Cheng-jun Zhou

The different expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and possible roles in gastric carcinomas

The purpose of this study was to investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its effects on promoting angiogenesis in gastric adenocarcinomas. Paraffin wax sections of 222 patients with gastric adenocarcinomas having undergone surgery between 2001 and 2006 were classified into three histotypes: intestinal, diffuse, and mixed carcinomas following the Laurén classification. Immunohistochemistry (IHC) was used to study the distribution of CEACAM1, and double-labeling immunohistochemistry was used to observe the relationship between CEACAM1 expression and neovascularization in carcinoma areas. No CEACAM1 expression was found in normal non-metaplastic mucosa adjacent to the tumors; but in metaplastic mucosa, CEACAM1 was expressed on the apical surface. However, all of the collected gastric carcinomas expressed CEACAM1 with cytoplasmic or membranous staining. CEACAM1 was expressed mainly with a membranous pattern in the intestinal carcinomas, and with a cytoplasmic pattern in the diffuse carcinomas. There was a significant difference between the expression patterns and the histotypes (P<0.0001). CEACAM1 expression was classified as high (> or =66% positive cells) and low (<66% positive cells), and high CEACAM1 expression was associated with lymph nodes metastasis (P<0.05). High microvessel density (MVD) was observed more frequently in the tumors with membranous expression, and low MVD in the tumors with cytoplasmic staining (P<0.0001). The transformation of CEACAM1 distribution from membrane to cytoplasm is an important incident for the reverse effects on the tumorous angiogenesis, and high expression of CEACAM1 facilitates the metastasis of carcinoma cells to lymph nodes. Moreover, the different distribution of CEACAM1 in the intestinal and diffuse carcinomas indicates a different tumorigenic pathway.

Upregulation of Nrf2 expression in non-alcoholic fatty liver and steatohepatitis.

BACKGROUND/AIMSnThe purpose of this study was to examine the expression of Nrf2 in the non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH) in mice.nnnMETHODOLOGYnMice were fed a high-fat diet for 8 or 12 weeks before the serum levels of 8-iso-prostaglandin F2α (F2-isoPG) were measured by ELISA; Liver Nrf2 expression was detected by immunohistochemistry.nnnRESULTSnLiver index, serum alanine aminotransferase (ALT), cholesterol (CHOL) and glucose (GLU) increased significantly (p<0.01) in the high fat diet group. The level of F2-isoPG was also statistically higher in the high fat diet group at both 8 and 12 weeks (p<0.05). Nrf2 expression showed robust upregulation in both the NAFL and NASH groups as compared to the control group (p<0.05). There was a statistically significant (p<0.05) difference in the overexpression of Nrf2 in the NASH group as compared to the NAFL group. Pearson correlation analysis showed a strong correlation between Nrf2 expression and the degree of hepatic steatosis and inflammation.nnnCONCLUSIONSnOur results showed that during the development of NAFL and NASH, F2-isoPG levels increased and Nrf2 expression was upregulated. Our findings suggest Nrf2 may play a key role during liver steatosis, and activation of Nrf2 may protect liver from inflammation damage induced by oxidative stress.

miR-124 inhibits cell proliferation, migration and invasion by directly targeting SOX9 in lung adenocarcinoma

Accumulating evidence indicates that dysregulation of microRNAs (miRNAs) may contribute to the initiation and progression of cancer. However, the role of miR-124 in lung adenocarcinoma (ADC) and the underlying mechanisms through which miR-124 exerts its functions are not completely understood. In the present study, we detected miR-124 and SOX9 expression in lung ADC tissues. The results showed that miR-124 was significantly downregulated in the lung ADC tissues compared with that noted in the corresponding non-cancerous lung tissues and the level of SOX9 protein was inversely associated with the expression of miR-124. The study in human lung ADC cell line A549 demonstrated that upregulation of miR-124 could inhibit cell proliferation, migration and invasion. The bioinformatic analysis showed that there was a putative miR-124 binding site in the 3 untranslated region (3UTR) of SOX9. Using a luciferase reporter assay, we verified that SOX9 is a direct target of miR-124. Furthermore, overexpression of miR-124 repressed SOX9 expression, whereas inhibition of miR-124 increased expression of SOX9 in the A549 cells. Finally, we identified that SOX9 was a functional mediator of miR-124 in A549 cells. Taken together, our results suggest that miR-124 functions as a tumor suppressor in lung ADC by directly targeting SOX9 and it may be a promising candidate for miR‑based therapy against lung ADC.

The distribution of IGF2 and IMP3 in osteosarcoma and its relationship with angiogenesis.

The aim of this study was to investigate the expression patterns of IGF2 and IMP3 in osteosarcoma as well as its relationship with angiogenesis in the tumor. IGF2 and IMP3 expression was detected by immunohistochemical staining in the serial sections of the osteosarcoma. The impacts of IGF2 and IMP3 expression patterns on tumor angiogenesis were evaluated by statistics. The IGF2 and IMP3 staining had different expression patterns in different osteosarcoma. Twelve out of the sixty-four cases of conventional osteosarcoma showed nuclear staining patterns, and twenty-nine showed cytoplasmic staining of IGF2 and IMP3 simultaneously. On the other hand, fourteen cases showed nuclear IGF2 staining but cytoplasmic IMP3 expression, and nine cases showed nuclear IMP3 staining and cytoplasmic IGF2 expression. Twenty-eight out of forty-seven cases of parosteal osteosarcoma showed nuclear IGF2 and IMP3 expression, nine showed cytoplasmic IGF2 and IMP3 expression simultaneously. Seven out of forty-seven cases of parosteal osteosarcoma expressed IGF2 with nuclear staining but expressed IMP3 with cytoplasmic staining. Meanwhile, three cases expressed IGF2 with cytoplasmic staining but expressed IMP3 with nuclear staining. Similar to the parosteal osteosarcoma, the periosteal osteosarcoma expressed IGF2 and IMP3 mainly with nuclear staining simultaneously, forty out of fifty-five cases of periosteal osteosarcoma did that. Five out of fifty-five cases expressed IGF2 and IMP3 with cytoplasmic staining at the same time. Four cases showed nuclear IGF2 staining and cytoplasmic IMP3 staining. In the parosteal and periosteal osteosarcoma, there was no significant difference in IGF and IMP3 expression patterns (Pxa0=xa00.216). However, compared with conventional osteosarcoma, the parosteal and periosteal osteosarcoma showed significant difference in IMP3 and IGF2 expression (Pxa0=xa00.016, Pxa0=xa00.023). IGF2 and IMP3 expression patterns were positive correlation in the different osteosarcoma (rxa0=xa00.1021, Pxa0=xa00.032). The Microvessel density (MVD) in osteosarcoma with IGF2 and IMP3 cytoplasmic staining was more than that with nuclear expression of IGF2 and IMP3, and the difference was significant (Pxa0=xa00.024). Moreover, the conventional osteosarcoma with cytoplasmic IGF and IMP3 showed more MVD than parosteal and periosteal osteosarcoma with cytoplasmic IGF and IMP3, and the difference was significant (Pxa0=xa00.035). IGF2 and IMP3 had different expression patterns, which might be associated with angiogenesis. However, cytoplasmic and nuclear expression of IGF2 and IMP3 might play different roles in the angiogenesis of osteosarcoma.

Evaluation of Nrf2 and IGF-1 expression in benign, premalignant and malignant gastric lesions.

The aim of this study was to investigate the expression of Nrf2 and IGF-1 in benign, premalignant, and malignant gastric lesions, and to explore the role of Nrf2 and IGF-1 in gastric carcinoma carcinogenesis. Nrf2 and IGF-1 expression was detected in normal gastric mucosa, hyperplastic polyp, intraepithelial neoplasia, and adenocarcinoma by immunohistochemistry. There was no expression of Nrf2 and IGF-1 in normal gastric mucous membrane. With the elevation of Nrf2, IGF-1 expression, their co-expressions were highly elevated from benign proliferative lesions to malignant lesions. There were significant differences between hyperplastic polyps, intraepithelial neoplasias, and adenocarcinoma (hyperplastic polys vs. intraepithelial neoplasia: P=0.012; hyperplastic polyps vs. adenocarcinoma: P=0.023; and intraepithelial neoplasia vs. adenocarcinoma: P=0.027; hyperplastic polyps vs. adenocarcinoma: P=0.0000, respectively). Nrf2 expression and IGF-1 expression were correlated positively (r=0.337, P=0.037). The increased expression of Nrf2 and IGF-1 may be related to gastric carcinogenesis. Elevated Nrf2 and IGF-1 may play important roles in promoting tumor progression.

The evaluation of SOX9 expression and its relationship with carcinoembryonic antigen-related cell adhesion molecule 1 in gastric neoplastic and nonneoplastic lesions.

The aims of this study were to investigate the expression of SOX9 (sex determining region Y [SRY]-related high-mobility group box 9) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in benign, premalignant, and malignant gastric lesions and to explore the association between SOX9 and CEACAM1 in gastric carcinogenesis. SOX9 and CEACAM1 expression was detected in normal gastric mucosa, hyperplastic polyp, intestinal metaplasia, gastric intraepithelial neoplasia, and adenocarcinoma by immunohistochemistry. There was low expression of SOX9 and no CEACAM1 expression in normal gastric mucosa and hyperplastic polyps. Intestinal metaplasia began to express CEACAM1 and showed more membranous staining of CEACAM1 than normal mucosa and hyperplastic polyps (P = .000), but SOX9 expression had no significant difference, and the coexpression of SOX9 and CEACAM1 ascended; therefore, the difference was significant (P = .000). Gastric intraepithelial neoplasia showed more SOX9 expression, coexpression of SOX9, and CEACAM1 than in intestinal metaplasia (P = .014 and P = .026, respectively). Carcinoma showed more cytoplasmic CEACAM1 (P = .010), more SOX9 expression (P = .001), and more their coexpression (P = .023) than gastric intraepithelial neoplasia. As to the histologic classification, poorly differentiated carcinoma showed more cytoplasmic CEACAM1 than well and moderately differentiated carcinoma (P = .006 and P = .024, respectively). In the Laurén classification, diffuse carcinoma showed more cytoplasmic CEACAM1 than intestinal carcinoma (P = .0035), but the SOX9 expression and their coexpresison showed no difference (P = .065 and P = .074, respectively). With the elevation of SOX9 expression and the changing of CEACAM1 expression patterns, the coexpressions of SOX9 and CEACAM1 were highly elevated from benign proliferative lesions to malignant lesions. Moreover, the SOX9 expression and the coexpression with CEACAM1 were correlated positively (r = 0.310; P = .015). In addition, SOX9 expression was positively correlated with CEACAM1 expression patterns (r = 0.124; P = .032). In addition, CEACAM1 expression patterns and coexpression of SOX9 and CEACAM1 show significant difference between T1 and T2 and T3 and T4 (P = .021 and P = .011, respectively). Accordingly, compared with N0, N2 and N3 showed significant difference in SOX9 expression (P = .018), CEACAM1 expression patterns (P = .010), and their coexpression (P = .010). SOX9 expression significantly increased from nonneoplastic lesions to neoplastic lesions, and CEACAM1 expression patterns markedly changed; their coexpression also showed signally elevated suggesting that SOX9, as a transcriptional regulator, play important roles in the changing of CEACAM1 expression patterns, which might promote the tumor progression.

Expression of ER, Ki-67 and CylinD1 in the Pre-cancerous Breast of Chinese Patients

To investigate the expression and association of ER, Ki-67 and cyclinD1 in usual ductal hyperplasia(UDH), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ(DCIS) in the breast. The study included 56 cases of pre-cancerous lesions which were surgically excised at Qi Lu Hospital of Shangdong University. Immunohistochemistry was used to determine the expression of ER, Ki-67 and cyclinD1 and double-labelling immunofluorescence technique was used to observe the coexpression of ER and Ki-67. The expression and distribution of ER-positive cells were significantly different in UDH, ADH and DCIS. The ER-positive cells were much more in UDH than in normal TDLUs (terminal duct lobular units). The distribution of ER-positive cells interspersed amid ER-negative cells within UDH. However , the ER positive cells showed marked increases in ADH and low grade nuclear DCIS (Pu2009<u20090.05), distributing in almost all constituent cells. The expression of ki-67 and cyclinD1 were significantly different between UDH and DCIS (Pu2009<u20090.05) , and a positive correlation was found between expression of Ki-67 and morphological classification of pre-cancerous lesions (ru2009=u20090.3522, Pu2009<u20090.05) as well as cyclinD1 (ru2009=u20090.3901, Pu2009<u20090.05). Double-labelling immunofluorescence showed that there was no coexpression of ER and Ki-67 in normal breast tissue. The coexpression of the two markers was found in ADH and increased in DCIS. Overexpression of ER, Ki-67 and cyclinD1 significantly accompanies the transition of normal cells and UDH to ADH and DCIS. The coexpression of ER and ki-67 may present the early change in carcinogenesis of breast cancer.

Repeating gastric biopsy for accuracy of gastric lymphoma diagnosis.

Gastric lymphoma is characterized by a good prognosis with slow progression and a nonspecific appearance under the endoscope. A biopsy is performed for accurate diagnosis. For this study, endoscopy and biopsy specimens were analyzed retrospectively to investigate the rate of accurate diagnosis of gastric lymphoma in first-, second-, and third-round endoscopic and biopsy procedures and to understand the causes of discrepancies. Fifty-four cases of gastric lymphoma were diagnosed in 32,000 patients. The rate of positive Helicobacter pylori infection was 70.4%. Of these, 13 cases were diffuse large B-cell lymphoma and 41 cases were marginal zone B-cell lymphoma. Thirty-two gastric lymphoma cases (59.3%) were diagnosed by first-round endoscopy and biopsy, 13 (24.1%) cases required second-round endoscopy and biopsy, and 9 (16.7%) cases were determined in the third round of endoscopic and biopsy procedures. Repeating endoscopy and biopsy reduced discrepancies in the diagnosis of gastric lymphoma by 40.8%, which can significantly improve the overall accuracy of diagnosis and treatment of gastric lymphoma.

The intrapapillary capillary loop (IPCL) changes in superficial esophageal lesions

The aims of this study were to investigate intrapapillary capillary loops (IPCLs) of superficial esophageal lesions changes in different types classified by the Japan Esophageal Society classification. The calibers, areas, and densities of IPCLs were detected in 34 cases of esophageal lesions using immunohistochemical analysis. Statistically significant differences in calibers, areas, and densities of IPCLs were observed between type A, type B1/B2, and type B3 area (Pu2009<u20090.001). In conclusion, the results of this observation showed the Japan Esophageal Society classification of IPCL would help endoscopists to diagnose the type and the invasion depth of lesion in esophagus, and decide the treatment strategy.

Different Expression Patterns of CEACAM1 and its Impacts on Angiogenesis in Gastric Nonneoplastic and Neoplastic Lesions

ObjectiveThis study was designed to investigate the expression patterns of CEACAM1 and its relationship with angiogenesis in nonneoplastic and neoplastic gastric lesions.MethodsCEACAM1 and TGF-β expression was detected by immunohistochemical staining and dual-labeling immunohistochemical staining in neoplastic and nonneoplastic lesions. MVD-CD31 and MVD-CD105 were counted in CEACAM1-positive areas by dual-labeling immunohistochemistry.ResultsThere was no expression of CEACAM1 in normal gastric mucosa. In IM and GIN, CEACAM1 was mainly expressed with membranous pattern. CEACAM1 was expressed with membranous pattern in well-differentiated adenocarcinoma, with cytoplasmic pattern in poorly differentiated adenocarcinoma, and with cytoplasmic and membranous pattern mixed together in intermediately adenocarcinoma. The expression patterns of CEACAM1 showed a significant difference (Pxa0<xa00.05) in nonneoplastic and neoplastic lesions. Coexpression of CEACAM1 and TGF-β was elevated and significantly different from nonneoplastic to neoplastic lesions (Pxa0<xa00.05). Moreover, CEACAM1 and TGF-β coexpression were related to carcinoma progression (rxa0=xa00.35; Pxa0<xa00.05). MVD-CD31 and MVD-CD105 showed significant differences from nonneoplastic to neoplastic lesions (Pxa0<xa00.05).ConclusionsCEACAM1 has different expression patterns in nonneoplastic and neoplastic lesions. The coexpression of CEACAM1 and TGF-β increased from nonneoplastic to neoplastic lesions and may be related with tumor progression via promoting tumorous angiogenesis.