Targeting the NLRP3 inflammasome as new therapeutic avenue for inflammatory bowel disease.

The incidence and prevalence of inflammatory bowel disease (IBD) are increasing worldwide. Current approved medication for IBD treatment in the clinic mainly includes corticosteroids and neutralization antibodies to pro-inflammatory cytokines. However, drug resistance and severe side effect hinder long-term efficacy of these agents. The NOD-like receptor family pyrin domain containing protein 3 (NLRP3) is exclusively expressed in several inflammatory and autoimmune diseases. Excessive expression, aberrant activation, polymorphism, and gain-of-function mutation of the NLRP3 inflammasome contribute to IBD pathogenesis. In this article, we summarize the regulatory factors to NLRP3, and review recently developed NLRP3 inhibitors and their preclinical and clinical applications in treating inflammatory and autoimmune diseases. We present our views on the therapeutic potential of NLRP3 inhibitors as emerging therapeutic avenue for IBD.

Surgical resection with hyperthermic intraperitoneal chemotherapy for gastric cancer patients with peritoneal dissemination.

BACKGROUND: The prognosis for gastric cancer patients with peritoneal dissemination is very poor. The purpose of this study was to evaluate the survival benefit from gastrectomy with hyperthermic intraperitoneal chemotherapy (HIPEC) for gastric cancer patients with peritoneal dissemination. METHODS: From 1992 to 2002, 128 gastric cancer patients with peritoneal dissemination underwent surgery at the Department of Surgery, Ruijin Hospital, Shanghai, China. The clinicopathological characteristics and survival were compared between the resection and the non-resection groups, and between the resection alone and the resection with HIPEC groups. RESULTS: The 5-year survival rates were 5.5% for patients in the resection group and 0% for patients in the non-resection group (P < 0.001). Multivariate analysis showed surgical resection was significantly associated with better prognosis in gastric cancer patients with peritoneal dissemination. In the patients who underwent resection, the survival difference between the resection alone and the resection with HIPEC groups was significant (P = 0.025), and HIPEC was an independent prognostic factor by multivariate analysis. CONCLUSIONS: The HIPEC procedure was an independent prognostic factor after resection for patients with peritoneal dissemination. Therefore, gastrectomy with HIPEC may be an option for those patients. The survival benefit of this strategy should be validated by large cohort prospective clinical trials.

[Value of multidetector-row CT in the preoperative prediction of peritoneal metastasis from gastric cancer: a single-center and large-scale study].

OBJECTIVE: To investigate the value of multidetector-row computed tomography (MDCT) in preoperatively predicting peritoneal metastasis of gastric cancer and to evaluate the indication for laparoscopic staging of gastric cancer on the basis of MDCT features. METHODS: Six hundred and forty gastric cancer patients underwent preoperative MDCT examination, and the results of MDCT were compared with surgical and pathological findings. In addition, the relationship between MDCT features (depth of invasion, lymph node metastasis status, tumor size, and thickness of tumor) and peritoneal metastasis of gastric cancer was analyzed. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MDCT in predicting peritoneal metastasis of gastric cancer were 51.0% (25/49), 99.3% (587/591), 86.2% (25/29), 96.1% (587/611), and 95.6% (612/640), respectively. Univariable analysis showed that all the four MDCT features (depth of invasion, lymph node metastasis status, tumor size, and tumor thickness) of gastric cancer were significantly correlated with the peritoneal metastasis of gastric cancer. None of the patients diagnosed with stage T(0~2)N(x)M(0) or T(x)N(0)M(0) gastric cancer by MDCT were found to have peritoneal metastasis. Receiver operating characteristic (ROC) analysis showed that the accuracy of the tumor size and thickness of gastric cancer in determining peritoneal metastasis was high(area under ROC curve was 0.83 and 0.75, respectively). Multivariable analysis showed that only tumor size was significantly correlated with the peritoneal metastasis from gastric cancer. CONCLUSIONS: The clinical value of MDCT in preoperative prediction of peritoneal metastasis from gastric cancer is favorable. Laparoscopy can be avoided in patients with small tumor size or stage T(0~2)N(x)M(0) or T(x)N(0)M(0) gastric cancer diagnosed by MDCT due to lower incidence of peritoneal metastasis.

[A comparative study on the efficacy of spleen-preserving modified D2 radical gastrectomy and D2 radical gastrectomy with splenectomy].

OBJECTIVE: To compare the efficacy of modified D(2) radical total gastrectomy with spleen-preserving and D(2) radical total gastrectomy with splenectomy in patients with gastric cancer located in the upper third, upper and middle third and entire stomach. METHODS: One hundred and twelve patients with gastric cancer in the upper third, upper and middle third, or entire stomach underwent radical total gastrectomy between January 1989 and December 1994. Modified D(2) total radical gastrectomy with spleen-preserving (spleen-preservation group) was performed in 61 patients, and 51 underwent D(2) total radical gastrectomy with splenectomy (splenectomy group). The differences in clinicopathological characteristics,5-year survival rate, incidence of postoperative complication and hospital stay between the two groups were analyzed retrospectively. RESULTS: There were no significant differences between the spleen-preservation group and the splenectomy group in gender, age, tumor size, T stage, N stage and TNM stage. The overall 5-year survival rate was 41.0% in the spleen-preservation group and 39.2% in the splenectomy group (P>0.05). The 5-year survival rates of patients with stage I, II, III and IIII were 100%, 66.7%, 27.8% and 17.4% in the spleen-preservation group, respectively, and were 100%, 70.0%, 26.7% and 5.6% in the splenectomy group, respectively (all P>0.05). The incidence of postoperative complication was lower in the spleen-preservation group (11.5% vs 27.5%, P<0.05). The mean hospital stay was longer in the splenectomy group (27.3 d vs 20.3 d, P=0.057). CONCLUSION: The efficacy of modified D(2) radical total gastrectomy with spleen-preserving for patients with gastric cancer in the upper third, upper and middle third or entire stomach is similar to that of D(2) radical total gastrectomy with splenectomy, and the spleen-preserving procedure is associated with decreased postoperative complication and improved survival.

Survival benefit of non-curative gastrectomy for gastric cancer patients with synchronous distant metastasis.

BACKGROUND: The prognosis for gastric cancer patients with distant metastasis is very poor. The purpose of this study was to evaluate the survival benefit of non-curative gastrectomy for gastric cancer patients with synchronous distant metastasis. METHODS: From 1992 to 2002, 253 gastric cancer patients with synchronous distant metastasis underwent surgery at the Department of Surgery, Ruijin Hospital, China. The clinicopathological characteristics and survival were compared between resection and non-resection groups. RESULTS: The 5-year survival rate was 6.5% for patients in resection group and 0% for patients in non-resection group (P < 0.001). Multivariate analysis showed that liver metastasis, peritoneal dissemination, and non-resection were significantly associated with poor prognosis in gastric cancer patients with distant metastasis. The survival difference between resection and non-resection groups was only observed in patients with single peritoneal dissemination (P < 0.001), but were not in patients with single liver metastasis (P = 0.428), distant nodes involvement (P = 0.490) and multiple metastatic sites (P = 0.192), respectively. CONCLUSIONS: Our results suggests that there were no survival benefit from non-curative gastrectomy for patients with single liver, distant nodes, or multiple sites metastasis. However, only patients with single peritoneal dissemination had survival benefit from non-curative resection. The value of non-curative resection should be evaluated by well-designed clinical trials.

Value of multidetector-row computed tomography in the preoperative T and N staging of gastric carcinoma: a large-scale Chinese study.

OBJECTIVES: To investigate the value of multidetector-row computed tomography (MDCT) in the preoperative T and N staging of gastric carcinoma and to further investigate the clinicopathological factors affecting the diagnostic accuracy. METHODS: Seven hundred ninety gastric carcinoma patients underwent preoperative MDCT examination. The results of MDCT were compared with surgical and pathological findings. RESULTS: Early gastric carcinoma patients whose primary tumor was detected by MDCT had higher incidence of lymph node metastasis, larger tumor size, and deeper invasion. The overall accuracy of MDCT in determining T stage of gastric carcinoma was 73.80% (T1 45.93%, T2 53.03%, T3 86.49%, and T4 85.79%). The overall accuracy of MDCT in preoperative N staging was 75.22% (N0 76.17%, N1 68.81%, and N2 80.63%). The overall diagnostic sensitivity, specificity, and accuracy of MDCT for determining lymph node metastasis was 86.26%, 76.17%, and 82.09%, respectively. Multivariate analysis showed that the diagnostic sensitivity of MDCT in determining lymph node metastasis related with tumor size, N stage, and number of metastatic lymph nodes. CONCLUSIONS: The clinical value of MDCT in the preoperative T and N staging of gastric carcinoma is relatively high. MDCT can be the first choice for the preoperative evaluation of patients with gastric carcinoma.

Gastric cancer surgery and its hazards: post operative infection is the most important complication.

BACKGROUND/AIMS: To evaluate early surgical outcome and analyze postoperative complications of gastric cancer surgery, on the basis of standard auditing system. METHODOLOGY: 357 patients who underwent operations for gastric cancer were included in this study. We applied POSSUM (Physiological and Operative Severity Score for the enumeration of Morbidity and mortality) system to predict morbidity. The observed to estimated morbidity ratio (O: E) was calculated to give risk adjusted morbidity. All the complications were stratified according to its severity and analyzed separately. RESULTS: Observed morbidity was not significantly different from predicted value, the O: E ratio was 1.01. Overall, 137 patients were observed to have postop complications (including 5 death); infection was the main complication which complicated about 17 per cent patients and occupying 44 per cent of all complications. Pulmonary infection rate was on the top. CONCLUSIONS: Post operative complication is higher in gastric cancer surgery. POSSUM system along with stratification of complications is a reliable algorithm in surgical audit to analyze various complications. Postoperative infection is the culprit of various complications. Postoperative infection especially the pulmo-nary infection stands on the top of all complications. More prospective study including basic researches is necessary to explore the etiology of different compilations.

[Capecitabine combined with cisplatin as first-line therapy in Chinese patients with advanced gastric carcinoma-a phase II clinical study].

OBJECTIVE: To evaluate the effectiveness and safety of the combination chemotherapy of capecitabine (X) with fractionated administration of cisplatin (C) in Chinese patients with advanced gastric cancer (AGC). METHODS: 141 patients with AGC were enrolled between July 2002 and August 2004. All patients had measurable tumor according to the criteria of RECIST, Karnofsky performance status > or = 60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was not permitted. Patients received oral administration of capecitabine at a dose of 1000 mg/m(2) twice a day on D1-D14, and intravenous infusion of fractionated cisplatin at a dose of 20 mg/m(2)/day on D1-D5. The regimen was repeated every 3 weeks, totally for 6 cycles. RESULTS: Of the 141 evaluable patients, there were 104 men and 37 women, with a median age of 54 years (range, 23 - 80 years). Metastases before chemotherapy were detected in lymph nodes (46.8%), liver (40.4%), lung (5.7%) and other area (10.6%). The median treatment duration was 6 cycles (range, 3 - 6 cycles). The objective response rate (RR) was 36.2% (51/141). The median follow-up period was 17.5 months. The median time to progress (TTP) was 9.0 months, and the median overall survival (OS) was 12.0 months. The most common treatment-related adverse events (grade 3/4) were: hand-foot syndrome (HFS) (2.1%), leucopenia (0.7%), abnormal alanine transaminase elevation (2.8%). There was no treatment-related death. CONCLUSION: Capecitabine combined with fractionated cisplatin is highly effective and well tolerated as a first-line treatment for advanced gastric cancer, with comparable results to 5-Fu plus cisplatin combination therapy.

[Prognostic significance of metastatic lymph nodes ratio in patients with T2-T3 stage gastric cancer].

OBJECTIVE: To evaluate the prognostic significance of metastatic lymph nodes ratio in patients with T(2)~T(3) stage gastric cancer. METHODS: Clinical data of 238 patients with T(2)-T(3) stage gastric cancer undergone radical gastrectomy and D(2) lymphadenectomy, at least 15 lymph nodes was dissected per patient, were analyzed retrospectively. Spearman correlation analysis was used to determine the correlation coefficient. Survival was determined by the Kaplan-Meier method and differences were assessed by the Log-rank test. Multivariate analysis was performed using the Cox proportional hazard regression model in forward stepwise regression. Receiver working characteristic curve was used to compare the accuracy of the metastatic lymph nodes ratio in predicting the death of patients 5 years postoperatively and that of metastatic lymph nodes number. RESULTS: The metastatic lymph nodes ratio didn't correlate with the total number of dissected lymph nodes, whereas metastatic lymph nodes number did. Kaplan-Meier survival analysis demonstrated the metastatic lymph nodes ratio significantly influenced the postoperative survival time and Cox proportional hazard regression model analysis showed the metastatic lymph nodes ratio was an independent poor prognostic factor. There was no significant difference between the area under the receiver working characteristic curve of metastatic lymph nodes ratio and metastatic lymph nodes number in predicting the death of patients 5 years postoperatively. CONCLUSIONS: The metastatic lymph nodes ratio in T(2)-T(3) stage gastric cancer patients is not correlated with the total number of dissected lymph nodes if at least 15 lymph nodes are dissected. The metastatic lymph nodes ratio is a major independent poor prognostic factor of the patients of T(2)-T(3) stage gastric cancer. The ability of the metastatic lymph nodes ratio in predicting the death of T(2)-T(3) stage gastric cancer patients 5 years postoperatively is the same as that of metastatic lymph nodes number.

[Chromosomal alterations analyzed by comparative genomic hybridization in primary gastric carcinoma].

OBJECTIVE: To identify genetic abnormalities in primary gastric carcinoma. METHODS: Comparative genomic hybridization (CGH) was used in screening DNA copy number changes along all chromosomes in 23 cases of primary gastric cancer. RESULTS: Twenty-one out of 23 cases showed chromosomal losses and gains for at least one of the chromosomal arms in primary gastric cancer. The mean number of chromosomal alterations was 7.52. Chromosomal gains predominated over chromosomal losses in a ratio of 5.38:2.14. The most often involved chromosomal gains were observed in 8q (9/21, 42.9%), 20q (9/21, 42.9%), 17q (8/21, 38.1%), 3q (7/21, 33.3%), 7q (7/21, 33.3%), 11q (6/21, 28.6%), 13q (6/21, 28.6%), 1q (5/21, 23.8%) and 20p (5/21, 23.8%). The chromosomal arms with frequent losses were 17p (7/21, 33.3%), 18q (6/21, 28.6%), 5q (5/21, 23.8%), 8p (5/21, 23.8%), and 9p (5/21, 23.8%). CONCLUSIONS: The phenomenon of gain and loss of chromosomal regions is observed in primary gastric cancer, which may induce the amplification of oncogenes and the loss of tumor suppressor genes to regulate the development and progression of gastric cancer.

The impact of hyperthermic chemotherapy on human gastric cancer cell lines: preliminary results.

In this preliminary study, we evaluated the impact of hyperthermia (HT) and hyperthermic chemotherapy (HTCT) on six human gastric cancer cell lines and explored the mechanisms of cell-killing effect under HTCT. Treatment conditions were categorized into 4 modes: i) normothermic control (NT), ii) HT, iii) normothermic chemotherapy (NTCT) and iv) HTCT. According to the data of MTT and LM observations, isolated HT only temporarily inhibited cell proliferation and had no cell-killing effect on gastric cancer cell lines employed in our study except for SNU-1. Combining with HT enhanced the cytotoxicity of CDDP in all gastric cell lines and the concentration inhibiting cell proliferation and inducing cell death of HTCT was much lower than that of NTCT. There was a synergistic effect of HT and chemotherapy on inhibiting proliferation in each cell line in a certain range of CDDP concentration. The data of TEM and FCM proved that HTCT induced cell death with two modes - apoptosis and necrosis, and apoptosis was the major type. Microarray illustrated that, under HTCT, a total of 58 gene expressions were regulated according to the filtering criteria, including 10 extra genes with an expression change below the threshold or even unchanged when treated with either HT or CDDP alone. Five of these 10 genes were verified by QRT-PCR. These genes may include the target genes for the enhancing effect of HT on chemotherapy and their effects should be further validated by functional analysis.

Efficacy and safety of intraoperative peritoneal hyperthermic chemotherapy for advanced gastric cancer patients with serosal invasion. A long-term follow-up study.

AIMS: This study was undertaken to investigate the clinical effects and safety of intraoperative peritoneal hyperthermic chemotherapy (IPHC) for advanced gastric cancer (AGC) patients. METHODS: A total of 118 AGC patients with serosal invasion were enrolled in this study from 1998 to 2001, 52 underwent IPHC after gastrectomy and 66 were treated with gastrectomy only. Among these cases, 96 patients without macroscopic peritoneal metastases were selected for the prophylactic study, 22 with peritoneal metastases were selected for the therapeutic study. Postoperative survival, recurrence pattern and incidences of postoperative complications between patients with and without IPHC were analyzed and compared. RESULTS: For the prophylactic study, the IPHC procedure improves postoperative survival rate and decrease the incidence of peritoneal recurrence, and is an independent prognostic factor for these patients. For the therapeutic study, postoperative survival times were longer if IPHC was undertaken. No surgery-related death occurred. The incidence of renal dysfunction was higher in the IPHC group, but all patients recovered without hemodialysis. CONCLUSION: IPHC is a safe procedure that improves the survival prognosis for AGC patients with serosal invasion. It is especially beneficial for patients without peritoneal metastasis due to the reduction of postoperative peritoneal recurrence.

[The relationship between frameshift mutations of transforming growth factor-beta type II receptor, insulin growth factor II receptor, bcl-2 associated X protein, E2F4 and microsatellite instability in gastric carcinoma].

OBJECTIVE: To determine the microsatellite instability in gastric carcinomas, examine the frameshift mutations of transforming growth factor-beta type II receptor (TGFbetaRII), insulin growth factor II receptor (IGFIIR), bcl-2 associated X protein (BAX) and E2F4, and investigate whether or how alterations of the TGFbetaRII, IGFIIR, BAX and E2F4 gene are associated with MSI in gastric cancer. METHODS: Formalin-fixed, paraffin-embedded gastrectomy specimens and matching normal tissues of 65 cases of gastric carcinomas were retrieved from shanghai Ruijin Hospital and Shanghai East Hospital. DNA was extracted from tissue sections using phenol chloral isoamyl alcohol. Sections with no more than 50% of tumor cell areas were isolated by microdissection. DNA was amplified by PCR-based single strand conformation polymorphism (SSCP) for microsatellite analysis and was sequenced directly. Frameshift mutations in the coding regions, repetitive mononucleotide tracts of (A)10 for TGFbetaRII, (G)8 for IGFIIR, (G)8 for BAX, and trinucleotide repeats of (AGC)13 for transcription factors E2F4 were detected using PCR. Tumors were classified as being microsatellite stable (MSS) or having a low frequency of MSI (MSI-L, one of markers different in the tumor) or a high frequency of MSI (MSI-H, two or more of markers different). RESULTS: Eleven cases (18.0%) showed MSI-L, 12 (19.7%) showed MSI-H and 38 (62.3%) cases showed MSS. The mutation rates of TGFbetaRII, IGFIIR, BAX and E2F4 gene were 19.7%, 4.9%, 6.6% and 16.4% respectively. Among the 12 MSI-H gastric cancers, there were 10 TGFbetaRII mutations, 3 IGFIIR mutations, 4 BAX mutations and 10 E2F4 gene mutations. The alterations in the repeats of the related genes presented polymorphisms. Associations of MSI-H status and mutations of the 4 genes were highly significant (P < 0.01, respectively). No repeat tracts mutations in TGFbetaRII, IGFIIR, BAX and E2F4 gene were found in MSS tumors. CONCLUSIONS: The repeat coding regions within TGFbetaRII, IGFIIR, BAX and E2F4 gene are the targets of microsatellite instability. Frameshift mutations of the 4 genes play an important role in the development and progression of gastric cancers with microsatellite instability.

[Clinical effect of intraoperative peritoneal hyperthermic chemotherapy for advanced gastric cancer].

OBJECTIVE: To investigate the clinical effect of intraoperative peritoneal hyperthermic chemotherapy (IPHC) for advanced gastric cancer (AGC). METHODS: A total of 118 AGC patients with serosal invasion were enrolled in this study from 1998 to 2001. Among these cases, 96 patients without macroscopic peritoneal metastases were selected for prophylactic study, including 42 cases with IPHC and 54 cases without IPHC as control. Other 22 patients with macroscopic peritoneal metastases were selected for therapeutic study, including 10 cases with IPHC and 12 without IPHC. Postoperative survival rate and peritoneal recurrence were compared. RESULTS: For prophylactic study, the 1, 2 and 4 years survival rates were 85.7%, 81.0% and 63.9% respectively in the patients with IPHC,significantly higher than 77.3%, 61.0% and 50.8% in the patients without IPHC. Cox ratio hazard model revealed that IPHC procedure was an independent prognostic factor. More patients in the control group suffered from peritoneal recurrence than those in IPHC group (34.7% vs 10.3%). For therapeutic study,the median survival period of the patients with IPHC was 10 months, higher than 5 months in the patients without IPHC. The overall 1, 2, 4 year survival rates were 76.9%, 69.2%, 55.2% respectively in all cases with IPHC, higher than 66.2%, 49.7%, 41.4% in the cases without IPHC. CONCLUSION: IPHC procedure can improve the prognosis of AGC patients with serosal invasion, reduce the risk for peritoneal recurrence, and is an independent prognostic factor.

[Inhibitory effect of dendritic cells pulsed with MAGE-3 peptide on transplanted murine gastric cancer in mice].

OBJECTIVE: To observe the inhibitory effect of MAGE-3 peptide pulsed DC on transplanted murine gastric cancer in 615 mice. METHODS: The CTL clones directed against MAGE-3 peptide were tested for the ability to lyse the gastric cancer cell line MFC which can express MAGE-3 antigen. In immunoprotection experiment, mice of the study group were immunized with MAGE-3 peptide pulsed DC (DC/MAGE-3) at the dosage of 1 x 10(6) on d0 and d7 by sc inoculation, mice of control groups were immunized with influenza virus peptide pulsed DC (DC/Nup) or unpulsed DC at the same dosage on days as the DC/MAGE-3 group. On d14, all the mice were challenged with sc injections of 5 x 10(5) MFC gastric cancer cells. In immunotherapy experiment, all the mice were sc injected 5 x 10(5) MFC gastric cancer cells on d0, and on d3, d10 mice of each groups were sc inoculated with DC/MAGE-3, DC/Nup or unpulsed DC at the dosage of 1 x 10(6) respectively. All mice were monitored closely with respect to tumor growth and survival times. RESULTS: The CTL clone induce by MAGE-3 peptide could lyse the MFC cells efficiently. Immunization of mice with DC pulsed with MAGE-3 generated partial protective immunity against MFC tumor, as well as significant inhibition of tumor growth in a 3-day tumor model. CONCLUSION: The tumor vaccine with DCs pulsed with MAGE-3 peptide possesses the ability to stimulate tumor specific CTL activity and to establish antitumor immunity when administered in vivo.

[COX- 2 expression in gastric cancer and its relationship with lymphangiogenesis and lymph node metastasis].

OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor-C (VEGF-C) in human gastric cancer, the relationship between their expression and the clinicopathological features,as well as the relationship between these two parameter expression and lymphangiogenesis and lymph node metastasis. METHODS: COX-2 and VEGF-C expressions were detected in 63 gastric cancer samples by immunostaining. Lymphangiogenesis was evaluated by immunostaining with the specific antibody LYVE-1. RESULTS: The expression rates of COX-2 and VEGF-C were 66.7% (42/63), 52.4% (33/63), respectively in 63 gastric cancer specimens. LYVE-1 was positive in 35 cases (35/63), which indicated lymphangiogenesis in the tumors. The expression of COX-2 was significantly correlated with the expression of VEGF-C, tumor lymphangiogenesis and lymphatic metastasis (P< 0.05), however not gender, tumor size, tumor location, Lauren classification and serosa invasion (P< 0.05). CONCLUSIONS: In gastric cancer, the expression of COX-2 is significantly associated with VEGF-C expression, lymphangiogenesis and lymphatic metastasis. COX-2 may up-regulate the expression of VEGF-C, which induces lymphangiogenesis and accordingly contributes to lymphatic metastasis.

[Study on amplification of ZNF217 in primary gastric carcinoma].

OBJECTIVE: To investigate amplification of zinc finger protein 217(ZNF217) and its association with clinicopathologic parameters in primary gastric carcinoma. METHODS: Semiquantitative polymerase chain reaction (PCR) was used to determine DNA copies of ZNF217 in the specimens from forty- seven cases with primary gastric carcinoma. RESULTS: There was no difference in DNA copies between tumor specimens and paratumor normal tissues. The incidence of ZNF217 amplification was 11.36% in gastric cancer. The amplification of ZNF217 was significantly associated with tumor size(P< 0.01) and intestinal type of stomach cancer(P< 0.05). CONCLUSION: Oncogene ZNF217 may play a role in specific tumor types or subtypes of gastric cancer. There may be other oncogenes associated with gastric carcinoma in 20(q)13.

[Study of hepatic injury during stop-flow chemotherapy].

OBJECTIVE: To observe the hepatic injury following stop- flow chemotherapy and investigate the potential mechanisms. METHODS: Twelve healthy hybrid female pigs were randomly divided into two groups as stop- flow group (SF) and stop- flow chemotherapy (SFC) group. The expression of IL- 8 and ICAM- 1 mRNA in hepatic biopsies was detected by RT- PCR, and the expression of NF- kappa B P65 subunit in nuclei was assessed by Western blot analysis. The levels of ALT and AST, and histopathologic alterations were examined to evaluate the hepatic function at different time before and after stop- flow procedure. RESULTS: The expression of NF- kappa B P65 subunit, IL- 8 and ICAM- 1mRNA increased at 30 min after stop- flow procedure, and gradually decreased at 3 h and 6 h after stop- flow procedure. The levels of ALT and AST decreased after reaching the peak at 24 h after stop- flow procedure, but removed one week after stop- flow procedure. Cytoplasmic microvascular steatosis developed with appreciable neutrophils infiltration after early stop- flow procedure without significant destroy occurred in the structure of hepatic lobule. No significant difference of various parameters above occurred between SF and SFC groups. CONCLUSION: The hepatic injury following stop- flow procedure was self-limited and reversible. There is no severe destroy of hepatic structure and disfunction during stop- flow chemotherapy.

[Value of transabdominal ultrasonography in preoperative assessment of gastric carcinoma].

OBJECTIVE: To investigate the value of transabdominal ultrasonography (TAUS) in preoperative assessment of TNM stage and tumor angiogenesis for patients with gastric carcinoma. METHODS: Sixty- four patients with gastric carcinoma preoperatively underwent TAUS, in whom transabdominal color Doppler ultrasonography was used for measuring color Doppler vascularity index (CDVI) of each tumor in 37 cases and microvessel density (MVD) was evaluated by using immunohistochemical staining of surgical specimens with anti- CD34 antibody. RESULTS: The overall accuracy rate was 56.0% for T staging of gastric carcinoma (T (1) 2/3 cases, T (2) 28.6% , T (3) 73.1% , T (4) 50.0% , respectively) by TAUS. The diagnostic accuracy rate was 63.3% for lymph node status of gastric carcinoma. The diagnostic sensitivity and specificity for lymph node metastasis was 37.9% and 100% respectively. The overall accuracy for N staging of gastric carcinoma was 57.1% (N (0) 100% , N (1) 16.7% , N (2) 35.3% , respectively). The diagnostic sensitivity and specificity for determining distant metastases was 58.3% and 100% respectively. The CDVI of gastric carcinoma determined by color Doppler ultrasonography was significantly correlated to vascular invasion (P=0.0418), a linear correlation between CDVI and MVD was determined by logistic regression analysis (r=0.5628, P< 0.01). CONCLUSION: TAUS can be a routine diagnostic approach for preoperative gastric carcinoma patients.

Hepatic preconditioning of doxorubicin in stop-flow chemotherapy: NF-kappaB/IkappaB-alpha pathway and expression of HSP72.

AIM: To provide hepatic protection through administration of doxorubicin before stop-flow chemotherapy (SFC) and to investigate the expression of heat shock protein 72 (HSP72) and role of nuclear factor kappa B (NF-kappaB) in this effect. METHODS: The hepatic preconditioning of doxorubicin was established in a porcine model by injection of doxorubicin (1 mg/kg) before SFC. The experimental animals were randomized into two groups: groups receiving doxorubicin (DOX) and normal saline (NS). Serial serum and tissue samples were taken from both groups to evaluate the protection of doxorubicin. Western blot and immuno-precipitation were applied to detect the expression of HSP72, NF-kappaB p65 protein, inhibitor kappaB-alpha (IkappaB-alpha) and phosphorylated IkappaB-alpha as well. The expression of tumor necrosis factor alpha (TNF-alpha) was estimated by semiquantitative RT-PCR. And the extent of the hepatic injury was estimated with the level of serum aminotransferases. RESULTS: An abundance production of HSP72 in porcine liver was observed after 24 h of intravenous administration of doxorubicin, but without any change in the expression of NF-kappaB p65 subunit in cytoplasm. NF-kappaB p65 subunit accumulated in nuclei at the end of SFC and reached its highest level at 30 min after the restoration of the abdominal circulation and decreased gradually during the 6 h after SFC in NS group, while there was little change in DOX group. There was also a slight decrease of IkappaB-alpha at 30 min after the restoration of the abdominal circulation in NS group accompanying with the appearance of phosphorylated IkappaB-alpha. The expression of TNF-alpha was significantly higher in NS group than that in DOX group (average 1.40+/-0.17 vs 0.62+/-0.22, P<0.01) at serial time points after SFC. Serum ALT and AST levels of NS group were higher after 24 h than those of DOX group (93.2+/-7.8 IU/L vs 53.3+/-13.9 IU/L, 217.0+/-29.4 IU/L vs 155.0+/-15.6 IU/L for ALT and AST respectively, P<0.05) and after 48 h than those of DOX group (66.6+/-18.1 IU/L vs 43.3+/-16.7 IU/L, 174.4+/-21.3 IU/L vs 125.7+/-10.5 IU/L for ALT and AST respectively, P<0.05). CONCLUSION: Doxorubicin renders the liver to be tolerant to the hepatic influence in SFC in a porcine model through the NF-kappaB/IkappaB-alpha pathway with the expression of HSP72.