Marcos Eduardo Machado Paschoal

Brazilian version of the QLQ-LC13 lung cancer module of the European Organization for Research and Treatment of Cancer: preliminary reliability and validity report.

This study reports the reliability and validity of the Brazilian Portuguese version of QLQ-LC13. After translation and cross-cultural adaptation, the questionnaire was administered, together with the QLQ-C30 core questionnaire, to 82 patients with lung cancer. The analysis was based on 60 patients who completed two interviews, and who received chemotherapy alone or in combination with radiotherapy. The reliability or internal consistency of dyspnea scale was 0.79. The pain scale needed to be combined with the QLQ-C30 pain items to reach a satisfactory value of 0.73. The construct validity was supported by the ability of the questionnaire to discriminate patients regarding their performance status and type of treatment. However, the change over time, although in the expected direction for all items, was statistically significant in four of the 10 items studied. The criterion-related validity was supported by the statistically significant correlation between all four side effect items and the physicians’ reports of toxicity, while the evolutive changes in the performance status were statistically significant in only four items. Most psychometric properties of the Brazilian version of the QLQ-LC13 were adequately supported in this analysis. However, a wider utilization of this module is necessary to fully ascertain its reliability and validity properties.

Marcadores moleculares no câncer de pulmão: papel prognóstico e sua relação com o tabagismo

Epidemiological studies have demonstrated a causal relationship between smoking and lung cancer. Although most lung cancer cases are linked to smoking, only a minority of heavy smokers develop lung cancer, leading to the notion that genetic factors affect individual susceptibility. The principal molecular changes in lung cancer are seen in tumor suppressor genes, proto-oncogenes, growth factors, telomerase activity, and methylation status of promoters. Well-known agents include angiogenesis-stimulating factors (such as vascular endothelial growth factor), as well as factors related to tumor cell proliferation and apoptosis (epidermal growth factor receptor, p53, K-ras, retinoblastoma and BCL-2). Several of these genetic factors have already been investigated, but no single parameter has yet presented sufficient selectivity regarding prognostic value or therapeutic efficacy. Treatment strategies to cure lung cancer should focus on these early genetic lesions in order to promote their repair or to eliminate these lung cancer cells.

The cigarette burden (measured by the number of pack-years smoked) negatively impacts the response rate to platinum-based chemotherapy in lung cancer patients

PURPOSE To evaluate the impact of the cigarette burden (CB) on the response rate to platinum-based chemotherapy (CT) in patients with lung cancer (LC). METHODS Retrospective study of patients with LC treated by CT from 2000 to 2005, in a tertiary referral center in Brazil. The CB was measured by the number of pack-years smoked (PY). To evaluate the response (by RECIST), it was necessary to accomplish two cycles of CT. The relevant variables were studied by univariate and multivariate statistical techniques. RESULTS Two hundred and eighty-five patients (203 men) were studied (mean age=60.6+/-10.1 years, mean PY=58.3+/-35.4). 62.8% were current smokers, 26.7% were former smokers, and 10.5% were non-smokers. 63.2% had non-small-cell lung cancer (NSCLC), and 36.8% had small-cell lung cancer (SCLC). The treatment intent was palliative in 63.9% and curative in 36.1%. All 285 patients received platinum-based CT (etoposide/cisplatin in 68.8% and etoposide/carboplatin in 31.2%). Of these, 155 patients (54.4%) received RT (median dose=50.0 Gy; range=45.0-80.0). The 94 patients (33.0%) who responded to treatment had a mean PY of 38.7+/-27.1, and the 191 patients (67.0%) who did not respond had a mean PY of 67.8+/-35.1, p<0.001. In the multivariate analysis, the main independent negative predictor was CB>or=40 PY (adjusted OR=10.42; 95% CI=5.13-21.28). The others independent negative predictors were: CT (no. of cycles=2-4) (adjusted OR=4.86; 95% CI=2.44-9.68), treatment regimen with CT alone (adjusted OR=3.38; 95% CI=1.67-6.84), and NSCLC histology (adjusted OR=2.75; 95% CI=1.12-6.76). CONCLUSION Patients with CB>or=40 PY have a worse response to platinum-based CT compared to those who have a CB<40 PY.

The relationship between lung cancer histology and the clinicopathological characteristics of bone metastases

OBJECTIVES Lung cancer is the leading cause of death due to cancer, and bone is one of the most frequent sites of metastasis. However, there is no published evidence regarding an association between lung cancer histology and skeletal complications. Therefore, we evaluated the influence of lung cancer histology on the frequency of bone metastases (BMs), skeletal-related events (SREs), and survival after BM. MATERIAL AND METHODS This retrospective study evaluated medical records from 413 patients who were diagnosed with lung cancer between 2003 and 2012. The prevalences of BMs and SREs were calculated, and their associations with the histological subtypes were evaluated using the chi-square test, odds ratios (OR), and 95% confidence intervals (CI). Overall survivals and associations with the histological subtypes were evaluated using the Kaplan-Meier method and the log-rank test. RESULTS The prevalences of BM, synchronous BM, and SREs were 28.2%, 70.4%, and 68.7%, respectively. Adenocarcinoma was the most common histological subtype (46.7%), and was significantly more frequent among patients with BM (58.3% vs. 42.1%; p=0.003; OR: 1.92; 95% CI: 1.29-2.97). Squamous cell was significantly less frequent among patients with BM (13.0% vs. 29.8%; p=0.0004; OR: 0.35; 95% CI: 0.19-0.64). The median survival time after the first BM diagnosis was 4 months, and there was no significant difference in the survival periods for the various histological subtypes. CONCLUSION Adenocarcinoma and squamous cell were significantly associated with higher and lower risks of developing BM, respectively.

Marcadores tumorais no câncer de pulmão: um caminho para a terapia biológica

Recent advances in genetics and molecular biology lead to the identification of genes and protein products overexpressed by tumors. Such products, called tumor markers, were previously used only as diagnostic and prognostic tools, but are currently being the target of extensive research, with growing evidence that some of them may have an important role in the development of new treatment modalities, targeting the tumor cell biological cycle. In this article, the authors review the role of some of the traditionally known tumor markers (CEA, p53, NSE, K-ras), and describe the prevalence and the role of the epidermal growth factor receptor (EGFR) overexpression and its protein product, p185neu. New drugs have been developed, aiming at the blockade of the signaling process initiated by the EGFR. Among these, the authors highlight ZD1839 (Iressa), a new orally administered drug that reversibly and selectively inhibits the EGFR tyrosine-kinase activity. This drug has demonstrated good results in the treatment of non-small-cell lung cancer, as an isolated drug or in combination with other chemotherapy agents. Targeting the EGFR could represent a significant contribution to cancer therapy, mainly the non-small-cell lung cancer.

Heparanase expression and localization in different types of human lung cancer.

BACKGROUND Heparanase is the only known mammalian glycosidase capable of cleaving heparan sulfate chains. The expression of this enzyme has been associated with tumor development because of its ability to degrade extracellular matrix and promote cell invasion. METHODS We analyzed heparanase expression in lung cancer samples to understand lung tumor progression and malignancy. Of the samples from 37 patients, there were 14 adenocarcinomas, 13 squamous cell carcinomas, 5 large cell carcinomas, and 5 small cell carcinomas. Immunohistochemistry was performed to ascertain the expression and localization of heparanase. RESULTS All of the tumor types expressed heparanase, which was predominantly localized within the cytoplasm and nucleus. Significant enzyme expression was also observed in cells within the tumor microenvironment, such as fibroblasts, epithelial cells, and inflammatory cells. Adenocarcinomas exhibited the strongest heparanase staining intensity and the most widespread heparanase distribution. Squamous cell carcinomas, large cell carcinomas, and small cell carcinomas had a similar subcellular distribution of heparanase to adenocarcinomas but the distribution was less widespread. Heparanase expression tended to correlate with tumor node metastasis (TNM) staging in non-small cell lung carcinoma. CONCLUSION In this study, we showed that heparanase was localized to the cytoplasm and nucleus of tumor cells and to cells within the microenvironment in different types of lung cancer. This enzyme exhibited a differential distribution based on the type of lung tumor. General significance Elucidating the heparanase expression patterns in different types of lung cancer increased our understanding of the crucial role of heparanase in lung cancer biology. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.

Efeito do álcool perílico na expressão gênica de células de adenocarcinoma de pulmão humano

OBJECTIVE: To study the effect of perillyl alcohol on the gene expression of human pulmonary adenocarcinoma cells. METHODS: Pulmonary adenocarcinoma cells were incubated with perillyl alcohol in dilutions ranging from 0.03% to 0.0003% for 48 hours. Alterations were observed in the cell morphology, and cell viability was quantified using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. Protein synthesis of samples previously targeted with S35 was analyzed using electrophoresis on a polyacrylamide gel. Expression of the proteins p53 and p44/42 was determined using the Western blot method. RESULTS: After 48 hours of incubation, greater nsumbers of morphological alterations were observed in cells treated with the 0.03% perillyl alcohol dilution than in those treated with perillyl alcohol diluted to 0.003% or further. Treatment with perillyl alcohol dilutions of 0.03%, 0.003% and 0.0003% inhibited cellular viability by 60.17% (p < 0.001), 15.62% (p < 0.001) and 11.53% (p < 0.05), respectively. The results show that 28-kDa, 42-kDa and 110-kDa proteins were induced. No statistically significant effect on p53 expression was observed. In comparison with the expression of a-tubulin, the 0.003% perillyl alcohol dilution induced an increase in p42 phosphorylation and a marked decrease in p44 phosphorylation. CONCLUSION: The results suggest that there are other, previously undescribed, metabolic pathways for perillyl alcohol effects in human pulmonary adenocarcinoma cells.

Primary Aneurysmal Bone Cyst of Long Bones Treated with a Single Dose ofCalcitonin and Methylprednisolone Percutaneous Intralesional Injection: A CaseSeries and Literature Review

Aneurysmal bone cyst is a rare benign bone tumor usually treated by surgery, which may in turn result in poor functional outcome and recurrence. This study aims to report a series of cases of primary ABC treated with a single dose of calcitonin and methylprednisolone injection. Six patients treated with a single-dose combination of calcitonin (200 UI) and methylprednisolone (120 mg) at a single institution from January 2011 to December 2013 were clinically and radiologically evaluated. After the follow-up period, all patients presented cyst healing. The mean time to healing was 2.8 months. The final mean overall functional score rating was 89.0%. We conclude that intralesional calcitonin and methylprednisolone injection results in aneurysmal bone cyst healing with good functional outcomes and thus can be an effective treatment method.

Profile of proteins complexed with circulating DNA of a lung cancer patient.

MÁRCIA TIE KAWAMURA,a MARCOS EDUARDO PASCHOAL,a,b AND MARIA DA GLORIA DA COSTA CARVALHOa,b,c aLaboratório de Controle da Expressão Gênica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Ilha do Fundão, Rio de Janeiro, R.J. CEP: 21949-900, Brazil bLaboratório de Oncologia Molecular, Serviço de Pneumologia do Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Cidade Universitária, Rio de Janeiro, R.J. CEP: 21949-900, Brazil

O impacto da histologia do carcinoma pulmonar na frequência das metástases ósseas

Objective  Lung cancer is the leading cause of death by cancer, and the bones are one of the most common sites of metastasis from this condition. This study aimed to evaluate the influence of lung carcinoma histology on the frequency of bone metastases. Methods  This retrospective study evaluated the medical records of 407 patients diagnosed with lung cancer between 2003 and 2012. The prevalence of bone metastases and their association with histological subtypes were evaluated using chi-squared tests, odds ratios (ORs) and 95% confidence intervals (CIs). The overall survival was evaluated using the Kaplan-Meier method. Results  The prevalence of bone metastases was 28.2% ( n  = 115), and the spine was the most frequently affected site (98 metastases; 32.1%). Adenocarcinoma was the most common histological subtype of lung carcinoma (46.7%), and it was significantly more frequent among patients with bone metastases (58.3% versus 42.1%; p  = 0.003; OR = 1.92; 95% CI: 1.29–2.97). Squamous cell carcinoma was significantly less frequent among patients with bone metastases (13.0% versus 29.8%; p  = 0.0004; OR = 0.35; 95% CI: 0.19–0.64). The median survival time after the first bone metastasis diagnosis was 4 months. Conclusion  Adenocarcinoma was the most common histological subtype of lung carcinoma, and it was significantly associated with a higher risk of developing bone metastases.