Expression of Thyroid Transcription Factor-1(TTF-1)in Lung Carcinomas and Its Correlations with Apoptosis and Angiogenesis

OBJECTIVE To investigate the correlations between the expression of thyroid transcription factor-1 （TTF-1） and apoptosis and angiogenesis in lung carcinomas. METHODS A 829 microarray of the paraffin tissue chips was constructed, which contained 196 lung carcinomas, 10 normal lung tissues, and 1 muscular tissue. Terminal deoxynucleotidyl transferase mediated nick end labeling （TUNEL） and immunohistochemical SP method were used to detect apoptosis and expression of TTF-1 and CD34 in different types of lung carcinomas. A Leica Q500 MC image analysis system was used to measure and calculate TTF-1 positive unit （PU）, apoptotic index （AI） and microvessel density （MVD）. RESULTS AI of lung small cell carcinoma and large cell carcinoma were smaller than those of lung adenocarcinoma and squamous cell carcinoma （P = 0.000）. AI of lung carcinomas with lymph node metastases was smaller than that of those without （P = 0.039）. AI of lung carcinomas in TNM stage I-IV was smaller than that in stage I （P = 0.008）. The PU of the TTF-1 was negatively correlated with AI in small cell lung carcinoma （r = -0.752, P = 0.000）. MVD of lung carcinomas without lymph node metastases was smaller than that of those with lymph node metastasis （P = 0.031）. MVD of lung carcinomas in TNM stage I was smaller than that in stage I-IV （P = 0.040）. The PU of TTF-1 was positively correlated with MVD in lung adenocarcinoma （r = 0.708, P = 0.000）. CONCLUSION There is a negative correlation between TTF-1 PU and AI in small cell lung carcinoma. TTF-1 PU and AI may be correlated with each other. There is a positive correlation between TTF-1 PU and MVD in lung adenocarcinoma. TTF-1 may induce the development of lung adenocarcinoma by inducing tumor angiogenesis.

Expression of SKP2 Protein in Non-small Cell Lung Carcinoma

Objective： To study the expressive characteristics of SKP2 protein in non-small cell lung carcinoma and it is affection to NSCLC patients＇ prognosis. Methods： The expression of SKP2 protein was detected in 89 NSCLC, 5 benign lung neoplasmas, 5 normal bronchus and lung tissues by Tissue Chip and immunohistochemistry technology. Results： The positive rate of SKP2 protein staining was （23.52±13.57）% in NSCLC tissues, significantly higher than that in benign lung neoplasmas, normal brochus and lung tissues （2.91±1.27）% （P=0.0000〈0.001）. The expressive level of SKP2 protein in NSCLC tissues was closely related to cell differentiation （PI=0.000〈0.001）, but not to age, sex, smoking history, pathological type, site, size, lymph node metastasis and TNM stage （each Pl〉0.05）. The survival analysis displayed that the NSCLC patients＇ 5 years survival rate was lower in positive expression group than that in negative expression group （P1=0.042/0.031〈0.05; r=-0.186, P2=0.000〈0.001）. Conclusion： The positive expression of SKP2 protein may play an enhancement role in the occurrence and development of NSCLC. Moreover, it may be a bad indicator to NSCLC patients＇ prognosis.

Expression of SKP2 Protein in Lung Carcinoma

Objective： To study the expressive characteristics of SKP2 protein in lung carcinoma and its implication for prognosis. Methods： The expression of SKP2 protein was detected in 89 non small cell lung carcinoma, 13 small cell lung carcinoma, 10 lung benign lesion tissues by Tissue Chip and Immunohistochemistry technology. Results： The positive rate of SKP2 protein staining was （23.52±13.57）% in non small cell lung carcinoma and （53.85±12.26）% in small cell lung carcinoma, which were significantly higher than （2.91±1.27）% in lung benign lesion tissues. It was highest in small cell lung carcinoma and lowest in lung benign lesion tissues, with a significant difference between them （P=0.000）. The expressive level of SKP2 protein in lung carcinoma tissues was closely related to cell differentiation, lymph node metastasis and pathological types, but not to age, sex, smoking history, tumor site and size, and TNM staging. The survival analysis revealed that the 5-year survival rate of lung carcinoma patients was lower in SKP2 protein positive expression group than that in negative expression group （P1=0.003/0.002; r=-0.275, P2=0.005）. Conclusion. The positive expression of SKP2 protein is higher in lung carcinoma than in lung benign lesion tissues, in particular, much higher in small cell lung carcinoma. In lung carcinoma, its expressive level was closely related to cell differentiation, lymph node metastasis and pathological types. Moreover, it may be an independent factor to prognosis of patients with lung carcinoma.

Bioprinting-Based High-Throughput Fabrication of Three-Dimensional MCF-7 Human Breast Cancer Cellular Spheroids

Cellular spheroids serving as three-dimensional(3D) in vitro tissue models have attracted increasing interest for pathological study and drug-screening applications. Various methods, including microwells in particular, have been developed for engineering cellular spheroids. However, these methods usually suffer from either destructive molding operations or cell loss and non-uniform cell distribution among the wells due to two-step molding and cell seeding. We have developed a facile method that utilizes cellembedded hydrogel arrays as templates for concave well fabrication and in situ MCF-7 cellular spheroid formation on a chip. A custom-built bioprinting system was applied for the fabrication of sacrificial gelatin arrays and sequentially concave wells in a high-throughput, flexible, and controlled manner. The ability to achieve in situ cell seeding for cellular spheroid construction was demonstrated with the advantage of uniform cell seeding and the potential for programmed fabrication of tissue models on chips. The developed method holds great potential for applications in tissue engineering, regenerative medicine, and drug screening.