Changes in the surface structure of cell membrane and the contents of membrane pro- teins and nuclear DNA of human gastric cancer (BGC-823) cells treated with organotin compound (Et_2SnCl_2phen) were studied with a sc...Changes in the surface structure of cell membrane and the contents of membrane pro- teins and nuclear DNA of human gastric cancer (BGC-823) cells treated with organotin compound (Et_2SnCl_2phen) were studied with a scanning electron microscope (SEM),a scanning tunneling,micro- scope (STM),and a cytofluorophotometer.It was found that Et_2SnCl_2Phen not only inhibited the cell growth but also remarkably changed the surface structure of the membrane of cancer cells.The surface of Et_2SnCl_2phen treated cancer cells was relatively smooth and showed fewer microvilli under SEM. STM images showed an uneven and loose distribution of the surface of the cell.In comparison with the untreated cancer cells,there was an evident decrease in the content of membrane proteins and nuclear DNA in Et_2SnCl_2phen treated cells.展开更多
Objective.Using monoclonal antibody (mAb) Fab′ fragment to develop mAb immunoconjugates for cancer. Methods.Fab′ fragment of mAb 3A5 was prepared by digestion of the antibody with pepsin and then reduced by dithioth...Objective.Using monoclonal antibody (mAb) Fab′ fragment to develop mAb immunoconjugates for cancer. Methods.Fab′ fragment of mAb 3A5 was prepared by digestion of the antibody with pepsin and then reduced by dithiothreitol (DTT),while Fab′ fragment of mAb 3D6 was obtained by digestion of the antibody with ficin and subsequently reduced by β mercaptoethanol.The conjugation between Fab′ fragment and pingyangmycin (PYM),an antitumor antibiotic,was mediated by dextran T 40.Immunoreactivity of Fab′ PYM conjugates with cancer cells was determined by ELISA,and the cytotoxicity of those conjugates to cancer cells was determined by clonogenic assay.Antitumor effects of the Fab′ PYM conjugates were evaluated by subcutaneously transplanted tumors in mice. Results.The molecular weight of Fab′ fragment was approximately 53 kD,while the average molecular weight of Fab′ PYM conjugate was 170 kD.The Fab′ PYM conjugates showed immunoreactivity with antigen relevant cancer cells and selective cytotoxicity against target cells.Administered intravenously,Fab′ PYM conjugates were more effective against the growth of tumors in mice than free PYM and PYM conjugated with intact mAb. Conclusion.Fab′ PYM conjugate may be capable of targeting cancer cells and effectively inhibiting tumor growth,suggesting its therapeutic potential in cancer treatment.展开更多
Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal...Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer. According to the literature, this agent might well satisfy clinical expectations with respect to a safe and effective chemopreventive agent.展开更多
AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation ...AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo. METHODS: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d. Then Cantide, DDP and Cantide+DDP were given intra peritonea Ily for 24 d respectively. The body weights of the tumor-bearing animals and their tumor mass were measured later to assess the effect of combination therapy in the nude mice. To evaluate the interaction of Cantide and these chemotherapeutic drugs, SAS software and Jin Zhengjun method were used. RESULTS: Combination treatments with 0.1μmol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29 μg/mL to 0.25,1.52 and 0.12 μg/mL respectively. The inhibition ability of DDP, 5-FU and ADM respectively in combination with Cantide in these tumor cells was higher than that of these drugs alone (P<0.0001). And synergism (Q≥1.15)was observed at the lower concentration of DDP (≤1μg/mL) and ADM (≤0.1 μg/mL) with combination of Cantide. In vivo, combination treatment with Cantide and DDP produced the greater growth inhibition of human liver carcinoma cells HepG2 in nude mice (0.65±0.19 g tumor) compared with that when only one of these drugs was used (Cantide group: 1.05±0.16 g tumor, P= 0.0009<0.001; DDP group: 1.13±0.09 g tumor, P= 0.0001<0.001). CONCLUSION: These findings indicate that Cantide may enhance therapeutic effectiveness of chemotherapeutic drugs over a wide range of tumor cells in vitro, and the combination use of Cantide and DDP can produce much higher inhibition rates, as compared with when either of these drugs was used only in vivo.展开更多
AIM： To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis （TBP） and peritoneal carcinoma- tosis （PC）. METHODS： A retrospective analysis of dat...AIM： To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis （TBP） and peritoneal carcinoma- tosis （PC）. METHODS： A retrospective analysis of data was per- formed on consecutive patients who underwent perito- neoscopic and abdominal computed tomography （CT） evaluations. Among 75 patients at the Seoul National University Hospital from January 2000 to June 2010 who underwent both tests, 27 patients （36.0%） and 25 patients （33.3%） were diagnosed with TBP and PC, re- spectively. Diagnosis was confirmed by peritoneoscopic biopsy. RESULTS： Serum c-reactive protein （7.88：1：6.62 mg/ dL vs 3.12 ＋ 2.69 mg/dL, P = 0.01）, ascites adenos- ine deaminase （66.76：1：32.09 IU/L vs 13.89 ：l： 8.95 IU/L, P 〈 0.01）, ascites lymphocyte proportion （67.77 ：1： 23.41% vs 48.36 ＋ 18.78%, P 〈 0.01）, and serum- ascites albumin gradient （0.72 ＋ 0.49 g/dL vs 1.05 ＋ 0.50 g/dL, P = 0.03） were significantly different be- tween the two groups. Among tumor markers, serum and ascites carcinoembryonic antigen, serum carbohy- drate antigen 19-9 showed significant difference be- tween two groups. Abdominal CT examinations showed that smooth involvement of the parietal peritoneum was more common in the TBP group （77.8% vs 40.7%） whereas nodular involvement was more common in the PC group （14.8% vs 40.7%, P = 0.04）. From receiver operating characteristic （ROC） curves ascites adeno- sines deaminase （ADA） showed better discriminative capability than tumor markers. An ADA cut-off level of 21 IU/L was found to yield the best results of differ- ential diagnosis; sensitivity, specificity, positive predic- tive value, and negative predictive value were 92.0%, 85.0%, 88.5% and 89.5%, respectively. CONCLUSION： Besides clinical and radiologic findings, ascitic fluid ADA measurement is helpful in the differen- tial diagnosis of TBP and PC.展开更多
文摘Changes in the surface structure of cell membrane and the contents of membrane pro- teins and nuclear DNA of human gastric cancer (BGC-823) cells treated with organotin compound (Et_2SnCl_2phen) were studied with a scanning electron microscope (SEM),a scanning tunneling,micro- scope (STM),and a cytofluorophotometer.It was found that Et_2SnCl_2Phen not only inhibited the cell growth but also remarkably changed the surface structure of the membrane of cancer cells.The surface of Et_2SnCl_2phen treated cancer cells was relatively smooth and showed fewer microvilli under SEM. STM images showed an uneven and loose distribution of the surface of the cell.In comparison with the untreated cancer cells,there was an evident decrease in the content of membrane proteins and nuclear DNA in Et_2SnCl_2phen treated cells.
基金This work was supported by the grants from the National Key Research Project Funds，国家重点基础研究发展计划(973计划)
文摘Objective.Using monoclonal antibody (mAb) Fab′ fragment to develop mAb immunoconjugates for cancer. Methods.Fab′ fragment of mAb 3A5 was prepared by digestion of the antibody with pepsin and then reduced by dithiothreitol (DTT),while Fab′ fragment of mAb 3D6 was obtained by digestion of the antibody with ficin and subsequently reduced by β mercaptoethanol.The conjugation between Fab′ fragment and pingyangmycin (PYM),an antitumor antibiotic,was mediated by dextran T 40.Immunoreactivity of Fab′ PYM conjugates with cancer cells was determined by ELISA,and the cytotoxicity of those conjugates to cancer cells was determined by clonogenic assay.Antitumor effects of the Fab′ PYM conjugates were evaluated by subcutaneously transplanted tumors in mice. Results.The molecular weight of Fab′ fragment was approximately 53 kD,while the average molecular weight of Fab′ PYM conjugate was 170 kD.The Fab′ PYM conjugates showed immunoreactivity with antigen relevant cancer cells and selective cytotoxicity against target cells.Administered intravenously,Fab′ PYM conjugates were more effective against the growth of tumors in mice than free PYM and PYM conjugated with intact mAb. Conclusion.Fab′ PYM conjugate may be capable of targeting cancer cells and effectively inhibiting tumor growth,suggesting its therapeutic potential in cancer treatment.
文摘Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer. According to the literature, this agent might well satisfy clinical expectations with respect to a safe and effective chemopreventive agent.
基金Supported by the National Nature Science Foundation of China, No. 39870879Key Technologies R and D Program of China, No. 2002AA2Z3337
文摘AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo. METHODS: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d. Then Cantide, DDP and Cantide+DDP were given intra peritonea Ily for 24 d respectively. The body weights of the tumor-bearing animals and their tumor mass were measured later to assess the effect of combination therapy in the nude mice. To evaluate the interaction of Cantide and these chemotherapeutic drugs, SAS software and Jin Zhengjun method were used. RESULTS: Combination treatments with 0.1μmol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29 μg/mL to 0.25,1.52 and 0.12 μg/mL respectively. The inhibition ability of DDP, 5-FU and ADM respectively in combination with Cantide in these tumor cells was higher than that of these drugs alone (P<0.0001). And synergism (Q≥1.15)was observed at the lower concentration of DDP (≤1μg/mL) and ADM (≤0.1 μg/mL) with combination of Cantide. In vivo, combination treatment with Cantide and DDP produced the greater growth inhibition of human liver carcinoma cells HepG2 in nude mice (0.65±0.19 g tumor) compared with that when only one of these drugs was used (Cantide group: 1.05±0.16 g tumor, P= 0.0009<0.001; DDP group: 1.13±0.09 g tumor, P= 0.0001<0.001). CONCLUSION: These findings indicate that Cantide may enhance therapeutic effectiveness of chemotherapeutic drugs over a wide range of tumor cells in vitro, and the combination use of Cantide and DDP can produce much higher inhibition rates, as compared with when either of these drugs was used only in vivo.
文摘AIM： To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis （TBP） and peritoneal carcinoma- tosis （PC）. METHODS： A retrospective analysis of data was per- formed on consecutive patients who underwent perito- neoscopic and abdominal computed tomography （CT） evaluations. Among 75 patients at the Seoul National University Hospital from January 2000 to June 2010 who underwent both tests, 27 patients （36.0%） and 25 patients （33.3%） were diagnosed with TBP and PC, re- spectively. Diagnosis was confirmed by peritoneoscopic biopsy. RESULTS： Serum c-reactive protein （7.88：1：6.62 mg/ dL vs 3.12 ＋ 2.69 mg/dL, P = 0.01）, ascites adenos- ine deaminase （66.76：1：32.09 IU/L vs 13.89 ：l： 8.95 IU/L, P 〈 0.01）, ascites lymphocyte proportion （67.77 ：1： 23.41% vs 48.36 ＋ 18.78%, P 〈 0.01）, and serum- ascites albumin gradient （0.72 ＋ 0.49 g/dL vs 1.05 ＋ 0.50 g/dL, P = 0.03） were significantly different be- tween the two groups. Among tumor markers, serum and ascites carcinoembryonic antigen, serum carbohy- drate antigen 19-9 showed significant difference be- tween two groups. Abdominal CT examinations showed that smooth involvement of the parietal peritoneum was more common in the TBP group （77.8% vs 40.7%） whereas nodular involvement was more common in the PC group （14.8% vs 40.7%, P = 0.04）. From receiver operating characteristic （ROC） curves ascites adeno- sines deaminase （ADA） showed better discriminative capability than tumor markers. An ADA cut-off level of 21 IU/L was found to yield the best results of differ- ential diagnosis; sensitivity, specificity, positive predic- tive value, and negative predictive value were 92.0%, 85.0%, 88.5% and 89.5%, respectively. CONCLUSION： Besides clinical and radiologic findings, ascitic fluid ADA measurement is helpful in the differen- tial diagnosis of TBP and PC.
