Recognition of antitussive components in Farfarae Flos based on grey relational analysis and partial least squares regression. / åŸºäºŽç°è‰²å ³è”åº¦åˆ†æžå’Œåæœ€å°äºŒä¹˜å›žå½’è¾¨è¯†æ¬¾å†¬èŠ±æ­¢å’³æ´»æ€§æˆåˆ†.

OBJECTIVES: Farfarae Flos has the effect of cough suppression and phlegm elimination, with cough suppression as the main function. Studies have revealed that certain components of Farfarae Flos may be related to its cough suppressant effect, and some components have been confirmed to have cough suppressant activity. However, the antitussive material basis of Farfarae Flos has not been systematically elucidated. This study aims to elucidate the group of active ingredients in Farfarae Flos with cough suppressant activity by correlating the high performance liquid chromatography (HPLC) fingerprint of Farfarae Flos extract with its cough suppressant activity. METHODS: HPLC was used to establish the fingerprint profiles of 10 batches of Farfarae Flos extract and obtain their chemical composition data. Guinea pigs were selected as experimental animals and the citric acid-induced cough model was used to evaluate the antitussive efficacy data of 10 batches of Farfarae Flos extract. SPF-grade healthy male Hartley guinea pigs were randomly divided into the S1 to S10 groups, a positive control group, and a blank control group (12 groups in total), with 10 guinea pigs in each group. The S1 to S10 groups were respectively administered Farfarae Flos extract S1 to S10 (4 g/kg), the positive control group was administered pentoverine citrate (10 mg/kg), and the blank control group was administered purified water. Each group received continuous oral administration for 5 days. The guinea pigs were placed in 5 L closed wide-mouth bottles, and 17.5% citric acid was sprayed into the bottle with an ultrasonic atomizer at the maximum spray intensity for 0.5 minutes. The cough latency period and cough frequency in 5 minutes were recorded for each guinea pig. Grey relational analysis (GRA) and partial least squares regression (PLSR) were used to conduct spectral-effect correlation analysis of the chemical composition data of Farfarae Flos extract and the antitussive efficacy data, and predict the group of active ingredients in Farfarae Flos with antitussive activity. The bioequivalence verification was conducted to verify the predicted group of active ingredients in Farfarae Flos with antitussive activity: SPF-grade healthy male Hartley guinea pigs were randomly divided into a S9 group, an active ingredient group, a positive control group, and a blank control group (4 groups in total), with 10 guinea pigs in each group. The S9 group was administered Farfarae Flos extract S9 (4 g/kg), the active ingredient group was administered the predicted combination of antitussive active ingredients (dose equivalent to 4 g/kg of Farfarae Flos extract S9), the positive control group was administered pentoverine citrate (10 mg/kg), and the blank control group was administered purified water. Each group received continuous oral administration for 5 days, and animal modeling and observation of efficacy indicators were the same as above. RESULTS: The HPLC fingerprint of 10 batches of Farfarae Flos extract was established, and the peak area data of 14 main common peaks were obtained. The antitussive effect data of 10 batches of Farfarae Flos extract were obtained. Compared with the blank control group, the cough latence in the positive control group and S1, S2, S3, S4, S6, S7, S8, S9, S10 groups was prolonged (all P<0.01), while the cough frequency in 5 minutes in the positive control group and S1, S2, S4, S6, S8, S9, S10 groups was decreased (all P<0.05). The analysis of spectrum-effect relationship revealed that isochlorogenic acid C, isochlorogenic acid A, chlorogenic acid, isochlorogenic acid B, isoquercitrin, and rutin had high contribution to the antitussive effect of Farfarae Flos, and the 6 components were predicted to be the antitussive component group of Farfarae Flos. The verification of bioequivalence showed that there were no statistically significant differences in the antitussive effect between the S9 group and the antitussive component composition group(all P>0.05), which confirmed that isochlorogenic acid C, isochlorogenic acid A, chlorogenic acid, isochlorogenic acid B, isoquercetin, and rutin were the antitussive component group of Farfarae Flos. CONCLUSIONS: The analysis of spectrum-effect relationship combined with the verification of bioequivalence could be used to study the antitussive material basis of Farfarae Flos. The antitussive effect of Farfarae Flos is the result of the joint action of many components.

Analysis of lymph node metastasis in early gastric cancer: a single institutional experience from China.

BACKGROUND: Lymph node metastasis (LNM) has a strong influence on the prognosis of patients with early gastric cancer (EGC). The aim of this study was to reveal the incidence of LNM and evaluate risk factors for LNM to determine the appropriate treatment for EGC in a Chinese population. METHODS: Patients who underwent radical gastrectomy with lymph node dissection for EGC between 2012 and 2017 were retrospectively analyzed. Univariate and multivariate analyses were conducted to identify clinicopathological features that were risk factors for LNM. RESULTS: A total of 1033 patients with EGC were enrolled. Of these patients, 668 (64.7%) were men, and 365 (35.3%) were women, ranging in age from 19 to 82 years (mean 56.9 ± 10.9 years). LNM was detected in 173(16.7%) patients with EGC. Among 508 patients with mucosal cancer, 44 (8.7%) patients had LNM. In 525 patients with submucosal cancer, the incidence of LNM was 24.6% (129/525). The age, gender, tumor size, type of differentiation, Lauren classification, and lymphovascular and perineural invasion showed a significant correlation with the rate of LNM in EGC by univariate and multivariate analyses. Patients with submucosal gastric cancer had an older age, a higher proportion of proximal lesion, larger tumor size, more frequent lymphovascular invasion, perineural invasion, and more LNM than patients with mucosal gastric cancer. CONCLUSIONS: Our study revealed a relatively high incidence of LNM in EGC, compared with Japanese and Korean cohorts. Female sex, large tumor size, undifferentiated-type, and lymphovascular invasion were independent risk factors for LNM in EGC. Radical gastrectomy with lymphadenectomy should be performed in EGC patients with a high risk of LNM.

Study protocol of a randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma: PREACT.

BACKGROUND: The prognosis of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma is still dismal. There are no standard treatment strategies for these patients. Multidisciplinary team (MDT) approach is a good choice for making a high-quality decision. Generally, MDT will recommend these patients to receive preoperative chemotherapy or preoperative chemoradiation based on all kinds of treatment guidelines. However, the preferred preoperative treatment is still not established. In order to solve this problem, we carry out this randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. METHODS: Eligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma are randomized to receive preoperative chemoradiation or preoperative chemotherapy, followed by surgery and postoperative chemotherapy. In the preoperative chemoradiation arm (Pre-CRT), patients receive two cycles of S-1 and oxaliplatin (SOX), chemoradiation, then followed by surgery and three more cycles of SOX chemotherapy. In the preoperative chemotherapy arm (Pre-CT), patients receive three cycles of SOX, following surgery three more cycles of SOX are given. The primary endpoint of this trial is to verify that preoperative chemoradiation could significantly improve the 3-year disease free survival (DFS) of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma compared to preoperative chemotherapy. DISCUSSION: The results from this trial will provide important information about whether preoperative chemoradiation could improve survival compared to preoperative chemotherapy among patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03013010. First posted January 6, 2017.

CircLMTK2 acts as a novel tumor suppressor in gastric cancer.

Recently, circRNAs have been found to play regulatory roles in cancer. In the present study, we aimed to investigate the characteristics and effect of circLMTK2, and its potential role as a novel biomarker in cases of gastric cancer (GC). About 111 pairs of clinical tissues from patients were collected for circLMTK2 expression investigation. Afterward, the relationship of circLMTK2 expression level and clinical features, such as survival, tumor size and so on, were analyzed, along with a multivariate Cox hazards analysis. Finally, malignant biological properties, like cell viability and mobility, were explored in cell line MGC-803. We found that circLMTK2 was a stable circRNA generated from the back-spliced Exon 10 and Exon 11 of the LMTK2 gene in GC cells. CircLMTK2 expression was significantly down-regulated in gastric carcinoma tissue specimens (P<0.001) compared with its expression in paired normal tissues. Furthermore, a Kaplan-Meier analysis revealed that lower levels of circLMTK2 expression were associated with decreased overall survival (OS) (P<0.001), and a multivariate Cox hazards analysis showed that high circLMTK2 expression was an independent factor for OS. Afterward, overexpression of circLMTK2 was performed in gastric cancer cell line MGC-803, and results indicated that malignant biological properties were inhibited by circLTMK2 overexpression. The present study showed the first evidence that circLMTK2 was down-regulated in GC, suggesting it as a novel biomarker for prognosis, and also as a therapeutic target in treatment of GC.

Aurora kinase B inhibitor barasertib (AZD1152) inhibits glucose metabolism in gastric cancer cells.

Barasertib is a highly selective Aurora kinase B (AURKB) inhibitor and has been widely applied in a variety of cancer cells to investigate the regulatory function of AURKB. However, the effect of barasertib on glucose metabolism in gastric cancer (GC) remains illustrated. Here, barasertib was identified to effectively reduce glucose uptake and lactate production in GC cells in a dose-dependent and time-dependent manner. The expression levels of GLUT1, LDHA and HK2 were decreased by barasertib treatment of GC cells. Furthermore, we found that barasertib induced the expression of ribosomal protein S7 (RPS7), as a tumor suppressor, to regulate glucose metabolism. Silencing of RPS7 rescued the effects of barasertib on glucose metabolism in GC cells. Overexpression of RPS7 suppressed the promoter activity of C-Myc, which has been identified as an important regulator of glucose metabolism in cancer cells. The clinical data showed that the expression level of AURKB in GC patients' sera and tissues were positively correlated with those of C-Myc, GLUT1 and LDHA, but negatively with that of RPS7. Therefore, these findings provide new evidence that barasertib regulates GC cell glucose metabolism by inducing the RPS7/C-Myc signal pathway, and have important implications for the development of therapeutic approaches using AURKB as a target protein to prevent tumor recurrence.

Phase II trial of preoperative chemoradiation plus perioperative SOX chemotherapy in patients with locally advanced gastric cancer.

BACKGROUND AND PURPOSE: The ideal treatment strategy of patients with locally advanced gastric adenocarcinoma is unclear. The aim of this study is to evaluate the efficacy and feasibility of preoperative chemoradiation in these patients. PATIENTS AND METHODS: All patients underwent laparoscopic exploration or exploratory laparotomy before chemoradiation. Patients received one cycle of S-1 and oxalipatin followed by concurrent radiation and chemotherapy, then underwent another cycle of S-1 and oxalipatin. Surgery was performed 6-8 weeks after completing radiochemotherapy. The rate of curative gastrectomy and survival were investigated. This trial was registered with ClinicalTrial.gov, number NCT02024217. RESULTS: From April 2012 to August 2014, 40 patients were enrolled in the trial, and 36 patients were assessable. The most common hematologic toxic effects were leukopenia (80.6%), neutropenia (69.4%), and thrombocytopenia (50%); the most common nonhematologic toxic effects were anorexia (50%), nausea (22.3%), and vomiting (13.9%). There were no treatment related deaths. A total of 33 patients underwent second exploratory laparotomy after preoperative chemoradiation, and 24 (67%) patients received curative gastrectomy. The rates of pathological complete response (pCR) were 13.9%. The medial survival time (MST) was 30.3 months. CONCLUSION: Preoperative chemoradiation may be an effective treatment strategy among patients with locally advanced gastric adenocarcinoma.

DC targeting DNA vaccines induce protective and therapeutic antitumor immunity in mice.

BACKGROUND: Anti-CD11c antibodies target to the CD11c receptor that mediates antigen presentation to T cells by dendritic cells (DCs). To exploit these properties for immunization purposes, we obtained DC-targeting DNA vaccines by fusing tumor-associated antigen HER2/neu ectodomain to single chain antibody fragment (scFv) from N418 (scFv(N418)), a monoclonal antibody binding the mouse DC-restricted surface molecule CD11c, and explored its antitumoral efficacy and underlying mechanisms in mouse breast cancer models. METHODS: Induction of humoral and cellular immune responses and antitumoral activity of the DNA vaccines were tested in transplantable HER2/neu-expressing murine tumor models and in transgenic BALB-neuT mice developing spontaneous Neu-driven mammary carcinomas. RESULTS: Upon injection of the breast tumor cell line D2F2/E2 (stably expressing human wild-type HER2), scFv(N418)-HER2 immunized mice were protected against tumor growth. Even more important for clinical applications, we were able to substantially slow the growth of implanted D2F2/E2 cells by injection of scFv(N418)-HER2 conjugates into tumor bearing hosts. The existing tumors were eradicated by treatment with scFv(N418)-HER2 combined with low-dose cyclophosphamide (CTX), which can make a temporary regulatory T cells (Treg) depletion. What's more, in combination with the low-dose CTX, vaccination with scFv(N418)-neu significantly retarded the development of spontaneous mammary carcinomas in transgenic BALB-neuT mice. CONCLUSION: Our results show that DNA vaccine which targeting of dendritic cells in situ by the means of antibody-antigen conjugates may be a novel way to induce long-lasting antitumor immunity.

Prognostic role of microRNA-100 in various carcinomas: evidence from six studies.

Recent studies have shown that microRNAs (miRNA) exhibit altered expression levels in cancers, and they may be considered as valuable prognostic biomarkers for patients with cancers. We performed this meta-analysis to provide a comprehensive evaluation of the role of miRNA-100 expression on the overall survival rate by calculating the pooled hazard ratio (HR) for overall survival (OS), which compared the high and low expression levels of miR-100 in patients of the available studies. Finally, a total of six studies dealing with various carcinomas were involved for this meta-analysis. The results indicated that lower expression of miR-100 in cancerous tissue could significantly predict poorer survival in various carcinomas with the pooled HR of 2.19 (95% CI 1.49-3.24, P = 0.0007). In conclusion, the findings from this present meta-analysis suggest that miR-100 expression is associated with OS in cancer patients and could be a useful clinical prognostic factor for those patients.

Impact of lymphatic and/or blood vessel invasion in stage II gastric cancer.

AIM: To determine the prognostic value of lymphatic and/or blood vessel invasion (LBVI) in patients with stage II gastric cancer. METHODS: From January 2001 to December 2006, 487 patients with histologically confirmed primary gastric adenocarcinoma were diagnosed with stage II gastric cancer according to the new 7th edition American Joint Committee on Cancer stage classification at the Department of Gastric Cancer and Soft Tissue Surgery, Fudan University Shanghai Cancer Center. All patients underwent curative gastrectomy with standard lymph node (LN) dissection. Fifty-one patients who died in the postoperative period, due to various complications or other conditions, were excluded. Clinicopathological findings and clinical outcomes were analyzed. Patients were subdivided into four groups according to the status of LBVI and LN metastases. These four patient groups were characterized with regard to age, sex, tumor site, pT category, tumor grading and surgical procedure (subtotal resection vs total resection), and compared for 5-year overall survival by univariate and multivariate analysis. RESULTS: The study was composed of 320 men and 116 women aged 58.9 ± 11.5 years (range: 23-88 years). The 5-year overall survival rates were 50.7% and the median survival time was 62 mo. Stage IIa cancer was observed in 334 patients, including 268 T3N0, 63 T2N1, and three T1N2, and stage IIb was observed in 102 patients, including 49 patients T3N1, 51 T2N2, one T1N3, and one T4aN0. The incidence of LBVI was 28.0% in stage II gastric cancer with 19.0% (51/269) and 42.5% (71/167) in LN-negative and LN-positive patients, respectively. In 218 patients (50.0%), there was neither a histopathologically detectable LBVI nor LN metastases (LBVI(-)/LN(-), group I); in 51 patients (11.7%), LBVI with no evidence of LN metastases was detected (LBVI(+)/LN(-), group II). In 167 patients (38.3%), LN metastases were found. Among those patients, LBVI was not determined in 96 patients (22.0%) (LBVI(-)/LN(+), group III), and was determined in 71 patients (16.3%) (LBVI(+)/LN(+), group IV). Correlation analysis showed that N category and the number of positive LNs were significantly associated with the presence of LBVI (P < 0.001). The overall 5-year survival was significantly longer in LN-negative patients compared with LN-positive patients (56.1% vs 42.3%, P = 0.015). There was a significant difference in the overall 5-year survival between LBVI-positive and LBVI-negative tumors (39.6% vs 54.8%, P = 0.006). Overall 5-year survival rates in each group were 58.8% (I), 45.8% (II), 45.7% (III) and 36.9% (IV), and there was a significant difference in overall survival between the four groups (P = 0.009). Multivariate analysis in stage II gastric cancer patients revealed that LBVI independently affected patient prognosis in LN-negative patients (P = 0.018) but not in LN-positive patients (P = 0.508). CONCLUSION: In LN-negative stage II gastric cancer patients, LBVI is an additional independent prognostic marker, and may provide useful information to identify patients with poorer prognosis.

Poor prognostic factors in patients with stage I gastric cancer according to the seventh edition TNM classification: a comparative analysis of three subgroups.

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate the prognosis of stage I gastric cancer and to compare clinicopathologic characteristics by subgroup. METHODS: Between January 2000 and December 2006, 384 patients with gastric cancer were reclassified as stage I according to the seventh edition classification. A comparative analysis was performed between three subgroups. Univariate and multivariate analyses were conducted. RESULTS: The 5-year overall survival rates in T1N0, T1N1, and T2N0 were 98.8%, 94.1%, 91.1%, respectively (P = 0.009). In patients with T2N0 gastric cancer, tumors in the upper third and larger tumors were more common than in patients with T1N0 and T1N1 gastric cancer (P < 0.001). In patients with T1N1 and T2N0 gastric cancer, the presence of lymphatic and/or blood vessel invasion (LBVI) and perineural invasion (PNI) were more common than in patients with T1N0 gastric cancer (P < 0.001). Univariate analysis showed tumor stage, depth of invasion, LBVI, and PNI were significant prognostic factors. However, multivariate analysis demonstrated that only tumor stage, LBVI, and PNI were significant variables. CONCLUSIONS: Survival data support the accuracy of new TNM classification for stage I gastric cancer. Tumor stage, the presence of LBVI and PNI are important independent prognostic factors in stage I gastric cancer.

miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition.

microRNAs (miRNAs) play an important role in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In the current study, we defined the target genes and biological functions of miR-27 with a luciferase reporter assay and Western blot analysis. We verified that miR-27 levels were increased in gastric cancer tissues. The overexpression of miR-27 promoted the metastasis of AGS cells, whereas its depletion decreased cell metastasis. Up-regulation of miR-27 increased the levels of the epithelial-mesenchymal transition (EMT)-associated genes ZEB1, ZEB2, Slug, and Vimentin, as well as decreased E-cadherin levels. We demonstrated that miR-27 promoted EMT by activating the Wnt pathway. Finally, the APC gene was identified as the direct and functional target of miR-27. These results suggest an important role of miR-27 in regulating metastasis of gastric cancer and implicate the potential application of miR-27 in gastric cancer therapy.

Defining a high-risk subgroup of pathological T2N0 gastric cancer by prognostic risk stratification for adjuvant therapy.

BACKGROUND: Adjuvant therapy is not usually recommended in AJCC T2N0M0 gastric cancer, yet sometimes is indicated for high-risk patients. The purpose of this study is to stratify the risk of pathological T2N0 gastric cancer after gastrectomy based on clinicopathological factors so as to predict prognosis and guide treatment. METHODS: We analyzed our documented clinical database of 233 patients with T2N0M0 gastric cancer who underwent radical resection between 2000 and 2007. No adjuvant chemotherapy was applied. RESULTS: For the entire study group, the overall 5-year survival rate was 88.5%. Multivariate analysis indicated there were three tumor characteristics which were independent prognostic factors: lymphatic and/or blood vessel invasion (p = 0.025), tumor diameter (p = 0.004), and perineural invasion (p = 0.009). Three risk groups were created based on weighted variables with overall 5-year survival of 97.7%, 83%, and 50.3% as low-risk, intermediate-risk, and high-risk groups, respectively (p < 0.001). CONCLUSION: Patients with T2N0 gastric cancer have a favorable prognosis after radical resection. A prognostic risk model of patients with pT2N0 gastric cancer undergoing radical resection is constructed based on lymphatic and/or blood vessel invasion, tumor diameter, and perineural invasion. The prognostic risk model identifies a small subgroup of patients with an increased risk of death, suggesting adjuvant therapy may be considered for these patients.

Survival after anatomic resection versus nonanatomic resection for hepatocellular carcinoma: a meta-analysis.

BACKGROUND AND OBJECTIVES: To compare the effect on survival of anatomic resection (AR) versus nonanatomic resection (NAR) in patients with hepatocellular carcinoma (HCC) from all published comparative studies in the literature. METHODS: Databases, including Pubmed, Embase, the Cochrane Library, Ovid, and Web of Science, were searched to identify studies comparing AR with NAR for HCC. In this meta-analysis, primary end points were the overall survival and disease-free survival; the secondary end point was local recurrence rate. The meta-analysis was performed by use of RevMan 4.2. RESULTS: Nine comparative studies comprising 1,503 patients (833 AR and 670 NAR) were identified. In the combined results, disease-free survival was significantly higher in the AR group than in the NAR group (OR 1.78, 95% CI 1.22-2.59, P = 0.003; heterogeneity P = 0.08). Overall survival (OR 1.31, 95% CI 0.92-1.85, P = 0.13; heterogeneity P = 0.04) did not suggest any significant difference between AR and NAR. No statistically significant difference was found for local recurrence rate between the two resection methods (OR 0.55, 95% CI 0.25-1.23, P = 0.15; heterogeneity P = 0.010). CONCLUSIONS: Anatomic resection is associated with better disease-free survival than nonanatomic resection. Because heterogeneity was detected, caution is needed in interpretation of the results. Better designed, adequately powered studies are required to address this issue.

Simultaneous vs. staged resection for synchronous colorectal liver metastases: a metaanalysis.

PURPOSE: The optimal timing of surgical resection for synchronous colorectal liver metastases (SCLMs) remains controversial. The aim of this metaanalysis was to compare outcomes between simultaneous resection and staged resection from all published comparative studies in the literature. MATERIALS AND METHODS: Databases, including PubMed, Embase, Cochrane Library, Ovid, and Web of Science, were searched to identify studies comparing outcomes following simultaneous resection with staged resection for SCLM. The metaanalysis was performed by RevMan 4.2. RESULTS: Fourteen comparative studies comprising 2,204 patients were identified. Patients undergoing simultaneous resection were found to have similar operative time (weighted mean difference [WMD], -34.19; 95% confidence interval [CI], -81.32-12.95, P = .16) and intraoperative blood loss (WMD, -161.33; 95% CI, -351.45-28.79, P = .10). Shorter hospital stay (WMD, -4.77; 95% CI, -7.26-2.28, P < .01) and lower morbidity rate (odds ratio [OR], 0.71; 95% CI, 0.57-0.88, P = .002) were observed in simultaneous resection group. The survival rate in the simultaneous resection group did not statistically differ with that in the staged resection group at 1 year (OR, 0.77; 95% CI, 0.51-1.16, P = .21), 3 years (OR, 1.12; 95% CI, 0.85-1.47, P = .43), and 5 years (OR, 1.14; 95% CI, 0.86-1.50, P = .37) postresection, respectively. CONCLUSIONS: Simultaneous resection is safe and efficient in the treatment of patients with SCLM while avoiding a second major operation. In appropriately selected patients, simultaneous resection might be considered as the preferred treatment. Since heterogeneity was detected, caution is needed in interpretation of the results. Better designed, adequately powered studies are required for addressing this issue.

[Clinicopathological and prognostic analysis of 23 poorly differentiated neuroendocrine carcinomas of the stomach].

OBJECTIVE: To evaluate the clinicopathological characteristics and prognosis of poorly differentiated neuroendocrine carcinoma of the stomach. METHODS: Twenty-three poorly differentiated neuroendocrine carcinomas of the stomach were treated in the Department of Abdominal Surgery at the Cancer Hospital, Fudan University between January 1996 and December 2007. Clinicopathological characteristics and survival data were analyzed. RESULTS: Poorly differentiated neuroendocrine carcinomas of the stomach accounted for 0.52% of all the gastric carcinomas. The tumor occurred more often in males (18 of 23), older patients (mean age of 62 years), upper third of the stomach (16 of 24,one patient had more than one lesion) with large size (mean diameter of 6.8 cm). TNM stages were as follows: stage II in 3 patients, stage III in 12, and stage IIII in 8. Thirteen patients underwent curative resection, while 8 underwent palliative resection and 2 others underwent exploratory laparotomy with biopsy. Of the 21 surgical resection specimens, vascular invasion was found in 18 patients (85.7%), perineural invasion in 16 patients (76.2%), and regional lymph node metastasis in 17 patients (81.0%). Follow up time ranged from 3 to 63 months. Mean overall survival time was 17.7 months. The 1-year, 2-year, and 5-year survival rates were 47.8%, 19.1%, and 4.3%, respectively. Statistically significant differences in survival curves were observed which were related to tumor staging and surgery type, but not related to gender, age, tumor location, or diameter. CONCLUSIONS: Poorly differentiated neuroendocrine carcinomas of the stomach are rare and with poor prognosis. Tumor stage and surgical type have potential impact on survival.

[Oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor].

OBJECTIVE: To characterize oncogenic KIT signaling mechanisms in gastrointestinal stromal tumor(GIST), and to determine which signaling pathway might be of potential relevance to imatinib acquired resistance. METHODS: The mutations of KIT and PDGFRa gene were evaluated and KIT downstream signaling profiles were evaluated in 8 specimen from 5 GIST patients who were evaluated treated between 2003 and 2008 in our hospital. Biochemical inhibition of the expression of related proteins in Ras/Raf/MAPK and PI3-K/AKT pathways, such as KIT, mitogen-activated protein kinase(MAPK),mammalian target of rapamycin(MTOR), AKT, Proliferating cell nuclear antigen (PCNA) and BCL-2, were determined by Western blotting for protein activation. RESULTS: Three cases who showed response to imatinib carried primary mutations in KIT gene, with 2 cases possessing mutation in exon 11, 1 case in exon 13. One case with imatinib-resistance developed KIT secondary mutation, but all the cases had no PDGFRa mutation. p-KIT and p-AKT expressions were higher in the samples of imatinib-resistant GIST than those of imatinib-responsive GIST. Total KIT, MAPK, p-MAPK, p-MTOR expressions were strong and comparable in all varied GISTs, which had no significant difference between imatinib-resistant and imatinib-responsive samples. PCNA and BCL-2 expression varied in samples of different therapy cycles and different location. CONCLUSIONS: Ras/Raf/MAPK and PI3-K/AKT/MTOR pathways are essential to GIST pathogenesis. The KIT secondary mutation and PI3-K/AKT/MTOR pathway are particularly relevant for therapeutic targeting in imatinib-resistant GIST.

[Value of preoperative barium contrast examination for the diagnosis and operative planning in gastric cancer].

OBJECTIVE: To investigate the value of preoperative barium contrast examination for the diagnosis and operative planning in gastric cancer. METHODS: Clinical data of 229 gastric cancer patients were analyzed retrospectively. Lesions were divided into three parts: the cardiac, the body, and the antrum. The diagnostic accuracy of localization and the extent of tumor between gastroscopy alone and gastroscopy plus barium contrast were compared with the results of surgical findings. RESULTS: The diagnostic accuracy of localization and the extent of tumor for gastroscopy in the cardiac, the body and the antrum cancers were 100% and 78.4%, 94.6% and 86.5%, 98.1% and 84.6%, respectively, while for gastroscopy plus barium contrast were 100% and 84.8%, 100% and 91.9%, 99.0% and 90.4%, respectively. The diagnostic accuracy of both the localization and the extent of tumor were not significantly different between gastroscopy alone and gastroscopy plus barium contrast (P>0.05). Diagnostic accuracy of the length of esophagus infiltrated by cardiac cancer in gastroscopy was 60.6%, while in gastroscopy plus barium contrast was 90.9%, which was significantly different (P<0.05). Gastroscopy plus barium contrast was more accurate in predicting the possibility of thoracotomy in cardiac cancer infiltrating the lower esophagus. CONCLUSIONS: It is necessary to perform preoperative barium contrast examination in cardiac cancer patients, so as to identify whether the lower esophagus is infiltrated and to measure the length of lesion, which can provide evidences for making a decision of thoracotomy. For gastric body and antrum cancer, there is no indication for barium contrast examination if gastroscopy findings are satisfied.