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This symposium is the third PSL (Paris Sciences & Lettres) Chemical Biology meeting (2016, 2019, 2023) held at Institut Curie. This initiative originally started at Institut de Chimie des Substances Naturelles (ICSN) in Gif-sur-Yvette (2013, 2014), under the directorship of Professor Max Malacria, with a strong focus on chemistry. It was then continued at the Institut Curie (2015) covering a larger scope, before becoming the official PSL Chemical Biology meeting. This latest edition was postponed twice for the reasons that we know. This has given us the opportunity to invite additional speakers of great standing. This year, Institut Curie hosted around 300 participants, including 220 on site and over 80 online. The pandemic has had, at least, the virtue of promoting online meetings, which we came to realize is not perfect but has its own merits. In particular, it enables those with restricted time and resources to take part in events and meetings, which can now accommodate unlimited participants. We apologize to all those who could not attend in person this time due to space limitation at Institut Curie., (© 2023 Wiley-VCH GmbH.)

Background: Cutaneous malignant melanoma (CMM) is curable if detected in its early stages. However, the clinical recognition of CMM is challenging. An American research group has shown promising results in detecting CMM based on RNA profiles sampled from suspicious lesions with tape strips. We aim to further develop this technique and validate if RNA profiles sampled with tape strips can detect CMM., Methods: This prospective cohort study will include approximately 200 lesions clinically suspected of CMM requiring surgical removal. Tape stripping of the lesions will be performed just before surgical excision. Subsequently, RNA on the tape strips is analyzed using quantitative real-time polymerase chain reaction with TaqMan technology. The results are combined into a binary outcome where positive indicates CMM and negative indicates no CMM. The histopathological diagnosis of the lesions will be used as the gold standard. The main outcome is the results of the RNA test and the histopathological diagnosis, which, combined, provide the sensitivity and specificity of the test., Discussion: The accuracy of the clinical examination in CMM diagnostics is limited. This clinical trial will explore the ability to use RNA analysis to improve the management of suspicious lesions by enhancing early diagnostic accuracy. Hopefully, it can reduce the number of benign lesions being surgically removed to rule out CMM and decrease patient morbidity., Trial Registration: The project was approved by The Committee on Health Research Ethics of the Capital Region of Denmark (H-15010559) and registered at the Danish Data Protection Agency (BFH-2015-065)., Competing Interests: The authors have declared that no competing interests exist.

Aims: Actinic keratosis (AK) is a precursor of cutaneous squamous cell carcinoma (SCC). No validated parameters can predict which AKs will progress into SCCs, but especially thick AKs are under suspicion. The clinical and histopathological thickness of AKs is strongly correlated. This study aimed to investigate the thicknesses and degree of dysplasia of AKs contiguous with SCCs assuming these AKs represent the AKs that have undergone malignant transformation., Methods: Files of the Pathology Department, Hospital of Southern Jutland, Denmark, were reviewed. 111 cases met the inclusion criteria: a skin biopsy containing an invasive SCC. All SCCs merged with an AK at the edge. Degree of dysplasia, epidermal thickness and stratum corneum thicknesses of AKs were measured., Results: All AKs showed severe dysplasia. Most AKs had a stratum corneum thickness under 0.1 mm and an epidermal thickness under 0.5 mm, corresponding to clinically thin and non-hyperkeratotic AKs., Conclusions: Our result suggests malignant progression potential of AKs regardless of thickness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In 2011, the St. Gallen Consensus Conference introduced the use of pathology to define the intrinsic breast cancer subtypes by application of immunohistochemical (IHC) surrogate markers ER, PR, HER2 and Ki67 with a specified Ki67 cutoff (>14%) for luminal B-like definition. Reports concerning impaired reproducibility of Ki67 estimation and threshold inconsistency led to the initiation of this quality assurance study (2013-2015). The aim of the study was to investigate inter-observer variation for Ki67 estimation in malignant breast tumors by two different quantification methods (assessment method and count method) including measure of agreement between methods., Material and Methods: Fourteen experienced breast pathologists from 12 pathology departments evaluated 118 slides from a consecutive series of malignant breast tumors. The staining interpretation was performed according to both the Danish and Swedish guidelines. Reproducibility was quantified by intra-class correlation coefficient (ICC) and Lights Kappa with dichotomization of observations at the larger than (>) 20% threshold. The agreement between observations by the two quantification methods was evaluated by Bland-Altman plot., Results: For the fourteen raters the median ranged from 20% to 40% by the assessment method and from 22.5% to 36.5% by the count method. Light's Kappa was 0.664 for observation by the assessment method and 0.649 by the count method. The ICC was 0.82 (95% CI: 0.77-0.86) by the assessment method vs. 0.84 (95% CI: 0.80-0.87) by the count method., Conclusion: Although the study in general showed a moderate to good inter-observer agreement according to both ICC and Lights Kappa, still major discrepancies were identified in especially the mid-range of observations. Consequently, for now Ki67 estimation is not implemented in the DBCG treatment algorithm.

Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and red tattoos may be associated with increased risk of skin cancer due to potential carcinogens in tattoo inks. This combination has not been studied previously. Immunocompetent C3.Cg/TifBomTac hairless mice (n=99) were tattooed on their back with a popular red tattoo ink. This often used ink is banned for use on humans because of high content of the potential carcinogen 2-anisidine. Half of the mice were irradiated with three standard erythema doses UVR thrice weekly. Time to induction of first, second and third squamous cell carcinoma (SCC) was measured. All UV-irradiated mice developed SCCs. The time to the onset of the first and second tumor was identical in the red-tattooed group compared with the control group (182 vs 186 days and 196 vs 203 days, P=ns). Statistically, the third tumor appeared slightly faster in the red-tattooed group than in the controls (214 vs 224 days, P=.043). For the second and third tumor, the growth rate was faster in the red-tattooed group compared with the control (31 vs 49 days, P=.009 and 30 vs 38 days, P=.036). In conclusion, no spontaneous cancers were observed in skin tattooed with a red ink containing 2-anisidine. However, red tattoos exposed to UVR showed faster tumor onset regarding the third tumor, and faster growth rate of the second and third tumor indicating red ink acts as a cocarcinogen with UVR. The cocarcinogenic effect was weak and may not be clinically relevant., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A cage molecule incorporating three electron donating monopyrrolotetrathiafulvalene units was synthesised to host electron accepting [60]fullerenes. Formation of a strong 1 : 1 donor-acceptor (D-A) complex C 60 ⊂1 was confirmed by solid state X-ray analysis as well as 1 H NMR and absorption spectroscopic analyses of the arising charge-transfer (CT) band (λ = 735 nm, ε ≈ 840 M -1 cm -1 ). Inserting Li + inside the [60]fullerene increased the binding 28-fold (K a = 3.7 × 10 6 M -1 ) and a large bathochromic shift of the CT band to the near infrared (NIR) region (λ = 1104 nm, ε ≈ 4800 M -1 cm -1 ) was observed.

The severity of dysplasia and expression of p53 in actinic keratosis (AK) is of importance for the transformation to squamous cell carcinoma. It is assumed that it is most important to treat thick AKs as they are believed to be more dysplastic than thin AKs. However, a relation between AK thickness and dysplasia or the expression of p53 has never been demonstrated. The aim of this study was to investigate this possible relation. Sixty-six AKs were included for clinical and histological examination. Prior to performing a punch biopsy, the clinical thickness of each AK was measured objectively using two scale bars with a thickness of 0.5 mm and 1 mm. Subsequently, the thickness of the epidermis, the severity of dysplasia and the expression of p53 were assessed histologically. We found a strong and significant positive correlation between measured clinical thickness of the AKs and the histological thickness of epidermis (p < 0.0001). However, the clinical thickness did not correlate with either the severity of dysplasia (p = 0.7) or the expression of p53 (p = 0.5). In conclusion, thin AKs show the same severity of dysplasia and expression of p53 as thicker AK lesions. Consequently, clinical thickness cannot predict aggressiveness.

Background: Black tattoos may involve risk of cancer owing to polycyclic aromatic hydrocarbons including benzo(a)pyrene (BaP) in inks. Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and black tattoo may therefore potentially be very problematic, but has not been previously studied., Methods: Immunocompetent C3.Cg/TifBomTac mice (n = 99) were tattooed on the back with Starbrite Tribal Black(™) . This ink has a high content of the carcinogen BaP. Half of the mice were irradiated with three standard erythema doses UVR thrice weekly. Time to induction of first, second and third squamous cell carcinoma (SCC) was measured. Controls were 'tattooed' without ink., Results: All irradiated mice developed SCCs while no malignant tumours were found in the nonirradiated group. In the tattooed and irradiated group, the development of the first, second and third SCC was significantly delayed in comparison with the irradiated controls without black tattoos (212, 232, 247 days vs. 163, 183, 191 days, P < 0.001)., Conclusion: In UVR-irradiated black tattoos, remarkably, the development of UVR-induced skin cancer was delayed by the tattoos. Skin reflectance measurement indicated that the protective effect of black pigment in the dermis might be attributed to UVR absorption by black pigment below the epidermis and thereby reduction of backscattered radiation., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Nutlin-3a increases p53 levels after UVB radiation, which could result in a decrease in DNA damage and thus lead to a lower risk of non-melanoma skin cancer. Especially, organ transplant recipients might derive benefit from such a topical formulation with an active ingredient to prevent DNA damage., Purpose: To investigate whether topical nutlin-3a can decrease photocarcinogenesis induced by simulated solar radiation., Methods: 72 hairless C3.Cg/TifBomTac mice were treated 3 days/week topically with 100 μl nutlin-3a (9 mM) [Groups 1 and 3 (120 days)) or 100 μl vehicle (Group 2). Three hours later, all mice were exposed to simulated solar radiation (a radiometric equivalent of three standard erythema dose units)., Results: The median time to tumours did not differ between the mice treated with nutlin-3a and with the vehicle. The median time to the first and second tumours did not differ between 'nutlin-3a-120 days' and vehicle-treated mice, but there was a small significant difference in the median time to the third tumour (211 vs. 196 days, P = 0.043). However, after Bonferroni correction, there was no difference at all., Conclusion: Nutlin-3a had no reductive effect on photocarcinogenesis and we do not believe in nutlin-3a as a potential drug against DNA damage in a topical formulation for organ transplant patients., (© 2012 John Wiley & Sons A/S.)

Topical photodynamic therapy (PDT) with methyl-aminolevulinate (MAL) is a well-established treatment for precancerous skin lesions and non-melanoma skin cancer. Treatment outcomes are less effective for thick than for superficial lesions, which are presumed to be due to insufficient PpIX biodistribution in tumour tissue. Hexyl-aminolevulinate (HAL) is a more lipophilic photosensitizer precursor than MAL and may penetrate the skin to a greater depth and more homogeneously. We compared HAL- and MAL-induced PpIX accumulation in specific skin compartments using concentrations of 2%, 6% and 20% HAL and MAL on long-term UV-irradiated mouse skin. Furthermore, 20% HAL and 20% MAL were applied to non-irradiated skin. Porphyrin fluorescence was measured by fluorescence microscopy in selected skin regions: the epidermis, superficial dermis, deep dermis and sebaceous gland epithelium down to a depth of 1 mm. We found higher PpIX fluorescence intensities in epidermis and sebaceous gland epithelium from 2%, 6% and 20% HAL (median 72-104 au) than in corresponding concentrations of MAL (median 35-69 au) (P < 0.01). Fluorescence intensities in the superficial (35 au) and deep dermis (32 au) were similar for HAL and MAL (P = 0.51) and lower than epidermal fluorescence intensities (P < 0.001). Significantly, higher median PpIX fluorescence intensities (64 au) were found in 20% MAL-incubated skin irradiated with UV than in non-irradiated skin (48 au) (P < 0.001). HAL-induced fluorescence intensities did not depend on UV exposure (HAL 20%, UV: 72 au, non-UV: 70 au) (P = 0.87). In conclusion, HAL express high affinity for epidermis and sebaceous gland epithelium, and MAL for actinically damaged skin, which raises future perspectives for improved selectivity in PDT., (© 2012 John Wiley & Sons A/S.)

Background: Squamous cell carcinoma (SCC) is linked with the lifelong cumulative effect of ultraviolet radiation (UVR). In contrast, epidemiological data have shown that sunburn in childhood is a stronger risk factor for cutaneous malignant melanoma than continuous UVR, indicating a higher carcinogenic sensitivity early in life., Methods: We investigated how a high neonatal dose of UVR affects the development of SCC in mice irradiated later in life. We used simulated solar radiation (sun) and solarium radiation (solarium). Ninety-nine C3.Cg/TifBomTac-immunocompetent hairless mice received 0, 25 or 35 standard erythema doses (SED) UVR when they were 4 days old followed by 4 SED sun or 4 SED solarium three times/weekly from 9 weeks of age., Results: Tumours developed faster in mice treated with 35 SED UVR + 4 SED sun compared with 4 SED sun, but no change was observed in the cumulative dose required to achieve tumours. Tumours also developed faster in mice treated with 35 SED UVR + 4 SED solarium compared with 4 SED solarium, and a difference was also observed in the cumulative dose required to achieve tumours. If the Skin Cancer Utrecht-Philadelphia-murine spectrum was used to weigh the delivered irradiance instead of the International Commission on Illumination erythema action spectrum, tumours developed after the same accumulated dose., Conclusion: In conclusion, this study does not indicate increased sensitivity to induction of SCC early in life., (© 2012 John Wiley & Sons A/S.)

Recently, 3% diclofenacnatrium gel (diclofenac) was introduced for the treatment of actinic keratoses. Data on photocarcinogenesis of topical diclofenac are limited, and we wished to investigate whether topical diclofenac can accelerate photocarcinogenesis using simulated solar radiation (SSR). Diclofenac was applied topically on the backs of hairless, female, C3.Cg/TifBomTac immunocompetent mice three times weekly followed by ultraviolet radiation (2, 3, or 4 Standard Erythema Dose) until death. There was a significant difference in survival between diclofenac-treated groups and control groups (P<0.0001). Physical examination of the diclofenac-treated mice showed peptic ulcers, oesophageal ulcers and gastrointestinal bleeding. To be sure that these side effects were not caused by topical absorption without oral ingestion, one group of mice was wearing Elizabethan collars and was single housed. Nevertheless, these mice also had gastrointestinal side effects. We terminated the experiment after 151 days when only a few mice remained in the diclofenac-treated groups and most had symptoms of discomfort and weight loss. No tumors developed as a result of the early termination., (© 2011 John Wiley & Sons A/S.)

Topical corticosteroids such as hydrocortisone-17-butyrate (HCB) and clobetasol-17-propionate (CP) and vitamin D(3) derivatives such as calcipotriol (CAL) are widely used to treat psoriasis. The immunosuppressive effects of corticosteroids make their topical use a concern for skin carcinogenicity. Few studies have assessed the effect of topical corticosteroids and topical vitamin D(3) derivatives on photocarcinogenesis induced by ultraviolet radiation. We investigated whether HCB, CP, or CAL can accelerate photocarcinogenesis using simulated solar radiation (SSR). HCB, CP, or CAL was applied topically to the backs of hairless, female, C3.Cg/TifBomTac-immunocompetent mice in 16 groups of 25 mice each. The drugs were applied three times weekly followed by 0, 2, 4, or 6 standard erythema doses (SED) of SSR for 365 days or until death. No change was observed in the time required for tumor development in mice treated with HCB and 2 SED (HCB-2SED) and HCB-6SED. However, the time required for tumor development increased with HCB-4SED treatment. Treatment with CP-2SED did not change the time to onset of the first and second tumor, but all other CP treatments in combination with SSR increased the time. CAL-2SED decreased the time to onset of the first tumor but not of the second and third tumor. CAL-4SED and CAL-6 SED did not change or increased the time to tumor development. Our data indicated that topical administration of HCB and CAL did not alter the photocarcinogenesis of SSR and that topical CP administration had a photoprotective effect. Thus, HCB, CP, and CAL do not increase photocarcinogenesis induced by SSR., (© 2010 John Wiley & Sons A/S.)

Background: Hexyl aminolevulinate (HAL) is a long-chained 5-aminolevulinic acid-ester that has been proposed as a novel photosensitizing agent to methyl aminolevulinate (MAL) in topical photodynamic therapy (PDT). The more lipophilic HAL, may improve treatment outcome for non-melanoma skin cancer., Objective: To compare the prophylactic and therapeutic effects of HAL- and MAL-PDT for ultraviolet-induced squamous cell carcinomas (SCCs) in hairless mice., Methods: Mice (n = 249) were irradiated with solar UV-radiation (UVR) until SCC occurred. Before any skin changes developed, two prophylactic PDT treatments were given, using creams of HAL (2%, 6%, 20%) or MAL (20%) followed by illumination (632 nm, Aktilite, Photocure). Two therapeutic PDT-treatments were given by randomization to the first developed SCC of 1 mm. Primary end-points were time to first SCC of 1 mm and complete SCC clearance. Secondary end-points were time to SCC-recurrence, PpIX fluorescence and skin reactions to PDT., Results: The median time to first SCC was significantly longer for mice treated with prophylactic HAL-PDT (2%, 6% and 20% HAL, 264 days) and MAL-PDT (20% MAL, 269 days) than mice exposed to UVR (186 days) and UVR + placebo-PDT (199 days) (P < 0.0001). The therapeutic efficacy of HAL- and MAL-PDT showed cure rates of 23-61.5% (P = 0.11). Similar PpIX fluorescence intensity and severity of clinical reactions were seen for HAL- and MAL-groups, although mice developed more intense hyper-pigmentation when treated with 20% MAL-PDT compared with 2% HAL-PDT., Conclusions: PDT with HAL (2%, 6% and 20%) and MAL (20%) is equally effective to prevent and treat UV-induced SCC in hairless mice.

Topical benzoyl peroxide (BPO) gel has long been used to treat acne vulgaris and has recently been combined with clindamycin (BPO-clin). No skin malignancies have been reported after clinical use of BPO, but there has been concern about the possible carcinogenicity of BPO alone and in combination with UV radiation. BPO can promote skin tumorigenesis in a mouse skin chemical carcinogenesis model. As acne vulgaris is frequently localized on sun-exposed areas, we investigated whether BPO or BPO-clin accelerates photocarcinogenesis in combination with simulated solar radiation (SSR) in 12 groups of 25 hairless female C3.Cg/TifBomTac-immunocompetent mice. BPO or BPO-clin was applied topically to the back five times each week, followed by SSR three times each week (2, 3, or 4 standard erythema doses) 3-4 h later, for 365 days or until death. Generally BPO and BPO-clin did not accelerate the time to first, second or third tumor. Therefore, there is no evidence suggesting that BPO or BPO-clin is photocarcinogenic. However, we found significantly higher mortality in the SSR exposed groups receiving BPO and BPO-clin compared with groups receiving only BPO or BPO-clin. Our results show that BPO and the combination of BPO and clindamycin do not accelerate photocarcinogenesis, but are toxic in hairless mice. Based on the current data, the cancer risk associated with the use of BPO and BPO-clin in sun-exposed areas is minimal. Thus, while the carcinogenic potential of BPO is not fully understood, at the present time, evidence suggests that this compound is safe to use.

Background: Ultraviolet (UV) radiation induces non-melanoma skin cancer (NMSC), and UV prophylaxis is essential to prevent skin cancer. It is unclear whether patients diagnosed with squamous cell carcinomas (SCC) may benefit from reduced UV exposures in terms of delaying the development of new tumors. The objective was to evaluate the significance of discontinued or reduced UV exposure for the development of subsequent skin tumors., Methods: Seven groups of mice (n = 175) were irradiated with UV doses of 2 and 4 standard erythema doses (SED) that were continued, reduced or discontinued at the time of appearance of the first skin tumor., Results: The development of new tumors was delayed, corresponding to the degree of reductions in UV dose in an inversely linear manner. Discontinuation of UV doses delayed the median times to the second tumor by 24 days (2 SED, P = 0.0549) and 33.5 days (4 SED, P < 0.0001), and when reduced to 1 SED, the median delays were 18 days (2 SED, P = 0.0469) and 33 days (4 SED, P < 0.0001). The median delay to the third tumor was after UV reduction 47 days (4 SED, P < 0.0001) and 35 days (2 SED, P = 0.151), and after UV discontinuation 49 days (4 SED, P < 0.0001) and 44 days (2 SED, P = 0.111)., Conclusion: This suggests that patients with SCC may benefit from reduced UV exposure.

Pimecrolimus and tacrolimus are topical calcineurin inhibitors developed specifically for the treatment of atopic eczema. Experience with long-term use of topical calcineurin inhibitors is limited and the risk of rare but serious adverse events remains a concern. We have previously demonstrated the absence of carcinogenic effect of tacrolimus alone and in combination with simulated solar radiation (SSR) on hairless mice. The aim of this study is to determine whether pimecrolimus accelerates photocarcinogenesis in combination with SSR or pimecrolimus and tacrolimus accelerate photocarcinogenesis in combination with UVA. We used 11 groups of 25 hairless female C3.Cg/TifBomTac immunocompetent mice (n = 275). Pimecrolimus cream or tacrolimus ointment was applied on their dorsal skin three times weekly followed by SSR (2, 4, or 6 standard erythema doses, SED) or UVA (25 J/cm(2)) 3-4 h later. This was done up to 365 days in the SSR-treated groups and up to 500 days in the UVA-treated groups. Pimecrolimus did not accelerate the time for development of the first, second or third tumor in any of the groups. Median time to the first tumor was 240 days for the control-2SED group compared with pimecrolimus-2SED group (233 days), control-4SED group (156 days) compared with pimecrolimus-4SED group (163 days) and control-6SED group (162 days) compared with pimecrolimus-6SED group (170 days). Only one mouse in each of the three UVA groups developed a tumor. We conclude that pimecrolimus in combination with SSR and both pimecrolimus and tacrolimus in combination with UVA do not accelerate photocarcinogenesis in hairless mice.

Numerous studies have demonstrated the utility of topical tacrolimus ointment in atopic dermatitis. However, there is a concern that local immunosuppression by calcineurin inhibitors may enhance dermal photocarcinogenesis and carcinogenesis. Therefore, we investigated the influence of topical tacrolimus ointment on squamous cell carcinoma formation in hairless female C3.Cg/TifBomTac immunocompetent mice exposed to solar simulated radiation (SSR). In a first experiment, mice (n = 200) had tacrolimus applied on their dorsal skin three times weekly followed by SSR (2, 4 or 6 standard erythema doses, SED) 3-4 h later. Tacrolimus did not reduce the time to tumor development and in the group receiving 4 SED it even had a protective effect (156 days vs 170 days, P = 0.008). In a second experiment, mice (n = 50) were irradiated with 6 SED three times weekly for 3 months and subsequently treated five times weekly with topical tacrolimus to mimic the use of tacrolimus on sun-damaged skin. The median time to the first skin tumor was 234 days in SSR + tacrolimus group compared with 227 days in the only SSR-irradiated group (P = 0.160). In a third experiment, mice (n = 25) had tacrolimus applied on their dorsal skin every day for 1 month, thereafter the group was irradiated with 4 SED three times weekly. The median time to the first skin tumor was 142 days in tacrolimus + SSR group compared with 156 days in the only SSR-irradiated group from experiment 1 (P = 0.363). We conclude that tacrolimus ointment does not accelerate photocarcinogenesis or induce any dermal carcinogenicity in hairless mice.

The synthesis of a rare example of a calix[2]pyrrole[2]thiophene derivative incorporating two tetrathiafulvalene units is described along with its X-ray crystal structure. Complexation studies between the bis(tetrathiafulvalene)-calix[2]pyrrole[2]thiophene and 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) were carried out in solution using absorption and ESR spectroscopies as well as in the solid state using X-ray crystallography and IR spectroscopy.

Short-wave ultraviolet radiation (UVB) is the most carcinogenic part of the ultraviolet spectrum. The target cells of skin cancer are believed to be the bulge stem cells and/or their offspring, the transit-amplifying cells that reside in the epidermis. However, the amount of UVB penetrating epidermis and reaching the bulge cells is very low, which questions if these cells suffer sufficient DNA damage to transform into cancer stem cells. We performed this study to determine whether UV-induced squamous cell carcinoma (SCC) originates from the epidermis or the hair follicles in mice. Hairless mice had their epidermis removed at different levels using CO(2) laser ablation. Simulated solar irradiations were administered either preoperatively (in total 7 weeks) or pre- and postoperatively (in total 30 weeks). Control groups were untreated or treated only with solar-simulated radiation or with laser. Blinded clinical assessments of skin tumors were carried out weekly during 12 months observation. Only mice irradiated with solar-simulated radiation both pre- and postoperatively developed tumors. Median time to first, second and third tumor ranged from 19 to 20.5 weeks and was not significantly different between the non-laser and laser-treated groups (P > 0.05). The tumor response was thus similar in UV-exposed mice whether they had their epidermis removed or not. No tumors appeared in control groups. Hence, UV-induced SCC of mice originates from cells of the hair follicle, presumably the bulge stem cells, indicating that ultraviolet radiation penetrates epidermis sufficiently to cause irreversible DNA damage in cells located beneath the epidermis.

Background: Comfort and lack of pain are important for optimal mobilization after hip replacement. We investigated the efficacy of double wound infiltration., Patients and Methods: 40 consecutive patients undergoing total hip replacement were randomized into two groups in this double-blinded study. They received wound infiltration at the end of surgery and through an intraarticular catheter 24 h postoperatively. The catheter was placed at the end of surgery. One group received solutions of ropivacaine, ketorolac, and adrenaline. Patients in the control group were injected with saline instead. The observation period was 6 weeks., Results: The patients who received the analgesic solution had less pain up to 2 weeks postoperatively. They reached an earlier and lower pain minimum during the first days postoperatively, had lower use of analgesia up to day 4 postoperatively, and were more satisfied. Use of analgesic solution resulted in less joint stiffness and better function 1 week postoperatively., Interpretation: Operative and postoperative wound infiltration with multimodal drugs reduces pain and the requirement for analgesics after hip replacement, leading to faster postoperative mobilization.

Background and Objectives: Carbon dioxide (CO(2)) laser resurfacing is primarily performed on photodamaged facial skin where patients are further exposed to ultraviolet radiation (UVR) postoperatively. We examined whether pre- and postoperative UVR influences the development of CO(2) laser-induced side effects., Study Design/materials and Methods: Hairless mice (n = 211) were treated with a Sharplan CO(2) laser with FeatherTouch scanner. Simulated solar irradiation was administered either preoperatively or pre- and postoperatively. Skin end-points (wounds, texture changes, and pigmentary changes) were evaluated blinded by clinical evaluations, skin reflectance spectroscopy, and histological examinations., Results: Pre- and postoperative UVR exposed mice obtained higher clinical scores of wounds (P < 0.02) and texture changes (P < 0.01) and developed more heavy fibrosis than mice treated with laser but no UVR. UVR exposure after CO(2) laser treatment induced significant hyperpigmentation compared to unexposed control mice (P < 0.003), whereas CO(2) laser treatment itself did not induce pigmentary changes., Conclusions: UVR increases in an animal model the occurrence of postoperative side effects from CO(2) laser resurfacing., ((c) 2005 Wiley-Liss, Inc.)

Background and Objectives: To examine whether carbon dioxide (CO2) laser treatment has a carcinogenic potential or may influence ultraviolet (UV)-induced carcinogenesis., Study Design/materials and Methods: Hairless mice (n = 211) were treated with a Sharplan CO2 laser with FeatherTouch scanner. Simulated solar irradiations were administrated either pre-operatively or pre- and post-operatively. Weekly clinical assessments of skin tumors were performed blinded during the entire observation period of 12 months., Results: No tumors appeared (a) in mice just treated with CO2 laser, (b) in mice exposed to UV irradiation only before CO2 laser treatment or (c) in untreated control mice. Tumors developed in CO2 laser treated mice that were exposed to UV-irradiation both pre- and post-operatively and in UV-irradiated control mice. The time to first, second, and third tumors ranged from 18 to 20 weeks and no significant differences were demonstrated., Conclusions: CO2 laser treatment does not have a carcinogenic potential in itself, nor does CO2 laser treatment influence UV-induced carcinogenesis.

Detection of autofluorescence at the skin surface is highly influenced by melanin and hemoglobin. Epidermal absorption and scattering may also be an influencing factor and is represented in this article as a quantitative parameter, epidermal thickness. To examine this parameter we measured the 370 nm fluorescence in vivo after excitation with 330 nm and the 455 nm fluorescence after excitation with 330 and 370 nm. Measurements were performed on sun-exposed skin at the dorsal aspect of the forearm and shoulder and on nonexposed buttock skin. Skin pigmentation and redness of the same body sites were measured by reflectance spectroscopy. The thickness of the stratum corneum and the cellular part of epidermis was quantified by light microscopy of skin biopsies. Multiple regression analysis was used to find correlations between autofluorescence and the potential influencing factors. We found a highly significant correlation of skin autofluorescence with pigmentation and redness for both emission wavelengths (Em). A small but significant correlation to epidermal thickness was found only for excitation wavelength (Ex) 370 nm and Em455 nm if body site was included in the analysis. No correlation between Ex330:Em370 and Ex330:Em455 and thickness of epidermis was found. For practical use, correction of skin autofluorescence for pigmentation is essential, correction for redness is of less importance and correction for epidermal thickness is unnecessary.

Epidermal thickness and its relationship to age, gender, skin type, pigmentation, blood content, smoking habits and body site is important in dermatologic research and was investigated in this study. Biopsies from three different body sites of 71 human volunteers were obtained, and thickness of the stratum corneum and cellular epidermis was measured microscopically using a preparation technique preventing tissue damage. Multiple regressions analysis was used to evaluate the effect of the various factors independently of each other. Mean (SD) thickness of the stratum corneum was 18.3 (4.9) microm at the dorsal aspect of the forearm, 11.0 (2.2) microm at the shoulder and 14.9 (3.4) microm at the buttock. Corresponding values for the cellular epidermis were 56.6 (11.5) microm, 70.3 (13.6) microm and 81.5 (15.7) microm, respectively. Body site largely explains the variation in epidermal thickness, but also a significant individual variation was observed. Thickness of the stratum corneum correlated positively to pigmentation (p = 0.0008) and negatively to the number of years of smoking (p < 0.0001). Thickness of the cellular epidermis correlated positively to blood content (P = 0.028) and was greater in males than in females (P < 0.0001). Epidermal thickness was not correlated to age or skin type.