Incidence Of Skin Tumors Research Articles

Clinicopathological study of skin tumors

Background: The diagnosis of skin tumors can cause difficulties due to their wide variety of overlapping differentiation and complicated nomenclature. Histopathological study is the most valuable means of diagnosis. Keeping in view these facts, an attempt is made to study the different varieties of tumors of the skin. Aims and Objectives: (1) The aim of this study was to study the histomorphology of different skin tumors with ancillary technique necessary and to correlate with the clinical features. (2) To find the proportion of various skin tumors. (3) To classify and identify various skin tumors and study its variation according to age, sex, site, etc., which will bear an impact on patient management and prognosis. Materials and Methods: This observational study included all cases of skin tumors received in the Department of Pathology, Kottayam Medical College, during a period of 1 year. Biopsy samples were collected, fixed in 10% formalin, processed and embedded in paraffin blocks, and stained with hematoxylin and eosin (H and E). The stained sections were studied under a microscope and histopathological diagnosis was correlated with clinical diagnosis. Results: Out of the 227 cases of skin tumors, 102 (44.9%) were male and 125 (55.1%) were female. The incidence of skin tumors peaks in individuals older than 60 years of age. The most common sites affected were face (40%). Keratinocytic tumors constituted the largest proportion of tumors (43%), followed by melanocytic tumors (31%), soft-tissue tumors (13%), appendage tumors (11%), neural (1%), and hematolymphoid tumors (1%). Conclusion: Out of the 227 cases in the present study, the clinical diagnosis of only 169 cases was correlating with the histopathological diagnosis. This emphasizes the role of microscopy in the correct diagnosis of skin tumors.

Incidence and Morphological Variations of Skin Tumors in Benghazi

Skin is the largest, most complicated organ in the body and it covers the body's entire external surface, that’s why skin diseases are one of the most difficult ailments to adjust to because of its ugliness and related problems. 10-20% of patients seeking medical guidance have skin diseases or complaints, skin conditions are prevalent across all parts of the world. The objective of this study is to evaluate the incidence of different skin histopathological benign tumors and their variations according to age, sex, clinical presentation, and site, and make comparisons with other studies. This retrospective study was conducted from January 2018 until February 2020, and this study included all cases with histological diagnosis of various skin tumors. Approval to handle all specimens for scientific research has been assured by the high graduate and university ethics committee. Out of 124 cases, the prevalence of benign tumors was the most common skin disease (79.83%), while malignant skin tumors were the least common skin diseases in this study (20.16%). However, the peak age group in benign skin tumors is 41-60 years, and in malignant skin tumors peak age is 61-80 years. We concluded that there was a significant relation between age, gender, clinical presentation, and site with different types of skin tumors, so histopathology is the most valuable means of diagnosis of skin diseases and a good guide for proper management.

Squamous cell carcinoma of the skin after cardiac transplantation: a clinical case

Background. Solid organ transplantation recipients have a high risk of non-melanoma skin tumors. Patients after heart transplantation are prone to a higher incidence of malignant skin tumors due to intensive immunosuppressive therapy. The most common histological type is squamous cell carcinoma, followed by basal cell carcinoma. These tumors have a more aggressive clinical course, including the frequency of recurrence and metastasis, and a tendency to multifocal lesions.
 Materials and methods. We present a clinical case of primary multiple squamous cell carcinoma with metastatic lesions of regional lymph nodes in a patient after heart transplantation.
 Results. A 67-year-old patient underwent an orthotopic heart transplant in September 2018 for ischemic cardiomyopathy. Subsequently, triple immunosuppressive therapy was administered, including tacrolimus combined with mycophenolate mofetil and prednisolone. In May 2022, a solid tumor with ulceration occurred on the skin of the right scapular region. After some time, similar tumors appeared on the skin of the temporal region on the left, the posterior surface of the auricle and the parietal region on the left. The patient later found a solid, painless tumor on the left jaw angle. As a part of the examination in the oncology dispensary, a biopsy of the scapular skin tumor, scrapings from tumors, and aspiration biopsy of the submandibular lymph nodes were performed. Histological and cytological studies of all neoplasms showed squamous cell keratinizing cancer with metastases to the submandibular lymph nodes. Additional examination methods showed no signs of progression. The diagnosis was made: primary multiple synchronous skin cancer: right scapular area, stage III, cT3N0M0; left parietal area, stage II, cT2N0M0; occipital area, stage I, cT1N0M0; left auricle, stage IV, cT1N2M0. Considering the localization of tumors, surgical treatment was performed, including of excision of tumors in the scapular and parietal regions. Radiation therapy was performed on lymph nodes with metastases. After 6 months, a tumor recurrence was detected in the irradiation area.
 Conclusion. After heart transplantation, squamous cell carcinoma of the skin is common. Usually, it affects the scalp and neck with metastases to the regional lymph nodes and is prone to recurrence. The primary treatment method is surgical and radiation therapy.

Advancements in clinical developments in neo/adjuvant drug therapy for resectable melanoma: ASCO Annual Congress – June 2022

In the structure of the incidence of skin tumors, melanoma accounts for a relatively smaller percentage, but that disease is associated with higher risk of an adverse outcome compared with many other malignancies.
 The study of innovative clinical developments in drug therapy for resectable melanoma, presented at the American Society of Clinical Oncology Annual Meeting June 2022.
 The best clinical developments in drug treatment of patients with resectable melanoma were selected for analysis: 1) phase 3 study KEYNOTE-716; 2) PRADO; 3) Neo Trio; 4) SWOG 1512. The presented developments bring extremely promising results for melanoma therapy workflows.
 The use of cutting-edge anti-cancer therapeutics acting on various molecular targets drastically improves the tumor response as well as straitens the appearance of treatment-related adverse events.

Profile of Skin Tumors at Dr. Zainoel Abidin General Hospital Dermatology and Venerology Outpatient Clinic in 2017 – 2021 : A Retrospective Study

Background: Skin tumors are swellings caused by proliferation or failure of cell death mechanisms. Based on the type of growth, skin tumors are divided into benign tumors and malignant tumors. Purpose: To investigate the incidence of skin tumors in Dr. Zainoel Abidin General Hospital outpatient clinic. Methods: This study is a descriptive study with total sampling. The diagnosis of skin tumors is assessed based on medical records filled by Dr. Zainoel Abidin General Hospital Dermatovenerologist in January 2017-September 2021. Result: The results showed patients diagnosed with benign skin tumors had as many as 360 subjects and malignant tumors had as many as 4 samples. The majority of women are affected by benign and malignant skin tumors. Based on the age of benign tumors dominated by the age of 22-45 years while in malignant tumors dominated by 45-64 years. The majority of the sample comes from Banda Aceh, based on where the most of them reside. Based on the size of lesions, benign tumors are dominated by lesions that are less than 0.5 cm in size, while malignant tumors are dominated by lesions that are larger than 0.5 cm in size. Based on the presence and absence of recursion the entire dominant sample has no recursion. Based on the physical treatment in benign tumors are dominated by electrocautery action while malignant tumors are the same number between general surgery and FNAB. Conclusion: most of the skin tumors found in Dr. Zainoel Abidin General Hospital dermatology and venerology outpatient clinic are benign

Statical Association between Clinical and Histopathological Parameters for Keratinocyte Carcinomas.

The most common tumor of the western world is comprised of forms of non-melanoma skin cancers, previously known as keratinocyte carcinomas (KCs) The purpose of this study was to determine de incidence of non-melanoma skin tumors and the relationship between histopathological risk factors in patients with skin cancers. The study was composed from 332 cases of skin malignancies for which clinical and histopathological aggressivity factors were statistically analyzed through comparison tests and also stored digitally. For basal cell carcinoma (BCC) statistical analysis indicated significant relationships between pT category and gender, tumor size, ulceration, depth of invasion and positive resection limits. For squamous cell carcinoma (SCC) statistical analysis indicated significant relationships between pT category and tumor size, depth of invasion and positive resection limits. Clinical and histological analysis of certain characteristics of the above-mentioned skin cancers is an essential step in documenting and improving both prognosis and therapy standards.

232 Characterization of the epigenetic profile of epidermis in response to co-exposure to ultraviolet radiations and Benzo[a]pyrene

Human skin is daily exposed to environmental stressors that can significantly impair skin homeostasis and trigger different disorders including aging and cancers. Ultraviolet radiations (UVR) and polycyclic aromatic hydrocarbons such as Benzo[a]pyrene (BaP) are two main pollutants that can harm the skin. UVR is a complete carcinogen while exposure to BaP is known to trigger pathologies such as immunotoxicity. Co-exposure to UVR and BaP increases skin tumor incidence compared to BaP- or UVR-exposure alone. However, few data are available to explain the biological processes that are altered following co-exposure of skin to BaP and UVR. To get insight into the epigenetic alterations triggered in epidermal cells in response to co-exposure, a comparative mass-spectrometry-based proteomic analysis was performed on skin explants following exposure to either no pollutant, UVR or BaP+UVR. The epidermis was separated, and epidermal proteins were extracted from different cellular fractions before an LC-MS analysis based on a label-free quantitative approach was done. Bioinformatic analyses using partial least squares discriminant analyses and differential expression using the EpiFactors database were used to highlight proteins involved in epigenetic processes that were differentially expressed following the co-exposure. Among all the proteins differentially expressed upon the co-exposure, we identified 12 proteins playing a role in epigenetic functions. 7 of these were in the cytosolic fraction (BRE, CTPB1, CUL2A, DDB1, HMGN5, SRSF1, SRSF3), 4 in the membrane fraction (HMGB1, PRKDC, SFPQ, UBE2N) and 1 in the nuclear fraction (SF3B1). A better understanding of these epigenetic alterations after co-exposure to UV and BaP is of special interest to devise topical treatments that potentially maintain skin homeostasis.

Combination of Optical Biopsy with Patient Data for Improvement of Skin Tumor Identification.

In this study, patient data were combined with Raman and autofluorescence spectral parameters for more accurate identification of skin tumors. The spectral and patient data of skin tumors were classified by projection on latent structures and discriminant analysis. The importance of patient risk factors was determined using statistical improvement of ROC AUCs when spectral parameters were combined with risk factors. Gender, age and tumor localization were found significant for classification of malignant versus benign neoplasms, resulting in improvement of ROC AUCs from 0.610 to 0.818 (p < 0.05). To distinguish melanoma versus pigmented skin tumors, the same factors significantly improved ROC AUCs from 0.709 to 0.810 (p < 0.05) when analyzed together according to the spectral data, but insignificantly (p > 0.05) when analyzed individually. For classification of melanoma versus seborrheic keratosis, no statistical improvement of ROC AUC was observed when the patient data were added to the spectral data. In all three classification models, additional risk factors such as occupational hazards, family history, sun exposure, size, and personal history did not statistically improve the ROC AUCs. In summary, combined analysis of spectral and patient data can be significant for certain diagnostic tasks: patient data demonstrated the distribution of skin tumor incidence in different demographic groups, whereas tumors within each group were distinguished using the spectral differences.

Radio-induced malignancies of the scalp in adult after depilatory radiotherapy for tinea capitis in childhood: 137 cases

Abstract Introduction: Radiation-induced malignancies are the most feared complications of radiotherapy. Depilatory radiotherapy for ringworm of the scalp in childhood was the cause of an increase in the incidence of skin tumours of the scalp in adults. The aim of our study was to describe the epidemiological, clinical and therapeutic characteristics of radiation-induced skin tumours of the scalp in order to highlight the characteristics of these tumours compared to non-radiation-induced tumours. Methods: This is a bi-centric retrospective study, extending over a period of 41 years, which collected 137 patients with 200 tumours of the scalp. These patients were selected after noting a history of depilatory radiotherapy for ringworm in childhood in the clinical records of all patients with scalp tumours. We studied the epidemiological, clinical, therapeutic and evolving characteristics of this population. Results: The average age of consultation was 56·6 years. The sex ratio M/F was 3. Radiation dermatitis was found in 33% of cases. The average latency between depilatory radiotherapy and the appearance of radiation-induced tumours was 42·6 years. Multiple carcinomas (&gt;2 tumours) were observed in 23·3% of cases. In 73% of cases, ulceration was the most frequent macroscopic aspect. The predominant histological type was basal cell carcinoma in 82% of cases. Radiation therapy has been the main treatment modality in 77·3% of cases, followed by surgery in 43% of cases. The appearance of new tumours on the scalp was observed in six patients. Conclusion: Radiation-induced tumours of the scalp are comparable in epidemiological and clinical characteristics to non-radiation-induced tumours. However, they may represent a challenge in therapeutic care and require regular monitoring.

The Knowledge and Photoprotective Behaviour of the Hungarian Population in Relation to Skin Cancer

Introduction. The carcinogenic ultraviolet range of sunlight plays a major role in the development of malignant skin tumours with a steadily increasing incidence. It shows a significant upward trend in our country, with 2,742 new cases registered in 2016, nearly 15% of which were under 40 years of age. With conscious behaviour and the use of sunscreen products, the incidence of skin tumours can be reduced. The aim of the study is to assess the Hungarian population’s knowledge about skin cancer and attitudes towards sun protection.Methods. Quantitative cross-sectional study was conducted in a dermatology clinic and among 7th and 8th-grade students and 11th and 12th-grade students of two high schools. The self-administered questionnaire used in the study included questions on socio-demographic data, addictions, skin type, family history of skin cancer, sunburns, sunbathing habits, sunscreen use, knowledge about sun protection and skin cancer, screening and self-testing.Results. 83.9% of respondents (n=356) have experien- ced sunburn 3 or more times, and 27.8% use sunscreen regularly (n=118). 62.7% of respondents (n=266) have never had a skin cancer/melanoma screening. A significant association was found between education, gender and sunscreen use (p&amp;lt;0.001). A significant association was also found between risky behaviour and going to a tanning salon (p&amp;lt;0.001).Conclusions. The Hungarian population has a lack of knowledge about skin cancer. The results indicate that more emphasis should be placed on increasing the knowledge and awareness of the population about sun protection and on developing good habits, starting at the primary and se- condary level.

Abstract 3141: Toll-like receptor 4 knockout promotes cutaneous tumorigenesis in mice lack of Ikka heterozygous loss in keratinocytes

Abstract Role of recognizing pathogen-associated molecular patterns in skin carcinogenesis has not been extensively studied. Toll-like receptor 4 (TLR4) recognizes gram-negative lipopolysaccharide. To explore the impact of interplay between TLR4-regulated microbiota and host epithelial cells on tumorigenesis, we adopted a mouse model that expresses hemizygous Ikkα gene induced by a keratin 5 Cre (K5.Cre, IkkααKC/+). IkkααKC mice die within 3 weeks after birth. Inducible Ikkα ablation mediated by K15.CrePR1 or K5.CreER results in spontaneous skin tumors. We found an increased incidence of spontaneous skin tumors in Tlr4-/-;IkkααKC/+ mice compared to Tlr4-/- or IkkααKC/+ mice. We detected markedly elevated bacteria numbers on the surface of skin tumors compared to the adjacent skin. Interestingly, the oral cavity of Tlr4-/-;IkkααKC/+ mice showed an elevated proportion of gram-negative bacteria compared to Tlr4-/- or IkkααKC/+ mice. To further determine the effect of bone marrow (BM)-derived hemopoietic cells on tumorigenesis, we performed BM transplant experiments. IkkααKC/+ mice with Tlr4-/- BM developed more cutaneous skin tumors than IkkααKC/+ mice with WT BM. Based on these findings, we hypothesized that Tlr4-/- hemopoietic cells regulate microbiota, which further results in altered skin carcinogenesis. We are revealing the detailed mechanism of how Tlr4-/- hemopoietic cells contribute to microbiota changes and tumorigenic promotion. Citation Format: Amit Kumar Singh. Toll-like receptor 4 knockout promotes cutaneous tumorigenesis in mice lack of Ikka heterozygous loss in keratinocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3141.

The medicinal mushroom Ganoderma lucidum attenuates UV-induced skin carcinogenesis and immunosuppression.

The medicinal mushroom Ganoderma lucidum is traditionally used for treating multiple diseases, including cancer. This study examined skin cancer preventive activity of a commercial product containing spore and fruiting body in 30:8 ratio (GLSF). Extracts of GLSF and spore component (GLS) were prepared using artificial gastrointestinal juice and examined on JB6 cells. GLSF and GLS dose-dependently inhibited epidermal growth factor-induced JB6 transformation at non-toxic concentrations. SKH-1 mice which were fed with diets containing GLSF (1.25%), GLS (0.99%) or the fruiting body (GLF) (0.26%) were exposed to chronic low-dose ultraviolet (UV) radiation to assess their effects on skin carcinogenesis. GLSF, but not GLS or GLF, reduced skin tumor incidence and multiplicity. In non-tumor skin tissues of mice, GLSF attenuated UV-induced epidermal thickening, expression of Ki-67, COX-2 and NF-κB, while in tumor tissues, GLSF increased expression of CD8 and Granzyme B. To examine the effects of GLSF on UV-induced immunosuppression, mice which were fed with GLSF were evaluated for the contact hypersensitivity (CHS) response to dinitrofluorobenzene (DNFB). GLSF significantly reversed UV-mediated suppression of DNFB-induced CHS by increasing CD8+ and decreasing CD4+ and FoxP3+ T-cells in mouse ears. Therefore, GLSF prevents skin cancer probably via attenuating UV-induced immunosuppression.

Diagnostic accuracy of basal cell carcinoma in dermatology setting in Serbia: A single-center study

Background/Aim. The growing incidence of skin tumors requires an accurate diagnosis. Dermoscopy, especially in vivo, enhances the diagnosis of basal cell carcinoma (BCC). Total body skin examination (TBSE), a visual inspection of the patient?s total body surface, is considered a basic step in the dermatological exam, especially in skin cancer screening. However, TBSE is still a matter of debate regarding its expediency in a real clinical setting. The aim of this study was to analyze the diagnostic accuracy of BCC detected and treated by referred dermatologists. Methods. The retrospective analysis included a five-year period of BCC detection during TBSE by visual inspection and dermoscopy. We calculated sensitivity, specificity and positive predictive value for BCC using histopathological results as the correct diagnosis. Results. Out of 3,346 biopsied skin tumors, 49.58% were malignant and 50.42% benign. The most common malignant tumor was BCC, accounting for 84.09%. Localization of BCCs was mainly on the trunk (38.92%) and the H-zone of the face (37.63%). Other localizations were face (non-H-zone) (6.67%), neck (3.01%), scalp (3.37%), arms (6.88%) and limbs (3.51%). Of all BCCs, 0.83% were recurrent BCC. The sensitivity for the diagnosis of BCC was 97.71%, and the positive predictive value was 95.08%. Conclusion. In the dermatology setting, TBSE and visual inspection with in vivo dermoscopy result in a very good diagnostic performance of BCC.

Corelaţia dintre apariţia tumorilor cutanate nonmelanocitare și expunerea la radiații UV

Introduction. In the last 30 years, the incidence of non-melanocytic skin tumors (NMRTs) has increased alarmingly. The most common subtype of TCNM is basal cell carcinoma followed by squamous cell carcinoma. Material and method. This retrospective study was performed on a group of 140 patients. Patients diagnosed with C44 nonmelanocytic malignancy according to ICD-10 were included in the study. Results. Of the 140 patients, 118 (84%) received the presumptive diagnosis of CBC and 17 (12%) the diagnosis of CSC. Histopathological examination confirmed the diagnosis of CBC in 76% of cases and that of CSC in 58% of cases. Regarding the number of lesions, cases with a single lesion predominate (94%). In terms of clinical form, the most common type of basal cell carcinoma in the study group was 75% nodular carcinoma. Conclusions. There is a need for more studies for the application of prevention and proper management from the family doctor to the specialist.

Detailed head localization and incidence of skin cancers

Skin cancers are the most common neoplasms; frequently, they localize on the face. The aim of paper is to present the incidence of skin tumors in a single center from 2017 to 2019, describe trends in its frequency and find relations between neoplasms and sex, type of cancer, and its size. An analysis of histopathological files from the surgical department between 2017 and 2019 was calculated. These items were selected: sex, age, type of skin cancer, subtype of basal cell carcinoma (BCC), grading of squamous cell carcinoma (SCC), localization and dimensions of the tumor. The study sample consisted of 387 cases. BCC was the most common cancer and its nodular type was the most frequent. In older patients, the vertical dimension of excised carcinoma was significantly larger. Moreover, this connection was detected only in women compared to men. There were statistically significant differences between dimensions of the skin cancer and sex. In men group, skin cancers had statistically higher vertical dimensions and larger surface areas. On the face and head, BCC more often localizes in the nasal area, while SCC on the auricle. It has been demonstrated that the older the patient, the larger the vertical dimension of the tumor. As such, tumor size is larger in men than in women, as women usually see their physicians sooner than men: cosmetic concerns are more important to them.

Malignant Tumours Presenting as Chronic Leg or Foot Ulcers.

Our purpose was to collect data on the incidence of malignant skin tumours presenting as chronic leg or foot ulcers in a tertiary centre, and to analyse the frequency and type of initial clinical misdiagnoses in these cases. A retrospective chart review of cases with melanoma or other malignant neoplasms of the skin of the lower extremity treated in a tertiary centre during January 2010 until February 2020 was conducted to identify cases that presented as chronic ulcers. Out of 673 cases, 26 (3.9%) were identified with a total of 27 malignant tumours presenting as chronic ulcers of the lower leg or foot. Therefrom, seven were diagnosed as melanoma, eight as squamous cell carcinoma, and twelve as basal cell carcinoma. The mean interval until diagnosis for all tumour types was 44.4 months (median 24 months). A delay in correct treatment occurred in 12 out of 26 cases (46%) as a result of misdiagnosis with subsequent treatment as chronic leg or foot ulcers of a different etiology. Misdiagnoses were venous ulcer, traumatic wound, mixed arterial and venous ulcer, arterial ulcer, and ulcer of an unknown origin. Malignant ulcers presenting as chronic ulcers are rare, but often lead to misdiagnosis.

Impact of delay in follow-up due to COVID-19 pandemic on skin cancer progression: a real-life experience from an Italian hub hospital.

BackgroundThe COVID‐19 pandemic required the setting of a national lockdown in Italy from March 9, 2020, until May 18, 2020; therefore, most of the non‐COVID‐19 activities were postponed. As a consequence, many follow‐up visits in patients with previously excised skin cancers were delayed. The aim of this retrospective real‐life case–control study is demonstrating that delay in follow‐up led to an increased incidence of advanced melanoma and keratinocyte cancers on the total of surgically excised skin cancers.MethodsThe incidence of excised advanced melanoma and keratinocyte cancers in our dermato‐surgery division in the period May 18 to November 18, 2020, was compared to the same time span of 2019. All data were collected from the electronic database of our department. Odds ratio with 95% confidence interval was used to assess the risk of excised advanced skin cancers in 2020 compared to 2019.ResultsFrom May to November 2019, we performed 265 surgical excisions, while during the pandemic in 2020, we completed 280 surgeries. The number of advanced skin cancers excised between May 18 and November 18, 2020, was significantly higher compared with the same period in 2019 (54 vs. 22, OR: 2.64; 95% CI: 1.56–4.47; P = 0.0003). Significant differences were also observed regarding the number of surgically removed advanced BCCs (OR 2.15; 95% CI 1.14–4.07; P = 0.0187) and advanced SCCs (OR 4.60; 95% CI 1.31–16.18; P = 0.0175).ConclusionThese results confirm that delay in follow‐up and, consequently, postponed surgical excisions are related to an increased incidence of advanced skin tumors, resulting in poorer prognosis lifelong. Follow‐up visits should be carried on even during COVID‐19 pandemic, avoiding significant delays as much as possible.

Use of local anesthetics with an epinephrine additive on fingers and penis - dogma and reality.

Epinephrine supplements in local anesthetics are regularly used for surgery in areas with terminal vessels. According to the pharmaceutical guidelines, the use of epinephrine as an additive to local anesthetics is contraindicated for these areas. This review provides an overview of the current scientific data as well as new clinical developments in various fields. It also reviews the current legal situation. A literature research was carried out to survey the current status of relevant data. Written inquiries to several German institutions (Institute for Quality and Efficiency in Health Care, National Association of Statutory Health Insurance Physicians, Center for Clinical Studies Tübingen, Federal Institute for Drugsand Medical Devices) were made to determine the legal situation. No evidence was found in the literature for a causal relationship between the use of epinephrine as a vasoconstrictor and necrosis of the finger or penis. Studies and reviews show that the use of local anesthetics with epinephrine on the fingers or penis is a safe procedure with many clinical and economic advantages. In routine clinical practice, the WALANT method (Wide Awake Local Anesthesia No Tourniquet) as well as the increasing incidence of skin tumors in acral areas has led to a tendency towards increasing use. However, its use is still legally contraindicated, and the pharmaceutical companies show no interest in supporting a drug study. Further clinical trials - regardless of the strength of the evidence - would not change the current legal contraindication.

3′-Hydroxypterostilbene Inhibits 7,12-Dimethylbenz[a]anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-Acetate (TPA)-Induced Mouse Skin Carcinogenesis

BackgroundA natural pterostilbene analogue isolated from the herb Sphaerophysa salsula, 3′-hydroxypterostilbene (HPSB), exhibits antiproliferative activity in several cancer cell lines; however, the inhibitory effects of HPSB on skin carcinogenesis remains unclear. PurposeThe aim of this study was to evaluate the inhibitory effects of HPSB on two-stage skin carcinogenesis in mice and its potential mechanism. Study Design and MethodsThis study investigated the anti-inflammatory and anti-tumor effects of HPSB in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated acute skin inflammation and 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced two-stage skin carcinogenesis model. In addition, the effects of HPSB on the modulation of the phase I and phase II metabolizing enzymes in the DMBA-induced HaCaT cell model were investigated. ResultsThe results provide evidence that topical treatment with HPSB significantly inhibits TPA-induced epidermal hyperplasia and leukocyte infiltration through the down-regulation of cyclooxygenase-2 (COX-2), matrix metalloprotein-9 (MMP-9), and ornithine decarboxylase (ODC) protein expression in mouse skin. Furthermore, HPSB suppresses DMBA/TPA-induced skin tumor incidence and multiplicity via the inhibition of proliferating cell nuclear antigen (PCNA), Cyclin B1 and cyclin-dependent kinase 1 (CDK1) expression in the two-stage skin carcinogenesis model. In addition, pretreatment with HPSB markedly reduces DMBA-induced cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) gene expression in human keratinocytes; however, HPSB does not significantly affect the gene expression of the phase II enzymes. ConclusionThis is the first study to show that topical treatment with HPSB prevents mouse skin tumorigenesis. Overall, our study suggests that natural HPSB may serve as a novel chemopreventive agent capable of preventing carcinogen activation and inflammation-associated tumorigenesis.

Autophagy induction on impaired spermatogenesis of xeroderma pigmentosum group A gene-deficient mice

Xeroderma pigmentosum (XP) involves a defect in the initial step of nucleotide excision repair (NER) and consists of eight genetic complementation groups (groups A-G and a variant). XP group A (XPA) patients have a high incidence of UV-induced skin tumors, immature testicular development, and neurological symptoms. In an earlier study, we have shown that XP group A (Xpa) gene-knockout mice (Xpa-/- mice) were highly sensitive to UV-induced skin carcinogenesis with a defect in NER and were highly susceptibility to spontaneous tumorigenesis with impaired spermatogenesis. However, the pathology of impaired spermatogenesis in Xpa-/- mice is unknown. To unravel the underlying pathology, we made a concerted effort using the testis of 3-month-old Xpa-/- mice. We found many large vacuoles in the seminiferous tubules of 3-month old Xpa-/- mice, while there were no large vacuoles in that of Xpa+/+ mice. Immunohistochemistry of microtubule-associated protein 1 light chain 3 (LC3), an autophagosome marker, showed degenerating cells with intense signal of LC3 in the seminiferous tubules, and immunoblotting revealed induction of LC3-II in the 3-month-old Xpa-/- mice. The results of the present study suggest autophagy induction as the possible mechanism underlying the impaired spermatogenesis in Xpa-/- mice. Therefore, Xpa-/- mice could be a useful model for investigating aging and male infertility with low expression of XPA.