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1.
Radiol Med ; 128(12): 1571-1579, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37642816

RESUMO

PURPOSE: Taste alteration (TA) is a frequent acute side effect of radiation treatment in HNSCC patients. Principal aim of our study was to investigate dosimetric parameters in relation to patient-assessed taste impairment in a prospective cohort treated with intensity-modulated radiotherapy. METHODS: All patients with locally advanced HNSCC and amenable to radical treatment were included. Chemotherapy-induced taste alteration scale (CITAS), EORTC QLQ-C30 and QLQ-HN43 questionnaires at baseline (T0), 3 weeks (T1) and 3 months (T2) after radiotherapy conclusion were used to assess taste impairment. Base of tongue, submandibular glands (SG), parotid glands (PG) and taste buds, along with anterior and medium third of the tongue, were considered as organs at risk and thus delineated according to consensus guidelines. The mean dose to the above-mentioned structures was correlated with patient-reported outcomes. RESULTS: Between September 2019 and November 2020, 33 patients were recruited, 31 of which analyzed. 71% had oropharyngeal carcinoma, mostly HPV-related (60%). All were treated with tomotherapy. 77.4% had concurrent cisplatin. Mean scores of general taste alterations, global health status and dry mouth and sticky saliva were assessed. The mean doses to the anterior third, medium third and base of the tongue were 23.85, 35.50 and 47.67 Gy, respectively. Taste buds received 32.72 Gy; right and left parotid 25 and 23 Gy; right and left submandibular glands 47.8 and 39.4 Gy. At univariate analysis, dysgeusia correlated with SG mean dose (95% CI 0-0.02 p = 0.05) and PG mean dose (95% CI 0-0.02 p = 0.05); dry mouth with mean dose to anterior (95% CI 0.03-1.47 p = 0.04) and medium third (95% CI 0.02-0.93 p = 0.04) of the tongue, to taste buds (95% CI 0.06-0.96 p = 0.03) and to SGs (95% CI 0.06-0.63 p = 0.02); pain mouth with mean dose to taste buds (95% CI 0-0.02 p = 0.04), to SGs (95% CI 0-0.03 p = 0.03) and to base tongue (95% CI 0-0.02 p = 0.02). CONCLUSIONS: Our analysis supports the influence of dose distribution on the development of TA in HNSCC patients. The contribution of dose to taste buds and tongue subvolumes remains unclear and worthy of further investigation.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias de Células Escamosas , Radioterapia de Intensidade Modulada , Xerostomia , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estudos Prospectivos , Disgeusia/induzido quimicamente , Paladar , Neoplasias de Cabeça e Pescoço/radioterapia , Xerostomia/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Doses de Radiação , Neoplasias de Células Escamosas/etiologia , Dosagem Radioterapêutica
2.
Mol Carcinog ; 60(3): 172-178, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33482042

RESUMO

Although beta 2 adrenergic receptors (ß2 ADR) are present in the keratinocytes, their role in cutaneous squamous cell tumorigenesis needs to be ascertained. For the first time, we report here that selective ß2 ADR antagonists by inhibiting ß2 ADR actions significantly retarded the progression of ultraviolet B (UVB) induced premalignant cutaneous squamous cell lesions. These antagonists acted by inhibiting vascular endothelial growth factor-A (VEGF) mediated angiogenesis to prevent UVB radiation-induced squamous cell carcinoma of the skin.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 2/farmacologia , Neoplasias de Células Escamosas/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Raios Ultravioleta/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Butoxamina/farmacologia , Humanos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Masculino , Camundongos Endogâmicos , Neoplasias Induzidas por Radiação/irrigação sanguínea , Neoplasias Induzidas por Radiação/tratamento farmacológico , Neoplasias Induzidas por Radiação/etiologia , Neoplasias de Células Escamosas/irrigação sanguínea , Neoplasias de Células Escamosas/etiologia , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Neoplasias Cutâneas/irrigação sanguínea , Neoplasias Cutâneas/etiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Xamoterol/farmacologia
3.
Int J Gynaecol Obstet ; 151(2): 253-259, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32683675

RESUMO

OBJECTIVE: To determine the prevalence and predictors of precancerous cervical lesions among HIV-positive women in Jos, Nigeria. METHODS: A cross-sectional study was conducted from October 2017 to January 2018 among 326 HIV-positive women. Cervical smears were collected for examination at the AIDS Preventive Initiative of Nigeria clinics of Jos University Teaching Hospital (JUTH) and Bingham University Teaching Hospital (BhUTH), Jos, Nigeria. Demographic characteristics of participants were documented using a structured questionnaire. Data were entered and analyzed using SPSS version 21. RESULTS: Of the 326 participants, precancerous cervical lesions were present in 40 (12.2%) women: 4 (1.2%) had atypical squamous cells of undetermined significance, 19 (5.8%) had low-grade squamous intraepithelial lesions, 1 (0.3%) had atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions, 13 (4.0%) had high-grade squamous intraepithelial lesions, and 3 (0.9%) had high-grade squamous intraepithelial lesions, suspected for invasion. The multivariate logistics regression model showed that parity (odds ratio 3.4, 95% confidence interval 1.3-9.5, P=0.043) was a significant predictor of precancerous cervical lesions. CONCLUSION: The prevalence of precancerous cervical lesions among HIV-infected women is relatively low compared to earlier reported prevalence in an HIV population in Jos. Increasing parity was a significant predictor.


Assuntos
Infecções por HIV , HIV-1 , Neoplasias de Células Escamosas/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/etiologia , Neoplasias de Células Escamosas/patologia , Nigéria/epidemiologia , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Adulto Jovem , Displasia do Colo do Útero/etiologia , Displasia do Colo do Útero/patologia
4.
Occup Environ Med ; 77(5): 293-300, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31959638

RESUMO

OBJECTIVE: To investigate the association between occupational exposure to welding and the risk of head and neck cancer in a large French population-based case-control study, the Investigation of occupational and environmental CAuses of REspiratory cancers study. METHODS: Analyses were restricted to men (2703 controls and 1588 cases of squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx). Welding activity and potential confounders were assessed by detailed questionnaires. ORs and CIs (95% CI) were estimated by unconditional logistic regression, adjusted for age, area of residence, tobacco smoking, alcohol consumption and occupational exposure to asbestos. RESULTS: Welding was associated with an increased risk of head and neck cancer overall (OR=1.31, 95% CI 1.03 to 1.67). The association was strongest for laryngeal cancer (OR=1.66, 95% CI 1.15 to 2.38) and the risk increased with the cumulative duration (p-trend <0.01) and the weighted duration (p-trend <0.01) of welding. A cumulative duration and a weighted duration of welding of more than 10 years were also associated with a significantly increased risk of oral cancer (OR=1.82, 95% CI 1.09 to 3.04; OR=2.10, 95% CI 0.99 to 4.45, respectively). A long duration of arc welding was associated with laryngeal cancer, whereas a long duration of spot welding was associated with oral cancer. Welding was not associated with the risk of oropharyngeal and hypopharyngeal cancer. CONCLUSION: Our findings suggest that welding and several welding-related tasks increase the risk of laryngeal cancer and to a lesser extent oral cancer.


Assuntos
Neoplasias Laríngeas/epidemiologia , Neoplasias de Células Escamosas/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Neoplasias Faríngeas/epidemiologia , Soldagem , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , França/epidemiologia , Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias Hipofaríngeas , Neoplasias Laríngeas/etiologia , Neoplasias Laríngeas/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/etiologia , Neoplasias de Células Escamosas/patologia , Doenças Profissionais/etiologia , Doenças Profissionais/patologia , Neoplasias Orofaríngeas , Neoplasias Faríngeas/etiologia , Neoplasias Faríngeas/patologia , Fatores de Risco , Adulto Jovem
5.
Oral Oncol ; 97: 137-138, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31445773

RESUMO

For patients with Lynch Syndrome (LS) (formerly known as hereditary nonpolyposis colorectal cancer or HNPCC), inheritance of one of several mutated mismatch repair genes (MMR) results in an increased risk for a variety of malignancies including colon, rectal, endometrial, urinary tract, gastric, small bowel and others [1]. Confirmation of increased risk of particular malignancies for patients harboring an MMR germline mutation has typically been the result of population studies of families tracked for the development of the possible associated cancer. When cancer results from inheritance of a particular mutated MMR gene, the malignancy has a characteristic fingerprint referred to as microsatellite instability-high (MSI-H), which results from deficient expression of the inherited MMR gene product (dMMR). Therefore, if sporadic tumors of a particular tissue of origin are only rarely dMMR, identifying a tumor as dMMR in a known LS family member suggests that, in that particular family, inheritance of the mutated MMR gene does predispose to that malignancy. Here we describe a patient diagnosed with a germline mutation in the MMR gene MSH6 who developed an oral pharynx cancer. Oral pharynx cancers are not known to be associated with LS. By confirming that the tumor was not dMMR and not MSI-H, it was concluded that his oral pharynx cancer was sporadic, rather than LS-related, and other family members carrying the mutated MSH6 are unlikely to be at above-average risk for the development of oral cancers, as a result of the LS. In additional, he would not be eligible for the so-called FDA agnostic approved immunotherapy which is endorsed for dMMR or MSI-H tumors [2].


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Bucais/etiologia , Neoplasias Bucais/genética , Neoplasias de Células Escamosas/etiologia , Neoplasias de Células Escamosas/genética , Idoso , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Risco
7.
J Cancer Res Clin Oncol ; 144(3): 607-615, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29362916

RESUMO

PURPOSE: Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in liver transplant (LT) recipients; it behaves more aggressively and it increases mortality. We used decision tree analysis to develop a tool to stratify and quantify risk of NMSC in LT recipients. METHODS: We performed Cox regression analysis to identify which predictive variables to enter into the decision tree analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR files of September 2016 (n = 102984). RESULTS: NMSC developed in 4556 of the 105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender, Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key predictive or protective factors for NMSC. These factors were entered into a decision tree analysis. The final tree stratified non-Caucasians as low risk (0.8%), and Caucasian males > 47 years, BMI < 40 who did not receive sirolimus, as high risk (7.3% cumulative incidence of NMSC). The predictions in the derivation set were almost identical to those in the validation set (r2 = 0.971, p < 0.0001). Cumulative incidence of NMSC in low, moderate and high risk groups at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p < 0.0001). CONCLUSIONS: The decision tree model accurately stratifies the risk of developing NMSC in the long-term after LT.


Assuntos
Técnicas de Apoio para a Decisão , Árvores de Decisões , Transplante de Fígado/efeitos adversos , Neoplasias Cutâneas/etiologia , Adulto , Idoso , Feminino , Humanos , Imunossupressores/uso terapêutico , Incidência , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasia de Células Basais/epidemiologia , Neoplasia de Células Basais/etiologia , Neoplasias de Células Escamosas/epidemiologia , Neoplasias de Células Escamosas/etiologia , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/estatística & dados numéricos
8.
Cornea ; 36(6): 743-746, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28350623

RESUMO

PURPOSE: To discuss the association between ocular surface squamous neoplasia (OSSN) and Papillon-Lefèvre syndrome (PLS) and present the long-term outcome in a patient with these diseases. METHODS: Case report. RESULTS: A 14-year-old boy presented with a raised pigmented mass lesion at the limbus in the right eye, which was clinically suggestive of OSSN. He also had palmoplantar hyperkeratosis and periodontosis suggestive of PLS. Excision biopsy of the lesion confirmed the diagnosis of OSSN. He was free of tumor recurrence for 2 years and was lost to follow-up thereafter. Seven years later, the patient presented with diffuse tumor recurrence with orbital extension in the right eye, regional lymph node metastasis, and ipsilateral parotid gland infiltration. The patient underwent exenteration of the right orbital contents, right parotidectomy, and radical neck dissection followed by concomitant external beam radiotherapy and systemic chemotherapy. Eleven years from initial presentation, the patient was detected to have OSSN in the contralateral eye and was managed by wide excision biopsy and adjuvant cryotherapy. One year after detection of OSSN in the left eye, the patient was found to have systemic metastases to the lungs and brain. The patient died of the disease within 3 months of detection of systemic metastasis. CONCLUSIONS: OSSN in PLS is associated with poor prognosis.


Assuntos
Doenças da Córnea/etiologia , Neoplasias Oculares/etiologia , Limbo da Córnea/patologia , Neoplasias de Células Escamosas/etiologia , Doença de Papillon-Lefevre/complicações , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Terapia Combinada , Doenças da Córnea/patologia , Doenças da Córnea/terapia , Neoplasias Oculares/patologia , Neoplasias Oculares/terapia , Evolução Fatal , Seguimentos , Humanos , Masculino , Neoplasias de Células Escamosas/patologia , Neoplasias de Células Escamosas/terapia , Estudos Retrospectivos
9.
Cancer Sci ; 108(5): 1058-1064, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28218985

RESUMO

Soft palatal melanosis can be detected by visual inspection during routine physical examination or even personally in a mirror. The aim of this study was to evaluate the association between squamous cell neoplasia in the upper aerodigestive tract (UAT) and soft palatal melanosis. We reviewed digitized records of high-quality endoscopic images of the soft palate of 1786 Japanese alcoholic men who underwent endoscopic screening. Soft palatal melanosis was observed in 381 (21.3%) of the subjects (distinct, 6.3%). Older age, an inactive heterozygous aldehyde dehydrogenase-2 genotype, smoking, and a high mean corpuscular volume were positively associated with the presence of soft palatal melanosis. The age-adjusted odds ratio (95% confidence interval) for UAT neoplasia was 1.92 (1.40-2.64) in the group with melanosis and 2.51 (1.55-4.06) in the group with distinct melanosis, compared with the melanosis-free group. A multivariate analysis showed that the presence of soft palatal melanosis was independently associated with a high risk of UAT neoplasia. We calculated the individual number of risk factors out of four easily identifiable and significant factors: age ≥55 years, current/former alcohol flushing, mean corpuscular volume ≥106 fL, and distinct soft palatal melanosis. Compared with the risk-factor-free condition, the odds ratio (95% confidence interval) values of UAT neoplasia for one, two, three, and four risk factors were 1.49 (0.97-2.30), 3.14 (2.02-4.88), 4.80 (2.71-8.51), and 7.80 (2.17-28.1), respectively. The presence of soft palatal melanosis provides a simple new strategy for identifying heavy drinkers with a high risk for UAT neoplasia.


Assuntos
Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/patologia , Melanose/complicações , Melanose/patologia , Palato Mole/patologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Aldeído Desidrogenase/metabolismo , Povo Asiático , Humanos , Masculino , Melanose/etiologia , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/etiologia , Neoplasias de Células Escamosas/patologia , Razão de Chances , Fatores de Risco , Fumar/efeitos adversos
10.
Photodiagnosis Photodyn Ther ; 17: 200-204, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27174210

RESUMO

INTRODUCTION: Photodynamic therapy (PDT) is a minimally invasive intervention used in the management of tissue disorders. In this retrospective study, a total of 62 patients with actinic keratosis (AKs) were treated with surface illumination PDT. Comparisons with the clinical features, rate of recurrence as well as malignant transformation and overall outcome were made. MATERIALS AND METHODS: The medical records of 62 consecutive patients who presented with suspicious skin lesions and diagnosed with AKs were examined. These patients with 178 AKs lesions were treated with surface illumination methyl aminolevulinate-photodynamic therapy (MAL-PDT). The 16% strength cream (MAL) was applied topically 3h prior to tissue illumination. A single-channel 628nm diode laser was used for illumination and light was delivered at 100J/cm2 per site. These patients were followed-up for a mean of 7.4 years. RESULTS: Eight recurrences were reported after the first round of MAL-PDT, and two recurrences after the second round. Malignant transformation to squamous cell carcinoma (SCC) was noted in 2 patients only. The 3-year outcome resulted in 60 patients with complete response (CR), and this was maintained at the final outcome (last clinic review). Assessment of lesional outcome vs. response showed that 175/178 treated lesions had complete response (CR) at 3-year follow-up, which increased to 176/178 lesions at the last clinic follow-up. CONCLUSION: MAL-PDT offers an effective treatment for AKs lesions with excellent cosmetic outcome.


Assuntos
Ácido Aminolevulínico/análogos & derivados , Ceratose Actínica/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Idoso , Ácido Aminolevulínico/uso terapêutico , Feminino , Humanos , Ceratose Actínica/complicações , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/etiologia , Fotoquimioterapia/efeitos adversos , Recidiva , Estudos Retrospectivos , Fatores de Risco
11.
Proc Natl Acad Sci U S A ; 113(27): 7614-9, 2016 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-27335465

RESUMO

The etiology of peripheral squamous cell lung cancer (PSCCa) remains unknown. Here, we show that this condition spontaneously develops in mice in which the genes for two oxysterol receptors, Liver X Receptor (LXR) α (Nr1h3) and ß (Nr1h2), are inactivated. By 1 y of age, most of these mice have to be euthanized because of severe dyspnea. Starting at 3 mo, the lungs of LXRα,ß(Dko) mice, but not of LXRα or LXRß single knockout mice, progressively accumulate foam cells, so that by 1 y, the lungs are covered by a "golden coat." There is infiltration of inflammatory cells and progressive accumulation of lipid in the alveolar wall, type 2 pneumocytes, and macrophages. By 14 mo, there are three histological lesions: one resembling adenomatous hyperplasia, one squamous metaplasia, and one squamous cell carcinoma characterized by expression of transformation-related protein (p63), sex determining region Y-box 2 (Sox2), cytokeratin 14 (CK14), and cytokeratin 13 (CK13) and absence of thyroid transcription factor 1 (TTF1), and prosurfactant protein C (pro-SPC). RNA sequencing analysis at 12 mo confirmed a massive increase in markers of M1 macrophages and lymphocytes. The data suggest a previously unidentified etiology of PSCCa: cholesterol dysregulation and M1 macrophage-predominant lung inflammation combined with damage to, and aberrant repair of, lung tissue, particularly the peripheral parenchyma. The results raise the possibility that components of the LXR signaling may be useful targets in the treatment of PSCCa.


Assuntos
Metabolismo dos Lipídeos , Receptores X do Fígado/fisiologia , Neoplasias Pulmonares/etiologia , Pulmão/metabolismo , Neoplasias de Células Escamosas/etiologia , Células Epiteliais Alveolares/metabolismo , Animais , Fibroblastos/metabolismo , Homeostase , Pulmão/patologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Pneumonia/etiologia , Análise de Sequência de RNA
12.
Ann Epidemiol ; 25(4): 293-296.e2, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25560876

RESUMO

PURPOSE: Human papillomavirus' (HPV's) role in skin cancer is controversial. To examine whether an individual is prone to develop a chronic oncogenic infection, we conducted a nationwide population-based cohort study of the risk of skin cancer after another HPV-related neoplasia-that is, cervical high-grade dysplasia or carcinoma-using cervical conization as a surrogate marker. METHODS: Using Danish registries, we identified all women who underwent conization from 1978 to 2011 (n = 87,164) and followed them until first-time skin cancer diagnosis, death, emigration, or 31 December 2011, whichever came first. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM) according to national incidence rates. RESULTS: The 1-year absolute risks were 0.0012%, 0.045%, and 0.029% for SCC, BCC, and MM, respectively. Conization was clearly associated with increased incidence of SCC (SIR = 1.37; 95% CI: 1.13-1.65), but not MM (SIR = 1.00; 95% CI: 0.91-1.11). BCC risk was slightly increased (SIR = 1.08; 95% CI: 1.02-1.13). CONCLUSIONS: The association between conization and cutaneous SCC provides evidence for conization as a marker of underlying general susceptibility to oncogenic HPV.


Assuntos
Colo do Útero/patologia , Melanoma/etiologia , Infecções por Papillomavirus/complicações , Neoplasias Cutâneas/etiologia , Displasia do Colo do Útero/epidemiologia , Adulto , Idoso , Biomarcadores , Carcinoma Basocelular/etiologia , Carcinoma Basocelular/virologia , Colo do Útero/virologia , Estudos de Coortes , Conização , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Melanoma/virologia , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/etiologia , Neoplasias de Células Escamosas/virologia , Fatores de Risco , Neoplasias Cutâneas/virologia , Displasia do Colo do Útero/virologia
13.
PLoS Genet ; 10(10): e1004721, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25329316

RESUMO

Exposure to ultraviolet (UV) radiation from sunlight accounts for 90% of the symptoms of premature skin aging and skin cancer. The tumor suppressor serine-threonine kinase LKB1 is mutated in Peutz-Jeghers syndrome and in a spectrum of epithelial cancers whose etiology suggests a cooperation with environmental insults. Here we analyzed the role of LKB1 in a UV-dependent mouse skin cancer model and show that LKB1 haploinsufficiency is enough to impede UVB-induced DNA damage repair, contributing to tumor development driven by aberrant growth factor signaling. We demonstrate that LKB1 and its downstream kinase NUAK1 bind to CDKN1A. In response to UVB irradiation, LKB1 together with NUAK1 phosphorylates CDKN1A regulating the DNA damage response. Upon UVB treatment, LKB1 or NUAK1 deficiency results in CDKN1A accumulation, impaired DNA repair and resistance to apoptosis. Importantly, analysis of human tumor samples suggests that LKB1 mutational status could be a prognostic risk factor for UV-induced skin cancer. Altogether, our results identify LKB1 as a DNA damage sensor protein regulating skin UV-induced DNA damage response.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Dano ao DNA/efeitos da radiação , Proteínas Serina-Treonina Quinases/metabolismo , Raios Ultravioleta/efeitos adversos , Proteínas Quinases Ativadas por AMP , Animais , Animais Recém-Nascidos , Apoptose/genética , Apoptose/efeitos da radiação , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/genética , Modelos Animais de Doenças , Fator de Crescimento de Hepatócito/genética , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Queratinócitos/efeitos da radiação , Camundongos Transgênicos , Neoplasias de Células Escamosas/etiologia , Neoplasias de Células Escamosas/patologia , Fosforilação , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Repressoras/metabolismo , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
14.
Arch Environ Occup Health ; 69(1): 3-10, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23930791

RESUMO

The authors examined the associations between farming and the risk for squamous cell (SCC) or urothelial cell (UC) carcinoma of the urinary bladder among Egyptians. The authors used data from a multicenter case-control study (1,525 male and 315 female cases, and 2,069 male and 547 female age- and residence-matched, population-based controls) to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Men in farming and who never smoked had increased risk for either SCC or UC (AOR [95% CI]: 4.65 [2.59-8.36] and 6.22 [3.82-10.15], respectively). If they ever smoked, their risks were 2.27 (1.75-2.95) and 1.93 (1.58-2.35), respectively. Women in farmer households were at increased risk for SCC (1.40 [0.93-2.09] and UC [1.25 (0.82-1.89]), although not statistically significant. Occupational and environmental exposures to farming increased the risk for bladder cancer among Egyptians.


Assuntos
Doenças dos Trabalhadores Agrícolas/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Doenças dos Trabalhadores Agrícolas/etiologia , Carcinoma/epidemiologia , Carcinoma/etiologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Egito/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/epidemiologia , Neoplasias de Células Escamosas/etiologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Razão de Chances , Fatores de Risco , Fumar/efeitos adversos , Neoplasias da Bexiga Urinária/etiologia
16.
Semin Respir Crit Care Med ; 34(3): 371-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23821511

RESUMO

Fungal infections continue to produce morbidity and mortality in lung transplant recipients despite the widespread use of antifungal prophylaxis. There has been a decline in Candida infections but Aspergillus species predominate. Other mold pathogens including Fusarium, Scedosporium, and Zygomycetes also cause infections in lung transplant recipients. Furthermore, the widespread use of antifungal prophylaxis has prompted a delay in onset of Aspergillus infection in lung transplant recipients. Pulmonary parenchymal disease has become the most common manifestation of invasive aspergillosis. Among the risk factors pre- or posttransplant Aspergillus colonization is the most important risk factor reported in several retrospective studies. Recently posttransplant colonization has been implicated in the development of bronchiolitis obliterans syndrome. Other factors that have been reported include preceding cytomegalovirus infections, hypogammaglobulinemia, and single-lung transplantation. The risk factors for other mold infections such as Scedosporium, Fusarium, and Zygomycetes are not well studied. The best antimold prophylaxis strategy and choice of drug remains to be elucidated. Most lung transplant centers use either voriconazole or inhaled amphotericin preparations. However, data have emerged regarding the increased risk of squamous cell cancer in lung transplant recipients on voriconazole prophylaxis. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in a significant decrease in mortality.


Assuntos
Antifúngicos/uso terapêutico , Pneumopatias Fúngicas/epidemiologia , Transplante de Pulmão/métodos , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Aspergilose/epidemiologia , Aspergilose/etiologia , Aspergilose/terapia , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/microbiologia , Fungos/isolamento & purificação , Humanos , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/prevenção & controle , Neoplasias de Células Escamosas/epidemiologia , Neoplasias de Células Escamosas/etiologia , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Fatores de Risco , Triazóis/efeitos adversos , Triazóis/uso terapêutico , Voriconazol
19.
Neuropathology ; 32(2): 171-3, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21692865

RESUMO

Craniopharyngiomas are histopathologically classified as adamantinomatous type (AD) and squamous-papillary type (SP). However coexistence of a mixed type seen on histopathologic specimens has not been reported. In this report, a patient diagnosed with mixed type craniopharyngioma is presented and the etiology and pathologic features are discussed.


Assuntos
Craniofaringioma/etiologia , Craniofaringioma/patologia , Neoplasias de Células Escamosas/etiologia , Neoplasias de Células Escamosas/patologia , Neoplasias Hipofisárias/etiologia , Neoplasias Hipofisárias/patologia , Idoso de 80 Anos ou mais , Craniofaringioma/complicações , Humanos , Masculino , Neoplasias de Células Escamosas/complicações , Neoplasias Hipofisárias/complicações
20.
Int J Cancer ; 130(12): 2949-60, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21796615

RESUMO

We investigated the development of esophageal neoplasia in biopsy specimens of the distinct iodine-unstained lesions (DIULs) ≥ 5 mm detected in 280 of 2,115 Japanese alcoholic men who underwent screening by esophageal iodine staining. Low-grade intraepithelial neoplasia (LGIN) was diagnosed in 155 of them, high-grade intraepithelial neoplasia (HGIN) in 57, and invasive SCC in 35. The size of the DIULs increased with the degree of neoplasia. Most LGINs were flat and were missed before iodine staining. Some DIULs became a light pink color (PC) about 2 min after staining, and 2.6, 56.1 and 96.0% of the LGIN, HGIN and invasive SCC lesions, respectively, were PC-sign-positive. Multiple DIULs of any size markedly increased the risk of LGIN [adjusted OR (95%CI) = 10.1 (7.12-14.5)], HGIN [27.9 (14.6-53.4)] and invasive SCC [21.6 (10.1-46.4)], and were strongly associated with the presence vs. absence of DIULs ≥ 5 mm [13.3 (9.21-19.1)], inactive heterozygous aldehyde dehydrogenase-2 (ALDH2*1/*2) vs. ALDH2*1/*1 [2.60 (1.79-3.78)], and less-active alcohol dehydrogenase-1B (ADH1B*1/*1) vs. ADH1B*2 allele [2.61 (1.87-3.64)]. The combination of ALDH2*1/*2 and ADH1B*1/*1 synergistically increased the risk of LGIN [4.53 (2.17-9.47)], HGIN [10.4 (4.34-24.7)] and invasive SCC [21.7 (7.96-59.3)]. Esophageal neoplasia developed at earlier ages in those with ALDH2*1/*2. Biopsy-proven HGIN was diagnosed as invasive SCC in 15 (39.5%) of 38 patients after endoscopic mucosectomy or surgery. In conclusion, large size, non-flat appearance, positive PC sign and multiplicity of DIULs and ALDH2*1/*2 and ADH1B*1/*1 were associated with development of esophageal neoplasia in Japanese alcoholics. Biopsy-proven HGIN should be totally resected for both diagnostic and therapeutic purposes.


Assuntos
Alcoólicos , Alcoolismo/complicações , Aldeído Desidrogenase/genética , Neoplasias Esofágicas/genética , Esôfago/patologia , Neoplasias de Células Escamosas/genética , Desidrogenase do Álcool de Açúcar/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/genética , Carcinoma in Situ/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/diagnóstico , Neoplasias de Células Escamosas/etiologia , Neoplasias de Células Escamosas/patologia , Fatores de Risco , Coloração e Rotulagem
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