OBJECTIVETo investigate the effect of recombinant adenovirus (phosphatidylinositol-3-kinases(PI3K)(I()-RNAi-AD which blocks the class I( PI3K signaling pathway on gastric carcinoma cells xenografts in nude mice.

METHODSSubcutaneous tumor models of nude mice were established with SGC7901 cells and randomly divided into PI3K(I()-RNAi-AD group, NC-RNAi-GFP-AD group and control group. The tumor size and the inhibitory rate of tumor growth on days 3, 6, and 9 after cell transplantation were measured. The expression of TNF-α, COX2, P53, PCNA, E-cadherin and nm23/DNPK in tumor tissues were detected by immunohistochemistry.

RESULTSTumor growth was significantly inhibited in the PI3K(I()-RNAi-AD group(14.2%, 21.0%, and 28.1%) on days 3, 6, 9 compared with NC-RNAi-GFP-AD group(1.3%, 1.9%, and 2.0%, all P<0.05). The expressions of TNF-α, P53, E-cadherin and nm23/DNPK were up-regulated, and the expressions of COX2 and PCNA were down-regulated in the PI3K(I()-RNAi-AD group by immunohistochemical staining(all P<0.05).

CONCLUSIONSPI3K(I()-RNAi-AD can inhibit the growth of SGC7901 cell transplantation tumor in vivo in nude mice by inhibiting cell growth, reducing the capacity of tumor invasion and inhibiting tumor angiogenesis.

Adenoviridae ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Class I Phosphatidylinositol 3-Kinases ; Heterografts ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Phosphatidylinositol 3-Kinases ; Phosphatidylinositols ; Stomach Neoplasms

OBJECTIVETo investigate the correlation of single nucleotide polymorphisms (SNP) of XRCC1 gene to hereditary susceptibility of colorectal cancer.

METHODSXRCC1 genotypes in 124 colorectal cancer patients and 214 matched healthy people as control were analyzed by SnaP Shot SNP-typing technique. Five different inheritance models including codominant, dominant, recessive, overdominant and log-additive were analyzed using logistic regression model. The haplotype distribution was estimated with phase and its correlation with the risk of colorectal cancer was evaluated.

RESULTSThe frequencies of mutant 25487G-A, 25489C-T and 1799782C-T alleles were 0.20, 0.11, 0.32 respectively in the patients, and 0.23, 0.13, 0.34 in the controls. There was no significant correlation of polymophisms of XRCC1 gene to the risk of colorectal cancer in 5 different inheritance models (P>0.05). GCT, GCC, ACC and GTC were the most common haplotypes and the odds ratios were 1, 1.35, 0.90 and 0.84 respectively. There was no significant difference of distribution between 2 groups in haplotypes.

CONCLUSIONPolymorphisms of XRCC1 gene, including rs25487, rs25489, rs1799782, are not associated with to the risk of colorectal cancer.

Colorectal Neoplasms ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Models, Genetic ; Polymorphism, Single Nucleotide ; X-ray Repair Cross Complementing Protein 1

BACKGROUNDSuperparamagnetic iron oxide (SPIO) particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging (MRI). Micrometer-sized superparamagnetic iron oxide (MPIO) particles and nanometer-sized ultrasmall superparamagnetic iron oxide (USPIO) are two kinds of SPIO widely used for monitoring stem cells migration. Here we compare the efficiency of two kinds of SPIO during the use of stem cells to treat acute myocardial infarction (AMI).

METHODSAn AMI model in swine was created by 60 minutes of balloon occlusion of the left anterior descending coronary artery. Two kinds of SPIO particles were used to track after intracoronary delivered 10(7) magnetically labeled mesenchymal stem cells (MR-MSCs). The distribution and migration of the MR-MSCs were assessed with the use of 3.0T MR scanner and then the results were confirmed by histological examination.

RESULTSMR-MSCs appeared as a local hypointense signal on T₂*-weighted MRI and there was a gradual loss of the signal intensity after intracoronary transplantation. All of the hypointense signals in the USPIO-labeled group were found on T₂*-weighted MRI, contrast to noise ratio (CNR) decreased in the MPIO-labeled group (16.07 ± 5.85 vs. 10.96 ± 1.34) and USPIO-labeled group (11.72 ± 1.27 vs. 10.03 ± 0.96) from 4 to 8 weeks after transplantation. However, the hypointense signals were not detected in MPIO-labeled group in two animals. MRI and the results were verified by histological examination.

CONCLUSIONSWe demonstrated that two kinds of SPIO particles in vitro have similar labeling efficiency and viability. USPIO is more suitable for labeling stem cells when they are transplanted via a coronary route.

Animals ; Cell Survival ; Contrast Media ; Ferric Compounds ; Magnetic Resonance Imaging ; methods ; Male ; Myocardial Infarction ; diagnosis ; pathology ; Stem Cells ; cytology ; Swine

OBJECTIVETo investigate the effect of phosphatidylinositol 3-kinase inhibitor LY294002 combined with NF-κB P65 nuclear translocation inhibitor SN50 on the tumor cell growth and apoptosis using a nude mouse model of gastric cancer.

METHODSHuman gastric cancer cell strain SGC7901 was transplanted subcutaneously to nude mice to establish tumor models. Model mice were randomly divided into the control group, the LY294002 treatment group, the SN50 treatment group, and the LY294002+SN50 treatment group, with 5 in each group. After being treated for 10 days, the inhibition rate of tumor growth was ascertained by measuring the size of tumor. Immunohistochemical method was used to detect the expression levels of Bcl-2, P53 and Bax proteins and transmission electron microscopy to investigate the apoptosis of tumor cells.

RESULTSOn the 10th day after treatment, the inhibition rate of gastric cancer cellular growth in the LY294002+SN50 group was (49.2±2.5)%, which was significantly higher than that in the LY294002 group(29.4±1.5)% and SN50 group (19.7±1.6)%(P<0.05). In comparison with the other two groups, LY294002+SN50 group exhibited more severe apoptosis, with expression of Bcl-2 decreased and that of P53 and Bax increased more significantly(P<0.05).

CONCLUSIONLY294002 combined with SN50 inhibits the growth of SGC7901 transplanted tumor and aggravates the apoptosis of gastric cancer cells in nude mice model.

Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chromones ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Morpholines ; pharmacology ; NF-kappa B ; antagonists & inhibitors ; Peptides ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism ; Xenograft Model Antitumor Assays ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo investigate the effects of damage-regulated autophagy modulator (DRAM) on radiosensitivity and the related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice.

METHODSNude mice were randomly divided into model control group, radiotherapy group, and DRAM treatment group and radiotherapy combined with DRAM treatment group. When volume of transplantation tumor were 1.0 cm(3), radiotherapy, DRAM treatment was given. On days 3, 6 and 9 after treatment, the inhibition rate of tumor growth, pathological changes in tumor specimens, expression levels of P53, proliferating cell nuclear antigen(PCNA), C-myc, Fas-L, as well as apoptosis indexes in tumor samples were observed.

RESULTSInhibition rates of tumor in DRAM combined with radiotherapy were 9.3%, 14.1%, 16.7% on day 3, 6 and 9, respectively, all significantly higher than those in the radiotherapy group(5.0%, 8.8%, 6.5%, P<0.05). The expressions of PCNA and C-myc protein were down-regulated, while the expressions of P53 and Fas-L were upregulated.

CONCLUSIONDamage-regulated autophagy modulator gene may promote cell apoptosis and inhibit cell growth to enhance the radiosensitivity of transplanted gastric tumor in vivo in nude mice.

Animals ; Autophagy ; genetics ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Radiation Tolerance ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; radiotherapy ; Tumor Cells, Cultured

OBJECTIVETo investigate the expression of cyclooxygenase-2(COX-2) and CEA in the tissues adjacent to the tumor within different distances.

METHODSA total of 42 colorectal cancer tissues were collected.The adjacent tissues within 3 cm to the tumor were procured every 1 cm. Normal tissue was also collected. RNA was extracted and the expression of CEA and COX-2 was detected by RT-PCR.

RESULTSThe CEA mRNA levels of the tumor, the tissues of every 1 cm adjacent to the tumor, and the normal tissue were 135.2 ± 23.3, 78.2 ± 17.3, 75.9 ± 16.5, 56.2 ± 10.7, 52.3 ± 12.8, 18.2 ± 7.9, 16.2 ± 6.5, and 16.6 ± 7.0. The levels of COX-2 mRNA in above positions were 134.9 ± 31.1, 79.2 ± 20.2, 77.0 ± 20.5, 62.7 ± 21.9, 58.0 ± 18.1, 21.2 ± 10.3, 18.3 ± 7.6, and 17.1 ± 6.3. These data showed a decreasing trend of CEA and COX-2 as the distance increased from the tumor. The CEA mRNA levels showed positive correlation with the levels of COX-2 mRNA(r=0.725, P<0.01).

CONCLUSIONCEA and COX-2 may be considered to be used as biomarkers for the study of molecular resection margin of colorectal cancer.

Adult ; Aged ; Carcinoembryonic Antigen ; metabolism ; Colorectal Neoplasms ; genetics ; immunology ; pathology ; Cyclooxygenase 2 ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging

Umbilical metastases from intraperitoneal malignancies are universally referred to Sister Mary Joseph's nodule (SMJN). The most frequent primary tumor sites include the stomach and ovaries. SMJN caused by colon cancer is uncommon. Likewise, carcinoma of the right side colon metastasizing to inguinal lymph nodes is considered almost impossible. To the best of our knowledge, there is no report of right side colon cancer synchronously involving both the umbilicus and inguinal lymph nodes in the literature. We present a case of right side colon cancer (RSCC) metastasizing to the umbilicus and inguinal lymph nodes, which was confirmed by routine pathological evaluation and immuohistochemistry.
Adenocarcinoma ; pathology ; secondary ; surgery ; Adult ; Carcinoembryonic Antigen ; blood ; metabolism ; Colectomy ; methods ; Colonic Neoplasms ; pathology ; surgery ; Groin ; Humans ; Keratin-20 ; metabolism ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Sister Mary Joseph's Nodule ; pathology ; secondary ; surgery

Umbilical metastases from intraperitoneal malignancies are universally referred to Sister Mary Joseph's nodule (SMJN).The most frequent primary sites include the stomach and ovaries. SMJN caused by colon cancer is very uncommon. Likewise, carcinoma of the right side colon metastasizing to inguinal lymph nodes is considered almost impossible. To the best of our knowledge, no report of right side colon cancer synchronously involving both the umbilicus and inguinal lymph nodes is available. We present a case of right side colon cancer(RSCC) metastasizing to the umbilicus and inguinal lymph nodes, which was confirmed by pathology and immuohistochemistry.

OBJECTIVETo screen the radiosensitivity-related genes of colorectal cancer cells.

METHODSGene expression profiles of two different radiosensitivity cells(colorectal cancer cell line Lovo and SW480) were obtained by cDNA array and the differences of gene expression profiles between the two cells were analyzed.

RESULTSGenes of more than 2-fold expressive differentiation were screened. In Lovo cells, 908 up-regulated genes were found, including higher expression genes CEACAM5, THBS1, SERPINE2, ARL7, HPGD, while 1312 genes were down-regulated. In SW480 cells, higher expression genes were SCD, NQ01, LYZ, KRT20 and ATP1B1.

CONCLUSIONGene profiles can reflect the radiosensitivity of colorectal cancer cells, which will provide the choice for the further study of radiosensitivity in colorectal cancer.

Cell Line, Tumor ; Colorectal Neoplasms ; genetics ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genome, Human ; Humans ; Oligonucleotide Array Sequence Analysis ; Radiation Tolerance ; genetics

Objective To observe the effect of intracoronary transfer of autologous HO-1 overexpressed MSCs in porcine model of myocardial ischemia ( 1 h)/reperfusion. Methods Apoptosis was assayed and cytokine concentrations in supernatant were measured in cells exposed to hypoxia-reoxygen in vitro. In vivo, Chinese male mini-pigs were allocated to the following treatment groups; control group (saline), MSCs group (MSCs), MSCs transfected with pcDNA3. 1-nHO-l (HO-1-MSCs). 1 x 107 of autologous stem cells or identical volume of saline was injected intracoronary into porcine hearts 1 h after ischemia. MRI assay and postmortem analysis were assessed 3 months after stem cell transplantation. Results In vitro, cell apoptosis rate post hypoxia-reoxygen was significantly reduced in HO-1- MSCs group ( 30. 30% ±7. 64% ) compared with that in MSCs group (56. 93% ±4. 68% , P <0. 001) and LacZ- MSCs group (55. 88% ± 4. 38% , P < 0. 001) , VEGF was also significantly upregulated in HO-1-MSCs group [(768.44±78.38)pg/ml] compared with that in MSCs group[ (555. 27 ±67. 67)pg/ml, P<0.001] and LacZ-MSCs group [ (522. 97 ± 71. 45 ) pg/ml, P < 0. 001 ] . In vivo, cardiac function was significantly improved in both MSCs transplantation groups compared to saline group (all P<0. 05 vs. saline) and the left ventricular ejection fraction was significantly higher in HO-1-MSCs group compared with that in MSCs group at 3 months after transplantation ( 53. 50% ± 2. 09% vs. 49. 54% ± 2. 74% , P = 0. 017 ), capillary density in the peri-infarct area was also significantly higher in HO-1-MSC group than that in MSCs group [ (14.59 ± 2. 39 )/HPF vs. (11.78 ± 2.48 )/HPF, P = 0.033 ] . Conclusions Efficacy of HO-1 overexpressed MSCs on improving cardiac function and promoting angiogenesis was greater than those by MSCs in this porcine ischemia/reperfusion model.