Effects of insulin-like growth factor 1 receptor and its inhibitor AG1024 on the progress of lung cancer / 华中科技大学学报（医学）（英德文版）

The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have been increasingly recognized to drive the development of malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the effects of IGF-1R and its inhibitor, AG1024, on the progression of lung cancer. Tissue microarray and immunohistochemistry were employed to detect the expressions of IGF-1 and IGF-1R in NSCLC tissues (n=198). Western blotting was used to determine the expressions of IGF-1 and phosphorylated IGF-1R (p-IGF-1R) in A549 human lung carcinoma cells, and MTT assay to measure cell proliferation. Additionally, the expressions of IGF-1, p-IGF-1R and IGF-1R in a mouse model of lung cancer were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively. The results showed that IGF-1 and IGF-1R were overexpressed in NSCLC tissues. The expression levels of IGF-1 and p-IGF-1R were significantly increased in A549 cells treated with IGF-1 as compared to those treated with IGF-1+AG1024 or untreated cells. In the presence of IGF-1, the proliferation of A549 cells was significantly increased. The progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF-1+AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF-1R at the protein and/or mRNA levels. It was concluded that IGF-1 and IGF inhibitor AG1024 promotes lung cancer progression.

Association of preoperative serum IGF- I concentration with clinicopathological parameters in patients with non-small cell lung cancer / 华中科技大学学报（医学）（英德文版）

Insulin-like growth factor-I (IGF-I) is a mitogenic and anti-apoptotic factor. Serum IGF-I concentration is related to some cancer risk and tumor progression. The aim of this research was to study the association of preoperative serum IGF-I concentration with clinicopathological parameters and prognosis of non-small cell lung cancer (NSCLC). Preoperative serum IGF-I concentration was measured in 80 consecutive patients with NSCLC who underwent radical lung cancer resection, and 45 patients with benign pulmonary lesion (BPL) by using enzyme linked immunosorbent assay (ELISA). The results showed that the serum IGF-I concentration was elevated and correlated with clinicopathological parameters and overall survival (OS) in NSCLC patients. Serum IGF-I concentration was significantly higher in patients with NSCLC than in those with BPL. The IGF-I concentrations were significantly higher in NSCLC patients with ≥T2, N1-3, and in IIIA-IV but not in those with <T2, N0, or IA-IIB. The increased serum IGF-I concentration was significantly correlated with poor prognosis. Our data show the positive correlation between IGF-I serum concentration and the tumor size for the first time. It seems that IGF-I related to the progression of lung cancer may depend on autocrine/paracrine function. In addition, our study reveals that higher serum IGF-I concentration is correlated with larger tumor size, advanced stages, local lymph node metastasis and worse prognosis, indicating that endocrine IGF-I is also important for the progression for NSCLC.

Association of preoperative serum IGF- I concentration with clinicopathological parameters in patients with non-small cell lung cancer / 华中科技大学学报（医学）（英德文版）

Insulin-like growth factor-I (IGF-I) is a mitogenic and anti-apoptotic factor. Serum IGF-I concentration is related to some cancer risk and tumor progression. The aim of this research was to study the association of preoperative serum IGF-I concentration with clinicopathological parameters and prognosis of non-small cell lung cancer (NSCLC). Preoperative serum IGF-I concentration was measured in 80 consecutive patients with NSCLC who underwent radical lung cancer resection, and 45 patients with benign pulmonary lesion (BPL) by using enzyme linked immunosorbent assay (ELISA). The results showed that the serum IGF-I concentration was elevated and correlated with clinicopathological parameters and overall survival (OS) in NSCLC patients. Serum IGF-I concentration was significantly higher in patients with NSCLC than in those with BPL. The IGF-I concentrations were significantly higher in NSCLC patients with ≥T2, N1-3, and in IIIA-IV but not in those with

Expression of PKB protein in human squamous-cell carcinoma and adenocarcinoma of lung / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of protein kinase B (PKB) in human-squamous cell carcinoma (SCC) and adenocarcinoma of lung (ADC) and in benign lung tissues (BD, lung tissues adjacent to cancer or from patients with benign lung diseases), and its association to clinicopathological characteristics.</p><p><b>METHODS</b>The PKB expression in 41 specimens from patients with SCC (26 cases) and ADC (15 cases) and in 12 specimens from patients with benign lung diseases (BD) were investigated by immunohistochemistry and Western blot analysis.</p><p><b>RESULTS</b>PKB in benign lung tissues was usually weakly stained and scattered in distribution. It was remarkably increased in lung cancer compared to benign lung tissue. The positive rates of PKB in SCC and ADC were 50% (13/26), 60% (9/15), respectively, and there was no significant difference between them. PKB expression was significantly stronger in lung cancer patients in advanced stages (stage III or IV) or with poor differentiation, than those in early stages (stage I or II) or with moderate or well differentiation. The expression was stronger in patients with local lymph node metastasis than those without (P = 0.0391).</p><p><b>CONCLUSION</b>PKB protein is over-expressed in human squamous-cell carcinoma and adenocarcinoma of lung.</p>

A study on the role of DNA repair gene O6-methylguanine-DNA methyltransferase in the development of human lung cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the role of O(6)-methylguanine-DNA methyltransferase (hMGMT) in the development of human lung cancer.</p><p><b>METHODS</b>Reverse transcription-polymerase chain reaction (RT-PCR) method was applied to measure hMGMT mRNA expression in 150 lung cancer specimens, 40 normal lung tissues, and in the peripheral mononuclear blood cells from 50 lung cancer cases and 50 normal controls. The protein expressions of p53, C-MYC and K-RAS were assessed by immuno-histochemistry. The effects of some exposure factors on the expression of hMGMT gene were analyzed. The relationships between hMGMT gene and cancer related genes p53, C-MYC and K-RAS were investigated.</p><p><b>RESULTS</b>The mRNA of hMGMT was low or absent in 49 of 150 (32.7%) lung cancer specimens, whereas 2 of 40 (5%) normal lung tissues had reduced the levels of hMGMT mRNA. The low expression of hMGMT seemed to be a risk factor of lung cancer, with a OR of 9.22 (2.05-57.65). Reduced expression levels of hMGMT mRNA were observed in 10 of 50 (20%) lung cancer patients' peripheral mononuclear blood cells, and 2 of 50 (4%) blood cells among normal controls. When investigating the exposure factors which affecting the expression of hMGMT gene, we noticed that smoking was suppressing the expression of hMGMT gene. Interestingly, over-expression of K-RAS oncogene was significantly correlated with low expression of hMGMT (P < 0.05). However, the expressions of p53 and C-myc were not correlated with the status of hMGMT gene.</p><p><b>CONCLUSION</b>hMGMT might play an important role in the development of human lung cancer. Low expression of hMGMT gene seemed to be a risk factor for lung cancer which could be used as a valuable biomarker on susceptibility of human lung cancers.</p>