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
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
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
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
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 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· 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
Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal c...Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.展开更多
上海交通大学医学院附属新华医院检验科沈立松教授领衔的科研团队在膀胱癌侵袭转移的机制研究中取得新发现。近日，肿瘤领域国际权威期刊Cancer Research正式发表了该课题组最新研究成果“ATF3 Suppresses Metastasis of Bladder Cancer...上海交通大学医学院附属新华医院检验科沈立松教授领衔的科研团队在膀胱癌侵袭转移的机制研究中取得新发现。近日，肿瘤领域国际权威期刊Cancer Research正式发表了该课题组最新研究成果“ATF3 Suppresses Metastasis of Bladder Cancer by Regulating Gelsolin-Mediated Remodeling of the Actin Cytoskeleton”[CancerRes，2013，73（12）：3625—3637]。展开更多
Hung T, Piris A, Lobo A, et al. Sentinel lymph node metastasis is not predictive of poor outcome in patients with problematic spitzoid melanoeytie tumors. Hum Pathol, 2013,44 （ 1 ） ： 87 - 94.伴有非典型特征的Spitz...Hung T, Piris A, Lobo A, et al. Sentinel lymph node metastasis is not predictive of poor outcome in patients with problematic spitzoid melanoeytie tumors. Hum Pathol, 2013,44 （ 1 ） ： 87 - 94.伴有非典型特征的Spitz样黑色素细胞肿瘤的诊断目前仍然是疑难的，其临床处理也是有争议性的。在过去的十年中，前哨淋巴结的评估一直作为恶性黑色素瘤从良性肿瘤中鉴别出来的诊断依据。最近的研究显示，尽管这些患者存在淋巴结转移，但几乎总是预后很好。为解决非典型Spitz肿瘤和Spitz样恶性黑色素瘤中前哨淋巴结转移在诊断和临床处理中的争议，作者对马萨诸塞州总医院病理科1998到2008年进行了前哨淋巴结活检的41例非典型Spitz肿瘤和Spitz样恶性黑色素瘤进行分析，其中非典型Spitz肿瘤23例，展开更多
Introduction Hematogenous metastasis is the mainly leading cause of death in breast carcinoma patients.A better understanding of the underlying molecular and cellular mechanisms is crucial for the development of effec...Introduction Hematogenous metastasis is the mainly leading cause of death in breast carcinoma patients.A better understanding of the underlying molecular and cellular mechanisms is crucial for the development of effective treatment for metastatic breast cancer<sup>[</sup>1].It has been well established that cell adhesion and invasion is mediated by a variety of transmembrane proteins,including integrins,cadherins,selectins,and intercellular adhesion molecules.Among these adhesion molecules,the integrins and their downstream signaling pathways have been extensively studied<sup>[2]</sup>.On the other hand,the specific events determining tumor cell interactions with endo-展开更多
Forced dissociation of selectin-ligand complex is crucial to such biological processes as leukocyte recruitment,thrombosis formation,as well as tumor metastasis<sup>[</sup>1].Although several assays and te...Forced dissociation of selectin-ligand complex is crucial to such biological processes as leukocyte recruitment,thrombosis formation,as well as tumor metastasis<sup>[</sup>1].Although several assays and techniques,e.g.,dynamic force spectroscopy（DFS）,have been applied to probe the complex at single-bond level,the discrepancies in the loading rate dependence of bond rupture force were found in the assays,presumably due to the different pathways in energy landscape and binding kinetics of molecular complexes<sup>[2]</sup>.However,the underlying mechanisms remain unclear.Here an optical trap（OT）assay was used to quantify the bond rupture at r<sub>f</sub>≤20 pN/s展开更多
Despite significant progress in cancer research during the past decades,yet there are no major breakthroughs that can be translated into major benefits for the general public in terms of treatment or therapy for the c...Despite significant progress in cancer research during the past decades,yet there are no major breakthroughs that can be translated into major benefits for the general public in terms of treatment or therapy for the complex neoplastic diseases,especially for the malignant solid tumors.This depressing but indisputable fact leads to a call for new ideas to target tumor metastasis by editors of Nature Medicine<sup>[1]</sup>.The real problems are that the fundamental issues of transformation and malignancy in vivo are poorly understood.In a recent review on cancer,展开更多
In order to investigate the effects of cytokine fusedgene transfection on tumor cell modification, threeretroviral vectors for human interleukin 6 (IL-6),interleukin 2 (IL-2) and, IL-6/IL-2 fusion gene wereconstructed...In order to investigate the effects of cytokine fusedgene transfection on tumor cell modification, threeretroviral vectors for human interleukin 6 (IL-6),interleukin 2 (IL-2) and, IL-6/IL-2 fusion gene wereconstructed. The retroviral vectors were introduced intomurine B16 melanoma cell line respectively and theeffects of single or fused cytokine gene on tumor cellbiology in vitro and in vivo were examined. In vivo, thethree cytokine gene-modified B16 cells all showeddecreased tumorigenicity and metastatic potentials,however, the reduction in tumorigenicity and展开更多
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)
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.
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Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.
文摘上海交通大学医学院附属新华医院检验科沈立松教授领衔的科研团队在膀胱癌侵袭转移的机制研究中取得新发现。近日，肿瘤领域国际权威期刊Cancer Research正式发表了该课题组最新研究成果“ATF3 Suppresses Metastasis of Bladder Cancer by Regulating Gelsolin-Mediated Remodeling of the Actin Cytoskeleton”[CancerRes，2013，73（12）：3625—3637]。
文摘Hung T, Piris A, Lobo A, et al. Sentinel lymph node metastasis is not predictive of poor outcome in patients with problematic spitzoid melanoeytie tumors. Hum Pathol, 2013,44 （ 1 ） ： 87 - 94.伴有非典型特征的Spitz样黑色素细胞肿瘤的诊断目前仍然是疑难的，其临床处理也是有争议性的。在过去的十年中，前哨淋巴结的评估一直作为恶性黑色素瘤从良性肿瘤中鉴别出来的诊断依据。最近的研究显示，尽管这些患者存在淋巴结转移，但几乎总是预后很好。为解决非典型Spitz肿瘤和Spitz样恶性黑色素瘤中前哨淋巴结转移在诊断和临床处理中的争议，作者对马萨诸塞州总医院病理科1998到2008年进行了前哨淋巴结活检的41例非典型Spitz肿瘤和Spitz样恶性黑色素瘤进行分析，其中非典型Spitz肿瘤23例，
基金The financial supports provided,in whole or in part,by the National Natural Science Foundation of China(11272083)the New Century Excellent Talents Program in Chinese Universities(NCET09-0263)
文摘Introduction Hematogenous metastasis is the mainly leading cause of death in breast carcinoma patients.A better understanding of the underlying molecular and cellular mechanisms is crucial for the development of effective treatment for metastatic breast cancer<sup>[</sup>1].It has been well established that cell adhesion and invasion is mediated by a variety of transmembrane proteins,including integrins,cadherins,selectins,and intercellular adhesion molecules.Among these adhesion molecules,the integrins and their downstream signaling pathways have been extensively studied<sup>[2]</sup>.On the other hand,the specific events determining tumor cell interactions with endo-
基金supported by National Natural Science Foundation of China grants 10902117, 31230027,30730032,and 10332060
文摘Forced dissociation of selectin-ligand complex is crucial to such biological processes as leukocyte recruitment,thrombosis formation,as well as tumor metastasis<sup>[</sup>1].Although several assays and techniques,e.g.,dynamic force spectroscopy（DFS）,have been applied to probe the complex at single-bond level,the discrepancies in the loading rate dependence of bond rupture force were found in the assays,presumably due to the different pathways in energy landscape and binding kinetics of molecular complexes<sup>[2]</sup>.However,the underlying mechanisms remain unclear.Here an optical trap（OT）assay was used to quantify the bond rupture at r<sub>f</sub>≤20 pN/s
基金supported by the funds from Huazhong University of Science and TechnologyUS NIH grant GM072744
文摘Despite significant progress in cancer research during the past decades,yet there are no major breakthroughs that can be translated into major benefits for the general public in terms of treatment or therapy for the complex neoplastic diseases,especially for the malignant solid tumors.This depressing but indisputable fact leads to a call for new ideas to target tumor metastasis by editors of Nature Medicine<sup>[1]</sup>.The real problems are that the fundamental issues of transformation and malignancy in vivo are poorly understood.In a recent review on cancer,
文摘In order to investigate the effects of cytokine fusedgene transfection on tumor cell modification, threeretroviral vectors for human interleukin 6 (IL-6),interleukin 2 (IL-2) and, IL-6/IL-2 fusion gene wereconstructed. The retroviral vectors were introduced intomurine B16 melanoma cell line respectively and theeffects of single or fused cytokine gene on tumor cellbiology in vitro and in vivo were examined. In vivo, thethree cytokine gene-modified B16 cells all showeddecreased tumorigenicity and metastatic potentials,however, the reduction in tumorigenicity and
