RESUMO
BACKGROUND: Young oncologists are at particular risk of professional burnout, and this could have a significant impact on their health and care of their patients. The coronavirus disease 2019 (COVID-19) pandemic has forced rapid changes in professionals' jobs and training, with the consequent physical and psychological effects. We aimed to characterize burnout levels and determinants in young oncologists, and the effects of the pandemic on their training and health. METHODS: Two online surveys were conducted among oncology residents and young oncology specialists in Spain. The first addressed professional burnout and its determinants before the COVID-19 pandemic, while the second analyzed the impact of the pandemic on health care organization, training, and physical and psychological health in the same population. RESULTS: In total, 243 respondents completed the first survey, and 263 the second; 25.1% reported significant levels of professional burnout. Burnout was more common among medical oncology residents (28.2%), mainly in their second year of training. It was significantly associated with a poor work-life balance, inadequate vacation time, and the burnout score. Nearly three-quarters of respondents (72%) were reassigned to COVID-19 care and 84.3% of residents missed part of their training rotations. Overall, 17.2% of this population reported that they had contracted COVID-19, 37.3% had scores indicating anxiety, and 30.4% moderate to severe depression. Almost a quarter of young oncologists (23.3%) had doubts about their medical vocation. CONCLUSIONS: Burnout affects a considerable number of young oncologists. The COVID-19 pandemic has had a profound impact on causes of burnout, making it even more necessary to periodically monitor it to define appropriate detection and prevention strategies.
Assuntos
Esgotamento Profissional , COVID-19 , Oncologistas , Esgotamento Profissional/epidemiologia , Esgotamento Psicológico/epidemiologia , Esgotamento Psicológico/prevenção & controle , Humanos , Oncologia , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema de Registros , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Platina/administração & dosagem , Platina/efeitos adversos , Intervalo Livre de Progressão , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: Anxiety and depression affect cancer patients' quality of life. Our objectives were to determine the prevalence of anxiety and depression and analyze the association between positive psychological factors, sociodemographic factors, and clinical factors in oncological patients initiating adjuvant treatment. METHODS: A prospective, multicenter cohort of 600 consecutive patients completed the Brief Symptom Inventory, Mini-Mental Adjustment to Cancer, Life Orientation Scale-Revised, and Multidimensional Scale of Perceived Social Support questionnaires. RESULTS: Prevalence of anxiety and depression was 49.8 and 36.6%, respectively. Women and younger individuals were more anxious and depressed than men and seniors. Employed participants suffered more anxiety than retirees, and singles exhibited more depression than married or partnered subjects. Logistic regression analysis showed that hope, optimism, social support, being male, and older were significantly associated with a lower risk of anxiety and depression (p < 0.001). CONCLUSIONS: The high prevalence of anxiety and depression among Spaniards with cancer starting adjuvant chemotherapy suggests that more attention should be paid to mental health in these individuals. These findings are important for cancer patients because they can benefit from interventions that increase positive psychological factors such as hope, optimism, and social support to reduce anxiety and depression.
Assuntos
Ansiedade/epidemiologia , Quimioterapia Adjuvante/estatística & dados numéricos , Depressão/epidemiologia , Neoplasias/epidemiologia , Neoplasias/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/complicações , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/psicologia , Terapia Combinada , Estudos Transversais , Depressão/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Prevalência , Qualidade de Vida , Fatores de Risco , Apoio Social , Espanha/epidemiologia , Inquéritos e QuestionáriosRESUMO
AIM: To assess the prevalence and prognostic significance of additional intrathoracic findings (AIFs) in patients with cancer and pulmonary embolism (PE). AIFs were considered alterations other than the characteristic ones intrinsic to PE or changes in cardiovascular morphology. METHODS: Subjects have been taken from a Spanish national multidisciplinary and multicenter study of PE and cancer who were treated between 2004 and 2015. The endpoint was the appearance of serious complications or death within 15 days. RESULTS: The registry contains 1024 eligible patients; 41% diagnosed by computed tomography pulmonary angiography versus 59% by non-angiographic CT. Serious complications occurred within 15 days in 18.9%, [95% confidence interval (CI), 16.6-21.4%] and 9.5% (95% CI 7.9-11.5%) died. At least one AIF was seen in 72.6%. The most common AIFs were as follows: pulmonary nodules (30.9%), pleural effusion (30.2%), tumor progression (28.3%), atelectasis (19.0%), pulmonary infarct (15.2%), emphysema (13.4%), pulmonary lymphangitic carcinomatosis (4.5%), and pneumonia (6.1%). Patients with AIF exhibited a higher complication rate at 15 days: 21.9% versus 13.0%, odds ratio (OR) 1.8 (95% CI 1.2-2.8), P = 0.03, and 15-day mortality: 15.0% versus 7.3%, OR 1.9 (95% CI 1.1-3.2), P = 0.020. Patients with pneumonia, pneumothorax, pulmonary edema, pulmonary nodules, tumor progression, pulmonary fibrosis, and pleural effusion showed an excess of adverse events. CONCLUSIONS: Additional intrathoracic findings are highly prevalent and significantly impact prognosis in patients with PE and cancer, making them germane to the classification of this population.
Assuntos
Neoplasias/complicações , Embolia Pulmonar/mortalidade , Embolia Pulmonar/patologia , Doenças Torácicas/fisiopatologia , Tórax/patologia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Embolia Pulmonar/etiologia , Medição de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sistema de RegistrosRESUMO
BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , Nomogramas , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/química , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Neoplasias Esofágicas/química , Neoplasias Esofágicas/patologia , Nível de Saúde , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Gradação de Tumores , Neutrófilos , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Trastuzumab/administração & dosagem , Carga Tumoral , População Branca , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to analyze the psychometric properties of the Shared Decision-Making Questionnaire-Physician version (SDM-Q-Doc) in a sample of medical oncologists who provide adjuvant treatment to patients with non-metastatic resected cancer and the correlations between the total SDM-Q-Doc score and physician satisfaction with the information provided. METHODS: Prospective, observational and multicenter study in which 32 medical oncologists and 520 patients were recruited. The psychometric properties, dimensionality, and factor structure of the SDM-Q-Doc were assessed. RESULTS: Exploratory factor analyses suggested that the most likely solution was two-dimensional, with two correlated factors: one factor regarding information and another one about treatment. Confirmatory factor analysis based on cross-validation showed that the fitted two-dimensional solution provided the best fit to the data. Reliability analyses revealed good accuracy for the derived scores, both total and sub-scale, with estimates ranging from 0.81 to 0.89. The results revealed significant correlations between the total SDM-Q-Doc score and physician satisfaction with the information provided (p < 0.01); between information sub-scale scores (factor 1) and satisfaction (p < 0.01), and between treatment sub-scale scores (factor 2) and satisfaction (p < 0.01). Medical oncologists of older age and those with more years of experience showed more interest in the patient preferences (p = 0.026 and p = 0.020, respectively). Patient age negatively correlated with SDM information (p < 0.01) and physicians appear to provide more information to young patients. CONCLUSION: SDM-Q-Doc showed good psychometric properties and could be a helpful tool that examines physician's perspective of SDM and as an indicator of quality and satisfaction in patients with cancer.
Assuntos
Atitude do Pessoal de Saúde , Tomada de Decisões , Oncologia , Neoplasias/cirurgia , Médicos/psicologia , Inquéritos e Questionários , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Estudos ProspectivosRESUMO
BACKGROUND: Our objective was to develop a prognostic stratification tool that enables patients with cancer and pulmonary embolism (PE), whether incidental or symptomatic, to be classified according to the risk of serious complications within 15 days. METHODS: The sample comprised cases from a national registry of pulmonary thromboembolism in patients with cancer (1075 patients from 14 Spanish centres). Diagnosis was incidental in 53.5% of the events in this registry. The Exhaustive CHAID analysis was applied with 10-fold cross-validation to predict development of serious complications following PE diagnosis. RESULTS: About 208 patients (19.3%, 95% confidence interval (CI), 17.1-21.8%) developed a serious complication after PE diagnosis. The 15-day mortality rate was 10.1%, (95% CI, 8.4-12.1%). The decision tree detected six explanatory covariates: Hestia-like clinical decision rule (any risk criterion present vs none), Eastern Cooperative Group performance scale (ECOG-PS; <2 vs ⩾2), O2 saturation (<90 vs ⩾90%), presence of PE-specific symptoms, tumour response (progression, unknown, or not evaluated vs others), and primary tumour resection. Three risk classes were created (low, intermediate, and high risk). The risk of serious complications within 15 days increases according to the group: 1.6, 9.4, 30.6%; P<0.0001. Fifteen-day mortality rates also rise progressively in low-, intermediate-, and high-risk patients: 0.3, 6.1, and 17.1%; P<0.0001. The cross-validated risk estimate is 0.191 (s.e.=0.012). The optimism-corrected area under the receiver operating characteristic curve is 0.779 (95% CI, 0.717-0.840). CONCLUSIONS: We have developed and internally validated a prognostic index to predict serious complications with the potential to impact decision-making in patients with cancer and PE.
Assuntos
Técnicas de Apoio para a Decisão , Árvores de Decisões , Neoplasias/complicações , Embolia Pulmonar/diagnóstico , Medição de Risco/métodos , Índice de Gravidade de Doença , Área Sob a Curva , Feminino , Seguimentos , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Embolia Pulmonar/etiologia , Embolia Pulmonar/mortalidade , Sistema de Registros , Taxa de SobrevidaRESUMO
PURPOSE: The clinical index of stable febrile neutropenia (CISNE) can contribute to patient safety without increasing the complexity of decision-making. However, febrile neutropenia (FN) is a diverse syndrome. The aim of this analysis is to assess the performance of CISNE according to the type of tumor and infection and to characterize these patients. METHODS: We prospectively recruited 1383 FN episodes in situations of apparent clinical stability. Bonferroni-adjusted z tests of proportions were used to assess the association between the infections suspected at the time of onset and the type of tumor with the risk of serious complications and mortality. The performance of CISNE was appraised in each category using the Breslow-Day test for homogeneity of odds ratios and Forest Plots. RESULTS: 171 patients had a serious complication (12.3 %, 95 % confidence interval 10.7-14.2 %). The most common initial assumptive diagnoses were: fever without focus (34.5 %), upper respiratory infection (14.9 %), enteritis (12.7 %), stomatitis (11.8 %), and acute bronchitis (10.7 %). Lung and breast were the most common tumors, accounting for approximately 56 % of the series. The distribution of complications, mortality, and bacteremia varies for each of these categories. However, Breslow-Day tests indicate homogeneity of the odds ratio of the dichotomized CISNE score to predict complications in all infection and tumor subtypes. CONCLUSION: Despite FN's clinical and microbiological heterogeneity, the CISNE score was seen to be consistent and robust in spite of these variations. Hence, it appears to be a safe tool in seemingly stable FN.
Assuntos
Neutropenia Febril/etiologia , Neutropenia Febril/patologia , Infecções/complicações , Neoplasias/complicações , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Acute symptomatic pulmonary embolism (PE) varies in its clinical manifestations in patients with cancer and entails specific issues. The objective is to assess the performance of five scores (PESI, sPESI, GPS, POMPE, and RIETE) and a clinical decision rule to predict 30-day mortality. METHODS: This is an ambispective, observational, multicenter study that collected episodes of PE in patients with cancer from 13 Spanish centers. The main criterion for comparing scales was the c-indices and 95% confidence intervals (CIs) of the models for predicting 30-day mortality. RESULTS: 585 patients with acute symptomatic PE were recruited. The 30-day mortality rate was 21.3 (95% CI; 18.2-24.8%). The specific scales (POMPE-C and RIETE) were equally effective in discriminating prognosis (c-index of 0.775 and 0.757, respectively). None of these best performing scales was superior to the ECOG-PS with a c-index of 0.724. The remaining scores (PESI, sPESI, and GPS) performed worse, with c-indexes of 0.719, 0.705, and 0.722, respectively. The dichotomic "clinical decision rule" for ambulatory therapy was at least equally reliable in defining a low risk group: in the absence of all exclusion criteria, 30-day mortality was 2%, compared to 5% and 4% in the POMPE-C and RIETE low-risk categories, respectively. CONCLUSION: The accuracy of the five scales examined was not high enough to rely on to predict 30-day mortality and none of them contribute significantly to qualitative clinical judgment.
Assuntos
Tomada de Decisão Clínica/métodos , Neoplasias/complicações , Neoplasias/diagnóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/terapia , Prognóstico , Embolia Pulmonar/mortalidade , Embolia Pulmonar/terapia , Risco , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to investigate the antitumour promoting effects and possible mechanisms of action of the most abundant polymeric black tea polyphenols (PBPs 1-5) or thearubigins, in vivo. MATERIALS AND METHODS: Effect of PBP pre-treatments on 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted skin papillomas was studied in 7,12-dimethylbenz(a)anthracene initiated mice over 40 weeks. Cell proliferation and apoptosis, in epidermis of the skin, were measured using appropriate immunohistochemical staining. Mitogen-activated protein kinase signalling studies were conducted with Western blot analysis at 10, 20, 30 and 40 weeks of promotion. RESULTS: Pre-treatments with PBP fractions differentially altered latency, multiplicity and incidence of skin papillomas as compared to TPA treatments thereby exhibiting antipromoting effects. Most PBP fractions decreased TPA-induced cell proliferation by decreasing activation of signalling kinases (c-Jun N-terminal protein kinase, extracellular signal-regulated protein kinase, p38 protein kinase and Akt), transcription factors (activator protein-1 and nuclear factor kappa B) and inflammatory protein (cyclooxygenase 2). TPA-induced epidermal cell apoptosis was also decreased by pre-treatment with most PBP fractions. Higher levels of p53 and p21 in skin cells pre-treated with PBP fractions followed by TPA treatment as compared to only TPA-treated animals suggested possible activation of a cell cycle checkpoint. CONCLUSIONS: PBP-2 was observed to be the most potent polymeric polyphenol fraction and PBP-4 and PBP-5 showed only marginal activity, whereas PBP-1 and PBP-3 displayed intermediate efficacies. In conclusion, the protective effects of PBP fractions could be attributed to inhibition of TPA-induced cellular proliferation.
Assuntos
Flavonoides/farmacologia , Fenóis/farmacologia , Polímeros/farmacologia , Lesões Pré-Cancerosas/patologia , Neoplasias Cutâneas/patologia , Chá/química , 9,10-Dimetil-1,2-benzantraceno , Animais , Apoptose/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Ativação Enzimática/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Epiderme/enzimologia , Epiderme/patologia , Feminino , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Ornitina Descarboxilase/metabolismo , Polifenóis , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Cutâneas/enzimologia , Acetato de Tetradecanoilforbol , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Inhalation of tobacco dust is responsible for elevated genotoxicity and pulmonary ailments in workers engaged in processing tobacco for the manufacture of bidis, the Indian version of cigarettes. Tracheal tissue being the major site of interaction with tobacco dust, the effects of different concentrations of an aqueous extract of bidi tobacco (ATE) on the growth of a hamster tracheal epithelial cell line (HTE) were investigated. Colony forming efficiency assay revealed that ATE was cytotoxic only at the highest concentration of 5.0 mg/ml. In cultures treated with 1.25 mg/ml ATE, the cell doubling time and growth rate were similar to that of the controls, while a significant increase in cell doubling time (29.4+/-0.3 h vs 14.0+/-3.75 h, P<0.001) was observed at 2.5 mg/ml ATE concentration. Exposure of HTE cells to the non-toxic ATE concentration of 2.5 mg/ml was found to stimulate ornithine decarboxylase (ODC) activity, incorporation of [3H] methyl thymidine into DNA and increase in the S phase fraction was seen by flow cytometry. However, a 56% reduction in the growth rate of cultures treated with 2.5 mg/ml ATE was related to the prolongation of the traverse of cells through S phase. ATE-induced growth suppression was reversed when cultures were grown in ATE-free medium or upon repeated exposure to ATE. The findings suggest that increased tracheal cell proliferation induced by chronic inhalation of tobacco dust may contribute to the development of pulmonary disorders and possibly neoplasia in exposed individuals.
Assuntos
Nicotiana/toxicidade , Plantas Tóxicas , Traqueia/efeitos dos fármacos , Traqueia/patologia , Animais , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Cricetinae , DNA/biossíntese , Poeira/efeitos adversos , Células Epiteliais/patologia , Citometria de Fluxo , Humanos , Mesocricetus , Ornitina Descarboxilase/biossíntese , Extratos Vegetais/toxicidade , Contagem de Cintilação , Timidina/química , Nicotiana/química , Traqueia/metabolismo , Trítio , Água/químicaRESUMO
Carcinogenicity of pan masala, a dry powdered chewing mixture of areca nut, catechu, lime, spices and flavoring agents was evaluated by means of the long-term animal bio-assay 6- to 7-week old male and female S/RVCri mice were divided randomly into intermediate and lifetime exposure groups and fed normal diet without pan masala-(zero dose) or diet containing 2.5% and 5% pan masala. Animals in the intermediate-exposure group (n = 10/gender/dose group) were killed after 6, 12 or 18 months of treatment, while those in the lifetime-exposure group (n = 54/gender/dose group) were killed when moribund or at the termination of the experiment at 24 months. Several tissues were processed for histopathological examination. The body weight and survival rate of mice fed pan masala were lower than that of the controls. Histopathological observations of tissues from control animals did not reveal any neoplastic alterations. However, lifetime feeding of pan masala induced adenoma of the liver, stomach, prostate and sebaceous glands, also forestomach papilloma, liver hamartoma, hepatoma and hemangioma, carcinoma of the forestomach, adenocarcinoma of the lung and liver, and testicular lymphoma. Neoplastic lesions appeared mainly in the liver (n = 13), stomach (n = 3) and lung (n = 8). Lung adenocarcinoma, the most frequent malignant tumor type, was observed in 2/120 mice in the intermediate-exposure group and in 8/216 animals in the lifetime-exposure group. Statistical analysis of tumor-induction data revealed a significant dose-related increase in lung adenocarcinomas but not in liver and stomach neoplasms indicating that lung is the major target tissue for the carcinogenic action of pan masala.
Assuntos
Areca/efeitos adversos , Catequina/efeitos adversos , Aromatizantes/efeitos adversos , Farinha/efeitos adversos , Alimentos Formulados/efeitos adversos , Plantas Medicinais , Especiarias/efeitos adversos , Animais , Testes de Carcinogenicidade , Feminino , Masculino , Camundongos , Neoplasias Experimentais/etiologia , Neoplasias Experimentais/patologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Fatores de TempoRESUMO
Pan masala, a dry powdered mixture of areca nut, catechu, lime, unspecified spices and flavoring agents, has gained widespread popularity as a chewing substitute in India. In this study, the carcinogenic and tumor-promoting potential of an ethanolic pan masala extract (EPME) was determined using skin of S/RVCri-ba mice and forestomach and esophagus of ICRC mice as the target tissues. Carcinogenic activity of pan masala was tested by painting the mouse skin for 40 weeks with EPME or by gavage feeding for 6 months. Following initiation with 9,10-dimethylbenz(a)anthracene (DMBA), carcinogenesis of mouse skin was promoted with different doses of EPME, while gastric- and esophageal-tumor-promoting activity was determined by administering EPME by gavage to animals initiated with diethylnitrosamine (DEN). The ability of EPME to effect progression of skin papilloma to carcinoma and cutaneous alterations after a single or multiple EPME treatment were also evaluated. EPME at 25 mg per dose promoted skin-papilloma formation between 30 and 40 weeks of treatment and enhanced the rate of conversion of papilloma to carcinoma. Induction of mild epidermal hyperplasia, dermal edema, increase in epidermal mitotic activity and the rate of epidermal and dermal DNA synthesis by EPME correlated well with its skin-tumor-promoting potential. In ICRC mice, EPME was inactive as a complete carcinogen, but effectively promoted the development of forestomach and esophageal papilloma and carcinoma in a concentration-dependent manner. The tumor incidence at 25 mg EPME per dose was comparable with that obtained in the 12-O-tetradecanoylphorbol-13 acetate(TPA)-treated group. The findings indicate that habitual pan-masala use may exert carcinogenic and co-carcinogenic influence.
Assuntos
Areca , Neoplasias Esofágicas/induzido quimicamente , Plantas Medicinais , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Gástricas/induzido quimicamente , 9,10-Dimetil-1,2-benzantraceno , Animais , Cocarcinogênese , Neoplasias Esofágicas/patologia , Feminino , Masculino , Camundongos , Camundongos Pelados , Camundongos Endogâmicos ICR , Pós , Neoplasias Cutâneas/patologia , Neoplasias Gástricas/patologia , Acetato de Tetradecanoilforbol/toxicidadeRESUMO
Workers engaged in processing tobacco for the manufacture of bidis, the most popular smoking devices in India, are exposed to tobacco dust, volatile components and flakes via nasopharyngeal and cutaneous routes. In order to evaluate the risk of occupational tobacco exposure, the complete carcinogenic action of an aqueous extract of bidi tobacco (ATE), its ability to initiate and promote skin papillomas and to convert these to carcinomas, was tested in hairless S/RV Cri-ba mice using the skin tumorigenesis protocol. Epidermal cell kinetics and tissue alterations were recorded after a single or multiple applications of ATE to 7,12-dimethylbenz[a]-anthracene(DMBA)- initiated mouse skin. While ATE did not exhibit complete carcinogenic, initiating or progressor activity, it effectively promoted skin papilloma formation in DMBA-initiated mice. An increase in papilloma yield per mouse above the control was noted only after 30 weeks of promotion, and at week 40 of promotion with 5 mg and 50 mg ATE it was significantly higher than that in the control mice (9.69 +/- 1.30 and 11.73 +/- 1.38 compared to 4.70 +/- 1.01; P < 0.01). Mild epidermal hyperplasia, increase in mitotic activity and dermal thickness induced by a single application of ATE persisted upon multiple treatment and correlated well with its tumour-promoting activity. The findings indicate that occupational exposure to bidi tobacco may pose a cancer risk among workers in the bidi industry.
Assuntos
9,10-Dimetil-1,2-benzantraceno , Cocarcinogênese , Nicotiana , Papiloma/induzido quimicamente , Extratos Vegetais/toxicidade , Plantas Tóxicas , Neoplasias Cutâneas/induzido quimicamente , Animais , Divisão Celular , Feminino , Camundongos , Camundongos Mutantes , Exposição Ocupacional , Pele/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia , Fatores de TempoRESUMO
To stimulate conditions wherein humans might be exposed to tumor promoters prior to carcinogenic stimulus, female S/RV Cri mice were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 10 weeks followed by a sc injection of 3-methylcholanthrene (MCA). Six weeks after MCA administration, tissue alterations in different skin layers were analysed by histology, morphometry and autoradiography. Multiple application of TPA prior to MCA injection induced moderate to marked epidermal hyperplasia with an increase in the thickness of nucleated cell layers and stratum granulosum. As compared to control, number of basal and suprabasal cells per 7.5 mm of interfollicular epidermal (IFE) length was significantly higher in the skin of animals treated with TPA + MCA. The hyperplastic response was accompanied by a significant increase in epidermal mitotic activity, number of cells in DNA-synthetic phase in epidermis, dermis and subcutis and subepidermal mast cell population. Histological observations of induced tumors revealed a significant increase in the incidence of carcinomas and mixed neoplasms of epithelial and mesenchymal histogenesis. The findings suggest that stimulated cellular proliferation in different layers of mouse skin by TPA treatment prior to MCA injection may play a major role in enhanced expression of histogenetically distinct tumors.
Assuntos
Transformação Celular Neoplásica/patologia , Metilcolantreno/toxicidade , Neoplasias Cutâneas/patologia , Pele/patologia , Acetato de Tetradecanoilforbol/toxicidade , Animais , Divisão Celular/efeitos dos fármacos , Transformação Celular Neoplásica/induzido quimicamente , Modelos Animais de Doenças , Feminino , Humanos , Hiperplasia , Camundongos , Camundongos Endogâmicos , Pele/efeitos dos fármacos , Neoplasias Cutâneas/induzido quimicamenteRESUMO
Previous studies on the influence of phorbol esters on mouse skin tumorigenesis have shown that 12-O-tetradecanoylphorbol-13-acetate (TPA) enhances development of malignant epithelial and mesenchymal skin tumors by a completely carcinogenic dose of 3-methylcholanthrene (MCA), while its congener phorbol-12, 13-diacetate (PDA) exerts an inhibitory effect. Differential effects of these two agents were analysed by histology, morphometry and cell kinetic techniques including autoradiography and estimation of labelled precursor incorporation into DNA by liquid scintillation counting. Epidermal hyperplasia induced on exposure of S/RV Cri mouse skin to a single or multiple TPA application after MCA injection was associated with a significant increase in the thickness of nucleated cell layers, stratum granulosum, number of suprabasal cells and dark basal cells. Enhancing effect of TPA on MCA-induced neoplastic development correlated well with an increase in mitotic activity, number of cells in S-phase and increased rate of DNA synthesis in the epidermis, dermis and subcutis as also mast cell number. In contrast, treatment of MCA-injected preneoplastic mouse skin with PDA resulted in epidermal hypoplasia and cellular damage evident as cytoplasmic vacuolation and nuclear pyknosis. Multiple PDA exposure also reduced the thickness, mitotic index and number of cells in S-phase in epidermis, dermis and subcutis. Thus, cellular toxicity and inability to recruit cells in DNA-synthetic phase may account for inhibition of progression of preneoplastic epithelial and mesenchymal cells into overt tumors by PDA.
Assuntos
Papiloma/induzido quimicamente , Ésteres de Forbol/farmacologia , Neoplasias Cutâneas/induzido quimicamente , Animais , Divisão Celular , Feminino , Cinética , Camundongos , Camundongos Endogâmicos , Neoplasias Cutâneas/patologiaRESUMO
The effects of short-term exposure to phorbol ester tumor promoters on epithelial and mesenchymal skin tumor induction, studied histologically in female S/RVCri mice, rendered precancerous by a subcutaneous (sc) injection of 3-methylcholanthrene (MCA). At 6 weeks after MCA injection, mice in Groups I to VI received topical twice weekly applications of 0.1 ml acetone, 1.8 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol didecanoate (PDD), phorbol dibenzoate (PDB), phorbol diacetate (PDA) or 6.1 nmol mezerein (MEZ) in 0.1 ml acetone, respectively, for four weeks. Animals were sacrificed after the development of palpable tumors. Data from various phorbol ester treatment groups were compared with the acetone control. Of the promoters tested, TPA treatment increased the percentage of tumor bearers and the number of combinations and expression of diverse neoplasms in the mixed growths. TPA-related phorbol esters such as PDD, PDB or MEZ did not alter the percentage of tumor bearers although the histological distribution into pure epithelial or mesenchymal and mixed tumor bearers differed significantly from the control treated with the solvent alone. However, PDA significantly inhibited MCA-induced skin tumorigenesis and increased the average time of tumor induction. All the promoters, except TPA, decreased the percentage of mixed tumor bearers, the development of hibernoma and fibrosarcoma, while allowing a selective expression of rhabdomyosarcoma.
Assuntos
Ésteres de Forbol/administração & dosagem , Neoplasias Cutâneas/induzido quimicamente , Animais , Cocarcinogênese , Feminino , Metilcolantreno , Camundongos , Camundongos Endogâmicos , Ésteres de Forbol/toxicidade , Neoplasias Cutâneas/prevenção & controleRESUMO
The effects of TPA, PDD, PDB, PDA, or MEZ on epithelial and mesenchymal skin tumors induced by a s.c. injection of MCA were studied histologically. Group-I mice received only MCA. At 6 weeks after MCA injection, mice in groups II to VII received acetone, 1.8 nmol TPA, PDD, PDB, PDA, or 6.1 nmol MEZ respectively in 0.1 ml acetone twice weekly until tumor development. Alterations in skin tumor induction patterns were also studied in animals that had been exposed to TPA or acetone for 10 weeks prior to s.c. injection of MCA. Exposure of mouse skin to TPA before or after carcinogen administration increased 2- to 3.5-fold, the incidence of carcinoma and mixed tumors of epithelial and mesenchymal histogenesis. The average time of tumor induction decreased in mice treated with MCA + TPA and 100% of the test animals in the TPA + MCA group developed tumors. In contrast, TPA-related phorbol esters inhibited skin tumor development, particularly trichoepithelioma and fibrosarcoma and increased the average time of tumor induction.