The two families of dyes that have been most extensively studied in relation to photodynamic therapy are the phthalocyanines and the porphyrins. Series of such dyes are available in a relatively pure form and are well suited for studies attempting to evaluate how the hydrophobicity of a dye influences its cellular uptake, its retention, and its photosensitizing efficiency. Derivatives of phthalocyanines and porphyrins decrease in lipophilicity as the number of sulfonate groups increases. The chapter demonstrates that the cellular uptake of the components of he-matoporphyrin derivative and PII increases with increasing lipophilicity of the components. Photoexcitation of cells containing PII results in a destruction of the binding sites of PII on proteins and a displacement of the dye molecules to other sites. A general finding for all sensitizers studied in our laboratory is that cells tend to accumulate in mitosis after being exposed to light in their presence.

Following curative-intent neoadjuvant therapy in locally advanced rectal cancer, metastatic progression is still dominant. We investigated if patients’ circulating 25-hydroxyvitamin D [25(OH)D] levels were associated with outcome. Serum 25(OH)D concentration was assessed by liquid chromatography-mass spectrometry in samples collected from 84 patients at baseline, completion of the neoadjuvant therapy, and treatment evaluation before surgery, and analyzed with respect to season, disease presentation, and treatment effects. In the cohort of patients residing at latitude 58–62°N, baseline 25(OH)D differed significantly over the seasons, with highest measures (mean of 71.2 ± 5.6 nmol/L) in summer and lowest (48.7 ± 4.5 nmol/L) in spring, and changed over the three-month neoadjuvant period till response evaluation solely owing to season. The patient subgroup with slightly reduced performance status, anemia, and T4 disease that did not respond to the neoadjuvant therapy (ypT4 cases), had significantly lower baseline 25(OH)D (below 50 nmol/L) than T4 cases with response (ypT0–3) and T2–3 cases (above 60 nmol/L). Compared to the T4 patients with levels above 50 nmol/L, regarded as sufficient for a healthy bone status, those presenting levels below had significantly heightened risk of disease progression (mainly metastasis) and death, with hazard ratio of 3 and 17, respectively, on adjustment for age, sex, body mass index, and season. Rectal cancer T4 cases had high risk of metastatic progression and death if circulating 25(OH)D levels were insufficient but obtained short-term and long-term outcome to neoadjuvant treatment no worse than patients with T2–3 disease when 25(OH)D was sufficient. ClinicalTrials.gov NCT00278694 ; registration date: 16 January 2006, retrospective to enrollment of the first 10 patients of the current report.

e15532 Background: Following curative intention neoadjuvant therapy in locally advanced rectal cancer, metastatic progression is still dominant. We investigated if patient’s circulating 25-hydroxyvitamin D [25(OH)D] level was associated with outcome. Methods: Serum 25(OH)D concentration was assessed in samples collected from 84 patients at baseline, completion of the neoadjuvant therapy, and treatment evaluation before surgery, and analyzed with respect to the season of diagnosis, disease presentation, and treatment effects. Results: In the cohort of patients residing at latitude 58-62°N, baseline 25(OH)D levels differed significantly over the seasons, with highest measures (mean of 71.2±5.6 nmol/L) in summer and lowest (48.7±4.5 nmol/L) in spring, and changed over the three-month neoadjuvant period till response evaluation solely owing to season. Patients with slightly reduced performance status or anemia, as well as those with T4 disease that did not respond to the neoadjuvant therapy (ypT4 cases), had significantly lower baseline 25(OH)D levels ( < 50 nmol/L) than T4 cases with response (ypT0-3) and T2-3 cases ( > 60 nmol/L). A third of patients with T4 disease had particularly low 25(OH)D ( < 35 nmol/L). Compared to the T4 patients with levels > 50 nmol/L, regarded as adequate for bone health, those presenting levels below had significantly heightened risk of disease progression (mainly metastasis) and death, with hazard ratio of 3.21 and 17.5, respectively. Conclusions: Rectal cancer T4 cases had high risk of metastatic progression and death if circulating 25(OH)D levels were insufficient but obtained short-term and long-term outcome to neoadjuvant treatment no worse than patients with T2-3 disease when 25(OH)D was sufficient. Clinical trial information: NCT00278694.25(OH)D, nmol/L T2-3 cases T4 cases < 50 ≥50 p1 < 50 ≥50 p1 PFS No. at risk 18 35 14 17 No. of events 4 12 9 6 Multivariable HR (95% CI)2 0.548 (0.176-1.71) Referent 0.30 3.21 (1.08-9.54) Referent 0.036 OS No. at risk 18 35 14 17 No. of events 2 5 7 1 Multivariable HR (95% CI)2 0.594 (0.110-3.22) Referent 0.55 17.5 (1.98-155) Referent 0.010 PFS = progression-free survival, OS = overall survival, HR = hazard ratio, CI = confidence interval 1 Estimated by Cox proportional hazard model 2 Adjusted for age, sex, and body mass index

To preliminarily evaluate the status of Vitamin D in Tibetan residents and explore the possible factors affecting the content of vitamin D,blood samples of 16 farmers (7 men and 9 women) who live in Nicang village,Shigatse and Tibet were collected for six times during 2008 and 2009,a total of 81 blood samples were taken.Blood samples of 15-50 residents in Lhasa,Tingri,Naqu and Shigatse were collected twice during 2012 and 2013,290 blood samples were eventually obtained.Of these,126 came from men and 164 from women.The blood sample was processed by the professional doctor of the people's Hospital of autonomous region to extract the serum.The contents of serum 25 (OH) D was measured by radioimmunoassay.After analyzing,the average concentration of serum 25(OH) D in Tibetans is 12.25 ng/mL.The concentration of serum 25 (OH) D was (12.8-± 4.9) ng/mL for males and (11.9 ± 5.3) ng/mL for females.According to the standard issued by the Osteoporosis Committee for the Gerontological Society of China,only 10.4％ in males and 4.2％ in females among the blood samples had sufficient Vitamin D (P ＜ 0.05).The concentration of serum 25 (OH)D for the youth is 20％ higher than the middle and the old.The concentration of serum 25 (OH)D in summer is about 30％ higher than was in winter.There are significant differences in serum 25 (OH) D levels among different occupations.The concentration of serum 25 (OH)D in herdsmen,teachers and students was higher than in farmers.In a word,the average concentration of serum 25 (OH) D in Tibetans is insufficient,which has a lot to do with the way people dress,their skin color,and their eating habits according to observation.The concentration of serum 25 (OH) D is different in terms of different seasons,age,sex and regions.The reasons behind the problem are worth our reflection and exploration.

BACKGROUND:Solar ultraviolet (UV) radiation varies with latitude, time of day, and season. Both spectral UV composition and ambient UV dose lead to different health outcomes at different latitudes. Finding the optimal time for sun exposure, whereby the positive effects of UV exposure (vitamin D) are facilitated and the negative effects (skin cancer, photoimmunosuppression) avoided are the most important consideration in modern skin cancer prevention programs.OBJECTIVES:This paper focuses on the latitude dependency of UVB, UVA, vitamin D production, and skin cancer risk in Caucasians.METHODS:Biologically effective UVB (280-315 nm) and UVA (315-400 nm) doses were calculated using radiative transfer models with appropriate climatologic data for selected locations. Incidences of squamous cell carcinoma (SCC) and cutaneous melanoma (CM) were retrieved from cancer registries and published articles.RESULTS:Annual doses of UVA radiation decrease much less with increasing latitude than annual doses of UVB. Incidences of CM also decrease less steeply with increasing latitude than incidences of SCC. As SCC is caused mainly by UVB, these observations support the assumption that UVA plays an important role in the development of CM. The variations in UVA (relevant to CM) and UVB (relevant to vitamin D production) over 1 day differ: the UVB : UVA ratio is maximal at noon.CONCLUSIONS:The best way to obtain a given dose of vitamin D with minimal carcinogenic risk is through a non-burning exposure in the middle of the day, rather than in the afternoon or morning.

SummaryBackgroundThe incidence rates of skin cancer increase with decreasing latitude in most western countries. Ultraviolet (UV) radiation is a main risk factor for skin cancer.MethodsWe have studied the relationship between UV exposure and skin cancer incidence rates of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and cutaneous melanoma (CM), and tried to fit different mathematical models to the experimental data.ResultsThe incidence–UV exposure relationship for all three cancers is best described by the power law: ln(RTD) = Ab·ln(annual UVEry dose), with relative tumor density (RTD) being age‐adjusted incidence rate per unit area of skin, and the power parameter Ab being the biological amplification factor. For SCC, the RTD is a factor of 16–19 times larger on the head than on the trunk. For BCC, this factor is 7 and for CM it is 0.9–1.3. Ab for CM has remained almost unchanged from the 1960s until recently.ConclusionsThe incidence–sun exposure relationship for all three cancers is well described by the power law. SCC is dependent on total UV exposures, while BCC, and even more CM, is dependent also on exposure patterns, with intermittent exposures being most carcinogenic.

Ultraviolet B (UVB) radiation increases vitamin D level, but the influence of different UV sources (broadband and narrowband UVB lamps, solar simulators and sunbeds) and exposure durations have not been well characterized. In this study the influence of different UV sources on serum 25-hydroxyvitamin-D3 (25(OH)D3) levels in humans are reviewed. Serum 25(OH)D levels before and after UV exposure, and UV doses were extracted from 18 papers published in the past eight years. It was found that the UV dose-response curve for vitamin D generation in humans, as measured by the increments of serum 25(OH)D, is not linear with increasing UV doses and reaches a plateau at about 55 nmol/L after 4-5 weeks. About a half of this increase is equal to the difference between winter and summer 25(OH)D levels, and may be reached after 23 SEDs. The increments decrease with increasing baseline concentration of serum 25(OH)D, and the efficiency of only 0.7 nmol/L per SED is expected on the average when initial concentrations are higher than 50-60 nmol/L. A whole body exposure to 2 SEDs of UVB radiation 3 times per week is expected to rise serum 25(OH)D with an initial rate of 3.9 nmol/L per SED, bringing a winter level of serum 25(OH)D up to a summer level.

BACKGROUND:Calcitriol [1,25(OH)2D] is hypothesized to lower the risk of cancer via binding to the vitamin D receptor (VDR). VDRs are also found in benign and malignant cells of mesenchymal origin. To our knowledge, vitamin D levels and dietary intake have not been previously evaluated in patients newly diagnosed with benign and malignant mesenchymal tumors.PATIENTS AND METHODS:Forty-eight patients with benign soft tissue tumors and 25 patients with sarcoma had their serum 25-hydroxyvitamin D [25(OH)D], 1,25(OH)2D and parathyroid hormone levels measured, vitamin D intake scored and body mass index [BMI] calculated.RESULTS:Vitamin D deficiency [25(OH)D level<50 nmol/l] was observed in 19% and 28% of patients with benign tumor and sarcoma, respectively.CONCLUSION:Serum 25(OH)D, 1,25(OH)2D and parathyroid hormone concentrations, BMI and daily vitamin D intake did not differ significantly between the two groups of patients. Higher vitamin D intake or UV exposure is needed to ensure that all patients achieve sufficient vitamin D levels.

AIMS:Ultraviolet (UV) radiation is a major source for vitamin D production. Furthermore, UV destroys cobalamins (also called vitamin B12) in solution. However, data from humans are scarce. The aim of the present study was to clarify if UV exposure has any effect on serum cobalamins, as compared to vitamin D levels, in healthy volunteers.METHODS:This single-center, open observational study was conducted in a research institute: 23 non-pregnant, non-lactating, healthy, fair-skinned female subjects had their serum cobalamin and 25-hydroxyvitamin D (25(OH)D, the marker for vitamin D status) levels measured before and after exposure to UV.RESULTS:UV exposure increased serum 25(OH)D levels from 61.6 nmol/L to 88.5 nmol/L (44%; p < 0.001). A statistically insignificant decay in serum cobalamin levels from 300 pmol/L to 260 pmol/L (13%; p = 0.142) was observed in the volunteers after the first UV exposure; however, no additional decline of statistical significance was seen after subsequent exposures.CONCLUSIONS:Multiple exposure to UV radiation give a significant increase in 25(OH)D levels, but has no detrimental effect on cobalamin concentrations.

Malignant melanoma is a tumor that arises from melanocytes and accounts for around 4% of all malignancies in Europe and Northern America and for about 11% in Australia and New Zealand. About 10% of primary melanomas arise from sites not exposed to sun. Acral lentiginous melanoma, mucosal melanoma (in the oral cavities, nasal sinuses, genital tract and rectum) and uveal melanoma are all on non-sun-exposed tissues. Epidemiologic aspects ofmelanomas on non-sun-exposed areas in comparison with melanomas in sun-exposed areas have been reviewed. We focus on the relationship between melanoma incidence, geographic latitude of residence, race/ethnicity and host factors as well as time trends.

Essential features of the epidemiology and photobiology of cutaneous malignant melanoma (CMM) in Norway were studied in comparison with data from countries at lower latitudes. Arguments for and against a relationship between ultraviolet radiation (UV) from sun and artificial light and CMM are discussed. Our data indicate that UV is a carcinogen for CMM and that intermittent exposures are notably melanomagenic. This hypothesis was supported both by latitude gradients, by time trends and by changing patterns of tumor density on different body localizations. However, even though UV radiation generates CMM, it may also have a protective action and/or an action that improves prognosis. There appears to be no, or even an inverse latitude gradient for CMM arising on non-UV exposed body localizations (uveal melanoma, CMMs arising in the vulva, perianal/anorectal regions, etc.). Furthermore, CMM prognosis was gradually improved over all years of increasing incidence (up to 1990), but during the past 20 years, incidence rates stabilized and prognosis was not improved significantly. Comparisons of skin cancer data from Norway, Australia and New Zealand indicate that squamous cell carcinoma and basal cell carcinoma are mainly related to annual solar UVB fluences, while UVA fluences play a larger role of CMM.

Background: Sigmoidal (S-shaped) dose-cancer incidence relationships are often observed in animal bioassays for carcinogenicity. Ultraviolet (UV) radiation is an established skin carcinogen. The aim of this study is to examine if S-shaped curves describe the relationship between solar UV doses and skin cancer incidences, and if such relationships can be used to estimate threshold levels of non-carcinogenic UV exposure, as well as maximal incidence rates.Methods: We studied the incidence rate-annual erythema-effective UV dose relationship for squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and cutaneous melanoma (CM) among different Caucasian populations in Europe, Australia and New Zealand.Results: Our analysis indicates that S-shaped associations describe the data well (P<0.0001). The age-adjusted incidence rates for cases expected to be due to other causes than solar UV exposure (at zero UV dose) were found to be around 0.6, 9.7 and 4.0 per 100,000 for women in 1997-2007 for SCC, BCC and CM, respectively, and around 1.2, 14.3 and 2.6 per 100,000 for men. The analysis indicates that SCC, BCC and CM have maximal incidence of 361 +/- 24, 1544 +/- 49 and 36 +/- 4 per 100,000 for women, and 592 +/- 35, 2204 +/- 109 and 50 +/- 4 per 100,000 for men.Conclusions: Between 89 and 95% of the annual CM cases, around 99.8% SCC and 99.4% BCC cases are caused by solar UV exposure. The analysis did not identify any "safe" UV dose below which the risk for skin cancer was absent. Avoidance of UV radiation has a potential to reduce the incidence of skin cancer in fair-skinned population. (C) 2014 Elsevier GmbH. All rights reserved.

Positive as well as negative health effects of exposure of human skin to UV radiation depend on spectra and fluence rates, both of which being dependent on latitude, time of the day and several other factors. The major positive effects are related to vitamin D photosynthesis and the major negative effect is skin cancer development. The action spectra for these effects are different. This lead us to conclude that for optimal vitamin D synthesis at minimal risk of cutaneous malignant melanoma (CMM), the best time for sun exposure is between 10 a.m. and 1 p.m. Thus, the common health recommendation (that sun exposure should be avoided between the hours of 10 a.m. and 4 p.m. and postponed to the afternoon) may be wrong.

Folate is essential for cell division and growth. Deficiency is linked to birth defects, magaloblastic anaemia, cardiovascular disease, etc. Folic acid is a synthetic form of folate and is used to fortify food and in supplements. In aqueous solutions, in blood and even in human skin, folic acid may be degraded by ultraviolet radiation. Consequently, photodegradation of folic acid in human blood may lead to folate deficiency. However, the degree and the health consequences of such photodegradation are unknown. It is not clear which spectral region plays the most important role in the photodegradation of folic acid.In this study the photodegradation of folic acid in aqueous solution under different wavelengths of ultraviolet radiation (260-400 nm) was investigated by fluorescence spectroscopy. The photodegradation rate of folic acid was dependent on wavelength. Action spectrum for 1 mu M folic acid photodegradation was determined. Its action spectrum is not identical to its absorption or fluorescence excitation spectra. The action spectrum demonstrated that UVB and UVA degrade folic acid. Protecting skin against UVB and UVA radiation by sunscreens may help to protect folic acid in human blood under intense solar radiation. (c) 2013 Elsevier B.V. All rights reserved.

Solar ultraviolet (UV) radiation is the main source of vitamin D production and is also the most important environmental risk factor for cutaneous malignant melanoma (CMM) development. In the present study the relationships between daily or seasonal UV radiation doses and vitamin D status, dietary vitamin D intake and CMM incidence rates at different geographical latitudes were investigated. North-South gradients of 25-hydroxyvitamin D (25(OH) D) generation and CMM induction were calculated, based on known action spectra, and compared with measured vitamin D levels and incidence rates of CMM. The relative roles of UVA and UVB in CMM induction are discussed. Latitudinal dependencies of serum 25(OH) D levels and CMM incidence rates can only partly be explained by ambient UV doses. The UV sensitivity is different among populations with different skin color. This is well known for CMM, but seems also to be true for vitamin D status. The fact that UV-induced vitamin D may reduce the risk of CMM complicates the discussion. To some extent high dietary vitamin D intake seems to compensate low UV doses.

Aims: Incidence rates of cutaneous melanoma (CM) in light skinned people in Norway are among the highest in the world. Sunbed use has increased in Norway since 1980. We will try to elucidate whether there is any correlation between the increase in sunbed use and the CM incidence rates, whether the increase in CM risk is similar for all age groups, and whether the possible difference between young and old persons can inform future healthcare strategies. Methods: The frequency of sunbed use by different age groups in the time period 1980–2011 and incidence rates (1980–2009) of CM at different age groups in Norway were studied. Time in minutes per day spent in front of screen of computers or TVs for boys and girls was also analysed. Results: The number of sunbed sessions per year in Norway increased throughout the entire period. The number of men and women diagnosed with CM per year, all ages combined, also increased. Sunbed use increased at a similar rate for three age groups (0–19, 20–50, and >50 years old), while the age-adjusted CM incidence rate increased only for the oldest group. Time spent in front of the screen of computers or TVs increased from 1985 to 2005 and is still increasing. Conclusions: CM incidence is decreasing while sunbed use is increasing in younger age groups. The present data indicate that more work needs to be done before one can know whether the overall health effects of sunbed exposure are positive or negative.

Ultraviolet (UV) radiation is liable to cause skin cancer but it is the main source of vitamin D. Vitamin D photosynthesis takes place in skin at sub-erythemogenic UV doses, while larger exposures destroy vitamin D and increase DNA damage. Proper UV dosimetry is needed to obtain an optimal vitamin D status when skin cancer risk is minimal. A simple approach to such dosimetry using physically measured accumulated UV dose cannot provide a satisfactory quantification of vitamin D because of the complexity of the processes involved in vitamin D synthesis. A biological dosimeter of vitamin D synthetic UV radiation ('D-dosimeter') has been introduced earlier on the basis of an in vitro model of previtamin D photosynthesis. In the present study in vivo generation of 25-hydroxyvitamin D (25(OH)D) in serum of healthy volunteers exposed to UV radiation from the sunbed was accompanied by in vitro measurements of vitamin D formation using 'D-dosimeter'. It was found that the increase in serum 25(OH)D concentration depended both on the initial 25(OH)D level and on the cumulative sunbed exposure time. The observed linear correlation between in vivo and in vitro data can be used to estimate changes in vitamin D status after UV exposure using only one pre-exposure blood sample combined with further in vitro measurements.

Aims: The incidence rates of cutaneous malignant melanoma (CMM) increase throughout the world, in spite of introduction of strategies for prevention. However, a decrease in incidence rates is observed in some countries. If the reason for this could be found, it might be useful to transfer the knowledge to other fields of medicine. Methods: CMM age-standardized incidence rates in different age groups in Norway were obtained from NORDCAN for the years 1970–1989 and 1990–2009. Results: Until 1990, the CMM rates increased, but after that time a stabilization or a decrease was observed for young age groups (15–54 years old), while in older generations (>55 years old) the rates continued to increase. Conclusions: The decreasing CMM pattern in young age groups may be due to changing patterns to sunlight in sunbathing and use of sunbeds.

For decades the beneficial (synthesis of vitamin D) and the adverse (induction of skin cancer) effects of solar UV radiation have been known and discussed. Nevertheless, no consensus exists concerning the optimal balance between positive and negative effects of UV radiation. Vitamin D can be obtained through UVB exposure or diet. Inadequate sun exposure or too low intake of vitamin D can lead to vitamin D deficiency. Deficiency has been reported for different latitudes and seasons. Higher UVB radiation doses are obtained by humans in the South than in the North, and one might suppose that people in southern regions have a better vitamin D status than people in northern regions. In contrast to such expectations, the vitamin D status is better in Scandinavia than in south Europe. This phenomenon has to be explained by other factors than ambient UVB, such as differences in skin color, diet, genetics or vitamin D supplementation. Such factors may play more important roles for the serum 25-hydroxyvitamin D (25(OH)D) levels than thought before. Solar UV radiation can induce direct (UVB) and indirect (UVA) oxidative DNA damage and can lead to carcinogenesis. Non-melanoma skin cancers (NMSC) have different sun exposure patterns. As suggested from etiologic studies, UVB is the Solar ultraviolet (UV) radiation is the main source of vitamin D production and is also the most important environmental risk factor for cutaneous malignant melanoma (CMM) development. In the present study the relationships between daily or seasonal UV radiation doses and vitamin D status, dietary vitamin D intake and CMM incidence rates at different geographical latitudes were investigated. North-South gradients of 25-hydroxyvitamin D (25(oH)D) generation and CMM induction were calculated, based on known action spectra, and compared with measured vitamin D levels and incidence rates of CMM. the relative roles of UVA and UVB in CMM induction are discussed. Latitudinal dependencies of serum 25(oH)D levels and CMM incidence rates can only partly be explained by ambient UV doses. the UV sensitivity is different among populations with different skin color. this is well known for CMM, but seems also to be true for vitamin D status. the fact that UV-induced vitamin D may reduce the risk of CMM complicates the discussion. to some extent high dietary vitamin D intake seems to compensate low UV doses. Biologically efficient solar radiation Vitamin D production and induction of cutaneous malignant melanoma