Establishment of BGC-823/pBaBb-puro-MACC1 gastric cancer cell line stably expressing MACC1 and its tumor-related gene expression profiles / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a gastric cancer cell line with stable expression of metastasis-associated in colon cancer 1 (MACC1) and detect the changes in tumor-related gene expression profiles for investigating the possible regulation mechanisms between MACC1 and the differentially expressed genes.</p><p><b>METHODS</b>The full-length MACC1 cDNA was amplified from human embryonic kidney 293FT cells and cloned into the pBaBb-puro vector. The recombinant pBaBb-puro-MACC1 expression vector, after identification with restriction enzyme digestion, was transfected into 293FT cells, and the expression of fluorescent reporter gene was observed. pBaBb-puro-MACC1 vector was transfected into human gastric cancer BGC-823 cell line to establish BGC-823/pBaBb-puro-MACC1 cell line stably expressing MACC1. Quantitative RT-PCR and Western blotting were used to detect MACC1 expression in both BGC-823/pBaBb-puro-MACC1 and control BGC-823 cells. High-throughout cDNA microarray was used to screen the effects of MACC1 on the gene expression profiles of gastric cancer cells.</p><p><b>RESULTS</b>The recombinant pBaBb-puro-MACC1 plasmid was successfully constructed and verified by PCR and sequencing. BGC-823/pBaBb-puro-MACC1 cells showed significantly increased MACC1 mRNA expression as compared with the control cells. The results of cDNA microarray identified 33 up-regulated and 24 down-regulated genes in the cells after MACC1 transfection involved were in various cellular functions.</p><p><b>CONCLUSION</b>The established BGC-823/pBaBb-puro-MACC1 gastric cancer cell line show some important molecular changes caused by MACC1.</p>

Ultrasound-mediated microbubble destruction enhances LMP-1 gene transfection into dendritic cells in vivo / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the transfection efficiency and the optimal conditions of delivering latent membrane protein-1 (LMP-1) gene to dendritic cells (DCs) by ultrasound exposure combined with contrast agent.</p><p><b>METHODS</b>Human DCs were cultured in vivo and transfected with the recombinant plasmid pEGFP-C3-LMP1 under varying conditions including ultrasound intensities, exposure time and microbubble contrast agent concentration. The transfection efficiency was assessed by fluorescent microscopy and flow cytometry, and the cell viability by trypan blue exclusion test.</p><p><b>RESULTS</b>An exposure time of 60 s at MI 1.0 with a microbubble contrast agent concentration of 20% resulted in the optimal effect of delivering the recombinant plasmid pEGFP-C3-LMP1 into the DCs, with a transfection efficiency of (14.37∓2.12)%. Over 90% of the transfected cells were viable after the transfection.</p><p><b>CONCLUSION</b>Microbubble contrast agent combined with ultrasound exposure can enhance the delivery of recombinant plasmid pEGFP-C3-LMP1 into the DCs.</p>

Short-term therapeutic effect and safety of endostar combined with XELIRI regimen in the treatment of advanced colorectal cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the short-term efficacy and toxicity of endostar in combination with XELIRI as the second-line treatment for advanced colorectal cancer.</p><p><b>METHODS</b>Twenty-one patients with advanced colorectal cancer were treated with intravenous infusion of endostar (15 mg/day for 14 consecutive days) and irinotecan (250 mg/m(2), single dose on the first day), and oral administration of capecitabine (1.0 mg/m(2), twice daily for 14 days), and the treatment cycle was repeated every 21 days. The efficacy and toxicity of the treatments were evaluated according to RECIST and NCI-CTCAE3.0 standard, respectively.</p><p><b>RESULTS</b>The overall response rate was 9.5% in these patients, with a median time to progression (mTTP) of 3.9 months. The main adverse effects associated with the treatment included leucopenia, nausea/vomiting and peripheral neuritis.</p><p><b>CONCLUSION</b>Endostar combined with XELIRI is effective and safe as the second-line treatment for advanced colorectal cancer, and further clinical investigation is warranted.</p>

Evaluation of tumor angiogenesis using microbubbles conjugated with RGD peptides and contrast enhanced ultrasound / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the feasibility of usage of microbubbles conjugated with RGD peptides and contrast enhanced ultrasound (CEU) in detection of tumor angiogenesis.</p><p><b>METHODS</b>Lipid microbubbles (MB) were prepared, and the RGD peptides were covalently conjugated to the lipid shell of MB (MB(RGD)). Six nude mice with tumor created by dorsal inoculation of HepG2 tumor cells were used as the test group. Six nude mice without tumor were served as the control group. 10 minutes after bolus injection of MB and MB(RGD) randomly (30 min interval) via a tail vein catheter, CEU was performed on the tumors of the test group and the thigh skeletal muscles of control group. The video intensity (VI) of tumors and the skeletal muscles were measured. The tumors and the skeletal muscles were harvested for immunohistochemical examination.</p><p><b>RESULTS</b>Only a slight contrast enhancement of the tumor was seen with MB, and the VI was 5.33 ± 1.71. While a remarkable enhancement of the tumor was observed after injection of MB(RGD). The VI was up to 17.03 ± 3.58, 3.18 folds higher as compared with that obtained by injection of MB (P < 0.05). As expected, there were no obvious contrast enhancement of the skeletal muscles with both MB(RGD) and MB. There was a high expression of αvβ3-integrin in tumor neovascular endothelium, however, no apparent expression of αvβ3-integrin was observed in the skeletal muscle vascular endothelium.</p><p><b>CONCLUSION</b>CEU with MB(RGD) can be used to effectively evaluate the angiogenesis of tumors, and it may greatly contribute to the early judgement of the nature of tumor.</p>

Clinical value of (18)F-FDG positron emission tomography-computed tomography in local liver neoplasm ablation / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in ultrasound-guided local ablation of malignant liver tumors.</p><p><b>METHODS</b>Thirteen patients with 35 local residual tumor foci following previous tumor ablation underwent (18)F-FDG PET-CT and ultrasound-guided local ablation with intratumoral alcohol injection.</p><p><b>RESULTS</b>After the second local ablation guided by (18)F-FDG PET-CT and ultrasound, radioactive defects were detected in the corresponding location in 31 of the 35 residual foci, and after the third local ablation, the other 4 foci also showed radioactive defects.</p><p><b>CONCLUSION</b>(18)F-FDG PET-CT can sensitively and accurately identify tissue necrosis and residual tumors, and serves as an excellent approach for ultrasound-guided local ablation of local residual tumors.</p>

Clinical significance of VEGF levels in serums of colorectal cancer patients at stage IV / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the clinical significance of vascular endothelial growth factor (VEGF) levels in serums of colorectal cancer patients at stage IV.</p><p><b>METHODS</b>Using enzyme linked immunosorbent assay (ELISA) to detect the VEGF levels in serums of 45 colorectal cancer patients at stage IV, and 20 healthy served as normal control.</p><p><b>RESULTS</b>The mean concentration of VEGF in 45 colorectal cancer patients at the 7 day after operation were significantly lower than that before operation (P<0.01). The mean concentration of VEGF in the patients who benefit from bevacizumab showed no statistical difference from the levels of who did not benefit (P=0.554).</p><p><b>CONCLUSION</b>The VEGF levels in colorectal patients at stage IV are lowed as the load of tumor decrease. The circulating levels of VEGF seem not predict the response to bevacizumab in colorectal cancer patients at stage IV.</p>

rAAV/BA46-transfected dendritic cells can induce specific cellular immunity / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the feasibility of transfecting breast cancer BA46 gene into dendritic cells (DCs) using adeno-associated virus (AAV) to induce specific cellular immunity.</p><p><b>METHODS</b>Mononuclear cells (DC precursor) were isolated from the peripheral blood of healthy donors by density gradient centrifugation and infected with rAAV/BA46/Neo virus stock (transfection group) or pulsed with 293 cell lysate (control group). In both groups, maturation of the DC precursor was induced by granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor-alpha(TNF-alpha). On day 7, the DCs were collected and mixed with T cells at the ratio of 1 to 20 to induce cytotoxic T lymphocytes (CTL). The capacity of the DCs in stimulating T lymphocyte proliferation was assessed using (3)H-thymidine incorporation assay. The expressions of interferon-gamma (IFN-gamma), IL-4, CD4, CD8, CD25 and CD69 in the CTLs were analyzed with cytometry, and the cytotoxicity of the CTLs was evaluated with (51)Cr-release assay using BA46-positive breast cancer cell line Hs578T as the target.</p><p><b>RESULTS</b>The DCs transfected with BA46 gene exhibited potent capacity to stimulate T lymphocyte proliferation. The CTL population induced by the transfected DCs expressed high levels of CD8, CD69 and IFN-gamma, and showed strong cytotoxicity against BA46-positive breast cancer cell line Hs578T, which was BA46 antigen-specific and MHC-limited.</p><p><b>CONCLUSION</b>The success in BA46 gene transfer in the DCs that induce specific cellular immunity provides the experimental basis for breast cancer immunotherapy using genetically modified cells.</p>

Effect of percutaneous chemotherapy pump placement for portal vein chemotherapy on hepatic metastasis of colorectal cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate safety and effect of percutaneous chemotherapy pump placement for portal vein chemotherapy in management of colorectal cancer with hepatic metastasis.</p><p><b>METHODS</b>Twenty-three cases of colorectal cancer with liver metastasis were treated with percutaneous chemotherapy pump placement for portal vein chemotherapy, and the therapeutic effect of this treatment was observed.</p><p><b>RESULTS</b>Partial remission of the hepatic lesions was achieved in 13 (56.5%) of the patients following the treatment, and the condition was stabilized in 5 patients (21.7%). No severe complications were observed in these patients.</p><p><b>CONCLUSION</b>Percutaneous chemotherapy pump placement for portal vein chemotherapy can be safe and effective for management of hepatic metastasis of colorectal cancer.</p>

Matrine-induced apoptosis in human colon adenocarcinoma SW620 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of matrine on the cell cycle and apoptosis in human colon adenocarcinoma SW620 cells and explore the possible mechanisms.</p><p><b>METHODS</b>The effect of matrine on cell proliferation was assessed using MTT assay, and the cell cycle arrest induced by matrine was determined by flow cytometry. The changes of cell morphology were observed through optical microscope, fluorescence microscope and electron microscope, and the cell apoptosis was detected using Annexin V-FITC apoptosis assay.</p><p><b>RESULTS</b>Matrine inhibited the proliferation of SW620 cells in a dose- and time-dependent manner. Compared with the control group, the matrine-treated cells showed increased cell percentage arrested in G 0/G1 phase with decreased S-phase cells. Morphologically, the SW620 cells treated with matrine exhibited cell shrinkage, cell size reduction, plasma condensation, cytoplasmic vacuolar changes, and formation of apoptotic body with also the presence of the signet-ring cells, all typical of apoptotic cells.</p><p><b>CONCLUSION</b>Matrine exposure of SW620 cells inhibits the cell proliferation, causes cell cycle arrest at G 0/G1 phase, and induces apoptosis in a dose- and time- dependent manner.</p>

Efficacy of Avastin in combination with irinotecan for metastatic colorectal cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy of Avastin in combination with irinotecan for metastatic colorectal cancer.</p><p><b>METHODS</b>Ninety patients were randomly divided into 3 equal groups to receive Avastin plus irinotecan (group A), FOLFIRI (group B) and FOLFOX7 (group C) for two cycles, respectively. The response rate and changes in tumor maker levels were observed.</p><p><b>RESULTS</b>The tumor response rate was 43.3% in group A, 27.7% in group B and 30.0% in group C. The disease control rate (complete response+partial response+stable disease) was 80% in group A, 53.3% in group B and 50.0% in group C. Obvious changes in tumor marker levels were observed in the 3 groups after treatment, which were most conspicuous in group A (P<0.05).</p><p><b>CONCLUSION</b>The addition of Avastin to irinotecan chemotherapy results in significant improvement of clinical efficacy in patients with metastatic colorectal cancer.</p>

Effect of Herceptin combined with Taxol on patients with Her-2/neu overexpressing metastatic breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and toxicity of recombinant humanized anti-Her-2/neu antibody (Herceptin) and Taxol for patients with Her-2/neu overexpressing metastatic breast cancer.</p><p><b>METHODS</b>Sixty patients with Her-2/neu overexpressing metastatic breast cancer were investigated. Of the 60 cases, 22 were treated with Herceptin and Taxol and 38 with Taxol and doxorubicin.</p><p><b>RESULTS</b>The total response rate (RR) of Herceptin and Taxol was 68.2%, and that of Taxol and doxorubicin was 44.7%. The RR of patients with Her-2/neu(+++) was 75%, while that of patients with Her-2/neu(++) was 50%. The major adverse effects were gastro-intestinal tract reactions, myopathy, bone marrow suppression and alopecia.</p><p><b>CONCLUSION</b>The treatment with Herceptin and Taxol is effective and safe for patients with Her-2/neu overexpressing metastatic breast cancer. The therapeutic effect is related to the degree of Her-2/neu overexpression.</p>