; an imprecise use of terms such as initiation has caused considerable confusion in the literature. In a completely peroxide-free lipid system, first chain initiation of a peroxidation sequence in a membrane or polyunsaturated fatty acid refers to the attack of any species that has sufficient reactivity to abstract a hydrogen atom from a methylene group.

Photodynamic Therapy

Abstract: Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (Photofrin) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered.