3.Neo-adjuvant therapy for locally advanced low rectal cancer.
Xiao DU ; Zhong CHENG ; Zong-guang ZHOU
Chinese Journal of Gastrointestinal Surgery 2012;15(10):1095-1098
Rectal cancer is one of the most malignant tumors in gastrointestinal tract, while low rectal cancer with locally advanced stage is the most common type in China. The concept of neo-adjuvant therapy has challenged the traditional treatment strategy for rectal cancer, and has showed encouraging effects in local relapse control, radical resection and sphincter preservation. However, some important issues still remain controversial, including course and dose of radiotherapy, choice of chemotherapy regimen, long-term benefits. This article aims to review and discuss related issues of neo-adjuvant therapy.
China
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Humans
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Neoadjuvant Therapy
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Neoplasm Recurrence, Local
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Rectal Neoplasms
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therapy
4.Expression of minichromosome maintenance protein 2 in colonic adenocarcinoma, adenoma and normal colonic mucosa and its clinical significance.
Yong WANG ; Zong-guang ZHOU ; Qing-jie XIA ; Wen-yan ZHANG ; Hong-guang LI ; Rong WANG
Chinese Journal of Gastrointestinal Surgery 2008;11(5):465-468
OBJECTIVETo investigate the expression differences of minichromosome maintenance 2 (MCM2) mRNA and protein among colon adenocarcinoma, colon adenoma and normal mucosa, and among different clinicopathological types of adenomas.
METHODSFifty specimens, including 33 colonic adenomas, 12 colonic adenocarcinomas and 5 normal colonic mucosa were selected. Each specimen was divided into two parts, one for immunohistochemistry and the other for real-time RT-PCR. Expression differences of MCM2 mRNA among the colonic adenocarcinoma, adenoma and normal colonic mucosa were evaluated by REST-XL software.
RESULTSThe expression of MCM2 was observed in the basal third to half of the colonic crypts in normal mucosa, while throughout the epithelium in the colonic adenocarcinomas and adenomas. However, the expression of MCM2 mRNA in the adenocarcinomas was significantly higher than that in the adenomas(P=0.001). The MCM2 mRNA expression was elevated in the adenoma with villous type, in the conditions of high-grade dysplasia, larger size, sessile morphology and in patients of older ages, but the difference was not significant by REST-XL (P>0.05).
CONCLUSIONThe difference of MCM2 expression between the adenoma and the adenocarcinoma indicates its potential value in the early diagnosis of colonic cancer.
Adenocarcinoma ; metabolism ; pathology ; Adenoma ; metabolism ; pathology ; Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Cell Cycle Proteins ; genetics ; metabolism ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Minichromosome Maintenance Complex Component 2 ; Nuclear Proteins ; genetics ; metabolism ; RNA, Messenger ; Young Adult
5.Phase IIa clinical trail of hemocoagulase acutus for injection.
Jun-jie ZHOU ; Zong-hai HUANG ; Jin-long YU ; Zhou LI ; Guang-jun ZHOU
Journal of Southern Medical University 2007;27(5):644-646
OBJECTIVETo evaluate the efficacy and safety of hemocoagulase acutus for injection and determine its curative dose.
METHODSForty-five patients on abdominal surgeries were randomly allocated into 2 study groups and 1 control group. Thirty minutes before the operation, the patients in the study groups received intravenous hemocoagulase acutus at 1 U and 2 U, respectively, and control group had no treatment. The hemostatic time, hemorrhagic volume, and hemoagglutination were observed in all the groups.
RESULTSThe average hemorrhagic volume and hemorrhagic volume per square were significantly lower in the two study groups than in the control group (P<0.05), and the average hemorrhagic volume per square were significantly lower in study group 2 U than in the 1 U group (P<0.05). No significant differences were found in adverse effects between the 3 groups.
CONCLUSIONHemocoagulase acutus for injection has good hemostatic effect for controlling capillary hemorrhage at the abdominal incisions and can be safely used in the surgical patients.
Abdomen ; surgery ; Adolescent ; Adult ; Aged ; Agkistrodon ; metabolism ; Animals ; Batroxobin ; administration & dosage ; therapeutic use ; Blood Coagulation ; drug effects ; Blood Loss, Surgical ; prevention & control ; Hemostasis, Surgical ; methods ; Hemostatics ; administration & dosage ; therapeutic use ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Treatment Outcome ; Young Adult
6.In vitro killing effect of adenovirus-mediated fusion gene system driven by KDR promoter on gastric cancer cells.
Guang-jun ZHOU ; Zong-hai HUANG ; Jin-long YU ; Zhou LI ; Guo-qiang SU
Journal of Southern Medical University 2006;26(4):402-405
OBJECTIVETo evaluate the killing effect of adenovirus(Ad)-mediated double suicide gene driven by kinase domain-containing receptor (KDR) promoter on gastric cancer MGC-803 cells.
METHODSThe 293 packaging cells were transfected by the plasmids pAdEasy-KDR-CDglyTK to generate infectious viruses. The gastric cancer MGC-803 cells were infected by the Ad followed by treatment with 5-FC and/or ganciclovir at different concentrations. The cell-killing effects were evaluated and the bystander effects analyzed after coculture of the cells without AdKDR-CDglyTK infection with the infected cells at different ratios. The cell cycle distribution was detected by flow cytometry and the pathological changes of the cells were observed by electron microscopy.
RESULTSThe infection rate of the resultant recombinant Ad in the cells increased gradually with increment of the multiplicity of infection (MOI) of the Ads. The killing effect of CD/TK fusion gene on the MGC-803 cells was much stronger than that of either of the single suicide gene (P<0.001), and considerable bystander effect was observed. The Ad infection caused MGC-803 cell growth arrest at G(1) phase with onset of apoptotic and necrotic morphologies of the cells as seen under electron microscope.
CONCLUSIONThe CD/TK fusion gene system driven by the KDR promoter possesses effective killing effect on the KDR-expressing gastric cancer MGC-803 cells.
Adenoviridae ; genetics ; Cell Line, Tumor ; Cytosine Deaminase ; genetics ; Genes, Transgenic, Suicide ; genetics ; Genetic Therapy ; Genetic Vectors ; Humans ; Promoter Regions, Genetic ; Receptor Protein-Tyrosine Kinases ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; Stomach Neoplasms ; pathology
7.E1AF gene expression and its clinical significance in human rectal cancer
Hai-Yi LIU ; Bing XU ; Yu-Jian ZENG ; Jun-Min SONG ; Yong-Yang YU ; Zong-Guang ZHOU ; Hong-Zhi LUO ; Lie YANG ; Ling WANG ; Bin ZHOU
Cancer Research and Clinic 2006;0(11):-
Objective To detect EIA factor expression in human rectal cancer and normal tissue and to determine whether it is correlated with invasion and metastasis of human rectal cancer. Methods Real- time RT-PCR was used to detect E1AF expression in matched rectal cancers and normal tissues from g6 in- patients.Results Among the 86 rectal cancer samples tested,55 cases E1AF mRNA overexpression was ob- served. The mRNA expression of E1AF in the sample group was remarkably different from that in the control group.In carcinomas,E1AF mRNA expression correlated significantly with histological type,depth of inva- sion,lymph node and distant metastasis and advanced Duke stage.Conclusion E1AF is correlated signifi- cantly with invasion and metastasis of human rectal cancer and may be an important factor in the invasion and metastasis.
8.Effect of 5-aminolevulinic acid-mediated photodynamic therapy on human gastric cancer xenografts in nude mice in vivo.
Guang-jun ZHOU ; Zong-hai HUANG ; Jin-long YU ; Zhou LI ; Lian-shu DING
Chinese Journal of Gastrointestinal Surgery 2008;11(6):580-583
OBJECTIVETo investigate the effect of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on human gastric cancer xenografts in vivo and to explore its potential tumoricidal mechanism.
METHODSCultured MGC-803 human gastric cancer cells were injected below the skins of the nude mice to develop the tumor model. The tumor-bearing nude mice were examined under the Leica LT-9 MACIMSYSPULS to detect the fluorescence. The tumor volume of day 1, 3, 7, 14, 21 after treatment were measured, and its histological changes were also studied. The tissues of the tumors in nude mice of the control group, light group, 5-ALA group and PDT group were examined with the electron microscope and apoptosis was detected by TUNEL assay.
RESULTSThe tumor model was successfully developed. The tumor in the nude mice emitted the red fluorescence under the Leica LT-9 MACIMSYSPULS. The tumor volumes were (0.189+/-0.010) cm(3), (0.183+/-0.011) cm(3), (0.185+/-0.019)cm(3), (0.182+/-0.015)cm(3) for the control group, light group, 5-ALA group, PDT group, respectively at day 1 after treatment, while at day 3, (0.294+/-0.010) cm(3), (0.280+/-0.013) cm(3), (0.278+/-0.016) cm(3), (0.183+/-0.014) cm(3); at day 7, (0.409+/-0.016) cm(3), (0.411+/-0.009) cm(3), (0.407+/-0.015) cm(3), (0.221+/-0.008) cm(3); at day 14, (0.970+/-0.055) cm(3), (0.976+/-0.054) cm(3), (0.981+/-0.032)cm(3), (0.318+/-0.005) cm(3); at day 21, (1.495+/-0.059) cm(3), (1.513+/-0.057) cm(3), (1.524+/-0.063) cm(3), (0.446+/-0.042) cm(3) (F=1003.086, P=0.000). The histology demonstrated that most tumor blood vessels were congested and necrosis developed after PDT while not in the control group, light group and 5-ALA group. Necrosis and apoptosis were observed in the cells of the tumors of the PDT group examined by TUNEL and electron microscope while not in the cells of the tumors of the other groups.
CONCLUSIONS5-aminolevulinic acid-mediated photodynamic therapy (PDT) can induce injury to human gastric cancer xenografts and inhibit the tumor growth while light only and 5-ALA only can not. 5-aminolevulinic acid-mediated photodynamic therapy (ALA- PDT) appears to be a promising therapy for human gastric cancer, whose mechanism involves in the destruction of the tumors partly by apoptosis other than necrosis.
Aminolevulinic Acid ; therapeutic use ; Animals ; Cell Line, Tumor ; Female ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental ; Photochemotherapy ; Stomach Neoplasms ; therapy ; Xenograft Model Antitumor Assays
9.Therapeutic effect of agonistic CD40 monoclonal antibody combined with CTL on hu-SCID mouse B lymphoma model.
Huan ZHOU ; Hong XI ; Qian-ru MA ; Cheng CHEN ; Feng ZHANG ; Xue-guang ZHANG ; Zong-jiang GU
Chinese Journal of Oncology 2007;29(3):181-185
OBJECTIVETo study the therapeutic effect of agonistic CD40 monoclonal antibody combined with tumor specific cytotoxic T lymphocyte (CTL) on B lymphoma.
METHODSHuman B lymphoma cell line, Daudi cells, were cultured with CD40 mAb (5C11) for 24 and 48 hours, respectively. Annexin V/PI-binding assay was employed to analyze apoptosis, and FCM to analyze Fas (CD95) expression. Human peripheral monocyte-derived DC were loaded with apoptotic Daudi cells and stimulated by SC11 for further maturation. Tumor specific CTL were generated in vitro by co-culture of mature DC with autologous T lymphocytes. DNA fragmentations of Daudi cells treated with 5C11, CTL or 5C11 combined with CTL were determined by JAM assay. To establish the B lymphoma model, Daudi cells were subcutaneously injected into humanized SCID mice (hu-SCID). 1 or 3 weeks after tumor transfer. tumor-bearing mice were respectively treated with SC11, CTL, 5C11 combined with CTL by intraperitoneal injection. Tumor volume in differently treated mice was measured every week after therapy, and the survival of tumor-bearing mice was recorded.
RESULTS5C11 significantly up-regulated FAS expression in Daudi cells, but had no significant effect on apoptosis rate of Daudi cells. Tumor-specific CTL could effectively kill Daudi cells. Fragmentation of Daudi cells co-cultured with CTL was remarkably enhanced by combination with SC11. Tumor growth in hu-SCID mice was apparently delayed by treatment with SC11, CTL, or SC11 combined with CTL. Moreover, minimal tumor burden mice got 30.0% or 70.0% complete remission (CR), respectively, when received CTL treatment or combination treatment of SC11 with CTL, and the lifespan of tumor bearing mice was also prolonged significantly.
CONCLUSIONSC11 may enhance the sensitivity of Daudi cells to apoptosis by up-regulation of Fas expression and promote cytotoxicity of CTL in vitro and therapeutic effect in vivo.
Animals ; Antibodies, Monoclonal ; immunology ; therapeutic use ; Apoptosis ; immunology ; CD40 Antigens ; immunology ; Cell Line, Tumor ; Coculture Techniques ; Female ; Flow Cytometry ; Humans ; Immunotherapy, Adoptive ; methods ; Lymphoma, B-Cell ; immunology ; pathology ; therapy ; Mice ; Mice, SCID ; Remission Induction ; Survival Analysis ; T-Lymphocytes, Cytotoxic ; cytology ; immunology ; Xenograft Model Antitumor Assays ; fas Receptor ; immunology
10.Expression of phosphatase of regeneration liver-3 in human colorectal carcinoma and its prognosis value.
Gao-ping ZHAO ; Zong-guang ZHOU ; Wen-zhang LEI ; Cun WANG ; Xue-lian ZHENG ; Yang-chun ZHENG
Chinese Journal of Gastrointestinal Surgery 2008;11(5):487-491
OBJECTIVETo investigate the expression of phosphatase of regeneration liver-3(PRL-3) protein and its relationship with tumor invasion and metastasis in human colorectal carcinoma,and elucidate prognostic value.
METHODSImmunohistochemistry method was applied to detect the PRL-3 expression in the primary tumor specimens and paired paratumor normal tissues from 46 colorectal carcinoma patients, the adenoma tissues from 6 patients with colorectal adenoma, all the metastatic lymph nodes from 29 cases and the metastatic liver lesions from 6 cases. The relationship between PRL-3 expression and clinicopathologic parameters was analyzed and a survival curve was achieved according to Kaplan-Meier method.
RESULTSNo or weak PRL-3 protein expression was detected in normal colorectal mucosa and colorectal adenoma. In colorectal carcinoma tissues, PRL-3 expression was confirmed in 26 of 46 cases (56.5%) of primary colorectal carcinomas (with lymph node metastasis 63.0%, without lymph node metastasis 37.0%, P=0.001), 26 of 29 (89.7%) lymph node metastases, and 5 of 6 liver metastases. The expression of PRL-3 was assembled in the cytoplasm of carcinoma cells and more intensively on the cell membrane.Analysis of the relationship between PRL-3 expression and the clinicopathologic features showed that PRL-3 expression was closely associated with tumor stage (P=0.019), lymph node metastasis (P=0.026), but no relationship with age, sex, tumor size, degree of differentiation was founded (P<0.05). The mean follow-up time was 41.4 months and results showed that patients with positive expression of PRL-3 had a significantly poorer prognosis than those with negative PRL-3 expression group(P=0.032).
CONCLUSIONSPRL-3 protein plays a novel role in tumor progression and metastasis of colorectal carcinoma. PRL-3 can be expected to be a potential predictive biomarker for identifying the prognosis in colorectal carcinoma patients.
Adult ; Aged ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; metabolism ; secondary ; Liver Regeneration ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neoplasm Staging ; Prognosis ; Protein Tyrosine Phosphatases ; metabolism