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Jian Huang,1,&ast; Li Li,2,&ast; Fu-Chen Liu,1 Bi-Bo Tan,3 Yun Yang,1 Bei-Ge Jiang,1 Ze-Ya Pan1 1Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China; 2Department of Nephrology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China; 3Department of Ultrasonic, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ze-Ya Pan; Bei-Ge Jiang, Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, No. 700, MoYu North Road, Jiading, Shanghai, People’s Republic of China, Tel +86-13391236437 ; +86-13764561303, Email hjluffy@126.com; jiang_beige@aliyun.comObjective: To investigate the survival and independent prognostic factors for single large hepatocellular carcinoma (SLHCC) after surgical resection.Methods: Patients with SLHCC who underwent radical resection from January 2013 to December 2017 were retrospectively analyzed. The Kaplan-Meier method was used to analyze the overall survival (OS) rate and recurrence-free survival (RFS) rates. Cox forward stepwise regression was performed to analyze the independent prognostic factors.Results: A total of 485 cases were included. The average age was 51.2± 11.2 years, 88.9% had a history of hepatitis B virus infection, and most patients had normal liver function. The average tumor diameter was 8.8± 3.0 cm. The 1-, 3-, and 5-year OS and RFS rates were 76.8%, 56.7%, and 45.7%, and 61.0%, 46.2%, and 34.7%, respectively. Multivariate analysis showed that liver cirrhosis (HR=1.456, P=0.004), total bilirubin (TB) ≥ 17.1 μmol/L (HR=1.437, P=0.011), glutamyl transferase (GGT) > 60 U/L (HR=1.438, P=0.020), lactate dehydrogenase (LDH) > 225 U/L (HR=1.442, P=0.007), blood loss ≥ 400 mL (HR=1.339, P=0.027), microvascular invasion (MVI) (HR=1.492, P=0.004), satellite lesions (HR=1.859, P< 0.0001) and Edmondson-Steiner grade III+IV (HR=1.740, P=0.018) were independent risk factors for reduced OS in SLHCC patients. Sex (HR=1.763, P=0.003), liver cirrhosis (HR=1.382, P=0.007), GGT > 60 U/L (HR=1.512, P=0.003), LDH > 225 U/L (HR=1.480, P=0.002), MVI (HR=1.545, P=0.001), and satellite lesions (HR=1.564, P=0.001) were independent risk factors for reduced RFS. OS and RFS nomograms were constructed using risk factors with C-index values of 0.692 (95% CI: 0.659– 0.724) and 0.659 (95% CI: 0.623– 0.693), respectively. The Hosmer-Leme test demonstrated the good fit of both nomograms.Conclusion: Surgical resection is the standard and effective treatment for SLHCC patients. Sex, liver cirrhosis, TB≥ 17.1 μmol/L, GGT> 60 U/L, LDH> 225 U/L, blood loss≥ 400 mL, MVI, Edmondson-Steiner grade III+IV, and satellite lesions were found to be independent prognostic factors in SLHCC patients following radical resection. The OS and RFS nomograms accurately predicted the prognosis of SLHCC patients.Keywords: SLHCC, cancer, hepatectomy, prognosis, risk factor

To compare the therapeutic efficacy and safety of percutaneous microwave ablation (MWA) with those of percutaneous radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC) adjacent to major vessels.From January 2010 to April 2011, 78 patients with a single nodule, no5 cm, adjacent to major vessels were enrolled in this study. Forty-four patients (forty-one men, three women; age range, 33-72 years) treated by MWA were compared with thirty-four patients (thirty-one men, three women; age range, 33-75 years) treated by RFA. Local tumor progression rate, overall survival rate, and disease-free survival rate were calculated using the Kaplan-Meier method, and differences between groups were estimated by log-rank test.No death related to treatment occurred in the two groups. The 1-, 2-, and 3-year local tumor progression rates were 6.8%, 11.4%, and 15.9%, respectively, in the microwave group versus 17.6%, 20.6%, and 20.6%, respectively in the radiofrequency group (P = 0.544). The rates of major complications associated with microwave and RFA were 2.3% (1/44) versus 0% (0/34; P = 0.376). The microwave group's 1-, 2-, and 3-year disease-free survival rates were 72.7%, 65.9%, and 51.8%, respectively, and those in the radiofrequency were 58.8%, 52.9%, and 47.1%, respectively (P = 0.471). The microwave group's 1-, 2-, and 3-year overall survival rates were 93.2%, 90.9%, and 83.6%, respectively, and those in the radiofrequency group were 91.2%, 88.2%, and 82.4%, respectively (P = 0.808) There was no significant difference in local tumor progression, complications related to treatment, and long-term results between the two modalities. The incidence of peritumoral structure damage on image scan was significantly higher in the microwave group than in the RFA group (P = 0.025).Both RFA and MWA are safe and effective techniques for HCC adjacent to major vessels and have the same clinical value.

The aim of the present study was to investigate the expression and clinical significance of oncofetal protein insulin-like growth factor (IGF) II mRNA-binding protein 3 (IMP3) in the differentiation of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). A total of 162 patients who were diagnosed with GEP-NEN, and who underwent surgical or endoscopic resection from January 2006 to March 2013, were enrolled in the study, including 85 cases of grade (G)1 neuroendocrine tumors, 40 cases of G2 neuroendocrine tumors, 28 cases of G3 neuroendocrine carcinomas and 9 cases of mixed stage adenoneuroendocrine carcinomas. The clinical and pathological data were recorded for analysis. The expression of IMP3, cluster of differentiation (CD)44, IGF1 receptor (IGF1R) and matrix metalloproteinase (MMP)2 was determined by immunohistochemistry. SPSS 13.0 software was used for data processing and analyses, and P

Objective: To explore the inhibitory effect of siRNA-Annexin A7 on growth, migration, and invasion of transplanted gastric cancer in nude mice. Methods: The siRNA sequence targeting to human Annexin A7 gene was designed, and based on that a pair of complementary oligonucleotides were synthesized, annealed, and cloned into plasmid pGenesil-1.1 to construct recombinant plasmid siRNA-Annexin A7. Transplanted gastric cancer model was established by injecting s.c. nude mice with human gastric cancer BGC823 cells, and siRNA-Annexin A7 was injected into the tumors formed. The nude mice were observed for clinical manifestation relying on the size and weight of transplanted tumors. The tumor tissue and angiogenesis were examined by pathologic sections. Flow cytometry was used to detect the changes of cell cycle. Western blot and qRT-PCR were used to analyze the expression of PCNA, P27, MMP-2, and TIMP-2. Results: Both the size and weight of transplanted tumors of nude mice injected with siRNA-Annexin A7 were less than those of control groups (P

In this study, the effects of hypoxia-inducible factor-1α (HIF-1α) on gastric carcinoma (GC) drug resistance through apoptosis-related genes are investigated. First, HIF-1α-specific siRNA was synthetized and transfected into drug-resistant GC cell line OCUM-2MD3/L-OHP. Then MTT assay was applied to test the inhibition rate of GC cells by 5-fluorouracil (5-FU) and oxaliplatin (L-OHP). After that, flow cytometry (FCM) was applied to measure apoptosis rate. qPCR and Western blot assay were employed to detect HIF-1α and apoptosis-related genes. Results showed that HIF-1α in OCUM-2MD3/L-OHP cells was higher than that in OCUM-2MD3 and gastric epithelial cells. After HIF-1α-siRNA transfection, inhibition rates of 5-FU and L-OHP to tumor cells increased significantly. FCM results showed that apoptosis rate of OCUM-2MD3/L-OHP cells increased significantly. After HIF-1α-siRNA transfection, survivin and Bcl-2 decreased, whereas Bax, caspase 3, and caspase 8 increased significantly. Results from this study seem to confirm that HIF-1α getting involved in GC drug resistance is possibly due to its regulation of some apoptosis-related genes. HIF-1α may be a potential target to reverse drug resistance of GC.

This study aimed to investigate the role of insulin-like growth factor II mRNA binding protein 3 (IMP3) in neuroendocrine tumor (NET). Mouse NET STC-1 cell line was chosen as the experimental model and three IMP3-targeting siRNAs and a non-specific scramble siRNA were transfected into STC-1 cells. The efficiency of IMP3 siRNA to knockdown IMP3 was evaluated by immunocytochemical staining. Cell proliferation was detected by MTT assay. Cell migration and invasion was analyzed with Transwell chamber assay. Protein expression was detected by Western blot analysis. We found that IMP3 silencing inhibited the proliferation of STC-1 cells potentially by downregulating the expression of cell proliferation associated proteins EGFR and Ki67. Furthermore, IMP3 silencing inhibited the migration and invasion of STC-1 cells potentially by downregulating the expression of metastasis associated proteins IGF1R, MMP2 and MMP9. In conclusion, this study provides the first evidence that IMP3 plays an oncogenic role in Net and is a promising therapeutic target for NET.

Approximately 40% to 50% of gastrointestinal stromal tumor (GIST) patients will have recurrence or metastases after resection of the primary lesion, and the most common affected sites will be liver and peritoneum. Imatinib has been considered as the first-line therapy of metastatic GIST. Surgery for metastases is proposed when possible. Furthermore, there are controversies concerning hepatic resection and systemic tyrosin kinase inhibitors (TKIs). The therapeutic conditions and long-term outcome of GIST patients with liver metastases in northern China remain unknown.The clinical, pathological, and follow-up data of 144 GIST patients, who had liver metastases between June 1996 and June 2014 from 3 tertiary cancer centers in northern China, were reviewed.Thirty-two cases (22.2%) had hepatectomy with 23 (23/32, 71.9%) R0 resections and 9 (9/32, 28.1%) R1/R2 resections, respectively. Twenty-three patients were given imatinib postoperatively. Furthermore, 98 (68.1%) patients were given TKIs only to control disease progression, and sunitinib was considered after imatinib failure in 12 patients. The 1-, 3- and 5-year survival rate was 82%, 51%, and 24%, with a median overall survival of 48 months for all patients. Patients who had hepatic resection combined with TKIs had a tendency of improved outcome, and the median survival time was 89 months. This was in contrast to patients who received TKIs only, in which median survival time was 53 months. Patients who received imatinib plus sunitinib had a tendency of longer survival time, compared with patients who received imatinib only (not reached vs 50 months).TKIs combined with hepatic resection had a role in improving the outcome of GIST patients with liver metastases.

Zinc finger protein 139 (ZNF139) gene is proved play an important role in gastric cancer. Aim of this study is to identify changes of proteins after ZNF139 gene was inhibited in gastric cancer cell line BGC823.siRNA-specific ZNF139 was synthesized and transfected into BGC823; 2-D fluorescence difference gel electrophoresis (2-D DIGE) and liquid chromatography-mass spectrometry (LC-MS) were applied to screen, identify differentially expressed proteins, and function of these proteins was analyzed; Western blot method was applied to verify the identified proteins.ZNF139 expression in siRNA transfected cancer cell BGC823 decreased significantly. Results of 2-D DIGE showed eight differential protein spots, of which seven were identified with LC-MS, including switches associated protein 70, far upstream element binding protein 1, heat shock protein 60, annexin A7, small ubiquitin-like modifier 1 activating enzyme, chaperonin-containing tail-less complex protein 1 and annexin A2. These proteins were found to be associated with proliferation, apoptosis, invasion, metastasis, adhesion of gastric cancer cells with bioinformatic analysis. Western blot analysis confirmed that expressions of these proteins in BGC823 were consistent with the proteomic results.ZNF139 gene may influence the biological behavior of gastric cancer cells in many ways by regulating multiple proteins.

Objective: To investigate the expression and clinical significance of annexin A7 in the differentiation and lymphatic metastasis of gastric cancer (GC). Methods: The clinical and pathological data were recorded for analysis. Immunohistochemical staining and Western blot were performed to analyze the expression of ANXA 7 in primary GC tissues. Logistic regression analyses were conducted to evaluate the associations between annexin A7 expression levels and differentiations of GC. Analyses of the ROC were conducted to determine the cut-off value of the ratio of pixel density of annexin A7 for predicting lymphatic metastasis of GC. Results: A total of 162 GC patients were enrolled in this study, and expression rate of annexin A7 was 65.4% in GC. The survival rate of patients with positive expression of annexin A7 was lower than that in patients with negative expression (P=0.000). The results of COX regression showed that the positive expression of annexin A7, submucosal confinement and pathological stage of GC were associated with poor clinical outcomes. The ratio of pixel density value of primary GC tissues with PN 1-3 lymphatic spread was significantly higher than those in tissues with PN 0 lymphatic spread (0.56±0.09 vs. 0.42±0.07, P < 0.05). ROC analysis showed a high area under the curve for the ratio of pixel density value of annexin A7 in primary GC tissues. At a cut-off level of > 0.505, the ratio of pixel density value of annexin A7 exhibited 76.7% sensitivity and 88.3% specificity for detecting lymphatic metastasis of GC. Conclusion: High annexin A7 expression is associated with poor differentiation in GC patients, and it may be a predictor for lymphatic metastasis of GC.

Zinc finger proteins (ZNFs) are a class of proteins widely distributed in the human genome, which have been found to play a role in the regulation of gene transcription and the occurrence and development of gastric cancer (GC). ZNF139 was found to be associated with GC in our previous experiments. The present study aimed to analyse the differences in ZNF139 protein expression in SGC7901 GC cells and in situ grafted GC tumors in nude mice prior to and following RNA interference inhibition, and to investigate the mechanisms underlying ZNF139 involvement in the occurrence, development and chemosensitivity of GC. A ZNF139-targeted small interfering (si)RNA plasmid was constructed and transfected into the cancer cells and in situ grafted tumors. The MTT assay was used to investigate the alterations in chemosensitivity prior to and following transfection of siRNA-ZNF139. The two-dimensional difference gel electrophoresis and liquid chromatography-mass spectrometry techniques were used to identify the different protein points prior to and following siRNA-ZNF139 transfection. Western blot analysis was performed to confirm the identified proteins. In the siRNA-ZNF139 group, the growth of the cancer cells and in situ grafted tumors significantly decreased. However, the post-interference chemosensitivity to 5-fluorouracil, cisplatin and mitomycin C significantly increased. In the in vivo and in vitro experiments, the expression of pyridoxal kinase (PDXK) was upregulated, whereas the expression levels of annexin A2 (ANXA2) and fascin were downregulated following transfection. Western blot analysis confirmed the results for PDXK, ANXA2 and fascin by proteomics. Therefore, ZNF139 may participate in the occurrence, development and chemosensitivity of GC by promoting the expression of ANXA2 and fascin, while inhibiting the expression of PDXK.

The purpose of this study was to investigate the efficacy and mechanism of oxaliplatin in combination with capecitabine (XELOX) regimen as neoadjuvant chemotherapy in the treatment of patients with advanced gastric cancer.Eighty-five patients with advanced gastric cancer (stage IIB and IIIC) were randomly divided into two groups: neoadjuvant chemotherapy group (40 cases) and surgery alone group (45 cases). In the neoadjuvant chemotherapy group, patients received oral administration of Xeloda 1000 mg/m(2) twice a day on days 1-14 and intravenous infusion of oxaliplatin 130 mg/m(2) on day 1 (XELOX regimen). The regimen was repeated every 21 days. In the surgery alone group, patients directly received radical resection of gastric cancer. The R0 resection rate, overall survival and disease free survival (DFS) were observed in all cases. The cycles and apoptosis rate of the gastric cancer cells were detected by flow cytometry. The expression of proliferating cell nuclear antigen (PCNA), p21, p53 and survivin was detected by Western blot.In the neoadjuvant chemotherapy group, the total effective rate was 32.5% (13/40), and the tumor control rate was 90% (36/40), with few side effects. Compared with the surgery alone group, R0 resection rate was significantly higher in the neoadjuvant chemotherapy group (P0.05). The survival analysis indicated that both the overall survival and DFS were longer in the neoadjuvant chemotherapy group in comparison with those in the surgery alone group, but no significant differences were found (P0.05). In the neoadjuvant chemotherapy group, both the apoptosis rate and the ratio of cells in stage G0 and G1 were significantly higher than those in the surgery alone group (P0.05). The expression of PCNA and survivin was lower in the neoadjuvant chemotherapy group, while the expression of p21 and p53 was higher.XELOX regimen as neoadjuvant chemotherapy in the treatment of patients with advanced gastric cancer can effectively improve the R0 resection rate and prolong the survival time of the patients. Its mechanism is probably that the neoadjuvant chemotherapy can markedly enhance apoptosis in gastric cancer cells and inhibit their proliferation.

Different differentiations of cancer have resulted in its unique biological characteristics. We screen and appraise differentially expressed proteins in different differentiated gastric adenocarcinoma with comparative proteomics technology in order to find regulatory factors of tumor differentiation related and finally reach the purpose of tumor differentiation reversal.With two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) and liquid chromatography in conjunction with tandem mass spectrometry (LC–MS/MS), the differentially expressed proteins from 8 patients with different differentiated gastric adenocarcinoma were identified and some factors identified were verified with application of QPCR and Western blot techniques.Significant differences in 35 protein spots were found and 48 kinds of proteins were identified. Other than structural proteins and non-specific protein, six possible proteins associated with tumor differentiation were determined - the serine protease inhibitor B1 (serine protease inhibitor, clade B, member 1, SERPINB1), calcium-phospholipid binding protein III (annexin A3), transcription factor Nm23-H1, adenine phosphoribosyl-transferase enzyme APRT (Adenine Phosphoribosyltransferase in APO and AMP), glutathione S-transferase P1-1 (GST-π-1), antimicrobial peptides Dermcidin-lL. The identified SERPINB1, annexin A3, Nm23-H1 and APRT were verified, confirming the expression of these factors was in line with proteomics identification.Protein expression in different differentiated gastric adenocarcinoma was varied.

We report on a case of a 65-year-old Chinese male with locally advanced gastric adenocarcinoma achieving pathological complete response after neoadjuvant chemotherapy with capecitabine and oxaliplatin (XELOX) regimen. He underwent esophagogastroduodenoscopy, which revealed a 6x5cm gastric ulcer. Biopsy of gastric ulcer revealed adenocarcinoma. Further workups with abdominal enhancement computed tomography (CT) staged his cancer as T4N2M0. He received 2 cycles of neoadjuvant chemotherapy with XELOX without severe toxicity. Afterwards, he underwent curative surgery consisting of total gastrectomy with extended D2 lymph node dissections and a Roux-en-Y esophagojejunostomy. On microscopic examination, no tumor cells were detected in the ulcer scar of the resected stomach and in the regional lymph nodes. The benefit of XELOX regimen as neoadjuvant chemotherapy in gastric cancer is worth further investigation.

The purpose of comprehensive treatment for early gastric cancer (EGC) is curing tumor, prevention of recurrence or metastasis. The aim of the present study was to analyze the clinical pathological characteristics of EGC, and to find out factors which influence lymph node metastasis.Records of 417 patients with EGC who underwent surgery from January 1996 to December 2006 were collected. The information including general characteristics, tumor relevant factors, surgical complications, clinical manifestations and pathological features, were evaluated.EGC accounted for 6.03% of total gastric cancer (GC) cases. In EGC subjects, mucosal cancer and sub-mucosal cancer accounted for 55.2% and 44.8%, respectively; 11.5% (48/417) of patients were found with positive lymph nodes metastasis, the incidence of lymph node metastasis was 5.64% (168/2979); 6 cases were found with liver metastasis; 96.64% of patients undertook radical surgical treatment; 5 cases with positive upper incisal margin (1.2%). Logistic regression analysis showed that multiple original tumors, lesions of over 2cm, tumor invasion to the submucosa, poor differentiation, and vascular tumor thrombus, were independent risk factors for lymph node metastasis in EGC.The risk factors of lymph node metastasis should be noticed and evaluated in EGC treatment.

Aims and background Cyclooxygenase-2 (COX-2) is involved in the progression of gastric cancer; however, the role of COX-2 in multidrug resistance (MDR) is still unclear. This study aimed to elucidate the relationship between COX-2 and MDR so as to show the heterogeneity of gastric primary tumors and regional lymph node metastases. Methods Between 2008 and 2009, 56 primary tumor samples and paired metastatic lymph node tissues from gastric cancer patients confirmed by surgery and pathological examination in our hospital were collected. The expression levels of COX-2 and MDR-associated factors such as P-glycoprotein (P-gp), glutathione S-transferase pi (GST-π) and topoisomerase II alpha (Topo-II-α) were determined by immunohistochemical staining. Tumor cells from these tissues were cultured and the cell chemosensitivities for 11 chemotherapeutic agents were measured by sulforhodamine B assay. Results The expression levels of COX-2, P-gp and GST-π were significantly higher in metastatic lymph node tissues than in primary tumors, while the expression level of Topo-II-α was lower in metastatic lymph node tissues than in primary tumors (all P Conclusion The expression of COX-2 and MDR-associated factors as well as cell chemosensitivities are different in primary tumors and regional lymph node metastases of gastric cancer, and this may be an indication of their heterogeneity.

Integrase interactor 1 (INI1), which encodes a component of the ATP-dependent chromatin remodeling hSWI-SNF complex, has been identified as a tumor suppressor in many tumors. Nonetheless, the role of INI1 in gastric tumor progression is not known exactly. The aim of this research was to investigate the effect of INI1 in the carcinogenesis and progression of gastric cancer.Gastric tumor tissues with different differentiation levels from clinical gastric carcinoma samples and adjacent control normal tissues were taken. Expression levels of INI1 were detected by quantitative reverse transcriptation-polymerase chain reaction (RT-PCR) and Western blotting. Gastric cancer cell line SGC7901 was transfected with INI1 eukaryotic expressing vector INI1-GFP. Cell proliferation activities were assessed by MTT; cell count and cell cycle were detected by flow cytometry (FCM); cell apoptosis were measured by TUNEL and FCM; cell migration and invasiveness were evaluated by wound healing and transwell assays. Expression levels of INI1 and proliferation-related genes including p16, p21, cyclin D1 and cyclin A, apoptosis genes p53, B-cell non-Hodgkin lymphoma-2 (Bcl-2), Bcl-2-associated x protein (Bax) and caspase-3, and invasion-related genes including intercellular adhesion molecule 1 (ICAM1), matrix metalloproteinase 2 (MMP2), MMP9 and tissue inhibitor of matrix metalloproteinase 1 (TIMP1), were detected by quantitative RT-PCR and Western blotting.INI1 expression levels were lower in gastric carcinoma compared with adjacent control normal tissues. Overexpression of INI1 in SGC7901 cells inhibited its proliferation and invasiveness, but increased anoikis and G(0)/G(1) cell number. INI1-GFP transfection upregulated expression of INI1 and proliferation related genes p16 and p21, apoptosis genes p53 and Bax, and invasion-related genes TIMP1; cyclin D1, cyclin A, Bcl2, ICAM1, MMP2 and MMP9 were downregulated, and there was no significant change in caspase 3 levels.INI1 plays a key role in gastric carcinogenesis by affecting proliferation, apoptosis and invasion.

To explore the effects of antisense oligodeoxynucleotides (ASODN) on proliferation and apoptosis in gastric cancer cell line BGC-823 cells and the molecular mechanisms induced by ASODN.survivin ASODN-1, survivin ASODN-2 and survivin ASODN-3 were transfected into BGC-823 cells by Lipofectamine(TM) 2000 transfection reagent. The growth activity of BGC-823 cells was detected by MTT assay. Apoptosis index (AI), proliferation index (PI), cell cycle and expressions of survivin, VEGF and Smac/DIABLO proteins were detected by flow cytometry (FCM). The changes of survivin mRNA, VEGF mRNA and Smac/DIABLO mRNA were detected by RT-PCR.The expression of survivin was down-regulated by the three ASODN sequences, especially the ASODN-2 was best. At 48 hours after transfection with 600 nmol/L survivin ASODN-2, the cells in G(1)/G(0) phase were significantly increased [(72.25 ± 2.95)%], apoptotic index increased [(11.31 ± 0.38)%], proliferation index decreased [(27.77 ± 2.97)%], compared with those in the control group [(56.25 ± 0.75)%, (1.62 ± 0.36)%, (43.80 ± 0.80)%, all P0.05]. The survivin mRNA and protein levels (0.523 ± 0.091, 0.733 ± 0.009) were down-regulated compared with those in the control group (0.861 ± 0.047, 0.997 ± 0.233), VEGF (0.519 ± 0.076, 0.75 ± 0.006) were down-regulated compared with those in the control group (0.779 ± 0.059, 1.000 ± 0.01), while those of Smac/DIABLO(0.899 ± 0.113, 1.637 ± 0.023)were up-regulated compared with those in the control group (0.558 ± 0.041, 1.000 ± 0.049, all P0.05).Survivin ASODN can induce apoptosis and inhibit the proliferation of gastric cancer cell line BGC-823 cells. Those effects are induced through up-regulation of Smac/DIABLO and down-regulation of survivin and VEGF expression simultaneously.

Little is known about the expression and significance of the proteins in regional lymph node metastases (LNMs) of gastric carcinoma (GC). In present study we intend to evaluate the expression of COX-2 and Survivin in primary tumors (PT) and LNMs of GC, keeping track of the correlation between the clinicopathologic factors, the tumor angiogenesis, patients' survival and prognosis.Surgical specimens were obtained and paired from 65 patients with advanced GC. The gastric operational pieces have been examined with usual histological, histochemical and immunohistochemical staining. Then relationship and significance of these data were analyzed.Expression of COX-2 was higher in LNMs than that in PT p0.05 with positive correlativity of COX-2 between PT and LNMs p0.01 and positive correlativity also existed between COX-2 and Survivin in PT p0.01. The patients with strong expression of COX-2 had lower cumulative survival rate than those with weaker COX-2 expressed (p0.01). In LNMs, strong expression of COX-2 was an independent prognostic factor for GC in PT and LNMs while strong expression of Survivin was not that case.The expression of COX-2 in PT and LNMs explained for the heterogeneity of GC and it has a tight correlation with GC cell's apoptosis. Strong expression of COX-2 in LNMs was associated with poor prognosis for patients with GC.

To investigate the differentiation-related proteins in human gastric carcinoma cell lines by comparative proteomics.The holoproteins of human gastric carcinoma cell lines MKN28, SGC7901 and BGC823 were measured by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Some proteins identified by proteomics were tested by Western blot in the cell strains and tissues of gastric carcinoma.14 differential protein spots were found in the 3 gastric carcinoma cell lines, among them 8 spots were identified by MALDI-TOF-MS. These proteins were probably thioredoxin peroxidase, glyceraldehyde-3-phosphate dehydrogenase (GAPD), beta-tubulin polypeptide, hypothetical protein, zinc finger protein (ZNF) 139, protein-tyrosine kinase, calreticulin precursor, and tropomyosin, proteins related with biological behavior of gastric carcinoma cells such as signal transduction, cellular homeostasis, glycolysis, antioxidation action, multidrug resistance(MDR), etc. The expressions of those proteins in gastric cancer cells and tissues identified by Western blot were consistent with the results obtained by proteomics.Differential proteins are found in 3 human gastric carcinoma cell lines, mainly, proteins related with cell signaling, maintenance of homeostasis, glycolysis, metabolism of anti-cancer drug and anti-oxidative injury, etc.

To investigate the relationship of cyclooxygenase-2 (COX-2), p-glycoprotein(P-gp), glutathione S-transferase-pi (GST-pi), and topoisomerase II alpha (Topo II alpha) to chemosensitivities in gastrointestinal tract carcinomas.The tumor tissue samples were collected from 84 specimens of gastrointestinal carcinomas. The expressions of COX-2, P-gp, GST-pi, and Topo II alpha were determined immunohistochemically. The chemosenisitivity of each sample to 9 drugs were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.The positive rates of COX-2, P-gp, GST-pi and Topo II alpha were 48.8%, 76.2%, 78.6% and 66.7% respectively. The expression of COX-2 was correlated with the expression of P-gp and Topo II alpha significantly (r = 0.287, 0.256, both P0.05). In terms of relationships of four MDR-related factors expression to inhibition rate of tumor cells, the inhibition rates of PTX, eADM and OPT in COX-2 strong expression group were significantly lower than those in COX-2 weak expression group (t = 2.21, 3.11, 2.09; all P0.05). The inhibition rates of PTX, OXA and DDP in P-gp strong expression group were lower than those in weak group (t = 2.54, 2.47, 2.05; all P0.05). There were lower inhibition rates for 5-Fu in GST-pi strong expression group (t = 2.13, P0.05), and higher inhibition rates for VCR, PTX and eADM in TopoII alpha strong expression group (t = -2.29, -2.12, - 2.26, all P0.05).The overexpressions of MDR-related factors in gastrointestinal carcinomas were only associated with the chemosensitivity to some of the chemotherapeutic agents, but not all. MDR related factors may be not specific and accurate predictors for the clinical chemosensitivity.

To investigate the expression features of P-glycoprotein (P-gp), glutathione S transferase-pi (GST-pi) and inhibitor of apoptosis proteins like p53, survivin and bcl-2 in lymph node metastases of gastrointestinal carcinomas.The expression of P-gp, GST-pi, p53, survivin and bcl-2 were determined by using immunohistochemistry technique in surgical specimens of primary tumor (PT) and lymph node metastases (LNMs) from 54 gastrointestinal cancer patients with metastasis of lymph nodes. The expression difference of 5 multi-drug resistance (MDR)-related factors between LNMs and PT were compared.Significant difference was found in the expression of P-gp and GST-pi between the two groups (both P0.05), and expression of p53 and bcl-2 showed positive correlation between LNMs and PT (r = 0.7248, 0.5524; both P0.05), respectively. In LNMs, P-gp expression was positively correlated with GST-pi (r = 0.4062, P0.05) and survivin (r = 0.6169, P0.05), and also GST-pi expression was related positively with survivin (r = 0.4027, P0.05). Statistically positive correlations were noted between bcl-2 and P-gp (r = 0.3986, P0.05), bcl-2 and survivin (r = 0.2937, P0.05), as well as GST-pi and survivin (r = 0.4481, P0.01) in PT. Only a positive correlation between GST-pi and survivin expression was simultaneously shown in both LNMs and PT.There is significant heterogeneity of MDR-related factors expression in LNMs of gastrointestinal carcinomas. Effective adjuvant chemotherapy after operation should target on the metastatic loci of the disease.

P-glycoprotein (P-gp) mediated classical drug resistance and inhibition of the apoptotic pathway are the two mostly investigated mechanisms of multidrug resistance (MDR). Coexpression and interaction of MDR-related factors result in pleiotropic drug resistance in cancer cells. This study was to investigate the correlation of expressions of multiple MDR-related factors, such as P-gp, p53, Survivin or bcl-2, to chemosensitivitity in gastrointestinal carcinomas.Eighty-four tissue specimens of gastrointestinal carcinomas were analyzed. Expressions of P-gp, p53, Survivin and bcl-2 were determined by immunohistochemistry (IHC). Drug chemosensitivity of nine drugs to cancer cells were measured by MTT assay.The positive staining of P-gp, p53, Survivin and bcl-2 were detected in 96.4%, 64.3%, 89.3% and 60.7% of all specimens, respectively. The expression of P-gp and bcl-2 (r=0.5072, P0.05), and the expression of survivin and bcl-2 (r=0.3027, P0.05) were positively correlated. The inhibition rates of paclitaxel (PTX), oxaliplatin (OXA) or cisplatin (DDP) on cancer cells were significantly lower in the group with strong P-gp expression than that with weak P-gp expression (all P0.05). The strong expression of p53 was correlated with decreased inhibition rates of PTX and DDP on cancer cells (P0.05, P0.01). When the expression of Survivin was increased, the inhibition rates of vincristine (VCR) or DDP on cancer cells were reduced significantly (P0.05, P0.01), but the inhibitory effect of OXA was remarkably increased (P0.01). The inhibition rates of 5-fluorouracil (5-FU), VCR, epirubicin (EADM) and OXA on cancer cells were lower in the group with strong expression of bcl-2 than in that with weak expression of bcl-2 (P0.05).The expression of MDR-related factors in gastrointestinal carcinomas is associated with drug resistance of only certain chemotherapy drugs. Multiple factors and mechanisms should be considered when assessing the influence of MDR related factors on drug resistance.