Cytoskeletal Proteins ; biosynthesis ; genetics ; physiology ; Humans ; Neoplasm Metastasis ; Neoplasms ; pathology ; Signal Transduction

Animals ; Cytoskeletal Proteins ; biosynthesis ; genetics ; Drugs, Chinese Herbal ; pharmacology ; Hepatocytes ; metabolism ; ultrastructure ; Rats ; Rats, Sprague-Dawley

Abnormal expression of E-cadherin/catenin complex in cancer has been associated with poor differentiation and acquisition of invasiveness, suggesting a possible role of this protein as an invasion suppressor. In this study, we conducted an immunohistochemical investigation of all components of the E-cadherin/catenin complex in 65 gastric cancer patients. Abnormal expression of E-cadherin and, alpha- and gamma-catenin occurred more frequently in diffuse than in intestinal type of gastric cancer, and correlated with poor differentiation. Abnormal expression of E-cadherin and beta-catenin correlated with poor survival. Abnormal expression of all four components of the complex was associated with poorly differentiated and diffuse-type carcinoma, and poor survival. In the multivariate analysis, abnormal expression of the E-cadherin/catenin complex was not an independent prognostic factor. These results suggest that the E-cadherin/catenin complex may be a useful marker of differentiation and prognosis in gastric cancer. Further studies are warranted to clarify the impact of the E-cadherin/catenin complex on prognostic factor of gastric cancer.
Adult ; Aged ; Cadherins/biosynthesis* ; Cytoskeletal Proteins/biosynthesis* ; Female ; Human ; Male ; Middle Age ; Prognosis ; Stomach Neoplasms/pathology ; Stomach Neoplasms/metabolism* ; Survival Analysis ; Tumor Markers, Biological/biosynthesis*

OBJECTIVETo investigate the effects of 8-methoxypsoralen on human melanocytes [Ca(2+)]i and cytoskeleton actin organization in vitro.

METHODSHuman melanocytes were obtained from normal foreskins. Laser confocal microscope was employed to measure [Ca(2+)]i and rhodamine-conjugated phalloidin was used to visualize the cytoskeleton actin.

RESULTS8-methoxypsoralen increased [Ca(2+)]i and induced organization of actin stress fiber cytoskeleton.

CONCLUSION8-methoxypsoralen might influence the migration of melanocytes by increasing the intracellular free Ca(2+) concentration and cytoskeleton actin reorganization.

Actins ; biosynthesis ; genetics ; Calcium ; metabolism ; Cell Movement ; drug effects ; Cells, Cultured ; Cytoskeletal Proteins ; biosynthesis ; genetics ; Humans ; Melanocytes ; cytology ; drug effects ; metabolism ; Methoxsalen ; pharmacology ; Skin ; cytology

OBJECTIVEResearch was done on the possible roles of beta-catenin, p53 and proliferating cell nuclear antigen (PCNA) in the carcinogenesis of colorectal adenoma (CRA).

METHODSbeta-catenin and p53 and PCNA expressions were studied with immunohistochemical stain in 77 specimens of CRA together with mild epithelial dysplasia (CRA-MD), CRA with moderate/severe epithelial dysplasia (CRA-D/SD) and CRA with cancerous changes (CRA-C).

RESULTSThe percentage of abnormal expression of beta-catenin increased during the transition from CRA-MD to CRA-D/SD to CRA-C (P < 0.01). The nuclear expressions of beta-catenin in CRA-D/SD and CRA-C were all significantly higher than that in CRA-MD. Expression of p53 and PCNA were increased from CRA-MD to CRA-D/SD to CRA-C, with the positive rates in these three groups of 10.3%, 43.8%, 75.0% for p53 and 17.2%, 62.5%, 87.5% for PCNA, respectively. 69.7% of cases with positive nuclear beta-catenin expression showed strong PCNA positivity which was much higher than the 36.4% of cases without nuclear beta-catenin expression (P < 0.05). The percentage of strong PCNA expression in the p53 positive cases was significant higher than that in cases with negative p53 expression (72.4% vs 37.5%, P < 0.05). Nuclear beta-catenin and p53 co-expression rates in CRA-C reached 50%.

CONCLUSIONbeta-catenin, p53 and PCNA may play important roles in the carcinogenesis of colorectal adenoma.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; biosynthesis ; Colorectal Neoplasms ; diagnosis ; metabolism ; Cytoskeletal Proteins ; biosynthesis ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prognosis ; Proliferating Cell Nuclear Antigen ; biosynthesis ; Trans-Activators ; biosynthesis ; Tumor Suppressor Protein p53 ; biosynthesis ; beta Catenin

OBJECTIVETo observe dystrophin and utrophin expression in muscle tissues of Duchenne muscular dystrophy (DMD) mouse model (dko mouse) after having been treated with bone marrow mesenchymal stem cells (MSC) transplantation.

METHODSThe fifth generation of MSCs, cultured in vitro, was transplanted into dko mice by tail vein. The fluorescent expression of dystrophin and utrophin in gastrocnemius muscle tissue of dko mouse was detected and the average optical density of positive fibers was calculated.

RESULTSMSCs that had been cultured for three generations had good homogeneousness and the immunological reaction after vein transplantation was low. There was an increasing tendency of dystrophin and utrophin fluorescent expression in sarcolemma of dko mouse within 5-20 weeks. Significant difference existed in fluorescent average optical density of positive fibers fifteen weeks before and after cell transplantation.

CONCLUSIONSMSC has strong plasticity both in vitro and in vivo. MSC has a trend to reach the injured muscle tissues and turn into muscle fibers, which express dystrophin and utrophin. There is some plerosis function for myatrophy of dko mouse by MSC transplantation.

Animals ; Bone Marrow Cells ; cytology ; Cytoskeletal Proteins ; biosynthesis ; Dystrophin ; biosynthesis ; Female ; Male ; Membrane Proteins ; biosynthesis ; Mesenchymal Stem Cell Transplantation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Skeletal ; metabolism ; Muscular Dystrophy, Duchenne ; metabolism ; surgery ; Rats ; Rats, Sprague-Dawley ; Utrophin

OBJECTIVETo detect the gene promoter methylation, mRNA and protein expression levels of E-cadherin and beta-catenin in primary and metastatic tumor samples of nasopharyngeal carcinoma (NPC), and to investigate the mechanism of invasion and metastasis of neoplastic cell in NPC.

METHODSTwenty-one patients with NPC were studied. The samples of primary tumor and paired lymph node metastatic tumor were collected and examined for aberrant gene promoter methylation in E-cadherin by DNA Methylation-specific polymerase chain reaction (MSP). Reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical staining were adopted to detect mRNA and protein levels of E-cadherin and beta-catenin.

RESULTS(1) The gene promoter methylation in E-cadherin was 52.4% (11/21) in primary tumor of NPC, and 80.9% (17/21) in lymph node metastatic tumor, which existed significant difference (P < 0.05). (2) In primary tumor, about 80% (0 approximately 100%) neoplastic cells expressed E-cadherin protein on the average, which was significantly higher than that of metastatic tumor (50% on the average, P = 0.004). The expression levels of beta-catenin protein were high in both primary and metastatic tumors, but with no statistic difference (P = 0.698). (3) By Western blotting analysis, the relative intensity of protein expression in E-cadherin was significantly higher in primary tumor (206.7 +/- 32.7) compared to that of metastatic tumor (65.0 +/- 15.9), while the expression of beta-catenin protein showed no difference between them (P = 0.754). (4) mRNA expression level of E-cadherin was higher in primary tumor than that of metastatic tumor.No remarkable difference was found for the mRNA expression of beta-catenin.

CONCLUSIONS(1) Downregulation of mRNA and protein expression of E-cadherin may play a critical role in neoplastic cell invasion and metastasis in NPC. The aberrant promoter methylation of E-cadherin may ultimately alter the mobility and scattering of tumor cells in NPC. (2) Downregulation of E-cadherin alone may be enough for the tumor cell to lose intercellular adhesions which results in tumor cell invasion and metastasis. However, mutant beta-catenin could also involve in this progress. (3) The detection of gene promoter hypermethylation of E-cadherin should be evaluated in the screening and surveillance of NPC.

Adult ; Aged ; Cadherins ; biosynthesis ; genetics ; Cytoskeletal Proteins ; biosynthesis ; genetics ; DNA Methylation ; Down-Regulation ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; Neoplasm Invasiveness ; Promoter Regions, Genetic ; RNA, Messenger ; genetics ; Trans-Activators ; biosynthesis ; genetics ; beta Catenin

OBJECTIVETo study the significance of beta -catenin, p53 and PCNA in PJS harmatoma.

METHODParaffin sections of 29 hamartomas of 18 patient with Peutz-Jeghers syndrome, 19 patients with colorectal mucosa and 10 persons with normal mucosa were examined using LSAB. Positive cells were detected under light microscope.

RESULTSAll 10 persons with normal mucosa showed p53 negative and beta - catenin positive. The beta - catenin protein was predominantly localized to the plasma membrane. PCNA index (PI) in normal mucosa was 10.56 +/- 7.51. The PI of hamartoma and cancer was 44.57 +/- 21.15 and 32.96 +/- 18.88. The PI of the two groups was significantly higher than that of the normal group. In hamartoma, the positive cells were mainly located in the low 1/3 part of the mucous glands. The positive rate of p53 was 24.1% (7/29) in hamartomatouspolyps and 57.9% (11/19) in colorectal carcinoma (chi(2) = 5.581, P < 0.05). Abnormal expression rate of beta- catenin in colorectal carcinoma was 73.7% (14/19) and 41.3% (12/29) in hamartomatous polyps. Some epithelial cells showed nuclear localization of beta- catenin and concentration of cytoplasm. (chi(2) = 4.825, P < 0.05).

CONCLUSIONSThe proliferation activity of hamartomatous polyps increased significantly by multifactory interaction. p53 and beta- catenin play a role in the early stage of hamartoma- adenoma-carcinoma sequence but have a different mechanism in inducing colorectal cancer.

Cytoskeletal Proteins ; biosynthesis ; genetics ; Gene Expression ; Hamartoma ; genetics ; metabolism ; Humans ; Peutz-Jeghers Syndrome ; genetics ; metabolism ; Proliferating Cell Nuclear Antigen ; biosynthesis ; genetics ; Trans-Activators ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics ; beta Catenin

OBJECTIVEStudy the improvement of locomotive faculty of dystrophin/utropin gene double knock-out mice (dko mice) by transplanting bone marrow stem cells.

METHODSThe bone marrow stem cells of C57BL/6 mice (4- to 5-weeks age) were cultured in vitro for three days, before transplanted intravenously (1.0 x 10(7) for each) into 11 dko mice (7- to 8-weeks age). The dko mice were irridiated with 7Gy gamma-ray before transplantation. 8-9 weeks after transplantation, the locomotroy function, electromyography items and expression of dystrophin in transplanted mice and controls were observed.

RESULTS8-9 weeks after transplantation, the dropping times of hauling wire were 3.09 +/- 2.47, compared with that of the control dko mice(16.78 +/- 3.60), there are distinct differences. About electromyography items, the duration of active potential and amplitude of maxim contractions were (4.99 +/- 1.62) ms and(2872 +/- 1474.33) microV, compare with those of control dko mice(3.69 +/- 0.40) ms and(1210.0 +/- 551.0) microV, respectively, about 7% fibers of the muscle tissue of transplanted dko mice expressed dystrophin protein.

CONCLUSIONS8-9 weeks after transplanted with homology bone marrow stem cells, the locomotive function and electromyography items of transplanted dko mice were obviously improved, and about 7% muscle tissue fibers of the mice expressing dystrophin protein were observed. It suggested that there is an ideal prospect for DMD therapy with bone marrow stem cells transplantation.

Animals ; Cytoskeletal Proteins ; biosynthesis ; deficiency ; genetics ; Dystrophin ; deficiency ; genetics ; Hematopoietic Stem Cell Transplantation ; Membrane Proteins ; biosynthesis ; genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; Muscular Dystrophy, Duchenne ; physiopathology ; surgery ; Utrophin

Colorectal signet-ring cell carcinoma (SRCC) is a rare type of adenocarcinoma and presents with distinctive clinicopathological features. This study was performed to assess the biological characteristics of colorectal SRCC regarding the E-cadherin expression. Seventeen patients with primary colorectal SRCC were identified and their clinicopathological characteristics were analyzed. The mean age of the 17 patients was 45.3 yr (14-68). Immunohistochemical staining of E-cadherin and beta-catenin were performed in ten colorectal SRCCs and in 30 ordinary colorectal adenocarcinomas as control. Primary colorectal SRCC occurred in 0.7% of 2,388 colorectal adenocarcinomas. Most patients had advanced stage tumor at surgery (stage III and IV, AJCC: 82%). Five-year survival rate was 16%. Peritoneal seeding was the most common recurrence pattern (41%) and liver metastasis was not identified. All SRCCs showed a markedly reduced or absent expression of E-cadherin on immunohistochemical staining, whereas seven (23.3%) of ordinary carcinomas showed reduced expression, thereby indicating a significant difference between the two groups (p<0.005). In immunohistochemical staining for beta-catenin, eight of ten SRCCs showed reduced membrane expression that did not attain statistical significance compared to ordinary adenocarcinomas. It is suggested that aberrant E-cadherin expression may explain the distinct clinicopathological features in primary colorectal SRCC.
Adolescent ; Adult ; Aged ; Cadherins/*biosynthesis ; Carcinoma, Signet Ring Cell/*metabolism/pathology ; Colorectal Neoplasms/*metabolism/pathology ; Cytoskeletal Proteins/biosynthesis ; Female ; Humans ; Immunohistochemistry/methods ; Male ; Middle Aged ; Retrospective Studies ; *Trans-Activators ; beta Catenin