Background and objective Approximately 30% of patients who are diagnosed with non-small cell lung cancer (NSCLC) are classified as N2 on the basis of metastasis to the mediastinal lymph nodes. The effectiveness of sur...Background and objective Approximately 30% of patients who are diagnosed with non-small cell lung cancer (NSCLC) are classified as N2 on the basis of metastasis to the mediastinal lymph nodes. The effectiveness of surgery for these patients remains controversial. Although surgeries in recent years are proved to be effective to some extent,yet due to many reasons,5-year survival rate after surgery varies greatly from patient to patient. Thus it is necessary to select patients who have a high probability of being be cured through an operation,who are suitable to receive surgery and the best surgical methods so as to figure out the conditions under which surgical treatment can be chosen and the factors that may influence prognosis. Methods 165 out of 173 patients with N2 NSCLC were treated with surgery in our department from January 1999 to May 2003,among whom 130 were male,43 female and the sex ratio was 3:1,average age 53,ranging from 29 to 79. The database covers the patients’ complete medical history including the information of their age,sex,location and size of tumor,date of operation,surgical methods,histologic diagnosis,clinical stage,post-operative TNM stage,neoadjuvant treatment and chemoradiotherapy. The methods of clinical stage verification include chest X-ray,chest CT,PET,mediastinoscopy,bronchoscope (+?),brain CT or MRI,abdominal B ultrasound (or CT),and bone ECT. The pathological classification was based on the international standard for lung cancer (UICC 1997). Survival time was analyzed from the operation date to May 2008 with the aid of SPSS (Statistical Package for the Social Sciences) program. Kaplan-Meier survival analysis,Log-rank test and Cox multiplicity were adopted respectively to obtain patients’ survival curve,survival rate and the impact possible factors may have on their survival rate. Results The median survival time was 22 months,with 3-year survival rate reaching 28.1% and 5-year survival rate reaching 19.0%. Age,sex,different histological classification and postoperative chemoradiotherapy seem to have no correlation with 5-year survival rate. In all N2 subtypes,5-year survival rate is remarkably higher for unexpected N2 discovered at thoractomy and proven N2 stage before preoperative work-up and receive a mediastinal down-staging after induction therapy (P<0.01),reaching 30.4% and 27.3% respectively. 5-year survival rate for single station lymph node metastasis were 27.8%,much higher compared with 9.3% for multiple stations (P<0.001). Induction therapy which downstages proven N2 in 73.3% patients gains them the opportunity of surgery. The 5-year survival rate were 23.6% and 13.0% for patients who had complete resection and those who had incomplete resection (P<0.001). Patients who underwent lobectomy (23.2%) have higher survival rate,less incidence rate of complication and mortality rate,compared with pneumonectomy (14.8%) (P<0.01). T4 patients has a 5-year survival rate as low as 11.1%,much less than T1 (31.5%) and T2 (24.3%) patients (P=0.01). It is noted through Cox analysis that completeness of resection,number of positive lymph node stations and primary T status have significant correlativity with 5-year survival rate. Conclusion It is suggested that surgery (lobectomy preferentially) is the best solution for T1 and T2 with primary tumor have not invaded pleura or the distance to carina of trachea no less than 2 cm,unexpected N2 discovered at thoractomy when a complete resection can be applied,and proven N2 discovered during preoperative work-up and is down-staged after induction therapy. Surgical treatment is the best option,lobectomy should be prioritized in operational methods since ite rate of complication and morality are lower than that of pneumonectomy. Patients’ survival time will not benefit from surgery if they are with lymph nodes metastasis of multiple stations (Bulky N2 included) and T4 which can be partially removed. Neoadjuvant chemotherapy increases long-term survival rate of those with N2 proven prior to surgery. However,postoperative radiotherapy decreases local recurrence rate but does not contribute to patients’ long-term survival rate.展开更多
OBJECTIVE Oxyresveratrol(OXY)has many biological activities including anti-inflammation,anti-oxida⁃tive stress,anti-cancer and immunomodulation.However,the mechanisms underlying its effects against hepatocellular carc...OBJECTIVE Oxyresveratrol(OXY)has many biological activities including anti-inflammation,anti-oxida⁃tive stress,anti-cancer and immunomodulation.However,the mechanisms underlying its effects against hepatocellular carcinoma(HCC)remain poorly understood.METHODS Two HCC cell lines,HepG2 and SMMC-7721 cells,were employed.Their proliferation was determined by CCK8 assay.The migration and invasion of cells were examined by wound healing and transwell assay.Metastasis of HCC was detected by in vivo experiment.Meanwhile,transcriptome analysis was applied to explore the mechanisms of OXY.The results of transcriptome analysis were validated by in vitro experiment.Further⁃more,western blot was used to measure the expression of LC3 and p62 protein.RESULTS OXY significantly inhibited the proliferation,migration and invasion of HCC cells in vitro.OXY suppressed the metastasis of HCC in Balb/c mice with attenuated side effects compared to Doxorubicin.Transcription profiling analysis revealed that OXY may affect autophagy related signaling pathway of HepG2 cells.Western blotting showed that OXY significantly inhibite autophagy by downregulating LC3 and upregulating p62 genes expression.CONCLUSION Our study demonstrated that OXY inhibits the metastasis of HCC by inhibiting autophagy,which suggested OXY to be a candidate for HCC metastasis.展开更多
OBJECTIVE Hepatocel ular carcinoma(HCC)is the most common cause of cancer-related mortality,with high incidence rates,robust metastatic propensity and acquired resistance to therapy.Metformin,an extensively prescribed...OBJECTIVE Hepatocel ular carcinoma(HCC)is the most common cause of cancer-related mortality,with high incidence rates,robust metastatic propensity and acquired resistance to therapy.Metformin,an extensively prescribed and well-tolerated first-linetherapeutic drug for type 2 diabetes mellitus,has recently been identified as a potential and attractive anticancer adjuvant drug combined with chemotherapeutics to improve treatment efficacy and lower doses.Curcumin,a botanical extracts,has been shown antitumorigenic properties.This study aims to investigate the combinational effect of metformin and curcumin on inbibition of tumor growth and metastasis in Hep G2 cells and the possible underlying mechanisms.METHODS The cell proliferation was determined by MTT,CCK-8 and colony formation assay.The protein expression was detected by Western blotting.Activity of MMP-2 and MMP-9 was estimated by gelatin zymography.Flow cytometry analysis was used to evaluate the influence of metformin and curcumin on cell cycle arrest and apoptosis,and morphology observation of apoptosis was detected by Hoechst33342.Scratch and transwell assay was performed to detect the cell migration and invasion.The suppression of this combination therapy oncapillary tube formation was detected by tube formation assay.RESULTS Combination of metformin and curcumin induced stronger inhibition on Hep G2 cells proliferation than monotherapywhich related to induction of cell cycle arrest in G2/M phase and apoptosis through regulation of the protein expression of cyclin B and Bcl-2/Bax.Moreover,the co-treatment of metformin with curcumin exerted an enhanced inhibitory effect on Hep G2 cell metastasis and synergistically inhibited the tube formation of HUVEC cells.The suppression of PI3K/AKT/m TOR pathway and inhibition the protein expression of STAT3,MMP9,MMP2 and VEGF might involve in this synergistic effects of combination treatment.CONCLUSION Combination of metformin and curcumin inhibited Hep G2 cells proliferationmore effectively than monotherapy and synergistically induced a greater inhibition on migration and invasion of Hep G2 cells.展开更多
Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided...Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided into group A (n = 20) with continuously constant arterial infusion, and group B (n = 22) with arterial chrono-modulated infusion. And the toxic effects and efficacy of two groups were compared. Results A significant difference was found in the toxic effects of digestive system between the two groups. The treatment response was similar in the two groups. Conclusions Intra-arterial chrono-chemotherapy may decrease the toxic effects and improve the life quality of these patients. (J Intervent Radiol, 2006, 15: 487-490)展开更多
Objective· To investigate the histone methyltransferase capability of DOT1L-long form and its role in breast cancer metastasis. Methods· The existence of DOT1L-long form was confirmed by PCR, and the mRNA le...Objective· To investigate the histone methyltransferase capability of DOT1L-long form and its role in breast cancer metastasis. Methods· The existence of DOT1L-long form was confirmed by PCR, and the mRNA level of DOT1L was tested by real-time PCR. In HEK293T cells in which DOT1L canonical and DOT1L-long were overexpressed respectively, Western blotting was used to test the expression level of DOT1L and the histone methyltransferase capability. In the MCF10A cell line with inducible expression of DOT1L-long, real-time PCR was used to detect the mRNA level of epithelial-mesenchymal transition(EMT) marker, and transwell assay was used to detect the migration of breast cancer cells in which the expression level of DOT1L is low or high. Results· PCR demonstrated the existence of DOT1L-long form, and real-time PCR showed it widely exists in HCT116, T98G, MCF10A cells, etc. Western blotting showed the expression of DOT1L-long form and its H3K79 methyltransferase activity. In MCF10A cells in which overexpressed canonical DOT1L and DOT1L-long, mRNA levels of N-cadherin and fibronectine increased. Transwell showed canonical DOT1L and DOT1L-long both substantially increased the migration of breast cancer cells. Conclusion· The existence of DOT1L-long was confirmed and investigated, which is 202 amino acids longer than the canonical DOT1L, and is coded by a new exon, located between exon 27 and 28. Further, the DOT1L-long has H3K79 methyltransferase activity, and is able to promote breast cancer metastasis.展开更多
Aim Oxyresveratrol （trans-2,3 ＇ ,4,5 ＇ -tetrahydroxystilbene, OXY） , a natural polyphenolic phyto- chemical presents in mulberry （Morus alba L. ） , has been reported to have various bioactivities. Though OXY has...Aim Oxyresveratrol （trans-2,3 ＇ ,4,5 ＇ -tetrahydroxystilbene, OXY） , a natural polyphenolic phyto- chemical presents in mulberry （Morus alba L. ） , has been reported to have various bioactivities. Though OXY has high structural similarity with resveratrol, which has been identified as a chemopreventive agent, little is known a- bout OXY＇s effect on cancer. The main objective of our study was to investigate the effect of OXY on metastasis in vivo. To establish an experimental metastasis model, male Kunming mice were challenged with H22 cells by tail vein injection, and were given different doses of OXY （20, 40,80 mg · kg^-1 body weight per day） for 14 days in- traperitoneally. Administration of OXY showed a clear anti-metastatic effect. Compared to control group （u - 10） , the numbers of pulmonary nodules and lung weight were significantly decreased in mice of 40 mg · kg^- 1 group （ n = 10, P 〈 0.05） , which results in 54.5% reduction in the number of metastases. Similar inhibitory effects were ob- served both at 20 and 80 mg · kg^-1 groups（n= 10, 34.2% and 35.7% , respectively）. OXY at the doses used caused an increase in spleen index （P 〈 0.05） but not thymus index. Further we observed animal body weights loss and food intake decrease （P 〈 0.05） , suggesting the toxicity of high dose used. Therefore, we suggest that oxyresveratrol may benefit human as a new preventive agent for cancer metastasis.展开更多
Background Signal transducer and activator of transcription 3 （STAT3） is constitutively activated in malignant tumors and has important roles in multiple aspects of cancer aggressiveness. Thus targeting STAT3 promi-...Background Signal transducer and activator of transcription 3 （STAT3） is constitutively activated in malignant tumors and has important roles in multiple aspects of cancer aggressiveness. Thus targeting STAT3 promi- ses to be an attractive strategy for treatment of advanced metastatic tumors. Although many STAT3 inhibitors targe- ting the SH2 domain have been reported, few have moved into clinical trials. Targeting the DNA-binding domain （DBD） of STAT3, however, has been avoided due to its ＇ undruggable＇ nature and potentially limited selectivity. Aim This study aims at developing effective and specific inhibitors targeting DNA binding domain of STAT3. Methods： This study reported an improved in-silico approach targeting the DBD of STAT3 that resulted in a small- molecule STAT3 inhibitor （inS3-54） and describe an extensive structure and activity-guided hit optimization and mechanistic characterization effort, which led to identification of an improved lead compound （inS3-54A18） with increased specificity and pharmacological properties. Results： InS3-54A18 not only binds directly to the DBD and inhibits the DNA-binding activity of STAT3 both in vitro and in situ but also effectively inhibits the constitutive and interleukin-6-stimulated expression of STAT3 downstream target genes. InS3-54A18 is completely soluble in an oral formulation and effectively inhibits lung xenograft tumor growth and metastasis with little adverse effect on animals. Conclusion： InS3-54A18 may serve as a potential candidate for further development as anticancer therapeutics tar-geting the DBD of human STAT3 and DBD of transcription factors may not be ＇ undruggable＇ as previously thought.展开更多
Aim Accumulated evidence suggests that M2-1ike polarized tumor associated macrophages （TAMs） plays an important role in cancer progression and metastasis, establishing TAMs, especially M2-1ike TAMs as an appealing t...Aim Accumulated evidence suggests that M2-1ike polarized tumor associated macrophages （TAMs） plays an important role in cancer progression and metastasis, establishing TAMs, especially M2-1ike TAMs as an appealing target for therapy intervention. Here we found that metformin significantly suppressed IL-13 induced M2- like polarization of macrophages, as illustrated by reduced expression of CD206, down-regulation of M2 marker mRNAs, and inhibition of M2-1ike macrophages promoted migration of cancer cells and endothelial cells. Metformin triggered AMPKαl activation in macrophage and silencing of AMPKotl partially abrogated the inhibitory effect of metformin in IL-13 induced M2-1ike polarization. Administration of AICAR, another activator of AMPK, also blocked the M2-1ike polarization of macrophages. Metformin greatly reduced the number of metastases of Lewis lung cancer without affecting tumor growth. In tumor tissues, the percentage of M2-1ike macrophage was decreased and the anti-metastatic effect of metformin was abolished the area of pericyte-coated vessels was increased. Further, when the animals were treated with macrophages eliminating agent clodronate liposome. These findings suggest that metformin is able to block the M2-1ike polarization of macrophages partially through AMPKαl, which plays an im- portant role in metformin inhibited metastasis of Lewis lung cancer.展开更多
Background and objective The rst aim was to measure the expressions of Annexin A7 (Anxa7) at mRNA level and protein level in two mice hepatocarcinoma ascites syngeneic cell
Induction of tumor-specific cellular immune responseis very important in the cancer therapy. In this study,we used tumor antigen obtained by thaw of melanomacells to pulse M-CSF or/and IFN-γ gene-modificdmacrophages ...Induction of tumor-specific cellular immune responseis very important in the cancer therapy. In this study,we used tumor antigen obtained by thaw of melanomacells to pulse M-CSF or/and IFN-γ gene-modificdmacrophages before in viro infusion. Tumor membraneantigens could be phagocytosed by macrophages inculture. Antigen processing and mcxlulation of thepresentation can be achieved before macrophageinjection. The tumor antigens will be processedintracellularly by macrophages and thereafter展开更多
Objective To elucidate the characteristics and metastastic pattern of skipping mediastinal lymph node metastasis (skipping N2) in non-small cell lung cancer (NSCLC), and investigate reasonable extent of lymph node dis...Objective To elucidate the characteristics and metastastic pattern of skipping mediastinal lymph node metastasis (skipping N2) in non-small cell lung cancer (NSCLC), and investigate reasonable extent of lymph node dissection. Methods From 1990 to 1998, lobectomy combined with systematic mediastinal lymph node dissection was performed in 109 patients with NSCLC. A retrospective study was carried out to elucidate the characteristics of skipping N2 disease and to compare the difference between skipping N2 and non-skipping N2 diseases. Results Twenty-one patients (19%) had skipping N2 diseases. Of the skipping N2 group, 18 cases (86%) were adenocarcinoma. Skipping N2 disease was more common in T1 and T2 group than that in T3 and T4 group (P<0.01). All skipping N2 diseases only involved one nodal station, and most of them were regional mediastinal nodal metastasis. Skipping N2 from upper lobe tumors mainly involved superior tracheobronchial or subaortic lymph nodes, and skipping N2 from lower lobe tumors involved subcarinal lymph nodes. Conclusion Skipping N2 disease presents certain clinical characteristics and metastastic pattern, and mediastinal nodal dissection might be modified according to the pattern.展开更多
Dysregulation of polycomb group protein Bmi-1 expression has been linked with an invasive phenotype of certain human cancers and poor prognosis of patients; however, the underlying mechanisms are
Background and Objective Lung cancer is the most lethal malignangy that threatens human health and lives nowadays in the world, The overall cure rate of lung cancer is only 13% -15%,
基金supported by grants from the Science and Research Department,belongs to China-Japan Friendship Hospital directly affiliated to Chinese Ministry of Health
文摘Background and objective Approximately 30% of patients who are diagnosed with non-small cell lung cancer (NSCLC) are classified as N2 on the basis of metastasis to the mediastinal lymph nodes. The effectiveness of surgery for these patients remains controversial. Although surgeries in recent years are proved to be effective to some extent,yet due to many reasons,5-year survival rate after surgery varies greatly from patient to patient. Thus it is necessary to select patients who have a high probability of being be cured through an operation,who are suitable to receive surgery and the best surgical methods so as to figure out the conditions under which surgical treatment can be chosen and the factors that may influence prognosis. Methods 165 out of 173 patients with N2 NSCLC were treated with surgery in our department from January 1999 to May 2003,among whom 130 were male,43 female and the sex ratio was 3:1,average age 53,ranging from 29 to 79. The database covers the patients’ complete medical history including the information of their age,sex,location and size of tumor,date of operation,surgical methods,histologic diagnosis,clinical stage,post-operative TNM stage,neoadjuvant treatment and chemoradiotherapy. The methods of clinical stage verification include chest X-ray,chest CT,PET,mediastinoscopy,bronchoscope (+?),brain CT or MRI,abdominal B ultrasound (or CT),and bone ECT. The pathological classification was based on the international standard for lung cancer (UICC 1997). Survival time was analyzed from the operation date to May 2008 with the aid of SPSS (Statistical Package for the Social Sciences) program. Kaplan-Meier survival analysis,Log-rank test and Cox multiplicity were adopted respectively to obtain patients’ survival curve,survival rate and the impact possible factors may have on their survival rate. Results The median survival time was 22 months,with 3-year survival rate reaching 28.1% and 5-year survival rate reaching 19.0%. Age,sex,different histological classification and postoperative chemoradiotherapy seem to have no correlation with 5-year survival rate. In all N2 subtypes,5-year survival rate is remarkably higher for unexpected N2 discovered at thoractomy and proven N2 stage before preoperative work-up and receive a mediastinal down-staging after induction therapy (P<0.01),reaching 30.4% and 27.3% respectively. 5-year survival rate for single station lymph node metastasis were 27.8%,much higher compared with 9.3% for multiple stations (P<0.001). Induction therapy which downstages proven N2 in 73.3% patients gains them the opportunity of surgery. The 5-year survival rate were 23.6% and 13.0% for patients who had complete resection and those who had incomplete resection (P<0.001). Patients who underwent lobectomy (23.2%) have higher survival rate,less incidence rate of complication and mortality rate,compared with pneumonectomy (14.8%) (P<0.01). T4 patients has a 5-year survival rate as low as 11.1%,much less than T1 (31.5%) and T2 (24.3%) patients (P=0.01). It is noted through Cox analysis that completeness of resection,number of positive lymph node stations and primary T status have significant correlativity with 5-year survival rate. Conclusion It is suggested that surgery (lobectomy preferentially) is the best solution for T1 and T2 with primary tumor have not invaded pleura or the distance to carina of trachea no less than 2 cm,unexpected N2 discovered at thoractomy when a complete resection can be applied,and proven N2 discovered during preoperative work-up and is down-staged after induction therapy. Surgical treatment is the best option,lobectomy should be prioritized in operational methods since ite rate of complication and morality are lower than that of pneumonectomy. Patients’ survival time will not benefit from surgery if they are with lymph nodes metastasis of multiple stations (Bulky N2 included) and T4 which can be partially removed. Neoadjuvant chemotherapy increases long-term survival rate of those with N2 proven prior to surgery. However,postoperative radiotherapy decreases local recurrence rate but does not contribute to patients’ long-term survival rate.
基金supported by grant from the scientif ic fund of the Ministry of Personnel for returned overseas expert (2006)Natural Science Foundation Project of CQ CSTC (to Mingjian GE)(CSTC, No.2008BB5210)
文摘OBJECTIVE Oxyresveratrol(OXY)has many biological activities including anti-inflammation,anti-oxida⁃tive stress,anti-cancer and immunomodulation.However,the mechanisms underlying its effects against hepatocellular carcinoma(HCC)remain poorly understood.METHODS Two HCC cell lines,HepG2 and SMMC-7721 cells,were employed.Their proliferation was determined by CCK8 assay.The migration and invasion of cells were examined by wound healing and transwell assay.Metastasis of HCC was detected by in vivo experiment.Meanwhile,transcriptome analysis was applied to explore the mechanisms of OXY.The results of transcriptome analysis were validated by in vitro experiment.Further⁃more,western blot was used to measure the expression of LC3 and p62 protein.RESULTS OXY significantly inhibited the proliferation,migration and invasion of HCC cells in vitro.OXY suppressed the metastasis of HCC in Balb/c mice with attenuated side effects compared to Doxorubicin.Transcription profiling analysis revealed that OXY may affect autophagy related signaling pathway of HepG2 cells.Western blotting showed that OXY significantly inhibite autophagy by downregulating LC3 and upregulating p62 genes expression.CONCLUSION Our study demonstrated that OXY inhibits the metastasis of HCC by inhibiting autophagy,which suggested OXY to be a candidate for HCC metastasis.
文摘OBJECTIVE Hepatocel ular carcinoma(HCC)is the most common cause of cancer-related mortality,with high incidence rates,robust metastatic propensity and acquired resistance to therapy.Metformin,an extensively prescribed and well-tolerated first-linetherapeutic drug for type 2 diabetes mellitus,has recently been identified as a potential and attractive anticancer adjuvant drug combined with chemotherapeutics to improve treatment efficacy and lower doses.Curcumin,a botanical extracts,has been shown antitumorigenic properties.This study aims to investigate the combinational effect of metformin and curcumin on inbibition of tumor growth and metastasis in Hep G2 cells and the possible underlying mechanisms.METHODS The cell proliferation was determined by MTT,CCK-8 and colony formation assay.The protein expression was detected by Western blotting.Activity of MMP-2 and MMP-9 was estimated by gelatin zymography.Flow cytometry analysis was used to evaluate the influence of metformin and curcumin on cell cycle arrest and apoptosis,and morphology observation of apoptosis was detected by Hoechst33342.Scratch and transwell assay was performed to detect the cell migration and invasion.The suppression of this combination therapy oncapillary tube formation was detected by tube formation assay.RESULTS Combination of metformin and curcumin induced stronger inhibition on Hep G2 cells proliferation than monotherapywhich related to induction of cell cycle arrest in G2/M phase and apoptosis through regulation of the protein expression of cyclin B and Bcl-2/Bax.Moreover,the co-treatment of metformin with curcumin exerted an enhanced inhibitory effect on Hep G2 cell metastasis and synergistically inhibited the tube formation of HUVEC cells.The suppression of PI3K/AKT/m TOR pathway and inhibition the protein expression of STAT3,MMP9,MMP2 and VEGF might involve in this synergistic effects of combination treatment.CONCLUSION Combination of metformin and curcumin inhibited Hep G2 cells proliferationmore effectively than monotherapy and synergistically induced a greater inhibition on migration and invasion of Hep G2 cells.
文摘Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided into group A (n = 20) with continuously constant arterial infusion, and group B (n = 22) with arterial chrono-modulated infusion. And the toxic effects and efficacy of two groups were compared. Results A significant difference was found in the toxic effects of digestive system between the two groups. The treatment response was similar in the two groups. Conclusions Intra-arterial chrono-chemotherapy may decrease the toxic effects and improve the life quality of these patients. (J Intervent Radiol, 2006, 15: 487-490)
基金National Natural Science Foundation of China,31471206Basic Science Foundation of Science and Technology Commission of Shanghai Municipality,14JC1404000~~
文摘Objective· To investigate the histone methyltransferase capability of DOT1L-long form and its role in breast cancer metastasis. Methods· The existence of DOT1L-long form was confirmed by PCR, and the mRNA level of DOT1L was tested by real-time PCR. In HEK293T cells in which DOT1L canonical and DOT1L-long were overexpressed respectively, Western blotting was used to test the expression level of DOT1L and the histone methyltransferase capability. In the MCF10A cell line with inducible expression of DOT1L-long, real-time PCR was used to detect the mRNA level of epithelial-mesenchymal transition(EMT) marker, and transwell assay was used to detect the migration of breast cancer cells in which the expression level of DOT1L is low or high. Results· PCR demonstrated the existence of DOT1L-long form, and real-time PCR showed it widely exists in HCT116, T98G, MCF10A cells, etc. Western blotting showed the expression of DOT1L-long form and its H3K79 methyltransferase activity. In MCF10A cells in which overexpressed canonical DOT1L and DOT1L-long, mRNA levels of N-cadherin and fibronectine increased. Transwell showed canonical DOT1L and DOT1L-long both substantially increased the migration of breast cancer cells. Conclusion· The existence of DOT1L-long was confirmed and investigated, which is 202 amino acids longer than the canonical DOT1L, and is coded by a new exon, located between exon 27 and 28. Further, the DOT1L-long has H3K79 methyltransferase activity, and is able to promote breast cancer metastasis.
文摘Aim Oxyresveratrol （trans-2,3 ＇ ,4,5 ＇ -tetrahydroxystilbene, OXY） , a natural polyphenolic phyto- chemical presents in mulberry （Morus alba L. ） , has been reported to have various bioactivities. Though OXY has high structural similarity with resveratrol, which has been identified as a chemopreventive agent, little is known a- bout OXY＇s effect on cancer. The main objective of our study was to investigate the effect of OXY on metastasis in vivo. To establish an experimental metastasis model, male Kunming mice were challenged with H22 cells by tail vein injection, and were given different doses of OXY （20, 40,80 mg · kg^-1 body weight per day） for 14 days in- traperitoneally. Administration of OXY showed a clear anti-metastatic effect. Compared to control group （u - 10） , the numbers of pulmonary nodules and lung weight were significantly decreased in mice of 40 mg · kg^- 1 group （ n = 10, P 〈 0.05） , which results in 54.5% reduction in the number of metastases. Similar inhibitory effects were ob- served both at 20 and 80 mg · kg^-1 groups（n= 10, 34.2% and 35.7% , respectively）. OXY at the doses used caused an increase in spleen index （P 〈 0.05） but not thymus index. Further we observed animal body weights loss and food intake decrease （P 〈 0.05） , suggesting the toxicity of high dose used. Therefore, we suggest that oxyresveratrol may benefit human as a new preventive agent for cancer metastasis.
文摘Background Signal transducer and activator of transcription 3 （STAT3） is constitutively activated in malignant tumors and has important roles in multiple aspects of cancer aggressiveness. Thus targeting STAT3 promi- ses to be an attractive strategy for treatment of advanced metastatic tumors. Although many STAT3 inhibitors targe- ting the SH2 domain have been reported, few have moved into clinical trials. Targeting the DNA-binding domain （DBD） of STAT3, however, has been avoided due to its ＇ undruggable＇ nature and potentially limited selectivity. Aim This study aims at developing effective and specific inhibitors targeting DNA binding domain of STAT3. Methods： This study reported an improved in-silico approach targeting the DBD of STAT3 that resulted in a small- molecule STAT3 inhibitor （inS3-54） and describe an extensive structure and activity-guided hit optimization and mechanistic characterization effort, which led to identification of an improved lead compound （inS3-54A18） with increased specificity and pharmacological properties. Results： InS3-54A18 not only binds directly to the DBD and inhibits the DNA-binding activity of STAT3 both in vitro and in situ but also effectively inhibits the constitutive and interleukin-6-stimulated expression of STAT3 downstream target genes. InS3-54A18 is completely soluble in an oral formulation and effectively inhibits lung xenograft tumor growth and metastasis with little adverse effect on animals. Conclusion： InS3-54A18 may serve as a potential candidate for further development as anticancer therapeutics tar-geting the DBD of human STAT3 and DBD of transcription factors may not be ＇ undruggable＇ as previously thought.
文摘Aim Accumulated evidence suggests that M2-1ike polarized tumor associated macrophages （TAMs） plays an important role in cancer progression and metastasis, establishing TAMs, especially M2-1ike TAMs as an appealing target for therapy intervention. Here we found that metformin significantly suppressed IL-13 induced M2- like polarization of macrophages, as illustrated by reduced expression of CD206, down-regulation of M2 marker mRNAs, and inhibition of M2-1ike macrophages promoted migration of cancer cells and endothelial cells. Metformin triggered AMPKαl activation in macrophage and silencing of AMPKotl partially abrogated the inhibitory effect of metformin in IL-13 induced M2-1ike polarization. Administration of AICAR, another activator of AMPK, also blocked the M2-1ike polarization of macrophages. Metformin greatly reduced the number of metastases of Lewis lung cancer without affecting tumor growth. In tumor tissues, the percentage of M2-1ike macrophage was decreased and the anti-metastatic effect of metformin was abolished the area of pericyte-coated vessels was increased. Further, when the animals were treated with macrophages eliminating agent clodronate liposome. These findings suggest that metformin is able to block the M2-1ike polarization of macrophages partially through AMPKαl, which plays an im- portant role in metformin inhibited metastasis of Lewis lung cancer.
文摘Background and objective The rst aim was to measure the expressions of Annexin A7 (Anxa7) at mRNA level and protein level in two mice hepatocarcinoma ascites syngeneic cell
文摘Induction of tumor-specific cellular immune responseis very important in the cancer therapy. In this study,we used tumor antigen obtained by thaw of melanomacells to pulse M-CSF or/and IFN-γ gene-modificdmacrophages before in viro infusion. Tumor membraneantigens could be phagocytosed by macrophages inculture. Antigen processing and mcxlulation of thepresentation can be achieved before macrophageinjection. The tumor antigens will be processedintracellularly by macrophages and thereafter
文摘Objective To elucidate the characteristics and metastastic pattern of skipping mediastinal lymph node metastasis (skipping N2) in non-small cell lung cancer (NSCLC), and investigate reasonable extent of lymph node dissection. Methods From 1990 to 1998, lobectomy combined with systematic mediastinal lymph node dissection was performed in 109 patients with NSCLC. A retrospective study was carried out to elucidate the characteristics of skipping N2 disease and to compare the difference between skipping N2 and non-skipping N2 diseases. Results Twenty-one patients (19%) had skipping N2 diseases. Of the skipping N2 group, 18 cases (86%) were adenocarcinoma. Skipping N2 disease was more common in T1 and T2 group than that in T3 and T4 group (P<0.01). All skipping N2 diseases only involved one nodal station, and most of them were regional mediastinal nodal metastasis. Skipping N2 from upper lobe tumors mainly involved superior tracheobronchial or subaortic lymph nodes, and skipping N2 from lower lobe tumors involved subcarinal lymph nodes. Conclusion Skipping N2 disease presents certain clinical characteristics and metastastic pattern, and mediastinal nodal dissection might be modified according to the pattern.
文摘Dysregulation of polycomb group protein Bmi-1 expression has been linked with an invasive phenotype of certain human cancers and poor prognosis of patients; however, the underlying mechanisms are
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and Objective Lung cancer is the most lethal malignangy that threatens human health and lives nowadays in the world, The overall cure rate of lung cancer is only 13% -15%,
