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1.
Medicine (Baltimore) ; 98(35): e16999, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31464953

ABSTRACT

RATIONALE: Adenoid cystic carcinoma (ACC) rarely occurs in the digestive tract, particularly in the gastroesophageal junction. PATIENT CONCERNS: A 44-year-old male vomiting blood was admitted to our hospital. Endoscopic ultrasound showed a 2.2 × 3.0 cm submucosal tumor in the gastroesophageal junction. DIAGNOSIS: According to the histopathological examination, the tumor was composed predominantly of ductal epithelial and myoepithelial cells. Immunohistochemical staining revealed that the tumor expressed cytokeratin, cluster of differentiation 117, p63, and calponin. Based on these findings, ACC was diagnosed. INTERVENTIONS: Endoscopic submucosal dissection (ESD) was performed to remove the tumor. As the margins of the ESD specimen were positive, the patient underwent total gastrectomy with D2 lymphadenectomy. Finally, neither residual tumor nor lymphatic metastasis was detected in the surgical specimens. OUTCOMES: No sign of recurrence has been detected during 36 months of follow-up as of October 2018. LESSONS: ESD may be an alternative treatment for cardial ACC invading the submucosa.


Subject(s)
Carcinoma, Adenoid Cystic/pathology , Esophagogastric Junction/pathology , Stomach Neoplasms/pathology , Adult , Carcinoma, Adenoid Cystic/surgery , Endoscopic Mucosal Resection/methods , Gastrectomy/methods , Humans , Male , Stomach Neoplasms/surgery
2.
Front Immunol ; 10: 1741, 2019.
Article in English | MEDLINE | ID: mdl-31417548

ABSTRACT

Background: The leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) is considered a cancer stem cell marker, and is often overexpressed in tumors. The interaction between Lgr5 and the immune-related tumor microenvironment is not completely understood. The aim of this study was to examine the role of Lgr5 in the microenvironment of gastric cancer (GC), and to explore possible immunological mechanisms influencing Lgr5 expression that are governed by regulatory T cells. Methods: Lgr5 expression was examined in 180 GC tumors by immunohistochemistry, and in 80 pairs of GC tumors for analysis of Th1/Th2 cytokines by ELISA. In addition, SGC7901 cells were co-cultured with patient-derived Tregs, varying concentrations of TGF-ß1, TGF-ß1 neutralizing antibody, or TGF-ß receptor inhibitor SB431542, and Lgr5 and ß-catenin expression were examined by qRT-PCR and western blot. Results: In this study, an immunosuppressive microenvironment was associated with high Lgr5 expression in GC. Furthermore, Lgr5 expression was up-regulated in GC cells co-cultured with Tregs or treated with exogenous TGF-ß1. This up-regulation was partially inhibited by the TGF-ß1 neutralizing antibody, or TGF-ß1 receptor antagonist SB431542. ß-catenin was up-regulated with high Lgr5 expression induced by exogenous TGF-ß1, and this up-regulation was inhibited by SB431542. An increased number of Tregs and high Lgr5 expression in GC tissues were significantly associated with low overall survival. Conclusion: Tregs promoted increased Lgr5 expression in GC cells via TGF-ß1 and TGF-ß1 signaling pathway, which may involve activation of the Wnt signaling pathway. High Lgr5 expression via TGF-ß confer poor prognosis in gastric cancer.


Subject(s)
Gene Expression Regulation, Neoplastic/immunology , Neoplasm Proteins/immunology , Receptors, G-Protein-Coupled/immunology , Stomach Neoplasms , T-Lymphocytes, Regulatory/immunology , Transforming Growth Factor beta1/immunology , Cell Line, Tumor , Disease-Free Survival , Female , Humans , Immune Tolerance , Male , Stomach Neoplasms/immunology , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Rate , T-Lymphocytes, Regulatory/pathology , Tumor Microenvironment/immunology , Wnt Signaling Pathway/immunology
3.
Medicine (Baltimore) ; 98(6): e14477, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30732216

ABSTRACT

RATIONALE: The efficiency and tolerance of long-term adjuvant imatinib treatment for patient who underwent complete resection of a localized recurrent gastrointestinal stromal tumor (GIST) was unknown. PATIENT CONCERNS: A 45-year-old man underwent complete resection of an intestinal GIST in August 2001. Four years later, a giant (11 × 8 × 6 cm) recurrent GIST located in the retroperitoneum was detected. DIAGNOSIS: The recurrent tumor was positive for CD117 by immunohistochemistry. INTERVENTIONS: The recurrent tumor was completely resected after 4 months of effective imatinib treatment (400 mg/day), and the patient continued imatinib treatment postoperatively. In June 2011, imatinib treatment was stopped for 3 weeks because of hepatitis B infection, and resumed with a reduced dose level of 300 mg/day when liver function recovered. In March 2017, imatinib treatment was interrupted again for 12 days because the patient underwent cholecystectomy. OUTCOMES: In December 2017, a computed tomography scan showed no signs of tumor recurrence. To date, the patient has been under adjuvant imatinib treatment for >12 years without severe side effects. The plasma concentration of imatinib (detected in February 2018) was trough concentration (Cmin) 1015.7 ng/mL and peak concentration (Cmax) 1550.5 ng/mL. LESSONS: This case report highlights the active role of long-term (>12 years) imatinib treatment after complete resection of localized recurrent GIST.


Subject(s)
Antineoplastic Agents/therapeutic use , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Imatinib Mesylate/therapeutic use , Antineoplastic Agents/administration & dosage , Chemotherapy, Adjuvant , Gastrointestinal Stromal Tumors/surgery , Humans , Imatinib Mesylate/administration & dosage , Male , Middle Aged , Neoplasm Recurrence, Local
4.
J Chemother ; 28(1): 59-64, 2016.
Article in English | MEDLINE | ID: mdl-25977986

ABSTRACT

This study aimed to evaluate the efficacy of FOLFOX6, SOX and XELOX as neoadjuvant chemotherapy for advanced gastric cancer. The study retrospectively assessed clinicopathological data of patients who received a radical D2 gastrectomy for gastric cancer from January 2010 to January 2013.The patients were either not administered neoadjuvant chemotherapy (control) or were given FOLFOX6, SOX and XELOX prior to surgery. The metastatic rate was also higher for the control group compared with the three chemotherapy regimens in N2 station lymph nodes (P < 0.001). The SOX group had significantly lower metastatic total and N2 station lymph nodes than FOLFOX6 and XELOX (P < 0.01). The frequency of metastatic lymph nodes relative to total lymph nodes examined was 9.9, 6.6, 3.9 and 5.3% for control, FOLFOX6, SOX and XELOX groups, respectively. In conclusion, SOX may be the most effective of these treatments as preoperative chemotherapy for Chinese patients with advanced gastric cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gastrectomy , Neoadjuvant Therapy , Stomach Neoplasms/drug therapy , Adult , Aged , Case-Control Studies , Chemotherapy, Adjuvant , China/epidemiology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/epidemiology , Stomach Neoplasms/secondary , Stomach Neoplasms/surgery , Survival Rate
5.
World J Gastroenterol ; 21(8): 2573-6, 2015 Feb 28.
Article in English | MEDLINE | ID: mdl-25741171

ABSTRACT

A 67-year-old female presented with a primary hepatic gastrointestinal stromal tumor that was detected by computed tomography and diagnosed based on histopathological and genetic analyses. The tumor was microscopically composed of spindle cells and epithelioid cells, and immunohistochemistry results showed positive staining for CD117 and CD34 expression. A genetic analysis revealed a heterozygous point mutation and deletion in exon 11 of c-KIT. After an R0 resection, imatinib mesylate was administered for 1 year until its use was discontinued due to severe side effects. Two years after the original operation, the tumor recurred in the residual liver and was completely resected again. Imatinib mesylate was administered for 2 years until it was replaced by sunitinib malate because of disease progression. The patient has survived for 53 mo after undergoing a sequential therapy consisting of surgical excision, imatinib and sunitinib.


Subject(s)
Antineoplastic Agents/administration & dosage , Benzamides/administration & dosage , Gastrointestinal Stromal Tumors/therapy , Hepatectomy , Indoles/administration & dosage , Liver Neoplasms/therapy , Piperazines/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Pyrroles/administration & dosage , Aged , Antineoplastic Agents/adverse effects , Benzamides/adverse effects , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Biopsy , Chemotherapy, Adjuvant , DNA Mutational Analysis , Drug Substitution , Female , Gastrointestinal Stromal Tumors/chemistry , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/pathology , Humans , Imatinib Mesylate , Immunohistochemistry , Liver Neoplasms/chemistry , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Mutation , Piperazines/adverse effects , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Sunitinib , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
6.
Cancer Sci ; 105(2): 150-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24261990

ABSTRACT

Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) play important roles in the immune escape of cancer. In this study, we investigated pDCs and pDC-induced inducible costimulator (ICOS)(+) Treg populations in peripheral blood from gastric cancer (GC) patients and healthy donors by flow cytometry. The distribution of these cells in carcinoma tissue, peritumor tissue, and normal gastric mucosa was detected by immunohistochemistry. Plasma and tissue concentration of the cytokines such as interleukin-10 and transforming growth factor-ß1 were also measured. We found that the numbers of pDCs, Tregs, and ICOS(+) Tregs in peripheral blood were increased in GC patients compared with healthy donors. In tissue, Tregs and ICOS(+) Tregs were found distributing mainly in carcinoma tissue, whereas pDCs were mainly found in peritumor tissue. Moreover, the Foxp3(+) ICOS(+) /Foxp3(+) cell ratio in carcinoma and peritumor tissue were higher than that in normal tissue. There were more ICOS(+) Tregs in tumor and peritumor tissue of late-stage GC patients. There was a positive correlation between pDCs and ICOS(+) Tregs in peripheral blood and peritumor tissue from GC patients. In conclusion, pDCs may play a potential role in recruiting ICOS(+) Tregs, and both participate in the immunosuppression microenvironment of GC.


Subject(s)
Dendritic Cells/immunology , Inducible T-Cell Co-Stimulator Protein/immunology , Stomach Neoplasms/immunology , T-Lymphocytes, Regulatory/immunology , Tumor Microenvironment/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Female , Humans , Immune Tolerance/immunology , Interferon-alpha/immunology , Interleukin-10/immunology , Male , Middle Aged , Stomach Neoplasms/pathology
7.
Int J Mol Sci ; 14(7): 13005-21, 2013 Jun 24.
Article in English | MEDLINE | ID: mdl-23797661

ABSTRACT

Mitofusin-2 (Mfn2) is a mitochondrial outer membrane protein involved in mitochondrial fusion. Its mutation can cause Charcot-Marie-Tooth disease. Recent studies of Mfn2 in cancer research have not included gastric cancer. We confirmed that Mfn2 expression was lower in tumor tissue than in normal gastric mucosal tissue and that it was negatively correlated with tumor size, indicating an anti-tumor role for Mfn2. In vitro experiments showed that Mfn2 overexpression suppressed gastric cancer cell proliferation and colony formation, weakened the invasion and migratory ability of cancer cells by downregulating MMP-2 and MMP-9, halted the cell cycle and induced apoptosis. Western blotting indicated the likely involvement of P21 and PI3K/Akt signaling. Therefore, Mfn2 is a potential anti-tumor gene and a potential therapeutic target for treating gastric cancer. The progress of gastric cancer may be delayed by controlling Mfn2 expression.


Subject(s)
GTP Phosphohydrolases , Mitochondrial Proteins , Charcot-Marie-Tooth Disease , GTP Phosphohydrolases/metabolism , Humans , Membrane Proteins/metabolism , Mitochondrial Proteins/metabolism , Mutation , Phosphatidylinositol 3-Kinases/genetics , Stomach Neoplasms
8.
PLoS One ; 8(3): e58990, 2013.
Article in English | MEDLINE | ID: mdl-23533596

ABSTRACT

PURPOSE: The tetraspanin CD151 acts as a promoter of metastasis and invasion in several tumors. However, the role of CD151 in human gastric cancer (HGC) remains unclear. METHODS: Twenty HGC specimens and matched nontumor samples, human gastric epithelial cells (HGEC), and four gastric cancer cell lines were used to analyze CD151 expression. Short hairpin RNA-mediated downregulation of CD151 expression in HGC cells was performed to examine the role of CD151 in the proliferation and metastasis/invasion of HGC cells in vivo and in vitro. The relationship of CD151 with integrin α3 in HGC cells was investigated by silencing integrin α3 followed by co-immunoprecipitation and immunofluorescence staining. Finally, the prognostic value of CD151 and integrin α3 was evaluated by immunohistochemistry in tissue microarrays of 76 HGC patients. RESULTS: CD151 was expressed at higher levels in HGC tissues and HGC cells than in nontumor tissues and HGEC cells. Down-regulation of CD151 by vshRNA-CD151 impaired metastasis and invasion of HGC-27 cells, but did not affect cell proliferation. CD151 formed a complex with integrin α3 in HGC cells. CD151-cDNA transfection rescued the metastatic potential and invasiveness of HGC-27-vshCD151 cells, but not those of HGC-27-vshintegrin α3 cells in vitro. Clinically, CD151 overexpression was significantly correlated with high TNM stage, depth of invasion and positive lymph node involvement (p<0.05), and high levels of integrin α3 were associated with large tumor size, high TNM stage, depth of invasion and lymph node involvement (p<0.05). Importantly, the postoperative 5-year overall survival of patients with CD151(low) and/or integrin α3(low) was higher than that of patients with CD151(high) and/or integrin α3(high). CONCLUSION: CD151 is positively associated with the invasiveness of HGC, and CD151 or the combination of CD151 and integrin α3 is a novel marker for predicting the prognosis of HGC patients and may be potential therapeutic targets.


Subject(s)
Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Tetraspanin 24/metabolism , Aged , Cell Line, Tumor , Cell Proliferation , Female , Humans , Immunoblotting , Immunoprecipitation , In Vitro Techniques , Integrin alpha3/genetics , Integrin alpha3/metabolism , Male , Middle Aged , Prognosis , Protein Binding , Reverse Transcriptase Polymerase Chain Reaction , Stomach Neoplasms/genetics , Tetraspanin 24/genetics
9.
World J Surg Oncol ; 10: 239, 2012 Nov 09.
Article in English | MEDLINE | ID: mdl-23140528

ABSTRACT

BACKGROUND: To conduct a meta-analysis to determine the relative merits of robotic thyroidectomy (RT) and endoscopic thyroidectomy (ET). METHODS: A literature search was performed to identify comparative studies reporting peri-operative outcomes for RT and ET. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence interval (95% CI) were calculated using either a fixed-effects or a random-effects model. RESULTS: Six studies matched the selection criteria, which reported on 2048 subjects, of whom 978 underwent RT and 1070 underwent ET. Comparing the outcomes of RT with ET, this meta-analysis indicated that RT was associated with more complications (WMD = 1.51, 95% CI 1.18 to 1.94) and greater amount of drainage fluid (WMD = 17.10, 95% CI 5.69 to 28.51). Meanwhile, operating time (WMD = 1.50, 95% CI -39.59 to 42.58), conversion (WMD = 0.63, 95% CI 0.07 to 6.17), post-operative hospital stay (WMD = -0.05; 95% CI -0.18 to 0.08), and the number of lymph nodes harvested (WMD = 0.62, 95% CI -0.29 to 1.53) were similar for both procedures. CONCLUSION: The results of this meta-analysis indicated that RT is associated with an increased risk of complications and a greater amount of drainage fluid. Therefore, RT does not appear to have any advantage over ET. Further studies are required to confirm these results.


Subject(s)
Endoscopy/methods , Robotics/methods , Thyroidectomy/methods , Humans , Thyroid Neoplasms/surgery , Thyroidectomy/adverse effects
10.
World J Gastroenterol ; 18(16): 1968-74, 2012 Apr 28.
Article in English | MEDLINE | ID: mdl-22563179

ABSTRACT

AIM: To study the therapeutic efficacy of a new transnasal ileus tube advanced endoscopically for adhesive small bowel obstruction. METHODS: A total of 186 patients with adhesive small bowel obstruction treated from September 2007 to February 2011 were enrolled into this prospective randomized controlled study. The endoscopically advanced new ileus tube was used for gastrointestinal decompression in 96 patients and ordinary nasogastric tube (NGT) was used in 90 patients. The therapeutic efficacy was compared between the two groups. RESULTS: Compared with the NGT group, the ileus tube group experienced significantly shorter time for relief of clinical symptoms and improvement in the findings of abdominal radiograph (4.1 ± 2.3 d vs 8.5 ± 5.0 d) and laboratory tests (P < 0.01). The overall effectiveness rate was up to 89.6% in the ileus tube group and 46.7% in the NGT group (P < 0.01). And 10.4% of the patients in the ileus tube group and 53.3% of the NGT group underwent surgery. For recurrent adhesive bowel obstruction, ileus tube was also significantly more effective than NGT (95.8% vs 31.6%). In the ileus tube group, the drainage output on the first day and the length of hospital stay were significantly different depending on the treatment success or failure (P < 0.05). The abdominal radiographic improvement was correlated with whether or not the patient underwent surgery. CONCLUSION: Ileus tube can be used for adhesive small bowel obstruction. Endoscopic placement of the ileus tube is convenient and worthy to be promoted despite the potential risks.


Subject(s)
Decompression, Surgical , Intestinal Obstruction/surgery , Intubation, Gastrointestinal/instrumentation , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Tissue Adhesions
11.
World J Gastroenterol ; 17(47): 5214-20, 2011 Dec 21.
Article in English | MEDLINE | ID: mdl-22215947

ABSTRACT

AIM: To conduct a meta-analysis to determine the relative merits of robotic surgery (RS) and laparoscopic surgery (LS) for rectal cancer. METHODS: A literature search was performed to identify comparative studies reporting perioperative outcomes for RS and LS for rectal cancer. Pooled odds ratios and weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) were calculated using either the fixed effects model or random effects model. RESULTS: Eight studies matched the selection criteria and reported on 661 subjects, of whom 268 underwent RS and 393 underwent LS for rectal cancer. Compared the perioperative outcomes of RS with LS, reports of RS indicated favorable outcomes considering conversion (WMD: 0.25; 95% CI: 0.11-0.58; P = 0.001). Meanwhile, operative time (WMD: 27.92, 95% CI: -13.43 to 69.27; P = 0.19); blood loss (WMD: -32.35, 95% CI: -86.19 to 21.50; P = 0.24); days to passing flatus (WMD: -0.18, 95% CI: -0.96 to 0.60; P = 0.65); length of stay (WMD: -0.04; 95% CI: -2.28 to 2.20; P = 0.97); complications (WMD: 1.05; 95% CI: 0.71-1.55; P = 0.82) and pathological details, including lymph nodes harvested (WMD: 0.41, 95% CI: -0.67 to 1.50; P = 0.46), distal resection margin (WMD: -0.35, 95% CI: -1.27 to 0.58; P = 0.46), and positive circumferential resection margin (WMD: 0.54, 95% CI: 0.12-2.39; P = 0.42) were similar between RS and LS. CONCLUSION: RS for rectal cancer is superior to LS in terms of conversion. RS may be an alternative treatment for rectal cancer. Further studies are required.


Subject(s)
Laparoscopy/instrumentation , Laparoscopy/methods , Rectal Neoplasms/surgery , Robotics/methods , Clinical Trials as Topic , Confidence Intervals , Databases, Factual , Humans , Treatment Outcome
12.
World J Gastroenterol ; 16(21): 2702-4, 2010 Jun 07.
Article in English | MEDLINE | ID: mdl-20518096

ABSTRACT

Acute cholecystitis is not a common complication of gastrectomy. Its clinical presentations and management strategies in old patients have not been well described in available literature. This report describes the clinical features, management strategies, and treatment outcome of acute cholecystitis immediately after gastrectomy. Acute cholecystitis immediately after gastrectomy in old patients has different clinical presentations, such as fever and high plasma C-reaction protein level. Abdominal computed tomography (CT) scan and ultrasonography showed acute cholecystitis in our cases, which was treated with antibiotics and ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD). The results indicate that abdominal CT scan and ultrasonography can effectively diagnose acute cholecystitis after gastrectomy, which can be effectively treated with antibiotics and PTGD.


Subject(s)
Cholecystitis, Acute/etiology , Gastrectomy/adverse effects , Postoperative Complications , Aged , Cholecystitis, Acute/diagnostic imaging , Cholecystitis, Acute/therapy , Cholecystostomy , Female , Gallbladder/pathology , Humans , Male , Middle Aged , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tomography, X-Ray Computed
13.
World J Gastroenterol ; 16(14): 1808-10, 2010 Apr 14.
Article in English | MEDLINE | ID: mdl-20380018

ABSTRACT

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the alimentary tract. To the best of our knowledge, few cases have been reported in the literature about the peripheral lymph node metastasis of GIST. Here we report an unusual case of gastric GIST with inguinal lymph nodes metastasis. After the metastatic lymph nodes were resected, the. patient started to take imatinib 400 mg/d for 12 mo. There were no signs of tumor recurrence at follow-up after 29 mo. This case suggests that the inguinal lymph nodes can be a potential metastatic site of GIST.


Subject(s)
Gastrointestinal Stromal Tumors/pathology , Stomach Neoplasms/pathology , Antineoplastic Agents/therapeutic use , Benzamides , Gastrointestinal Stromal Tumors/secondary , Gastrointestinal Stromal Tumors/therapy , Humans , Imatinib Mesylate , Inguinal Canal , Lymphatic Metastasis , Male , Middle Aged , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Stomach Neoplasms/therapy
14.
J Surg Oncol ; 100(7): 606-10, 2009 Dec 01.
Article in English | MEDLINE | ID: mdl-19697360

ABSTRACT

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) occur rarely in the duodenum. The characteristics of duodenal GIST have not been well clarified. The aim of this study is to clarify the characteristics and surgical prognosis of patients with primary duodenal GIST. METHODS: Data of patients with surgically treated primary duodenal GIST were retrospectively analyzed. Immunohistochemical expressions of p53, p16, and Ki-67 were evaluated to explain the prognosis. RESULTS: Compared with gastric or small intestinal GISTs in historical studies, duodenal GISTs had a relatively smaller size, lower mitotic count, lower Ki-67 LI, lower p16 loss, and similar p53 expression. The 1- and 3-year recurrence-free survival rates of patients with complete resection were 100 and 95.2%. CONCLUSION: Patients with completely resected primary duodenal GIST seem to have a more favorable prognosis. This may be related to the different expressions of some immunohistological makers compared with GISTs of other locations.


Subject(s)
Duodenal Neoplasms/metabolism , Duodenal Neoplasms/mortality , Gastrointestinal Stromal Tumors/metabolism , Gastrointestinal Stromal Tumors/mortality , Adult , Aged , Aged, 80 and over , Cyclin-Dependent Kinase Inhibitor p16 , Duodenal Neoplasms/pathology , Duodenal Neoplasms/surgery , Female , Follow-Up Studies , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/surgery , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Male , Middle Aged , Neoplasm Proteins/metabolism , Neoplasm Recurrence, Local , Prognosis , Retrospective Studies , Survival Rate , Tumor Suppressor Protein p53/metabolism
15.
Hepatobiliary Pancreat Dis Int ; 8(1): 53-8, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19208516

ABSTRACT

BACKGROUND: Urinary trypsin inhibitor (UTI) inhibits the inflammatory response and protects against ischemia-reperfusion (I/R) injury. The inflammatory response is mediated by nuclear factor-kappa B (NF-kappaB) and its related target genes and products such as vascular endothelial cell adhesion molecule and CXC chemokines. We aimed to assess the roles of those mediators in a UTI-treated mouse model of hepatic I/R injury. METHODS: Treatment group 1 (UTI given 5 minutes prior to liver ischemia), treatment group 2 (UTI given 5 minutes after the anhepatic phase) and a control group were investigated. Blood and liver samples were obtained and compared at 1, 3, 6 and 24 hours after reperfusion. RESULTS: Attenuation of pathological hepatocellular damage was greater in the treatment groups than in the control group (P<0.05). Compared with the control group, the UTI treatment groups showed significantly lower serum alanine aminotransferase and aspartate aminotransferase levels, decreased myeloperoxidase activity, and reduced NF-kappaB activation. Also downregulated was the expression of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2 at the mRNA level. P-selectin protein and intercellular adhesion molecule-1 protein expression were also downregulated. In addition, the treatment group 1 showed a better protective effect against I/R injury than the treatment group 2. CONCLUSIONS: UTI reduces NF-kappaB activation and downregulates the expression of its related mediators, followed by the inhibition of neutrophil aggregation and infiltration in hepatic I/R injury. The protective role of UTI is more effective in prevention than in treatment.


Subject(s)
Glycoproteins/metabolism , Glycoproteins/pharmacology , Liver Diseases/drug therapy , NF-kappa B/metabolism , Reperfusion Injury/drug therapy , Acute-Phase Reaction/immunology , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Chemokine CXCL1/genetics , Chemokine CXCL1/metabolism , Chemokine CXCL2/genetics , Chemokine CXCL2/metabolism , Disease Models, Animal , Down-Regulation/drug effects , Down-Regulation/immunology , E-Selectin/genetics , E-Selectin/metabolism , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Liver Diseases/immunology , Liver Diseases/metabolism , Mice , Mice, Inbred BALB C , Neutrophils/immunology , P-Selectin/genetics , P-Selectin/metabolism , Peroxidase/metabolism , RNA, Messenger/metabolism , Reperfusion Injury/immunology , Reperfusion Injury/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
16.
Zhonghua Zhong Liu Za Zhi ; 30(2): 107-11, 2008 Feb.
Article in Chinese | MEDLINE | ID: mdl-18646691

ABSTRACT

OBJECTIVE: To investigate the specific anti-breast cancer immune response induced by dendritic cells (DC) loaded with trastuzumab and apoptotic Her-2+ breast cancer cells. METHODS: DCs were generated from healthy peripheral blood mononuclear cells (PBMCs) in the presence of recombinant cytokines GM-CSF, IL-4 and TNF-alpha. Mature DCs were harvested after 7 days' co-culture of PBMCs and trastuzumab-treated apoptotic SKBr3 cells. The morphologic characteristics and ultrastructure of the DC were observed under the inverted phase-contrast microscope and transmission electron microscope (TEM), respectively. Flow cytometry (FCM) was used to check the expression of several DC specific markers: CD14, CD1a, CD64, CD80, CD83, CD86, HLA-ABC and HLA-DR. DC-cytokine induced killer (DC-CIK) cells were prepared by co-culture of DCs and peripheral blood lymphocytes in the presence of anti-CD3 antibodies and human IL-2 at an appropriate concentration. The number of antigen-specific T cells was analyzed by human interferon gamma enzyme linked immunospot (ELISPOT) assay. MTT assay was employed to assess the lysis of breast cancer cell line induced by DC-CIK cells. RESULTS: 5 minutes after the adding of DCs to SKBr3 cells pretreated with trastuzumab, the apoptotic SKBr3 cells were found to be circled by DCs. 48 hours later, many membrane-wrapped organelles of the apoptotic target cells in the cytoplasm of DCs were found by TEM. The majority of the organelles were degraded. Fewer organelles from the apoptotic cells were found in DCs without Herceptin. More than 60% in every group of DCs expressed a high-affinity receptor for IgG (FcgammaRI or CD64). CD14 expression on the mature DCs were comparatively lower, and HLA-DR and HLA-ABC expressions were higher in the trastuzumab group. The expression of CD1a, CD80, CD83 and CD86 in trastuzumab group were higher than those in immature DCs group (P < 0.05). ELISPOT assay suggests that the spot number of antigen-specific T cells were higher in trastuzumab group than that in the antigen unloaded DCs group (P < 0.05). The lysis of SKBr3 cells induced by the SKBr3 antigen loaded DC-CIK cells were 1.7 times higher than that of CIK. CONCLUSION: The lysis of SKBr3 cells induced by DC-CIK was increased after that DCs were combined with trastuzumab to capture antigen from SKBr3 cells. These findings support further investigation into the use of combination immunotherapy of the humanized monoclonal antibody, DC vaccines and immunological effector cells.


Subject(s)
Antibodies, Monoclonal/pharmacology , Cytokine-Induced Killer Cells/immunology , Cytokines/metabolism , Cytotoxicity, Immunologic/immunology , Dendritic Cells/immunology , Antibodies, Monoclonal, Humanized , Apoptosis , Cell Line, Tumor , Coculture Techniques , Dendritic Cells/cytology , Dendritic Cells/metabolism , Dendritic Cells/ultrastructure , Humans , Receptor, ErbB-2/metabolism , Receptors, IgG/metabolism , Trastuzumab
17.
Zhonghua Zhong Liu Za Zhi ; 30(12): 940-3, 2008 Dec.
Article in Chinese | MEDLINE | ID: mdl-19173999

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine , Cisplatin/administration & dosage , Cisplatin/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Follow-Up Studies , Foot Dermatoses/chemically induced , Hand Dermatoses/chemically induced , Humans , Leukopenia/chemically induced , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Remission Induction , Stomach Neoplasms/pathology , Survival Rate , Vomiting/chemically induced , Young Adult
18.
Scand J Gastroenterol ; 42(9): 1138-40, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17710683

ABSTRACT

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the GI tract. Although a great deal of experience has been obtained with imatinib mesylate in patients with unresectable or metastatic GISTs, its role in the neoadjuvant setting is not well established. In this paper, we describe a case of successful resection of a giant recurrent GIST with imatinib mesylate as neoadjuvant therapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Gastrointestinal Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Adult , Benzamides , Chemotherapy, Adjuvant , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/pathology , Humans , Imatinib Mesylate , Male , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology
19.
Zhonghua Wei Chang Wai Ke Za Zhi ; 9(5): 383-7, 2006 Sep.
Article in Chinese | MEDLINE | ID: mdl-17043955

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of postoperative adjuvant chemotherapy with imatinib in gastrointestinal stromal tumor(GIST) patients who had high risk of recurrence. METHODS: A prospective, open-label, multi-center trial conducted in sixteen teaching hospitals in China was carried out. The criteria of the enrolled patients included age more than 18 years old, CD117 positive GIST, tumor size more than 5 cm, pathological mitosis counts more than 5/50 HPF, and treatment beginning within 4 weeks after complete resection and with imatinib (400 mg, once a day) for at least 12 months. The 1, 3 year recurrence rates, disease free survival, overall survival rate and quality of life were evaluated. RESULTS: From Aug. 16th 2004 to Sep. 13th 2005, there were totally 74 patients screened and 57 patients (34 men, 23 women) enrolled in the imatinib treatment group. The primary tumors were located in the stomach in 50.9%, the small intestine in 38.6% and the colorectum in 10.5% of the cases. All the patients received radical resection. Until the cut-off date of interim analysis, there was no evidence of tumor relapse or metastasis in all patients and no death was reported either. Among the 57 enrolled patients with intention to treat(ITT), twelve patients finished the protocol (per protocol, PP). The disease free survival was (268.3 +/-120.2) d in ITT analysis, and (396.7+/-38.2) d in the PP analysis. The incidence of adverse effect was 44.4% . The score in quality of life showed no statistically significant difference between the baseline visit and the follow-up visits. CONCLUSION: Imatinib is a promising postoperative adjuvant chemotherapy in GISTs patients with high risk of recurrence, and the adverse effects are receivable.


Subject(s)
Gastrointestinal Stromal Tumors/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Adult , Aged , Aged, 80 and over , Benzamides , Chemotherapy, Adjuvant , Female , Humans , Imatinib Mesylate , Male , Middle Aged , Neoplasm Recurrence, Local , Postoperative Period , Prospective Studies , Young Adult
20.
Zhonghua Zhong Liu Za Zhi ; 28(3): 188-91, 2006 Mar.
Article in Chinese | MEDLINE | ID: mdl-16875602

ABSTRACT

OBJECTIVE: To investigate the effects of immunologic effector cells to enhance apoptosis induced by adriamycin (ADR) in multi-drug resistant human breast cancer cell line MCF7/ADR. METHODS: The immunologic effector cells were induced and expanded by IFN-gamma, McAb CD3, IL-1 and IL-2. The expression of P-glycoprotein (P-gp) and its relation to apoptosis in target cells were detected by TUNEL technique and immunohistochemical staining. Flow cytometry (FCM) was carried out to determine the expression level of human breast cancer related P185 antigen and the positive rate of Annexin V-FITC/PI expression. The subcellular distribution of ADR and Annexin V expression in the target cells were detected by fluorescence microscopy. RESULTS: The immunologic effector cells down-regulated the expression of P185 and P-gp in MCF7/ADR cells. The accumulation and subcellular distribution of ADR in MCF7/ADR cells were increased after co-culture with the immunologic effector cells. After treatment with the immunologic effector cells in combination with ADR, apoptosis rate of the target cells was 10 times higher than that induced by ADR alone, and 13 times higher than that induced by the immunologic effector cells alone. CONCLUSION: Immunologic effector cells can simultaneously down-regulate the expression of P185 and P-gp in MCF7/ADR cell line, and increase the apoptosis rate of MCF7/ADR cells in combination with ADR.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Breast Neoplasms/pathology , Doxorubicin/pharmacology , Drug Resistance, Neoplasm , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Breast Neoplasms/immunology , Breast Neoplasms/metabolism , Cell Line, Tumor , Down-Regulation , Drug Resistance, Multiple , Female , Humans , Killer Cells, Lymphokine-Activated/immunology , Receptor, ErbB-2/metabolism
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