Aim To investigate the influences of melatonin (MT) on the growth of HeLa cells in vitro. Methods Theantiprolfferation activities of MT were evaluated in HeLa cells by means of trypan blue dye exclusion and MTT vital ...Aim To investigate the influences of melatonin (MT) on the growth of HeLa cells in vitro. Methods Theantiprolfferation activities of MT were evaluated in HeLa cells by means of trypan blue dye exclusion and MTT vital staining.The morphological changes of HeLa cells induced by MT were observed under transmission electronic microscope. Cell divisioncycle influenced by MT was assessed by a flow cytometry. Results MT produced a certain inhibition of HeLa cells at the con-centration of 2 mmol@ L-1 and prolonged the TD. The fraction of cells inhibited was 61.0%. The IC. so of HeLa cells exposed toMT for 96 h was 2.039 mmol@ L- 1. The flow cytometric analyses showed that exposure to MT for 72 h reduced the number ofHeLa cells in phase S. Under electronic microscope, the HeLa cells exposed to MT for 72 h displayed morphological changesof necrosis, apoptosis, more hetero-chromosome and less somatic chromosome. Conclusion MT showed certain influences onthe growth of HeLa cells. Its mechanism may probably be attributable to reduction of the number of cells in phase S.展开更多
AIM: To select the optimal antisense accessible sites of survivin, a highly expressed gene in tumor tissues, in order to explore a novel approach to improve biological therapy of gastric cancer. METHODS: The 20 mer ra...AIM: To select the optimal antisense accessible sites of survivin, a highly expressed gene in tumor tissues, in order to explore a novel approach to improve biological therapy of gastric cancer. METHODS: The 20 mer random oligonucleotide library was synthesized, hybridized with in vitro transcribed total survivin cRNA, then digested by RNase H. After primer extension and autoradiography, the antisense accessible sites (AAS) of survivin were selected. Then RNADraw software was used to analyze and choose the AAS with obvious stem-loop structures, according to which the complementary antisense oligonucleotides (AS-ODNs) were synthesized and transferred into survivin highly- expressing gastric cancer cell line MKN-45. Survivin expression was detected by RT-PCR and Western Blotting. Cellular growth activities were assayed by tetrazolium bromide (MTT) colorimetry. Cellular ultrastructure was observed by electronic microscopy, while apoptosis was detected by annexin V-FITC and propidium iodide staining flow cytometry. RESULTS: Thirteen AAS of survivin were selected In vitro. Four AAS with stem-loop structures were chosen, locating at 207-226 bp, 187-206 bp, 126-145 bp and 44-63 bp of survivin cDNA respectively. When compared with non-tranfection controls, their corresponding AS-ODNs (AS-ODN1, AS-ODN2, AS-ODN3 and AS-ODN4) could reduce Survivin mRNA levels in MKN-45 cells by 54.3±±1.1% (t= 6.12, P<0.01), 86.1±±1.0% (t= 5.27, P<0.01), 32.2±±1.3% (t= 7.34, P<0.01) and 56.2±±0.9% (t = 6.45, P<0.01) respectively, while survivin protein levels were decreased by 42.2±±2.5% (t = 6.26, P<0.01), 75.4±±3.1% (t= 7.11, P<0.01), 28.3±±2.0% (t= 6.04, P<0.01) and 45.8±±1.2% (t = 6.38,P<0.01) respectively. After transfection with 600 nmol/L AS-ODN1-AS-ODN4for 24 h, cell growth was inhibited by 28.12±±1.54% (t= 7.62, P<0.01), 38.42±±3.12% (t= 7.75, P<0.01), 21.46±±2.63% (t= 5.94, P<0.01) and 32.12±1.77% (t = 6.17, P<0.01) respectively. Partial cancer cells presented the characteristic morphological changes of apoptosis, with apoptotic rates being 19.31±1.16% (t= 7.16,P<0.01), 29.24±1.94% (t = 8.15,P<0.01), 11.87±0.68% (t = 6.68, P<0.01) and 21.68±2.14% (t = 7.53, P<0.01) respectively. CONCLUSION: The MS of survivin could be effectively selected in vitro by random oligonucleotide library/RNase H cleavage method combined with computer software analysis, this has important reference values for further studying survivin-targeted therapy strategies for gastric cancer.展开更多
Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistan...Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warhurg＇s discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. This review highlights the importance of the main features of cancer metabolism, summarizes recent remarkable advances in this field, and points out the potentials to translate these scientific findings into life-saving diagnosis and therapies to help cancer patients.展开更多
AIM： To evaluate the efficacy of combination chemotherapy with interferon-α （IFNα） and 5-fluorouracil （5-FU） in patients with advanced hepatocellular carcinoma （HCC）. METHODS： Twenty-eight HCC patients in ad...AIM： To evaluate the efficacy of combination chemotherapy with interferon-α （IFNα） and 5-fluorouracil （5-FU） in patients with advanced hepatocellular carcinoma （HCC）. METHODS： Twenty-eight HCC patients in advanced stage were enrolled in the study. They were treated with IFNα/ 5-FU combination chemotherapy. One cycle of therapy lasted for 4 wk. IFNα （3×10^6 units） was subcutaneously injected thrice weekly on days 1, 3, and 5 for 3 wk, and 5-FU （500 mg/d） was administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. No drugs were administered during the 4th wk. The effect of combination chemotherapy was evaluated in each patient alter every cycle based on the reduction of tumor volume. RESULTS： Alter the 1^st cycle of therapy, 16 patients showed a partial response （PR, 57.1%） but none showed a complete response （CR, 0%）. At the end of therapy, the number of patients who showed a CR, PR, or no response （NR） was 1, 10, and 17, respectively. The response rate for therapy （CR＋PR） was 21.5%. Biochemical tests before therapy were compared between responsive （CR＋PR） and non-responsive （NR） patients, but no significant differences were found for any of the parameters examined, indicating that no reasonable predictors could be identified in our analysis. CONCLUSION： Attempts should be made to discriminate between responders and non-responders by evaluating tumor size alter the first cycle of IFNα/5-FU combination chemotherapy. For non-responders, therapy should not proceed to the next cycle, and instead, different combination of anticancer drugs should be explored. 2005 The WJG Press and Elsevier Inc. All rights reserved展开更多
文摘Aim To investigate the influences of melatonin (MT) on the growth of HeLa cells in vitro. Methods Theantiprolfferation activities of MT were evaluated in HeLa cells by means of trypan blue dye exclusion and MTT vital staining.The morphological changes of HeLa cells induced by MT were observed under transmission electronic microscope. Cell divisioncycle influenced by MT was assessed by a flow cytometry. Results MT produced a certain inhibition of HeLa cells at the con-centration of 2 mmol@ L-1 and prolonged the TD. The fraction of cells inhibited was 61.0%. The IC. so of HeLa cells exposed toMT for 96 h was 2.039 mmol@ L- 1. The flow cytometric analyses showed that exposure to MT for 72 h reduced the number ofHeLa cells in phase S. Under electronic microscope, the HeLa cells exposed to MT for 72 h displayed morphological changesof necrosis, apoptosis, more hetero-chromosome and less somatic chromosome. Conclusion MT showed certain influences onthe growth of HeLa cells. Its mechanism may probably be attributable to reduction of the number of cells in phase S.
基金Supported by National Natural Science Foundation of China, No.30200284Science Foundation of Huazhong University of Science and Technology
文摘AIM: To select the optimal antisense accessible sites of survivin, a highly expressed gene in tumor tissues, in order to explore a novel approach to improve biological therapy of gastric cancer. METHODS: The 20 mer random oligonucleotide library was synthesized, hybridized with in vitro transcribed total survivin cRNA, then digested by RNase H. After primer extension and autoradiography, the antisense accessible sites (AAS) of survivin were selected. Then RNADraw software was used to analyze and choose the AAS with obvious stem-loop structures, according to which the complementary antisense oligonucleotides (AS-ODNs) were synthesized and transferred into survivin highly- expressing gastric cancer cell line MKN-45. Survivin expression was detected by RT-PCR and Western Blotting. Cellular growth activities were assayed by tetrazolium bromide (MTT) colorimetry. Cellular ultrastructure was observed by electronic microscopy, while apoptosis was detected by annexin V-FITC and propidium iodide staining flow cytometry. RESULTS: Thirteen AAS of survivin were selected In vitro. Four AAS with stem-loop structures were chosen, locating at 207-226 bp, 187-206 bp, 126-145 bp and 44-63 bp of survivin cDNA respectively. When compared with non-tranfection controls, their corresponding AS-ODNs (AS-ODN1, AS-ODN2, AS-ODN3 and AS-ODN4) could reduce Survivin mRNA levels in MKN-45 cells by 54.3±±1.1% (t= 6.12, P<0.01), 86.1±±1.0% (t= 5.27, P<0.01), 32.2±±1.3% (t= 7.34, P<0.01) and 56.2±±0.9% (t = 6.45, P<0.01) respectively, while survivin protein levels were decreased by 42.2±±2.5% (t = 6.26, P<0.01), 75.4±±3.1% (t= 7.11, P<0.01), 28.3±±2.0% (t= 6.04, P<0.01) and 45.8±±1.2% (t = 6.38,P<0.01) respectively. After transfection with 600 nmol/L AS-ODN1-AS-ODN4for 24 h, cell growth was inhibited by 28.12±±1.54% (t= 7.62, P<0.01), 38.42±±3.12% (t= 7.75, P<0.01), 21.46±±2.63% (t= 5.94, P<0.01) and 32.12±1.77% (t = 6.17, P<0.01) respectively. Partial cancer cells presented the characteristic morphological changes of apoptosis, with apoptotic rates being 19.31±1.16% (t= 7.16,P<0.01), 29.24±1.94% (t = 8.15,P<0.01), 11.87±0.68% (t = 6.68, P<0.01) and 21.68±2.14% (t = 7.53, P<0.01) respectively. CONCLUSION: The MS of survivin could be effectively selected in vitro by random oligonucleotide library/RNase H cleavage method combined with computer software analysis, this has important reference values for further studying survivin-targeted therapy strategies for gastric cancer.
基金supported by the National Institutes of Health through The University of Texas MD Anderson Cancer Center’s Support Grant CA016672National Cancer Institute grant RO1CA 089266 (MHL)+3 种基金Directed Medical Research Programs Department of Defense Synergistic Idea Development Award BC062166 (SCY, MHL)the Susan G.Komen Breast Cancer Research Foundation Promise Grant KG081048 (SCY, MHL)Vietnam Education Foundation, Rosalie B.Hite FoundationDepartment of Defense Breast Cancer Research Program (Award # W81XWH-10-0171)
文摘Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warhurg＇s discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. This review highlights the importance of the main features of cancer metabolism, summarizes recent remarkable advances in this field, and points out the potentials to translate these scientific findings into life-saving diagnosis and therapies to help cancer patients.
文摘AIM： To evaluate the efficacy of combination chemotherapy with interferon-α （IFNα） and 5-fluorouracil （5-FU） in patients with advanced hepatocellular carcinoma （HCC）. METHODS： Twenty-eight HCC patients in advanced stage were enrolled in the study. They were treated with IFNα/ 5-FU combination chemotherapy. One cycle of therapy lasted for 4 wk. IFNα （3×10^6 units） was subcutaneously injected thrice weekly on days 1, 3, and 5 for 3 wk, and 5-FU （500 mg/d） was administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. No drugs were administered during the 4th wk. The effect of combination chemotherapy was evaluated in each patient alter every cycle based on the reduction of tumor volume. RESULTS： Alter the 1^st cycle of therapy, 16 patients showed a partial response （PR, 57.1%） but none showed a complete response （CR, 0%）. At the end of therapy, the number of patients who showed a CR, PR, or no response （NR） was 1, 10, and 17, respectively. The response rate for therapy （CR＋PR） was 21.5%. Biochemical tests before therapy were compared between responsive （CR＋PR） and non-responsive （NR） patients, but no significant differences were found for any of the parameters examined, indicating that no reasonable predictors could be identified in our analysis. CONCLUSION： Attempts should be made to discriminate between responders and non-responders by evaluating tumor size alter the first cycle of IFNα/5-FU combination chemotherapy. For non-responders, therapy should not proceed to the next cycle, and instead, different combination of anticancer drugs should be explored. 2005 The WJG Press and Elsevier Inc. All rights reserved
