The expression of core fucosylated E-cadherin in cancer cells and lung cancer patients: prognostic implications

It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E- cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since α-1,6 Fucosyltransferase (α-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by α-1,6 FucT targeted RNAi and transfecting α-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E- cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after α-1,6 FucT over expression. Our data indicated that α-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asym- metry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.

Clinical significance of matrix metalloproteinase-9 expression in esophageal squamous cell carcinoma

AIM: To evaluate the expression of matrix metalloproteinase9 (MMP-9) and its clinical significance in esophageal squamous cell carcinoma (ESCC).METHODS: The expression of MMP-9 in 208 cases of ESCC was detected by immunohistochemistry (IHC) and its clinical significance in ESCC especially the relationship with the clinicopathological parameters was analyzed.RESULTS: The percentage of positive cases for MMP-9detected by IHC was 49.0%. MMP-9 was mainly expressed in the cytoplasm of cancer cells especially in the invasive front. Only weak expression was detected in the stromal cells and no expression in non-cancerous mucosa. The expression of MMP-9 was positively correlated with poorer differentiation (P = 0.001＜0.01), existence of vessel permeation (P = 0.027＜0.05) and lymph node metastasis (P = 0.027＜0.05).CONCLJSION: The expression of MMP-9 correlates with the cancer cell differentiation, vessel permeation and lymph node metastasis. It may be a novel biomarker for the diagnosis and treatment of ESCC.

Expression of MRP14 gene is frequently down-regulated in Chinese human esophageal cancer

Migration inhibitory factor-related protein 14 (MRP 14) is one of calcium-binding proteins,referred as S 100A9. The heterodimeric molecule formed by MRP 14 with its partner MRP8 (S 100A8) is the major fatty acid carrier in neutrophils.The MRP8/14 complex has been also implicated in the intracellular transport of arachidonic acid and its precursors in keratinocytes. We show here the involvement of MRP14 in human esophageal cancer. In an initial study,mRNA differential display - reverse transcription polymerase chain reaction (DD-PCR) was performed with two esophageal carcinomas,one esophageal adenocarcinoma and matched normal adjacent mucosa. DD-PCR with the arbitrary primer OPA3 showed that one cDNA band was highly expressed in normal tissues,but disappeared or substantially decreased in tumor counterparts. It was later identified to be the 3'-end of migration inhibitory factor-related protein 14 (MRP14).Northern blotting,RT-PCR and Western blotting corroborated the down-regulation of MRP14 in 58/64 squamous cell carcinomas and 2/2 adenocarcinomas as compared with adjacent normal epithelia of the esophagus. MRP14 was undetectable in 3/3 esophageal-carcinoma cell lines. Immunochemistry demonstrated that expression of MRP14 was restricted to normal esophageal epithelia. No mutation was found in the genomic DNA of the MRP14 gene by PCR and directed DNA sequencing. Our finding suggested that the reduction of MRP14 expression is a frequent event in Chinese human esophageal cancer.

Expression of e-cadherin and β-catenin in human esophageal squamous cell carcinoma: relationships with prognosis

AIM: To elucidate the expression of E-cadherin and β-catenincorrelating with its clinical outcome in patients withesophageal squamous cell carcinoma (ESCC), by analyzingtheir interrelationship with clinicopathological variables andtheir effects on progress and prognosis.METHODS: Expression of E-cadherin and β-catenin wasdetermined by SP immunohistochemical technique inpatients with ESCC consecutively, their correlation withclinical characteristics was evaluated and analyzed bymultivariate analysis.RESULTS: The rate of expression of E-cadherin decreasedto 66.03 % (70/106) in ESCC and the protein level wasnegative correlated with histologic grade, tumor size, clinicalstaging, lymph node metastasis and venous invasion.Whereas the expression rate of β-catenin was reduced to69.8 % (74/106) and the level of protein expressioncorrelated only with histologic grade. There obviously existedinverse correlation between level of E-cadherin protein andsurvival, especially in .stage I, IIa, IIb (P=0.0033), Patientswith low-expressing tumors for β-catenin and non-expressingtumors for E-cadherin/β-catenin had lower survival periodthan those with normal-expressing ones (P=0.0501 andP=0.0080, respectively). Patients with diminished expressionof E-cadherin as grade Ⅱ or Ⅲ had shorter survival periodthan those with normally expressing and grade Ⅰ, nosignificance existed between grade I and grade Ⅱ or Ⅲwith respect to different status of E-cadherin expression.Furthermore, Correlation analysis showed level of E-cadherincorrelated with that of β-catenin (P=0.005). Cox proportionalhazards model analysis suggested downregulation of E-cadherin was an important factor indicating poor prognosis.CONCLUSION: As a probable independent prognosticfactor, it correlates with overall and disease free survivalperiod, expression of E-cadherin but not β-catenin maypredict prognosis in patients with ESCC.

Genetic susceptibility and environmental factors of esophageal cancer in Xi'an

AIM: To analyse the role of genetic susceptibility and environmental factors in the process of esophageal cancer (EC) formation in Xi'an, China. METHODS: A hospital based case-control study, combined with molecular epidemiological method, was carded out. A total of 127 EC cases and 101 controls were interviewed with questionnaires containing demographic items, habit of tobacco smoking, alcohol drinking, and family history of EC. Polymorphism of CYPIA1 and GSTM1 of 127 EC cases and 101 controls were detected by PCR method. The interactions between genetic susceptibility and environmental factors were also discussed. RESULTS: Tobacco smoking, alcohol drinking and a family history of EC were risk factors for EC with an OR of 2.04 (95% CI 1.15-3.60), 3.45(95% CI 1.74-6.91), 3.14 (95% CI 1.28-7.94), respectively. Individuals carrying CYP1A1 Val/Val genotype compared to those with CYP1A1 Ile/Ile genotype had an increased risk for EC (OR 3.35, 95% CI 1.49-7.61). GSTM1 deletion genotype was a risk factor for EC (OR1.81, 95% CI 1.03-3.18). Gene-environment interaction analysis showed that CYPIA1 Val/Val genotype, GSTM1 deletion genotype had synergetic interactions with tobacco smoking, alcohol drinking and family history of EC. CONCLUSION: Tobacco smoking, alcohol drinking and a family history of EC are risk factors for EC. CYP1A1 Val/Val and GSTM1 deletion genotypes are genetic susceptibility biomarkers for EC. There are synergic interactions between genetic susceptibility and environmental factors.

Long-term effect on carcinoma of esophagus of distal subtotal gastrectomy

AIM:To investigate the surgical treatment and long-term survival for patients with carcinoma of esophagus after distal subtotal gastrectomy.METHODS: Resections of the tumor through left thoracotomy were performed in 85 patients with esophageal carcinoma following distal subtotal gastrectomy.The procedure involved preserving the left short gastric artery and transporting the residual stomach, the spleen and tail of the pancreas into the left thoracic cavity, and using the residual stomach to reconstruct the alimentary tract.RESULTS: The resectable rate was 91.8%, complication rate 10.3%, and no death occurred in the postoperative period. The 1-,3-,5-,and 10-year survival rates were 85.7%, 50.7%, 30.6% and 18.8%, respectively.CONCLUSION:Surgical resection is the optimal management method for the patients with esophageal carcinoma after distal subtotal gastrectomy. The reconstruction of digestive tract using anastomosis of the esophagus and the residual stomach is not only simple but also can achieve a better curative effect, promoting the digestive function and improving the quality of life.

Long-term outcome of esophageal myotomy for achalasia

AIM:Modified Heller's myotomy is still the first choice for achalasia and the assessment of surgical outcomes is usually made based on the subjective sensation of patients.This study was to objectively assess the long-term outcomes of esophageal myotomy for achalasia using esophageal manometry, 24-hour pH monitoring,esophageal scintigraphy and fiberoptic esophagoscopy.METHODS:From February 1979 to October 2000, 176 patients with achalasia underwent modified Heller's myotomy, including esophageal myotomy alone in 146 patients, myotomy in combination with Gallone or Dor antirefiux procedure in 22 and 8 patients, respectively. Clinical score,pressure of the lower esophageal sphincter (LES),esophageal clearance rate and gastroesophageal reflux were determined before and i to 22 years after surgery.RESULTS: After a median follow-up of 14 years, 84.5% of patients had a good or excellent relief of symptoms,and clinical scores as well as resting pressures of the esophageal body and LES were reduced compared with preoperative values (P<0.001).However,there was no significant difference in DeMeester score between pre-and postoperative patients(P=0.51).Esophageal transit was improved in postoperative patients, but still slower than that in normal controls. The incidence of gastroesophageal reflux in patients who underwent esophageal myotomy alone was 63.6% compared to 27.3% in those who underwent myotomy and antirefiux procedure (P=-0.087). Three (1.7%) patients were complicated with esophageal cancer after surgery.CONCLUSION: Esophageal myotomy for achalasia can reduce the resting pressures of the esophageal body and LES and improve esophageal transit and dysphagia. Myotomy in combination with antireflux procedure can prevent gastroesophageal reflux to a certain extent,but further randomized studies should be carried out to demonstrate its efficacy.

Long-term effects of proglumide on resection of cardiac adenocarcinoma

AIM: Patients with advanced stage cardiac adenocarcinoma have a very poor prognosis. Surgery is the first choice of treatment for this kind of patients. Peptide hormone gastrin is a recognized growth factor for gastric cancer, and gastrin receptor antagonist proglumide can block the effects of gastrin. The aim of this study was to investigate the actions of proglumide as an adjuvant treatment to improve the postoperative longterm survival rate of patients with cardiac adenocarcinoma. METHODS: We performed a randomized, controlled study of gastrin receptor antagonist proglumide in 301 patients with cardiac adenocarcinoma after proximal subtotal gastrectomy.The oral dose of 0.4 g proglumide thrice daily preprandially was maintained for more than 5 years in 153 cases (proglumidetreatment group). In the control group, 148 patients underwent operation only. In clinicopathologic features, there was no significant difference between the two groups (P＞0.05). Allpatients were followed up during their lifetime, and the survival rates were analyzed combined with clinicopathologic factors by SPSS 11.5 statistical software.TESULTS: The 1, 3, 5 and 10-year survival rate of the patients was 88.4%, 48.8% , 22.6% and 13.4% , respectively. The1, 3, 5 and 10-year survival rate of the proglumide treatment group was 90.2% , 49.7% , 26.8% and 17.6% compared to 86.5% , 48.0% , 18.2% and 8.9% of the control group. There was a significant difference between the two groups (P = 0.0460). The patients in proglumide treatment group had no obvious side effects after administration of the drug, and no definite hepatic and renal function damage was found. According to single factor log-rank analysis, the long-term survival rate was correlated with the primary tumor position (P = 0.0205), length of the tumor (P = 0.0000), property of the operation (P= 0.0000), histopathologic grading(P = 0.0003), infiltrating degree of the tumor (P = 0.0000),influence of lymph node metastasis (P = 0.0000),clinicopathologic staging (P = 0.0000) and administration of proglumide (P = 0.0460). Cox regression analysis demonstrated the infiltrating degree of tumor (P = 0.000),influence of lymph node metastasis (P = 0.039) and the clinicopathologic staging (P = 0.003) were independent prognostic factors. Administration of proglumide (P = 0.081), length of the tumor (P = 0.304), radical status of the resection (P = 0.224) and histopathologic types (P = 0.072) were not the independent prognostic factors. CONCLUSION: Proglumide is convenient to use with no obvious toxic side effects, and prolonged postoperative administration of proglumide as a postoperative adjuvant treatment can increase the survival rate of patients after resection of cardiac adenocarcinoma. Proglumide may provide a new effective approach of endocrinotherapy for patients with gastric cardiac cancer.

Surgical management of esophageal strictures after caustic bums:A 30 years of experience

AIM: To analyze a 30-year historical series of patients treated in our hospital, who ingested corrosive substances, and to assess the effectiveness of surgical therapy administered in patients with strictures after caustic injury in esophagus during this period.METHODS: A total of 79 cases of caustic burns in esophagus were treated in Tangdu Hospital from 1971 to 2001. Their clinical and pathological data were reviewed, and collected from the medical records of patients and interviews with them.RESULTS: More men (n = 61) than women (n = 18) ingested caustic substances with a sex ratio of 3.4:1 during the30-year period. The caustic materials were liquid lye and acids (54 cases and 25 cases, respectively). Sixty-eight patients were given esophageal replacement in more than three months after caustic injury with no postoperative death, of which 17 cases developed postoperative complications making a complication rate of 25%. The most common one was cervical anastomotic leakage. All patients had improvement in swallowing afterwards. CONCLUSION: The presence and severity of injuries are correlated with the amount of caustic substances ingested. Surgical treatment is a good option in patients with severe strictures, and colonic interposition might be the best surgical process. The most important factors to guarantee a successful outcome for surgery are good vascular supply and absence of tension in the anastomosis.

NON-INVASIVE IMAGING OF CORONARY ARTERY WITH 16-SLICE SPIRAL COMPUTED TOMOGRAPHY

To evaluate the value of 16-slice spiral CT in the demonstration of coronary artery and in the diagnose of coronary artery stenosis. Methods Plain and enhanced CT scans were performed with a 16-slice CT scanner (Sensation 16, Siemens, Germany) in 230 patients with suspected coronary heart disease (CHD). Parameters of the plain scan were: 120 kV, 133 mA, slice col-limation 16 mm×1.5 mm, rotation time 0.42 seconds, increment 1.5 mm, and slice width 3 mm. Parameters of the enhanced scan were: 120 kV, 500 mA, slice collimation 16 mm×0.75 mm, rotation time 0.42 seconds, increment 0.5 mm, and slice width 1 mm. Enhanced CT scan was performed with a rapid intravenous injection of 100 mL iothalamate meglumine (Ultravist) (370 mgI/mL) or Omnipaque (350 mgI/mL) and 30 mL 0.9% NaCl chaser bolus at a flow rate of 3.5 mL/s. Calcium scoring with plain scan images and two and three dimensional reconstruction with enhanced scan images were made in all cases, among which 30 cases underwent conventional coronary angiography. Demonstration of coronary arteries and their stenosis were evaluated and the factors that might influence the image quality were analyzed. Results Coronary calcium scores were calculated and coronary artery was demonstrated in our study. In the evaluationof image quality with volume rendering technique (VRT) images, 78.3% of the images were of the first class, 12.2% the sec-ond class, and 9.6% the third class. Multi-planar reconstruction (MPR) and maximal intensity projection (MIP) were better than VRT in the demonstration of small branches. The image quality was related to the heart rate, with or without arrhythmia, and breath-hold ability of patients. Comparative study of the stenosis of coronary arteries in 30 cases showed that the sensi-tivity and specificity of 16-slice coronary CT angiography (CTA) to diagnose significant stenosis were 95.8% and 94.8% resp-ectively. Conclusion As a non-invasive and quick method, 16-slice coronary CTA is sensitive and specific to diagnose the stenosis of coronary arteries and can be used as a screening method in the diagnosis of CHD.

Immunocytochemical detection of HoxD9 and Pbx1 homeodomain protein expression in Chinese esophageal squamous cell carcinomas

AIM: To evaluate the expression pattern of two novel oncofetal antigens, the HoxD9 and Pbx1 homeoproteins in esophageal squamous cell carcinomas (ESCCs) to determine what role they would play in the carcinogenesis of ESCC.METHODS: We obtained tissue samples of ESCC from 56 patients who underwent esophagectomy but not preoperative chemotherapy or radiotherapy. The diagnosis of ESCC was established and confirmed by staff pathologists. We used a highly sensitive, indirect,immunocytochemical method to detect HoxD9 and PbX1 proteins. We qualitatively and quantitively evaluated cells that exhibited and staining using a light microscope.RESULTS: In all observed carcinoma tissue samples, more than 60% of neoplastic cells stained lightly or strongly for HoxD9, and more than 50% of neoplastic cells stained lightly or strongly for Pbx1.CONCLUSION: Our data suggest that HoxD9 and Pbx1 are inappropriately expressed in most human esophageal squamous cell carcinoma. Understanding the role of Hox genes in esophageal epithelial cell carcinogenesis may not only augment early detection but also offer new avenues for treatment of this disease.

Synthesis of ribozyme against vascular endothelial growth factor_(165) and its biological activity in vitro

AIM: To investigate the designation, synthesis and biological activity of against vascular endothelial growth factor165 (VEGF165) ribozyme.METHODS: The ribozyme against VEGF165 was designed with computer. The transcriptional vector was constructed which included the anti-VEGF165 ribozyme and 5', 3' selfsplicing ribozymes. The hammerhead ribozyme and substrate VEGF165 mRNA were synthesized through transcription in vitro.The cleavage activity of the ribozyme on target RNA was observed in a cell-free system.PESULTS: The anti-VEGF165 ribozyme was released properly from the transcription of pGEMRz212 cleaved by 5' and 3' self-splicing ribozymes which retained its catalytic activity,and the cleavage efficiency of ribozyme reached 90.7%.CONCLUSION: The anti-VEGF165 ribozyme designed with computer can cleave VEGF165 mRNA effectively.

Mitochondrial DNA sequence analysis of two mouse hepatocaranoma cell lines

AIM: To study genetic difference of mitochondrial DNA (mtDNA)between two hepatocarcinoma cell lines (Hca-F and Hca-P)with diverse metastatic characteristics and the relationship between mtDNA changes in cancer cells and their oncogenic phenotype.METHODS: Mitochondrial DNA D-loop, tRNAMet+Glu+Ile and ND3gene fragments from the hepatocarcinoma cell lines with 1100, 1126 and 534 bp in length respectively were analysed by PCR amplification and restriction fragment length polymorphism techniques. The D-loop 3' end sequence of the hepatocarcinoma cell lines was determined by sequencing.RESULTS: No amplification fragment length polymorphism and restriction fragment length polymorphism were observed in tRNAMet+Glu+Ile,ND3 and D-loop of mitochondrial DNA of the hepatocarcinoma cells. Sequence differences between Hca-F and Hca-P were found in mtDNA D-loop.CONCLUSION: Deletion mutations of mitochondrial DNA restriction fragment may not play a significant role in carcinogenesis. Genetic difference of mtDNA D-loop between Hca-F and Hca-P, which may reflect the environmental and genetic influences during tumor progression, could be linked to their tumorigenic phenotypes.

Skipping Metastasis to Mediastinal Lymph Nodes in Non-small Cell Lung Cancer: A Clinical Study on the Reasonable Extent of Dissection

Objective To elucidate the characteristics and metastastic pattern of skipping mediastinal lymph node metastasis (skipping N2) in non-small cell lung cancer (NSCLC), and investigate reasonable extent of lymph node dissection. Methods From 1990 to 1998, lobectomy combined with systematic mediastinal lymph node dissection was performed in 109 patients with NSCLC. A retrospective study was carried out to elucidate the characteristics of skipping N2 disease and to compare the difference between skipping N2 and non-skipping N2 diseases. Results Twenty-one patients (19%) had skipping N2 diseases. Of the skipping N2 group, 18 cases (86%) were adenocarcinoma. Skipping N2 disease was more common in T1 and T2 group than that in T3 and T4 group (P<0.01). All skipping N2 diseases only involved one nodal station, and most of them were regional mediastinal nodal metastasis. Skipping N2 from upper lobe tumors mainly involved superior tracheobronchial or subaortic lymph nodes, and skipping N2 from lower lobe tumors involved subcarinal lymph nodes. Conclusion Skipping N2 disease presents certain clinical characteristics and metastastic pattern, and mediastinal nodal dissection might be modified according to the pattern.

Carinal Resection and Reconstruction for Primary Carinal Tumors—Report of 9 Cases

From Oct.1989 to Cec.1998,9 patients aged 12-67 years underwent carinal resection and reconstruction through right or left intercostal space thoraotomy.No important postoperative complications occurred and there were no perioperative deaths.Leiomyoma,neurofibroma,carcioid and squamous cell carcinoma was found in one patient respectively,adenocarcioma in 2 patients,adenoid cystic carcinoma in 3 patients.The actuarial 3-year survival rate for patients with malignant tumors was 42.9%.In order to diagnose early and correctly,bronchoscopy and computed tomography should be used.The end-to-end anastomosis of trachea with bilateral bronchi is the optimal choice among the modes of carinal reconstruction.Some principles of surgery and perioperative care are discussed.

Human γδT-cell subsets and their involvement in tumor mmunity

γδT cells are a conserved population of innate lymphocytes with diverse structural and functional heterogeneity that participate in various immune responses during tumor progression. γδT cells perform potent immunosurveillance by exerting direct cytotoxicity, strong cytokine production and indirect antitumor immune responses. However, certain γδT-cell subsets also contribute to tumor progression by facilitating cancer-related inflammation and immunosuppression. Here, we review recent observations regarding the antitumor and protumor roles of major structural and functional subsets of human γδT cells, describing how these subsets are activated and polarized, and how these events relate to subsequent function in tumor immunity. These studies provide insights into the manipulation of γδT-cell function to facilitate more targeted approaches for tumor therapy.