Objective To evaluate the prognostic factors in locally advanced non-small-cell lung cancer (LA-NSCLC) for selectively carrying out prophylactic cranial irradiation (PCI).Methods 114 patients with LA-NSCLC between Jun 2006 and Oct 2010 were retrospectively analyzed. Related risk factors and features about brain metastases were analyzed.Results The 2-year incidence rate of brain metastases was 31.58 ％ (36/114),the first brain metastases was 20.18 ％ (23/114),and sole brain metastases was 9.65 ％(11/114),respectively.Variables involved in the equation of binary logistic regression analysis were pathology (OR =5.892) and treatment mode(OR =2.888).The incidence rate of brain metastases in patients of non-squamous carcinoma and single treatment mode was higher than others (P ＜ 0.01) Model fitting is better (P ＞ 0.05).Overall accuracy rate of predicting brain metastases is 67.7 ％.The increased rate of lactate dehydrogenase in the patients with brain metastases or death was 17.54 ％, which was higher than that in the survival patients without brain metastases (P ＜ 0.01).At the same time,the station number and the number of mediastinal lymph node metastases were positively correlated (r =0.716, P ＜ 0.01).The incidence rate of brain metastases or mortality rate was higher in the adenocarcinoma cases than that in the squamous carcinoma cases (P ＜ 0.01,P ＜ 0.05),with more frequent occurrence of mediastinal metastases.The mean diameter of squamous carcinoma and adenocarcinoma were 5.8 cm and 3.9 cm, respectively (P ＜ 0.01).Conclusions The incidence rate of brain metastases was higher in patients with single treatment.Large primary tumors, high lactate dehydrogenase, non-squamous carcinoma, multiple stations, and multiple mediastinal lymph nodes metastases can be regarded as risk factors of brain metastases to perform PCI.

OBJECTIVETo observe and analyze the antitumor effect of endostar combined with docetaxel under different administration sequences.

METHODSNude mice with xenograft tumor (A549 cell line) were randomized into 3 groups, 8 mice/group: (1) Concurrent administration group (each mouse: endostar 400 µg/d, d1-d35, docetaxel 10 mg/kg, every 3 days, d1-d19); (2) Endo-first group (each mouse: endostar 400 µg/d, d1-d35, docetaxel 10 mg/kg, every 3 days, d16-d34); (3) Model group (positive control, tumor-bearing mice without treatment, each mouse: physiological saline, 100 µl/d, d1-d35, water for injection, 200 µl/d, d1-d35, every 3 days), and blank control group (negative control, normal mice without treatment, 8 mice), the administration method was the same to the model group. The volume of tumor and the weight of mouse were measured during treatment. Circulating endothelial cells (CECs) were detected by flowcytometry, and the expression of matrix metalloproteinase (MMP-2, MMP-9), the tissue inhibitor of MMP (TIMP-1, TIMP-2), the extracellular MMP inducer (EMMPRIN), CD34, α-smooth muscle actin (α-SMA) were determined by immunohistochemistry.

RESULTSThe tumor growth of concurrent administration group (39.94 mm(3)) was lower than that of the endo-first group [(99.57 ± 74.48) mm(3)] during treatment, both of them were smaller than that of the model group [(217.67 ± 95.44) mm(3), P < 0.05]. The amount of CECs in the endo-first group [(77.25 ± 24.02) cells/10(4) cells] was more than that of the concurrent administration group [(25.86 ± 11.77) cells/10(4) cells], the model group [(14.71 ± 11.07) cells/10(4) cells], and the blank control group [(12.90 ± 11.20) cells/10(4) cells, P < 0.01]. The expression of MMPs in the treatment groups was obviously downregulated. The expressions of TIMP-1 in the endo-first group and TIMP-2 in the concurrent administration group were upregulated (P < 0.05). The expression of EMMPRIN was significantly down-regulated in the concurrent administration group (P < 0.05). The MVD and α-SMA expressions of the treatment groups were less than that of the model group (P < 0.05).

CONCLUSIONIn comparison with the endo-first group, the anti-tumor effect and survival quality of the concurrent administration group are better. Both of the administration groups may have "vascular normalization effect" by down-regulating MMPs expression through different points, and inhibit the cancer-induced stromal reaction, restraining the cancer progress to a certain extent. The changes of CECs should be a dynamic process with an initial rise in the early-stage suggesting the decrease of vascular bed and subsequent decline ascribed to apoptosis of CECs and the tumor-regression after combined therapy. Investigation of its dynamic changes may be helpful to know the change of tumor burden and vascular bed and predict the antitumor effect.

Actins ; metabolism ; Angiogenesis Inhibitors ; administration & dosage ; pharmacology ; Animals ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Basigin ; metabolism ; Cell Line, Tumor ; Drug Administration Schedule ; Endostatins ; administration & dosage ; pharmacology ; Endothelial Cells ; cytology ; Female ; Lung Neoplasms ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; drug effects ; Neoplasm Transplantation ; Taxoids ; administration & dosage ; pharmacology ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Tumor Burden ; drug effects

The identification of the components absorbed in serum of platycosides in total saponins fraction of Platycodonis Radix is great significance, but there are still great challenges. In this study, 8 types of 44 primordial components from Platycodon saponins were firstly identified using the ultra-performance liquid chromatography-linear ion trap electrostatic field orbitrap high resolution mass spectrometry (UPLC-LTQ-Orbitrap-MS) equipped with the software of Compound Discoverer 3.2 and Trace finder 2.1. Then, the platycosides and their deglycosylated metabolites were used as the template molecules to construct the intestinal microbiota mediated method to identify the primary components and the prototypes in serum. As results, 57 components originating from 44 prototypes of platycosides were identified from drug-containing plasma. Those compounds consist of 12 prototypes of platycosides and 45 metabolites, while the prototypes in serum are also deglycosylated metabolites of other platycosides. The results showed that the intestinal microbiota mediated method could be applied to identify the metabolites of platycosides in total saponins fraction of Platycodonis Radix; and reveal the potential existing forms of prototypes of platycosides in plasma; In addition, it could clearly illustrate the one to many and many to one network of the prototypes and metabolites of platycosides. All animal protocols were approved by the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (No.JZLLSC-202100322).