OBJECTIVETo evaluate the effect of IL-1beta on the expression of CDX2 in human gastric epithelial cell line GES-1 and its role in the intestinal metaplasia.

METHODSGES-1 cells were treated with IL-1beta in different concentrations and the expressions of CDX2 mRNA and protein were detected by real-time PCR, immunocytochemistry and Western blot at different time points. GES-1 cells were then pre-treated with NF-KappaB pathway inhibitor PDTC, and the expression of CDX2 mRNA and protein induced by IL-1beta were detected. The cell ultra-structure of GES-1 cells was observed by electronic microscope after GES-1 being treated with IL-1beta for 25 days.

RESULTSLevels of CDX2 mRNA and protein were 0.0749 + or - 0.0021 and 0.56 + or - 0.04 in the cells treated with 1 microg/L IL-1beta(P<0.05). After pre-treatment with PDTC, levels of CDX2 mRNA and protein were 0.0006 + or - 0.0002 and 0.40 + or - 0.06(P<0.05). Some changes in the cell ultra-structure of GES-1 were found by electronic microscope when GES-1 was treated with IL-1beta for 25 days.

CONCLUSIONIL-1beta can stimulate CDX2 mRNA and protein expression in GES-1 cells through the NF-KappaB signal pathway, indicating that IL-1beta plays an important role in the intestinal metaplasia.

CDX2 Transcription Factor ; Cell Line ; Epithelium ; metabolism ; pathology ; Gastric Mucosa ; cytology ; metabolism ; pathology ; Homeodomain Proteins ; metabolism ; Humans ; Interleukin-1beta ; pharmacology ; Metaplasia ; RNA, Messenger ; genetics

OBJECTIVETo investigate the expressions of CDX2 and β-catenin and their correlation in acute myeloid leukemia (AML).

METHODSReal-time PCR was used to examine the expressions of CDX2 and β-catenin mRNA in 92 de novo AML and 30 non-malignant patients (control), and Western blot was employed to detect CDX2 and β-catenin protein expressions in 26 de novo AML and 8 non-malignant patients.

RESULTSThe positivity rates of CDX2 mRNA and protein expressions in AML group were 84.78% and 76.92%, respectively, but no CDX2 mRNA or protein expression were detected in control group (P<0.01). The expressions of β-catenin mRNA and protein were detected in all the patients in both groups but its expressions in AML group were significantly higher (P<0.01). The expressions of CDX2 and β-catenin mRNA were significantly correlated with WBC counts and LDH levels (P<0.01). The expression of CDX2 mRNA was not detected and the expression of β-catenin mRNA was decreased to normal level in AML patients with complete remission, while the expressions of CDX2 and β-catenin mRNA were increased again in those with disease relapse. There were significantly positive correlations between CDX2 and β-catenin expressions at both mRNA and protein levels (P<0.01).

CONCLUSIONUp-regulation of CDX2 gene and activation of Wnt/β-catenin pathway co-exist in AML patients and the expressions of CDX2 and β-catenin are positively correlated.

Blotting, Western ; CDX2 Transcription Factor ; Homeodomain Proteins ; metabolism ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; RNA, Messenger ; Up-Regulation ; Wnt Signaling Pathway ; beta Catenin ; metabolism

This study was aimed to investigate the expression of cdx2 gene in pediatric patients with acute leukemia and its clinical implication. The bone marrow and peripheral blood were collected from 33 newly diagnosed pediatric patients with acute leukemia, the cdx2 gene expression in each AL subtypes and normal controls was detected by RT-PCR, the relationship between cdx2 expression and response to treatment was observed. The results showed that the expression of cdx2 was positive in 25 out of 30 AL cases (83.3%), to be exact, in 20 of 21 ALL cases (95.2%) and in 5 of 9 AML cases (55.6%), which showed statistical difference (p < 0.05). The cdx2 mRNA could be detected also in 1 of 3 CML cases. However, no expression of cdx2 was observed in all normal control which revealed significant difference between patient group and normal control group. 21 AL patients with cdx2 positive expression (17 ALL and 4 AML patients) and 4 AL patients with cxd2 negative expression (1 ALL and 3 AML patients) all reached complete remission (CR) after treatment, which showed no correlation with CR rate. 8 patients with positive cdx2 expression were followed up. As a result, the cdx2 positive expression at initial diagnosis of patients remained positive at reaching CR, but it gradually turned to negative along with prolonging of CR, while the cdx2 negative expression at initial diagnosis of patients remained negative at CR in bone marrow level. It is concluded that cdx2 positive expression is observed in the majority of pediatric AL patients, even positive rate in ALL patients is higher than that in AML patients, while the cdx2 expression also can be observed in CML patients. The cdx2 positive expression is not related to the CR rate in AL patients.
CDX2 Transcription Factor ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Gene Expression ; Homeodomain Proteins ; genetics ; Humans ; Infant ; Leukemia ; genetics ; Male ; Prognosis ; RNA, Messenger ; genetics ; Treatment Outcome

OBJECTIVETo investigate the expressions of homeobox transcription factor-2 (CDX(2)) and E-cadherin and their relations to the clinicopathological characteristics of gastric carcinoma.

METHODSImmunohistochemistry was performed on 83 human gastric carcinoma specimens and 40 normal gastric mucosa specimens for examining the expressions of CDX(2) and E-cadherin, and the relations of their expression with the tumor differentiation, infiltration and metastasis were analyzed.

RESULTSAccording to the LaurAn classification, the positive expression rate of CDX(2) in intestinal type of gastric carcinoma was 56.86%, and 34.38% in the diffuse type, showing significant difference between the two types (P<0.05). The positivity rate of E-cadherin was also significantly different between the two types (66.67% vs 28.13%, P<0.01). In regard to tumor differentiation, the positivity of CDX(2) and E-cadherin expressions was significantly different between moderately to well differentiated tumors and poorly differentiated ones (P<0.01). The tumors infiltrating mucosal and submucosal layers were significantly different from those infiltrating the muscular and serous membrane layer in the positivity of CDX(2) and E-cadherin expressions (P<0.01), which were also different for the presence of lymph node metastasis (P<0.05). Regression analysis did not reveal significant correlations between CDX(2) and E-cadherin expression in gastric carcinoma (P>0.05).

CONCLUSIONThe abnormal expression of CDX(2) and E-cadherin plays an important role in the development of gastric carcinoma, especially the intestinal type. CDX(2) and E-cadherin may serve as useful markers to predict the prognosis of patients with gastric carcinoma.

Adult ; Aged ; Biomarkers, Tumor ; genetics ; metabolism ; CDX2 Transcription Factor ; Cadherins ; genetics ; metabolism ; Female ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; genetics ; metabolism ; pathology

Aged ; CDX2 Transcription Factor ; Cysts ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Homeodomain Proteins ; metabolism ; Humans ; Keratin-20 ; metabolism ; Mucous Membrane ; pathology ; Peritoneal Neoplasms ; metabolism ; pathology ; surgery ; Pseudomyxoma Peritonei ; metabolism ; pathology ; surgery ; Rupture ; Splenic Neoplasms ; metabolism ; pathology ; surgery

This study was aimed to investigate the expression and clinical significance of CDX1, CDX2 and CDX4 genes in acute lymphocytic leukemia (ALL). Expressions of CDX1, CDX2, and CDX4 in 51 adult acute lymphocytic leukemia patients and 14 healthy subjects were detected by reverse transcription polymerase chain reaction (RT-PCR). The results indicated that CDX1, CDX2 and CDX4 were not expressed in 14 healthy persons and 15 CR ALL patients, the positive expression rate of CDX2 gene in de novo ALL patients was 60.8%, while it obviously decreased in patients with complete remission (CR) (p < 0.05); the expression of CDX2 was increased again in relapsed patients (81.8%). When the expression of CDX2 was analyzed in different risk groups of ALL patients, the CDX2 expression rate in high risk (HR) patients was 91.7%, and that in the standard risk (SR) group was 45.7%. Furthermore, analyses of CDX1 and CDX4 expression in series of ALL samples did not show the expression of these genes. In patients with adult ALL at diagnosis and relapse, the CR rate of patients with CDX2 positive expression was lower than that of patients with CDX2 negative expression (p < 0.05). The median survival time in CDX2 positive expression patients was shorter than that in negative expression patient. It is concluded that expression of CDX2 may correlated with pathogenesis and relapse of adult ALL, but the expression of CDX1 and CDX4 don' t associated with pathogenesis and relapse of adult ALL; the CR rate and prognosis of patients with CDX2 positive expression is lower and poor. The expression of CDX2 may be used as a marker for occurrence, relapse and poor prognosis of adult ALL patients.
Adolescent ; Adult ; Aged ; CDX2 Transcription Factor ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Homeobox ; Homeodomain Proteins ; genetics ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Young Adult

OBJECTIVETo dynamically investigate the morphology of human gastric cancer SGC-7901 cell clones, and then compare the tumorigenic ability of different clones in order to identify the tumor stem cell clones.

METHODSClones derived from gastric cancer SGC-7901 cells were assessed by morphological observation, and the clone formation rate and proportion of each clone were calculated. The expression of CD44 and CDX2 in different clones was detected by immunofluorescence microscopy and Western blot. Furthermore, different clones were isolated and cultured, and their self-renewal property was assayed. Cells of different clones were subcutaneously inoculated into nude mice and the tumorigenic ability of each group was determined.

RESULTSClones derived from gastric cancer SGC-7901 cells had three types, i.e. clones of tight, transitional and loose types. The total clone formation rate was (9.80 ± 1.07)%, and the proportion of tight, transitional and loose type clones was 10.2%, 56.0% and 33.8%, respectively. The results of immunofluorescence microscopic examination showed that the signal of CD44 was significantly stronger in the tight clones than in the transitional and loose clones, however, the signal of CDX2 was weakest in the tight colonies. The results of Western blot were consistent with that of immunofluorescence microscopic observation. SGC-7901 cells of tight clones possessed strong ability of self-renewal and in vivo tumorigenicity in the nude mice.

CONCLUSIONSGC-7901 cell clones vary in morphology and differentiation, and the tight type clones may include rich gastric cancer stem cells.

Animals ; CDX2 Transcription Factor ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Clone Cells ; classification ; Female ; Homeodomain Proteins ; metabolism ; Humans ; Hyaluronan Receptors ; metabolism ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplastic Stem Cells ; cytology ; metabolism ; Random Allocation ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo study the expression of CDX2 in normal and tumor tissues, and to evaluate the value of CDX2 immunostaining in the diagnosis of gastrointestinal adenocarcinoma.

METHODSeventy-six samples of normal tissue and 612 samples of tumor tissue were studied by tissue microarray technology and immunohistochemistry for CDX2.

RESULTSCDX2 was strongly expressed in surface epithelium of 13 samples of normal intestine and in ductal epithelium of 8 samples of normal pancreas, as well as in 47 samples (92.2%) of colonic adenocarcinoma and 58 samples (66.9%) of gastric adenocarcinoma. As for other tumor types, there was only weak or patchy CDX2 positivity. The positivity rates were as follows: ovarian mucinous adenocarcinoma 15.6% (10/64), pancreatic cancer 33.3% (3/9), thyroid cancer 27.3% (3/11) and extrahepatic biliary cancer 25% (4/16). On the other hand, primary tumors of breast, prostate, kidney, adrenal and liver were negative for CDX2.

CONCLUSIONSCDX2 is expressed mainly in normal epithelium of intestinal tract and small pancreatic ducts, as well as in primary adenocarcinoma of gastrointestinal tract. CDX2 may thus play an important role in distinguishing primary non-intestinal adenocarcinoma from metastatic adenocarcinoma of gastric or colorectal primary.

Adenocarcinoma ; diagnosis ; metabolism ; CDX2 Transcription Factor ; Colonic Neoplasms ; diagnosis ; metabolism ; Female ; Gastrointestinal Neoplasms ; diagnosis ; metabolism ; Gastrointestinal Tract ; chemistry ; pathology ; Homeodomain Proteins ; metabolism ; Humans ; Immunohistochemistry ; Male ; Stomach Neoplasms ; diagnosis ; metabolism ; Tissue Array Analysis

OBJECTIVETo explore the expression and clinical significance of Caudal-type homeobox transcription factor 2 (CDX2) gene in acute myeloid leukemia (AML) patients.

METHODReal time quantitative PCR (RQ-PCR) was used to test the expression level of CDX2 gene in 108 de novo AML patients and the clinical features of these patients were analyzed.

RESULTSCDX2 gene transcript levels were detectable in bone marrow mononuclear cells from 108 AML patients and 7 healthy donors, the median expression level were 1179.44 (range 14.15 - 867 961.10) and 105.30 (range 22.30 - 453.11). There was a statistically significant difference in expression level of CDX2 gene between the AML patients and normal donor (P < 0.01). All 14 patients with FLT3-ITD(+) were in CDX2 gene higher expression group (P = 0.018), including 10 patients with normal karyotype. In the 83 treated AML patients (P = 0.046) and 57 higher WBC count (≥ 10×10(9)/L, P = 0.048) patients, the higher expression level of CDX2 gene was associated with lower complete remission (CR) rates.

CONCLUSIONSHigher expression level of CDX2 gene was seen mostly in AML patients with FLT3-ITD mutation and with lower CR rates. CDX2 gene might be a prognostic molecular marker in AML patients with normal karyotype.

Adolescent ; Adult ; Aged ; CDX2 Transcription Factor ; Case-Control Studies ; Female ; Homeodomain Proteins ; genetics ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Male ; Middle Aged ; Mutation ; Prognosis ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics

OBJECTIVETo investigate the clinicopathologic characteristics, prognosis and histologic origin of the mucinous tumor of the peritoneum.

METHODSAccording to 2010 WHO classification of tumours of the digestive system, 34 cases diagnosed as "pseudomyxoma peritonei (PMP) " were reevaluated and divided into low grade and high grade. Immunohistochemistry was applied to investigate the expression of SATB2 and the histologic origin of the mucinous tumor of the peritoneum, using antibodies against SATB2, CK7, CK20 and CDX-2. The relationship between clinicopathologic characteristics and prognosis of the low grade and high grade tumors were analyzed.

RESULTSTwenty five patients had low grade mucinous tumors (two of them were no cell type), nine patients had high grade mucinous tumors. There was no significant difference between low grade and high grade mucinous tumors in age, sex, recurrence and organs involvement (P>0.05). Thirty patients were followed up, the overall survival rates of patients with low grade and high grade mucinous tumors were 13/21 (61.9%) and 3/9, respectively. The median survival time was 74 and 24 months in low and high grade patients, and the difference was statistically significant (P=0.002).Immunohistochemistry showed the expression rates of CDX-2, CK20, and CK7 in totally 32 cases (excluding 2 cases of no cell type) were 30/32(93.8%), 31/32 (96.9%), and 3/16, respectively; the expression rates of CDX-2, CK20, and CK7 in 16 cases with distinct primary site were 15, 16, and 1, respectively; fifteen of 16 cases of tumors of unknown primary site were positive for CDX-2 and CK20, two of the them were positive for CK7. There was no difference in the expression of CDX-2, CK20 and CK7 between tumors with distinct primary site and tumors with unknown primary site (P>0.05). The expression rate of SATB2 in the cases was 56.3% (18/32), excluding 2 cases of no cell type. There was no significant difference between low grade and high grade tumors in the expression of SATB2 [15/23(65.2%) vs 3/9, P=0.102], also SATB2 was not related to the prognosis of the tumor (P=0.786).

CONCLUSIONThe prognosis of the mucinous tumor of the peritoneum was significantly different between low grade and high grade according to WHO 2010 classification, and most mucinous tumor of the peritoneum originated from the appendix.

Adenocarcinoma, Mucinous ; metabolism ; pathology ; secondary ; surgery ; Adult ; Aged ; Aged, 80 and over ; Appendiceal Neoplasms ; pathology ; surgery ; CDX2 Transcription Factor ; Female ; Follow-Up Studies ; Homeodomain Proteins ; metabolism ; Humans ; Keratin-20 ; metabolism ; Keratin-7 ; metabolism ; Lymphatic Metastasis ; Male ; Matrix Attachment Region Binding Proteins ; metabolism ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Peritoneal Neoplasms ; metabolism ; pathology ; secondary ; surgery ; Pseudomyxoma Peritonei ; metabolism ; pathology ; surgery ; Survival Rate ; Transcription Factors ; metabolism