RESUMEN
To identify the characteristics of peripheral small lung mass lesions on high-resolution computed tomography (HRCT) and discriminate between malignant and benign, 223 mass lesions 2 cm or less resected surgically were evaluated about following points. 1) Density : 90.7% of lesions with mixed solid and ground-glass opacity (GGO) components were adenocarcinomas. Pure GGO lesions without scale-down between several months were all adenocarcinomas or atypical adenomatous hyperplasia (AAH). Thereby, patients with these findings are good candidates for surgical resection. 2) Spicular or pleural indentation :75.2% (88 of 117 cases) of adenocarcinomas and all squamous cell carcinomas (18 cases) showed these findings, but 26.6% (41 of 154 cases) of positive cases were benign lesion (non-specific inflammation, mycobacterisis, and so on). Accordingly, they are not peculiar to malignancy. 3) Satellite lesion : all lesions with this one showed benign, therefore it was thought that this finding could exclude malignant lesion. Thus, recognition of certain characteristics at HRCT can be helpful in discrimination between small malignant mass and benign mass.
Asunto(s)
Enfermedades Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Pulmón/patología , Nódulo Pulmonar Solitario/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Pequeñas/diagnóstico por imagen , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Diagnóstico por Computador , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares/patología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Nódulo Pulmonar Solitario/patologíaRESUMEN
Histone deacetylases (HDACs) play a crucial role in tumorigenesis, however, the expression status of HDACs in lung cancer tissues has not been reported. We have investigated that HIDAC 1 mRNA levels and other clinico-pathological data, including MTA 1 mRNA expression in lung cancer. The study included 102 lung cancer cases. The HDAC1 mRNA levels were quantified by real time reverse transcription-polymerase chain reaction (RT-PCR) using LightCycler (Roche Molecular Biochemicals, Mannheim, Germany). The HDAC1/GAPDH mRNA levels were not significantly different in tumor tissues from lung cancer (30.654 +/- 33.047) and adjacent non-malignant lung tissues (18.953 +/- 56.176 , P = 0.1827). No significant difference in HDAC1/GAPDH mRNA levels was found among age, gender, and lymph node metastasis. The HDAC1/GAPDH mRNA levels were significantly higher in stage III or IV lung cancer (50.929 +/- 120.433) than in stage I lung cancer (11.430 +/- 25.611, P = 0.0472). HDAC1/GAPDH mRNA levels were significantly higher in T3 or T4 lung carcinoma (54.326 +/- 127.018) than in T1 or T2 lung cancers (14.790 +/- 48.670, P = 0.1601). HDAC1/GAPDH mRNA levels were correlated with MTA1/GAPDH mRNA levels (y = 0.0106x + 2.5827 , P = 0.0352 ). HDAC1/GAPDH mRNA levels were also correlated with HDAC1 protein (P = 0.0484) expression by immunohistochemistry. Using the LightCycler RT-PCR assay, the HDAC1 gene expression might correlate with progression of lung cancers. However, further studies are needed to confirm the impact of HDAC1 for the molecular target of the lung cancer.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Carcinoma de Células Pequeñas/genética , Carcinoma de Células Pequeñas/fisiopatología , Perfilación de la Expresión Génica , Histona Desacetilasas/biosíntesis , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Histona Desacetilasa 1 , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Human homologues of yeast Rad 6 (Hrad6B) encode ubiquitin-conjugating enzymes and complement the DNA repair and UV mutagenesis defects of Saccharomyces cerevisiae rad6 mutant. There is a larger subgroup with reduced DNA repair capacity that is likely to be at increased cancer risk. The authors investigated Hrad6B expression in lung cancer. An attempt was made to determine the influence of Hrad6B expression on clinicopathological features for patients with lung cancer who had undergone surgery. Expression of Hrad6B messenger RNA was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 110 lung carcinomas and adjacent histological non-malignant lung samples from patients for whom follow-up data were available using LightCycler. The Hrad6B/glyceraldehydes-3-phosphate dehydrogenase (GAPDH) mRNA expression was significantly decreased in the lung cancer tissue (4.078+/-5.674) as compared with the non-malignant lung tissue (10.495+/-12.976, p<0.001). There was no relationship between Hrad6B/GAPDH expression and age, clinical stages, T-status, N-status, and pathological subtypes in lung cancer tissues. Hrad6B/GAPDH mRNA levels in males (3.521+/-4.280) and in females (6.420+/-8.167) were significantly different (p=0.0443) in lung cancer tissues, but not in non-malignant lung tissues. Heavy smokers had a slight non-significant tendency (p=0.0857) towards lower Hrad6B/GAPDH mRNA levels (3.453+/-4.743) in their lung cancer tissues as compared with light or non-smokers. Thus decreased Hrad6B mRNA expression might be a biomarker for decreased DNA repair capacity and the dysfunction of Hrad6B might play a role in the tobacco-related oncogenesis of lung cancer.
Asunto(s)
Reparación del ADN , Perfilación de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Enzimas Ubiquitina-Conjugadoras/biosíntesis , Enzimas Ubiquitina-Conjugadoras/genética , Anciano , ADN de Neoplasias/análisis , Femenino , Gliceraldehído 3-Fosfato Deshidrogenasa (NADP+)/genética , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Fumar/efectos adversosRESUMEN
Intravenous endostatin gene transfection results in tumor suppression in a murine pulmonary metastasis model. We transfected the endostatin gene at different times, in order to achieve an optimal protective effect. pST2-Endo encoding murine endostatin was injected in a complex with cationic lipid. Pulmonary metastases were caused by intravenous injection of murine fibrosarcoma cells. Mice were observed for 14 days following fibrosarcoma cell inoculation (FSI). In the study groups, the animals were transfected with pST2-Endo at three different times: 2 days before and 3 and 7 days after FSI. In the group transfected with pST2-Endo 2 days before FSI, the weights of the lungs and tumor-occupied area ratio were significantly less than in the other groups. Significant inhibition of tumor neovascularization was documented by means of CD31 immunohistochemistry. The effect of repeated endostatin transfection on survival after FSI was determined. Animals repeatedly transfected with the endostatin gene survived significantly longer than the groups treated with a single endostatin gene transfection. A stable endostatin-expressing fibrosarcoma transfectant was created and tested for migration and invasion. Compared with controls, endostatin expression reduced migration and invasion by 15%. It is concluded that endostation gene transfection before FSI and repeated transfection thereafter results in significant tumor suppression.
Asunto(s)
Endostatinas/genética , Fibrosarcoma/genética , Terapia Genética , Lípidos , Neoplasias Pulmonares/genética , Transfección , Animales , Supervivencia Celular/genética , Endostatinas/biosíntesis , Endostatinas/inmunología , Fibrosarcoma/patología , Fibrosarcoma/terapia , Vectores Genéticos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos C3H , Neovascularización Patológica/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/biosíntesis , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/inmunología , Transfección/métodosRESUMEN
The CDKN2 gene is located on the short arm of chromosome 9p and encodes two unrelated proteins, p16(INK4a) and p14(ARF), through the use of independent first exons and shared exons 2 and 3. p16(INK4a) is a cyclin-dependent kinase inhibitor, whereas p14(ARF) regulates the cell cycle through a p53 and MDM2-dependent pathway. We have examined the expression of p16(INK4a) and p14(ARF) using competitive RT-PCR in 60 non-small cell lung cancers (NSCLCs) and matching normal lung tissues. The intensities of bands for p16(INK4a) and p14(ARF) were nearly equal or the intensity of the p16(INK4a) band slightly exceeded that of p14(ARF) in the normal lung tissues (n = 60). In 38 tumors the intensity of the p16(INK4a) band was similar to or slightly weaker than that of p14(ARF). In 6 tumors the intensity of the p16(INK4a) band was weaker than that of p14(ARF). In 15 tumors the intensity of the p14(ARF) band was very strong and the p16(INK4a) band was barely visible. In only one tumor was the intensity of the p16(INK4a) band very strong, while the band of p14(ARF) was barely visible. The ratio of the intensity of p16(INK4a) to p14(ARF) had an interesting correlation with the tumor's clinicopathological characteristics. The p stage II - IV tumors had significantly lower p16(INK4a) to p14(ARF) ratios than the p stage I tumors (P = 0.036). The T2 - 4 tumors had significantly lower p16(INK4a) to p14(ARF) ratios than the T1 tumors (P = 0.005). The N1 - 3 tumors had significantly lower p16(INK4a) to p14(ARF) ratios than the N0 tumors (P = 0.014). Our results suggest that the ratio of expression of p16(INK4a) to p14(ARF) tends to decrease during the progression of NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Neoplasias Pulmonares/patología , Proteína p14ARF Supresora de Tumor/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Transforming growth factor-beta (TGF-beta) is capable of affecting the proliferation of many cell types. beta IGH3, TGF-beta inducible gene, was originally isolated from lung adenocarcinoma cell line (A549). We have hypothesized that beta IGH3 mRNA levels could be predictors of the development and invasion of lung cancer. METHODS: The study included 71 lung cancer cases. The beta IGH3 mRNA levels were quantified by real time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler. RESULTS: The beta IGH3 mRNA levels were elevated in tumor tissues from lung cancer (1.058 +/- 1.212) compared with non-malignant lung tissues (0.304 +/- 0.159) (p = 0.0001). No significant difference in beta IGH3 mRNA levels was found among gender, age, pathological subtype and lymph node metastasis. The beta IGH3 mRNA levels were elevated in tumor tissues from T4 lung cancer (1.425 +/- 1.470) compared with those from T1 lung cancer (0.702 +/- 0.655) (p = 0.05) and T2 lung cancer (0.736 +/- 0.734) (p = 0.044). CONCLUSION: Using the LightCycler RT-PCR assay, the determination of beta IGH3 mRNA level might provide a potential marker for the aggressiveness of lung cancer. However, further studies and a longer follow-up are needed to confirm the impact of beta IGH3 on the biological behavior of the tumor.
Asunto(s)
Proteínas de la Matriz Extracelular , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Factor de Crecimiento Transformador beta/genética , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Invasividad Neoplásica , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Activation of the nuclear hormone receptor perioxisome proliferator-activated receptor gamma (PPARgamma) inhibits cell growth and induces apoptosis in several human cancers. We have hypothesized that PPARgamma mRNA levels could be predictors of the differentiation and survival of lung cancer. The study included 77 lung cancer cases. The mRNA levels were quantified by real time reverse transcription-polymerase chain reaction (RT-PCR) using LightCycler. The PPARgamma mRNA levels were decreased in tumor tissues from lung cancer (0.579 +/- 1.255) compared to the normal adjacent lung tissues (4.191 +/- 2.868) (P = 0.0001). No significant difference in PPARgamma mRNA levels was found among gender, age, and pathological subtype. The PPARgamma mRNA levels were higher in tumor tissues from higher differentiated lung cancer. The NSCLC patients with low PPARgamma mRNA expression (< 0.5) had significantly worse survival than the patients without low PPARgamma mRNA levels (P = 0.0438, Breslow-Gehan-Wilcoxon test; P = 0.0168, Cox's proportional-Hazards regression model). Thus, PPARgamma mRNA levels may serve as a prognostic marker in lung cancer. Using the LightCycler RT-PCR assay, the determination of PPARgamma mRNA levels might provide a potential marker for treatment of lung cancer by PPARgamma agonist. However, further studies and a longer follow up are needed to confirm the impact of PPARgamma in the biological behavior of the tumor.
Asunto(s)
Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Cartilla de ADN/química , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Factores de Transcripción/metabolismoRESUMEN
The MTA1 gene is a recently identified metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in non-small cell lung cancer (NSCLC). Expression of MTA1 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 74 non-small cell lung carcinoma samples using LightCycler. The data was analyzed in reference to clinicopathological data. There was no relationship between MTA1 gene expression and age and gender. MTA1/GAPDH mRNA level in stage II-IV NSCLC (3.465+/-3.675) was significantly higher than the level in stage I NSCLC (1.614+/-2.434, P=0.0153). MTA1/GAPDH mRNA levels in T4 NSCLC (4.377+/-4.169) was significantly higher than the level in T1 NSCLC (1.966+/-2.148, P=0.0351) and in T2 NSCLC (2.048+/-1.899, P=0.0269), respectively. MTA1/GAPDH mRNA level in NSCLC with lymph node metastasis (4.242+/-3.758) was significantly higher in NSCLC without lymph node metastasis (P=0.0169). Our results show that the expression of the MTA1 gene is closely related to invasiveness and metastasis in NSCLC. The gene MTA1 could thus potentially provide information on the mechanism of cancer invasion and metastasis.