BACKGROUNDChemotherapy is a main method for patients with advanced non-small cell lung cancer (NSCLC). NSCLC is usually a drug-resistant neoplasm. Innate or acquired drug-resis-tance contributes to the chief cause for bad effect in the treatment of patients with NSCLC. To search for a new anti-cancer drug becomes a goal of clinical oncologists. The aim of the present study is to evaluate the curative effect and side reactions of IRESSA in the treatment of patients with advanced refractory NSCLC.

METHODSThe curative investigation was carried out after 100-day oral IRESSA by a dosage of 250mg/d in patients with advanced refractory NSCLC. The patients had ever experienced at least one regimen of chemotherapy.

RESULTSTotally 33 patients enrolled in this study and all were stage IV. There were 25 males and 8 females. All enrolled patients except one patient who died of severe adverse side reaction completed treatment by IRESSA. Thirty-two cases were evaluated. Complete response was obtained in 1 patient (3.1%). Partial response was seen in 11 patients (34.4%). The overall effective rate was 37.5% (12/32). The disease-control rate was 65.6% (21/32). Time to progression was 5.7 months. Overall survival time was 3.3 to 25.9 months (median survival time was 9.6 months). One-year survival rate was 28.1% (9/32). Two-year survival rate was 6.3% (2/32). The longest survivor lived for 25.9 months. The curative effect was correlated with the pathological type, in sequence of alveolar cell carcinoma, adenocarcinoma and squamous cell carcinoma. Almost all the adverse reactions were acceptable. The main adverse reactions included rash, itching of skin, arthralgia, diarrhea, anorexia, nausea, vomiting, dizziness, headache, chest distress and abdominal pain. No patients showed abnormal in liver or kidney function. No electrocardiogram abnormality was found. One patient who had chronic pulmonary fibrosis before died of respiratory failure due to severe interstitial pneumonia.

CONCLUSIONSIRESSA takes better effect on the advanced drug-resistant patients with NSCLC. So IRESSA may be accepted as third line in the treatment of advanced NSCLC and as first line in the treatment of patients with bad constitution who have no opportinities for operation, irradiation therapy or chemotherapy.

Objective To explore the difference in inhibitory control ability between DRD2 gene subtype of heroin addicts with fMRI.Methods Thirty-seven heroin-dependent patients were divided into DRD2 Taq IA+ group (A+,22)and matched DRD2 Taq IA-group (A-,15).Functional MRI was performed in all patients while they were executing an event-related go/nogo task at 3.0T MR scanner.The differences of brain activated images and behavioral data between the two groups were analyzed with SPM8 and SPSS1 6.0 software,respectively.Results There were no significant differences in reaction time,accuracy and false alarm rates between the two groups (P>0.05).Compared with A-group,weaker activation in the medial prefrontal cortex,dorsal anterior cingulate,middle cingulate,supplementary motor area,temporal lobe,fusiform gyrus,lingual gyrus,hippocampus and parahippocampal gyrus in response inhibition condition were demonstrated in A+ group (voxel number>228,t=2.11,Alphasim correction,P<0.05).There was no corrlation between the intensity within the activated brain regions and the usage of heroin,morphine urine test positive number(P>0.05).Conclusion DRD2 Taq IA+ group exist deactivation of the brain area on memory,inhibitory control,visual spatial attention. It may be the neural basis that contribute to easy addiction and relapse for A+ carriers.

Objective Toinvestigatethechangesinbrainfunctionofheroindependentindividualsafternucleusaccumbens(NAC) ablativesurgery.Methods Twenty-fourheroindependentindividualsafterNACablativesurgery(NACgroup),27heroindependent individualsinshort-termabstinence(HDgroup)and32healthycontrol(HCgroup)wereincludedaresting-statefMRIstudy.Amplitudeoflow-frequencyfluctuations(ALFF)valuesofeachparticipantswerecalculated.DiffernecesinALFFvalueamongthethreegroupswere analyzed by One-Way ANOVA .Results Brain regions with statistically significant A L F F differences a m ong the three groups included left cerebellum,rightposteriorcentralgyrus,leftcaudatenucleus,rightmiddlefrontalgyrus,leftcuneusandbilateralinferiortemporal gyrusI.ntherightcentralposteriorgyrus,theALFFvalueofHDgroupwaslowerthanthatofNACandHCgroupI.ntheleftcerebellum,the ALFFvalueofHDgroupwashigherthanthatofNACandHCgrouprespectivelyI.nbilateralinferiortemporalgyrusandleftcaudatenucleus, ALFFvaluesofNACandHDgroupswerelowerthanHCgroup.ALFFvaluesofNACandHDgroupswerehigherthanHCgroup inrightmedialfrontalgyrusandleftcuneus.Conclusion InheroindependentindividualsafterNACablativesurgery,theALFFvaluesofleft cerebellumandrightposteriorcentralgyrustendtobenormal.NodifferenceinALFFvalueinregionsofdefaultmodenetworkbetweenNACand HDgroups.

Objective: To establish a nude mouse model of subcutaneous lung cancer using dual fluorescence reporting genes of luciferase (Luc) and near-infrared fluorescent protein (iRFP). Methods: The Luc and iRFP expressed lentiviral vector was constructed by Gateway method. After verified by sequencing, the lentivirus particle was prepared and infected into lung cancer A549 cells. Successfully infected A549 (mA549) cells were selected by puromycin and amplified. The expression of Luc and iRFP were observed under fluorescence microscope, and the expression of c-Met protein on the cell surface was detected by immunofluorescence. Twelve female nude mice were randomly divided into 2 groups, 6 in each group. A549 and mA549 cells were inoculated subcutaneously into the right forelimb of nude mice. The growth and fluorescence expression of the tumor were observed by in vivo imaging. The tumor formation was evaluated by hematoxylin-eosin (HE) staining and immunohistochemistry. Results: The Luc and iRFP stably expressed mA549 cell line was successfully constructed. The expressions of iRFP and Luc in mA549 cells were observed under fluorescence microscope. The results of immunofluorescence showed that c-Met protein expressed in both A549 cells and mA549 cells. The growth period of mA549 xenograft in nude mice was moderate and the tumorigenesis rate was 100%. The growth trend of mA549 cells in vivo was not significantly different from that of A549 cells (P>0.05). HE staining and immunohistochemistry results showed that the tumor issues displayed typical histopathological features of tumor. Immunohistochemistry results showed that both A549 and mA549 tumors expressed c-Met protein. Conclusion A stable, real-time monitoring model of iRFP-Luc-A549 lung cancer cell xenograft in nude mice was successfully constructed.

OBJECTIVE: To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines. METHODS: Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively. RESULTS: MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC₅₀) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC₅₀ values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC₅₀ values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G₁ phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3β and APC, while down-regulate that of β-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/β-catenin pathway of HT-29 cells. CONCLUSION Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/β-catenin pathway-related mRNA and protein expressions.
Humans ; beta Catenin/metabolism* ; Caco-2 Cells ; Quinones/pharmacology* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Cell Proliferation ; Colorectal Neoplasms/metabolism* ; Cell Line, Tumor ; Apoptosis ; Benzoquinones/pharmacology* ; RNA, Messenger ; Wnt Signaling Pathway