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1.
BMC Cancer ; 19(1): 132, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736741

RESUMO

BACKGROUND: There are inconsistencies in the literature regarding the prevalence and assessment of chemotherapy-induced peripheral neuropathy (CIPN). This study explored CIPN natural history and its characteristics in patients receiving taxane- and platinum-based chemotherapy. PATIENTS AND METHODS: Multi-country multisite prospective longitudinal observational study. Patients were assessed before commencing and three weekly during chemotherapy for up to six cycles, and at 6,9, and 12 months using clinician-based scales (NCI-CTCAE; WHO-CIPN criterion), objective assessments (cotton wool test;10 g monofilament); patient-reported outcome measures (FACT/GOG-Ntx; EORTC-CIPN20), and Nerve Conduction Studies. RESULTS: In total, 343 patients were recruited in the cohort, providing 2399 observations. There was wide variation in CIPN prevalence rates using different assessments (14.2-53.4%). Prevalence of sensory neuropathy (and associated symptom profile) was also different in each type of chemotherapy, with paclitaxel (up to 63%) and oxaliplatin (up to 71.4%) showing the highest CIPN rates in most assessments and a more complex symptom profile. Peak prevalence was around the 6-month assessment (up to 71.4%). Motor neurotoxicity was common, particularly in the docetaxel subgroup (up to 22.1%; detected by NCI-CTCAE). There were relatively moderately-to-low correlations between scales (rs = 0.15,p < 0.05-rs = 0.48 p < 0.001), suggesting that they measure different neurotoxicity aspects from each other. Cumulative chemotherapy dose was not associated with onset and course of CIPN. CONCLUSION: The historical variation reported in CIPN incidence and prevalence is possibly confounded by disagreement between assessment modalities. Clinical practice should consider assessment of motor neuropathy for neurotoxic chemotherapy. Current scales may not be all appropriate to measure CIPN in a valid way, and a combination of scales are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Doenças do Sistema Nervoso Periférico/diagnóstico , Prevalência , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença
2.
Support Care Cancer ; 27(12): 4753-4762, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30972646

RESUMO

CONTEXT/OBJECTIVES: This is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy. METHODS: Cancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score. RESULTS: There was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = - 0.722, p < 0.001 and r = - 0.518, p < 0.001, respectively; T3: r = - 0.699; p < 0.001 and r = - 0.523, p < 0.001, respectively). The correlation between the change scores of the Ntx subscale and the QLQ-CIPN20 autonomic subscale was poor (T2: r = - 0.354, p < 0.001; T3: r = 0.286, p < 0.001). Based on the MCID derived using distribution-based method, the MCID for the QLQ-CIPN20 sensory subscale was 2.5-5.9 (6.9% to 16.4% of the subdomain score) and for motor subscale was 2.6-5.0 (8.1%-15.6% of the subdomain score). CONCLUSION: The MCID for the EORTC QLQ-CIPN20 established using distribution-based approaches was 2.5-5.9 for the sensory subscale and 2.6-5.0 for the motor subscale. When noted in assessments even with small change in scores, clinicians can be alerted for appropriate intervention.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Compostos Organoplatínicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Síndromes Neurotóxicas/diagnóstico , Compostos Organoplatínicos/administração & dosagem , Doenças do Sistema Nervoso Periférico/diagnóstico , Qualidade de Vida , Inquéritos e Questionários , Taxoides/administração & dosagem , Taxoides/efeitos adversos
3.
Nicotine Tob Res ; 18(11): 2057-2064, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27107433

RESUMO

INTRODUCTION: Previous studies revealed that some indoor air pollutants and fine particle matter can interact with active smoking, enhancing lung cancer risk in smokers. Secondhand smoke (SHS), with remarkable differences from active smoking, contributes significantly to indoor air pollution and generates a considerable amount of fine particle matter, may cause a similar interaction with active smoking. METHODS: Information on lifetime SHS along with active smoking and other confirmed or suspected risk factors for lung cancer was collected in this case-referent study. Odds ratios and the 95% confidence intervals (95% CIs) of smoking status in different levels of SHS were evaluated. Potential multiplicative and additive interactions were explored. RESULTS: Compared with never-smokers without SHS, current smokers who were exposed to a high level of SHS demonstrated the highest odds ratio (15.13, 95% CI: 8.60, 26.65), almost doubles the effect in the current smokers without SHS. Significant additive interactions between current smoking and high level of SHS were observed for all lung cancers (synergy index = 1.80, 95% CI: 1.02, 3.24) and the squamous carcinoma subgroup. CONCLUSIONS: High level of SHS exposure greatly enhanced lung cancer risk among current smokers, consistent with an additive interaction; while this interaction was predominant for the squamous carcinoma. The results provide new evidence to the rationale of promoting global smoking cessation. IMPLICATIONS: Some indoor air pollutants can interact with active smoking, yielding a synergistic effect on inducing lung cancer. SHS, with noticeable differences from active smoking, is a major source of indoor air pollution. However, little has been known about the effect of SHS in smokers and whether there is a similar interaction between SHS and active smoking. In this study, we evaluated their separate and joint effects and indeed found a more than additive interaction between them. This finding suggests a potential problem of gathering smoking aggravating by venue restriction policies and re-advocates policy efforts on smoking cessation.


Assuntos
Adenocarcinoma/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Adenocarcinoma/induzido quimicamente , Idoso , Poluição do Ar em Ambientes Fechados/efeitos adversos , Carcinoma de Células Escamosas/induzido quimicamente , Estudos de Casos e Controles , Hong Kong/epidemiologia , Humanos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Saúde do Homem , Razão de Chances , Fatores de Risco , Abandono do Hábito de Fumar
4.
RNA Biol ; 8(1): 125-31, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21289483

RESUMO

MicroRNAs (miRNAs) are emerging as important modulators in cellular pathways and they appear to play a key role in tumorigenesis. MiR-145 is downregulated in several human malignancies, including lung cancer, but the responsible molecular mechanisms remain unclear. We previously reported that restoration of hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. This study showed that hsa-miR-145 targets EGFR and nucleoside diphosphate linked moiety X-type motif 1 (NUDT1 or MTH1) in lung adenocarinoma cells. The mRNA expressions of EGFR and NUDT1 were significantly downregulated after miR-145 transfection in human lung adenocarcinoma cells. Our results demonstrated miR-145 in the negative regulation of EGFR and NUDT1 expressions at both mRNA and protein levels. Further analysis showed that miR-145 has the ability to inhibit cell proliferation on transfected lung adenocarcinoma cells over three time points (24, 48 and 72 hours). Upregulation of miR-145 appeared to be an important gene regulation mechanism for the proliferation of lung adenocarcinoma cells and it correlated strongly with the downregulation of EGFR and NUDT1. Interestingly, our study revealed that the altered proliferation in lung cancer cells is not accompanied by changes in apoptosis. Our findings provided new insight into the complex regulating pathway comprising of miR-145, EGFR, NUDT1 and other unknown factors which function in cell proliferation but not in apoptosis. Understanding miR-145's targets and its regulating pathways may lead to new therapeutic strategies for lung adenocarcinoma.


Assuntos
Proliferação de Células , Enzimas Reparadoras do DNA/metabolismo , Receptores ErbB/metabolismo , MicroRNAs/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma de Pulmão , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Biologia Computacional , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , MicroRNAs/uso terapêutico , Análise em Microsséries , Pessoa de Meia-Idade , Mutação , Transfecção
5.
Am J Epidemiol ; 169(5): 533-41, 2009 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-19126588

RESUMO

No studies have specifically reported the association of lung adenocarcinoma with environmental tobacco smoke (ETS) exposure among nonsmoking males. The objective of this study was to examine the exposure-response relation between ETS exposure and lung cancer among nonsmoking males. In particular, the association with adenocarcinoma of the lung was studied. This is a population-based, case-referent study in Hong Kong during 2004-2006. A total of 132 Chinese male nonsmokers with newly diagnosed primary lung cancer and 536 nonsmoking community referents were interviewed about ETS exposures from the household and/or workplace, including ever ETS exposure, sources of exposure, number of smoking cohabitants/coworkers, and smoker-years. Univariate logistic regression analyses showed a weak association between all lung cancers and ever ETS exposure from the household and/or workplace (odds ratio (OR) = 1.11, 95% confidence interval (CI): 0.74, 1.67), but an increased risk was restricted to adenocarcinoma (OR = 1.68, 95% CI: 1.00, 2.38). After adjustment for family cancer history and other confounders, excess risk (OR = 1.62, 95% CI: 0.91, 2.88) still persisted for adenocarcinoma, although it was no longer statistically significant. Exposure-response relations for adenocarcinoma were found with increasing levels of all ETS indices when exposures from the household and workplaces were combined. The consistent exposure-response relations between ETS exposures and adenocarcinoma suggested a probable causal link, which would have to be confirmed by future larger studies.


Assuntos
Adenocarcinoma/epidemiologia , Adenocarcinoma/etiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Distribuição por Idade , Idoso , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Grandes/etiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Hong Kong/epidemiologia , Humanos , Entrevistas como Assunto , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Fatores de Risco , Abandono do Hábito de Fumar , Poluição por Fumaça de Tabaco/análise
6.
Cancer Causes Control ; 20(5): 757-63, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19169896

RESUMO

Chinese women in Hong Kong have among the highest incidence and mortality of lung cancer in the world, in spite of a low prevalence of smoking. We carried out this population-based case-control study to evaluate the associations of previous lung disease and family cancer history with the occurrence of lung cancer among them. We selected 212 cases that were newly diagnosed with primary lung cancer, and randomly sampled 292 controls from the community, frequency matched by age group. All the cases and controls were lifetime nonsmokers. We estimated the main effects of preexisting asthma, pulmonary tuberculosis, pneumonia, chronic bronchitis, and family lung/all cancer history, using unconditional logistic regression, accounting for various potential risk factors and confounders. All of the previous lung diseases, except chronic bronchitis, were related to an elevated risk for lung cancer, and the association with asthma was significant. Those who had more than one previous lung disease tended to be at higher risk than those with only one of them. Positive family history of any cancer was associated with over 2-fold risk than negative family history. The joint effect of positive history of previous pulmonary diseases and positive family cancer history appeared to be additive, indicating the two factors acted independently. The results support an etiological link of preexisting lung disease and family cancer history to the risk of lung cancer.


Assuntos
Pneumopatias/complicações , Neoplasias Pulmonares/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Hong Kong/epidemiologia , Humanos , Pneumopatias/epidemiologia , Neoplasias Pulmonares/etiologia , Estudos Prospectivos , Fatores de Risco
7.
Cancer Invest ; 26(2): 128-35, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18259942

RESUMO

Half of the female patients with adenocarcinoma in East Asia are never-smokers. Proteomic analysis of tumor tissue may throw important light on the pathogenesis of this interesting subgroup of lung cancer. The cancer and adjacent normal lung tissue were taken from 21 never-smoked adenocarcinoma and profiled using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Fifty-two proteins were significantly discriminatory between tumor and normal lung tissues. Ninety-three proteins were found to have high accuracy in discriminating between adenocarcinoma with or without smoking history. These proteins may yield new insights about the altered pathogenetic pathways of never-smoked lung cancers.


Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Neoplasias Pulmonares/química , Proteômica , Adenocarcinoma/etnologia , Adenocarcinoma/patologia , Povo Asiático/etnologia , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/patologia , Biologia Computacional , Feminino , Hong Kong/epidemiologia , Humanos , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/patologia , Masculino , Análise Serial de Proteínas , Proteoma/análise , Fumar , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
8.
Cancer Res ; 66(9): 4961-7, 2006 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-16651454

RESUMO

The high incidence of lung cancer among Chinese females, despite a low smoking prevalence, remains poorly explained. Cooking fume exposure during frying could be an important risk factor. We carried out a population-based case-control study in Hong Kong. Cases were Chinese female nonsmokers with newly diagnosed primary lung cancer. Controls were female nonsmokers randomly sampled from the community, frequency matched by age groups. Face-to-face interviews were conducted using a standardized questionnaire. The "total cooking dish-years," categorized by increments of 50, was used as a surrogate of cooking fumes exposure. Multiple unconditional logistic regression was used to estimate the odds ratios (OR) for different levels of exposure after adjusting for various potential confounding factors. We interviewed 200 cases and 285 controls. The ORs of lung cancer across increasing levels of cooking dish-years were 1, 1.17, 1.92, 2.26, and 6.15. After adjusting for age and other potential confounding factors, the increasing trend of ORs with increasing exposure categories became clearer, being 1, 1.31, 4.12, 4.68, and 34. The OR of lung cancer was highest for deep-frying (2.56 per 10 dish-years) followed by that of frying (1.47), and stir-frying had the lowest OR (1.12) among the three methods. Cumulative exposure to cooking by means of any form of frying could increase the risk of lung cancer in Hong Kong nonsmoking women. Practical means to reduce exposures to cooking fumes should be given top priority in future research.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Culinária , Neoplasias Pulmonares/epidemiologia , Adenocarcinoma/epidemiologia , Adulto , Idoso , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Feminino , Hong Kong/epidemiologia , Humanos , Exposição por Inalação , Pessoa de Meia-Idade , Fatores de Risco , Fumaça
9.
Biomed Pharmacother ; 61(9): 570-7, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17913442

RESUMO

Previous studies on the serum proteome are hampered by the huge dynamic range of concentration of different protein species. The use of Equalizer Beads coupled with a combinatorial library of ligands has been shown to allow access to many low-abundance proteins or polypeptides undetectable by classical analytical methods. This study focused on never-smoked lung cancer, which is considered to be more homogeneous and distinct from smoking-related cases both clinically and biologically. Serum samples obtained from 42 never-smoked lung cancer patients (28 patients with active untreated disease and 14 patients with tumor resected) were compared with those from 30 normal control subjects using the pioneering Equalizer Beads technology followed by subsequent analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Eighty-five biomarkers were significantly different between lung cancer and normal control. The application of classification algorithms based on significant biomarkers achieved good accuracy of 91.7%, 80% and 87.5% in class-prediction with respect to presence or absence of disease, subsequent development of metastasis and length of survival (longer or shorter than median) respectively. Support vector machine (SVM) performed best overall. We have proved the feasibility and convenience of using the Equalizer Beads technology to study the deep proteome of the sera of lung cancer patients in a rapid and high-throughput fashion, and which enables detection of low abundance polypeptides/proteins biomarkers. Coupling with classification algorithms, the technologies will be clinically useful for diagnosis and prediction of prognosis in lung cancer.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/análise , Impressões Digitais de DNA , Neoplasias Pulmonares/genética , Proteoma/genética , Adenocarcinoma/classificação , Adenocarcinoma/cirurgia , Algoritmos , Biomarcadores Tumorais/classificação , Biomarcadores Tumorais/genética , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/genética , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/cirurgia , Espectrometria de Massas , Metástase Neoplásica/genética , Valor Preditivo dos Testes , Prognóstico , Fumar , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Análise de Sobrevida
10.
Chin J Cancer ; 36(1): 21, 2017 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-28187735

RESUMO

BACKGROUND: Alcohol consumption and some other dietary habits are thought to be associated with lung cancer incidence. However, the effects of these habits on lung cancer prognosis have been studied rarely. The purpose of this study was to address these gaps in knowledge. METHODS: We studied a cohort of 1052 Chinese men in Hong Kong who were diagnosed with primary lung cancer. Cox proportional hazards models were used to determine the prognostic values of consumption of alcohol, fresh fruits or vegetables, meat, and fried or preserved food. RESULTS: Compared with never drinkers, men who drank alcohol 1-3 days per week had a more favorable lung cancer prognosis (hazard ratio [HR]: 0.82, 95% confidence interval [CI] 0.68-0.97); however, this survival advantage was not significant in men who drank alcohol more frequently (HR: 0.91, 95% CI 0.73-1.14). Compared with men who consumed preserved or fried food only occasionally, men who consumed these foods frequently had a higher risk of lung cancer mortality (HR: 1.20, 95% CI 1.00-1.42). CONCLUSIONS: Occasional consumption of alcohol was a favorable survival factor for Chinese men with lung cancer. However, this survival benefit did not exist for frequent drinkers of alcohol. Chinese men with lung cancer who were frequent consumers of fried or preserved food had a worse prognosis than those who consumed these foods only occasionally.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Comportamento Alimentar , Neoplasias Pulmonares/epidemiologia , Idoso , Povo Asiático , Alimentos em Conserva , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais
11.
Front Genet ; 8: 8, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28210267

RESUMO

Non-small cell lung cancer (NSCLC) comprises about 84% of all lung cancers. Many treatment options are available but the survival rate is still very low due to drug resistance. It has been found that phosphoinositide-3-kinase (PI3K) affects sensitivity to tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib. Expression level of seven in absentia homolog 2 (SIAH2), an E3 ubiquitin-protein ligase, is upregulated in NSCLC and correlated with tumor grade. However, the relationship between PI3K and SIAH2 remains unclear and therefore it is not known whether they can act as treatment co-targets and theranostic dual markers for overcoming TKI resistance. It is worthy to note that PI3K and SIAH2 are potentially regulated by a common group of microRNAs in miR-30 family. Our bioinformatics analyses showed upregulated SIAH2 expression in NSCLC based on mass spectrometry data, explored its indirect interaction with PI3K and predicted their targeting microRNAs in common. We have also explored the potential role of miR-30 family in the modulation of PI3K-SIAH2 interaction in NSCLC.

12.
J Clin Oncol ; 23(28): 6966-75, 2005 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-16192584

RESUMO

PURPOSE: This randomized study compared the results achieved by concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone for nasopharyngeal carcinoma (NPC) with advanced nodal disease. PATIENTS AND METHODS: Patients with nonkeratinizing/undifferentiated NPC staged T1-4N2-3M0 were randomized to CRT or RT. Both arms were treated with the same RT technique and dose fractionation. The CRT patients were given cisplatin 100 mg/m2 on days 1, 22, and 43, followed by cisplatin 80 mg/m2 and fluorouracil 1,000 mg/m2/d for 96 hours starting on days 71, 99, and 127. RESULTS: From 1999 to January 2004, 348 eligible patients were randomly assigned; the median follow-up was 2.3 years. The two arms were well-balanced in all prognostic factors and RT parameters. The CRT arm achieved significantly higher failure-free survival (72% v 62% at 3-year, P = .027), mostly as a result of an improvement in locoregional control (92% v 82%, P = .005). However, distant control did not improve significantly (76% v 73%, P = .47), and the overall survival rates were almost identical (78% v 78%, P = .97). In addition, the CRT arm had significantly more acute toxicities (84% v 53%, P < .001) and late toxicities (28% v 13% at 3-year, P = .024). CONCLUSION: Preliminary results confirmed that CRT could significantly improve tumor control, particularly at locoregional sites. However, there was significant increase in the risk of toxicities and no early gain in overall survival. Longer follow-up is needed to confirm the ultimate therapeutic ratio.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Análise de Sobrevida , Resultado do Tratamento
13.
Radiother Oncol ; 79(1): 27-33, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16626829

RESUMO

BACKGROUND AND PURPOSE: To define the dose-response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66 Gy when the basic radiotherapy (RT) course was given by the 2D Ho's technique. PATIENTS AND METHODS: Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n = 2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho's technique. The primary endpoint was local control. The prognostic significance of dose-escalation ('boost') after 66 Gy, T-stage, N-stage, use of chemotherapy, sex and age (< or =40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed. RESULTS: On multivariate analysis, T-stage (P < 0.01; hazard ratio [HR], 1.58) and optimal boost (P = 0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P = 0.01; HR, 0.33); use of a boost (P < 0.01; HR, 0.60) and age (P = 0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20 Gy-boost gave a lower local failure rate than a 10 Gy-boost. There was no apparent excess mortality attributed to RT complications. CONCLUSIONS: Within the context of a multi-center retrospective study, dose-escalation above 66 Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho's technique without additional chemotherapy. 'Boosting' in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity.


Assuntos
Carcinoma/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Adulto , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/mortalidade , Carcinoma/patologia , Quimioterapia Adjuvante , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Hong Kong , Humanos , Prontuários Médicos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
Sci Rep ; 6: 26692, 2016 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-27225309

RESUMO

In this report, we showed that two tumor cell characteristics, namely the malignancy and drug-resistance status can be evaluated by their membrane resealing response. Specifically, membrane pores in a number of pairs of cancer and normal cell lines originated from nasopharynx, lung and intestine were introduced by nano-mechanical puncturing. Interestingly, such nanometer-sized holes in tumor cells can reseal ~2-3 times faster than those in the corresponding normal cells. Furthermore, the membrane resealing time in cancer cell lines exhibiting resistance to several leading chemotherapeutic drugs was also found to be substantially shorter than that in their drug-sensitive counterparts, demonstrating the potential of using this quantity as a novel marker for future cancer diagnosis and drug resistance detection. Finally, a simple model was proposed to explain the observed resealing dynamics of cells which suggested that the distinct response exhibited by normal, tumor and drug resistant cells is likely due to the different tension levels in their lipid membranes, a conclusion that is also supported by direct cortical tension measurement.


Assuntos
Membrana Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos , Modelos Biológicos , Neoplasias Nasofaríngeas/metabolismo , Linhagem Celular Tumoral , Membrana Celular/patologia , Humanos , Neoplasias Nasofaríngeas/patologia
15.
Autophagy ; 12(8): 1340-54, 2016 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-27245989

RESUMO

Reactive oxygen species (ROS) have been commonly accepted as inducers of autophagy, and autophagy in turn is activated to relieve oxidative stress. Yet, whether and how oxidative stress, generated in various human pathologies, regulates autophagy remains unknown. Here, we mechanistically studied the role of TRPM2 (transient receptor potential cation channel subfamily M member 2)-mediated Ca(2+) influx in oxidative stress-mediated autophagy regulation. On the one hand, we demonstrated that oxidative stress triggered TRPM2-dependent Ca(2+) influx to inhibit the induction of early autophagy, which renders cells more susceptible to death. On the other hand, oxidative stress induced autophagy (and not cell death) in the absence of the TRPM2-mediated Ca(2+) influx. Moreover, in response to oxidative stress, TRPM2-mediated Ca(2+) influx activated CAMK2 (calcium/calmodulin dependent protein kinase II) at levels of both phosphorylation and oxidation, and the activated CAMK2 subsequently phosphorylated BECN1/Beclin 1 on Ser295. Ser295 phosphorylation of BECN1 in turn decreased the association between BECN1 and PIK3C3/VPS34, but induced binding between BECN1 and BCL2. Clinically, acetaminophen (APAP) overdose is the most common cause of acute liver failure worldwide. We demonstrated that APAP overdose also activated ROS-TRPM2-CAMK2-BECN1 signaling to suppress autophagy, thereby causing primary hepatocytes to be more vulnerable to death. Inhibiting the TRPM2-Ca(2+)-CAMK2 cascade significantly mitigated APAP-induced liver injury. In summary, our data clearly demonstrate that oxidative stress activates the TRPM2-Ca(2+)-CAMK2 cascade to phosphorylate BECN1 resulting in autophagy inhibition.


Assuntos
Proteína Beclina-1/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Estresse Oxidativo , Canais de Cátion TRPM/metabolismo , Acetaminofen/química , Animais , Autofagia , Cálcio/metabolismo , Sinalização do Cálcio , Linhagem Celular Tumoral , Overdose de Drogas , Células HEK293 , Células HeLa , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutagênese , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Serina/química , Transdução de Sinais
16.
Int J Radiat Oncol Biol Phys ; 61(4): 1107-16, 2005 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-15752890

RESUMO

PURPOSE: To analyze the treatment results achievable for nasopharyngeal carcinoma in the modern era to identify the key failures for future improvement and to provide an updated baseline for future trials. METHODS AND MATERIALS: The results of 2687 consecutive patients treated at all public oncology centers in Hong Kong during 1996-2000 were retrospectively analyzed. The stage distribution (by American Joint Committee on Cancer and International Union Against Cancer staging system, 1997) was 7% Stage I, 41% Stage II, 25% Stage III, and 28% Stage IVA-B. All patients were irradiated with 6-MV photons and the median total dose was 66 Gy. Only 23% of patients had additional treatment with chemotherapy. RESULTS: The 5-year local, nodal, and distant failure-free rates were 85%, 94%, and 81%, respectively; patients with local failure had significantly higher risk of nodal and distant failures. The 5-year progression-free, overall, and cancer-specific survival rates were 63%, 75%, and 80%, respectively. The presenting stage was the most important prognostic factor for all endpoints: with overall survival decreasing from 90% for Stage I to 58% for Stage IVA-B. The results achieved by the 2070 patients treated by radiotherapy alone were almost identical to that of the whole series, the distant failure-free rate among patients with locoregional control was 89% for Stage I-II and 75% for Stage III-IVB. The 860 patients (32%) staged with magnetic resonance imaging achieved significantly better results than those staged by computed tomography, the overall survival being 93% vs. 83% for Stages I-II, and 72% vs. 63% for Stages III-IVB (p = 0.001). CONCLUSIONS: Treatment results for nasopharyngeal carcinoma have substantially improved in the modern era; future trials should be based on updated baseline results. Further reduction of distant failure is important for future breakthrough, particularly for patients with advanced disease.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , Falha de Tratamento
17.
Clin Cancer Res ; 10(1 Pt 1): 43-52, 2004 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-14734450

RESUMO

PURPOSE: Nasopharyngeal cancer (NPC) is a common cancer in Hong Kong, and relapse can occur frequently. Using protein chip profiling analysis, we aimed to identify serum biomarkers that were useful in the diagnosis of relapse in NPC. EXPERIMENTAL DESIGN: Profiling analysis was performed on 704 sera collected from 42 NPC patients, 39 lung cancer patients, 30 patients with the benign metabolic disorder thyrotoxicosis (TX), and 35 normal individuals (NM). Protein profile in each NPC patient during clinical follow up was correlated with the relapse status. RESULTS: Profiling analysis identified two biomarkers with molecular masses of 11.6 and 11.8 kDa, which were significantly elevated in 22 of 31 (71%) and 21 of 31 (68%) NPC patients, respectively, at the time of relapse (RP) as compared with 11 patients in complete remission (CR; RP versus CR, P = 0.009), 30 TX (RP versus TX, P < 0.001), or 35 NM (RP versus NM, P < 0.001). The markers were also elevated in 16 of 39 (41%) lung cancer patients at initial diagnosis. By tryptic digestion, followed by tandem mass spectrometry fragmentation, the markers were identified as two isoforms of serum amyloid A (SAA) protein. Monitoring the patients longitudinally for SAA level both by protein chip and immunoassay showed a dramatic SAA increase, which correlated with relapse and a drastic fall correlated with response to salvage chemotherapy. Serum SAA findings were compared with those of serum Epstein-Barr virus DNA in three relapsed patients showing a similar correlation with relapse and chemo-response. CONCLUSIONS: SAA could be a useful biomarker to monitor relapse of NPC.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Nasofaríngeas/sangue , Recidiva Local de Neoplasia/diagnóstico , Proteômica , Proteína Amiloide A Sérica/metabolismo , Adulto , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Herpesvirus Humano 4/genética , Hong Kong , Humanos , Estudos Longitudinais , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/virologia , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/secundário , Neoplasias Nasofaríngeas/virologia , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/virologia , Reação em Cadeia da Polimerase , Estudos Prospectivos , Proteoma , Indução de Remissão , Tireotoxicose/sangue , Tireotoxicose/virologia
18.
Int J Radiat Oncol Biol Phys ; 56(2): 413-26, 2003 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-12738316

RESUMO

PURPOSE: To critically evaluate the American Joint Commission on Cancer (AJCC)/International Union Against Cancer (UICC) 1997 staging system and look back on its achievements by comparing it with the AJCC/UICC 1992 and Ho 1978 staging systems. To identify areas for additional refinement, we analyzed the prognostic heterogeneity within each stage in depth, which provided important clues for the addition or better categorization of the different defining criteria. METHODS AND MATERIALS: We performed a retrospective review of the data from 1294 consecutive biopsy-proven nonmetastatic nasopharyngeal carcinoma patients and staged the extent of disease according to the defining criteria of the three staging systems. All patients had undergone detailed pretreatment assessment by fiberoptic endoscopy and CT. Radical-intent radiotherapy was given using the Ho technique according to our standard protocol. RESULTS: The AJCC/UICC 1997 staging system was superior to the other two staging systems, because it assigned patients to more uniform-size stage groupings and correlated better with prognosis. Parapharyngeal space involvement was not an independent predictor for survival, local control, or metastasis. On the other hand, carotid space involvement correlated with a greater likelihood of metastasis. Prognostic heterogeneity was found. Those with orbit, cranial nerve, or intracranial involvement fared worse within Stage T4; those with a maximal lymph node size >3 cm fared worse within Stage N2; and those with bilateral lymph node metastasis fared worse within Stage N3. CONCLUSION: The prognostic accuracy of the AJCC/UICC 1997 staging system can be improved further by recategorization of the T, N, and group stage criteria.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Ásia , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/etnologia , Neoplasias Nasofaríngeas/mortalidade , Organizações/normas , Prognóstico , Modelos de Riscos Proporcionais , Controle de Qualidade , Estudos Retrospectivos , Fatores Sexuais
19.
Lung Cancer ; 45(2): 143-52, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15246184

RESUMO

The gender difference in epidemiology of lung cancer has been postulated to be due to the higher susceptibility of women to risk factors especially tobacco smoking. Alternatively, such difference may also be explained by some unknown gender-specific etiological factors, which can have been masked if both the female and male prevalence of smoking are high. Hong Kong has a low female smoking prevalence rate and therefore the trend of the female incidence of lung cancer is particularly interesting because it can reflect the effects of the non-smoking related risk factors more clearly. The present study examined the trends of incidence rates for the major histologic types and smoking prevalence from 1983 to 2000 in Hong Kong with respect to gender. The prevalence of daily smokers decreased from 39.7% in 1982 to 22% in 2000 in males and from 5.6 to 3.5% in females. The time trends of the lung cancer incidence (overall or with respect to age and histology) were similar for both genders. The overall incidence decreased progressively throughout the study period, attributable to the decrease in squamous cell, small cell and large cell carcinoma. The decline occurred in all age groups but to a greater extent in the younger age groups. The incidence of adenocarcinoma increased until 1988-1990 and then stabilized. The initial increase was restricted to the older age groups. These temporal patterns suggested that the same etiological factors affected both genders to a different extent but manifested as similar changes in the direction of incidence over time. To confirm this hypothesis, further studies were needed to clarify the nature of these etiological factors for the non-smoking related lung cancer cases.


Assuntos
Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Invasividade Neoplásica/patologia , Fumar/efeitos adversos , Fumar/tendências , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Feminino , Hong Kong/epidemiologia , Humanos , Imuno-Histoquímica , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Probabilidade , Sistema de Registros , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Análise de Sobrevida
20.
Ann N Y Acad Sci ; 1022: 263-70, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15251971

RESUMO

Nineteen Chinese patients with lymphoepithelioma-like carcinoma (LELC) of the lung were tested for Epstein-Barr virus (EBV) DNA in their serum samples by a quantitative polymerase chain reaction (PCR) technique. There was prospective serial monitoring of the serum in seven patients with advanced inoperable or relapsing disease. Five other patients at first diagnosis and two patients at relapse had only a single serum sample available. Serum samples were also taken from three other patients who had prior curative surgery and two patients with prolonged disease remission. Measurable levels of EBV DNA were detected in 11 of 12 patients with a pre-therapy serum sample and a clinically evident tumor. A low level of EBV DNA was also detectable in one of the two other patients whose first serum samples were obtained after some chemotherapy. There was no detectable EBV DNA in the five patients without evidence of tumor. The longitudinal serum EBV DNA profile of seven patients showed consistent correlation with response to therapy and clinical outcome. Patients with a pre-therapy serum EBV DNA >10,000 copies/mL had significantly inferior overall survival. This study suggests that circulating serum EBV DNA can be used as a tumor marker in the clinical management of patients with LELC of the lung.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , DNA Viral/sangue , Herpesvirus Humano 4/genética , Neoplasias Pulmonares/sangue , Capsídeo/imunologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , China , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Taxa de Sobrevida
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