Functional study of the eukaryotic fluorescent expression vector of truncated lymphoid enhancer-binding factor 1 (LEF-1) gene in SW480 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a eukaryotic fluorescent expression vector of truncated lymphoid enhancer-binding factor 1 (LEF-1) gene and investigate its effect on the proliferation and apoptosis of human colonic carcinoma cell line SW480.</p><p><b>METHODS</b>Truncated LEF-1 gene was obtained by PCR and DNA recombination from human lymphoid node cDNA library. The PCR product of LEF-1 gene was inserted into the plasmid pMD-18T and sequenced. The truncated LEF-1 gene was inserted into the eukaryotic expression plasmid pcDNA3.1 and fused with mRFP for tracing. Using Lipofectamine 2000, the plasmid pcDNA3.1-LEF-1-mRFP was transfected into Hela cells and detected by Western blotting and fluorescence activated cell sorting (FACS). The changes in the growth, proliferation and apoptosis of the SW480 cells were observed after transfection with the plasmids.</p><p><b>RESULTS</b>The truncated LEF-1 gene was successfully cloned. After transfection with the plasmid pcDNA3.1-LEF-1-mRFP, the Hela cells expressed the product of LEF-1 as detected by Western blotting and FACS. The growth and proliferation of SW480 cells was inhibited and the cell apoptosis increased after transfection with the plasmid pcDNA3.1-LEF-1-mRFP, which also caused cell cycle arrest in G0/1 phase.</p><p><b>CONCLUSION</b>The eukaryotic expression fluorescent vector pcDNA3.1-LEF-1-mRFP has been constructed and expressed in eukaryotic cell line successfully. The truncated LEF-1 protein expressed in the transfected SW480 cells results in inhibition of the cell growth and proliferation with increased cell apoptosis and cell cycle arrest in G0/1 phase.</p>

A randomized phase II trial of docetaxel and doxorubicin in treatment for patients with non-small-cell lung cancer who have failed previous platinum-based chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to evaluate the efficacy, toxicity and safety of doxorubicin combined with domestically produced docetaxel versus with taxotere, and to investigate whether these two regimens result in similar outcomes in the treatment for non-small-cell lung cancer (NSCLC) patients who failed previous platinum-based chemotherapy.</p><p><b>METHODS</b>Eighty-eight NSCLC patients were enrolled into this clinical phase II trial. The patients randomly received either domestic docetaxel (study arm) or taxotere (control arm) at a dose of 70 mg/m2 on D2, while doxorubicin at a dose of 40 mg/m2 on D1 was administered in both groups. It was repeated every 3 weeks, totally for three cycles. No granulocyte colony-stimulating factor was used to prevent granulocytopenia. The response rate and toxicity were evaluated using World Health Organization toxicity scale and Karnofsky performance status scale.</p><p><b>RESULTS</b>Of the 88 patients, 81 were evaluable in terms of efficacy. There was no complete responder in this series. The response rate (RR) was 17.1% in the study arm versus 7.5% in the control arm, and the clinical benefit rate (CBR) was 80.5% in the study group versus 72.5% in the control group. The most frequent grade 3 or 4 toxicities were neutropenia, leucopenia and gastrointestinal symptoms. Other toxicities such as alopecia and vomiting were mild and generally well tolerated. No fluid retention was noticed.</p><p><b>CONCLUSION</b>The administration of doxorubicin 40 mg/m2 on D1 combined with domestic docetaxel 70 mg/m2 on D2 is proved to be as effective and tolerable as with taxotere. The domestic drug docetaxel may be considered as an alternative for patients with non-small-cell lung cancer who failed previous platinum-based chemotherapy.</p>

Effect of extract of Ginkgo biloba on doxorubicin-associated cardiotoxicity in patients with breast cancer / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of extract of Ginkgo biloba (Egb761) on doxorubicin-associated cardiotoxicity in patients with breast cancer (BC).</p><p><b>METHODS</b>Sixty BC patients in stage IV were randomly assigned to two groups, the control group was treated with chemotherapy, using 4 cycles of PA protocol alone and the treated group with the same chemotherapy and Egb761. Changes in electrocardiogram (ECG), myocardial enzyme spectrum (MES) and ultrasono-cardiogram (USCG) before and after treatment were observed.</p><p><b>RESULTS</b>After treatment, the incidence of abnormal ECG was lower in the treated group than in the control group (6.7% vs 30.0%); significant differences were found between the two groups in the parameters of MES (P< 0.05); USCG showed significant difference between the two groups in left ventricular diastolic diameter (LVDd), left ventricular systolic diameter (LVDs), ratio of early and late diastolic transmitral peak flow velocity (E/A) and fractional shortening (FS), while there was no significant difference in ejection fraction (EF).</p><p><b>CONCLUSION</b>Egb761 is an ideal drug for preventing and reducing the acute doxorbincin-induced cardiotoxicity; it could also be helpful for alleviating the chronic cardiotoxicity.</p>

Effect of small interfering RNA-induced LKB1 gene silencing on the biological behavior of lung carcinoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of the small interfering RNA (siRNA)-mediated LKB1 gene silencing on the biological behavior of lung carcinoma cells.</p><p><b>METHODS</b>RNA interference technique was used to silence LKB1 gene in lung carcinoma cells, and the expression of LKB1 protein were subsequently detected by Western blotting. The cell proliferation was then assessed by observing the growth curve and clone formation of the cells, and cell cycle and apoptosis were assayed by flow cytometry.</p><p><b>RESULTS</b>LKB1 siRNA resulted in remarkable suppression of LKB1 expression in the lung carcinoma cells. LKB1 gene silencing resulted in accelerated cell proliferation, but cell apoptosis underwent no significant changes.</p><p><b>CONCLUSION</b>Down-regulation of LKB1 gene expression can stimulate malignant biological behavior of lung carcinoma cells.</p>

Phase II multicenter clinical trial of nedaplatin in the treatment of malignant tumors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate and compare the efficacy and safety of Nedaplatin (NDP)-based regimen and cisplatin (DDP)-based regimen for head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), esophageal cancer and ovary epithelial cell carcinoma.</p><p><b>METHODS</b>Single agent group: NDP was administered at a dose of 100 mg/m(2) on D1, every 3 weeks for at least 2 cycles. Combination chemotherapy group: combined with 5-Fu, NVB, VDS + 5-Fu, PTX or CTX respectively, NDP 80 mg/m(2) on D1 or DDP 30 mg/m(2) on D1-3, every 3 weeks for at least 2 cycles was given.</p><p><b>RESULTS</b>Of 237 patients in this trial, 37 were treated by single Nedaplatin, 139 by NDP-based regimen, 61 by DDP-based regimen in the control group. The response rate of single Nedaplatin chemotherapy for advanced NSCLC was 10.5% (2/19), for ovary carcinoma (1/3) and HNSCC (1/1). For NSCLC and ovary carcinoma patients who had failed in the previous DDP-based chemotherapy, the response rates by single NDP chemotherapy were still 9.1% and 33.3%. The response rate of NDP-based combination regimen for NSCLC, ovary carcinoma, HNSCC and esophageal cancer was 33.9% (21/62), 44.8% (13/29), 20.0% (3/15) and 18.2% (4/22), respectively, which was not statistically different from the rate of controlled group treated by DDP-based regimen. For chemonaive NSCLC, the effect of NDP-based combination regimen (35.7%) was significantly superior to the effect of DDP-based regimen (17.1%) (P = 0.045). The most common adverse events of nedaplatin were myelosuppression (leukopenia, thrombocytopenia, anemia), nausea and vomiting. The myelosuppression and renal toxicity of NDP-based regimen were similar to that of DDP-based regimen, but vomiting was milder than that of DDP-based regimen (54% vs. 75.4%), and grade I/II liver toxicity was more common in the NDP-based regimen than in DDP-based regimen (10.8% vs. 0).</p><p><b>CONCLUSION</b>Nedaplatin is effective in the treatment for HNSCC, NSCLC and ovary carcinoma. Compared with the control group treated by DDP-based regimen, nedaplatin-based combination chemotherapy has similar effect on HNSCC, NSCLC, ovary carcinoma and esophageal cancer. Gastrointestinal reaction of nedaplatin is milder than that of cisplatin but the liver function during chemotherapy must be monitored closely.</p>

Phase I/II clinical trial of weekly administration of docetaxel plus cisplatin for advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this phase I/II study is to investigate the safety/toxicity profile of weekly administration of docetaxel in combination with cisplatin for the chemo-naive patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the efficacy of this regime.</p><p><b>METHODS</b>In phase I trial, 15 patients were included. IV infusion of escalating doses of docetaxel consisting of four levels from 25 to 40 mg/m2 (25, 30, 35, 40 mg/m2) on D1, 8, 15 and cisplatin of 75 mg/m2 on D1 was administered. The regime was repeated every 4 weeks. Blood samples were obtained on D1, 15 in the first cycle to measure the PK. Dose limiting toxicity (DLT) was determined in cycle 1 and defined as any grade 3 non-hematologic toxicity which could not be reverted into grade less than grade 2 within 4 days or any grade 4 hematologic toxicity. Eighty-three patients completed their phase II study with administration of docetaxel at a dose of 35 mg/m2 based on the data of phase I trial.</p><p><b>RESULTS</b>In the phase I trial, grade 3/4 neutropenia was mainly observed in patients who received docetaxel of 40 mg/m2 (level 4) with one patient suffering from an infection signifying dose limiting toxicity (DLT). Non-hematological toxicities including nausea/vomiting, alopecia, fluid retension and asthenia were tolerable. Based on these data, the maximum tolerence dose (MTD) did not reach the level of weekly giving docetaxel at a dose of 40 mg/m2 in combination with cisplatin 75 mg/m2 every 4 weeks. The pharmacokinetic/dynamics results There was no statistically significant difference between clearance value among the 4 dose levels of docetaxel from 25 to 40 mg/m2 when measured by Cmax and AUC. The pharmacokinetics of docetaxel was not influenced by the presence of co-administration of cisplatin when compared D1 with D15 as based on CmaxN, AUCN and CL. In the phase II trial, totally 83 patients received 216 cycles of chemotherapy. One CR (complete response) and 22 PR (partial response) were achieved with an objective response rate of 27.7% in this series and 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3-34 months). Hematologic toxicities were the major side effects, though most were mild; grade III/IV neutropenia developed in 15%. The common non-hematologic toxicities were nausea, vomiting and asthenia.</p><p><b>CONCLUSION</b>Weekly consecutive administration of docetaxel on D1, 8, 15 for 3 weeks plus cisplatin on D1 is tolerable and effective with minimal myelosuppression in chemo-naive patients with advanced NSCLC.</p>

Docetaxel in the treatment of advanced breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy, toxicity and safety of an new domestic docetaxel in the treatment of pretreated advanced breast cancer.</p><p><b>METHODS</b>Fourty-four breast cancer patients who had failed in first-line chemotherapy were included in this trial. They received docetaxel as the second-line chemotherapy. Docetaxel was administered alone at a dose of 70 mg/m2 every 3 weeks. The use of granulocyte colony-stimulating factor to prevent granulocytopenia was not permitted. The response rate and toxicity were evaluated by World Health Organization toxicity scale and performance status by Karnofsky scale.</p><p><b>RESULTS</b>Of the 41 evaluable patients, 4 achieved complete response and 14 partial remission, with a response rate and clinical benefit rate of 43.9% and 85.4%, respectively. Grade 3 or grade 4 neutropenia developed in 42.9%, alopecia in 7.1% and vomiting in 4.8% of these patients. Fluid retention was not observed in this series.</p><p><b>CONCLUSION</b>Three-week administration of docetaxel alone at a dose of 70 mg/m2 is effective and tolerable. It provides an alternative for the pretreated advanced breast cancer patients.</p>