OBJECTIVETo analyze the association between the EGFR protein level and the EGFR gene mutation status in advanced non-small cell lung cancer (NSCLC), and to explore whether the EGFR protein level is related to the efficacy and survival of the EGFR-TKI drug Gifitinib-treated patients with advanced NSCLC.

METHODSNinety-nine cases were enrolled in this study. Pathological tissue specimens and paired peripheral blood samples were collected. Exons 19 and 21 of the EGFR gene mutation were detected by direct sequencing. The concentration of plasma EGFR protein was detected by ELISA. Univariate and multivariate statistical analyses of the efficacy and survival were performed using SPSS 13.0 software.

RESULTSThe response rate (RR) and clinical benefit rate (CBR) of Gefitinib-treated patients were 51.5% and 79.8%, respectively. There were 35 (35.4%) with positive EGFR gene mutation of the 99 samples. The concentration limit of EGFR protein was 55.42 µg/L. The RR and CBR of patients with EGFR gene mutation was significantly higher than those without mutation (65.7% vs. 43.8%, P = 0.037; 94.3% vs. 71.9%, P = 0.008). The median PFS was prolonged (23 months vs. 10 months, P = 0.014). The CBR of patients with high EGFR protein expression (concentration ≥ 55.42 µg/L) was significantly higher than those with low expression (90.0% vs 64.1%, P = 0.004), and the median PFS was prolonged (21 months vs. 8 months, P = 0.016). EGFR protein level was an independent factor affecting the EGFR gene mutation status. The Correlation between EGFR gene mutation status and EGFR protein level was positive.

CONCLUSIONSGefitinib is effective in the treatment of advanced NSCLC patients with EGFR gene mutation and high EGFR protein expression. EGFR protein level in peripheral blood may be a molecular biomarker in prediction of efficacy and survival of the Gefitinib treatment in patients with advanced NSCLC.

Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; genetics ; pathology ; Disease-Free Survival ; Exons ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; blood ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; blood ; genetics ; Remission Induction ; Survival Rate

OBJECTIVETo investigate the expression of forkhead box M1 (FOXM1) and its correlation with clinicopathological features and prognosis in patients with non-small cell lung cancer (NSCLC).

METHODSThe expression of FOXM1 in 68 cases of NSCLC was detected by immunohistochemistry. The FOXM1 expression in 6 tumor tissues (3 cases with negative and 3 cases with positive expression of FOXM1) was analyzed by Western blotting to confirm the immunohistochemical results. The correlation of the expression of FOXM1 with clinicopathalogical features and overall survival of the NSCLC patients was analyzed.

RESULTSThe expression of FOXM1 protein was detected in the nuclei or cytoplasms of the tumor cells. The positive expression rate of FOXM1 was 36.8% (25/68). Western blotting confirmed the immunohistochemical results. The expression level of FOXM1 in advanced stage cancer was significantly higher than that in early stage NSCLC (P = 0.001). The median OS was 23.0 months in patients with negative expression of FOXM1 and 13.0 months in those with positive expression (P = 0.001). Univariate analysis revealed that histological grade, lymph nodes status, TNM stage and FOXM1 expression were significantly associated with prognosis in the NSCLC patients (P < 0.05). The Cox multivariate analysis demonstrated that lymph nodes status, TNM stage and FOXM1 expression were independent poor prognostic factors (P < 0.05).

CONCLUSIONThe expression status of FOXM1 in NSCLC is an independent prognostic factor and negatively correlated with prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Female ; Follow-Up Studies ; Forkhead Box Protein M1 ; Forkhead Transcription Factors ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models

OBJECTIVETo investigate the expression variation and significance of ERK1/2 MAPK signaling transduction pathway in the pathogenesis of esophageal squamous cell carcinoma (ESCC) in Kazakh patients.

METHODSThe expression level of p-ERK1/2 after serum starvation and treatment with U0126 inhibitor was detected in esophageal cancer cell line EC9706 by Western blot assay. The mRNA level of total ERK1/2 (t-ERK1/2) and expression level of t-ERK1/2 and p-ERK1/2 proteins of 25 pairs of ESCC and adjacent normal esophageal mucosal tissues of Kazakh patients were examined and identified by real-time quantitative PCR (qRT-PCR) and Western blotting, respectively. The expression of p-ERK1/2 protein was verified by immunohistochemistry in 126 paraffin-embeded specimens, including 19 normal esophageal mucosa, 55 esophageal carcinomas in situ and 52 invasive carcinomas.

RESULTSERK1/2 MAPK signaling transduction pathway was in an active status in the EC9706 cells. The expression level of p-ERK1/2 in Ec9706 cells reached a peak at 10 min after transient serum stimulation, and p-ERK1/2 expression was totally restrained after the treatment with 50 µmol/L U0126. In the 25 pairs of ESCC and adjacent normal mucosa, the t-ERK1 mRNA level was 1.92 ± 3.49 in the ESCC tissues and 3.67 ± 7.47 in the adjacent normal mucosa. The t-ERK1 mRNA level in ESCC tissues was significantly lower than that in adjacent normal mucosa (P < 0.05), whereas there was no significant difference of t-ERK2 mRNA level between them(P > 0.05). The expression levels of p-ERK1 and p-ERK2 proteins were 0.87 ± 0.14 and 0.79 ± 0.10 in the ESCC tissues, and 1.10 ± 0.13 and 1.32 ± 0.12 in the adjacent normal mucosae. p-ERK1/2 protein in the ESCC tissues was significantly lower than that in the adjacent normal tissue (P < 0.01). However, there was no significant difference between their t-ERK1/2 protein levels (P > 0.05). In the 126 cases of paraffin-embeded specimens, positive expressions of both p-ERK1 and p-ERK2 in esophageal cancer tissues were 7.7% (4/52), significantly lower than those in adjacent normal mucosa (31.6%, 6/19) and carcinoma in situ (85.5%, 47/55, P < 0.05).

CONCLUSIONSERK1/2 MAPK signaling pathway is in an active status in esophageal cancer and adjacent normal mucosa. Our results imply that the activation of p-ERK1/2 MAPK signaling transduction pathway plays a role in the early pathogenesis of ESCC in Kazakh patients.

Butadienes ; pharmacology ; Carcinoma in Situ ; enzymology ; pathology ; Carcinoma, Squamous Cell ; enzymology ; pathology ; Cell Line, Tumor ; China ; ethnology ; Enzyme Inhibitors ; pharmacology ; Esophageal Neoplasms ; enzymology ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 1 ; genetics ; metabolism ; Mitogen-Activated Protein Kinase 3 ; genetics ; metabolism ; Nitriles ; pharmacology ; Phosphorylation ; RNA, Messenger ; metabolism

OBJECTIVETo compare the effect of rh-endostatin on micrangium in tumor and myocardial tissue in nude mice.

METHODSNude mice were randomized into 4 groups (10 mice in each group), blank control group (without tumor burden, received NS 100 µl×d(-1) injection), drug control group (without tumor burden, received rh-endostatin 400 µg×d(-1) injection), model group (with tumor burden, received NS 100 µl×d(-1) injection) and treatment group (with tumor burden, received rh-endostatin 400 µg×d(-1) injection) for 28 days. The tumor volume and body weight of the mice were measured before and after administration. The expression of CD34, MMP-2, MMP-9, HIF-1α and VEGF in the myocardium and tumor were detected by immunohistochemistry. The vascular structure was observed by immunoenzymatic CD34 and Masson double staining.

RESULTSThe increase of tumor volume of the treatment group [(48.18 ± 37.31) mm(3)] was significantly lower than that in the model group [(113.80 ± 73.27) mm(3)). The changes of body weight was not significant different among the four groups. After treated with rh-endostatin, the expressions of MMP-9 and VEGF in tumors were significantly down-regulated, but the expressions of MMP-2 and HIF-1α in the tumor were not. The microvessel density (MVD) in the tumors of treatment group was significantly decreased compared with that of model group. The proportion of tumor vessels covered by collagen in the treatment group was increased compared with that of the model group. However, MVD and micrangium in myocardium were not changed significantly.

CONCLUSIONRh-endostatin can decrease the expression of MMP-9, VEGF and MVD, inhibit the tumor growth and normalize tumor micrangium in tumor but not weaken the MMPs and MVD of mature micrangium in myocadium.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Antigens, CD34 ; metabolism ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Endostatins ; pharmacology ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; pathology ; Myocardium ; metabolism ; Neoplasm Transplantation ; Neovascularization, Pathologic ; pathology ; Random Allocation ; Recombinant Proteins ; pharmacology ; Tumor Burden ; drug effects ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo explore the silencing effects of RNA interference on the expression of 3-phosphoinositide-dependent protein kinase 1 (PDK1) gene, and the effects on malignant phenotypes of esophageal carcinoma EC9706 cells.

METHODSPDK1 siRNAs was transfected into the EC9706 cells. The expression of PDK1 mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). At the same time, expressions of PDK1, Akt and phosphorylated Akt proteins were detected by Western blot. Methyl thiazolyl tetrazolium assay (MTT) was used to examine the cell proliferation after transfection. Flow cytometry was used to determine the percentage of apoptosis cells, and Transwell chambers were used to detect the invasion ability of the cells. Tumor formation in nude mice was used to assess the tumorigenic characteristics in vivo.

RESULTSCompared with the non-transfected group, PDK1 siRNA effectively inhibited the expression of PDK1 mRNA in EC9706 cells, with an inhibition rate of (28.5 ± 4.2)% at 24 h, (51.1 ± 5.7)% at 48 h and (60.6 ± 4.1)% at 72 h after transfection. The expressions of PDK1 and phosphorylated Akt protein were also knocked down by PDK1 siRNA (P < 0.05). PDK1 siRNA significantly inhibited the cell proliferation and invasion, promoted the cell apoptosis, and inhibited the EC9706 cells proliferation in vivo and the expression of PDK1 protein in the transplanted tumors (P < 0.05).

CONCLUSIONPDK1 may play an important role in esophageal cancer cell proliferation, invasion and apoptosis, and may serve as an effective target for cancer gene therapy.

3-Phosphoinositide-Dependent Protein Kinases ; Animals ; Apoptosis ; Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Esophageal Neoplasms ; genetics ; metabolism ; pathology ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Phosphorylation ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Transfection ; Tumor Burden

OBJECTIVETo study the chemosensitivity of lung adenocarcinoma cell line A549 cells to liposome-encapsulated paclitaxel after treatment by nm23-H1-small interference RNA (nm23-H1-siRNA) in vitro.

METHODSThe A549 cells were divided into two groups: non-transfected group and nm23-H1-siRNA-transfected group. Western blot analysis was used to detect the expression of nm23-H1. MTT and flow cytometry were used to determine the cell mortality rate, apoptosis rate and cell cycle after liposome-encapsulated paclitaxel treatment in both groups.

RESULTSThe expression of nm23-H1 in A549 cells was significantly decreased after transfection with nm23-H1-siRNA. After treatment for 48 hours with liposome-encapsulated paclitaxel, the cell mortality rate was increased with the increasing concentration of liposome-encapsulated paclitaxel in both groups, but increased higher in the nm23-H1-siRNA-transfected group. When the concentration of liposome-encapsulated paclitaxel was above 5 µg/ml, the cell mortality rate was significantly higher than that in the non-transfected group (P < 0.05). The proportion of apoptotic cells also increased in the nm23-H1-siRNA-transfected group, compared with that of the non-transfected group (t = 3.812, P < 0.05), while the proportion of cells at S and G(2)/M phase decreased after transfection with nm23-H1-siRNA (S phase:t = 8.356, P < 0.05; G(2)/M phase:t = 7.256, P < 0.05).

CONCLUSIONSNm23-H1 is related with the chemoresistance to liposome-encapsulated paclitaxel in lung adenocarcinoma cell line A549 cells. Inhibition of the expression of nm23-H1 by nm23-H1-siRNA can improve the in vitro chemosensitivity of A549 cells to liposome-encapsulated paclitaxel.

Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Humans ; Lung Neoplasms ; metabolism ; pathology ; NM23 Nucleoside Diphosphate Kinases ; genetics ; metabolism ; Paclitaxel ; administration & dosage ; pharmacology ; RNA, Small Interfering ; genetics ; Transfection

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoembryonic Antigen ; blood ; Catheter Ablation ; methods ; Colorectal Neoplasms ; pathology ; Combined Modality Therapy ; Fluorouracil ; therapeutic use ; Humans ; Leucovorin ; therapeutic use ; Liver Neoplasms ; blood ; drug therapy ; secondary ; surgery ; Neoplasm Recurrence, Local ; Organoplatinum Compounds ; therapeutic use

Antineoplastic Agents, Phytogenic ; therapeutic use ; Drugs, Chinese Herbal ; isolation & purification ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Neoplasms ; drug therapy ; Patents as Topic ; Phytotherapy ; methods ; Plants, Medicinal ; chemistry

OBJECTIVETo evaluate the efficacy of short-term intermittent prophylactic use of a recombinant human thrombopoietin (rhTPO) in chemotherapy-induced severe thrombocytopenia in lung cancer patients.

METHODS24 advanced non-small cell lung cancer (NSCLC) patients who experienced severe thrombocytopenia in the last chemotherapy cycle received prophylactic rhTPO treatment in the next chemotherapy cycle (prophylactic treated cycle, PTC). rhTPO was given subcutaneously 300 U×kg(-1)×d(-1) on days 2, 4, 6, and 9 after the initiation of chemotherapy. Platelet count was monitored and compared with that in the previous treatment cycle (control cycle, CC).

RESULTSThe lowest platelet count in the prophylactic rhTPO cycle was significantly higher than that in control cycle [(56 ± 16) × 10(9)/L vs. (28 ± 13) × 10(9)/L, P < 0.001]. The duration of thrombocytopenia was also shortened by the prophylactic rhTPO [(8 ± 2) d vs. (12 ± 3) d, P < 0.001]. The area under curve (AUC) of platelet count (21 days) was significantly increased [(3517 ± 685) × 10(9)/L vs. (2063 ± 436) × 10(9)/L, P < 0.001]. The time to platelet nadir and peak was not affected.

CONCLUSIONProphylactic use of rhTPO can attenuate the severity and shorten the duration of chemotherapy-induced thrombocytopenia in lung cancer patients.

Adenocarcinoma ; blood ; drug therapy ; pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Area Under Curve ; Carboplatin ; administration & dosage ; adverse effects ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Dizziness ; chemically induced ; Female ; Fever ; chemically induced ; Humans ; Lung Neoplasms ; blood ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Platelet Count ; Recombinant Proteins ; adverse effects ; therapeutic use ; Thrombocytopenia ; blood ; chemically induced ; drug therapy ; Thrombopoietin ; adverse effects ; therapeutic use

OBJECTIVETo evaluate the efficacy and toxicity of Yanshu injection (a compound Chinese traditional medicine from Sophora flauescens Ait) combined with concomitant radiochemotherapy in patients with stage III nasopharyngeal carcinoma.

METHODSSixty patients with stage III nasopharyngeal carcinoma were randomized into Yanshu group and control group (n = 30, each). Patients in the Yanshu group received Yanshu injection in addition to intensity modulated radiation therapy (IMRT) and concomitant chemotherapy, and those in the control group were treated with IMRT and concurrent chemotherapy.

RESULTSThe 1-year, 2-year, 3-year and 4-year overall survival rates were 100%, 93.3%, 86.7%, 80.0% for Yanshu group, and 96.7%, 90.0%, 83.3%, 76.7% for the control group, respectively, with no significant difference between the two groups (P = 0.565). The 1-year, 2-year, 3-year and 4-year progression-free survival rates were 96.7%, 90.0%, 83.3%, 70.0% for Yanshu group, and 90.0%, 86.7%, 76.7%, 66.7% for control group, respectively, with no significant difference (P = 0.554). However, the reaction of mucosa of oral cavity, myelosuppression and thrombocytopenia in the Yanshu group were significantly lower than that in the control group (P < 0.05). The quality of life of the patients in the Yanshu group was significantly higher than that in the control group (P < 0.05).

CONCLUSIONSYanshu injection combined with radiochemotherapy in patients with stage III nasopharyngeal carcinoma show a good efficacy and can reduce the side effects of radiochemotherapy of nasopharygeal carcinoma, and improve the quality of life of the patients.

Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; therapy ; Chemoradiotherapy ; methods ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Disease-Free Survival ; Drugs, Chinese Herbal ; adverse effects ; isolation & purification ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; etiology ; Male ; Medicine, Chinese Traditional ; Mucositis ; chemically induced ; etiology ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; therapy ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Plants, Medicinal ; chemistry ; Quality of Life ; Radiotherapy, Intensity-Modulated ; adverse effects ; Sophora ; chemistry ; Survival Rate ; Thrombocytopenia ; chemically induced ; etiology