692 results on '"Carcinoma, Squamous Cell chemically induced"'
Search Results
2. [Translated article] Risk of Skin Cancer Associated with Disease-Modifying Therapies in Multiple Sclerosis: A Comprehensive Evidence Review.
- Author
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Brufau-Cochs M, Mansilla-Polo M, and Morgado-Carrasco D
- Subjects
- Humans, Fingolimod Hydrochloride therapeutic use, Fingolimod Hydrochloride adverse effects, Immunosuppressive Agents adverse effects, Immunosuppressive Agents therapeutic use, Alemtuzumab adverse effects, Alemtuzumab therapeutic use, Sphingosine 1 Phosphate Receptor Modulators therapeutic use, Sphingosine 1 Phosphate Receptor Modulators adverse effects, Melanoma drug therapy, Cladribine therapeutic use, Cladribine adverse effects, Carcinoma, Squamous Cell etiology, Carcinoma, Squamous Cell chemically induced, Skin Neoplasms, Multiple Sclerosis drug therapy, Multiple Sclerosis complications, Carcinoma, Basal Cell drug therapy
- Abstract
The use of disease-modifying therapies (DMT) has led to a paradigm shift in the management of multiple sclerosis. A comprehensive narrative review was conducted through an extensive literature search including Medline and Google Scholar to elucidate the link between DMT and the propensity of cutaneous malignancies. Sphingosine-1-phosphate receptor modulators, such as fingolimod and siponimod are associated with a higher risk of basal cell carcinoma (BCC), but not squamous cell carcinoma, or melanoma. The associated physiopathological mechanisms are not fully understood. Alemtuzumab and cladribine show isolated associations with skin cancer. Regarding other DMT, no increased risk has ever been found. Given the evidence currently available, it is of paramount importance to advocate for necessary dermatological assessments that should be individualized to the risk profile of each patient. Nonetheless, additional prospective studies are still needed to establish efficient dermatological follow-up protocols., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)
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- 2024
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3. A retrospective analysis of drugs associated with the development of cutaneous squamous cell carcinoma reported by patients on the FDA's adverse events reporting system.
- Author
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Jean-Pierre P and Nouri K
- Subjects
- Humans, United States epidemiology, Male, Female, Retrospective Studies, Aged, Middle Aged, Adult, Risk Factors, Immunosuppressive Agents adverse effects, Aged, 80 and over, Thalidomide adverse effects, Thalidomide analogs & derivatives, Calcineurin Inhibitors adverse effects, Calcineurin Inhibitors administration & dosage, Adrenal Cortex Hormones adverse effects, Adrenal Cortex Hormones therapeutic use, Sex Factors, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell chemically induced, Skin Neoplasms epidemiology, United States Food and Drug Administration, Adverse Drug Reaction Reporting Systems statistics & numerical data
- Abstract
Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer arising from squamous cells of the epidermis. Most cases of cSCC have a good prognosis if detected and treated early; however, certain cases can be aggressive. The primary risk factor for cSCC is prolonged ultraviolet radiation from sun exposure, leading to DNA mutations. Other risk factors have also been observed, including adverse reactions to medications, particularly immunosuppressants. A query of the Food and Drug Administration Adverse Events Reporting System (FAERS) was done, and all reported events of cSCC as adverse events to medication were recorded along with demographic data of patients affected. A total of 4,792 cases of cSCC as an adverse event to medication were reported between 1997 and 2023. Lenalidomide, a chemotherapeutic drug, had the most cases of cSCC as an adverse event. Nine of the top 10 drugs associated with cSCC had immunosuppressive characteristics. While males had higher odds of cSCC associated with corticosteroids and calcineurin inhibitors, females had higher odds of cSCC related to monoclonal antibodies. Geriatric patients accounted for the majority of cSCC cases at 59.7%. Drawing on data from the FAERS database, there's been a consistent increase in cSCC cases as a side-effect to certain medications, with most having immunosuppressive characteristics. Since there is a lack of up-to-date literature overviewing the most implicated medications for cSCC, we aimed to illustrate this better, as well as patient demographics, to better guide clinicians when prescribing these medications., (© 2024. The Author(s).)
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- 2024
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4. DNA repair ability in a patient with voriconazole-related squamous cell carcinoma that required differential diagnosis from xeroderma pigmentosum.
- Author
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Fukumoto T, Harada T, Ito T, Fukushima S, Ono R, Furue M, and Nishigori C
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- Humans, Male, Diagnosis, Differential, Middle Aged, Antifungal Agents, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell chemically induced, DNA Repair, Skin Neoplasms diagnosis, Skin Neoplasms pathology, Skin Neoplasms genetics, Skin Neoplasms chemically induced, Voriconazole adverse effects, Xeroderma Pigmentosum genetics, Xeroderma Pigmentosum diagnosis
- Abstract
Competing Interests: Conflicts of interest The authors have no conflict of interest to declare.
- Published
- 2024
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5. Screening the critical protein subnetwork to delineate potential mechanisms and protective agents associated with arsenic-induced cutaneous squamous cell carcinoma: A toxicogenomic study.
- Author
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Koushki M, Amiri-Dashatan N, Rezaei-Tavirani M, Robati RM, Fateminasab F, Rahimi S, Razzaghi Z, and Farahani M
- Subjects
- Humans, Quercetin, Molecular Docking Simulation, Toxicogenetics, Protective Agents, Folic Acid adverse effects, Membrane Proteins, Molecular Chaperones, HSP40 Heat-Shock Proteins, Arsenic toxicity, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Skin Neoplasms chemically induced, Skin Neoplasms genetics, Skin Neoplasms metabolism
- Abstract
Recent studies show that complex mechanisms are involved in arsenic-induced malignant transformation of cells. This study aimed to decipher molecular mechanisms associated with arsenic-induced cutaneous squamous cell carcinoma (cSCC) and suggest potential protective factors. RNA-seq-based differentially expressed genes between arsenic-exposed human keratinocytes (HaCaT) and controls were used to construct a protein-protein interaction (PPI) network and discover critical subnetwork-based mechanisms. Protective compounds against arsenic toxicity were determined and their target interactions in the core sub-network were identified by the comparative toxicogenomic database (CTD). The binding affinity between the effective factor and target was calculated by molecular docking. A total of 15 key proteins were screened out as critical arsenic-responsive subnetwork (FN1, IL-1A, CCN2, PECAM1, FGF5, EDN1, FGF1, PXDN, DNAJB9, XBP1, ERN1, PDIA4, DNAJB11, FOS, PDIA6) and 7 effective protective agents were identified (folic acid, quercetin, zinc, acetylcysteine, methionine, catechin, selenium). The GeneMANIA predicted detailed interactions of the subnetwork and revealed terms related to unfolded protein response as the main processes. FN1, IL1A and CCN2, as top significant genes, had good docking affinity with folic acid and quercetin, as selected key compounds. Integration of gene expression and protein-protein interaction related to arsenic exposure in cSCC explored the potential mechanisms and protective agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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6. Letter to the editors: Development of malignant melanoma and squamous cell carcinoma in a patient receiving fingolimod treatment.
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Karabas M, Tepe N, and Esmeli F
- Subjects
- Humans, Fingolimod Hydrochloride adverse effects, Melanoma, Cutaneous Malignant, Melanoma drug therapy, Melanoma pathology, Skin Neoplasms chemically induced, Skin Neoplasms drug therapy, Skin Neoplasms pathology, Carcinoma, Squamous Cell chemically induced
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- 2024
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7. Epidermal growth factor receptor inhibitors in advanced cutaneous squamous cell carcinoma: A systematic review and meta-analysis.
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Pham JP, Rodrigues A, Goldinger SM, Sim HW, and Liu J
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- Humans, Retrospective Studies, Prospective Studies, Protein Kinase Inhibitors adverse effects, ErbB Receptors, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell chemically induced, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms, Skin Neoplasms drug therapy, Skin Neoplasms chemically induced, Antineoplastic Agents adverse effects
- Abstract
Patients with advanced cutaneous squamous cell carcinoma (cSCC) who are not eligible for or who fail to respond to anti-PD1 immunotherapy have few treatment options. Epidermal growth factor receptor (EGFR) inhibitors have been investigated as a therapeutic option for advanced cSCC; however, data are limited to small single-arm trials or retrospective studies. A systematic review and meta-analysis was conducted to PRISMA guidelines (CRD42023394300). Studies reporting on outcomes of EGFR inhibition in advanced cSCC were identified. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse event (AE) rate were pooled using a random effects model and the inverse variance method. Twelve studies (six prospective, six retrospective) were identified, representing 324 patients. Pooled ORR was 26% (95% confidence interval [CI] 18-36), median PFS was 4.8 months (95% CI 3.9-6.6) and median OS was 11.7 months (95% CI 9.2-14.1). Any grade AEs occurred in 93% of patients (95% CI 85-97) while grade 3 and higher AEs occurred in 30% (95% CI 14-54). These results were similar between anti-EGFR monoclonal antibodies (MAbs) and tyrosine kinase inhibitors (TKIs). EGFR inhibitors can be considered in patients with advanced cSCC who are contraindicated for or progress on first-line anti-PD1 immunotherapy. Future studies should evaluate their activity and safety following anti-PD1, identify predictive biomarkers for their efficacy and explore combination approaches., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)
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- 2024
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8. Exogenous hormone therapy and non-melanoma skin cancer (keratinocyte carcinoma) risk in women: a systematic review and meta-analysis.
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Li L, Pei B, and Feng Y
- Subjects
- Humans, Female, Contraceptives, Oral adverse effects, Gonadal Steroid Hormones adverse effects, Keratinocytes pathology, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell epidemiology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell complications, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology
- Abstract
Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I
2 = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I2 = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones., (© 2023. BioMed Central Ltd., part of Springer Nature.)- Published
- 2023
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9. Use of sirolimus as an adjuvant therapy for kidney transplant recipients with high-risk cutaneous squamous cell carcinomas: a prospective non-randomized controlled study.
- Author
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Fázio MR, Cristelli MP, Tomimori J, Koga CE, Ogawa MM, Beneventi GT, Tedesco-Silva H, and Medina-Pestana J
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- Humans, Male, Middle Aged, Aged, Female, Sirolimus adverse effects, Immunosuppressive Agents adverse effects, Prospective Studies, Calcineurin Inhibitors therapeutic use, Graft Rejection epidemiology, Graft Rejection prevention & control, Kidney Transplantation adverse effects, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell chemically induced, Skin Neoplasms drug therapy, Skin Neoplasms epidemiology, Skin Neoplasms chemically induced
- Abstract
Introduction: Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability., Methods: This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions. Incidence densities of high-risk cSCC over 3-years after conversion to sirolimus-monotherapy were compared to a non-randomized group with high-risk cSCC but unsuitable/not willing for conversion., Results: Forty-four patients were included (83% male, mean age 60 ± 9.7years, 62% with skin type II, mean time after transplantation 9 ± 5.7years). There were 25 patients converted to SRL and 19 individuals kept on CNI. There was a tendency of decreasing density of incidence of all cSCC in the SRL group and increasing in the CNI group (1.49 to 1.00 lesions/patient-year and 1.74 to 2.08 lesions/patient-year, p = 0.141). The density incidence of moderately differentiated decreased significantly in the SRL group while increasing significantly in the CNI group (0.31 to 0.11 lesions/patient-year and 0.25 to 0.62 lesions/patient-year, p = 0.001). In the SRL group, there were no sirolimus discontinuations, no acute rejection episodes, and no de novo DSA formation. Renal function remained stable., Conclusions: This study suggests that sirolimus monotherapy may be useful as adjuvant therapy of high-risk cSCC in kidney transplant recipients. The conversion strategy used was well tolerated and safe regarding key mid-term transplant outcomes.
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- 2023
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10. NITROSOGENESIS LESSONS FROM DERMATOLOGISTS-NITROSAMINES/ NDSRIS CONTAMINATION OF THE POLIMEDICATION IN POLIMORBID PATIENTS AS THE MOST POWERFUL SKIN CANCER INDUCTOR: DOUBLE HATCHET FLAP FOR SCC OF THE SCALP OCCURRING DURING TREATMENT WITH VALSARTAN/ HYDROCHLOROTHIAZIDE AND LERCANIDIPINE.
- Author
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Tchernev G
- Subjects
- Humans, Aged, 80 and over, Scalp, Dermatologists, Quality of Life, Valsartan, Carcinogens toxicity, Hydrochlorothiazide, Nitrosamines, Skin Neoplasms chemically induced, Skin Neoplasms drug therapy, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy
- Abstract
Nitrosogenesis remains to be a topic that is and, in all likelihood, will be relevant in the near and distant future. The reason for this actuality is mainly due to the official data of the regulatory authorities in the face of the FDA, starting back in 2018 with the announcement of the contamination of Valsartan with nitrosamines. This issue only became more profound in April 2023, when again the FDA declared over 250 of the most widely distributed drugs worldwide as actually or potentially contaminated with ˝hypothetical˝ carcinogens. Unfortunately, according to the literature, it is the intake of ˝hypothetical carcinogens˝ that is associated with the development of real carcinomas, including cutaneous tumours. Additionally, the type of carcinogens that could ˝hypothetically˝ be found in these drugs (in the regulatory agency recommendations) has been added to the list, and they are categorized as having a ˝hypothetical carcinogenic potency˝ between 1 to 5 according to the FDA regulation as to pharmaceutical companies from August 2023. Reference values have also been established for each carcinogen. Interestingly, in certain geographic regions such as Eastern Europe, for example, in certain institutions, over periods of 10 years or more, over 98.9% of cases of actual cutaneous tumours (keratinocytic, melanocytic, etc.), could be linked/associated primarily (not hypothetically) to polymedication, which according to official FDA data from April 2023, could be defined as actually/potentially contaminated with up to several ˝hypothetical˝ carcinogens simultaneously. The lack of official data on the contamination of these batches of drugs (with nitrosamines/ NDSRIs) remain even for the period 2018-2023 more than worrying and are one indirect evidence of their real rather than hypothetical availability. Nonetheless, the 2023 FDA data cast considerable doubt as to whether, within the polymorbidity and contamination of polymedication, the allowable daily doses of carcinogens are being substantially exceeded. An open question for regulators remains: Did the giant Pfizer withdraw its high blood pressure drugs in 2022 (hydrochlorothiazide, quinapril) due to the presence of ˝hypothetical carcinogens˝? In practice, Pfizer appears to be one of the few or only companies to have openly stated the reason for withdrawing their preparations due to contamination with real carcinogens and thus protect end users. With this official preventive act, the Giant Pfizer gained the trust of patients worldwide. Another and even more serious dilemma remains whether this is a controlled contamination of certain batches of medicines in certain geographical regions? Indicative therefore are recently published data on the absence of contamination of all batches of a certain class of medicines in certain geographical regions. The genesis of the 'sporadicity' and the 'selectivity' of contamination remain for the time being unresolved and open new and novel questions. We present an 82-year-old patient with arterial hypertension taking hydrochlorothiazide, valsartan and lercanidipine for 3 years who developed a short-term squamous cell carcinoma of the scalp after taking them (1,5- 2 years later) , operated successfully by double hatchet flap. The pathogenesis of the skin tumor/keratinocytic cancer is commented in the context of nitrosogenesis and the officially announced contamination by the FDA with ˝hypothetical carcinogens˝ leading once again to the appearance of a real squamous cell carcinoma of the skin. The polycontamination of multimedication within polymorbidity appears to be problematic. It is thanks to the official FDA data that the strength of these interrelationships is beginning to become clearer although not at the desired speed of clinicians and end users. Discovering the logical relationship between databases (concerning the incidence of skin cancer, but not only) from different periods should only be relative or consistent with current bulletins of regulators and contaminated polymedication. This is what guarantees that the objective truth will be brought to the surface and ensure, through the possible rapid elimination of the contaminants: 1) better survival for patients and 2) better quality of life.
- Published
- 2023
11. Nivolumab for locally advanced and metastatic cutaneous squamous cell carcinoma (NIVOSQUACS study)-Phase II data covering impact of concomitant haematological malignancies.
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Lang R, Welponer T, Richtig E, Wolf I, Hoeller C, Hafner C, Nguyen VA, Kofler J, Barta M, Koelblinger P, Hitzl W, Emberger M, and Laimer M
- Subjects
- Humans, Aged, 80 and over, Nivolumab therapeutic use, Nivolumab adverse effects, B7-H1 Antigen, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell chemically induced, Skin Neoplasms drug therapy, Skin Neoplasms chemically induced, Hematologic Neoplasms
- Abstract
Background: Monoclonal antibodies, such as cemiplimab and pembrolizumab, against the programmed death receptor (PD)-1 have become the current standard of care and first-line treatment of advanced cutaneous squamous cell carcinoma (cSCC), proving remarkable clinical benefit and acceptable safety., Objectives: To assess efficacy and safety of the anti-PD-1 antibody nivolumab in patients with locally advanced and metastatic cSCC., Methods: Patients received open-label nivolumab 240 mg intravenously every 2 weeks for up to 24 months. Patients with concomitant haematological malignancies (CHMs), either non-progressing or stable under active therapy, were eligible for inclusion., Results: Of 31 patients with a median age of 80 years, 22.6% of patients achieved an investigator assessed complete response, resulting in an objective response rate (ORR) of 61.3% and a disease control rate (DCR) of 64.5%. Progression-free survival (PFS) was 11.1 months, and the median overall survival (OS) was not reached after 24 weeks of therapy. Median follow-up was 23.82 months. Subgroup analysis of the CHM cohort (n = 11; 35%) revealed an ORR of 45.5%, a DCR of 54.5%, a median PFS of 10.9 months, and median OS of 20.7 months. Treatment related adverse events were reported in 58.1% of all patients (19.4% grade 3, the remaining grade 1 or 2). PD-L1 expression and CD-8+ T-cell infiltration did not significantly correlate with clinical response, although a trend towards a shorter PFS of 5.6 months was observed with PD-L1 negativity and low CD8+ intratumoral infiltration., Conclusion: This study demonstrated robust clinical efficacy of nivolumab in patients with locally advanced and metastatic cSCCs and a tolerability comparable to data of other anti-PD-1 antibodies. Favourable outcomes were obtained despite involving the oldest hitherto reported study cohort for anti-PD-1 antibodies and a significant proportion of CHM patients prone to high risk tumours and an aggressive course otherwise typically excluded from clinical trials., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
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- 2023
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12. Eruptive Squamous Cell Carcinomas Following Treatment With Fludarabine and Discussion of Treatment.
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Shah M, Wald J, and Hanke C
- Subjects
- Humans, Vidarabine adverse effects, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell pathology, Skin Neoplasms chemically induced, Skin Neoplasms diagnosis, Skin Neoplasms drug therapy
- Published
- 2023
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13. Use of methotrexate and risk of skin cancer: a nationwide case-control study.
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Polesie S, Gillstedt M, Schmidt SAJ, Egeberg A, Pottegård A, and Kristensen K
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- Humans, Methotrexate adverse effects, Case-Control Studies, Risk Factors, Melanoma, Cutaneous Malignant, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell epidemiology, Psoriasis chemically induced, Psoriasis drug therapy, Psoriasis epidemiology
- Abstract
Background: Methotrexate (MTX) use has been suspected of increasing the risk of skin cancer. The aim of this investigation was to examine the association between the use of MTX and the risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous malignant melanoma (CMM)., Methods: In a nationwide Danish case-control study, we identified incident, histologically verified cases of BCC (n = 131,447), cSCC (n = 18,661) or CMM (26,068) from 2004 to 2018. We matched 10 controls to each case on sex and birth year using risk-set sampling and computed crude and adjusted odds ratios (ORs) using conditional logistic regression for the use of MTX (≥2.5 g) compared with never-use., Results: Use of MTX was associated with increased risk of BCC, cSCC and CMM with adjusted ORs of (95% confidence interval) 1.29 (1.20-1.38), 1.61 (1.37-1.89) and 1.35 (1.13-1.61), respectively. For BCC and cSCC, ORs increased with higher cumulative doses. When restricting the study population to patients with psoriasis, the ORs were 1.43 (1.23-1.67), 1.18 (0.80-1.74) and 1.15 (0.77-1.72), respectively., Conclusions: We observed an increased risk of BCC and cSCC associated with the use of MTX with evidence of a dose-response pattern; however, the association was not consistent when restricting the study population to patients with psoriasis., (© 2023. The Author(s).)
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- 2023
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14. Population pharmacokinetics modeling and exposure-response analyses of cemiplimab in patients with recurrent or metastatic cervical cancer.
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Nguyen JH, Epling D, Dolphin N, Paccaly A, Conrado D, Davis JD, and Al-Huniti N
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- Female, Humans, Neoplasm Recurrence, Local drug therapy, Antineoplastic Agents, Immunological adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell pathology, Lung Neoplasms drug therapy, Skin Neoplasms drug therapy, Uterine Cervical Neoplasms drug therapy, Uterine Cervical Neoplasms chemically induced
- Abstract
A population pharmacokinetic (PopPK) model was previously developed for cemiplimab in patients with solid tumors, including advanced cutaneous squamous cell carcinoma (CSCC). Here, we update the existing PopPK model and characterize exposure-response relationships using efficacy and safety data obtained in patients with recurrent or metastatic cervical cancer (R/M CC). To improve model stability and robustness of the existing PopPK model in 1062 patients, the random-effect error model was revised, and structural covariates were removed from the base model to be tested in the covariate analysis. The updated model was used for external validation of cemiplimab pharmacokinetics (PK) in patients with R/M CC on cemiplimab monotherapy (350 mg every 3 weeks intravenously) from a phase III study (NCT03257267). Exposure-response relationships for cemiplimab efficacy (overall survival [OS], progression-free survival [PFS], duration of response [DOR], objective response rate [ORR]), and safety (immune-related adverse events [irAEs]) were analyzed in 295 patients with R/M CC from the aforementioned study. The updated PopPK model showed improved stability with 94.8% successful bootstrap runs vs. 47.6% in the prior model. Cemiplimab exposure was similar across tumor types, including basal cell carcinoma, CSCC, and non-small cell lung cancer. External validation showed the updated model adequately described cemiplimab PK in patients with R/M CC. In exposure-response efficacy analyses, Cox proportional hazard modeling (CPHM) showed no trend between exposure and OS, Kaplan-Meier plots showed no trend between exposure and PFS or DOR, and logistic regression analyses conducted on ORR showed no exposure-response relationship. In exposure-response safety analyses, CPHM showed no trend between exposure and irAEs., (© 2022 Regeneron Pharmaceuticals, Inc. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
- Published
- 2022
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15. Occurrence of voriconazole-induced cutaneous squamous cell carcinoma in Japan: data mining from different national pharmacovigilance databases.
- Author
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Tanaka H, Okuma M, and Ishii T
- Subjects
- Humans, Pharmacovigilance, Adverse Drug Reaction Reporting Systems, Voriconazole adverse effects, Japan epidemiology, Databases, Factual, Data Mining, Epithelial Cells, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology, Drug-Related Side Effects and Adverse Reactions
- Abstract
Long-term voriconazole use may increase the risk of cutaneous squamous cell carcinoma (cSCC), especially in immunocompromised patients. However, relatively little is known regarding voriconazole-induced cSCC in Japan. Thus, the purpose of this study was to evaluate the association between voriconazole use and cSCC in Japan using different national pharmacovigilance databases. First, using the Japanese Adverse Drug Event Report (JADER) database, we evaluated the association between voriconazole use and cSCC in Japan. Second, using the U. S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, we examined regional differences in the occurrence of voriconazole-induced cSCC between Japan and other countries. We calculated reporting odds ratios (RORs) as disproportionality analysis to evaluate voriconazole-induced cSCC. In this study, cases in which one or more of "Bowen's disease", "Carcinoma in situ of skin", "Keratoacanthoma", "Squamous cell carcinoma in skin", or "Squamous cell carcinoma" were reported as adverse events were considered to be cSCC cases. The analysis based on the JADER database showed an association between voriconazole use and cSCC in Japan, with a ROR (95% confidence interval) of 35.37 (25.60-48.87). Further, the analysis based on the FAERS database revealed that signals were detected in Japan as well as in Western countries and Australia. This study is the first in which the association between voriconazole use and cSCC in Japan is assessed using national pharmacovigilance databases. Healthcare providers need to be fully aware of the potential for cSCC development owing to voriconazole use and in all countries, including Japan, ensure careful follow-up of patients' skin.
- Published
- 2022
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16. Hydrochlorothiazide use is associated with the risk of cutaneous and lip squamous cell carcinoma: A systematic review and meta-analysis.
- Author
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de Macedo Andrade AC, Felix FA, França GM, Ribeiro ILA, Barboza CAG, de Castro RD, and de Lisboa Lopes Costa A
- Subjects
- Aged, Female, Humans, Hydrochlorothiazide adverse effects, Lip pathology, Male, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell complications, Carcinoma, Squamous Cell epidemiology, Lip Neoplasms chemically induced, Lip Neoplasms complications, Lip Neoplasms epidemiology, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology
- Abstract
Purpose: The aim of this study is to investigate the association between hydrochlorothiazide (HCTZ) use and the risk of cutaneous and lip squamous cell carcinoma development., Methodology: We performed a systematic review and meta-analysis of case-control studies. We searched the Cochrane Library, PubMed, Scopus, Web of Science and LILACS. This study was registered in PROSPERO under protocol CRD42019129710. The meta-analysis was performed using the software Stata (version 12.0)., Results: A total of 2181 published studies referring to the theme were identified, from which six were included in this systematic review. Men were more frequently affected by cutaneous and lip squamous cell carcinoma than women, with a 1.42:1 ratio. The mean age for cutaneous and lip squamous cell carcinoma development was 73.7 years. This meta-analysis demonstrated a chance of developing cutaneous and lip squamous cell carcinoma in any region of the body in hydrochlorothiazide users of 1.76-fold higher than in non-users. In addition, a risk factor of 1.80 higher (CI 95% = 1.71-1.89) of cutaneous squamous cell carcinoma in the head and neck region was observed in HCTZ users. Moreover, in the analysis of the dose used, the chance of developing squamous cell carcinoma was 3.37-fold lower when the concentration of HCTZ used was less than 50,000 mg., Conclusions: Our results confirm the association between the use of hydrochlorothiazide and the cutaneous and lip squamous cell carcinoma development., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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17. Antidiabetic Treatment in Patients at High Risk for a Subsequent Keratinocyte Carcinoma.
- Author
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Misitzis A, Stratigos A, Mastorakos G, and Weinstock M
- Subjects
- Aged, Female, Humans, Hypoglycemic Agents adverse effects, Keratinocytes, Male, Retrospective Studies, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell epidemiology, Carcinoma, Basal Cell prevention & control, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell prevention & control, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 pathology, Metformin adverse effects, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology, Skin Neoplasms prevention & control
- Abstract
Background: Metformin and sulfonylureas are the most commonly prescribed drugs used for the treatment of type II diabetes. Type II diabetes has been linked to the development of keratinocyte carcinoma (KC), consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Previously we have demonstrated lower risk for a subsequent KC in metformin users. In this study, we aim to investigate the association between sulfonylureas use and the development of KC in patients with KC history. We performed a retrospective cohort study of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial, which was a randomized double-blind vehicle-control cream originally investigating the effect of 5-fluorouracil on KC development. 932 patients with a history of KC were enrolled (98% male, 99% white, median age of 70 years) and followed for a median duration of 2.8 years. 153 patients were on metformin and 94 on sulfonylureas. We performed a survival analysis with cox regression and controlled for body mass index and known predictors: number of prior BCCs and age (for BCC) and for number of prior SCCs (invasive and in situ), number of actinic keratoses at baseline (for SCC). Sulfonylurea-users com-pared to non-users had a HR of 0.67 (CI: 0.40–1.56; P=0.49) and 0.94 (CI: 0.63–1.40; P= 0.77), for SCC and BCC, respectively. Diabetic patients at high risk for KC might benefit from the use of metformin versus sulfonylureas. J Drugs Dermatol. 2022;21(5):502-505. doi:10.36849/JDD.6087.
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- 2022
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18. Arsenical keratoses with squamous cell carcinoma.
- Author
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Neema S and Radhakrishnan S
- Subjects
- Humans, Skin pathology, Arsenicals, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell pathology, Keratosis, Skin Neoplasms chemically induced, Skin Neoplasms diagnosis, Skin Neoplasms pathology
- Published
- 2022
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19. Statin Use and Skin Cancer Risk: A Prospective Cohort Study.
- Author
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Al Rahmoun M, Ghiasvand R, Cairat M, Mahamat-Saleh Y, Cervenka I, Severi G, Boutron-Ruault MC, Robsahm TE, Kvaskoff M, and Fournier A
- Subjects
- Aged, 80 and over, Cohort Studies, Female, Humans, Male, Proportional Hazards Models, Prospective Studies, Risk Factors, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell epidemiology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Melanoma chemically induced, Melanoma epidemiology, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology
- Abstract
Epidemiological studies on statin use in relation to skin cancer risk are scarce and yielded conflicting results. We explored this association in Etude Epidémiologique auprès de femmes de l'Education Nationale, a prospective cohort of French women born in 1925-1950. Health and lifestyle data were self-reported biennially and matched with drug reimbursement data, allowing the identification of participants' statin use since 2004. Multivariable cause-specific hazards regression models adjusted for skin cancer risk factors estimated hazard ratios with 95% confidence intervals. Over 2004-2014, 455 cutaneous melanoma, 1,741 basal cell carcinoma, and 268 squamous cell carcinoma cases were ascertained among 62,473 women. Compared with never use, there were no associations between ever use of statins and melanoma (hazard ratio = 1.16, 95% confidence interval = 0.94-1.44) or squamous cell carcinoma (hazard ratio = 0.89, 95% confidence interval = 0.66-1.19) risks and a decrease in basal cell carcinoma risk with ever use of statins (hazard ratio = 0.89, 95% confidence interval = 0.79-0.996). We found no trend of increasing or decreasing risks with dose, duration of use, time since first use, or age at first use and no statistically significant effect modification by pigmentary traits or residential UVR exposure. Because of the limited number of studies evaluating the associations between the use of statins and the risks of melanoma, basal cell carcinoma, and squamous cell carcinoma, these findings would deserve further investigation in other settings., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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20. Cohort and nested case-control study of cutaneous squamous cell carcinoma in solid organ transplant recipients, by medication.
- Author
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Dusendang JR, Carlson E, Lee DS, Marwaha S, Madani S, Alexeeff SE, Webber A, Goes NB, and Herrinton LJ
- Subjects
- Case-Control Studies, Humans, Transplant Recipients, Voriconazole, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Lung Transplantation adverse effects, Organ Transplantation adverse effects, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology
- Abstract
Background: Knowledge is needed about the risk of cutaneous squamous cell carcinoma (cSCC) in solid organ transplant recipients (SOTRs) using contemporary immunosuppressive regimens., Objective: Evaluate the risk of cSCC in relation to medications used by SOTRs., Methods: The cohort and nest case-control study included 3308 SOTRs and 65,883 persons without transplantation during 2009-2019. Incident cSCC was identified from pathology data, and medications were identified from pharmacy data. Adjusted hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards analysis, with voriconazole examined as a time-dependent variable., Results: The annual incidence of cSCC was 1.69% in SOTRs and 0.30% in persons without transplantation. The adjusted hazard ratio of cSCC associated with lung transplant was 14.83 (95% CI, 9.85-22.33) for lung and 6.53-10.69 for other organs. Risk in Latinx persons was higher than in other non-White groups. Among lung recipients, the hazard ratio was 1.14 for each month of voriconazole use (95% CI, 1.04-1.26). Azathioprine use for ≥7 months, relating to mycophenolate mofetil intolerance, was associated with a 4.22-fold increased risk of cSCC (95% CI, 1.90-9.40). Belatacept and other immunsuppressive medications were not associated with risk., Limitation: The number of events was somewhat small., Conclusions: The knowledge of risks and benefits in diverse patients can translate to improvements in care., Competing Interests: Conflicts of interest Authors Dusendang, Carlson, Lee, Marwaha, Madani, Alexeeff, Webber, Goes, and Herrinton are partners or staff of The Permanente Medical Group. Dr Webber is an employee of the University of California at San Francisco., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
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- 2022
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21. COX-2 inhibitors show no preventive effect in the development of skin cancer.
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Yen H, Yen H, Drucker AM, Han J, Li WQ, Li T, Qureshi A, and Cho E
- Subjects
- Cyclooxygenase 2 Inhibitors therapeutic use, Follow-Up Studies, Humans, Prospective Studies, Risk Factors, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell epidemiology, Carcinoma, Basal Cell prevention & control, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell prevention & control, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology, Skin Neoplasms prevention & control
- Abstract
Background: Some clinical trials found that cyclooxygenase-2 (COX-2) inhibitor use lowered the risk of skin cancer in high-risk groups., Patients and Methods: To determine whether COX-2 inhibitor use is associated with lower risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, we analyzed COX-2 inhibitor use and risk of skin cancer based on three prospective cohort studies, the Nurses' Health Study (NHS), NHS II, and the Health Professionals Follow-up Study, including 153,882 participants. Multivariable hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association of COX-2 inhibitor use with risk of BCC, cSCC, and melanoma were estimated using Cox proportional hazards models. We pooled the results using a fixed effects model., Results: 16,142 BCC, 1,973 cSCC, and 631 melanoma cases were documented. Ever vs. never use of COX-2 inhibitor was associated with a modestly increased risk of BCC (multivariable HR 1.09, 95 % CI 1.05-1.14). The hazard ratio was similar for cSCC (multivariable HR 1.12, 95 % CI 1.00-1.27) and melanoma (multivariable HR 1.10, 95 % CI 0.89-1.38), but was not statistically significant., Conclusions: Ever use of COX-2 inhibitor was not associated with a decreased skin cancer risk but was instead associated with a modest, increased risk of BCC., (© 2022 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)
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- 2022
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22. Effectiveness of neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: A prospective cohorts study.
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Bergón-Sendín M, Pulido-Pérez A, Nieto-Benito LM, Barchino-Ortiz L, Díez-Sebastián J, and Suárez-Fernández R
- Subjects
- Humans, Methotrexate, Neoadjuvant Therapy, Prospective Studies, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy, Skin Neoplasms pathology
- Abstract
Intralesional methotrexate (il-MTX) has been used in cutaneous squamous cell carcinoma (cSCC) achieving important reductions in tumor size. However, there is a lack of controlled studies on this regard. The primary objective was to analyze the effect of il-MTX on tumor size in cSCC. As a secondary objective, we evaluated its impact on the surgical approach. We conducted a prospective cohorts study that included 200 patients with histologically confirmed cSCC. Patients in Group 1 (Cases) received neoadjuvant treatment with il-MTX prior to surgery. Patients in Group 2 (Controls) underwent scheduled surgery without prior neoadjuvant therapy. Clinical measurements of lesions were made at the time of inclusion in the study and before surgery. No intergroup statistical differences were found between the assessed variables. In Group 1, tumor size reduction occurred in 93% of the patients after il-MTX therapy. Tumor surface was reduced by 54%. Complex reconstructions were needed in 15% of these patients. In Group 2, tumor surface increased by 33.1% and complex reconstructions were needed in 40% of patients. Intergroup differences were statistically significant (p < 0.001). Neoadjuvant Il-MTX therapy achieves very important tumor size reduction and significantly simplifies surgical treatment., (© 2021 Wiley Periodicals LLC.)
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- 2022
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23. Delineating the Effects of Passaging and Exposure in a Longitudinal Study of Arsenic-Induced Squamous Cell Carcinoma in a HaCaT Cell Line Model.
- Author
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Banerjee M, Al-Eryani L, Srivastava S, Rai SN, Pan J, Kalbfleisch TS, and States JC
- Subjects
- HaCaT Cells, Humans, Longitudinal Studies, Arsenic toxicity, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Skin Neoplasms chemically induced, Skin Neoplasms genetics
- Abstract
Cutaneous squamous cell carcinoma (cSCC) is a major deleterious health effect of chronic arsenic (iAs) exposure. The molecular mechanism of arsenic-induced cSCC remains poorly understood. We recently demonstrated that chronic iAs exposure leads to temporally regulated genome-wide changes in profiles of differentially expressed mRNAs and miRNAs at each stage of carcinogenesis (7, 19, and 28 weeks) employing a well-established passage-matched HaCaT cell line model of arsenic-induced cSCC. Here, we performed longitudinal differential expression analysis (miRNA and mRNA) between the different time points (7 vs 19 weeks and 19 vs 28 weeks) within unexposed and exposed groups, coupled to expression pairing and pathway analyses to differentiate the relative effects of long-term passaging and chronic iAs exposure. Data showed that 66-105 miRNA [p < .05; log2(fold change) > I1I] and 2826-4079 mRNA [p < .001; log2(fold change) > I1I] molecules were differentially expressed depending on the longitudinal comparison. Several mRNA molecules differentially expressed as a function of time, independent of iAs exposure were being targeted by miRNA molecules which were also differentially expressed in a time-dependent manner. Distinct pathways were predicted to be modulated as a function of time or iAs exposure. Some pathways were also modulated both by time and exposure. Thus, the HaCaT model can distinguish between the effects of passaging and chronic iAs exposure individually and corroborate our previously published data on effects of iAs exposure compared with unexposed passage matched HaCaT cells. In addition, this work provides a template for cell line-based longitudinal chronic exposure studies to follow for optimal efficacy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2022
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24. Isolation of cancer stem cells from skin squamous cell carcinoma.
- Author
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Joshi P, Ghadi DS, and Waghmare SK
- Subjects
- 9,10-Dimethyl-1,2-benzanthracene adverse effects, Animals, Carcinogenesis, Carcinogens, Disease Models, Animal, Humans, Mice, Neoplastic Stem Cells pathology, Tetradecanoylphorbol Acetate adverse effects, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell complications, Carcinoma, Squamous Cell genetics, Papilloma chemically induced, Papilloma pathology, Skin Neoplasms chemically induced, Skin Neoplasms genetics
- Abstract
Skin squamous cell carcinoma (skin SCC) is the most frequently occurring cancer. Skin is the first line of defense that provides protection from the external environment. Skin consists of epidermis, dermis, and hypodermis. The epidermis comprises of inter-follicular epidermis, hair follicles, sebaceous glands, and sweat glands. Stem cells within these epidermal compartments play crucial role in epidermal regeneration and repair. Various factors such as higher exposure to ultraviolet light (UV) of sun, genetic predisposition, exposure to carcinogens, etc. that give rise to skin cancer. Within the skin SCC, there exists a pool of cancer stem cells (CSCs) that are highly quiescent with self-renewal capacity. Further, isolation and molecular characterization of CSCs would enable to unravel mechanism involved in tumor progression, metastasis, relapse, and resistance to chemotherapeutic agents. To understand the sequential events of carcinogenesis, the two-stage skin carcinogenesis murine model is proposed, which employs the topical application of a chemical carcinogen, DMBA that causes several activating mutations occurring in the genes responsible for cell proliferation and growth. Further, initiation is followed by tumor promotion, which is induced by repeated application of tumor-promoting agent, TPA, which fixes the activating mutations resulting in the formation of a benign papilloma. Subsequently, papilloma further progresses to highly malignant SCC. Here, using the two-stage skin carcinogenesis murine model, we provide a detailed protocol for the isolation of CSCs from murine skin SCC. FACS sorting of CSCs is followed by assays such as invitro-spheroid assay, in vivo-tumorigenesis-limiting dilution and in vivo-tumorigenesis-serial transplantation assay and expression profiling., Competing Interests: Disclosures P.J., D.S.G. and S.K.W. have no conflicts of interest to disclose. P.J. and D.S.G. supported by ACTREC fellowship. The work was funded by Department of Biotechnology, India., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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25. Management of immune-related adverse events in anti-PD-1-treated patients with advanced cutaneous squamous cell carcinoma.
- Author
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Gambichler T, Scheel CH, Reuther J, and Susok L
- Subjects
- Humans, Immune Checkpoint Inhibitors, Immunosuppression Therapy, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy, Organ Transplantation, Skin Neoplasms drug therapy
- Abstract
Immune checkpoint inhibitors (ICI) have shown very promising results in the management of patients with inoperable or metastatic cutaneous squamous cell carcinoma (cSCC). However, ICI can cause a range of immune-related adverse events (irAEs) affecting a multitude of organs including skin, gastrointestinal tract, endocrine system, heart, lung, kidneys and the nervous system. In principle, clinical management irAEs does not change significantly with respect to the kind of cancer treated with ICI. However, advanced cSCC typically occurs in a clinically challenging patient population typically presenting with advanced age and/or significant comorbidities such as immunosuppression due to haematological malignancies and their respective treatment. Moreover, many patients with advanced cSCC are organ transplant patients taking immunosuppressants. As a consequence use of ICI per se and management of ICI-induced irAEs generates more complexity and difficulties in patients with cSCC compared to other entities. Here, we provide a brief review on the management of anti-programmed cell death protein 1-induced irAEs in patients with cSCC focusing on the characteristic clinical challenges present in this population., (© 2021 European Academy of Dermatology and Venereology.)
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- 2022
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26. BASAL CELL CARCINOMA AND SQUAMOUS CELL CARCINOMA IN A PATIENT TREATED WITH FINGOLIMOD FOR MULTIPLE SCLEROSIS - A CASE REPORT AND LITERATURE REVIEW.
- Author
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Zięba N, Gębka-Kępińska B, and Sowa P
- Subjects
- Aged, Fingolimod Hydrochloride adverse effects, Humans, Immunosuppressive Agents adverse effects, Male, Neoplasm Recurrence, Local drug therapy, Carcinoma, Basal Cell, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy, Skin Neoplasms chemically induced, Skin Neoplasms drug therapy
- Abstract
Objective: The aim: Multiple sclerosis (MS) is a disease of the central nervous system (CNS) characterized by inflammation and demyelination, which leads to chronic progressive disability. Fingolimod is the first registered oral disease-modifying drug (DMD) approved for the treatment of highly active relapsing-remitting multiple sclerosis (RRMS). Fingolimod statistically significantly reduced the number of relapses, clinical and radiological disease activity and disability progression. However, fingolimod can be associated with an increased risk of cancer. This study is aimed to underline how important is regular specialist follow-up during fingolimod therapy., Patients and Methods: Materials and methods: The literature review was conducted using the key words: "fingolimod", "multiple sclerosis", "fingolimod and cancer", "relapsing-remitting multiple sclerosis", "fingolimod adverse effects", "basal cell carcinoma fingolimod", "squamous cell carcinoma fingolimod". The study is based on the case report of a 67-year-old male patient with metachronous skin cancer treated with fingolimod. The drug had an influence on the inhibition of clinical and radiological activity of the disease. Despite the control of the underlying disease, skin cancers occurred during treatment. Basal cell carcinoma and squamous cell carcinoma were diagnosed at an early stage when complete resection was possible and negative (R0) margin resection was achieved., Conclusion: Conclusions: Dermatological examination should be performed at the beginning and during treatment with fingolimod. Patients need to be informed about the risk of malignancy. Patient education are crucial during treatment, which allows achieving a good therapeutic effect, thus minimizing the risk of malignancy and enabling its early detection and cure.
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- 2022
27. Increased Expression of Flightless I in Cutaneous Squamous Cell Carcinoma Affects Wnt/β-Catenin Signaling Pathway.
- Author
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Yang GN, Strudwick XL, Bonder CS, Kopecki Z, and Cowin AJ
- Subjects
- Animals, Carcinoma, Squamous Cell chemically induced, Cell Line, Tumor, Cell Proliferation, Disease Models, Animal, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Humans, Methylcholanthrene adverse effects, Mice, Skin Neoplasms chemically induced, Carcinoma, Squamous Cell genetics, Microfilament Proteins genetics, Skin Neoplasms genetics, Trans-Activators genetics, Up-Regulation, Wnt Signaling Pathway
- Abstract
Cutaneous squamous cell carcinoma (cSCC) accounts for 25% of cutaneous malignancies diagnosed in Caucasian populations. Surgical removal in combination with radiation and chemotherapy are effective treatments for cSCC. Nevertheless, the aggressive metastatic forms of cSCC still have a relatively poor patient outcome. Studies have linked actin cytoskeletal dynamics and the Wnt/β-catenin signaling pathway as important modulators of cSCC pathogenesis. Previous studies have also shown that the actin-remodeling protein Flightless (Flii) is a negative regulator of cSCC. The aim of this study was to investigate if the functional effects of Flii on cSCC involve the Wnt/β-catenin signaling pathway. Flii knockdown was performed using siRNA in a human late stage aggressive metastatic cSCC cell line (MET-1) alongside analysis of Flii genetic murine models of 3-methylcholanthrene induced cSCC. Flii was increased in a MET-1 cSCC cell line and reducing Flii expression led to fewer PCNA positive cells and a concomitant reduction in cellular proliferation and symmetrical division. Knockdown of Flii led to decreased β-catenin and a decrease in the expression of the downstream effector of β-catenin signaling protein SOX9. 3-Methylcholanthrene (MCA)-induced cSCC in Flii overexpressing mice showed increased markers of cancer metastasis including talin and keratin-14 and a significant increase in SOX9 alongside a reduction in Flii associated protein (Flap-1). Taken together, this study demonstrates a role for Flii in regulating proteins involved in cSCC proliferation and tumor progression and suggests a potential role for Flii in aggressive metastatic cSCC.
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- 2021
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28. Chemopreventive Role of Black Tea Extract in Swiss Albino Mice Exposed to Inorganic Arsenic.
- Author
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Ghosh A, Mukherjee S, and Roy M
- Subjects
- Animals, Antioxidants pharmacology, Arsenic Poisoning complications, Carcinoma, Squamous Cell chemically induced, DNA Damage drug effects, Disease Models, Animal, Mice, Reactive Oxygen Species metabolism, Skin Neoplasms chemically induced, Arsenic Poisoning drug therapy, Arsenicals, Carcinoma, Squamous Cell prevention & control, Plant Extracts pharmacology, Skin Neoplasms prevention & control, Tea
- Abstract
Objective: Chronic exposure to inorganic arsenic (iAs) may cause a number of health problems including skin cancer. Present study is aimed to look into the potential of black tea extract (BTE) to prevent the development of skin carcinoma in Swiss albino mice., Methods: The study was done on Swiss albino mice, chronically exposed to inorganic arsenic. 150 mice were housed in different cages, 5 in each cage. The control mice did not receive any treatment. Mice were sacrificed at 30, 90, 180, 270 and 330 days. Development of carcinogenesis was assessed by histological studies. Generation of Reactive Oxygen Species (ROS) and Reactive Oxygen Species (RNS) were estimated using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and Greiss reagent respectively, and their consequences on DNA (by Micronuclei and Comet assay), protein (by protein carbonyl assay kit) and lipid (by lipid peroxidation) were estimated. Activity of antioxidant enzymes, along with total antioxidant capacity were measured by respective kits. Repair percentage was obtained by Comet assay. Western blotting was employed to study the expression of repair enzymes and expression of cytokines. Sandwich Enzyme-linked Immunosorbent Assay (ELISA) technique was employed to study the activity of various cytokines., Results: At 330 days, invasive squamous cell carcinoma of the skin developed. With increasing time generation of ROS and RNS increased, causing damage to DNA, protein and lipid. Antioxidant defence system gets repressed with time. Capacity to repair the DNA damage is inhibited by iAs, due to alteration in repair enzymes - XRCC I, DNA Ligase I, PARP I, ERCC1, ERCC2, XPA, DNA Ligase IV, DNA PKc and Ku-70. Another consequence of iAs exposure is chronic inflammation due to disrupted cytokine level. Intervention with BTE reverses these deleterious effects, preventing development of skin carcinogenesis.
- Published
- 2021
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29. Nobiletin-loaded composite penetration enhancer vesicles restore the normal miRNA expression and the chief defence antioxidant levels in skin cancer.
- Author
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Bayoumi M, Arafa MG, Nasr M, and Sammour OA
- Subjects
- Animals, Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic pharmacology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Cell Line, Tumor, Drug Carriers chemistry, Drug Compounding, Flavones chemistry, Flavones pharmacology, Gene Expression Regulation, Neoplastic drug effects, Humans, Inhibitory Concentration 50, Male, Mice, Particle Size, Skin Neoplasms chemically induced, Skin Neoplasms genetics, Xenograft Model Antitumor Assays, Anthracenes adverse effects, Antineoplastic Agents, Phytogenic administration & dosage, Carcinoma, Squamous Cell drug therapy, Flavones administration & dosage, MicroRNAs genetics, Piperidines adverse effects, Skin Neoplasms drug therapy
- Abstract
Skin cancer is one of the most dangerous diseases, leading to massive losses and high death rates worldwide. Topical delivery of nutraceuticals is considered a suitable approach for efficient and safe treatment of skin cancer. Nobiletin; a flavone occurring in citrus fruits has been reported to inhibit proliferation of carcinogenesis since 1990s, is a promising candidate in this regard. Nobiletin was loaded in various vesicular systems to improve its cytotoxicity against skin cancer. Vesicles were prepared using the thin film hydration method, and characterized for particle size, zeta potential, entrapment efficiency, TEM, ex-vivo skin deposition and physical stability. Nobiletin-loaded composite penetration enhancer vesicles (PEVs) and composite transfersomes exhibited particle size 126.70 ± 11.80 nm, 110.10 ± 0.90 nm, zeta potential + 6.10 ± 0.40 mV, + 9.80 ± 2.60 mV, entrapment efficiency 93.50% ± 3.60, 95.60% ± 1.50 and total skin deposition 95.30% ± 3.40, 100.00% ± 2.80, respectively. These formulations were selected for cytotoxicity study on epidermoid carcinoma cell line (A431). Nobiletin-loaded composite PEVs displayed the lowest IC
50 value, thus was selected for the in vivo study, where it restored skin condition in DMBA induced skin carcinogenesis mice, as delineated by histological and immuno-histochemical analysis, biochemical assessment of skin oxidative stress biomarkers, in addition to miRNA21 and miRNA29A. The outcomes confirmed that nobiletin- loaded composite PEVs is an efficient delivery system combating skin cancer., (© 2021. The Author(s).)- Published
- 2021
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30. Increased cutaneous squamous cell carcinoma risk with hydrochlorothiazide use: is there a safe alternative?
- Author
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Hollestein LM and Arnspang Pedersen S
- Subjects
- Case-Control Studies, Humans, Hydrochlorothiazide adverse effects, Carcinoma, Basal Cell, Carcinoma, Squamous Cell chemically induced, Skin Neoplasms chemically induced
- Published
- 2021
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31. Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer.
- Author
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Banerjee M, Ferragut Cardoso A, Al-Eryani L, Pan J, Kalbfleisch TS, Srivastava S, Rai SN, and States JC
- Subjects
- Carcinogenesis chemically induced, Carcinogenesis genetics, Cell Culture Techniques, Humans, RNA, Messenger genetics, Arsenic toxicity, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, MicroRNAs genetics, MicroRNAs metabolism, Skin Neoplasms chemically induced, Skin Neoplasms genetics, Skin Neoplasms pathology
- Abstract
Chronic arsenic exposure causes skin cancer, although the underlying molecular mechanisms are not well defined. Altered microRNA and mRNA expression likely play a pivotal role in carcinogenesis. Changes in genome-wide differential expression of miRNA and mRNA at 3 strategic time points upon chronic sodium arsenite (As
3+ ) exposure were investigated in a well-validated HaCaT cell line model of arsenic-induced cutaneous squamous cell carcinoma (cSCC). Quadruplicate independent HaCaT cell cultures were exposed to 0 or 100 nM As3+ for up to 28-weeks (wk). Cell growth was monitored throughout the course of exposure and epithelial-mesenchymal transition (EMT) was examined employing immunoblot. Differentially expressed miRNA and mRNA profiles were generated at 7, 19, and 28-wk by RNA-seq, followed by identification of differentially expressed mRNA targets of differentially expressed miRNAs through expression pairing at each time point. Pathway analyses were performed for total differentially expressed mRNAs and for the miRNA targeted mRNAs at each time point. RNA-seq predictions were validated by immunoblot of selected target proteins. While the As3+ -exposed cells grew slower initially, growth was equal to that of unexposed cells by 19-wk (transformation initiation), and exposed cells subsequently grew faster than passage-matched unexposed cells. As3+ -exposed cells had undergone EMT at 28-wk. Pathway analyses demonstrate dysregulation of carcinogenesis-related pathways and networks in a complex coordinated manner at each time point. Immunoblot data largely corroborate RNA-seq predictions in the endoplasmic reticulum stress (ER stress) pathway. This study provides a detailed molecular picture of changes occurring during the arsenic-induced transformation of human keratinocytes.- Published
- 2021
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32. Loss of DLX3 tumor suppressive function promotes progression of SCC through EGFR-ERBB2 pathway.
- Author
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Bajpai D, Mehdizadeh S, Uchiyama A, Inoue Y, Sawaya A, Overmiller A, Brooks SR, Hasneen K, Kellett M, Palazzo E, Motegi SI, Yuspa SH, Cataisson C, and Morasso MI
- Subjects
- Aged, Animals, Carcinogens toxicity, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Disease Models, Animal, ErbB Receptors genetics, ErbB Receptors metabolism, Female, Homeodomain Proteins metabolism, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoplasm Grading, Receptor, ErbB-2 genetics, Signal Transduction, Skin Neoplasms chemically induced, Skin Neoplasms genetics, Skin Neoplasms metabolism, Survival Rate, Tetradecanoylphorbol Acetate toxicity, Transcription Factors metabolism, 9,10-Dimethyl-1,2-benzanthracene toxicity, Carcinoma, Squamous Cell pathology, Homeodomain Proteins genetics, Receptor, ErbB-2 metabolism, Skin Neoplasms pathology, Transcription Factors genetics
- Abstract
Cutaneous squamous cell carcinoma (cSCC) ranks second in the frequency of all skin cancers. The balance between keratinocyte proliferation and differentiation is disrupted in the pathological development of cSCC. DLX3 is a homeobox transcription factor which plays pivotal roles in embryonic development and epidermal homeostasis. To investigate the impact of DLX3 expression on cSCC prognosis, we carried out clinicopathologic analysis of DLX3 expression which showed statistical correlation between tumors of higher pathologic grade and levels of DLX3 protein expression. Further, Kaplan-Meier survival curve analysis demonstrated that low DLX3 expression correlated with poor patient survival. To model the function of Dlx3 in skin tumorigenesis, a two-stage dimethylbenzanthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA) study was performed on mice genetically depleted of Dlx3 in skin epithelium (Dlx3cKO). Dlx3cKO mice developed significantly more tumors, with more rapid tumorigenesis compared to control mice. In Dlx3cKO mice treated only with DMBA, tumors developed after ~16 weeks suggesting that loss of Dlx3 has a tumor promoting effect. Whole transcriptome analysis of tumor and skin tissue from our mouse model revealed spontaneous activation of the EGFR-ERBB2 pathway in the absence of Dlx3. Together, our findings from human and mouse model system support a tumor suppressive function for DLX3 in skin and underscore the efficacy of therapeutic approaches that target EGFR-ERBB2 pathway.
- Published
- 2021
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33. Arsenical Squamous Cell Carcinoma.
- Author
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Panigrahi A, Chakraborty S, and Sil A
- Subjects
- Back, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell pathology, Hand, Humans, Male, Middle Aged, Skin Neoplasms chemically induced, Skin Neoplasms pathology, Arsenic Poisoning complications, Carcinoma, Squamous Cell diagnosis, Skin Neoplasms diagnosis
- Published
- 2021
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- View/download PDF
34. Multiple eruptive squamous cell carcinomas: a possible clinical sign in melanoma patients treated with vemurafenib.
- Author
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Jovic A, Tiodorovic D, Popovic D, Vidovic N, Zlatanovic Z, Cekic S, Kocic H, and Damiani G
- Subjects
- Brain Neoplasms secondary, Female, Humans, Keratoacanthoma chemically induced, Melanoma genetics, Melanoma secondary, Middle Aged, Proto-Oncogene Proteins B-raf genetics, Skin Neoplasms genetics, Skin Neoplasms pathology, Antineoplastic Agents adverse effects, Brain Neoplasms drug therapy, Carcinoma, Squamous Cell chemically induced, Melanoma drug therapy, Skin Neoplasms drug therapy, Vemurafenib adverse effects
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- 2021
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35. Association between hydrochlorothiazide and the risk of in situ and invasive squamous cell skin carcinoma and basal cell carcinoma: A population-based case-control study.
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Adalsteinsson JA, Muzumdar S, Waldman R, Hu C, Wu R, Ratner D, Ungar J, Silverberg JI, Olafsdottir GH, Kristjansson AK, Tryggvadottir L, and Jonasson JG
- Subjects
- Aged, Aged, 80 and over, Carcinogenesis drug effects, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell pathology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell pathology, Case-Control Studies, Female, Humans, Hypertension drug therapy, Iceland epidemiology, Male, Middle Aged, Risk Factors, Skin drug effects, Skin pathology, Skin Neoplasms chemically induced, Skin Neoplasms pathology, Time Factors, Antihypertensive Agents adverse effects, Carcinoma, Basal Cell epidemiology, Carcinoma, Squamous Cell epidemiology, Hydrochlorothiazide adverse effects, Skin Neoplasms epidemiology
- Abstract
Background: Population-based studies analyzing hydrochlorothiazide's (HCTZ's) effect on keratinocyte carcinoma, and particularly invasive squamous cell carcinoma (SCC), are lacking., Objectives: To characterize the association between HCTZ use and invasive SCC, SCC in situ (SCCis), and basal cell carcinoma (BCC)., Methods: This population-based case-control study included all 6880 patients diagnosed with first-time BCC, SCCis, and invasive SCC between 2003 and 2017 in Iceland and 69,620 population controls. Conditional logistic regression analyses were used to calculate multivariate odds ratios (ORs) for keratinocyte carcinoma associated with HCTZ use., Results: A cumulative HCTZ dose above 37,500 mg was associated with increased risk of invasive SCC (OR, 1.69; 95% confidence interval [CI], 1.04-2.74). Users of HCTZ also had an increased risk of SCCis (OR, 1.24; 95% CI, 1.01-1.52) and BCC (OR, 1.14; 95% CI, 1.02-1.29)., Limitations: Limitations include this study's retrospective nature with the resulting inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities., Conclusions: High cumulative exposure to HCTZ is associated with the development of keratinocyte carcinoma and, most importantly, invasive SCC. Sun protective behaviors alone may not eliminate the carcinogenic potential of HCTZ., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
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- 2021
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36. Risk of Nonmelanoma Skin Cancer in Association With Use of Hydrochlorothiazide-Containing Products in the United States.
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Eworuke E, Haug N, Bradley M, Cosgrove A, Zhang T, Dee EC, Adimadhyam S, Petrone A, Lee H, Woodworth T, and Toh S
- Subjects
- Adult, Age Factors, Aged, Angiotensin-Converting Enzyme Inhibitors administration & dosage, Angiotensin-Converting Enzyme Inhibitors adverse effects, Antihypertensive Agents administration & dosage, Carcinoma, Basal Cell epidemiology, Carcinoma, Basal Cell ethnology, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell ethnology, Dose-Response Relationship, Drug, Female, Humans, Hydrochlorothiazide administration & dosage, Incidence, Male, Middle Aged, Photosensitizing Agents administration & dosage, Propensity Score, Proportional Hazards Models, Racial Groups statistics & numerical data, Retrospective Studies, Risk Factors, Sex Factors, Skin Neoplasms epidemiology, Skin Neoplasms ethnology, Ultraviolet Rays, United States epidemiology, United States ethnology, White People, Antihypertensive Agents adverse effects, Carcinoma, Basal Cell chemically induced, Carcinoma, Squamous Cell chemically induced, Hydrochlorothiazide adverse effects, Photosensitizing Agents adverse effects, Skin Neoplasms chemically induced
- Abstract
Background: European studies reported an increased risk of nonmelanoma skin cancer associated with hydrochlorothiazide (HCTZ)-containing products. We examined the risks of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) associated with HCTZ compared with angiotensin-converting enzyme inhibitors (ACEIs) in a US population., Methods: We conducted a retrospective cohort study in the US Food and Drug Administration's Sentinel System. From the date of HCTZ or ACEI dispensing, patients were followed until a SCC or BCC diagnosis requiring excision or topical chemotherapy treatment on or within 30 days after the diagnosis date or a censoring event. Using Cox proportional hazards regression models, we estimated the hazard ratios (HRs), overall and separately by age, sex, and race. We also examined site- and age-adjusted incidence rate ratios (IRRs) by cumulative HCTZ dose within the matched cohort., Results: Among 5.2 million propensity-score matched HCTZ and ACEI users, the incidence rate (per 1000 person-years) of BCC was 2.78 and 2.82, respectively, and 1.66 and 1.60 for SCC. Overall, there was no difference in risk between HCTZ and ACEIs for BCC (HR = 0.99, 95% confidence interval [CI] = 0.97 to 1.00), but there was an increased risk for SCC (HR = 1.04, 95% CI = 1.02 to 1.06). HCTZ use was associated with higher risks of BCC (HR = 1.09, 95% CI = 1.07 to 1.11) and SCC (HR = 1.15, 95% CI = 1.12 to 1.17) among Caucasians. Cumulative HCTZ dose of 50 000 mg or more was associated with an increased risk of SCC in the overall population (IRR = 1.19, 95% CI = 1.05 to 1.35) and among Caucasians (IRR = 1.27, 95% CI = 1.10 to 1.47)., Conclusions: Among Caucasians, we identified small increased risks of BCC and SCC with HCTZ compared with ACEI. Appropriate risk mitigation strategies should be taken while using HCTZ., (Published by Oxford University Press 2021.)
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- 2021
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37. Hydroxyurea-induced squamous cell carcinoma.
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Brown H and Lamrock E
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- Aged, 80 and over, Female, Humans, Thrombocytosis drug therapy, Carcinoma, Squamous Cell chemically induced, Hydroxyurea adverse effects, Neoplasms, Multiple Primary chemically induced, Nucleic Acid Synthesis Inhibitors adverse effects, Skin Neoplasms chemically induced
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- 2021
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38. C3 Drives Inflammatory Skin Carcinogenesis Independently of C5.
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Jackson WD, Gulino A, Fossati-Jimack L, Castro Seoane R, Tian K, Best K, Köhl J, Belmonte B, Strid J, and Botto M
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- 9,10-Dimethyl-1,2-benzanthracene administration & dosage, 9,10-Dimethyl-1,2-benzanthracene toxicity, Animals, Carcinogens administration & dosage, Carcinogens toxicity, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell pathology, Complement Activation genetics, Complement Activation immunology, Complement C3 genetics, Complement C5 metabolism, Complement Membrane Attack Complex metabolism, Disease Models, Animal, Disease Progression, Humans, Mice, Mice, Knockout, Mice, Transgenic, Neoplasms, Experimental blood, Neoplasms, Experimental chemically induced, Neoplasms, Experimental pathology, Receptor, Anaphylatoxin C5a genetics, Receptor, Anaphylatoxin C5a metabolism, Receptors, Complement genetics, Receptors, Complement metabolism, Signal Transduction genetics, Signal Transduction immunology, Skin drug effects, Skin immunology, Skin pathology, Skin Neoplasms chemically induced, Skin Neoplasms pathology, Tumor Escape, Carcinoma, Squamous Cell immunology, Complement C3 metabolism, Neoplasms, Experimental immunology, Skin Neoplasms immunology
- Abstract
Nonmelanoma skin cancer such as cutaneous squamous cell carcinoma (cSCC) is the most common form of cancer and can occur as a consequence of DNA damage to the epithelium by UVR or chemical carcinogens. There is growing evidence that the complement system is involved in cancer immune surveillance; however, its role in cSCC remains unclear. Here, we show that complement genes are expressed in tissue from patients with cSCC, and C3 activation fragments are present in cSCC biopsies, indicating complement activation. Using a range of complement-deficient mice in a two-stage mouse model of chemically-induced cSCC, where a subclinical dose of 7,12-dimethylbenz[a]anthracene causes oncogenic mutations in epithelial cells and 12-O-tetradecanoylphorbol-13-acetate promotes the outgrowth of these cells, we found that C3-deficient mice displayed a significantly reduced tumor burden, whereas an opposite phenotype was observed in mice lacking C5aR1, C5aR2, and C3a receptor. In addition, in mice unable to form the membrane attack complex, the tumor progression was unaltered. C3 deficiency did not affect the cancer response to 7,12-dimethylbenz[a]anthracene treatment alone but reduced the epidermal hyperplasia during 12-O-tetradecanoylphorbol-13-acetate-induced inflammation. Collectively, these data indicate that C3 drives tumorigenesis during chronic skin inflammation, independently of the downstream generation of C5a or membrane attack complex., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2021
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39. Methotrexate Use for Patients with Psoriasis and Risk of Cutaneous Squamous Cell Carcinoma: A Nested Case-control Study.
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Giannopoulos F, Gillstedt M, Laskowski M, Bruun Kristensen K, and Polesie S
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- Case-Control Studies, Humans, Methotrexate adverse effects, Sweden epidemiology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Psoriasis chemically induced, Psoriasis diagnosis, Psoriasis drug therapy, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology
- Abstract
An association between methotrexate use and risk of cutaneous squamous cell carcinoma has been reported in patients with rheumatoid and psoriatic arthritis. A nested case-control study was performed to investigate if methotrexate use among patients with psoriasis was associated with increased risk of cutaneous squamous cell carcinoma. Data were obtained from Swedish registers and included 623 patients with psoriasis and a first cutaneous squamous cell carcinoma from 2010 to 2016. Ten randomly selected patients with psoriasis were matched on age and sex to each case. Among cases, 160 (26%) were ever-users of metho-trexate. The corresponding number among the controls was 1,370 (22%), yielding an unadjusted odds ratio (OR) of 1.23 (95% confidence interval (95% CI) 1.02-1.49); p = 0.034. After adjusting for use of other immunosuppressive drugs the association was close to unity (OR 1.09; 95% CI 0.89-1.34); p = 0.39. The slightly increased risk of cutaneous squamous cell carcinoma associated with methotrexate-exposure in patients with psoriasis does not seem to be associated with metho-trexate, but rather with disease severity, other anti-psoriatic treatments, and ultraviolet exposure.
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- 2021
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40. Development of cutaneous squamous cell carcinoma during pembrolizumab therapy.
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Mizutani K, Nakanishi T, Ikejiri M, Yuasa H, Matsushima Y, Kondo M, Nakai Y, Habe K, Nakatani K, and Yamanaka K
- Subjects
- Antibodies, Monoclonal, Humanized adverse effects, Humans, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy, Skin Neoplasms chemically induced, Skin Neoplasms drug therapy
- Published
- 2021
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41. Association between Use of Hydrochlorothiazide and Risk of Keratinocyte Cancers in Kidney Transplant Recipients.
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Letellier T, Leborgne F, Kerleau C, Gaultier A, Dantal J, and Ville S
- Subjects
- Adult, Age Factors, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell diagnosis, Carcinoma, Basal Cell epidemiology, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell epidemiology, Databases, Factual, Female, France, Humans, Immunosuppressive Agents adverse effects, Incidence, Male, Middle Aged, Risk Assessment, Risk Factors, Sex Factors, Skin Neoplasms diagnosis, Skin Neoplasms epidemiology, Skin Pigmentation, Time Factors, Carcinoma, Squamous Cell chemically induced, Diuretics adverse effects, Hydrochlorothiazide adverse effects, Kidney Transplantation adverse effects, Pancreas Transplantation adverse effects, Skin Neoplasms chemically induced
- Abstract
Background and Objectives: Keratinocyte cancers, which primarily comprise squamous cell carcinomas and basal cell carcinomas, represent a major concern and potential risk for kidney transplant recipients. Hydrochlorothiazide, a diuretic widely used to treat hypertension, has been implicated in skin photosensitivity reaction. Recent studies conducted in the general population have found that hydrochlorothiazide use is associated with a higher risk of keratinocyte cancer, especially squamous cell carcinomas. High-risk groups, however, including transplant recipients were excluded from these. Our aim was to investigate whether hydrochlorothiazide use was associated with keratinocyte cancer in kidney transplant recipients on immunosuppressive therapy., Design, Setting, Participants, & Measurements: In a single-center cohort of kidney ( n =2155), combined kidney-pancreas ( n =282), and pancreas ( n =59) transplant recipients from the Données Informatisées VAlidées Transplantation (DIVAT) database transplanted between 2000 and 2017 in Nantes, France, we evaluated the association between hydrochlorothiazide exposure and keratinocyte cancers. Multivariable cause-specific, time-varying Cox models were used to estimate the relationship between hydrochlorothiazide exposure and the hazard of squamous cell carcinoma and basal cell carcinoma, with hydrochlorothiazide designated as the time-dependent variable., Results: Among the participants, 279 of 2496 (11%) were exposed to hydrochlorothiazide after the transplantation. Cumulative incidence rates of keratinocyte cancer by 10 and 15 years were 7% and 9% for squamous cell carcinomas, respectively, and 8% and 11% for basal cell carcinomas, respectively. We found a relationship between exposure to hydrochlorothiazide and the risk of squamous cell carcinomas (hazard ratio, 2.04; 95% confidence interval, 1.27 to 3.28). In contrast, we found no association between hydrochlorothiazide exposure and basal cell carcinomas (hazard ratio, 0.63; 95% confidence interval, 0.35 to 1.15)., Conclusions: In a single-center cohort of kidney, combined kidney-pancreas, and pancreas transplant recipients, exposure to hydrochlorothiazide was associated with a two-fold higher risk of squamous cell carcinoma and no higher risk of basal cell carcinoma., (Copyright © 2020 by the American Society of Nephrology.)
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- 2020
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42. In Brief: Hydrochlorothiazide and skin cancer.
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- Drug Labeling, Humans, Risk, Antihypertensive Agents adverse effects, Carcinoma, Basal Cell chemically induced, Carcinoma, Squamous Cell chemically induced, Hydrochlorothiazide adverse effects, Skin Neoplasms chemically induced
- Published
- 2020
43. The incidence of cutaneous squamous cell carcinoma in patients receiving voriconazole therapy for chronic pulmonary aspergillosis.
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Kosmidis C, Mackenzie A, Harris C, Hashad R, Lynch F, and Denning DW
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell epidemiology, Chronic Disease, England epidemiology, Female, Humans, Incidence, Male, Middle Aged, Pulmonary Aspergillosis diagnosis, Pulmonary Aspergillosis microbiology, Retrospective Studies, Risk Assessment, Risk Factors, Skin Neoplasms diagnosis, Skin Neoplasms epidemiology, Time Factors, Treatment Outcome, Young Adult, Antifungal Agents adverse effects, Carcinoma, Squamous Cell chemically induced, Pulmonary Aspergillosis drug therapy, Skin Neoplasms chemically induced, Voriconazole adverse effects
- Abstract
Voriconazole has been associated with cutaneous squamous cell carcinoma (cSCC) in transplant patients but less is known about the risk in less severely immunosuppressed patients. Our aim was to estimate the incidence of cSCC after voriconazole exposure in patients with chronic pulmonary aspergillosis on a background of chronic lung disease. The notes of patients seen at a tertiary referral centre from 2009 to 2019 with chronic pulmonary aspergillosis were reviewed for the diagnosis of cSCC and voriconazole use documented. Among 1111 patients, 668 (60.1%) received voriconazole for longer than 28 days. Twelve patients received a diagnosis of cSCC; nine had used voriconazole. Mean duration of voriconazole use was 36.7 months. The crude incidence rate was 4.88 in 1000 person/years in those who had voriconazole and 2.79 in 1000 patient/years in those who did not receive voriconazole for longer than 28 days. On Cox regression, age (HR 1.09, 95% CI 1.02-1.16, p = 0.01) and male gender (HR 3.97, 95% CI 0.84-18.90, p = 0.082) were associated with cSCC. Voriconazole use was associated with a slightly increased risk, which was not significant (HR 1.35, 95% CI 0.35-5.20, p = 0.659). Voriconazole use beyond 28 days did not lead to a significantly increased risk of cSCC in a large cohort of patients with chronic pulmonary aspergillosis.
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- 2020
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44. The association of metformin use with keratinocyte carcinoma development in high-risk patients.
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Misitzis A, Stratigos AJ, Beatson M, Mastorakos G, Dellavalle RP, and Weinstock MA
- Subjects
- Humans, Keratinocytes, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell epidemiology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Metformin adverse effects, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology
- Abstract
Keratinocyte carcinoma (KC) is the most common malignancy in white skinned populations. Metformin one of the most commonly prescribed drugs and has been reported to protect against solid cancers. The association between metformin and KC has not been studied in patients at high risk for a subsequent KC. The purpose of this study is to evaluate the association between metformin and KC development in high-risk patients. We performed a secondary analysis of patients enrolled in the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial to compare risk for KC development between metformin users and non-users. Metformin-users compared to non-users had a significantly lower risk for squamous cell carcinoma with an adjusted Hazard ratio (HR): 0.45, (CI: 0.24-0.84, P < .01) and basal cell carcinoma (HR: 0.70, CI: 0.49-0.97, P < .03). Patients at high risk might benefit from metformin use against a subsequent KC., (© 2020 Wiley Periodicals LLC.)
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- 2020
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45. Possible Roles of Proinflammatory Signaling in Keratinocytes Through Aryl Hydrocarbon Receptor Ligands for the Development of Squamous Cell Carcinoma.
- Author
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Sato Y, Fujimura T, Hidaka T, Lyu C, Tanita K, Matsushita S, Yamamoto M, and Aiba S
- Subjects
- Animals, Anthracenes toxicity, Carbazoles toxicity, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Cytokines genetics, Cytokines immunology, Humans, Inflammation chemically induced, Inflammation genetics, Inflammation immunology, Inflammation pathology, Keratinocytes pathology, Mice, Mice, Inbred BALB C, Mice, Transgenic, Neoplasm Proteins genetics, Piperidines toxicity, Receptors, Aryl Hydrocarbon genetics, Signal Transduction drug effects, Skin Neoplasms chemically induced, Skin Neoplasms genetics, Skin Neoplasms pathology, Carcinoma, Squamous Cell immunology, Keratinocytes immunology, Neoplasm Proteins immunology, Receptors, Aryl Hydrocarbon immunology, Signal Transduction immunology, Skin Neoplasms immunology
- Abstract
Aryl hydrocarbon receptor (AhR) provides a deeper insight into the pathogenesis of cutaneous squamous cell carcinoma (cSCC). AhR ligands, such as 6-formylindolo[3,2-b] carbazole (FICZ), and 7,12-Dimethylbenz[a]anthracene (DMBA), constitute major substrates for the cytochrome P450 (CYP) family, and influence the expression of various cytokine genes, including IL-17 and IL-23 -related genes via the AhR. On the other hand, proinflammatory cytokines could drive tumor progression through the TRAF-ERK5 signaling pathway in cSCC. From the above findings, we hypothesized that AhR ligands might enhance the mRNA expression of proinflammatory cytokines via the AhR, leading to the development of cSCC. The purpose of this study was to investigate (1) the immunomodulatory effects of FICZ and DMBA on normal human keratinocytes (NHKCs), focusing on IL-17, and related cytokines/chemokines (IL-23, IL-36γ, and CCL20), (2) the expression of these factors in AhR-dependent pathways using a two-stage chemically induced skin carcinogenesis mouse model, and (3) the expression of these factors in lesion-affected skin in cSCC. Both FICZ and DMBA augmented the expression of CYP1A1, p19, CCL20, and IL-36γ mRNA in NHKCs in vitro . Moreover, the mRNA expression of these proinflammatory factors, as well as IL-17, in mouse cSCC is significantly decreased in the AhR-(fl/fl) Krt5-(Cre) mice compared to wild type mice, leading to a decrease in the number of developed cSCC lesions. Furthermore, CCL20, IL-23, as well as IL-17, are detected in the lesion-affected skin of cSCC patients. Our study demonstrates a possible mechanism for the development of cSCC involving AhR-mediated signaling by epidermal keratinocytes and recruitment of Th17 cells., (Copyright © 2020 Sato, Fujimura, Hidaka, Lyu, Tanita, Matsushita, Yamamoto and Aiba.)
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- 2020
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46. Association Between Topical Calcineurin Inhibitor Use and Keratinocyte Carcinoma Risk Among Adults With Atopic Dermatitis.
- Author
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Asgari MM, Tsai AL, Avalos L, Sokil M, and Quesenberry CP Jr
- Subjects
- Adult, Aged, Calcineurin Inhibitors administration & dosage, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell pathology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell pathology, Female, Follow-Up Studies, Glucocorticoids administration & dosage, Humans, Incidence, Keratinocytes drug effects, Keratinocytes pathology, Male, Middle Aged, Product Surveillance, Postmarketing statistics & numerical data, Retrospective Studies, Risk Assessment statistics & numerical data, Skin Neoplasms chemically induced, Skin Neoplasms pathology, Calcineurin Inhibitors adverse effects, Carcinoma, Basal Cell epidemiology, Carcinoma, Squamous Cell epidemiology, Dermatitis, Atopic drug therapy, Glucocorticoids adverse effects, Skin Neoplasms epidemiology
- Abstract
Importance: Topical calcineurin inhibitors (TCIs), primarily used to treat atopic dermatitis (AD), carry a black box label warning users about the potential for increased skin cancer risk. The risk associated with keratinocyte carcinoma (KC), the most common cancer, defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), remains poorly defined because findings from large-scale postmarketing surveillance studies have not been reported., Objectives: To examine KC risk overall and by subtype (BCC and SCC) among adults with AD exposed to TCIs compared with those exposed to topical corticosteroids (primary comparator group) and those unexposed to TCIs or topical corticosteroids (alternative comparator group) as well as alterations in risk with TCI dose, frequency, and duration of exposure., Design, Setting, and Participants: A retrospective cohort study was conducted at Kaiser Permanente Northern California, a large, integrated health care delivery system, of adults 40 years or older (n = 93 746) with a physician-rendered diagnosis of AD or dermatitis. Patients who were diagnosed from January 1, 2002, to December 31, 2013, were included, with follow-up through December 31, 2017. Data analysis was conducted from June 1, 2016, to October 1, 2018., Exposures: Time-varying pharmacy-dispensed TCI exposure (n = 7033) over the study period was compared with topical corticosteroids (n = 73 674) and no TCI or topical corticosteroid exposure (n = 46 141)., Main Outcomes and Measures: Electronic pathologic testing-validated incident KCs (n = 7744)., Results: Among a cohort of 93 746 members, the mean (SD) age was 58.5 (12.7) years, and 55 023 patients (58.7%) were women. Multivariable Cox proportional hazards regression revealed no association between TCI exposure and KC risk (adjusted hazard ratio [aHR], 1.02; 95% CI, 0.93-1.13) compared with topical corticosteroid exposure. Similarly, there were no significant differences in BCC risk (aHR, 1.01; 95% CI, 0.90-1.14, TCI vs topical corticosteroids) or SCC risk (aHR, 0.94; 95% CI, 0.82-1.08, TCI vs topical corticosteroids). Changing the comparator group to unexposed individuals yielded similar findings (aHR, 1.04; 95% CI, 0.91-1.19, TCI vs unexposed for basal cell carcinoma). There were no associations between TCI dose, frequency, and duration of use and BCC, SCC, or overall KC risk., Conclusions and Relevance: The results of this postmarketing surveillance study of adult health plan members with AD revealed no apparent association between TCI exposure and overall KC, BCC, or SCC risk. Secondary analyses examining dose, frequency, and duration of TCI exposure revealed no associations. These findings suggest that use of TCIs may be safe with respect to KC risk among adults with AD.
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- 2020
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47. Morbidity burden in survivors of multiple myeloma who underwent autologous transplantation: A Bone Marrow Transplantation Survivor Study.
- Author
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Arora M, Chen Y, Hageman L, Wu J, Landier W, Francisco L, Kung M, Ness E, Bosworth A, Pamukcuoglu M, Weisdorf DJ, Forman SJ, Armenian SH, and Bhatia S
- Subjects
- Aged, Alabama epidemiology, Carcinoma, Squamous Cell chemically induced, Chronic Disease epidemiology, Cyclophosphamide adverse effects, Female, Follow-Up Studies, Graft Rejection drug therapy, Humans, Immunosuppressive Agents adverse effects, Incidence, Male, Melanoma chemically induced, Middle Aged, Minnesota epidemiology, Morbidity, Risk Factors, Siblings, Skin Neoplasms chemically induced, Transplantation, Autologous, Bone Marrow Transplantation methods, Cancer Survivors, Carcinoma, Squamous Cell epidemiology, Melanoma epidemiology, Multiple Myeloma epidemiology, Multiple Myeloma therapy, Skin Neoplasms epidemiology
- Abstract
Background: Autologous blood or bone marrow transplantation (aBMT) is considered the standard of care for patients with multiple myeloma (MM). Significantly improved survival necessitates an understanding of the morbidity burden borne by the growing survivor population., Methods: The authors evaluated severe and/or life-threatening chronic health conditions (CHCs) and subsequent neoplasms (SNs) in patients with MM who were treated with aBMT using the Bone Marrow Transplant Survivor Study. A total of 630 study participants had undergone aBMT for MM at 1 of 3 BMT centers, had survived ≥2 years after aBMT, and were aged ≥18 years at the time of survey completion. Survivors of aBMT identified 289 nearest-age siblings to constitute an unaffected comparison group. Scoring of CHCs was based on version 5 of the National Cancer Institute Common Terminology Criteria for Adverse Events to determine severity (with grade 3 indicating serious and grade 4 indicating life-threatening)., Results: The 10-year cumulative incidence of any grade 3 to 4 CHC among survivors of aBMT was 57.6 ± 3.2%. Survivors of MM were found to be at 40% higher odds of developing grade 3 to 4 CHCs when compared with siblings (95% confidence interval [95% CI], 1.0-1.9). Among SNs, 96% were solid tumors, yielding a 10-year cumulative incidence of 13.6% ± 2.5%. Pre-aBMT exposure to cyclophosphamide (hazard ratio [HR], 3.5; 95% CI, 1.5-8.1) and immunomodulatory drugs (HR, 3.9; 95% CI, 1.5-10.1) were associated with an increased risk of solid tumors. Melanoma (10-year cumulative incidence: 3.3% ± 1.2%) and squamous cell carcinoma (10-year cumulative incidence: 5.1% ± 1.8%), were the most common SNs. Pre-aBMT exposure to cyclophosphamide (HR, 6.02; 95% CI, 1.4-26.1) and immunomodulatory drugs (HR, 7.9; 95% CI, 0.9-68.5) was associated with an increased risk of melanoma., Conclusions: The 10-year cumulative incidence of severe and/or life-threatening CHCs was found to approach 60% in long-term survivors of MM, with solid SNs constituting a large morbidity burden. The current study has provided evidence supporting the close monitoring of survivors to manage morbidity., (© 2020 American Cancer Society.)
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- 2020
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48. Eruption of squamous cell carcinomas after beginning nilotinib therapy.
- Author
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Crain CB, Winsett FT, Woolridge KF, Wilson JM, and Goodwin BP
- Subjects
- Aged, Carcinoma, Squamous Cell pathology, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Male, Pyrimidines therapeutic use, Skin Neoplasms pathology, Carcinoma, Squamous Cell chemically induced, Protein-Tyrosine Kinases antagonists & inhibitors, Pyrimidines adverse effects, Skin Neoplasms chemically induced
- Abstract
Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between the long arms of chromosomes 9 and 22 leading to the formation of a constitutively active tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are the treatment of choice for patients diagnosed with CML and have many associated side effects including the rarely-reported eruption of squamous cell carcinomas (SCCs). Herein, we report a patient with CML who presented with sudden onset of multiple scaly lesions on his legs and trunk after beginning treatment with nilotinib, a novel TKI. Six biopsies were performed at his initial presentation and four of these lesions were confirmed to be keratoacanthoma-type SCCs. One month later, the patient reported the development of multiple new similar lesions on his legs, arms, and face. Four more biopsies were performed revealing keratoacanthoma-type and well-differentiated SCCs. Certain tyrosine kinase inhibitors such as sorafenib and quizartinib have been reported to cause eruptive keratoacanthoma (KA)-type SCCs as seen in our patient. However, there is only one other report in the literature of nilotinib promoting the development of SCCs or KAs. Physicians should be aware of this potential adverse effect and patients taking nilotinib should be closely monitored by a dermatologist.
- Published
- 2020
49. Hydrochlorothiazide Use and Increased Squamous Cell Carcinoma Burden in a High-Risk Mohs Population: A Cross-Sectional Study.
- Author
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Han S, Wolfe CM, Angnardo L, Pedersen SA, Gaist D, Pottegård A, and Cognetta AB Jr
- Subjects
- Aged, Cross-Sectional Studies, Female, Florida, Humans, Male, Mohs Surgery, Risk, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell surgery, Diuretics adverse effects, Hydrochlorothiazide adverse effects, Skin Neoplasms chemically induced, Skin Neoplasms surgery
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- 2020
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50. Assessing potential mechanisms of arsenic-induced skin lesions and cancers: Human and in vitro evidence.
- Author
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Zeng Q and Zhang A
- Subjects
- Environmental Pollutants toxicity, Humans, Skin drug effects, Arsenic toxicity, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell physiopathology, Skin Neoplasms chemically induced, Skin Neoplasms physiopathology
- Abstract
Environmental exposure to arsenic is a major public health challenge worldwide. In detailing the hallmark signs of chronic arsenic exposure, previous studies have shown that epigenetic and immune dysfunction are associated with arsenic-induced skin lesions; however, knowledge regarding interactions between the mechanisms listed above is limited. In this study, a total of 106 skin samples were collected over the past 20 years. Based on the presence or absence of high arsenic exposure, the participants were divided into arsenic exposure (72) and reference (34) groups. Additionally, the arsenic exposure group was further divided into the non-cancer group (31, including skin hyperpigmentation and hyperkeratosis) and the skin cancer group (41, including Bowen's disease, basal cell carcinoma and squamous cell carcinoma) according to a skin histopathological examination. First, the associations among miR-155, NF-AT1 with immunological dysfunction and arsenic-induced skin lesions and carcinogenesis were confirmed using these skin samples. In the arsenic-exposed group, miR-155-5p, keratin 1(Krt1), keratin 10 (Krt10), and keratin 6c (Krt6c) were significantly increased in the skin (p < 0.05), while NF-AT1, interleukin-2 (IL-2), and interferon-γ (IFN-γ) were significantly decreased (p < 0.05). Clear correlations were observed among these factors (p < 0.05). In immortalized human keratinocytes, silencing and overexpression of NF-AT1 could alter the expression and secretion of immunological dysfunction indicators (IL-2 and IFN-γ) that are induced by arsenic exposure (p < 0.05); however, miR-155-5p levels did not change significantly (p > 0.05). The miR-155-5p mimic and inhibitor could regulate the NF-AT1-mediated immunological dysfunction caused by arsenic (p < 0.05). Our study provides some limited evidence that miR-155-5p regulates the NF-AT1-mediated immunological dysfunction that is involved in the pathogenesis and carcinogenesis of arsenic. The second major finding was that Krt1 and Krt10 are markers of hyperkeratosis caused by arsenic, and Krt6c is a potential biomarker that can reflect arsenic carcinogenesis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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