RESUMEN
OBJECTIVE: To assess the expression of HER-2 and leptin in gastric cancer and evaluate their relationship with VEGF expression and clinicopathological features, and their prognostic value for gastric cancer patients. METHODS: One hundred and ten gastric cancer specimens and the corresponding metastatic lymph nodes were detected for HER-2 by immunohistochemistry (IHC). All primary cancer tissues were detected for leptin, OB-Rb and VEGF. Ninty-six specimens of normal gastric mucosa served as the control. RESULTS: The expression level of HER-2, leptin and OB-Rb in gastric cancer tissues were significantly higher than those in normal tissues (19.1% vs. 8.0%, 49.1% vs. 34.0%, and 60.9% vs. 46.0%, P < 0.05). HER-2 overexpression was moderately homogenous in primary gastric cancer and matastatic lymph nodes (P = 0.607, Kappa = 0.581). There was a correlation between the expression of HER-2 and leptin, both of which were significantly correlated with tumor invasion depth, metastatic lymph nodes ratio (NR), distal metastasis, TNM stage and VEGF expression. However, there was no significant correlation between OB-Rb expression and the clinicopathological features evaluated. Cox regression multivariate analysis showed that tumor size, histological grade, NR, stage, chemotherapy and HER-2 expression were independent prognostic factors. CONCLUSIONS: HER-2 is stably expressed in primary gastric cancer and metastatic lymph nodes. HER-2 and leptin play an important role in the progression and angiogenesis of gastric cancer. High expression of HER-2 is a prognostic factor for poor outcome.
Asunto(s)
Adenocarcinoma/metabolismo , Leptina/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Gastrectomía , Humanos , Ganglios Linfáticos/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Receptores de Leptina/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Tasa de Supervivencia , Carga Tumoral , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Gefitinib has shown evidence of antitumor activity in advanced non-small cell lung cancer (NSCLC). CASE REPORT: A female Asian nonsmoker with adenocarcinoma was given gefitinib as first-line treatment with significant efficacy. However, after approximately 1.5 years, progression occurred. She then received chemotherapy (pemetrexed/carboplatin) until progression, followed by treatment with gefitinib to which the patient responded a second time. After progression, treatment with chemotherapy (docetaxel/cisplatin) was instituted and again followed by gefitinib. A recent positron emission tomography/computed tomography (PET/CT) scan showed complete remission under gefitinib. CONCLUSIONS: This case report indicates that resistance to gefitinib in NSCLC can be reversed after chemotherapy. Thus, re-exposure to gefitinib may be justified in selected cases.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/secundario , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Quinazolinas/administración & dosificación , Antineoplásicos/administración & dosificación , Femenino , Gefitinib , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: The human epidermal growth factor receptor 2 (HER-2) and leptin/OB-R system have been reported to be intertwined in several cancer types. However, limited research has been conducted with regard to this interaction in lung cancers. In this study, we investigated the relationship between the expression levels of these proteins and the development, progression and prognosis of non-small-cell lung cancer (NSCLC). METHODS: The expression of leptin, OB-Rb and HER-2 was evaluated in 100 NSCLC specimens by immunohistochemistry, with normal lung tissue as controls. The relationships between their expression levels and clinicopathological factors were evaluated by correlation analysis. Univariate and multivariate analyses were used to determine the associations between the expression levels of these proteins and the survival of NSCLC patients. RESULTS: Leptin was expressed in 71 and 25% (P < 0.05) of NSCLC and normal lung tissues, respectively, while OB-Rb was expressed in 62 and 31% (P < 0.05), respectively. Overexpression of HER-2 was detected in 53% of NSCLC tissues versus 0% of normal lung tissues (P < 0.05). A significant association was found between the expression levels of leptin and OB-Rb (P = 0.024), and between tumor-node-metastasis (TNM) stage and HER-2 expression (P = 0.003). Univariate survival analysis showed that TNM stage (P < 0.001) and leptin expression (P = 0.009) influenced survival time. Multivariate analysis suggested that TNM stage [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.30-2.04, P < 0.001] and leptin expression (HR 1.69, 95% CI 1.01-2.80, P = 0.044) were independent prognostic factors for NSCLC. CONCLUSIONS: The expression of leptin, OB-Rb and HER-2 was significantly higher in NSCLC tissues than in normal lung tissues. The expression of leptin is an independent prognostic factor for NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/química , Leptina/análisis , Neoplasias Pulmonares/química , Receptor ErbB-2/análisis , Receptores de Leptina/análisis , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Pulmón/química , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient. PURPOSE: To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC), a study of single agent treatment with gefitinib in Chinese patients was conducted. METHODS: 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily) until the disease progression or intolerable toxicity. RESULTS: Among the 45 patients, 15 patients achieved partial response (PR), 17 patients experienced stable disease (SD), and 13 patients developed progression disease (PD). None of the patients achieved complete response (CR). The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively). The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively). In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively). CONCLUSIONS: Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.