[Pharmacological effects of site specific conjugated anti-human epidermal growth factor receptor 2-antibody drug conjugate using unnatural amino acid technology].

OBJECTIVE: To investigate inhibitory activities of a homogenous anti-human epidermal growth factor receptor 2 (HER2)-antibody drug conjugate (ADC) on the proliferation of nine tumor cell lines with different levels of HER2 expressions, and its activities on the tumor growth of five xenograft mouse models. METHODS: The HER2 expression levels of BT-474, Calu-3, MCF-7, MDA-MB-231, MDA-MB-468, SK-BR-3, SK-OV-3, HCC1954, NCI-N87 tumor cell lines were measured using QIFI KIT. For the in vitro anti-proliferation assay, serial diluted anti-HER2-ADC, ado-trastuzumab emtansine, AS269, pAF-AS269 and paclitaxel were added to the seeded cells, and after 72 or 96 hours of incubation, the cell proliferation was analyzed. For the in vivo activity, 5-6 weeks old mice were inoculated with four HER2 positive tumor cell lines HCC1954, BT-474, SK-OV-3, NCI-N87 or one HER2 negative tumor cell line MDA-MB-468. Different amounts of anti-HER2-ADC, ado-trastuzumab emtansine, trastuzumab, paclitaxel and phosphate buffered saline control were injected after the tumor volume reached a certain size, then the tumor growth inhibition was analyzed. RESULTS: The expression levels of the six high HER2-expression cell lines SK-OV-3, NCI-N87, SK-BR-3, Calu-3, HCC1954, BT-474 were between 430 000 to 800 000 receptors per cell, which were 50 times higher than those of the other three low HER2 expression tumor cell lines MDA-MB-231, MCF-7, MDA-MB-468. Anti-HER2-ADC had inhibition effects on cell lines with high level of HER2 expression in the in vitro anti-proliferation assay. The half maximal inhibitory concentrations of anti-HER2-ADC on SK-OV-3, NCI-N87, SK-BR-3, Calu-3, HCC1954, BT-474 tumor cell lines were 46 pmol/L, 17 pmol/L, 17 pmol/L, 161 pmol/L, 125 pmol/L, 50 pmol/L, respectively. Anti-HER2-ADC had a dose dependent antitumor activity in vivo in all the HER2 positive xenograft mouse models. In NCI-N87 xenograft tumor model, the same dose of anti-HER2-ADC showed better anti-tumor activity compared with trastuzumab and ado-trastuzumab emtansine, and its relative tumor proliferation rates were about 1/30 to 1/20 of the two. In HCC1954 xenograft tumor model, the complete regression of the tumor was observed. As expected, anti-HER2-ADC had no tumor inhibitory effects on MDA-MB-468 xenograft models with low HER2 expression. The antitumor activities of anti-HER2-ADC in HER2 positive xenograft tumor models were the same as or better than the activities of ado-trastuzumab emtansine. CONCLUSION: The homogenous site-specific anti-HER2-ADC obtained using unnatural amino acid technology can inhibit the growth of high HER2-expression tumor cells with high potency both in vivo and in vitro.

Prognostic and predictive significance of plasma hepatocyte growth factor and carcinoembryonic antigen in non-small lung cancer after surgery.

OBJECTIVES: Scatter factor, also known as hepatocyte growth factor (SF/HGF), is a polypeptide growth factor with a number of biologic activities, including cell scattering, stimulation of cell motility, mitogenesis, morphogenesis, angiogenesis, and cellular invasiveness, it is thought to be important in the growth and spread of several carcinomas. We assessed whether preoperative plasma levels of HGF and carcinoembryonic antigen (CEA) can enhance the accuracy of standard models for predicting pathologic features and clinical outcomes. PATIENTS AND METHODS: The study comprised 45 consecutive patients treated with surgery for clinically localized non-small-cell lung cancer. HGF and CEA were measured using the commercially available immunoassay. Multivariate logistic regression was used to assess the relationship between plasma HGF/CEA and pathologic features. Multivariate Cox regression was used to predict disease recurrence. RESULTS: Patients with lung squamous cell cancer (SCC) more frequently had higher plasma HGF, whereas CEA levels were significantly elevated in patients with non-SCC histology. Preoperative plasma HGF and CEA levels were not the independent predictors of overall survival. CONCLUSIONS: Preoperative plasma levels of HGF and CEA are not the independent predictors of non-small lung cancer disease recurrence and metastasis after surgery; HGF is a predictor of lung squamous cell cancer. Use of HGF may help in therapeutic decision-making and estimate the histological type of NSCLC.

[Clinical observation on effect of chemotherapy combined with Chinese medicine in treating advanced tumor patients and on immunologic parameters].

OBJECTIVE: To observe the effects of chemotherapy combined with Chinese herbal medicine (Spleen-Kidney tonifying) in treating advanced tumor patients and on immune parameters. METHODS: One hundred and one advanced tumor patients were randomly divided into the treated group (54 patients) treated by Chinese medicine combined with chemotherapy, and the control group (47 patients) treated by chemotherapy alone. After being treated for 8 weeks (2 treatment courses), the changes of tumor size, body weight, Karnofsky scores, immunologic parameters, peripheral blood cells, as well as the toxic and side-effects were also studied. RESULTS: Improvement of various degree was obtained on the immunologic parameters such as CD3, CD4, CD4/CD8, NK cells, and the quality of life, as Karnofsky score in the treated group, in comparing with those in the control group the difference was significant (P < 0.05, P < 0.01). But on behalf of the toxic and side-effects in advanced patients, there was no significant difference between the two groups. CONCLUSION: Chemotherapy combined with Chinese Spleen-Kidney tonifying drugs could improve the immunologic functions in the advanced tumor patients.