Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.944
Filtrar
1.
Rev Med Suisse ; 17(720-1): 80-84, 2021 Jan 13.
Artigo em Francês | MEDLINE | ID: mdl-33443836

RESUMO

The main pharmacovigilance updates in 2020 are reviewed. Remdesivir in COVID-19: relatively safe but turns out to be less effective than expected. Hydroxychloroquine in COVID-19 : lack of efficacy and risk of arrhythmias. Cytokines storm in COVID-19: may impact pharmacokinetics. VEGF inhibitors: risk of aneurysm and artery dissection. Tofacitinib: dose-dependant risk of venous thromboembolic events. Ondansetron in the first trimester of pregnancy : a highly debated risk of orofacial cleft defects. Fingolimod : contraindicated during pregnancy due to suspected risk of congenital malformations. Ranitidine: global market withdrawal due to contamination with nitrosamines. Ulipristal for uterine fibroids : market withdrawal due to risk of severe liver injury. Ingenol mebutate : market withdrawal due to paradoxical risk of skin cancers.


Assuntos
Farmacovigilância , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Fenda Labial/prevenção & controle , Contraindicações de Medicamentos , Síndrome da Liberação de Citocina/virologia , Feminino , Cloridrato de Fingolimode/efeitos adversos , Humanos , Hidroxicloroquina/efeitos adversos , Leiomioma/tratamento farmacológico , Norpregnadienos/uso terapêutico , Farmacocinética , Gravidez , Ranitidina/efeitos adversos , Retirada de Medicamento Baseada em Segurança , Neoplasias Cutâneas/induzido quimicamente
2.
Dermatol Online J ; 26(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32815690

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas/induzido quimicamente , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/efeitos adversos , Neoplasias Cutâneas/induzido quimicamente , Idoso , Carcinoma de Células Escamosas/patologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pirimidinas/uso terapêutico , Neoplasias Cutâneas/patologia
3.
Dermatol Online J ; 26(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32815691

RESUMO

Cutaneous side effects such as acneiform eruption, xerosis, and paronychia are frequently observed in patients undergoing treatment with epidermal growth factor receptor (EGFR) inhibitors for non-small cell lung cancer and other solid tumors. Interestingly, these side effects appear to positively correlate with length of remission, indicating that disruption of homeostatic EGFR signaling in the skin may serve as a marker of therapeutic EGFR inhibition in tumors. We report the case of a woman with metastatic lung cancer in remission being treated with the EGFR inhibitor, erlotinib, who experienced numerous commonly occurring adverse cutaneous reactions early in her treatment, and after two years of treatment developed eruptive nevi as well as a nevoid melanoma. Changes in pigmented lesions and the development of melanoma have been described during treatment with the BRAF inhibitor, vemurafenib, and are believed to relate to paradoxical activation of BRAF and the MAPK pathway. We speculate that a similar mechanism may occur during treatment with EGFR inhibitors. Therefore, thorough skin examinations are essential for patients undergoing long term treatment with erlotinib.


Assuntos
Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/efeitos adversos , Nevo/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Neoplasias Cutâneas/induzido quimicamente , Idoso , Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/induzido quimicamente
4.
An Bras Dermatol ; 95(5): 615-618, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32711929

RESUMO

Biological therapies, including anti-TNF agents, are important in the treatment of various chronic inflammatory diseases, including psoriasis, rheumatoid arthritis or inflammatory bowel disease. The increased use of these drugs translates into an increasing awareness of its adverse effects, which include malignancy. In this paper, we describe the case of a 28-year-old woman who developed a spitzoid melanocytic tumor after starting infliximab therapy for ulcerative colitis. The evidence for causality between anti-TNF and melanocytic proliferations is still sparse; nonetheless, treatment-associated immunosuppression seems to play a key role in this phenomenon. Therefore, a regular follow-up with a rigorous skin examination is essential in these patients. Noninvasive techniques such as dermoscopy or reflectance confocal microscopy are particularly useful diagnostic tools in these circumstances.


Assuntos
Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Infliximab/efeitos adversos , Nevo de Células Epitelioides e Fusiformes/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Fator de Necrose Tumoral alfa
5.
Dermatol Online J ; 26(4)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621690

RESUMO

Dupilumab is a monoclonal antibody that inhibits interleukin-4 and interleukin-13 signaling. It is the first biologic agent to demonstrate efficacy in treating moderate-to-severe refractory atopic dermatitis [1, 2]. Although dupilumab provides promise for the treatment of atopic and allergic conditions, clinicians should take into account its novelty and the potential for unexpected adverse events. We present a patient who developed Sézary syndrome following the initiation of dupilumab.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Subunidade alfa de Receptor de Interleucina-4/antagonistas & inibidores , Síndrome de Sézary/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente , Anticorpos Monoclonais Humanizados/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade
6.
Chemosphere ; 258: 127305, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32563914

RESUMO

Chronic arsenic toxicity has become a global concern due to its adverse pathophysiological outcome and carcinogenic potential. It is already established that arsenic induced reactive oxygen species alters mitochondrial functionality. Major regulatory genes for mitochondrial biogenesis, i.e., PGC1α, Tfam, NRF1and NRF2 are located in the nucleus. As a result, mitochondria-nucleus crosstalk is crucial for proper mitochondrial function. This previous hypothesis led us to investigateinvolvement of epigenetic alteration behindenhanced mitochondrial biogenesis in chronic arsenic exposure. An extensive case-control study was conducted with 390 study participants (unexposed, exposed without skin lesion, exposed with skin lesion and exposed skin tumour) from highly arsenic exposed areas ofWest Bengal, India. Methylation specific PCRrevealed significant promoter hypomethylation oftwo key biogenesis regulatory genes, PGC1αandTfam in arsenic exposed individuals and also in skin tumour tissues. Linear regression analysis indicated significant negative correlation between urinary arsenic concentration and promoter methylation status. Increased expression of biogenesis regulatory genes wasobtained by quantitative real-time PCR analysis. Moreover, altered mitochondrial fusion-fission regulatory gene expression was also observed in skin tumour tissues. miR663, having tumour suppressor gene like function was known to be epigenetically regulated through mitochondrial retrograde signal. Promoter hypermethylation with significantly decreased expression of miR663 was found in skin cancer tissues compared to non-cancerous control tissue. In conclusion, results indicated crucial role of epigenetic alteration in arsenic induced mitochondrial biogenesis and arsenical skin carcinogenesis for the first time. However, further mechanistic studies are necessary for detailed understanding of mitochondria-nucleus crosstalk in arsenic perturbation.


Assuntos
Arsênico/toxicidade , Epigênese Genética , Mitocôndrias/fisiologia , Arsênico/metabolismo , Intoxicação por Arsênico , Carcinogênese/induzido quimicamente , Estudos de Casos e Controles , Metilação de DNA , Epigenômica , Feminino , Humanos , Índia , Masculino , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Biogênese de Organelas , Regiões Promotoras Genéticas , Dermatopatias/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente
7.
Transplant Proc ; 52(6): 1775-1777, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32299709

RESUMO

OBJECTIVES: This study analyzed clinical characteristics of renal transplant recipients who developed malignancy with immunosuppression after transplantation by applying a competing risk analysis to reduce the effects of competing events. METHODS: All patients who underwent renal transplantation at our institution from 1973 to 2017 were included in this analysis. All data were collected from patient medical records and retrospectively analyzed. The cumulative incidence of malignancy before allograft loss and its risk factors were calculated by a competing risk analysis, the Gray test, and the Fine-Gray proportional hazard model. RESULTS: Of the 596 recipients, 78 developed malignancies. The mean age at transplantation was 38.5 ± 13.1 years. The median time from transplantation to the initial malignancy was 147.0 (5.2-407.3) months. The most common initial malignancy was skin cancer (21.8%), followed by posttransplant lymphoproliferative disease (14.1%). The cumulative incidence of malignancy at 20 years was 16.2% according to a competing risk analysis, whereas the conventional Kaplan-Meier method estimated the cumulative incidence at 20 years to be 25.6%. Increasing age at transplantation was significantly associated with the incidence of malignancy (P = .0091). Overall 10-year survival rates of recipients with and without malignancy were 81.7% and 88.5%, respectively (P < .001). CONCLUSIONS: Results of time-to-event analysis must be interpreted with caution in situations with competing events when estimating the cumulative incidence of malignancy with immunosuppression after renal transplantation. Renal transplant recipients with increasing age should be more carefully monitored as a high-risk population for developing malignancies.


Assuntos
Imunossupressão/mortalidade , Transplante de Rim/mortalidade , Transtornos Linfoproliferativos/mortalidade , Neoplasias/mortalidade , Complicações Pós-Operatórias/mortalidade , Adulto , Feminino , Humanos , Incidência , Transtornos Linfoproliferativos/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Complicações Pós-Operatórias/induzido quimicamente , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida
8.
J Nutr ; 150(6): 1535-1544, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32221600

RESUMO

BACKGROUND: In prior studies, higher citrus consumption was associated with higher risk of cutaneous malignant melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). Furocoumarins, compounds with phototoxicity and photocarcinogenicity in citrus, may be responsible for the association. OBJECTIVES: The objective of the study was to investigate the association between furocoumarin intake and skin cancer risk. METHODS: A total of 47,453 men from the Health Professionals Follow-Up Study (HPFS) and 75,291 women from the Nurses' Health Study (NHS) with diet data collected every 2-4 y in the 2 prospective cohort studies were included. A furocoumarin food composition database for 7 common furocoumarins [bergaptol, psoralen, 8-methoxypsoralen, bergapten, 6',7'-dihydroxybergamottin (6'7'-DHB), epoxybergamottin, and bergamottin] was developed and used to calculate participants' cumulative average and energy-adjusted furocoumarin intake. Multivariate HRs and 95% CIs of the associations between furocoumarin intake and skin cancer risk were estimated using Cox proportional hazards models. Analyses were performed separately in each cohort as well as pooled using a fixed-effects model. RESULTS: Throughout follow-up (1984-2012 in the NHS and 1986-2012 in the HPFS), we identified 1593 melanoma, 4066 SCC, and 28,630 BCC cases. Higher intake of total furocoumarins was associated with an increased risk of BCC; the pooled HR comparing the top with the bottom quintile was 1.16 (95% CI: 1.11, 1.21; P-trend = 0.002). Higher intakes of bergaptol, bergapten, 6'7'-DHB, and bergamottin were also significantly associated with increased BCC risk. No significant associations were found between intake of total furocoumarins and the risks of SCC or melanoma. CONCLUSIONS: Intakes of total furocoumarins as well as some individual furocoumarins were associated with an increased risk of skin cancer, especially BCC, in 2 cohorts of US health professionals.


Assuntos
Citrus , Furocumarinas/administração & dosagem , Neoplasias Cutâneas/induzido quimicamente , Adulto , Feminino , Furocumarinas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/epidemiologia , Reino Unido , Estados Unidos/epidemiologia
9.
Cancer ; 126(8): 1700-1707, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31943154

RESUMO

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma arising in the skin. Geographic clustering of CTCL has recently been reported, but its association with environmental factors is unknown. Benzene and trichloroethylene (TCE) are environmental toxins with carcinogenic properties. The authors investigated associations between geographic clustering of CTCL incidence in the state of Georgia with benzene and TCE exposure. METHODS: The statewide county-level incidence of CTCL within Georgia was obtained from the Georgia Cancer Registry for the years 1999 to 2015. Standardized incidence ratios (SIRs) were calculated by dividing observed cases by expected cases using national incidence rates by age, sex, and race. Clustering of CTCL was analyzed using spatial analyses. County-level concentrations of benzene and TCE between 1996 and 2014 were collected from the Environmental Protection Agency's National Air Toxics Assessment database. Linear regression analyses on CTCL incidence were performed comparing SIRs with levels of benzene and TCE by county. RESULTS: There was significant geographic clustering of CTCL in Georgia, particularly around Atlanta, which was correlated with an increased concentration of benzene and TCE exposure. Among the 4 most populous counties in Georgia, CTCL incidence was between 1.2 and 1.9 times higher than the state average, and benzene and TCE levels were between 2.9 and 8.8 times higher. CONCLUSIONS: The current results demonstrate nonrandom geographic clustering of CTCL incidence in Georgia. To the authors' knowledge, this is the first analysis to identify a correlation between geographic clustering of CTCL and environmental toxic exposures.


Assuntos
Benzeno/toxicidade , Exposição Ambiental/efeitos adversos , Linfoma Cutâneo de Células T/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente , Tricloroetileno/toxicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Bases de Dados Factuais , Feminino , Georgia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Adulto Jovem
11.
Environ Pollut ; 260: 113919, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31995775

RESUMO

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.


Assuntos
Arsênico , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Arsênico/toxicidade , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/fisiopatologia , Poluentes Ambientais/toxicidade , Humanos , Pele/efeitos dos fármacos , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/fisiopatologia
12.
Dig Dis Sci ; 65(4): 1172-1179, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31493039

RESUMO

BACKGROUND: Retrospective studies observe an increased risk of keratinocyte carcinomas (KCs) in patients with inflammatory bowel disease (IBD) on thiopurine (TP) medication. The role of traditional risk factors such as skin type and sun protection behavior has not been studied in this population. This study aimed to examine traditional KC risk factors and thiopurine use on skin cancer development in an IBD cohort. METHODS: Consecutive IBD patients were recruited from four specialist centers in Australia and New Zealand, each with varying UV exposure indices. Data pertaining to race, skin color, freckling and sun protection behavior, dose of TP therapy, and skin cancer development were elicited through a self-reported questionnaire. RESULTS: A total of 691 IBD patients were included with 62 reporting KC development. Thiopurine usage was similar among patients who developed skin cancer compared with those who did not (92% vs. 89%, p = 0.3). There was no statistically significant association between KC development and TP dose or 6-thioguanine nucleotide levels. In multivariate modeling, four factors were independently and significantly associated with KC: age over 61 years old versus less than 30 years old (OR 6.76; 95% CI 2.38-19.18), residing in Brisbane versus Christchurch (OR 3.3; 95% CI 1.6-6.8), never staying in the shade versus staying in the shade ≥ 50% of the time (OR 3.8; 95% CI 1.4-10.5), and having a skin type that never tanned versus other skin types (OR 6.9; 95% CI 2.9-16.0). CONCLUSION: Skin type, age, and sun protection behavior are more important risk factors for KC development than thiopurine medication use in this IBD population.


Assuntos
Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/epidemiologia , Queratinócitos/efeitos da radiação , Neoplasias Cutâneas/epidemiologia , Pigmentação da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Adulto , Fatores Etários , Austrália/epidemiologia , Azatioprina/efeitos adversos , Azatioprina/farmacologia , Azatioprina/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Fatores de Risco , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/etiologia , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/fisiologia
14.
J Am Acad Dermatol ; 82(2): 326-335, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31150714

RESUMO

BACKGROUND: Several antiepileptic drugs are photosensitizing; however, it is not known whether this confers an increased risk of skin cancer. OBJECTIVE: To examine the association between common antiepileptic drugs and basal cell carcinoma, squamous cell carcinoma (SCC), and malignant melanoma. METHODS: We conducted a nested case-control study identifying skin cancer patients in Denmark from 2004 through 2015 matched 1:10 with disease-free controls. We estimated odds ratios (ORs) for skin cancer associated with high cumulative use of antiepileptic drugs (≥500 defined daily doses) compared with nonuse. RESULTS: Most antiepileptic drugs were not associated with skin cancer. SCC was associated with use of carbamazepine (OR, 1.88; 95% confidence interval, 1.42-2.49) and lamotrigine (OR, 1.57; 95% confidence interval, 1.12-2.22) with evidence of a dose-response relationship for carbamazepine. The estimated absolute risks were low; for example, 6335 person-years of high cumulative exposure to carbamazepine were required for 1 additional SCC to occur. LIMITATIONS: Data on important risk factors for skin cancer, such as sun exposure, were not available. CONCLUSIONS: Most antiepileptic drugs were not associated with skin cancer; however, carbamazepine and lamotrigine were associated with SCC. These findings need to be replicated and characterized further in other settings and have no direct clinical implications.


Assuntos
Anticonvulsivantes/efeitos adversos , Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Carbamazepina/efeitos adversos , Carcinoma Basocelular/induzido quimicamente , Carcinoma de Células Escamosas/induzido quimicamente , Estudos de Casos e Controles , Dinamarca/epidemiologia , Epilepsia/tratamento farmacológico , Feminino , Humanos , Incidência , Lamotrigina/efeitos adversos , Masculino , Melanoma/induzido quimicamente , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Neoplasias Cutâneas/induzido quimicamente
15.
Nutr Cancer ; 72(1): 24-32, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31074648

RESUMO

Furocoumarins are a group of phototoxic compounds found in numerous edible plants. Data from cohort studies have suggested that consumption of certain furocoumarin-rich foods may increase skin cancer risk. However, no study has specifically tested this hypothesis by estimating furocoumarin intake and assessing its relationship with skin cancer. This study aimed to estimate average daily furocoumarin intake of US adults using the National Health and Nutrition Examination Survey (NHANES) 2003-2012 and to examine the relationship between furocoumarin intake and melanoma history. A database of the contents of seven furocoumarins in 29 popular foods was linked to dietary data in NHANES 2003-2012. Mean total intake of the selected furocoumarins among US adults was 81.4 µg/day (standard error = 5.5). A total of 75 participants reported a history of melanoma. Using non- and low consumers (<50th percentile) as a reference, and after adjusting for potential confounders, OR (with 95% confidence interval) of melanoma history for the top 10 percent, 80-90th percentiles, and 50-80th percentiles were 1.75 (0.43-7.20), 1.66 (0.39-7.16), and 0.90 (0.45-1.78), respectively. Furocoumarins are widely consumed among US adults, and a trend towards higher odds of melanoma history was observed among those with higher furocoumarin intake, although this relationship was not statistically significant.


Assuntos
Dieta/efeitos adversos , Furocumarinas/efeitos adversos , Melanoma/epidemiologia , Inquéritos Nutricionais/estatística & dados numéricos , Fármacos Fotossensibilizantes/efeitos adversos , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Melanoma/induzido quimicamente , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia , Estados Unidos/epidemiologia , Adulto Jovem
16.
Cell Prolif ; 53(1): e12710, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31663659

RESUMO

OBJECTIVE: Clinical trials have demonstrated the efficacy of indigo naturalis, a traditional Chinese medicine ingredient, against psoriasis, a skin disease characterized by keratinocyte hyperproliferation and inflammation. The present study investigates the efficacy of tryptanthrin, a bioactive compound in indigo naturalis, against non-melanoma skin cancer (NMSC) and the signalling events involved. METHODS: Efficacy of tryptanthrin against NMSC was assessed using DMBA/PMA-induced skin carcinogenesis model in Swiss albino mice. Immunostaining for PCNA and ki-67 was used to mark proliferating cells in tissues. Haematoxylin and eosin staining and toluidine staining were employed to assess inflammation, and TUNEL assay was used to detect apoptosis in tissues. The signalling events were evaluated using Western blot, imunohistochemistry and immunofluorescence staining. MTT assay and clonogenic assay were performed to assess the viability and proliferation of cancer cells, in vitro. RESULTS: In mice, topical application of tryptanthrin suppressed skin carcinogenesis. It attenuated inflammation, impeded the proliferation of hair follicle (HF) cells and suppressed the activation of ß-catenin, a major driver of HF cell proliferation. Additionally tryptanthrin suppressed the activation of ERK1/2 and p38, both of which promote ß-catenin activation and lowered the expression of c-Myc and cyclin-D1. Tryptanthrin suppressed the proliferation of the human NMSC cell line, A431 and abrogated EGF-induced activation of ß-catenin and subsequent cytoskeletal rearrangement. CONCLUSION: The study demonstrates with molecular evidence that tryptanthrin is an effective suppressor of NMSC.


Assuntos
Quinazolinas/farmacologia , Neoplasias Cutâneas/prevenção & controle , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Antígeno Ki-67/metabolismo , Camundongos , Proteínas de Neoplasias/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Acetato de Tetradecanoilforbol/toxicidade , Ácido gama-Aminobutírico/análogos & derivados , Ácido gama-Aminobutírico/toxicidade
17.
Am J Epidemiol ; 189(4): 314-329, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-31665225

RESUMO

We investigated the influence of premenopausal use of progestogens on melanoma using data from E3N (Etude Epidémiologique Auprès de Femmes de l'Education Nationale), a prospective cohort of 98,995 French women, aged 40-65 years at inclusion. We used Cox models to adjust for age and melanoma risk factors. Over 1992-2008, 540 melanoma cases were ascertained among 79,558 women. We found a modest association between self-reported progestogen use and melanoma risk (hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.02, 1.47), which was reduced after adjustment for melanoma risk factors (HR = 1.15, 95% CI: 0.95, 1.39). There was no heterogeneity across types of progestogens (P = 0.22), and use of multiple progestogens was positively associated with melanoma risk (HR = 1.33, 95% CI: 1.04, 1.70). Among users, we found no relationship with duration of progestogen use, age at start and last use, and time since first and last use. Although our results did not show evidence of a confounding effect of sun exposure, progestogen users had lower levels of residential sun exposure and were more likely to report sunscreen use, suggesting specific sun exposure profiles in users. Our findings do not support a strong influence of progestogens on melanoma risk. Further research is needed to confirm these results.


Assuntos
Melanoma/epidemiologia , Progestinas/efeitos adversos , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Feminino , França/epidemiologia , Humanos , Melanoma/induzido quimicamente , Pessoa de Meia-Idade , Pré-Menopausa , Progestinas/administração & dosagem , Estudos Prospectivos , Neoplasias Cutâneas/induzido quimicamente
18.
Mater Sci Eng C Mater Biol Appl ; 107: 110263, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761163

RESUMO

A modified facile biomimetic Temozolomide Chitosan nanogel (TCNL) was developed offering pH responsive, charge attracted and microenvironment dependent tumor targeting nanotherapy. USFDA approved chemotherapeutic TMZ (Temozolomide) was encapsulated in a cationic biocompatible chitosan nanogel subsequently surface modified with nonionic Transcutol by inotropic gelation method and evaluated for its combined anti-metastatic and antitumor efficiency. The in-vitro results authenticated that TMZ encapsulated TCNL was effectively uptake and distributed in HaCaT cell line inducing high apoptosis and necrosis of tumor cells prior to the electron microscopic (TEM & SEM) and thermal evaluations (DSC, DTA & TG) suggesting spherical and thermo-stable nanogel system. An accelerated sustained release pattern of TMZ from TCNL was displayed in mildly acidic conditions (pH 6) signifying ultra-sensitivity of TCNL. In-vivo evaluation over 16 week DMBA/croton oil tumor induced mice model showed noteworthy tumor targeting with down regulation of overexpressed COX-2, cytokines and nuclear factors on western blot analysis. Moreover, advanced gamma scintigraphy analysis displayed significant drug accommodation and expressing potent tumor accumulation, suppression and metastasis effect on carcinogenic mice. The TCNL outcomes displayed effective tumor targeting on transdermal delivery for operative nanotherapy against skin cancer.


Assuntos
Géis/química , Nanoestruturas/química , Animais , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Linhagem Celular , Quitosana/química , Regulação para Baixo/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Masculino , Melanoma/induzido quimicamente , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos , Compostos de Organotecnécio/química , Tamanho da Partícula , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Temozolomida/química , Temozolomida/farmacologia , Temozolomida/uso terapêutico
19.
Sci Total Environ ; 704: 135388, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31837846

RESUMO

Telomere integrity is considered to be one of the primary mechanisms during malignant transformation. Arsenic, a group 1 carcinogenic metalloid, has been reported to cause telomere lengthening in a telomerase-independent manner. Recent studies suggest a significant role for epigenetic modifications in regulating telomeric length and integrity. Here, we have explored the role of epigenetic deregulation in alternative lengthening of telomeres (ALT) in arsenic-exposed skin cancer tissues and corresponding non-tumor tissues. The relative telomere length (RTL) was analyzed by qRT-PCR using 2-ΔΔCt method. The subtelomeric methylation pattern of the four chromosomes (7q, 18p, 21q and XpYp) were analysed by Methylation Specific PCR (MSP) in 40 pairs of arsenic exposed skin cancer tissues and its corresponding control. The role of constitutive heterochromatin histone marks in the regulation of telomere length (TL) was analyzed by targeted ELISA. A 2-fold increase of relative telomere length in 85% of the arsenic-induced skin cancer tissues was observed. Among the four chromosomes, subtelomere of XpYp was found to be hypermethylated (p < 0.001) whereas 18p was hypomethylated (p < 0.01). Additionally, the level of H4K20me3, a heterochromatic mark was found to be significantly down-regulated (p < 0.0003), and inversely correlated with telomere length indicating loss of heterochromatinization of telomeric DNA. These observations highlight the novel role of epigenetic regulation in the maintenance of constitutive heterochromatin structure at telomere. Alteration in subtelomeric DNA methylation patterns and depletion of H4K20me3 might lead to loss of heterochromatinization resulting in arsenic-induced telomeric elongation. We provide novel data indicating possible alternative determinants of telomere elongation through epigenetic modifications during arsenic-induced skin carcinogenesis which could be used as early 'epimarkers' in the near future. The findings provide new insights about the mechanism of arsenic-induced carcinogenesis.


Assuntos
Arsênico/toxicidade , Epigênese Genética , Neoplasias Cutâneas/induzido quimicamente , Homeostase do Telômero , Carcinogênese , Transformação Celular Neoplásica , Metilação de DNA , Humanos , Telomerase , Telômero
20.
In Vivo ; 34(1): 441-445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882511

RESUMO

A 59-year-old woman, undergoing treatment with encorafenib for metastatic BRAF mutated colorectal cancer, developed during the first two months of therapy multiple eruptive nevi and changes in pre-existing nevi. Development of eruptive nevi has increasingly been reported in association with medications, most frequently conventional immunosuppressants and biologics. Some drugs are associated with eruptive nevi through an indirect effect of their mechanism of action, whereas other drugs are directly implicated in melanocyte proliferation. In this regard, BRAF inhibitors have been demonstrated to activate the MAPK pathway, and to promote cellular proliferation and survival, therefore leading to the development of new melanocytic nevi and to an increase in the size and hyperpigmentation of pre-existing nevi. A dermatological assessment and follow-up should be recommended in all patients presenting with eruptive nevi, regardless of the pathogenesis, because a high number of acquired melanocytic nevi may represent an adjunctive risk factor for melanoma.


Assuntos
Carbamatos/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Melanoma/induzido quimicamente , Nevo Pigmentado/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/induzido quimicamente , Sulfonamidas/efeitos adversos , Neoplasias Colorretais/secundário , Feminino , Humanos , Melanoma/patologia , Pessoa de Meia-Idade , Mutação , Nevo Pigmentado/patologia , Prognóstico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA