ABSTRACT
Non-small cell lung cancer (NSCLC) is currently the leading cause of cancer-related deaths worldwide. Angiogenesis, the formation of new vasculature, is a complex and strictly regulated process that promotes metastasis and disease progression in lung cancer and other malignancies. Anti-angiogenic therapy is an anti-cancer strategy that targets the new vessels. Most anti-cancer agents used in the clinic include cytotoxic drugs, which target all rapidly dividing cells, resulting in severe adverse effects. These effects in-clude immunosuppression, intestinal problems, and hair loss. By contrast, anti-angiogenic agents theoretically exhibit fewer side effects because angiogenesis rarely occurs in healthy adults, except in the uterine endometrium. Various angiogenic factors may contribute to the regulation of angiogenesis in the individual tumor;thus, the proper selection of patients who may benefit from a specific therapy is important, considering the increasing number of clinically tested agents. This study provides an overview of angiogenic molecules cur-rently being investigated as prognostic and predictive biomarkers in NSCLC. Clinical examples are presented to show the rationales for investigating various biomarkers of pre-clinical studies.
ABSTRACT
Objective To compare the dosimetric differences among three-dimensional conformal radiotherapy(3D-CRT),intensity-modulated radiotherapy(IMRT)and RapidArc for prophylactic carnial irradiation(PCI)in small cell lung cancer(SCLC)patients.Methods Ten patients with SCLC were enrolled into this study.3D-CRT,9-field IMRT(IMRT)and double arc RapidArc plans were designed and optimized for each patient.The goal was to deliver 25 Gy to ≥ 95％ of the planning target volume(PTV)while the same normal-tissue dose constraints were achieved.The dose distribution and conformal index (CI),homogeneity index(HI)of target volume,the maximum dose(D2 ％),the minimum dose(D98 ％),target coverage of PTV(V95 and V100),and Dmean and Dmax of organs at risk(OAR)were analyzed by using the dose volume histogram(DVH).The monitor units and delivery time were also evaluated.Results All plans met the clinical requirements.PTV dosimetric parameters(CI,HI,D2％,D98％,V95 and V100)of RapidArc and IMRT were superior to those of 3D-CRT with significant difference(P＜0.05).The maximum doses to the optic nerves,brainstem and the mean dose to the parotid glands of the IMRT and RapidArc plans were all significantly lower than those of the 3D-CRT plan(P＜0.05),while 3D-CRT plan provided the lowest maximum doses and mean dose of the lens and eyes(P＜0.05).Compared with IMRT plan,no obvious advantage in PTV dosimetric parameters could be observed in RapidArc plans.In terms of organ sparing,no statistical difference was observed between IMRT and RapidArc plans.The number of monitor units for 3D-CRT,IMRT and RapidArc were 287.8,1388.8 and 346.6,respectively.Conclusions Compared with 3D-CRT,IMRT and RapidArc show better dosimetric quality.The 3D-CRT plan has a significantly lower dose on the lens and eyes,less MU and shorter delivery time than IMRT and RapidArc plans.
ABSTRACT
Objective To observe the effect of amylin on the islet β-cells voltage-gated L-calcium channels in rats. Method Patch clamp technique was employed in the observation of the features and changes of electric current of islet β-cells voltage-gated L-calcium channels before and after using amylin. Results In the glucose environment of 5. 5 mmoL/L, the electric current of rat islet β-cells voltage-gated L-calcium channels was activated at-40 mV and reached the peak at about +20 mV, with a peak value of about-120 pA and the insulin secretion level was(0. 76±0. 12) μg/L. Under the stimulation of glucose of 16. 7 mmol/L, the peak current voltage moved to the left and increased up to-140 pA and the level of insulin secretion measured (1.78±0. 13) μg/L. Hatch islet β-cells in amylin at the concentrations of 0. 5, 1.0, 5.0 and 10.0 μmol/L, respectively. It was observed that in the 0. 5 μmol/L and 1.0 μmol/L groups,there was no remarkable change in the peak potential activation voltage, current, and insulin secretion volume in comparison with the control group. However, in the environment of 5.5 mmol/L glucose, the increase of activation voltage of the 5.0 and 10.0 μmol/L groups was-30 mV, with the peak current reduced to approximately-80 pA and-60 pA and the insulin secretion decreased to (0. 49±0. 11) μg/L and (0. 36±0. 12) μg/L respectively. Under the concentration of 16. 7 mmol/L glucose, the activation voltage increased from-40 mV up to-30 mV and the peak current reduced to-80 pA and-40 pA. In the meantime, the insulin secretion decreased respectively to (1.20±0. 13) μg/L and (0. 89±0. 14) μg/L, which is of significance. Conclusion The secretion of insulin is synchronized with the opening of the islet β-cells voltage-gated L-calcium channels at the stimulation of glucose. The amylin inhibition of the insulin secretion is also synchronized with the opening of islet β-cells voltage-gated L-calcium channels and it's in a positive concentration-dependent manner.