Magdalena Ciążyńska

Impact of Ultraviolet Radiation on Expression of Transforming Growth Factor β, Smad2, Metalloproteinases-1, -3, -8, -9, Cathepsin K and Progerin

Ultraviolet radiation (UVR) is one of the most important environmental factors involved in photoaging. Exposure to UVR leads to dysregulation of expression of cell cycle‐related proteins which play key role in skin photodegradation that pretends to develop carcinogenesis. This study examines the role of various UVB doses on the expression of transforming growth factor beta (TGF‐β), Smad2, cathepsin K, progerin and matrix metalloproteinases (MMPs)‐1,‐3,‐8,‐9. A group consisting of 63 healthy individuals underwent one of the following treatments: (1) whole body exposed to UVB irradiation on each of 10 consecutive days with 0.7 MED, or (2) whole‐body irradiation as described followed by a single erythemal UVB dose on a small body area, or (3) irradiated only with a single erythemal UVB dose on small body area, or (4) were not irradiated at all (control group). When we compared all irradiated groups to the control group, there was significantly higher expression of TGF‐β, MMP‐1,‐3,‐9 and cathepsin K proteins evaluated by Western blot method. The results suggest the role of UVB in impairment of proteins expression that is involved in cell cycles regulation. Changes in the protein expression involved by acute and chronic UVR confirm its essential role in skin photodestruction. Moreover, obtained result indicates the tendency to occurrence of photoadaptation phenomenon.

Proteins involved in cutaneous basal cell carcinoma development

Basal cell carcinoma (BCC) is the most common skin malignancy type in the Caucasian population, with a continuously increasing incidence rate. The etiology of BCC remains unknown, but it appears to have a multifactorial origin resulting from intrinsic and extrinsic factors, including short-wavelength ultraviolet B radiation. The role of specific proteins in BCC that are known to be responsible for the regulation of cell division and are involved in skin aging, including transforming growth factor (TGF)-β, Smad2, matrix metalloproteinases (MMPs)-1, -3, -8 and -9, cathepsin-K and progerin, remains unknown. The aim of the present study was to assess the mRNA and protein expression profile of samples with diagnosed nodular BCC (nBCC) compared with that of healthy skin samples collected from matched areas. The study group included 22 patients (10 men and 12 women; mean age, 59 years; range, 44-82 years) with pathologically confirmed nBCC, and 22 healthy volunteers (10 men and 12 women; mean age, 59 years; range, 43-78 years) as a control group. The expression of the studied proteins was assessed in all samples by western blotting and reverse transcription-quantitative polymerase chain reaction analysis. Statistically significant increases in the expression of TGF-β, Smad2, cathepsin-K, progerin and MMP-1, -3, -8 and -9 were detected in skin biopsies with diagnosed nBCC compared with the control group, confirming the important role of these proteins in skin carcinogenesis.

Trends in basal cell carcinoma incidence rates: a 16-year retrospective study of a population in central Poland

Introduction Basal cell carcinoma (BCC) is the most commonly occurring cancer worldwide, and the overall incidence is still rising. Unfortunately, the cancer registry in Poland does not record BCC individually. Thus, the incidence of BCC in a defined population is unknown. Aim Analysis of incidence rates of primary BCC in central Poland during 16 years considering sex, site distribution and age to determine trends. Material and methods We retrospectively included all cases of BCC which were diagnosed and treated in the Department of Dermatology and Venereology, Medical University of Lodz, during the 16-year period from 1999 to 2015. Results We recorded 945 BCCs occurring in 890 patients (504 females – 57%, 386 males – 43%). Patient’s age was between 21 and 94. A distinct increase in BCC was observed after 1999, while after 2010 during the next 2-year period a slight decrease was noted. A statistically significant correlation was observed between histopathological types of BCC and the location of the lesions. The superficial type predominates on photoprotected areas, especially on the trunk, while the nodular type occurs mainly in facial areas. No statistically significant correlation was observed between histopathological types of BCC and sex. We found a significant increase in incidence for superficial BCC among middle-age patients, while the nodular type was observed more frequently among elderly subjects. Conclusions Basal cell carcinoma is quite common in Poland and predominantly develops in the facial area. In middle-age patients the most common is superficial BCC, while in elderly people the nodular type is most common. Based on our results we assume that there is a strong need to educate general physicians to enable them to diagnose BCC in the early stages.

The incidence and management of cutaneous adverse events of the epidermal growth factor receptor inhibitors

Overexpression of the epidermal growth factor receptor (EGFR) is found in many cancers, including those of the head and neck area, non-small-cell lung cancer, and colorectal, cervical, prostate, breast, ovary, stomach, and pancreatic cancer. The EGFR inhibitors are used at present in the treatment of such cancers. Skin lesions that develop during and after cancer treatment may be due to specific cytostatics, molecular-targeted drugs, radiation therapy, complementary therapy, or the cancer itself, and hence knowledge is essential to distinguish between them. The mechanism through which skin toxicity arises during treatment with EGFR inhibitors is not well known, but seems to be due to the modification of the RAS/RAF/MEK/ERK signal path associated with its activation, which results in the similarity between the adverse effects of EGFR inhibitors and the treatment of melanoma with BRAF and MEK inhibitors. The most common side effects are pruritus, xerosis, papulopustular rash, hand-foot skin reaction, alopecia and dystrophy of the hair, and paronychia. This work presents options for prevention and suggestions for managing these adverse events, which are of importance in the care of patients undergoing oncological treatment.

Necrobiosis lipoidica – an old but challenging dermatosis

Introduction. Necrobiosis lipoidica (NL) is a rare skin condition associated with diabetes that occurs in 0.3–1% of diabetic patients. Nevertheless, there are patients who develop this entity in the absence of diabetes mellitus. Objective. To highlight some problems in differential diagnosis and treatment of NL. Case report. We report a case of a 44-year-old woman with a 3-year history of undiagnosed skin lesions. Clinical examination revealed atrophic plaques on an erythemal background located on both shins. The first histopathological examination revealed infiltrated granulomatous lesions, later confirmed as deep tuberculoides chronic granulomatous dermatitis. However, after 6-month anti-tubercular treatment skin lesions were still present. Based on another skin biopsy we restricted the diagnosis to polyarteritis nodosa, necrobiosis lipoidica and granuloma annulare. Further examination led us to establish a diagnosis of necrobiosis lipoidica. The patient was treated with many therapeutic regimens without a satisfactory response. Conclusions. Lack of treatment guidelines and therapy based on dermatologists’ clinical experience suggest that NL needs to be evaluated in the near future. A large retrospective study and systematic review are required to establish diagnostic and treatment regimens.