1.Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance.
Lin CHEN ; Zhao-long CAO ; Fang HAN ; Zhan-cheng GAO ; Quan-ying HE
Chinese Medical Journal 2010;123(4):463-470
BACKGROUNDThe persistence of sleep disordered breathing (SDB) symptoms after tonsil and/or adenoid (T&A) surgery are common in children with obstructive sleep apnea (OSA). We tested the hypothesis that disturbances of glucose transporters (GLUTs) in intraabdominal adipose tissue caused by chronic intermittent hypoxia (CIH) from the pedo-period could facilitate the appearance of periphery insulin resistance in Sprague-Dawley (SD) rats. We tested the hypothesis that the changes of GLUTs in adipose tissue may be one of the reasons for persistent SDB among clinical OSA children after T&A surgery.
METHODSThirty 21-day-old SD rats were randomly divided into a CIH group, a chronic continuous hypoxia (CCH) group, and a normal oxygen group (control group) and exposed for 40 days. The changes of weight, fasting blood glucose and fasting blood insulin levels were measured. Hyperinsulinemic-euglycemic clamp techniques were used to measure insulin resistance in each animal. Real-time quantitative PCR and Western blotting were used to measure GLUT mRNA and proteins in intraabdominal adipose tissue. Additional intraabdomial white adipose tissue (WAT) was also processed into paraffin sections and directly observed for GLUTs1-4 expression.
RESULTSWhen compared with control group, CIH increased blood fasting insulin levels, (245.07 +/- 53.89) pg/ml vs. (168.63 +/- 38.70) pg/ml, P = 0.038, and decreased the mean glucose infusion rate (GIR), (7.25 +/- 1.29) mg x kg(-1) x min(-1) vs. (13.34 +/- 1.54) mg x kg(-1) x min(-1), P < 0.001. GLUT-4 mRNA and protein expression was significantly reduced after CIH compared with CCH or normal oxygen rats, 0.002 +/- 0.002 vs. 0.039 +/- 0.009, P < 0.001; 0.642 +/- 0.073 vs. 1.000 +/- 0.103, P = 0.035.
CONCLUSIONSCIH in young rats could induce insulin resistance via adverse effects on glycometabolism. These findings emphasize the importance of early detection and treatment of insulin insensitivity in obese childhood OSA.
Adipose Tissue ; metabolism ; Animals ; Blood Glucose ; metabolism ; Blotting, Western ; Glucose Clamp Technique ; Glucose Transporter Type 4 ; metabolism ; Hypoxia ; physiopathology ; Immunohistochemistry ; Insulin ; blood ; Insulin Resistance ; physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction
2.Diagnosis and treatment of gastrointestinal stromal tumors: report of 135 cases.
Xin-Hua ZHANG ; Yu-Long HE ; Wen-Hua ZHAN ; Shi-Rong CAI ; Chang-Hua ZHANG
Chinese Journal of Gastrointestinal Surgery 2007;10(1):17-20
OBJECTIVETo analyze the relationships between smooth-muscle tumors of gastrointestinal (GI) tract and gastrointestinal stromal tumors (GISTs), and the efficacy of surgical management.
METHODSThe clinical and pathological data of 135 cases of GISTs were collected, including cases of leiomyomas/leiomyosarcoma between 1993 and 2003 and GIST between Jan. 2000 and Jul. 2005. The surgical outcomes were analyzed retrospectively.
RESULTS82.1% of former leiomyomas/leiomyosarcomas was corrected to GISTs. Overall 5-year survival rate was 79.7%. Univariate analysis revealed preoperative metastasis, tumor size, mitotic index, and postoperative metastasis or recurrence were correlated with overall survival in patients with completed resection. Multivariate analysis showed that only postoperative metastasis or recurrence were the indicators of poor prognosis, but without statistical significance (P=0.064). However, multivariate analysis for disease-free survival showed that preoperative metastasis and mitotic index were two independent predictors of poor prognosis (P=0.001 and P<0.001).
CONCLUSIONSMost former leiomyomas/leiomyosarcomas of GI tract should be corrected to the diagnosis of GISTs. Complete surgical resection is the choice of treatment for GISTs. Preoperative metastasis and mitotic index are two independent predictors of poor prognosis.
Female ; Gastrointestinal Stromal Tumors ; diagnosis ; surgery ; Humans ; Male ; Prognosis ; Survival Rate
3.Low and ultralow anterior resection with hand-assisted laparoscopic surgery for rectal cancer.
Fang-hai HAN ; Hong-ming LI ; Hao-chen WANG ; Jian-hai WU ; Yu-long HE ; Wen-hua ZHAN
Chinese Journal of Gastrointestinal Surgery 2012;15(6):633-636
OBJECTIVETo summarize the experience and short-term clinical outcomes of hand-assisted laparoscopic surgery (HALS) in sphincter-preserving surgery for low and ultralow rectal cancer.
METHODSData of 49 patients with rectal cancer who underwent HALS for low or ultralow anterior resection between January 2010 and January 2011 were analyzed retrospectively.
RESULTSThe proximal resection margin was (14.3±6.9) cm and the distal margin was(4.3±1.9) cm. The mean operative time was(128.3±70.9) min. On postoperative macroscopic evaluation, the mesorectum was intact in 42 cases, nearly intact in 7 cases. The circumferential resection margin was more than 2 mm in 42 cases, and less than 2 mm in 7 cases. Forty-six patients underwent R0 resection, and 3 cases underwent R1 resection. The median retrieved lymph node (LN) was 16.20±9.23, and the median positive LN was 1.12±2.19. Postoperative pathological examination showed TNM stage was I( in 12 patients, II(A in 18, II(B in 1, III(A in 2, III(B in 8, III(C in 5, IIII( in 3. The median postoperative hospital stay was (6.25±3.87) d. There were no anastomotic leakage, ileus, intra-abdominal or anastomotic bleeding. There were two wound infections.
CONCLUSIONLow and ultralow anterior resection for rectal cancer using HALS approach is safe and feasible with favorable short-term outcome.
Adult ; Aged ; Aged, 80 and over ; Anal Canal ; surgery ; Female ; Hand-Assisted Laparoscopy ; methods ; Humans ; Male ; Middle Aged ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Treatment Outcome
4.Comparison of nutritional status between pancreaticojejunostomy and pancreaticogastrostomy following pancreaticoduodenectomy.
Jin-ping MA ; Chuang-qi CHEN ; Shi-rong CAI ; Han-ping SHI ; Yu-long HE ; Wen-hua ZHAN
Chinese Journal of Gastrointestinal Surgery 2012;15(5):457-459
OBJECTIVETo compare the nutritional status between pancreaticojejunostomy(PJ) and pancreaticogastrostomy(PG) following pancreaticoduodenectomy.
METHODSA retrospective clinical analysis was performed on 37 patients undergoing pancreaticoduodenectomy(PD) for duodenal carcinoma and pancreatic non-epithelial tumor with PG(n=19) and PJ(n=18) in the First Hospital of Sun Yat-sen University from April 2006 to December 2010. All the patients had a needle catheter jejunostomy inserted at the conclusion of laparotomy. Postoperative early enteral nutrition and parenteral nutrition was performed for all the patients. Nutritional status of two groups was compared in body mass index (BMI), serum nutritional parameters such as albumin, transferrin and prealbumin before surgery and on 1, 3, and 6 months postoperatively.
RESULTSThere were no significant differences between PG and PJ groups in operative time, blood loss, pancreatic fistula, perioperative death, or postoperative length of hospital stay. One month after surgery, there were no significant differences in BMI [(17.1±7.0) vs. (19.0±4.8) kg/m(2), P>0.05], albumin [(30.1±0.5) vs. (32.1±1.3) g/L, P>0.05], transferrin [(1.89±0.57) vs. (2.01±0.61) g/L, P>0.05] and prealbumin[(0.18±0.05) vs. (0.18±0.09) g/L, P>0.05]. These parameters were decreased at 1 month after surgery, and gradually recovered to baseline or higher than the preoperative levels at 6 months after surgery. However, the differences were still not statistically significant between two groups.
CONCLUSIONSThe influence of PJ and PG on the postoperative nutritional status are comparable.
Adult ; Aged ; Female ; Gastrostomy ; Humans ; Male ; Middle Aged ; Nutritional Status ; Pancreas ; surgery ; Pancreaticoduodenectomy ; Pancreaticojejunostomy ; Postoperative Period ; Retrospective Studies
5.Epigallocatechin-3-gallate inhibits growth and angiogenesis of gastric cancer and its molecular mechanism.
Bao-He ZHU ; Wen-Hua ZHAN ; Yu-Long HE ; Shi-Rong CAI ; Zhao WANG ; Chang-Hua ZHANG
Chinese Journal of Gastrointestinal Surgery 2009;12(1):82-85
OBJECTIVETo investigate the inhibitory effect of epigallocatechin-3-gallate (EGCG) on growth and angiogenesis of gastric cancer and to explore its molecular mechanism.
METHODSHeterotopic tumor was established by subcutaneously injection with SGC-7901 cells in nude mice. Once the tumor was established, the mice were allocated randomly into two groups and received intraperitoneal injection of EGCG or phosphate buffered saline respectively. Tumor growth was measured by caliper in two dimensions, and angiogenesis was determined with tumor microvessel density (MVD) by immunohistochemistry. Protein levels of vascular endothelial growth factor (VEGF) and activation of signal transducer and activator of transcription 3(Stat3) in tumor cells and tumor tissues were examined by Western blot. VEGF release in tumor culture medium was determined by ELISA and VEGF mRNA expression in tumor cells by RT-PCR.
RESULTSIntraperitoneal injection of EGCG significantly inhibited the growth of gastric cancer[(0.32+/-0.08) g vs(0.81+/-0.12) g, t=7.24, P<0.01], and an average of 60.4% suppression of primary tumor growth was observed. Microvessel density in tumor tissues receiving EGCG treatment was also markedly reduced(15.2+/-4.3 vs 24.6+/-6.6,t=3.41,P<0.01),and an average of 38.2% suppression was observed. EGCG treatment markedly reduced VEGF protein level in vitro and in vivo. Secretion and mRNA expression of VEGF in tumor cells were also suppressed by EGCG in a dose-dependent manner. This inhibitory effect was associated with reduced activation of Stat3. Stat3 activation was dose-dependently suppressed by EGCG in tumor cells, and an average of 53.5% reduction was observed in tumor tissues, but EGCG treatment did not change total Stat3 expression.
CONCLUSIONEGCG reduces expression of VEGF in gastric cancer by inhibiting activation of Stat3, thereby inhibits tumor growth and angiogenesis of gastric cancer.
Animals ; Catechin ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Female ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neovascularization, Pathologic ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Stomach Neoplasms ; blood supply ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays
6.(-)-Epigallocatechin-3-gallate reduces vascular endothelial growth factor expression in gastric cancer cells via suppressing activity.
Bao-he ZHU ; Yu-long HE ; Wen-hua ZHAN ; Shi-rong CAI ; Zhao WANG ; Chang-hua ZHANG ; Hua-yun CHEN
Chinese Journal of Gastrointestinal Surgery 2011;14(8):631-635
OBJECTIVETo investigate the molecular mechanism involved in the downregulation of vascular endothelial growth factor(VEGF) expression through the suppression of signal transducer and activator of transcription 3(Stat3) by(-)-Epigallocatechin-3-gallate (EGCG).
METHODSAfter human gastric cancer cells (AGS) were treated with IL-6 (50 μg/L) and EGCG(0, 5, 10, 25 or 50 μmol/L), the expression levels of VEGF, total Stat3(tStat3), and activated Stat3(pStat3) in tumor cells were examined by Western blotting. The influence of the inhibitor of Stat3 pathway on the IL-6-induced VEGF expression was investigated. VEGF protein level in tumor cell culture medium was determined by ELISA and VEGF mRNA expression in tumor cells by RT-PCR. Tumor cell nuclear extract was prepared and nuclear expression of pStat3 was detected. Stat3-DNA binding activity was examined with chromatin immunoprecipitation (ChIP) assay.
RESULTSIL-6 significantly increased VEGF expression in AGS gastric cancer cells. Compared with the group without IL-6, the expression and secretion of VEGF protein, and mRNA expression increased by 2.4 fold,2.8 fold, and 3.1 fold(all P<0.01), respectively. EGCG treatment markedly reduced VEGF protein, release and mRNA expression in a dose-dependent manner. When compared with the control group induced by IL-6, EGCG and AG490(a Stat3 pathway inhibitor) significantly inhibited VEGF expression induced by IL-6 (P<0.01). EGCG dose-dependently inhibited pStat3 induced by IL-6(P<0.05), but not tStat3 (P>0.05). Stat3 nuclear translocation and Stat3-DNA binding activity in AGS cells or that induced by IL-6 were directly inhibited by EGCG(P<0.05).
CONCLUSIONEGCG reduces expression of VEGF in gastric cancer cells through the inhibition of Stat3 activity.
Catechin ; analogs & derivatives ; pharmacology ; Humans ; Interleukin-6 ; metabolism ; RNA, Messenger ; genetics ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Cells, Cultured ; Vascular Endothelial Growth Factor A ; metabolism
7.Clinical and molecular biologic characteristics of childhood acute leukemia with mixed lineage leukemia gene rearrangement
Yu-Lan SUN ; Hai-Long HE ; Xue-Jun SHAO ; Shi-Hong ZHAN ; Ya-Xiang HE ; Chun-Ming SHI
Chinese Journal of Applied Clinical Pediatrics 2013;28(3):207-209
Objective To analyze the frequency of mixed lineage leukemia (MLL) gene rearrangement,the frequent types of fusion genes and clinical characteristics of childhood acute leukemia (AL) with MLL gene rearrangement.Methods Morphological and molecular characteristics of 87 AL patients with MLL gene rearrangement were studied and analyzed.MLL fusion gene was detected by way of reverse transcription polymerase chain reaction (RTPCR).Results Eighty-seven cases with MLL gene rearrangement were found in 1209 AL patients with incidence of 6.41% and 9.36% respectively in ALL and in acute myelocytic leukemia (AML) respectively.Fifty-eight cases of ALL were all B-ALL,28 cases of AML included 17 cases of M5,5 cases of M4,4 cases of M2,1 case of M3 and 1 case of M6.While there was 1 case of mixed of lineage leukemia and myeloid and T-lymphoblastic antigen presentation.The clonal chromosomal aberration was detected in 45 out of 76 cases (59.21%),and chromosome 11q23 aberration were observed in 28 cases (36.84%).There were 7 different kinds of fusion genes,including MLL-AF9 in 25 cases,dupMLL in 25 cases,MLL-AF4 in 17 cases,MLL-AF10 in 9 cases,MLL-ENL in 8 cases,MLL-AFlq in 2 cases,and MLL-AF6 in 1 case.Among the cases of MLL-AF4,MLL-AF9,MLL-AF10,MLL-ENL and dupMLL,there were statistical differences in lineage,age and initial white blood cell count (WBC) (all P < 0.05).Conclusions In childhood AL with MLL gene rearrangement,B-ALL is more common in ALL,whereas M5 and M4 are more common in AML.The common types of fusion genes are dupMLL,MLL-AF9 and MLL-AF4.Patients with the different kinds of MLL fusion gene may present different clinical characteristics.The most common ALL cases are those with MLL/AF4 and MLL/ENL who may be younger with higher WBC than the others.
8.Comparison of clinicopathological characteristics and prognosis of mucinous and poorly differentiated gastric cancer.
Jin-ping MA ; Jian-hui CHEN ; Shi-rong CAI ; Chuang-qi CHEN ; Ji CUI ; Zhao WANG ; Kai-ming WU ; Yu-long HE ; Wen-hua ZHAN
Chinese Journal of Gastrointestinal Surgery 2010;13(12):903-906
OBJECTIVETo investigate the clinicopathological characteristics between mucinous gastric cancer (MGC) and poorly differentiated gastric cancer(PDGC) and factors associated with prognosis.
METHODSMedical records of 1016 consecutive patients with gastric cancer were retrospectively reviewed. Sixty-eight patients with MGC and 508 with PDGC were identified. Clinicopathologic characteristics and overall survival data were analyzed.
RESULTSAs compared to PDGC patients, patients with MGC were significantly older [(59.2±11.9) years vs. (54.1±13.2) years], had significantly more distant metastasis(36.8% vs. 23.8%), more peritoneal seeding(29.4% vs. 16.9%), and less radical resection(60.3% vs. 76.6%). There were no significant differences in 5-year survival rate between MGC and PDGC patients(29.4% vs. 35.5%). However, for tumors in the middle third of the stomach, the survival rate of MGC patients was lower than that of PDGC. Using a Cox proportional hazard ratio model, lymph node involvement and radical resection were independent prognostic factors for survival of MGC patients, while tumor invasion, lymph node involvement, and radical resection were associated with survival in patients with PDGC.
CONCLUSIONAlthough MGC and PDGC differ in age, frequencies of peritoneal seeding, distant metastasis, and rate of radical resection, overall survival is comparable.
Aged ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; classification ; pathology
9.Effect of simian vacuolating virus 40 on development and differentiation of dendritic cells from Rhesus macaque.
Chang-Yong GE ; Hong-Jun LI ; Zhan-Long HE ; Guang-Ming ZHANG ; Mao-Sheng SUN ; Nan-Ping WU
Chinese Journal of Virology 2009;25(5):344-348
To study the effect of simian vacuolating virus 40 (SV40) on development and differentiation of dendritic cells (DC) from rhesus macaque, the peripheral blood-derived dendritic cells from rhesus monkey were pulsed with inactivated SV40 and infective SV40, respectively at the 5th day post DC cultivation. Expressions of CD1a, HLA-DR, CD86 and CD83 on the cell surface at the 7th, 9th day post DC cultivation were analyzed by flow cytometry (FCM). The results showed that expressions of CD1a, HLA-DR, CD86 and CD83 on the cell surface in the inactivated SV40-pulsed experimental group were higher than those in the infective SV40-pulsed experimental group (P < 0.05). These cell surface molecules represented characteristic development and differentiation phase of DC. Down-regulation of expressions of these cell surface molecules indicated that infective SV40 might hamper differentiation and maturation of dendritic cells from rhesus monkey.
Animals
;
Antigens, CD
;
metabolism
;
Antigens, CD1
;
metabolism
;
B7-2 Antigen
;
metabolism
;
Cell Differentiation
;
Cells, Cultured
;
Dendritic Cells
;
cytology
;
immunology
;
virology
;
Flow Cytometry
;
HLA-DR Antigens
;
metabolism
;
Immunoglobulins
;
metabolism
;
Macaca mulatta
;
Membrane Glycoproteins
;
metabolism
;
Polyomavirus Infections
;
physiopathology
;
Simian virus 40
;
physiology
10.Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers on lymphangiogenesis of gastric cancer in a nude mouse model.
Liang WANG ; Shi-rong CAI ; Chang-hua ZHANG ; Yu-long HE ; Wen-hua ZHAN ; Hui WU ; Jian-jun PENG
Chinese Medical Journal 2008;121(21):2167-2171
BACKGROUNDAngiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) can inhibit tumor growth by inhibition of angiogenesis. This study was designed to study the anticancer effects of ACEI and ARB on tumor growth and lymphangiogenesis in an implanted gastric cancer mouse model.
METHODSA model of gastric cancer was established by subcutaneously inoculating human gastric cancer cell line SGC-7901 into 60 nude mice. One week later, all mice were randomly divided into 5 groups. A control group received physiologic saline once daily for 21 days. Mice in the 4 treatment groups received one of the following agents by gavage once daily for 21 days: perindopril, 2 mg/kg; captopril, 5 mg/kg; losartan, 50 mg/kg; or valsartan, 40 mg/kg. Twenty-one days after treatment, all the mice were sacrificed and the tumors were removed. Tumor sections were processed, and immunohistochemical methods were used to observe the expressions of vascular endothelial growth factor C (VEGF-C), matrix metalloproteinase 7 (MMP-7), and lymphatic microvessel density (LMVD).
RESULTSTumor volume was significantly inhibited in all ACEI and ARB groups, compared with the control group (all P < 0.01). LMVD in the ACEI and ARB groups was also significantly lower than that of the control group (all P < 0.01). In the ACEI groups, the expressions of VEGF-C and MMP-7 were both significantly decreased, compared with the control group (all P < 0.05). In the ARB groups, expression of VEGF-C was significantly decreased compared with the control group (all P < 0.05). However, no significant difference was found in the expression of MMP-7 between ARB groups and the control group.
CONCLUSIONIn a mouse model, ACEI and ARB might inhibit gastric cancer tumor growth by suppressing lymphangiogenesis.
Angiotensin II Type 1 Receptor Blockers ; pharmacology ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; therapeutic use ; Animals ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Humans ; Lymphangiogenesis ; drug effects ; Male ; Matrix Metalloproteinase 7 ; analysis ; Mice ; Mice, Nude ; Stomach Neoplasms ; drug therapy ; pathology ; physiopathology ; Vascular Endothelial Growth Factor C ; analysis