Expression of human chorionic gonadotropin, CD44v6 and CD44v4/5 in esophageal squamous cell carcinoma

AIM: To study the relationship between the expression of human chorionic gonadotropin (HCG), CD44v6,CD44v4/5 and the infiltration, metastasis of esophageal squamous cell carcinoma. METHODS: By labeled streptavidin-biotin technique,the expressions of HCG, CD44v6, and CD44v4/5 in 42 patients with esophageal squamous cell carcinoma were examined.RESULTS: The positive rate of HCG expression in patients with lymph node metastasis was 85.71%(18/21), higher than that (57.14%, 12/21) in those without lymph node metastasis (P＜0.05). The positiverate of CD44v6 expression was 71.43% (15/21) in lymph node metastasis group, and 38.09% (8/21) in nonmetastasis group; there was a significant difference between the two groups (P＜0.05). The positive rateof CD44v4/5 expression was 76.19% (16/21) inlymph node metastasis group, and 42.86% (9/21) in non-metastasis group; there was also a significant difference between them (P＜0.05). From grade I to grade Ⅲ in differentiation, the positive rate of HCG expression was 84.62% (11/13), 70.59% (12/17) and 58.33% (7/12), respectively; there was no significant difference among them (P＞0.05). The positive rate of CD44v6 expression in grades Ⅰ -Ⅲ of cancer tissues was 76.92% (10/13), 52.94% (9/17), and 33.33%(4/12) respectively; there was no significant difference among them. The positive rate of CD44v4/5 expression in grades Ⅰ-Ⅲ of cancer tissues was 69.23% (9/13),64.71% (11/17), and 41.67% (5/12) respectively; there was no significant difference among the three groups. There was no correlation between the positive rates ofHCG and CD44v6, CD44v4/5 expression. Cancer cells in carcinomatous emboli and those infiltrating into vascular wall strongly expressed HCG, CD44v6, and CD44v4/5. CONCLUSION: Expression of HCG, CD44v6, and CD44v4/5 in esophageal squamous cell carcinoma is related to its infiltration and metastasis. HCG, CD44v6, and CD44v4/5 have different effects on the infiltration and metastasis of esophageal squamous cell carcinoma.

Expression of the EphA2 Gene in Esophageal Carcinoma Tissues

OBJECTIVE To investigate the relationship of the EphA2 gene with the occurrence, invasion and metastasis of esophageal carcinoma. METHODS The expression of EphA2 mRNA was detected by RT-PCR and the EphA2 protein was estimated by immunohistochemistry (SP method) in both esophageal cancerous tissues and normal epithelial tissues. RESULTS The expression of EphA2 mRNA showed no difference between esophageal cancerous tissues and normal epithelium, and there appeared to be no correlation with differentiation of the cancerous tissues, the depth of infiltration or lymph node metastasis (P>0.05). However, the expression of the EphA2 protein was significantly higher in cancerous tissues compared to normal epithelial tissues (P<0.05). The expression of the EphA2 protein in a deeper invasive group and in a group with lymph node metastasis was significantly higher compared to a superficially invasive group and a group without lymph node metastasis (P<0.05). Its expression did not appear to be correlated with differentiation of cancerous tissues (P>0.05). CONCLUSION The occurrence of esophagus carcinoma and the formation of invasion and metastasis may be related to overexpression of the EphA2 protein but not to the level of mRNA, a finding which may due to up-regulation at the translation level or by increased protein stability.

Expression of Vascular Endothelial Growth Factor C and Its Clinical Significance in Human Esophageal Squamous Cell Carcinoma

OBJECTIVE To examine the expression of vascular endothelial growth factor C(VEGF-C)in human esophageal squamous cell carcinoma(ESCC), and to clarify its role in lymphatic metastasis in ESCC patients. METHODS Esophageal carcinoma EC9706 cel s and samples from 49 patients with primary ESCC were investigated by using S-P immunohisto- chemistry(IHC),the semi-quantitative reverse transcriptase-polymerase chain reaction(RT-PCR)and in situ hybridization(ISH)methods for VEGF-C expression. RESULTS VEGF-C positive expression was found in EC9706 cells through IHC,ISH and RT-PCR.Positive IHC for VEGF-C was observed in 36 of 49 cases of ESCC.There was a significant difference between the expres- sion of VEGF-C in a lymph-node-positive group compared to a node-nega- tive group(χ2=4.7,P<0.05).Positive ISH for VEGF-C mRNA was observed in 23 of 49 cases of ESCC.There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group(χ2=31.3,P<0.01).The expression of VEGF-C was significantly higher in the lymph-node-positive group compared to the node-negative group.Of 49 ESCC tissues,RT-PCR for VEGF-C mRNA was observed positively in 29 cases.There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group(χ2=23.3, P<0.01).The expression of VEGF-C was significantly higher in the lymph- node-positive group compared to the node-negative group.Expressions of VEGF-C were not significantly associated with age,gender,and pathological grade.There was a relationship between VEGF-C mRNA expressions by RT-PCR and ISH(χ2=18.5,P<0.01)in ESCC cases,but with no significant difference between the two methods. CONCLUSION VEGF-C expression may induce lymphangiogenesis in human ESCC.There was a close correlation between VEGF-C expression and lymph node metastasis.VEGF-C can serve as a useful prognostic factor for ESCC patients.

Bcl-XL反义寡核苷酸转染对食管癌细胞系和裸鼠人食管癌移植瘤增殖、生长抑制作用的实验研究(英文)

Objective:The aim of our study was to investigate the biological effects of Bcl-XL antisense oligodeoxynucleotide(ASODN) transfected into cultured esophageal carcinoma cells and human esophageal carcinoma xenograft in nude mice.Methods:Cationic liposome-mediated ASODN was used to transfect esophageal carcinoma cells.RT-PCR, Western blot, MTT assay, flow cytometry, and in situ apoptosis cells detection(TUNEL detection) were used to systematically study the biological effects of transfected cells both in vitro and in vivo.Results:In this study, the results showed that the proliferation of esophageal carcinoma cells in ASODN group decreased significantly when compared with the control group(P < 0.05), at 57.3% Bcl-XL mRNA inhibitory rate, and a significant decreasing of Bcl-XL protein expression, at the apoptosis rates of(31.1 ± 5.8)% and 35.0% by flow cytometry and TUNEL assay respectively(P < 0.01, when compared with control groups).It also showed that the growth of human esophageal carcinoma in nude mice of ASODN group was significantly inhibited(P < 0.05), together with a significant decreased expression level of Bcl-XL mRNA and protein, and an induced tumor cell apoptosis in nude mice.Conclusion:Our result indicates Bcl-XL ASODN can effectively inhibit the proliferation of esophageal carcinoma cells in vitro and tumor growth in vivo.The suppression of Bcl-XL expression by ASODN may offer both a therapeutic approach and an important theoretic foundation for gene therapy against esophageal carcinoma.

New insights into the interplay between long non-coding RNAs and RNA-binding proteins in cancer

With the development of proteomics and epigenetics,a large number of RNA-binding proteins(RBPs)have been discovered in recent years,and the inter-action between long non-coding RNAs(lncRNAs)and RBPs has also received increasing attention.It is extremely important to conduct in-depth research on the lncRNA-RBP interaction network,especially in the context of its role in the occurrence and development of cancer.Increasing evidence has demonstrated that lncRNA-RBP interactions play a vital role in cancer progression;there-fore,targeting these interactions could provide new insights for cancer drug discovery.In this review,we discussed how lncRNAs can interact with RBPs to regulate their localization,modification,stability,and activity and discussed the effects of RBPs on the stability,transport,transcription,and localization of lncRNAs.Moreover,we explored the regulation and influence of these inter-actions on lncRNAs,RBPs,and downstream pathways that are related to can-cer development,such as N6-methyladenosine(m6A)modification of lncRNAs.In addition,we discussed how the lncRNA-RBP interaction network regulates cancer cell phenotypes,such as proliferation,apoptosis,metastasis,drug resis-tance,immunity,tumor environment,and metabolism.Furthermore,we sum-marized the therapeutic strategies that target the lncRNA-RBP interaction net-work.Although these treatments are still in the experimental stage and various theories and processes are still being studied,we believe that these strategiesmay provide new ideas for cancer treatment.

Targeting PI3K/Akt signal transduction for cancer therapy

The phosphatidylinositol 3-kinase(PI3K)/Akt pathway plays a crucial role in various cellular processes and is aberrantly activated in cancers,contributing to the occurrenee and progression of tumors.Examining the upstream and downstream nodes of this pathway could allow full elucidation of its function.Based on accumulating evidenee,strategies targeting major components of the pathway might provide new in sights for can cer drug discovery.Researchers have explored the use of some in hibitors targeti ng this pathway to block survival pathways.However,because oncogenic PI3K pathway activation occurs through various mechanisms,the clinical efficacies of these inhibitors are limited.Moreover,pathway activation is accompanied by the development of therapeutic resista nee.Therefore,strategies involvi ng pathway in hibitors and other can cer treatments in combinati on might solve the therapeutic dilemma.In this review,we discuss the roles of the PI3K/Akt pathway in various cancer phenotypes,review the current statuses of different PI3K/Akt in hibitors,and in troduce combi nation therapies con sisti ng of signaling in hibitors and conven tional cancer therapies.The information presented herein suggests that cascading inhibitors of the PI3K/Akt signaling pathway,either alone or in combi nation with other therapies,are the most effective treatment strategy for can cer.