Discovery of natural product derivative triptolidiol as a direct NLRP3 inhibitor by reducing K63-specific ubiquitination.

Background And Purpose: NLRP3 is up-regulated in inflammatory and autoimmune diseases. The development of NLRP3 inhibitors is challenged by the identification of compounds with distinct mechanisms of action avoiding side effects and toxicity. Triptolide is a natural product with multiple anti-inflammatory activities, but a narrow therapeutic window.

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.

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.

[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).

[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.

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.

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.

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.

[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.

[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.

[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 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.

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.

[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.

[Transcription factor Sp1 expression in gastric cancer and its prognostic value].

Objective: To investigate the expression of transcription factor Sp1 in human gastric cancer tissues and normal gastric mucosa, and its prognostic significance.

Methods: By using immunohistochemistry, we studied the Sp1 expression patterns in 65 cases of gastric cancer with various clinico-pathologic characteristics, and 40 normal gastric mucosa specimens obtained from patients who underwent partial gastrectomy for benign gastric diseases. The significance of Sp1 expression on the survival of patients was evaluated.

[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.

[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.

[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.

[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.

[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.

[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.

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).

Expression of vascular endothelial growth factor C and chemokine receptor CCR7 in gastric carcinoma and their values in predicting lymph node metastasis.

Aim: To study the expression of vascular endothelial growth factor C (VEGF-C) and chemokine receptor CCR7 in gastric carcinoma and to investigate their associations with lymph node metastasis of gastric carcinoma and their values in predicting lymph node metastasis.

Methods: The expression of VEGF-C and CCR7 in gastric carcinoma tissues obtained from 118 patients who underwent curative gastrectomy was examined by immunohistochemistry. Among these patients, 39 patients underwent multi-slice spiral CT (MSCT) examination.

Antitumor effects of vaccine consisting of dendritic cells pulsed with tumor RNA from gastric cancer.

Aim: To investigate the immunotherapeutic potential of vaccine consisting of dendritic cells (DCs) pulsed with total RNA from MFC gastric cancer cells.

Methods: DCs were prepared from the spleens of strain 615 mice by magnetic cell sorting (MACS). After culture for 24 h, DCs were pulsed with total RNA from MFC gastric cancer cells.

Correlation of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells to 5-fluorouracil and 5-fluoro-2'-deoxyuridine.

Aim: To determine the expression levels of three metabolic enzymes of fluoropyrimidines: thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in seven human gastrointestinal cancer cell lines, and to compare the enzyme levels with the sensitivity to 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd).

Methods: TS, TP and DPD mRNA levels were assessed by semi-quantitative RT-PCR, TP and DPD protein contents were measured by ELISA. Fifty percent inhibitory concentrations of growth (IC50), representing the sensitivity to drugs, were determined by MTT assay.