No abstract available.
Aged, 80 and over ; Biopsy ; Carcinoma, Papillary/chemistry/*secondary ; Female ; Humans ; Immunohistochemistry ; Liver Neoplasms/chemistry/*secondary ; Pancreatic Neoplasms/chemistry/*pathology ; Tumor Markers, Biological/analysis

The proliferation potentials and the level of apoptosis were compared in paired primary colorectal adenocarcinomas and their liver metastases within each individual. From a total of 22 patients 44 specimens of paired primary and metastatic tumors were obtained for analysis. The levels of spontaneous apoptosis (a spontaneous apoptosis index, SAI: % apoptotic nuclei among a total of 1000 nuclei) and of proliferation (KI-67 index: % positively stained cells for KI-67 among a total of 1000 cells) were analyzed between primary and metastatic tumors. Survival rates and its relationship with the clinical parameters were also analyzed. The overall survival rate at 5 years was 16.9% with the median survival time of 45 months. T-stage (p=0.005) and time to liver metastasis (synchronous versus metachronous, p=0.03) showed statistical significance in relation to survival. The mean SAI of primary tumors was 1.35 +/- 0.25, which was not statistically different from the 1.58 +/- 0.18 of metastatic tumors (p=0.33). The mean KI-67 indices in primary and metastatic tumors were 23.9 +/- 3.4 and 16.4 +/- 2.5, respectively, and this difference was statistically significant (p=0.016). Subset analysis showed significant difference in the KI-67 index in the synchronous group but not in the metachronous group. No significant difference was shown in the relative ratios of apoptosis to proliferation between the primary tumor and the metastasis within each individual. The results in this study may partly explain the indolent behavior of liver metastasis from colorectal cancer and provides a rationale for the active treatment of metastatic tumors as well as of primary disease.
Adenocarcinoma/chemistry/*secondary ; Adult ; Aged ; *Apoptosis ; Cell Division ; Colorectal Neoplasms/chemistry/*pathology ; Female ; Human ; Liver Neoplasms/chemistry/*secondary ; Male ; Middle Aged ; Support, Non-U.S. Gov't

OBJECTIVETo detect serum HER-2 oncoprotein levels in patients with operable and metastatic breast cancers, and to study the correlations between serum HER-2 level and lymph node status as well as other clinical parameters.

METHODSA total of 120 women were studied consisting of 10 healthy volunteers, 31 benign breast disease, 53 operable breast cancer, and 26 metastatic breast cancer patients. The levels of serum HER-2 were measured using an enzyme-liked immunosorbent assay (ELISA).

RESULTSThe mean serum HER-2 levels were 9.6 +/- 1.5 ng/mL in healthy volunteers, 11.9 +/- 1.6 ng/mL in benign breast disease, 13.2 +/- 4.2 ng/mL in operable breast cancer, and 30.5 +/- 30.8 ng/mL in metastatic breast cancer patients. The former is much lower than the latter three (P = 0.02, 0.001, 0.03, respectively). If using 15 ng/mL as a normal baseline, elevated serum HER-2 levels were observed in none of the healthy volunteers as well as patients with benign disease, but in 18.9% (10/53) operable breast cancer patients and 61.5% (16/26) metastatic patients. In patients with operable breast cancer, there was a positive correlation between serum concentrations of HER-2 and the size of primary tumor (P < 0.05), whereas there was no correlation between serum concentration and axillary lymph node or estrogen receptor status. In patients with metastatic disease, there was no correlation with site of metastases (P > 0.05).

CONCLUSIONSerum HER-2 level was strongly correlated with tumor loads and clinical stages, thus acting as a promising predictor of cancer recurrence in breast cancer patients.

Biomarkers, Tumor ; blood ; Breast Neoplasms ; blood ; pathology ; Female ; Humans ; Liver Neoplasms ; chemistry ; secondary ; Lung Neoplasms ; chemistry ; secondary ; Lymph Nodes ; pathology ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Receptor, ErbB-2 ; blood ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo observe the effect of Tiam-l gene silencing on the metastasis of human colorectal carcinoma cell line SW480 in nude mice by real-time whole-body fluorescence imaging.

METHODSEnhanced green fluorescence protein (EGFP)-labeled human colorectal carcinoma cells, SW480/EGFP(+)/Tiam-1(-) and SW480/EGFP(+), were implanted into nude mice via tail vein injection or orthotopic colonal inoculation, and real-time whole-body fluorescence imaging was performed to compare the difference in tumor progression and metastasis between the two cells.

RESULTSBoth SW480/EGFP(+) and SW480/ EGFP(+)/Tiam-1(-) cells stably expressed EGFP, and Tiam1 gene expression was reduced in SW480/EGFP(+)Tiam-1(-) to 30% of the expression level in SW480/EGFP(+) cells. The growth rate of the two cell lines had no significant difference in vitro (P>0.05), but SW480/EGFP(+)/Tiam1(-) cell proliferation and metastasis were depressed obviously in comparison with SW480/EGFP(+) in vivo (P<0.05).

CONCLUSIONTiam-1 gene may play an important role in invasion and metastasis of human colorectal cancer.

Animals ; Blotting, Western ; Bone Neoplasms ; genetics ; metabolism ; secondary ; Cell Line, Tumor ; Cell Survival ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Diagnostic Imaging ; methods ; Female ; Fluorescence ; Gene Silencing ; Green Fluorescent Proteins ; chemistry ; genetics ; metabolism ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; Immunohistochemistry ; Liver Neoplasms ; genetics ; metabolism ; secondary ; Lung Neoplasms ; genetics ; metabolism ; secondary ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Neoplasm Transplantation ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; Transplantation, Heterologous

OBJECTIVETo construct the yeast two-hybrid system, and screen the proteins which interact with FasL, and investigate the relationship of FasL and hepatic metastasis of colorectal carcinoma.

METHODSWe have cloned the FasL gene into the pGBKT7 vector as the bait, then screened the fetal liver cDNA library, and have got a series of specific proteins that interact with FasL protein. Using the bioinformatics, we analyzed the interacting proteins in the mechanism of hepatic metastasis of colorectal carcinoma.

RESULTSWe have screened several proteins that interaction with FasL protein, including metallothionein 1K, 1G, 2A, cathepsin B, fatty acid synthase, interferon alpha-inducible protein 27, phospholipid scramblase, Ser/Thr-like kinase, anchor attachment protein, fibulin-5.

CONCLUSIONSWe have successfully constructed the yeast two-hybrid system, and preliminary identified that the interaction between FasL, metallothionein, cathepsin and anchor attachment protein is radically related to the hepatic metastasis of colorectal carcinoma.

Cathepsin B ; metabolism ; Cloning, Molecular ; Colorectal Neoplasms ; chemistry ; pathology ; Fas Ligand Protein ; Gene Library ; Humans ; In Vitro Techniques ; Liver Neoplasms ; chemistry ; secondary ; Membrane Glycoproteins ; genetics ; metabolism ; Metallothionein ; metabolism ; Protein Binding ; Tumor Necrosis Factors ; genetics ; metabolism ; Two-Hybrid System Techniques ; Yeasts ; genetics

OBJECTIVETo observe the expression of galectin-3 in the liver metastasis of colon cancer in mice and the inhibitory effect of modified citrus pectin (MCP) on galectin-3 expression.

METHODSSeventy-five Balb/c mice were randomized into 5 groups, namely the negative control, positive control, low-concentration MCP, moderate-concentration MCP and high-concentration MCP groups. CT26 colon cancer cells were injected into the subcapsule of the mouse spleen to establish liver metastasis models of colon cancer, but the mice in the negative control group received no tumor cell injection. MCP was added into the drinking water of the mice at the concentrations of 0, 1.0%, 2.5% and 5.0% (m/V). The liver metastasis was observed 3 weeks after tumor cell inoculation. Enzyme-linked immunosorbent assay was performed to determine the serum galectin-3 level. A tissue microarray of the liver metastasis was prepared for immunohistochemical detection of galectin-3 expression in the liver metastasis.

RESULTSIn the positive control, low-, moderate- and high-concentration MCP groups, the rates of liver metastasis were 100%, 80%, 73.3% and 60%, respectively. The number of liver metastases in high-concentration MCP group was significantly smaller than that in the positive control group (P<0.05). In the 4 groups with tumor cell inoculation, the median volume of the primary lesions in the spleen was 1.51, 0.93, 0.77 and 0.70 cm(3), respectively, which were significantly smaller in the moderate- and high-concentration MCP groups than in the positive control group (P<0.05). The serum galectin-3 level in the positive control group and MCP-treated groups were significantly higher than that in the negative control group (P<0.01), but similar between the positive control group and the MCP-treated groups (P>0.05). In the positive control and the MCP-treated groups, the expression of galectin-3 in the liver metastases showed no significant differences (P>0.05).

CONCLUSIONThe expression of galetin-3 is significantly increased in the liver metastasis of colon cancer, and MCP can effectively inhibit the liver metastasis.

Animals ; Cell Line, Tumor ; Citrus ; chemistry ; Colonic Neoplasms ; drug therapy ; metabolism ; pathology ; Female ; Galectin 3 ; biosynthesis ; Immunohistochemistry ; Liver Neoplasms ; drug therapy ; metabolism ; secondary ; Mice ; Mice, Inbred BALB C ; Pectins ; therapeutic use ; Phytotherapy ; Random Allocation

OBJECTIVETo separate and detect membrane phospholipids and study the relationship of metabolism and signal transduction pathways of membrane phospholipids with genesis and hepatic metastasis of large intestinal carcinoma.

METHODSForty-eight cases of colorectal cancer were detected with high performance liquid chromatography. Membrane phospholipids of phosphatidylinosital (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in primary foci, paratumor intestinal mucosa and hepatic metastasis of large intestine cancer were separated and analyzed.

RESULTSIn primary foci, paratumor intestinal mucosa, and hepatic metastasis of the 48 cases, the contents (mg/g) of PI were: 0.92 +/- 0.12, 1.57 +/- 0.14, 1.54 +/- 0.15 respectively, and PC 56.47 +/- 5.33, 108.57 +/- 6.37, 116.35 +/- 6.85. The contents of PI and PC were higher in primary foci and hepatic metastasis than in paratumor mucosa (F = 363.10, 870.10, P < 0.01). The contents of PE in the three tissues were 18.23 +/- 3.56, 42.02 +/- 4.33, 79.51 +/- 5.52, and in hepatic metastasis was the highest (F = 1 149.63, P < 0.01). PI and PC in primary foci of hepatic metastatic group and nonmetastasis group were not significantly different (t = 3.55, P > 0.05). But the PE content was higher in hepatic metastasis than in primary foci (t = 115.87, P < 0.01).

CONCLUSIONSMembrane phospholipids have obvious variations in genesis and hepatic metastasis of large intestine cancer. Rises of PI and PC were associated with genesis of large intestine carcinoma. The increase of PE content is closely related to invasion and hepatic metastasis of large intestine cancer.

Adult ; Aged ; Aged, 80 and over ; Chromatography, High Pressure Liquid ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Intestinal Mucosa ; chemistry ; Liver Neoplasms ; secondary ; Male ; Membrane Lipids ; analysis ; Middle Aged ; Phospholipids ; analysis

OBJECTIVETo explore the inhibitory effect of combined administration of bear bile powder (BBP) and cyclophosphamide (Cytoxan, CTX) on colorectal cancer liver metastasis by regulating tumor promotion inflammation microenvironment.

METHODThe CRC liver metastasis mode in mice was established through in situ spleenic injection of SL4 tumor cells into spleens. The mice were randomly divided into 5 groups: the model group, the CTX (80 mg x kg(-1)) treatment group, the CTX + BBP high dose (300 mg x kg(-1)) group, the CTX + BBP middle dose (150 mg x kg(-1)) group and the CTX + BBP low dose (75 mg x kg(-1)) group. Mice were orally administered with drugs for 12 days, and sacrificed on the 13'h day for weighing their spleens and lives, HE staining, and immunofluorescence analysis. Their peripheral blood, and metastatic tumor in spleens and lives were analyzed with flow cytometry.

RESULTSpleen and liver weights of the: CTX treatment group and other doses groups were significantly lower than that of the model group. HE staining and immunofluorescence analysis showed that lymphocyte infiltration was detected in normal tissues, and macrophages infiltration was observed around the tumor tissues. Flow cytometry analysis showed that the number of T-lymphocytes in peripheral blood of different doses groups were much higher than that of the CTX treatment group (P < 0.05), with the rise in the ratio of CD4/CD8; the total number of lymphocytes in spleen cell suspension increased in different doses groups, compared to the CTX treatment group, with notable increase in B cells (P < 0.05) and significant decrease in CD11b, F4/80 cells (P < 0.05). The combined treatment showed less monocyte macrophages in liver metastasis than that of the CTX treatment group.

CONCLUSIONThe combined treatment of bear bile powder and cyclophosphamide has the effect in not only protecting liver and increase immunity, but also in anti-inflammation and antitumor by regulating tumor microenvironment and reducing the collection of mononuclear macrophages. Particularly, the combined administration of low dose of bear bile powder and CTX shows the most significant effect in reducing inflammatory cell infiltration.

Animals ; Bile ; chemistry ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Combined Modality Therapy ; Cyclophosphamide ; administration & dosage ; Humans ; Liver Neoplasms ; drug therapy ; mortality ; physiopathology ; secondary ; Male ; Mice ; Mice, Inbred C57BL ; Tumor Microenvironment ; drug effects ; Ursidae

OBJECTIVETo clone a novel liver cancer associated gene, and to explore the molecular basis of liver cancer genesis.

METHODSUsing mRNA differential display polymerase chain reaction (DDPCR) and screening the human placenta cDNA library, we got a full-length cDNA of the gene. We prepared and purified the GST fusion protein and the special polyclonal antibody, engaged in the Western blot and immunohistochemical staining analysis, and analyzed the second structures and predicted the function of the protein by the computer soft.

RESULTSWe have got a full-length cDNA of the liver cancer associated gene and identified that the full-length cDNA of the gene could be expressed in 293 eukaryocytes by Western blot assay. We localized the target protein in cytoplasm using the immunohistochemical staining methods, and found two SH3 binding domains and several protein kinase phosphorylation sites by analyzing the second structures.

CONCLUSIONSWe have got a novel full-length cDNA of human liver cancer associated gene.

Amino Acid Sequence ; Cell Line ; Cloning, Molecular ; Cytoplasm ; chemistry ; DNA, Neoplasm ; Gene Expression Profiling ; methods ; Gene Expression Regulation, Neoplastic ; Gene Library ; Humans ; Liver Neoplasms ; genetics ; Molecular Sequence Data ; Neoplasm Proteins ; biosynthesis ; chemistry ; genetics ; Nuclear Proteins ; Phosphorylation ; Polymerase Chain Reaction ; methods ; Protein Structure, Secondary ; Proteins ; chemistry ; genetics ; Recombinant Proteins ; biosynthesis ; chemistry ; genetics ; Trans-Activators ; Transcription Factors

OBJECTIVETo detect the biological factor association with metastasis and recurrence of hepato cellular carcinoma (HCC).

METHODSLabeled streptavidin biotin method was performed to study VEGF, uPA and ICAM-1 protein, and antigen of PCNA expression in 123 patients with HCC. Venous invasion was observed under microscope at the same time.

RESULTSThe expression rate of VEGF was higher in HCC with intra-hepatic metastasis in group B than in HCC without PVTT/metastasis in group A (P < 0.01) and higher in HCC with PVTT in group C and PVTT in group D higher than in group B (P < 0.05). The expression rate of uPA protein was higher in group B than in group A (P < 0.01), but no significant difference in groups B and C. The expression rate of ICAM-1 showed no significant difference in the four groups. MVD and PCNA-LI increased gradually from group A to D. The rate of microscopic venous invasion in group B was higher than in group A (P < 0.05), in group D higher than in group B (P < 0.05), but no significant difference was observed between groups B and C, groups C and D (P = 0.16, 0.13 respectively). The rate of postoperative recurrence of HCC was higher in group B than in group A, and lower than in group C. Multivariate regression analysis: showed postoperative recurrence was correlated very well with microscopic venous invasion (r = 0.783, P < 0.01), and MVD (r = 0.143, P < 0.05). Metastasis of HCC were associated very well with PCNA-LI (r = 0.590, P < 0.01) and MVD (r = 0.179, P < 0.05), and negatively correlated with the rate of ICAM-1 expression (r = -0.183, P < 0.01).

CONCLUSIONSVEGF, uPA and ICAM-1 protein expression and proliferation of cancer cells could contribute to the formation of PVTT, metastasis and postoperative recurrence of HCC. Over-proliferated cancer cells in HCC could be the direct factor of intrahepatic metastasis and formation of PVTT, and microscopic venous invasion may be a significant factor to predict postoperative recurrence of HCC.

Carcinoma, Hepatocellular ; blood supply ; pathology ; secondary ; Endothelial Growth Factors ; analysis ; Humans ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; analysis ; Intercellular Signaling Peptides and Proteins ; analysis ; Liver Neoplasms ; blood supply ; chemistry ; pathology ; Lymphokines ; analysis ; Neoplasm Recurrence, Local ; Proliferating Cell Nuclear Antigen ; analysis ; Urokinase-Type Plasminogen Activator ; analysis ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors