Aim To study the distribution pattern, antineoplastic activity and immunocompetence of a novel organoselenium compound Eb and investigate its in vivo antineoplastic potential. Methods Eb was administered to Kunming ...Aim To study the distribution pattern, antineoplastic activity and immunocompetence of a novel organoselenium compound Eb and investigate its in vivo antineoplastic potential. Methods Eb was administered to Kunming mice (dosage, 0.1 g·kg^(-1)·d^(-1)) intragastrically for 7 successive days. The contents of selenium in heart, liver, spleen, kidneys, lungs, stomach, brain, muscle, and bone were determined by fluorometric method on the eighth day. MTT assay was used to study tumor growth inhibition of Eb in vitro, and lymphocyte transformation, hemolysin formation and phagocytosis assay were used to study its immunocompetence. Results After 7 days′ administration of Eb, the tissue contents of sele-(nium) in liver, spleen, lungs, kidneys, and bone of mice increased, especially those in liver and spleen increased significan-tly, compared with controls; but no significant changes of such contents were found in muscle, heart, brain, and stomach. Eb demonstrated inhibitory effects on human Bel-7402, BGC-823, and Calu-3 cancer cell lines in vitro. Eb also showed ability to enhance lymphocyte transformation and serum hemolysin formation in vitro and increase the phagocytosis of macrophages. Conclusion The validated antitumor and immunostimulatory activities of Eb suggest a hypothesis that Eb may behave as a biological response modifier when used as an antitumor agent. Eb is worthy of further study in developing a new antineoplastic and immunity enhancing agent in the light of its antitumor activity, immunocompetence and specific distribution in liver, lungs, kidneys, bone, and spleen.展开更多
Derangements of several cell signaling pathways have been implicated in the initiation, progression, and development ofhepatocellular carcinoma （HCC）. One of such pathways is the activated TGF-β/Smad pathway. TGF-...Derangements of several cell signaling pathways have been implicated in the initiation, progression, and development ofhepatocellular carcinoma （HCC）. One of such pathways is the activated TGF-β/Smad pathway. TGF-β inhibitsproliferation and induces apoptosis in various cells types in the early tumor, and accumulation of loss-of-functionmutations in the TGF-β receptor or Smad genes in tumor classify the pathway as a tumor suppressor. However, inchronic hepatitis, the cytostatic effect of TGF-β for hepatocytes attenuates as liver disease progresses from cirrhosis toHCC under persistent inflammatory microenvironments. In the later cancer period, TGF-β promotes tumor growth bymodulating processes such as cell invasion, immune regulation, and microenvironment modification. Here we evaluatethe suppressive and accelerant roles of TGF-β in HCC, discuss how a tumor-suppressor pathway can be so radicallyturned on its head and further provide some new molecular insights that may aid efforts towards targeted antitumortherapies. Moreover, we discussed the potential anti-tumor herbs through TGF-β signaling pathways.展开更多
Few clinical studies have demonstrated an anti-proliferative activity of somatostatin (SST) analogs in carcinoids. We report the case of a woman with liver metastases of neuroendocrine tumor and no evidence of the pri...Few clinical studies have demonstrated an anti-proliferative activity of somatostatin (SST) analogs in carcinoids. We report the case of a woman with liver metastases of neuroendocrine tumor and no evidence of the primary tumor. The liver metastases were characterized by high proliferation index, immunoreactiviy for somatostatin receptor (SSTR)-l, 2, 3 and 5 and positive octreoscan. Urinary 5-hydroxyindolacetic acid, serum serotonin and chromogranin A were elevated. Slow release lanreotide (SR-LAN) therapy for 3 mo controlled clinical and biochemical signs of carcinoid tumor and caused a clear-cut reduction in the diameter of two liver metastases and disappearance of another lesion, with further reduction after 6 and 18 mo. We demonstrated a clear-cut long-lasting anti-proliferative effect of SR-LAN on liver metastases of occult carcinoid with high proliferation index and immunoreactivity for SSTR-1, 2, 3, and 5. Immunohistochemistry for SSTRs could be a suitable method for the selection of patients with metastatic carcinoid that may benefit from SST analog therapy.展开更多
AIM: To predict the HLA-A2-restricted CTL epitopes of tumor antigens associated with hepatocellular carcinoma (HCC).METHODS: MAGE-1, MAGE-3, MAGE-8, P53 and AFP were selected as objective antigens in this study for th...AIM: To predict the HLA-A2-restricted CTL epitopes of tumor antigens associated with hepatocellular carcinoma (HCC).METHODS: MAGE-1, MAGE-3, MAGE-8, P53 and AFP were selected as objective antigens in this study for the close association with HCC. The HLA-A*0201 restricted CTL epitopes of objective tumor antigens were predicted by SYFPEITHI prediction method combined with the polynomial quantitative motifs method. The threshold of polynomial scores was set to -24.RESULTS: The SYFPEITHI prediction values of all possible nonamers of a given protein sequence were added together and the ten high-scoring peptides of each protein were chosen for further analysis in primary prediction. Thirtyfive candidates of CTL epitopes (nonamers) derived from the primary prediction results were selected by analyzing with the polynomial method and compared with reported CTL epitopes.CONCLUSION: The combination of SYFPEITHI prediction method and polynomial method can improve the prediction efficiency and accuracy. These nonamers may be useful in the design of therapeutic peptide vaccine for HCC and as immunotherapeutic strategies against HCC after identified by immunology experiment.展开更多
AIM: To investigate the effects and mechanisms of Verapamil on cultured human colonic tumor (HCT) cells.METHODS: HCT cells were treated with different concentrations of Verapamil, and their proliferation was examined ...AIM: To investigate the effects and mechanisms of Verapamil on cultured human colonic tumor (HCT) cells.METHODS: HCT cells were treated with different concentrations of Verapamil, and their proliferation was examined by MTT assay. The areas of sub-diploid peak were measured by flow cytometry, and the DNA ladder was found by agarose gel electrophoresis. The characteristic changes in morphology were observed under light microscopy. The cell nuclei (propidium iodide labeled, PI-labeled) and cellular distribution and concentration of calcium (Fluo-3-labeled) were studied by using laser confocal scanning microscope.RESULTS: The proliferation of HCT cells was inhibited by different concentrations of Verapamil. With the increase in concentration of Verapamil, the percent of G0-G1 phase cells in HCT cells increased and that of S phase cells decreased. After treating with different concentrations of Verapamil, flow cytometry showed that HCT cells were enlarged in areas of sub-diploid in a dose-dependent manner. Gel electrophoresis results displayed a typical DNA ladder. On staining with Wrights-Giemsa, the typical cellular apoptosis morphologic changes were also observed. PI-labeled cell nuclei were found markedly changed. In addition, we inspected that the 100 μmol/L Verapamil could increase the intracellular calcium ion concentration [Ca2+]i in HCT cells.CONCLUSION: Verapamil can inhibit proliferation of HCT cells via inducing cell apoptosis.展开更多
The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apop...The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apoptosis. In the present study, the degradation of pRB was observed in apoptotic gastric tumor cells treated with a new potent anti-tumor component, tripchlorolide (TC). The inhibition of pRB degradation by a general cysteine protease inhibitor IDAM resulted in the reduction of the apoptotic cells. Furthermore, the survival of the gastric tumor cells under the TC treatment was enhanced by an over-expression of exogenous pRB. These results suggest that the pRB degradation of the gastric tumor cells under the TC treatment involves in the apoptotic progression. In addition, the same extent of TC- induced pRB-degradation was detected in the gastric tumor cells containing a p53 dominant-negative construct, indicat- ing that this kind of pRB degradation is p53-independent.展开更多
Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was ...Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was induced by retrograde injection of 5% sodium taurocholate into the bile-pancreatic duct. Somatostatin octapeptide (SS-OP) (2μg/kg)was injected into the femoral vein imme- diately in rats of the treatment group after inductive AHNP. Rats of the sham operative group received in- jection of saline. Sixty animals of the AHNP and sham operative groups at the designated time(0. 2h, 0. 5 h, 2h, 4h, 8h, after the operation,six animals at each time point)and tweleve animals of treatment group at 4h after the operation were sacrificed for samples of pancreas, liver and lung. The expressions of TNF α mRNA within the pancreas, liver and lung were established by RT－PCR. Results. TNF α mRNA became detectable in the pancreas as early as 0. 2h after inductive AHNP, while it was undetectable in other organs until 0. 5h. Expression of TNF α mRNA in each tissue increased continuously and reached a peak at 4h,demonstrating a significant difference compared with that at 0. 5h and 8h. Expressions of TNF α mRNA from pancreas, liver and lung were decreased 50-80% in the treat- ment group, the pancreatic necrosis was also attenuated dramatically. Conclusion. TNF α mRNA was detectable in pancreas,liver and lung tissues at the early stage of AH- NP.SS-OP can significantly inhibit the expression of TNF α mRNA and attenuate the pancreatic necrosis. We feel that this may be an important mechanism of SS-OP in the treatment of AHNP.展开更多
文摘Aim To study the distribution pattern, antineoplastic activity and immunocompetence of a novel organoselenium compound Eb and investigate its in vivo antineoplastic potential. Methods Eb was administered to Kunming mice (dosage, 0.1 g·kg^(-1)·d^(-1)) intragastrically for 7 successive days. The contents of selenium in heart, liver, spleen, kidneys, lungs, stomach, brain, muscle, and bone were determined by fluorometric method on the eighth day. MTT assay was used to study tumor growth inhibition of Eb in vitro, and lymphocyte transformation, hemolysin formation and phagocytosis assay were used to study its immunocompetence. Results After 7 days′ administration of Eb, the tissue contents of sele-(nium) in liver, spleen, lungs, kidneys, and bone of mice increased, especially those in liver and spleen increased significan-tly, compared with controls; but no significant changes of such contents were found in muscle, heart, brain, and stomach. Eb demonstrated inhibitory effects on human Bel-7402, BGC-823, and Calu-3 cancer cell lines in vitro. Eb also showed ability to enhance lymphocyte transformation and serum hemolysin formation in vitro and increase the phagocytosis of macrophages. Conclusion The validated antitumor and immunostimulatory activities of Eb suggest a hypothesis that Eb may behave as a biological response modifier when used as an antitumor agent. Eb is worthy of further study in developing a new antineoplastic and immunity enhancing agent in the light of its antitumor activity, immunocompetence and specific distribution in liver, lungs, kidneys, bone, and spleen.
文摘Derangements of several cell signaling pathways have been implicated in the initiation, progression, and development ofhepatocellular carcinoma （HCC）. One of such pathways is the activated TGF-β/Smad pathway. TGF-β inhibitsproliferation and induces apoptosis in various cells types in the early tumor, and accumulation of loss-of-functionmutations in the TGF-β receptor or Smad genes in tumor classify the pathway as a tumor suppressor. However, inchronic hepatitis, the cytostatic effect of TGF-β for hepatocytes attenuates as liver disease progresses from cirrhosis toHCC under persistent inflammatory microenvironments. In the later cancer period, TGF-β promotes tumor growth bymodulating processes such as cell invasion, immune regulation, and microenvironment modification. Here we evaluatethe suppressive and accelerant roles of TGF-β in HCC, discuss how a tumor-suppressor pathway can be so radicallyturned on its head and further provide some new molecular insights that may aid efforts towards targeted antitumortherapies. Moreover, we discussed the potential anti-tumor herbs through TGF-β signaling pathways.
基金Supported by the Grants From the Italian Ministry of University and Scientific and Technological Research (MIUR 2003069821-001 60%, 2003)
文摘Few clinical studies have demonstrated an anti-proliferative activity of somatostatin (SST) analogs in carcinoids. We report the case of a woman with liver metastases of neuroendocrine tumor and no evidence of the primary tumor. The liver metastases were characterized by high proliferation index, immunoreactiviy for somatostatin receptor (SSTR)-l, 2, 3 and 5 and positive octreoscan. Urinary 5-hydroxyindolacetic acid, serum serotonin and chromogranin A were elevated. Slow release lanreotide (SR-LAN) therapy for 3 mo controlled clinical and biochemical signs of carcinoid tumor and caused a clear-cut reduction in the diameter of two liver metastases and disappearance of another lesion, with further reduction after 6 and 18 mo. We demonstrated a clear-cut long-lasting anti-proliferative effect of SR-LAN on liver metastases of occult carcinoid with high proliferation index and immunoreactivity for SSTR-1, 2, 3, and 5. Immunohistochemistry for SSTRs could be a suitable method for the selection of patients with metastatic carcinoid that may benefit from SST analog therapy.
基金Supported by Natural Scientific Foundation of China, No. 39830420
文摘AIM: To predict the HLA-A2-restricted CTL epitopes of tumor antigens associated with hepatocellular carcinoma (HCC).METHODS: MAGE-1, MAGE-3, MAGE-8, P53 and AFP were selected as objective antigens in this study for the close association with HCC. The HLA-A*0201 restricted CTL epitopes of objective tumor antigens were predicted by SYFPEITHI prediction method combined with the polynomial quantitative motifs method. The threshold of polynomial scores was set to -24.RESULTS: The SYFPEITHI prediction values of all possible nonamers of a given protein sequence were added together and the ten high-scoring peptides of each protein were chosen for further analysis in primary prediction. Thirtyfive candidates of CTL epitopes (nonamers) derived from the primary prediction results were selected by analyzing with the polynomial method and compared with reported CTL epitopes.CONCLUSION: The combination of SYFPEITHI prediction method and polynomial method can improve the prediction efficiency and accuracy. These nonamers may be useful in the design of therapeutic peptide vaccine for HCC and as immunotherapeutic strategies against HCC after identified by immunology experiment.
基金Supported by the Foundation of the National New Drug Research of China, No. 96-901-05-197
文摘AIM: To investigate the effects and mechanisms of Verapamil on cultured human colonic tumor (HCT) cells.METHODS: HCT cells were treated with different concentrations of Verapamil, and their proliferation was examined by MTT assay. The areas of sub-diploid peak were measured by flow cytometry, and the DNA ladder was found by agarose gel electrophoresis. The characteristic changes in morphology were observed under light microscopy. The cell nuclei (propidium iodide labeled, PI-labeled) and cellular distribution and concentration of calcium (Fluo-3-labeled) were studied by using laser confocal scanning microscope.RESULTS: The proliferation of HCT cells was inhibited by different concentrations of Verapamil. With the increase in concentration of Verapamil, the percent of G0-G1 phase cells in HCT cells increased and that of S phase cells decreased. After treating with different concentrations of Verapamil, flow cytometry showed that HCT cells were enlarged in areas of sub-diploid in a dose-dependent manner. Gel electrophoresis results displayed a typical DNA ladder. On staining with Wrights-Giemsa, the typical cellular apoptosis morphologic changes were also observed. PI-labeled cell nuclei were found markedly changed. In addition, we inspected that the 100 μmol/L Verapamil could increase the intracellular calcium ion concentration [Ca2+]i in HCT cells.CONCLUSION: Verapamil can inhibit proliferation of HCT cells via inducing cell apoptosis.
基金This work was supported by a grant of Na-tional Natural Science Foundation#30230110a grant of Science and Technology Commission of Shanghai Mu-nicipality#O4DZ14901+1 种基金a grant of Chinese Academy of Sciences#KSCX2-SW-203a grant of the Shanghai-Hong Kong-Anson Research Foundation for CAS and CUHK(Chinese University of Hong K ong)in Molecular Biosciences(SHARF)to Jia Rui WU.
文摘The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apoptosis. In the present study, the degradation of pRB was observed in apoptotic gastric tumor cells treated with a new potent anti-tumor component, tripchlorolide (TC). The inhibition of pRB degradation by a general cysteine protease inhibitor IDAM resulted in the reduction of the apoptotic cells. Furthermore, the survival of the gastric tumor cells under the TC treatment was enhanced by an over-expression of exogenous pRB. These results suggest that the pRB degradation of the gastric tumor cells under the TC treatment involves in the apoptotic progression. In addition, the same extent of TC- induced pRB-degradation was detected in the gastric tumor cells containing a p53 dominant-negative construct, indicat- ing that this kind of pRB degradation is p53-independent.
文摘Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was induced by retrograde injection of 5% sodium taurocholate into the bile-pancreatic duct. Somatostatin octapeptide (SS-OP) (2μg/kg)was injected into the femoral vein imme- diately in rats of the treatment group after inductive AHNP. Rats of the sham operative group received in- jection of saline. Sixty animals of the AHNP and sham operative groups at the designated time(0. 2h, 0. 5 h, 2h, 4h, 8h, after the operation,six animals at each time point)and tweleve animals of treatment group at 4h after the operation were sacrificed for samples of pancreas, liver and lung. The expressions of TNF α mRNA within the pancreas, liver and lung were established by RT－PCR. Results. TNF α mRNA became detectable in the pancreas as early as 0. 2h after inductive AHNP, while it was undetectable in other organs until 0. 5h. Expression of TNF α mRNA in each tissue increased continuously and reached a peak at 4h,demonstrating a significant difference compared with that at 0. 5h and 8h. Expressions of TNF α mRNA from pancreas, liver and lung were decreased 50-80% in the treat- ment group, the pancreatic necrosis was also attenuated dramatically. Conclusion. TNF α mRNA was detectable in pancreas,liver and lung tissues at the early stage of AH- NP.SS-OP can significantly inhibit the expression of TNF α mRNA and attenuate the pancreatic necrosis. We feel that this may be an important mechanism of SS-OP in the treatment of AHNP.
