Evaluation of a multi-slice spiral computed tomography perfusion for the prediction of the recurrence of gastric cancer.

AIM: The study aimed to elucidate the value of multislice spiral computed tomography (MSCT) perfusion for the early prediction of gastric cancer (GC) recurrence. METHODS: MSCT perfusion scans were performed to obtain values pertaining to blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface (PS). Logistic regression analysis was employed to evaluate the risk factors of postoperative recurrence in GC. RESULTS: The maximum diameter of GC has a positive relationship with PS. The maximum enhancement of GC was positively correlated with BF, blood volume and PS. PS, BF, vascular thrombus and Tumor, Node, Metastasis staging were found to be significant risk factors in relation to the recurrence of GC (p = 0.006, p = 0.002, p < 0.001). CONCLUSION: MSCT perfusion is strongly correlated with postoperative recurrence of GC, and PS and BF values, vascular thrombus and Tumor, Node, Metastasis staging were discovered as being prominent factors influencing the recurrence of GC.

Clinical investigation of combined Billroth II with Braun anastomosis for patients with gastric cancer.

BACKGROUND/AIMS: This study gives insight into the effect of combined Billroth II with Braun anastomosis for patients with gastric cancer. METHODOLOGY: The clinical data of 720 patients with gastric cancer who underwent surgical treatment in our hospital from 1997 to 2011 were reviewed retrospectively. The results of different operative approaches were analyzed. RESULTS: Combined Billroth II with Braun anastomosis was performed in 378 cases, and Billroth II in 342 cases. The Gastrointestinal Quality of Life Index (GIQLI) was used to evaluate postoperative quality of life. CONCLUSIONS: If the indications for combined Billroth II with Braun anastomosis are strictly controlled, and more attention is paid to perioperatively support, combined Billroth II with Braun anastomosis can prolong the life span of the patients with gastric cancer rather than increase the surgical complications and the mortality.

Clinicopathologic characteristics and prognosis of gastric cancer patients underwent gastrectomy combined with splenectomy.

BACKGROUND/AIMS: This study gives insight into the effect of splenectomy in radical surgery for gastric cancer. METHODOLOGY: The study included 631 patients who underwent radical resection for gastric cancer. Of these 631 patients, 105 underwent splenectomy and 526 had splenic preservation. The clinicopathologic features of 105 patients underwent gastrectomy combined with resection of the spleen (splenectomy group) and 526 patients underwent gastrectomy (spleen-preservation group) were compared. RESULTS: Gastric cancer with splenectomy was characterized by tumor located in gastric cardia (33.3%), positive lymph node metastasis (91.4%), and serosal invasion (94.3%). For age, gender, and tumor size, there was no significant difference between the patients with splenectomy and spleen-preservation. The 5-year survival of splenectomy group was 21.3% as compared with 38.6% for spleen-preservation group (P<0.001). With respect to patients with splenectomy, multivariate analysis showed that lymph node metastasis was significant factors affecting survival. CONCLUSIONS: Compared with spleen-preservation group, patients who underwent gastrectomy combined with splenectomy have a greater chance of tumor located in gastric cardia, positive lymph node metastasis, and serosal invasion and a significantly poor prognosis.

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor.

BACKGROUND: The development and progression of gastric cancer (GC) are closely linked to the nutritional status of patients. Although immunotherapy has been demonstrated to be clinically effective, the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors (ICIs) in patients with gastric cancer remain to be characterized. AIM: To assess the effects of sarcopenia and myosteatosis on the clinical outcomes of patients with GC undergoing treatment with an ICI. METHODS: We performed a retrospective study of patients who were undergoing immunotherapy for GC. For the evaluation of sarcopenia, the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level. Myosteatosis was defined using the mean skeletal muscle density (SMD), with a threshold value of < 41 Hounsfield units (HU) for patients with a body mass index (BMI) < 25 kg/m² and < 33 HU for those with a BMI ≥ 25 kg/m². The log-rank test was used to compare progression-free survival (PFS) and overall survival (OS), and a Cox proportional hazard model was used to identify prognostic factors. Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses. RESULTS: We studied 115 patients who were undergoing ICI therapy for GC, of whom 27.4% had sarcopenia and 29.8% had myosteatosis. Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions. Furthermore, both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI. The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781, respectively. CONCLUSION: The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

Prognostic significance of serum inflammation indices for different tumor infiltrative pattern types of gastric cancer.

BACKGROUND: Inflammatory indices are considered to be potential prognostic biomarkers for patients with gastric cancer (GC). However, there is no evidence defining the prognostic significance of inflammatory indices for GC with different tumor infiltrative pattern (INF) types. AIM: To evaluate the significance of inflammatory indices and INF types in predicting the prognosis of patients with GC. METHODS: A total of 962 patients who underwent radical gastrectomy were retrospectively selected for this study. Patients were categorized into the expansive growth type (INFa), the intermediate type (INFb), and the infiltrative growth type (INFc) groups. The cutoff values of inflammatory indices were analyzed by receiver operating characteristic curves. The Kaplan-Meier method and log-rank test were used to analyze overall survival (OS). The chi-square test was used to analyze the association between inflammatory indices and clinical characteristics. The independent risk factors for prognosis in each group were analyzed by univariate and multivariate analyses based on logistic regression. Nomogram models were constructed by R studio. RESULTS: The INFc group had the worst OS (P < 0.001). The systemic immune-inflammation index (P = 0.039) and metastatic lymph node ratio (mLNR) (P = 0.003) were independent risk factors for prognosis in the INFa group. The platelet-lymphocyte ratio (PLR) (P = 0.018), age (P = 0.026), body mass index (P = 0.003), and postsurgical tumor node metastasis (pTNM) stage (P < 0.001) were independent risk factors for prognosis in the INFb group. The PLR (P = 0.021), pTNM stage (P = 0.028), age (P = 0.021), and mLNR (P = 0.002) were independent risk factors for prognosis in the INFc group. The area under the curve of the nomogram model for predicting 5-year survival in the INFa group, INFb group, and INFc group was 0.787, 0.823, and 0.781, respectively. CONCLUSION: The outcome of different INF types GC patients could be assessed by nomograms based on different inflammatory indices and clinicopathologic features.

Nomograms predicting prognosis of patients with pathological stages T1N2-3 and T3N0 gastric cancer.

BACKGROUND: Patients with pathological stages T1N2-3 (pT1N2-3) and pT3N0 gastric cancer (GC) have not been routinely included in the target population for postoperative chemotherapy according to the Japanese Gastric Cancer Treatment Guideline, and their prognosis is significantly different. AIM: To identify the high-risk patients after radical surgery by analyzing biomarkers and clinicopathological features and construct prognostic models for them. METHODS: A total of 459 patients with pT1N2-3/pT3N0 GC were retrospectively selected for the study. The Chi-square test was used to analyze the differences in the clinicopathological features between the pT1N2-3 and pT3N0 groups. The Kaplan-Meier analysis and log-rank test were used to analyze overall survival (OS). The independent risk factors for patient prognosis were analyzed by univariate and multivariate analyses based on the Cox proportional hazards regression model. The cutoff values of continuous variables were identified by receiver operating characteristic curve. The nomogram models were constructed with R studio. RESULTS: There was no statistically significant difference in OS between the pT1N2-3 and pT3N0 groups (P = 0.374). Prealbumin (P = 0.040), carcino-embryonic antigen (CEA) (P = 0.021), and metastatic lymph node ratio (mLNR) (P = 0.035) were independent risk factors for prognosis in the pT1N2-3 group. Age (P = 0.039), body mass index (BMI) (P = 0.002), and gastrectomy (P < 0.001) were independent risk factors for prognosis in the pT3N0 group. The area under the curve values of the nomogram models for predicting the 5-year prognosis of the pT1N2-3 group and pT3N0 group were 0.765 and 0.699, respectively. CONCLUSION: Nomogram model combining prealbumin, CEA, and mLNR levels can be used to predict the prognosis of pT1N2-3 GC. Nomogram model combining age, BMI, and gastrectomy can be used to predict the prognosis of pT3N0 GC.

Metastatic lymph nodes and prognosis assessed by the number of retrieved lymph nodes in gastric cancer.

BACKGROUND: The prognostic value of quantitative assessments of the number of retrieved lymph nodes (RLNs) in gastric cancer (GC) patients needs further study. AIM: To discuss how to obtain a more accurate count of metastatic lymph nodes (MLNs) based on RLNs in different pT stages and then to evaluate patient prognosis. METHODS: This study retrospectively analyzed patients who underwent GC radical surgery and D2/D2+ LN dissection at the Cancer Hospital of Harbin Medical University from January 2011 to May 2017. Locally weighted smoothing was used to analyze the relationship between RLNs and the number of MLNs. Restricted cubic splines were used to analyze the relationship between RLNs and hazard ratios (HRs), and X-tile was used to determine the optimal cutoff value for RLNs. Patient survival was analyzed with the Kaplan-Meier method and log-rank test. Finally, HRs and 95% confidence intervals were calculated using Cox proportional hazards models to analyze independent risk factors associated with patient outcomes. RESULTS: A total of 4968 patients were included in the training cohort, and 11154 patients were included in the validation cohort. The smooth curve showed that the number of MLNs increased with an increasing number of RLNs, and a nonlinear relationship between RLNs and HRs was observed. X-tile analysis showed that the optimal number of RLNs for pT1-pT4 stage GC patients was 26, 31, 39, and 45, respectively. A greater number of RLNs can reduce the risk of death in patients with pT1, pT2, and pT4 stage cancers but may not reduce the risk of death in patients with pT3 stage cancer. Multivariate analysis showed that RLNs were an independent risk factor associated with the prognosis of patients with pT1-pT4 stage cancer (P = 0.044, P = 0.037, P = 0.003, P < 0.001). CONCLUSION: A greater number of RLNs may not benefit the survival of patients with pT3 stage disease but can benefit the survival of patients with pT1, pT2, and pT4 stage disease. For the pT1, pT2, and pT4 stages, it is recommended to retrieve 26, 31 and 45 LNs, respectively.

Clinicopathologic characteristics and prognosis of mucinous gastric carcinoma.

BACKGROUND AND OBJECTIVES: Reports of clinicopathological features and prognosis in patients with mucinous gastric carcinoma (MGC) are conflicting. The aim was to describe the clinicopathological features and prognosis of patients with MGC in comparison with nonmucinous gastric carcinoma (NMGC). METHODS: We reviewed the records of 1,278 consecutive patients diagnosed with gastric carcinoma who were resected surgically from 1993 to 2003. Among them, 48 patients (3.8%) with MGC were compared to 1,230 patients with NMGC. RESULTS: There were significant differences in tumor location, stage of disease, lymphatic invasion, and vascular invasion between the patients with MGC and NMGC. The overall 5-year survival of patients with MGC was 27.2% as compared with 42.8% for patients with NMGC (P = 0.031). For the patients with the same stage, there was no significant difference between MGC and NMGC. With respect to patients with MGC, multivariate analysis showed that lymph node metastasis and curative resection were significant factors affecting survival. CONCLUSIONS: MGC is rare and detected mostly in an advanced stage. Mucinous histology type itself is not an independent prognostic factor.

The relationship of prognosis to surgery and pathologic characteristics of stage IV (M0) gastric cancer patients.

BACKGROUND AND OBJECTIVE: The proportion of stage IV gastric cancer in the whole gastric cancer population in China is still high. This study was to investigate the surgery and pathologic characteristic and prognostic factors of stage IV (M0) gastric cancer. METHODS: Clinical data of 630 patients with pathologically confirmed stage IV (M0) gastric cancer treated at the affiliated Tumor Hospital of Harbin Medical University between January 1993 and August 2004 were analyzed using Cox proportional hazard model. Of the 630 patients, 338 received radical excision and 292 received palliative resection. RESULTS: The overall 1-, 3-, 5-year survival rates were 63.8%, 31.4% and 14.3%, respectively. Univariate analysis showed that Borrmann type, lymphatic metastasis, organ involvement, tumor location, tumor size, pathologic type, radical excision and other organ excision were significant prognostic factors affecting 1-year survival rate (P < 0.05); Borrmann type, lymphatic metastasis, organ involvement, pathologic type and radical excision affected 3-year survival rate (P < 0.05); only organ involvement and pathologic type affected 5-year survival rate (P < 0.05). Multivariate analysis showed that pathologic type was independent prognostic factor for poor survival. CONCLUSIONS: Radical resection and combined organ resection could prolong the survival of stage IV (M0) gastric cancer patients. Chemotherapy, radiotherapy and targeted therapy should be considered for individual therapeutic regimen.

Prognostic significance of Borrmann type combined with vessel invasion status in advanced gastric cancer.

BACKGROUND: Borrmann classification (types I-IV) for the detection of advanced gastric cancer has been accepted worldwide, and lymphatic and/or blood vessel invasion (LBVI) status is related to the poor prognosis after gastric cancer. AIM: To evaluate the significance of Borrmann type combined with LBVI status in predicting the prognosis of advanced gastric cancer. METHODS: We retrospectively studied the clinicopathological characteristics and long-term survival data of 2604 patients who were diagnosed with advanced gastric adenocarcinoma at Harbin Medical University Cancer Hospital from January 2009 to December 2013. Categorical variables were evaluated by the Pearson's χ 2 test, the Kaplan-Meier method was used to identify differences in cumulative survival rates, and the Cox proportional hazards model was used for multivariate prognostic analysis. RESULTS: A total of 2604 patients were included in this study. The presence of LVBI [LBVI (+)] and Borrmann type (P = 0.001), tumor location (P < 0.001), tumor size (P < 0.001), histological type (P < 0.001), tumor invasion depth (P < 0.001), number of metastatic lymph nodes (P < 0.001), and surgical method (P < 0.001) were significantly correlated with survival. When analyzing the combination of the Borrmann classification and LBVI status, we found that patients with Borrmann type III disease and LBVI (+) had a similar 5-year survival rate to those with Borrmann IV + LBVI (-) (16.4% vs 13.1%, P = 0.065) and those with Borrmann IV + LBVI (+) (16.4% vs 11.2%, P = 0.112). Subgroup analysis showed that the above results were true for any pT stage and any tumor location. Multivariate Cox regression analysis showed that Borrmann classification (P = 0.023), vascular infiltration (P < 0.001), tumor size (P = 0.012), pT stage (P < 0.001), pN stage (P < 0.001), and extent of radical surgery (P < 0.001) were independent prognostic factors for survival. CONCLUSION: Since patients with Borrmann III disease and LBVI (+) have the same poor prognosis as those with Borrmann IV disease, more attention should be paid to patients with Borrmann III disease and LBVI (+) during diagnosis and treatment, regardless of the pT stage and tumor location, to obtain better survival results.

Changing trends of clinicopathologic features and survival duration after surgery for gastric cancer in Northeast China.

BACKGROUND: Through analyzing the data from a single institution in Northeast China, this study revealed the possible clinicopathologic characteristics that influence the prognosis of patients with gastric cancer (GC). AIM: To evaluate the changing trends of clinicopathologic features and survival duration after surgery in patients with GC in Northeast China, which is a high-prevalence area of GC. METHODS: The study analyzed the difference in clinicopathologic features and survival duration after surgery of 5887 patients who were histologically diagnosed with GC at the Harbin Medical University Cancer Hospital. The study mainly analyzed the data in three periods, 2000 to 2004 (Phase 1), 2005 to 2009 (Phase 2), and 2010 to 2014 (Phase 3). RESULTS: Over time, the postoperative survival rate significantly increased from 2000 to 2014. In the past 15 years, compared with Phases 1 and 2, the tumor size was smaller in Phase 3 (P < 0.001), but the proportion of high-medium differentiated tumors increased (P < 0.001). The proportion of early GC gradually increased from 3.9% to 14.4% (P < 0.001). A surprising improvement was observed in the mean number of retrieved lymph nodes, ranging from 11.4 to 27.5 (P < 0.001). The overall 5-year survival rate increased from 24% in Phase 1 to 43.8% in Phase 3. Through multivariate analysis, it was found that age, tumor size, histologic type, tumor-node-metastasis stage, depth of invasion, lymph node metastasis, surgical approach, local infiltration, radical extent, number of retrieved lymph nodes, and age group were independent risk factors that influenced the prognosis of patients with GC. CONCLUSION: The clinical features of GC in Northeast China changed during the observation period. The increasing detection of early GC and more standardized surgical treatment effectively prolonged lifetimes.

Nipple aspirate fluid collection, related factors and relationship between carcinoembryonic antigen in nipple aspirate fluid and breast diseases in women in Harbin, PRC.

This study aimed to examine the factors related to the ability to obtain nipple aspirate fluids in Chinese women and to evaluate the diagnostic value of carcinoembryonic antigen (CEA) in nipple aspiration fluids. Cross-sectional and case-control studies were used to examine the factors associated with the ability to obtain nipple aspiration fluids. A matched case-control study was used to explore the association of CEA level in nipple aspiration fluids with breast disease. CEA level was log10-transformed to normalize the distribution. Univariate and multivariate logistic regression were adopted to analyze the variables in relation to obtaining fluid and the association of its CEA levels and breast diseases. Receiver operating characteristic curve was used to evaluate the value of CEA levels for the detection of breast disease. The nipple aspiration fluid collection rate was 34.24% (201 of 587). Multivariate logistic regression analysis results showed the following to be significantly associated with a greater ability to obtain nipple aspiration fluids: earlier age at menarche [odds ratio (OR), 2.61; 95% confidence interval (95% CI), 1.15-5.91], lactating>12 months (OR, 2.28; 95% CI, 1.44-3.60), wet-type ear wax (OR, 3.80; 95% CI, 2.39-6.02), and fatty diet (OR, 1.56; 95% CI, 1.02-2.39). CEA levels in nipple aspiration fluids of cancerous breasts were significantly higher than those from breasts with benign disease and healthy controls (ORadj, 5.39; P<0.01). However, the sensitivity of CEAs was 35.42% and the specificity was 85.42% whereas the CEA cutoff value was 307.61 ng/mL. The area under the receiver operating characteristic curve was 0.65. The nipple aspiration fluid collection rate in Chinese native women is lower compared to non-Asian-descendant women. CEA level does not seem to be a useful diagnostic tool for early cancer detection; it can only be used in conjugation with other methods.

[Expression of hepatocyte growth factor, transcription factor SP1, vascular endothelial growth factor and CD34 in serosa-infiltrative gastric cancer and their relations with defluxion of gastric cancer cell and prognosis].

OBJECTIVE: To observe the expression of hepatocyte growth factor (HGF), transcription factor SP1, vascular endothelial growth factor (VEGF) and CD34 (demonstrating by microvessel density, MVD) in serosa-infiltrative gastric cancer (T3) and their relations with the pathobiological behavior of the tumor, and to investigate the molecular basis of the defluxion of gastric cancer cells in abdominal cavity and its influence on prognosis. METHODS: Selective collection of peritoneal lavage was obtained from 80 patients with serosa-infiltrative gastric cancer received operation from April to December in 2007. The cancer cells were detected by using peritoneal lavage cytology (PLC) and immunochemistry of cytokeratin 18 (CK18). Immunohistochemistry was applied to detect the HGF, SP1, VEGF and CD34 in serosa-infiltrative gastric cancer tissues. The rigorous follow-up was carried out for the patients. RESULTS: The positive rate of PLC was 63.8% (51/80), and the positive rate of immunochemistry of CK18 was 75.0% (60/80). The positive cases in PLC were positive in immunochemistry of CK18 also, while 9 negative cases in PLC were positive with CK18, and of them 6 cases were determined positive with exfoliated cancer cells through pathological consulting. So the positive rate of exfoliated cells of this group was 71.3% (57/80). The positive rates of HGF, SP1 and VEGF in gastric cancer tissues were 57.5%, 52.5% and 55.0%, respectively, and were all significantly correlated with the MVD (P < 0.05). HGF, SP1, VEGF and MVD were correlated with the positive rate of exfoliated cells (P < 0.05). HGF, SP1, VEGF and MVD were found significantly related to prognosis on univariate analysis (P < 0.05), and it was demonstrated that HGF, SP1 and VEGF were independent prognostic influential factors on Logistic regression analysis (P < 0.05). CONCLUSIONS: The expression of HGF, SP1, VEGF and MVD are related with the biological behaviour of serosa-infiltrative gastric cancer. The detection of these factors might be helpful in predicting the defluxion of gastric cancer cells and postoperative recurrence.

[Reversal effect and mechanism of arsenic trioxide on multidrug resistance of gastric carcinoma cells SGC7901].

The purpose of this study is to investigate the reversal effect and its mechanism of arsenic trioxide (As2O3) on multidrug resistance of gastric carcinoma cells. The concentration of vincristine (VCR) increased gradually to induce the drug resistance of gastric carcinoma cell SGC7901. MTT assay was used to determine the lethal effect of anticarcinogens on tumor cells and Western blotting assay was applied to determine the expression of P-glucoprotein (P-gp) and glutathione S-transferase (GST-s) in tumor cells. As a result, the resistance of SGC7901/VCR cells to VCR, fluorouracil and epirubicin was 16.56, 2.69 and 13.05 times, respectively, more than that of SGC7901 cells. After 24 h precondition with As2O3, RI of vincristine, fluorouracil and epirubicin decreased significantly (P < 0.05). Expression of P-gp and GST-s in resting SGC7901/VCR cells was significantly higher than that in carcinogen-sensitive SGC7901 cells. As2O3 decreased the expression of P-gp and GST-s in SGC7901/VCR cells significantly, while it showed no significant effect on carcinogen-sensitive SGC7901 cells. The result suggested that As2O3 could partly reverse drug resistance of SGC7901/VCR cells by probably the mechanism of decreasing the expression of P-gp and GST-s.

The value of contrast-enhanced computed tomography in predicting gastric cancer recurrence and metastasis.

BACKGROUND: The present study aimed to illustrate the clinical value of contrast-enhanced computed tomography (CECT) in predicting gastric cancer (GC) recurrence and metastasis. METHODS: From March 2012 to March 2014, 131 GC patients who underwent initial treatment at the Tumor Hospital of Harbin Medical University were enrolled in this study, and 64-slice spiral CT was used for CECT. CECT parameters were recorded, including CT values in the arterial and venous phases, as well as the enhancement patterns in the arterial phase. All GC patients were followed for one year. The receiver operating characteristic (ROC) curve was used to evaluate the clinical values of the CECT parameters in predicting GC recurrence and metastasis. RESULTS: Significantly higher CT values in the arterial and venous phases were found in patients with higher tumor node metastasis (TNM) staging, lymph node metastasis (LNM), advanced Borrmann type and postoperative chemotherapy. TNM stage I-II patients showed less significant enhancement and significant heterogeneous enhancement than TNM stage III-IV patients. Compared with patients without recurrence and metastasis, patients with recurrence and metastasis demonstrated higher CT values in the arterial and venous phases, as well as a higher proportion of significant enhancement and significant heterogeneous enhancements. For the CT value in the arterial phase, the area under the ROC curve was 0.858, with 70.3% sensitivity and 95.7% specificity, and in the venous phase, it was 0.801, with 73.0% sensitivity and 83.0% specificity. CONCLUSION: Our study suggests that CECT has a high accuracy rate for predicting postoperative GC recurrence and metastasis.

Downregulation of Notch1 inhibits the invasion and metastasis of human gastric cancer cells SGC7901 and MKN74 in vitro through PTEN activation and dephosphorylation of Akt and FAK.

Migration and invasion are both vital causes of mortality in patients with gastric cancer. Therefore, the inhibition of these tumour cell processes is of great importance in gastric cancer therapy. Activation of Notch has been reported in many cancers. The critical role of Notch and its regulation in tumourigenesis has been noted. Although the studies on Notch in the field of cancer have been performed extensively, the role of Notch1 signalling in gastric cancer requires further study. Inactivation of PTEN has been observed in the development of many malignant tumors, and loss of PTEN function has been implicated in tumorigenic processes. Notch acts as an upstream signalling pathway that regulates PTEN activities. However, the effect of Notch on invasion and metastasis in gastric cancer and the regulation of PTEN during this process remain poorly understood. In the present study, small interfering RNA (siRNA) was used to knock down Notch1 expression in gastric cancer cell lines SGC7901 and MKN74. The mRNA and protein expression of Notch1, PTEN, Akt and FAK were measured upon depletion of Notch1. phospho­PTEN, phospho­Akt and phospho­FAK expression were measured using western blot analysis. Migration and invasion assays were also used after Notch1 depletion. Our results showed that the knockdown of Notch1 leads to the inhibition of cell invasion and metastasis of human gastric cancer cells SCG7901 and MKN74 in vitro. Compared to control and mock groups, PTEN activities were significantly promoted following depletion of Notch1, and the expression of Phospho­Akt and Phospho­FAK were downregulated. Taken together, our findings suggest that Notch1 could be used as a therapeutic target to inhibit cell invasion and migration in gastric cancer.

[Clinicopathologic significance of CD105 mRNA expression in human breast carcinoma].

OBJECTIVE: To study endoglin (CD105) gene expression in breast cancer and its clinicopathologic significance. METHODS: In 40 patients with breast cancers, CD105 mRNA was detected at center and periphery of tumor and at nearby normal tissue by RT-PCR. RESULTS: The difference in CD105 mRNA expressions between cancer and normal breast tissue was significant (t = 12.08, P < 0.05), and the expression was significantly higher at the tumor periphery than at the tumor center (t = 7.52, P < 0.05). CD105 over-expression was related to lymph node metastases (t = 2.71, P < 0.05), but not to age, tumor size, pathologic grade or pathologic type (P > 0.05). CONCLUSION: CD105 over-expression may play a crucial role in the progression of breast cancer and lymph node metastasis.

Expression of cyclooxygenase-2 and clinicopathologic features in human gastric adenocarcinoma.

AIM: To study the expression of cyclooxygenase-2 (COX-2) gene in gastric cancer and the relationship between COX-2 expression and clinicopathologic features of gastric cancer. METHODS: With reference to the expression of beta-actin gene, COX-2 mRNA level was examined in cancerous tissues and adjacent noncancerous mucosa from 33 patients by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Quantitation of relative band Adj volume counts was performed using molecular Analyst for windows software. The COX-2 index was determined from the band Adj volume counts ratio of COX-2 to constitutively expressed actin. RESULTS: The COX-2 index in gastric carcinoma was significantly higher than that in normal mucosa (0.5966+/-0.2659 vs 0.2979+/-0.171, u=5.4309, P<0.01). Significantly higher expression of COX-2 mRNA was also observed in patients with lymph node involvement than that in those without (0.6775+/-0.2486 vs 0.4105+/-0.2182, t=2.9341, P<0.01). Furthermore, the staging in the UICC TNM classification significantly correlated with COX-2 overexpression (F=3.656, P<0.05), the COX-2 index in stage III and IV was significantly higher than those in stage I and II (q=3.2728 and q=3.4906, P<0.05). The COX-2 index showed no correlation with patient's age, sex, blood group, tumor location, gross typing, depth of invasion, differentiation, and the greatest tumor dimension (P>0.05). CONCLUSION: Expression of COX-2 mRNA in gastric carcinoma was significantly higher, which may enhance lymphatic metastasis in patients with gastric carcinoma. The staging in the UICC TNM classification was significantly correlated with COX-2 over-expression. COX-2 may contribute to progression of tumor in human gastric adenocarcinoma.

Peptide nucleic acids arrest the growth of gastric cancer cells SGC7901.

BACKGROUND: Peptide nucleic acid (PNA) has many characteristics useful in molecular biology. This paper described an effective way to raise the cell ingestion rate of PNA so as to kill gastric cancer cells. METHODS: Heteroduplexes of PNAs and oligonucleotides, wrapped by Lipofectamine 2000, were used to infect SGC7901 cells. The inhibitive effect of heteroduplexes was evaluated by analyzing cell clone forming and cell growth rate. Telomerase activity of SGC7901 cells was detected by polymerase chain reaction enzyme-linked immunosorbent assay (PCR-ELISA) and silver staining assay. RESULTS: PNAs showed a dose-dependent inhibition of cell proliferation. The percentage of proliferation inhibition was 99.4% after 7 days; the rate of cloning inhibition was 98.2% after 8 days; whereas for oligonucleotide groups, at the same concentration, the percentages were 50.1% and 67.5% respectively. Antisense PNA-DNA-Lipofectamine 2000 group (AP-D-L group) exhibited significantly different percentages from the control groups (P < 0.05). The test result indicated that telomerase activity of the AP-D-L group was inhibited (P < 0.05). At the same time, the impact on cell morphology was observed. CONCLUSIONS: The results showed that PNAs are potent antisense reagents. The telomerase-associated therapies are very promising for the treatment of malignant tumours.

[Expression of the cyclooxygenase-2 gene in human breast carcinoma].

OBJECTIVE: To study the expression of the cyclooxygenase-2 (COX-2) gene in breast cancer in contrast to that of normal breast tissues or benign breast tumors and its significance in the carcinogenesis and development of breast cancer. METHODS: With reference to the expression of the beta-actin gene, the expression of COX-2 mRNA was examined in cancerous tissues and adjacent normal breast tissue from 30 patients and benign breast tumors from 15 patients by reverse transcription-polymerase chain reaction (RT-PCR). Quantitation of relative band densities was performed using densitometry-scanning software. Estrogen receptors of 30 breast cancers were investigated by immunohistochemistry. RESULTS: Enhanced expression of COX-2 was observed in ninety percent of cancers tissue with a range of 0.05 - 0.91 (median 0.53). Rare cases showed significant COX-2 expression in normal breast tissues with a range of 0 - 0.09 (median 0). In part of benign breast tumors, COX-2 expressions were obviously elevated with a range of 0 - 0.68 (median 0.07). The difference of expression of COX-2 mRNA among breast cancers, normal breast tissues, mastopathy or fibroadenomas was significant (rank-sum test, P < 0.05) and the difference of that between estrogen receptor negative and positive was also observed (rank-sum test, P < 0.01). CONCLUSION: The level of expression of COX-2 mRNA is obviously higher in breast cancer tissue than in normal breast tissue, mastopathy or fibroadenomas. The expression of COX-2 in hormone-dependent breast cancer is higher than that in hormone-independent breast cancer. The overexpression of COX-2 may play a crucial role in the carcinogenesis and development of cancer in patients with breast carcinoma.