The Experts below are selected from a list of 34401 Experts worldwide ranked by ideXlab platform
Sélim Aractingi - One of the best experts on this subject based on the ideXlab platform.
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Sickle cell disease induces resistance to cutaneous carcinogenesis
Orphanet Journal of Rare Diseases, 2020Co-Authors: Boutros Soutou, Patricia Senet, François Lionnet, Anoosha Habibi, Sélim AractingiAbstract:BACKGROUND: While Skin Carcinomas are reported in chronic ulcers and in patients treated with hydroxyurea (HU) for myeloproliferative neoplasms, no Skin Carcinoma has been reported in patients with sickle cell disease (SCD), presenting chronic Skin ulcers or treated with HU. The objective was to estimate the risk of cutaneous malignant transformation in SCD patients with prolonged leg ulcers or under HU therapy. RESULTS: In this cross-sectional study, the cohort consisted of 1543 patients. In the first series, 29 patients presented a total of 53 ulcers lasting more than two years. The median age was 35 ± 8.4 years old. The median duration for a single ulcer was 9.2 ± 7 years. None of the examined ulcers showed any suspicious area of malignant transformation. In the second series, 187 patients treated with HU for more than two years were identified. The median age was 31.3 ± 9.9 years old. The median duration of treatment with HU was 6 ± 3.2 years. No Skin Carcinoma or actinic keratosis was recorded. CONCLUSIONS: This study showed that Skin carcinogenesis did not occur in our series of SCD patients exposed to transforming events such as long term HU treatment or prolonged leg ulcers.
Mathieu Bollen - One of the best experts on this subject based on the ideXlab platform.
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Enhanced DNA-repair capacity and resistance to chemically induced carcinogenesis upon deletion of the phosphatase regulator NIPP1
Oncogenesis, 2020Co-Authors: Iris Verbinnen, Shannah Boens, Monica Ferreira, Kathelijne Szekér, Louise Wijk, Aleyde Eynde, Mathieu BollenAbstract:Nuclear Inhibitor of PP1 (NIPP1) is a conserved regulatory subunit of protein phosphatase PP1. The selective deletion of NIPP1 in mouse liver parenchymal cells or Skin epidermal cells culminates in a late-onset hyperproliferation of a subset of resident progenitor cells. Although a hyperplastic phenotype is usually tumor promoting, we show here that the absence of NIPP1 conferred a strong resistance to chemically induced hepatocellular or Skin Carcinoma. The ablation of NIPP1 did not affect the metabolism of the administered mutagens (diethylnitrosamine or 7,12-dimethylbenz[a]anthracene), but reduced the conversion of mutagen-induced covalent DNA modifications into cancer-initiating mutations. This reduced sensitivity to mutagens correlated with an enhanced DNA-damage response and an augmented expression of rate-limiting DNA-repair proteins (MGMT in liver, XPD and XPG in Skin), hinting at an increased DNA-repair capacity. Our data identify NIPP1 as a repressor of DNA repair and as a promising target for novel cancer prevention and treatment therapies.
Leena Brucknertuderman - One of the best experts on this subject based on the ideXlab platform.
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injury driven stiffening of the dermis expedites Skin Carcinoma progression
Cancer Research, 2016Co-Authors: Venugopal Rao Mittapalli, Josef Madl, Stefanie Loffek, Dimitra Kiritsi, Johannes S Kern, Winfried Romer, Alexander Nystrom, Leena BrucknertudermanAbstract:Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic Skin fragility disorder characterized by injury-driven blister formation, progressive soft-tissue fibrosis, and a highly elevated risk of early-onset aggressive cutaneous squamous cell Carcinoma (cSCC). However, the mechanisms underlying the unusually rapid progression of RDEB to cSCC are unknown. In this study, we investigated the contribution of injury-induced Skin alterations to cSCC development by using a genetic model of RDEB and organotypic Skin cultures. Analysis of RDEB patient samples suggested that premalignant changes to the dermal microenvironment drive tumor progression, which led us to subject a collagen VII hypomorphic mouse model of RDEB to chemical carcinogenesis. Carcinogen-treated RDEB mice developed invasive tumors phenocopying human RDEB-cSCC, whereas wild-type mice formed papillomas, indicating that the aggressiveness of RDEB-cSCC is mutation-independent. The inherent structural instability of the RDEB dermis, combined with repeated injury, increased the bioavailability of TGFβ, which promoted extracellular matrix production, cross-linking, thickening of dermal fibrils, and tissue stiffening. The biophysically altered dermis increased myofibroblast activity and integrin β1/pFAK/pAKT mechanosignaling in tumor cells, further demonstrating that cSCC progression is governed by pre-existing injury-driven changes in the RDEB tissue microenvironment. Treatment of three-dimensional organotypic RDEB Skin cultures with inhibitors of TGFβ signaling, lysyl oxidase, or integrin β1–mediated mechanosignaling reduced or bypassed tissue stiffness and limited tumor cell invasion. Collectively, these findings provide a new mechanism by which RDEB tissue becomes malignant and offer new druggable therapeutic targets to prevent cSCC onset. Cancer Res; 76(4); 940–51. ©2015 AACR.
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injury driven stiffening of the dermis expedites Skin Carcinoma progression
Cancer Research, 2016Co-Authors: Venugopal Rao Mittapalli, Josef Madl, Stefanie Loffek, Dimitra Kiritsi, Johannes S Kern, Winfried Romer, Alexander Nystrom, Leena BrucknertudermanAbstract:Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic Skin fragility disorder characterized by injury-driven blister formation, progressive soft-tissue fibrosis, and a highly elevated risk of early-onset aggressive cutaneous squamous cell Carcinoma (cSCC). However, the mechanisms underlying the unusually rapid progression of RDEB to cSCC are unknown. In this study, we investigated the contribution of injury-induced Skin alterations to cSCC development by using a genetic model of RDEB and organotypic Skin cultures. Analysis of RDEB patient samples suggested that premalignant changes to the dermal microenvironment drive tumor progression, which led us to subject a collagen VII hypomorphic mouse model of RDEB to chemical carcinogenesis. Carcinogen-treated RDEB mice developed invasive tumors phenocopying human RDEB-cSCC, whereas wild-type mice formed papillomas, indicating that the aggressiveness of RDEB-cSCC is mutation-independent. The inherent structural instability of the RDEB dermis, combined with repeated injury, increased the bioavailability of TGFβ, which promoted extracellular matrix production, cross-linking, thickening of dermal fibrils, and tissue stiffening. The biophysically altered dermis increased myofibroblast activity and integrin β1/pFAK/pAKT mechanosignaling in tumor cells, further demonstrating that cSCC progression is governed by pre-existing injury-driven changes in the RDEB tissue microenvironment. Treatment of three-dimensional organotypic RDEB Skin cultures with inhibitors of TGFβ signaling, lysyl oxidase, or integrin β1-mediated mechanosignaling reduced or bypassed tissue stiffness and limited tumor cell invasion. Collectively, these findings provide a new mechanism by which RDEB tissue becomes malignant and offer new druggable therapeutic targets to prevent cSCC onset.
Boutros Soutou - One of the best experts on this subject based on the ideXlab platform.
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Sickle cell disease induces resistance to cutaneous carcinogenesis
Orphanet Journal of Rare Diseases, 2020Co-Authors: Boutros Soutou, Patricia Senet, François Lionnet, Anoosha Habibi, Sélim AractingiAbstract:BACKGROUND: While Skin Carcinomas are reported in chronic ulcers and in patients treated with hydroxyurea (HU) for myeloproliferative neoplasms, no Skin Carcinoma has been reported in patients with sickle cell disease (SCD), presenting chronic Skin ulcers or treated with HU. The objective was to estimate the risk of cutaneous malignant transformation in SCD patients with prolonged leg ulcers or under HU therapy. RESULTS: In this cross-sectional study, the cohort consisted of 1543 patients. In the first series, 29 patients presented a total of 53 ulcers lasting more than two years. The median age was 35 ± 8.4 years old. The median duration for a single ulcer was 9.2 ± 7 years. None of the examined ulcers showed any suspicious area of malignant transformation. In the second series, 187 patients treated with HU for more than two years were identified. The median age was 31.3 ± 9.9 years old. The median duration of treatment with HU was 6 ± 3.2 years. No Skin Carcinoma or actinic keratosis was recorded. CONCLUSIONS: This study showed that Skin carcinogenesis did not occur in our series of SCD patients exposed to transforming events such as long term HU treatment or prolonged leg ulcers.
Jaakko Karvonen - One of the best experts on this subject based on the ideXlab platform.
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Psoriasis, its Treatment, and Cancer in a Cohort of Finnish Patients
Journal of Investigative Dermatology, 2000Co-Authors: A. Hannuksela-svahn, K. Poikolainen, Esa Laara, Eero Pukkala, Jaakko KarvonenAbstract:This study was designed to estimate the relative cancer risk of patients with moderate to severe psoriasis, with reference to different treatments. A cohort of 5687 hospitalized patients with psoriasis obtained from the Finnish Hospital Discharge Register in 1973–84 was linked with the records of the Finnish Cancer Registry. Standardized incidence ratios for cancer were calculated by dividing the observed number of cases by the expected cases, which were based on the national sex-specific and age-specific cancer incidence rates. By the end of 1995, 533 cancer cases were observed in the cohort. The overall cancer incidence was increased (standardized incidence ratio 1.3, 95% confidence interval 1.2–1.4). The estimated relative risks were highest for Hodgkin's disease (standardized incidence ratio 3.3, 95% confidence interval 1.4–6.4), squamous cell Skin Carcinoma (standardized incidence ratio 3.2, 95% confidence interval 2.3–4.4), non-Hodgkin's lymphoma (standardized incidence ratio 2.2, 95% confidence interval 1.4–3.4), and laryngeal cancer (standardized incidence ratio 2.9, 95% confidence interval 1.5–5.0). The role of prior oral antipsoriatic medications or phototherapy on the development of these cancers was assessed in a nested case-control study, for which 67 cases and 199 sex and age matched controls were selected from the psoriasis cohort. The relative risks were estimated using conditional logistic regression analysis. Oral 8-methoxy-psoralen plus ultraviolet-A radiation therapy and the use of retinoids were associated with an increased risk of squamous cell Skin Carcinoma (relative risk adjusted for the other treatment variables 6.5, 95% confidence interval 1.4–31, and 7.4, 95% confidence interval 1.4–40, respectively), whereas none of the treatments could be linked with the occurrence of non-Hodgkin's lymphoma.
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basal cell Skin Carcinoma and other nonmelanoma Skin cancers in finland from 1956 through 1995
Archives of Dermatology, 1999Co-Authors: A Hannukselasvahn, Eero Pukkala, Jaakko KarvonenAbstract:Objective To study trends of nonmelanoma Skin cancer in Finland. Design Descriptive analysis of incidence and mortality rates for basal cell Skin Carcinoma (BCC) and other nonmelanoma Skin cancers (NMSCs) from 1966 and 1956, respectively, through 1995 in relation to sex, age, anatomical distribution, place of residence, and occupation. Setting Data were obtained from the nationwide Finnish Cancer Registry, to which reporting of Skin cancer is compulsory. Patients Inhabitants of Finland (5.1 million in 1998). Main Outcome Measures Age- and sex-specific incidence and mortality rates and overall rates adjusted for age to the world standard population; occupation-specific standardized incidence ratios, with the total Finnish population as reference. Results The age-adjusted incidence rate in 1991 through 1995 for BCC was 49 per 100,000 person-years in men and 45 in women. For NMSC it was 8.7 in men and 5.3 in women. Both cancer types showed an increasing trend in incidence rates. The proportion of tumors in the face, scalp, and neck was 59% for BCC and 67% for NMSC. The incidence rate of NMSC increased from north to south, while there was no great urban-rural or occupational variation in the occurrence of NMSC. The incidence rate for BCC was higher in urban than in rural regions. Farmers, forestry workers, and fishermen showed low incidence of BCC, whereas occupations with a high level of education or compulsory health checkups and medical care occupations appeared to have an increased incidence of BCC. The mortality rate for BCC in 1991 through 1995 was 0.08 per 100,000 person-years in men and 0.05 in women, and for NMSC, it was 0.38 in men and 0.23 in women. The mortality trend was decreasing for both cancer types. Conclusions The incidence of NMSC is fairly low in Finland, accounting for 3.5% of all new cancer cases. Conversely, BCC is the most common cancer type. The incidence trend is increasing for both Skin cancer types, but mortality remains low.
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Trioxsalen Bath PUVA Does Not Increase the Risk of Squamous Cell Skin Carcinoma: A Joint Analysis of 1124 Swedish and Finnish Patients Followed Up for 10 Years
Skin Cancer and UV Radiation, 1997Co-Authors: A. Hannuksela-svahn, K. Poikolainen, Eero Pukkala, B. Sigurgeirsson, B. Lindelöf, Berit Berne, M. Hannuksela, Jaakko KarvonenAbstract:Cancer incidence with special reference to nonmelanoma Skin cancer was studied by combining the results of the two largest follow-up studies on trioxsalen (TMP) bath PUVA. The study cohort comprised 527 psoriasis patients treated at the Oulu University Hospital, Finland, in 1977–1988 and 597 patients treated with TMP bath PUVA at the Uppsala University Hospital, Sweden, in 1974–1985, of whom two thirds had psoriasis and the remaining on third other Skin diseases. The average follow-up time in the combined cohort was 10 years. The observed and expected numbers of cases from the two studies were added up, and the combined standardized incidence ratios (SIR) were calculated. The expected numbers of cases were based on the national cancer incidence rates in the respective countries. Two cases of squamous cell Skin Carcinoma were found, while the expected number was 1.8 (SIR 1.1,95% CI 0.1-4.0). A fourfold or higher excess risk could be excluded. The overall risk of cancer was significantly increased in women (SIR 1.9,95% CI 1.4-2.6), but not in men. Kidney cancer (SIR 8.3,95% CI 2.7-19) and non-Hodgkin’s lymphoma (SIR 6.5,95% CI 1.4-19) were significantly more common than expected in women. In conclusion, the occurrence of squamous cell Skin Carcinoma was not increased in patients treated with TMP bath PUVA. The result indicates that TMP bath PUVA is a safer treatment than oral methoxsalen PUVA.
