Cancer Treatment Strategies by Targeting the Oncoprotein c-Myc / 中国生物化学与分子生物学报

c-Myc is a transcription factor involved in the Myc/Max/Mxd signal regulatory network. c-Myc plays important roles in human development and the oncogenesis or progression of different types of tumors. Current studies have shown that c-Myc mutations or expression changes are present in more than 70% of tumors. Therefore, c-Myc-targeted inhibitors might become a new strategy for tumor therapy. Currently, there is no clinical treatment for targeting c-Myc. With the continuous study aiming at the c-Myc targeted clinical application, Omomyc has become a representative c-Myc inhibitor by direct inhibition of c-Myc in tumors, which may be a feasible clinical treatment strategy. Although targeting c-Myc has broad prospects in cancer treatment, direct inhibition of c-Myc still has many risks and challenges. Therefore, in this review, firstly, we will summarize the regulatory network and biological functions of c-Myc in cells. Secondly, the potential significance of targeting c-Myc or its homologues in tumor therapy will be discussed. Additionally, the challenges faced by c-Myc as a potential therapeutic target in clinical application will be summarized. Finally, we will also discuss the advantages and disadvantages of some c-Myc inhibitors that have been discovered to date, such as small molecule inhibitors and protein and peptide inhibitors, therefore providing the theoretical basis for c-Myc targeted clinical therapy in cancer.

Variation of serum thyroid transcription factor-1 protein and its value in the diagnosis of lung carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the variation of serum thyroid transcription factor-1 (TTF-1) in different patients and explore its significance in the diagnosis of lung carcinoma.</p><p><b>METHODS</b>Dot-enzyme linked immunosorbent assay (dot-ELISA) and Leica Q500 MC image analysis system were used to quantitatively detect TTF-1 protein in the serum samples from normal healthy adults and from patients with benign lung disease, lung cancer, thyroid carcinoma and non-thyroid carcinoma.</p><p><b>RESULTS</b>The sensitivity, specificity, standardized positive predicative value, standardized negative predicative value, standardized accuracy and standardized wrong diagnostic rate of the method were 90.91%, 82.22%, 83.64%, 90.04%, 86.57% and 13.43%, respectively. The cutoff value of serum TTF-1 in healthy normal adults was 36.39, with a ROC value of 0.95. Serum TTF-1 PU was significantly higher in patients with lung adenocarcinoma, squamous cell lung carcinoma and thyroid carcinoma than in healthy adults and patients with benign lung diseases and non-thyroid carcinoma (P=0.000). Serum TTF-1 PU was similar in lung adenocarcinoma, squamous cell lung carcinoma, small cell lung carcinoma, large cell lung carcinoma and thyroid carcinoma (P=0.744, 0.677, and 0.333, respectively). Serum TTF-1 PU was greater than the PU in the corresponding homogenate of lung adenocarcinoma, squamous cell lung carcinoma, small cell lung carcinoma, large cell lung carcinoma and thyroid carcinoma (P=0.000). Serum and homogenate TTF-1 PU was correlated to TNM stage of lung cancer patients (P=0.000) but not to gender, tumor types, differentiation or lymph node metastasis.</p><p><b>CONCLUSIONS</b>Lung adenocarcinoma, squamous cell lung carcinoma and thyroid carcinoma are suspected when serum TTF-1 PU is higher than 36.39. Serum TTF-1 is not helpful in differentiating the types of lung carcinomas and thyroid carcinoma. After exclusion of thyroid carcinoma, detection of serum TTF-1 can be helpful in the diagnosis of lung cancer. In different lung carcinomas and thyroid carcinomas, the serum TTF-1 is higher than the corresponding homogenate TTF-1 level. Serum TTF-1 increases with the progression of TNM stage of lung carcinoma.</p>

Quantitative analysis of thyroid transcription factor-1 mRNA expressions in primary lung cancer and its metastatic foci / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the expression of thyroid transcription factor-1 (TTF-1) mRNA in human normal adult type II alveolar epithelial cells, embryonic alveolar epithelial cells, and primary lung carcinoma and lymph nodes, thereby exploring the role of TTF-1 mRNA expression in the tumorigenesis, development and metastasis of lung carcinoma.</p><p><b>METHODS</b>TTF-1 mRNA was detected using tissue microarray and in situ hybridization in 1320 different paraffin-embedded tissue specimens. The intensity of TTF-1 mRNA in these tissues was assessed quantitatively using Leica Q500MC image analysis system.</p><p><b>RESULTS</b>TTF-1 mRNA expression was significantly less intense in embryonic lung than in normal adult lung tissues (P= 0.000), and the two tissues both had significantly greater expression than lung adenocarcinoma, squamous cell carcinoma, small cell carcinoma and large cell carcinoma (P=0.000). Lung adenocarcinoma and small cell carcinoma, with similar expression intensity (P= 0.068), showed stronger expression than squamous cell carcinoma and large cell carcinoma (P=0.000), and squamous cell carcinoma showed stronger expression than large cell carcinoma (P=0.018). In lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma, the intensity of TTF-1 mRNA expression was stronger in lymph node metastases than in the primary foci (P=0.003, P=0.000, P=0.019, respectively). The lymph node metastases had more intense expression than the primary foci of small cell lung carcinoma (P=0.078). The intensity of TTF-1 mRNA expression was greater in primary lung carcinomas with lymph node metastases than in those without metastases (P=0.026). Tumors of TNM stage II-IV had stronger expression than those of stage I (P=0.010). The intensity of TTF-1 mRNA expression was not associated with the patients' gender or the general types and differentiation of the tumor.</p><p><b>CONCLUSION</b>The amount of TTF-1 mRNA expression lowers in the order of normal adult lung, embryonic lung and lung carcinoma tissues. In lung carcinomas, TTF-1 mRNA expression differs between the histological types, high in lung adenocarcinoma and small cell carcinoma and rather low in squamous cell carcinoma and large cell carcinoma. Strong expression of TTF-1 mRNA often indicates high likeliness of lung carcinoma metastasis, and highlights the high metastatic potentials of lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma.</p>

Simulation and data analysis of stereological modeling based on virtual slices / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a computer-assisted stereological model for simulating the process of slice section and evaluate the relationship between section surface and estimated three-dimensional structure.</p><p><b>METHODS</b>The model was designed by mathematic method as a win32 software based on the MFC using Microsoft visual studio as IDE for simulating the infinite process of sections and analysis of the data derived from the model. The linearity of the fitting of the model was evaluated by comparison with the traditional formula.</p><p><b>RESULTS</b>The win32 software based on this algorithm allowed random sectioning of the particles distributed randomly in an ideal virtual cube. The stereological parameters showed very high throughput (>94.5% and 92%) in homogeneity and independence tests. The data of density, shape and size of the section were tested to conform to normal distribution. The output of the model and that from the image analysis system showed statistical correlation and consistency.</p><p><b>CONCLUSION</b>The algorithm we described can be used for evaluating the stereologic parameters of the structure of tissue slices.</p>

Quantitative study of thyroid transcription factor-1 protein expression in lung carcinoma cell nucleus by tissue microarray / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate thyroid transcription factor-1 (TTF-1) expression in normal human adult type II alveolar epithelial cells, embryonic pneumocytes, lung carcinoma cells and lymph node metastases of lung cancer.</p><p><b>METHODS</b>Lung carcinoma tissue microarray was constructed containing 765 cores of 20 normal adult lung tissues, 15 embryonic lung tissues, 100 lung carcinomas and 55 corresponding lymph node metastases. TTF-1 protein expression on the microarray was detected by immunohistochemical SP method using TTF-1 monoclonal antibody and assessed quantitatively with Leica Q500MC image analysis system.</p><p><b>RESULTS</b>The number TTF-1 positive units (PU) was smaller in the nuclei of embryonic pneumocytes than in those of normal adult type II alveolar epithelial cells (P<0.001). The nuclei of lung carcinoma cells had smaller TTF-1 PU than normal adult type II alveolar epithelial cells and embryonic pneumocyte nuclei (P<0.001). The lung adenocarcinoma and small cell lung carcinoma cell nuclei had greater TTF-1 PU than squamous cell carcinoma and large cell lung carcinoma cell nuclei (P<0.001). TTF-1 PU was greater in squamous cell carcinoma cell nuclei than in large cell lung carcinoma cell nuclei (P<0.001). In lung adenocarcinoma, squamous cell lung carcinoma and large cell lung carcinoma, TTF-1 PU was greater in the cancerous cell nuclei of lymph node metastases than in the corresponding primary carcinoma cell nuclei (P<0.001, P<0.001, and P<0.05, respectively). In small cell lung carcinoma, TTF-1 PU of the cancerous cell nuclei of lymph node metastases was similar to that of primary carcinomas (P>0.05). TTF-1 PU was greater in lung carcinoma with lymph node metastases than in those without metastalsis (P<0.001). TTF-1 PU of the cell nuclei was not associated with the tumor growth pattern, differentiation and patients' gender (P>0.05), but was greater in TNM stage II-IV than in stage I (P<0.001).</p><p><b>CONCLUSIONS</b>The amount of TTF-1 in the cell nuclei decreases in the order of normal adult type II alveolar epithelial cells, embryonic pneumocytes and lung carcinoma cells. TTF-1 expression is higher in adenocarcinoma and small cell carcinoma and lower in squamous carcinoma and large cell carcinoma. Stronger TTF-1 expression is associated with greater likeliness of lung carcinoma metastatie, and can be an important hallmark for metastasis potential of lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma.</p>