scholarly journals Hydrochlorothiazide Use and Risk of Nonmelanoma Skin Cancers: A Biological Plausibility Study

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Elisabetta Bigagli ◽  
Lorenzo Cinci ◽  
Mario D’Ambrosio ◽  
Patrizia Nardini ◽  
Francesca Portelli ◽  
...  
Keyword(s):  
Dna Repair ◽  
Safety Data ◽  
Human Keratinocytes ◽  
Ultrastructural Level ◽  
Biological Plausibility ◽  
Preneoplastic Lesions ◽  
Skin Cancers ◽  
Pathway Activation ◽  
Increased Risk ◽  
Nonmelanoma Skin Cancers

Recent studies reported the association between increased risk of nonmelanoma skin cancers (NMSCs) and the use of hydrochlorothiazide (HCTZ), one of the most commonly prescribed diuretic, antihypertensive drug, over the world. Although HCTZ is known to be photosensitizing, the mechanisms involved in its potential prophotocarcinogenic effects remain unclear. Under acute exposure, therapeutically relevant concentrations of HCTZ (70, 140, and 370 ng/mL) amplified UVA-induced double-strand breaks, oxidative DNA, and protein damage in HaCaT human keratinocytes, and this effect was associated to a defective activity of the DNA repair enzyme, OGG1. Oxidative damage to DNA, but not that to proteins, was reversible within few hours. After chronic, combined exposure to HCTZ (70 ng/mL) and UVA (10 J/cm2), for 9 weeks, keratinocytes acquired a dysplastic-like phenotype characterized by a multilayered morphology and alterations in cell size, shape, and contacts. At the ultrastructural level, several atypical and enlarged nuclei and evident nucleoli were also observed. These transformed keratinocytes were apoptosis resistant, exhibited enhanced clonogenicity capacity, increased DNA damage and inflammation, defective DNA repair ability, and increased expression of the oncogene ΔNp63α and intranuclear β-catenin accumulation (a hallmark of Wnt pathway activation), compared to those treated with UVA alone. None of these molecular, morphological, or functional effects were observed in cells treated with HCTZ alone. All these features resemble in part those of preneoplastic lesions and NMSCs and provide evidence of a biological plausibility for the association among exposure to UVA, use of HCTZ, and increased risk of NMSCs. These results are of translational relevance since we used environmentally relevant UVA doses and tested HCTZ at concentrations that reflect the plasma levels of doses used in clinical practice. This study also highlights that drug safety data should be followed by experimental evaluations to clarify the mechanistic aspects of adverse events.

scholarly journals Risk of Subsequent Neoplasms During the Fifth and Sixth Decades of Life in the Childhood Cancer Survivor Study Cohort

2015 ◽  
Vol 33 (31) ◽  
pp. 3568-3575 ◽  
Author(s):  
Lucie M. Turcotte ◽  
John A. Whitton ◽  
Debra L. Friedman ◽  
Sue Hammond ◽  
Gregory T. Armstrong ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Cumulative Incidence ◽  
Absolute Risk ◽  
Multivariable Analysis ◽  
Malignant Neoplasms ◽  
Study Cohort ◽  
Skin Cancers ◽  
Increased Risk ◽  
Survivors Of Childhood Cancer ◽  
Nonmelanoma Skin Cancers

Purpose Survivors of childhood cancer have an increased risk for subsequent neoplasms (SNs), but the incidence beyond the age of 40 years and associations with therapeutic exposures have not been well described. Patients and Methods Among 14,364 survivors of childhood cancer diagnosed between 1970 and 1986, 3,171 had an attained age of 40 years or older at the time of last contact. Cumulative incidence of SNs, standardized incidence ratios (SIRs), excess absolute risk of subsequent malignant neoplasms (SMNs), and relative risks (RRs) for SMNs and nonmelanoma skin cancers were calculated. Results In total, 679 SNs were diagnosed in patients age 40 years or older. These included 196 SMNs, 419 nonmelanoma skin cancers, 21 nonmalignant meningiomas, and 43 other benign neoplasms. At age 55 years, the cumulative incidence of new SNs and SMNs occurring after age 40 years was 34.6% (95% CI, 28.7 to 40.6) and 16.3% (95% CI, 11.7 to 20.9), respectively. Survivors were four times as likely as the general population to receive a diagnosis of SMN after age 40 years (SIR, 4.4; 95% CI 3.8 to 5.0). Among SMNs, risk was most increased for soft tissue sarcoma (SIR, 12.3; 95% CI, 7.2 to 21.0), breast cancer (SIR, 8.3; 95% CI, 6.9 to 10.0), renal cancer (SIR, 6.1; 95% CI, 3.2 to 11.6), and thyroid cancer (SIR, 5.1; 95% CI, 2.8 to 9.4). Female sex (RR, 1.5; 95% CI, 1.1 to 2.1; P = .008), platinum chemotherapy (RR, 3.4; 95% CI, 1.5 to 7.7; P = .003), epipodophyllotoxins (RR, 2.4; 95% CI, 1.0 to 5.8; P = .05), and therapeutic radiation exposure (RR, 2.0; 95% CI, 1.4 to 3.1; P < .001) were associated with higher risk for SMN in multivariable analysis. Conclusion Even after age 40 years, survivors of childhood cancer remain at increased risk for treatment-related SNs. These data suggest the need for life-long monitoring and should inform anticipatory guidance provided to survivors of childhood cancer.

Increased Risk for Nonmelanoma Skin Cancers in Patients Who Receive Thiopurines for Inflammatory Bowel Disease

2011 ◽  
Vol 141 (5) ◽  
pp. 1621-1628.e5 ◽  
Author(s):  
Laurent Peyrin–Biroulet ◽  
Kiarash Khosrotehrani ◽  
Fabrice Carrat ◽  
Anne–Marie Bouvier ◽  
Jean–Baptiste Chevaux ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Skin Cancers ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Nonmelanoma Skin Cancers

Increased Risk of Nonmelanoma Skin Cancers Among Individuals With Inflammatory Bowel Disease

2011 ◽  
Vol 141 (5) ◽  
pp. 1612-1620 ◽  
Author(s):  
Harminder Singh ◽  
Zoann Nugent ◽  
Alain A. Demers ◽  
Charles N. Bernstein
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Skin Cancers ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Nonmelanoma Skin Cancers

scholarly journals Rapid development of multiple nonmelanoma skin cancers secondary to ruxolitinib: a case report

2021 ◽  
Vol 7 (4) ◽  
pp. 572
Author(s):  
Trevor A. Nessel ◽  
Jeffrey B. Morris ◽  
Tyler Roshak ◽  
Bryan D. Sofen
Keyword(s):  
Prostate Cancer ◽  
Rapid Development ◽  
Janus Kinase ◽  
Cellular Growth ◽  
Graft Versus Host ◽  
Skin Cancers ◽  
Immunosuppressive Medications ◽  
Increased Risk ◽  
Nonmelanoma Skin Cancers ◽  
Stat Pathway

<p class="abstract">Janus kinase (JAK) inhibitors are immunosuppressive medications that function by deactivating the JAK-STAT pathway causing inhibition of cellular growth. Ruxolitinib is a JAK inhibitor that is commonly used to treat disease processes such as myelofibrosis, polycythemia vera and graft versus host disease, with some evidence of benefit with prostate cancer as well. Side effects of ruxolitinib include increased risk of infection, pancytopenia, cardiovascular disease and malignancy relating to the medication’s immunosuppressive effects. Here we reported a 69-year-old male with prostate cancer being treated with ruxolitinib who developed multiple nonmelanoma skin cancers over a 13-month period.</p>

scholarly journals Squamous Cell Carcinoma as a Complication of Long-Term Hydroxyurea Treatment

2021 ◽  
pp. 542-546
Author(s):  
Miłosz Lewandowski ◽  
Paweł Łukowicz ◽  
Jerzy Jankau ◽  
Jan Romantowski ◽  
Wioletta Barańska-Rybak
Keyword(s):  
Squamous Cell Carcinoma ◽  
Skin Lesion ◽  
Cell Carcinoma ◽  
Polycythemia Vera ◽  
Squamous Cell ◽  
Randomized Clinical Trials ◽  
Skin Cancers ◽  
Hydroxyurea Treatment ◽  
Increased Risk ◽  
Nonmelanoma Skin Cancers

Hydroxyurea therapy is commonly used in the treatment of patients suffering from myeloproliferative diseases, such as polycythemia vera. It is supported by evidence that this type of therapy can generate mild skin lesions like leg ulcers, erythema, and hyperpigmentation. There are also some studies that show an increased risk of development of nonmelanoma skin cancers. We report a 56-year-old man with a 13-year history of polycythemia vera, treated chronically with hydroxyurea. In April 2020, the patient presented a skin lesion on the forehead, skin horn on the left forearm, and hyperkeratosis on the rims of both ears. In the patient’s history, in October 2019, complete excision of the skin lesion in the central area of the forehead was performed. After 4 months, a new skin lesion appeared at the same area of the forehead, which in May 2020 after resection in the histopathological examination was diagnosed as recurrence of squamous cell carcinoma. The aim of the case is to draw the clinicians’ attention to the increased risk of squamous cell carcinoma and basal cell carcinoma in patients treated with hydroxyurea. Increased vigilance would make it possible to recognize them earlier, and thus potentially reduce the undesirable effects associated with the delayed radical treatment of these skin cancers. Randomized clinical trials assessing the potential benefits of oral retinoids for chemoprevention of nonmelanoma skin cancers in the hydroxyurea-treated population should also be considered.

Ingenol Mebutate: A Promising Treatment for Actinic Keratoses and Nonmelanoma Skin Cancers

2013 ◽  
Vol 17 (3) ◽  
pp. 173-179 ◽  
Author(s):  
Aditya K. Gupta ◽  
Maryse Paquet
Keyword(s):  
Safety Data ◽  
Mechanisms Of Action ◽  
Scientific Meeting ◽  
Ingenol Mebutate ◽  
Actinic Keratoses ◽  
Skin Cancers ◽  
The Us ◽  
New Treatment ◽  
Skin Conditions ◽  
Nonmelanoma Skin Cancers

Background: A new treatment for actinic keratoses, ingenol mebutate, was recently approved by the US Food and Drug Administration. Objective: To review the mechanisms of action, efficacy and safety data, and practical recommendations for ingenol mebutate. Methods: The PubMed and clinicaltrials.gov databases were searched in March/April 2012 using the terms PEP005, ingenol mebutate, and ingenol 3-angelate. The abstracts from the Annual Scientific Meeting of the Australian College of Dermatologists (2009–2011) and the Annual Meeting of the American Academy of Dermatology (2009–2012) were also searched. Results: Due to its multiple mechanisms of action, ingenol mebutate treatment resulted in short- and long-term efficacy similar to other topical treatments for actinic keratoses in a shorter period of 2 or 3 days. This short therapy would reduce the duration of adverse events. Premarketing trials for treatment of nonmelanoma skin cancers also showed promising results for ingenol mebutate. Conclusion: Ingenol mebutate is a convenient, safe, and effective intervention for precancerous and cancerous skin conditions.

Short-term Risk of Total Malignancy and Nonmelanoma Skin Cancers with Certolizumab and Golimumab in Patients with Rheumatoid Arthritis: Metaanalysis of Randomized Controlled Trials

2012 ◽  
Vol 39 (4) ◽  
pp. 712-715 ◽  
Author(s):  
PIERRE LE BLAY ◽  
GAEL MOUTERDE ◽  
THOMAS BARNETCHE ◽  
JACQUES MOREL ◽  
BERNARD COMBE
Keyword(s):  
Rheumatoid Arthritis ◽  
Control Group ◽  
Chi Square ◽  
American College Of Rheumatology ◽  
Skin Cancers ◽  
European League Against Rheumatism ◽  
Increased Risk ◽  
Statistical Heterogeneity ◽  
Nonmelanoma Skin Cancers ◽  
Necrosis Factor

Objective.To assess the risk of total malignancy and nonmelanoma skin cancers (NMSC) in patients with rheumatoid arthritis (RA) receiving certolizumab and golimumab through a metaanalysis of data from randomized control trials (RCT).Methods.We systematically reviewed the literature up to May 2011 in Medline databases, as well as abstracts from the 2009 and 2010 annual meetings of the European League Against Rheumatism and the American College of Rheumatology. Mantel-Haenszel method was used to determine a common odds ratio (OR). Statistical heterogeneity was assessed by chi-square Q test. We selected only RCT including more than 30 RA subjects randomly assigned to an anti-tumor necrosis factor (TNF) or a nonbiological disease-modifying antirheumatic drug (DMARD) control group.Results.The literature search identified 793 articles; 6 (2 with certolizumab and 4 with golimumab) were selected for metaanalysis. A total of 2710 patients received at least 1 dose of certolizumab or golimumab. For anti-TNF-treated patients, 18 cancers (excluding NMSC) and 9 NMSC were observed versus 4 cases of total malignancy and 3 NMSC in control groups. Metaanalysis revealed a pooled OR of 1.06 (95% CI 0.39–2.85) for risk of total malignancy and 0.69 (95% CI 0.23–2.11) for risk of NMSC with certolizumab and golimumab versus DMARD. Heterogeneity was not significant.Conclusion.Metaanalysis of RCT of golimumab and certolizumab did not find an increased risk of total malignancy and NMSC. These results must be confirmed with longterm extension studies and registry studies, and careful monitoring remains mandatory.

scholarly journals Risk of Nonmelanoma Skin Cancers and Parkinson’s Disease—Meta-Analysis and Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 587
Author(s):  
Danuta Krasowska ◽  
Agnieszka Gerkowicz ◽  
Radosław Mlak ◽  
Milena Leziak ◽  
Teresa Małecka-Massalska ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Carcinoma ◽  
Meta Analysis ◽  
Control Group ◽  
Skin Cancers ◽  
Increased Risk ◽  
Comprehensive Search ◽  
Nonmelanoma Skin Cancers

Patients with Parkinson’s disease (PD) have an increased risk of melanoma compared with the general population. Considering that Nonmelanoma Skin Cancers (NMSCs) share similar risk factors with melanoma, there is a need to understand a possible connection between PD and NMSCs. The aim of the study was the evaluation of NMSC risk among PD patients via meta-analysis and systematic review. A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted, including studies from January 2000 to April 2020. We identified 16 eligible studies including 140291 PD patients. Upon statistical analysis, a significantly higher risk of developing NMSCs in PD patients was found compared with the control group (odds ratio (OR) = 1.25, 95% CI: 1.17–1.33; p < 0.0001). Among all NMSCs, the risk of developing basal cell carcinoma in PD patients was significantly higher (OR = 1.30, 95% confidence interval (CI): 1.15–1.47; p < 0.0001), contrary to squamous cell carcinoma. Further analysis revealed a significantly higher risk of developing NMSCs in patients with previously diagnosed PD (OR = 1.26, 95% CI: 1.19–1.33; p < 0.0001). Our data suggest the necessity for regular skin examination of PD patients, though further studies are required to explore the mechanisms forming this relationship.

scholarly journals The E6 and E7 Proteins of the Cutaneous Human Papillomavirus Type 38 Display Transforming Properties

2003 ◽  
Vol 77 (3) ◽  
pp. 2195-2206 ◽  
Author(s):  
Sandra Caldeira ◽  
Ingeborg Zehbe ◽  
Rosita Accardi ◽  
Ilaria Malanchi ◽  
Wen Dong ◽  
...  
Keyword(s):  
Human Keratinocytes ◽  
Human Papillomaviruses ◽  
Host Cells ◽  
Primary Human Keratinocytes ◽  
Transition Control ◽  
Skin Cancers ◽  
E6 And E7 ◽  
E7 Proteins ◽  
Nonmelanoma Skin Cancers

ABSTRACT Several studies have suggested the involvement of cutaneous human papillomaviruses (HPVs) in the development of nonmelanoma skin cancers. Here we have characterized the in vitro properties of E7 proteins of three cutaneous HPV types, 10, 20, and 38, which are frequently detected in skin specimens. We show that HPV38 E7 is able to inactivate the tumor suppressor pRb and induces loss of G1/S transition control, a key event in carcinogenesis. In contrast, HPV10 and HPV20 E7 proteins do not display these in vitro transforming activities. We also show that the two early proteins E6 and E7 of HPV38 are sufficient to corrupt the cell cycle and senescence programs in primary cells, inducing active and long-lasting proliferation of primary human keratinocytes, the natural host cells. Our study shows that E6 and E7 of this cutaneous HPV type have transforming activity in primary human cells, suggesting a role for HPV38 infection in skin carcinogenesis. In further support of such a role, we detected HPV38 DNA in approximately 50% of nonmelanoma skin cancers, but only in 10% of healthy skin specimens (P < 0.001).

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