MicroRNAs （miRNAs） are a class of naturally occurring small non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level. Our previous studies suggest that mir-21 functions as an oncogene and h...MicroRNAs （miRNAs） are a class of naturally occurring small non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level. Our previous studies suggest that mir-21 functions as an oncogene and has a role in tumorigenesis, in part through regulation of the tumor suppressor gene tropomyosin 1 （TPM1）. Given that TPM1 has been implicated in cell migration, in this study we further investigated the role of mir-21 in cell invasion and tumor metastasis. We found that suppression of mir-21 in metastatic breast cancer MDA-MB-231 cells significantly reduced invasion and lung metastasis. Consistent with this, ectopic expression of TPM1 remarkably reduced cell invasion. Furthermore, we identified two additional direct mir-21 targets, programmed cell death 4 （PDCD4） and maspin, both of which have been implicated in invasion and metastasis. Like TPM1, PDCD4 and maspin also reduced invasiveness of MDA-MB-231 cells. Finally, the expression of PDCD4 and maspin inversely correlated with mir-21 expression in human breast tumor specimens, indicating the potential regulation of PDCD4 and maspin by mir-21 in these tumors. Taken together, the results suggest that, as an oncogenic miRNA, mir-21 has a role not only in tumor growth but also in invasion and tumor metastasis by targeting multiple tumor/metastasis suppressor genes. Therefore, suppression of mir-21 may provide a novel approach for the treatment of advanced cancers.展开更多
AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, a...AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.展开更多
The importance of cancer stem cells （CSCs） in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression,...The importance of cancer stem cells （CSCs） in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression, particularly with respect to metastasis, has not been well-defined. Cancer metastasis requires the seeding and successful colonization of specialized CSCs at distant organs. The biology of normal stem cells and CSCs share remarkable similarities and may have important implications when applied to the study of cancer metastasis. Furthermore, overlapping sets of molecules and pathways have recently been identified to regulate both stem cell migration and cancer metastasis. These molecules constitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by the primary tumor and the formation of a nurturing organ microenvironment for migrating CSCs. In this review, we surveyed the recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume a central role in both tumorigenesis and metastasis. Better understanding of CSCs as a fundamental component of the metastatic cascade will lead to novel therapeutic strategies against metastatic cancer.展开更多
The cell-biological program termed the epithelial-to-mesenchymal transition （EMT） plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circui...The cell-biological program termed the epithelial-to-mesenchymal transition （EMT） plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenehymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.展开更多
Traditional Chinese medicine （TCM）, an important component of complementary and alternative medicine, has evolved over thousands of years with its own unique system of theories, diagnostics and therapies. TCM has be...Traditional Chinese medicine （TCM）, an important component of complementary and alternative medicine, has evolved over thousands of years with its own unique system of theories, diagnostics and therapies. TCM has been increasingly used in the last decades and become well known for its significant role in preventing and treating cancer. We believe that TCM possesses advantages over Western medicine in specific aspects at a certain stage of cancer treatment. Here we summarize the advantages of TCM from three aspects： preventing tumorigenesis; attenuating toxicity and enhancing the treatment effect; and reducing tumor recurrence and metastasis.展开更多
AIM:The prognosis of early gastric carcinoma (EGC) is generally excellent after surgery. The presence or absence of lymph node metastasis in EGC is an important prognostic factor. The survival and recurrence rates of ...AIM:The prognosis of early gastric carcinoma (EGC) is generally excellent after surgery. The presence or absence of lymph node metastasis in EGC is an important prognostic factor. The survival and recurrence rates of node-negative EGC are much better than those of node-positive EGC. This study examined the factors related to lymph node metastasis in EGC to determine the appropriate treatment for EGC.METHODS: We investigated 748 patients with EGC who underwent surgery between January 1985 and December 1999 at the Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Hospital. Several clinicopathologic factors were investigated to analyze their relationship to lymph node metastasis: age, sex, tumor location, tumor size, gross type, histologic type, depth of invasion, extent of lymph node dissection, type of operation,and DNA ploidy.RESULTS:Lymph node metastases were found in 75 patients (10.0%). Univariate analysis showed that male sex, tumor size larger than 2.0cm, submucosal invasion of tumor, histologic differentiation, and DNA ploidy pattern were risk factors for regional lymph node metastasis in EGC patients. However, a multivariate analysis showed that three risk factors were associated with lymph node metastasis:large tumor size, undifferentiated histologic type and submucosal invasion. No statistical relationship was found for age, sex, tumor location, gross type, or DNA ploidy in multivariate analysis. The 5-year survival rate was 94.2% for those without lymph node metastasis and 87.3% for those with lymph node metastasis, and the difference was significant (P<0.05).CONCLUSION: In patients with EGC, the survival rate of patients with positive lymph nodes is significantly worse than that of patients with no lymph node metastasis. Therefore,a standard D2 lymphadenectomy should be performed in patients at high risk of lymph node metastasis: large tumor size, undifferentiated histologic type and submucosal invasion.展开更多
BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost import...BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost importance. Circulating diagnostic and prognostic biomarkers could be used in proper postoperative treatment of patients at an early stage of HCC development. This review summarizes recent studies of the specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. DATA SOURCES: An English-language literature search was conducted using MEDLINE (June 1998 to Spetember 2006) on researches of some valuable specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. RESULTS: Hepatoma tissues can synthesize various tumor-related proteins, polypeptides, and isoenzymes, such as alpha-fetoprotein (AFP), hepatoma-specific gamma-glutamyl transpeptidase (HS-GGT), etc, and then secrete into blood. The valuable early diagnostic and prognostic biomarkers could predict the development an metastases of HCC. Recent researches have confirmed that circulating hepatoma-specific AFP subfraction, transforming growth factor (TGF)-beta 1, HS-GGT, and free insulin-like growth factor (IGF)-II may be more specific markers than total AFP level for early diagnosis for HCC. The circulating genetic markers such as AFP-mRNA, TGF-beta 1-mRNA, IGF-II-mRNA, etc from peripheral blood mononuclear cells of HCC patients have been most extensively used in monitoring distal metastasis or postoperative recurrence of HCC. CONCLUSIONS: Hepatoma tissues synthesize and secrete valuable molecular markers into blood. The analyses of circulating hepatoma-specific biomarkers are useful to early diagnosis of HCC or monitoring metastasis or postoperative recurrence of HCC.展开更多
Objectives To determine the pre-therapeutic serum level of vascular endothelial growth factor (VEGF) in patients with hepatocellular carcinoma (HCC) and to elucidate the relation between the serum level and clinical ...Objectives To determine the pre-therapeutic serum level of vascular endothelial growth factor (VEGF) in patients with hepatocellular carcinoma (HCC) and to elucidate the relation between the serum level and clinical characteristics and metastasis of HCC. Methods One-hundred and fifteen HCC patients, 40 patients with benign liver lesions, and 30 healthy control subjects were included in this study. The serum VEGF level was measured with the quantitative sandwich enzyme linked immunosorbent assay (ELISA, R&D systems). Results The serum VEGF levels in the HCC group (465.62±336.24 pg/ml) was significantly elevated as compared with those in patients with benign liver lesions (159.54±120.58 pg/ml) and those in normal controls (123.53±51.84 pg/ml). The VEGF levels were not significantly different between the patients with benign liver lesions and the normal controls. The serum VEGF levels showed a positive rate of 77.4%, 25%, and 3.3% in the HCC patients, benign liver lesion patients and normal controls, respectively. In the 115 HCC patients, the serum VEGF levels in patients with portal vein (PV) emboli (n=26, 582.76±441.89 pg/ml), with metastasis (n=43, 548.29±438.57 pg/ml) or with large HCC lesions (≥5 cm in diameter) (n=69, 554.43±369.99 pg/ml) were significantly higher than those without PV-emboli (n=89, 431.39±292.84 pg/ml), without metastasis (n=72, 416.24±247.27 pg/ml) or with small HCC lesions (n=42, 328.67±227.47 pg/ml). The serum VEGF levels in stage Ⅰ, Ⅱ, Ⅲ, Ⅳa and Ⅳb HCC patients were 340.6 pg/ml, 451.55±307.84 pg/ml, 397.44±257.18 pg/ml, 486.10±397.73 pg/ml and 647.93±344.56 pg/ml, respectively. Conclusion The pre-therapeutic serum VEGF levels in HCC patients appear to reflect the disease’s potential activity of vascular invasion and metastasis.展开更多
Objective To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).Methods ...Objective To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).Methods Seventy-six NSCLC samples were stained for VEGF-C, VEGFR-3 and CD34 with immunohistochemical methods. Assessment of lymphatic vessel density (LVD) and microvessel density (MVD) was performed. The expressions of VEGF-C in 24 fresh NSCLC samples were determined with Western blot assay.Results Of the 76 NSCLC cases, 55 were VEGF-C positive and 40 were VEGFR-3 positive in cancer cells. A significant positive correlation was found between VEGF-C expression and VEGFR-3 expression in cancer cells (P<0.05). VEGF-C expression was negatively associated with differentiation of tumor cells (P<0.05). VEGF-C expression and VEGFR-3 expression were positively associated with lymph node metastasis and lymphatic invasion (P<0.05). LVD was positively related to VEGF-C expression, lymph node metastasis, lymphatic invasion and clinical stage (P<0.05). There was a significant correlation between LVD and MVD (R=0.732, P<0.05). Patients with positive VEGF-C expression had worse outcomes than those with negative VEGF-C expression (P<0.01).Conclusions In NSCLC, VEGF-C and VEGFR-3 are related to the lymphangiogenesis, angiogenesis, and occurrence and development of lung cancers. VEGF-C expression could be a useful predictor of poor prognosis in NSCLC.展开更多
AIM To investigate the predictors forrecurrence or metastasis of HCC,and toevaluate the effect of antiangiogenic therapy onthe growth of transplantable human HCC in nudemice.METHODS RT-PCR was used to measure theexpre...AIM To investigate the predictors forrecurrence or metastasis of HCC,and toevaluate the effect of antiangiogenic therapy onthe growth of transplantable human HCC in nudemice.METHODS RT-PCR was used to measure theexpression of matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)in 56 pairs of nontumorous liver andtumor samples.Sixty blood samples from humanHCC were examined by nested RT-PCR to find outAFP mRNA.Recombinant human endostatin andpolyclonal antibody against VEGF wereadministered to treat human HCC transplanted innude mice.RESULTS Thirty of 56 HCC samples showedstronger expression of MMP-9 in tumoroustissues than in nontumorous tissues.Fifteen ofthe 26 patients with relative expression level ofMMP-9 more than 0.34 developed tumorrecurrence or metastasis,whereas only 7 of 30patients with relative expression level less than0.34 developed tumor recurrence(P【0.05).There was no significant difference in therelative expression level of VEGF betweenpatients with postoperative recurrence ormetastasis and those without recurrence.AFPmRNA was detectable in 53.3% of patients withHCC.The sensitivity and specificity of AFPmRNA as a marker to detect hematogenousdissemination of HCC cells was 81.8% and84.4%,respectively.Recombinant human endostatin and polyclonal antibody against VEGFinhibited the growth of transplantable HCC innude mice by 52.2% and 45.7%,respectively.CONCLUSION MMP-9 expression in HCCcorrelates with the postoperative recurrence ormetastasis of HCC.Patients with high level ofMMP-9 expression in HCC are susceptible tometastasis.AFP mRNA could serve as anindicator of hematogenous spreading of HCCcells in circulation and a predictor of recurrenceor metastasis of HCC.Antiangiogenesis may bean adjuvant therapy for HCC.展开更多
The TGFβ signaling pathway is conserved from flies to humans and has been shown to regulate such diverse pro- cesses as cell proliferation, differentiation, motility, adhesion, organization, and programmed cell death...The TGFβ signaling pathway is conserved from flies to humans and has been shown to regulate such diverse pro- cesses as cell proliferation, differentiation, motility, adhesion, organization, and programmed cell death. Both in vitro and in vivo experiments suggest that TGF[~ can utilize these varied programs to promote cancer metastasis through its effects on the tumor microenvironment, enhanced invasive properties, and inhibition of immune cell function. Recent clinical evidence demonstrating a link between TGFβ signaling and cancer progression is fostering interest in this signaling pathway as a therapeutic target. Anti-TGFβ therapies are currently being developed and tested in pre- clinical studies. However, targeting TGFβ carries a substantial risk as this pathway is implicated in multiple homeostatic processes and is also known to have tumor-suppressor functions. Additionally, clinical and experimental results show that TGFβ has diverse and often conflicting roles in tumor progression even within the same tumor types. The development of TGFβ inhibitors for clinical use will require a deeper understanding of TGFβ signaling, its consequences, and the contexts in which it acts.展开更多
Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bid...Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bidirectional interactions between tumor cells and cells that make up bone result in a selective advantage for tumor growth and can lead to bone destruction or new bone matrix deposition. This review discusses our current understanding of the molecu- lar components and mechanisms that are responsible for those interactions.展开更多
文摘MicroRNAs （miRNAs） are a class of naturally occurring small non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level. Our previous studies suggest that mir-21 functions as an oncogene and has a role in tumorigenesis, in part through regulation of the tumor suppressor gene tropomyosin 1 （TPM1）. Given that TPM1 has been implicated in cell migration, in this study we further investigated the role of mir-21 in cell invasion and tumor metastasis. We found that suppression of mir-21 in metastatic breast cancer MDA-MB-231 cells significantly reduced invasion and lung metastasis. Consistent with this, ectopic expression of TPM1 remarkably reduced cell invasion. Furthermore, we identified two additional direct mir-21 targets, programmed cell death 4 （PDCD4） and maspin, both of which have been implicated in invasion and metastasis. Like TPM1, PDCD4 and maspin also reduced invasiveness of MDA-MB-231 cells. Finally, the expression of PDCD4 and maspin inversely correlated with mir-21 expression in human breast tumor specimens, indicating the potential regulation of PDCD4 and maspin by mir-21 in these tumors. Taken together, the results suggest that, as an oncogenic miRNA, mir-21 has a role not only in tumor growth but also in invasion and tumor metastasis by targeting multiple tumor/metastasis suppressor genes. Therefore, suppression of mir-21 may provide a novel approach for the treatment of advanced cancers.
基金Supportod ty the State Key Basic Research Program Grant G1998051211 the Fund for Leading Specialty of Shanghai Metropolitan Bureau of Public Health.
文摘AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.
文摘The importance of cancer stem cells （CSCs） in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression, particularly with respect to metastasis, has not been well-defined. Cancer metastasis requires the seeding and successful colonization of specialized CSCs at distant organs. The biology of normal stem cells and CSCs share remarkable similarities and may have important implications when applied to the study of cancer metastasis. Furthermore, overlapping sets of molecules and pathways have recently been identified to regulate both stem cell migration and cancer metastasis. These molecules constitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by the primary tumor and the formation of a nurturing organ microenvironment for migrating CSCs. In this review, we surveyed the recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume a central role in both tumorigenesis and metastasis. Better understanding of CSCs as a fundamental component of the metastatic cascade will lead to novel therapeutic strategies against metastatic cancer.
文摘The cell-biological program termed the epithelial-to-mesenchymal transition （EMT） plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenehymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.
文摘Traditional Chinese medicine （TCM）, an important component of complementary and alternative medicine, has evolved over thousands of years with its own unique system of theories, diagnostics and therapies. TCM has been increasingly used in the last decades and become well known for its significant role in preventing and treating cancer. We believe that TCM possesses advantages over Western medicine in specific aspects at a certain stage of cancer treatment. Here we summarize the advantages of TCM from three aspects： preventing tumorigenesis; attenuating toxicity and enhancing the treatment effect; and reducing tumor recurrence and metastasis.
文摘AIM:The prognosis of early gastric carcinoma (EGC) is generally excellent after surgery. The presence or absence of lymph node metastasis in EGC is an important prognostic factor. The survival and recurrence rates of node-negative EGC are much better than those of node-positive EGC. This study examined the factors related to lymph node metastasis in EGC to determine the appropriate treatment for EGC.METHODS: We investigated 748 patients with EGC who underwent surgery between January 1985 and December 1999 at the Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Hospital. Several clinicopathologic factors were investigated to analyze their relationship to lymph node metastasis: age, sex, tumor location, tumor size, gross type, histologic type, depth of invasion, extent of lymph node dissection, type of operation,and DNA ploidy.RESULTS:Lymph node metastases were found in 75 patients (10.0%). Univariate analysis showed that male sex, tumor size larger than 2.0cm, submucosal invasion of tumor, histologic differentiation, and DNA ploidy pattern were risk factors for regional lymph node metastasis in EGC patients. However, a multivariate analysis showed that three risk factors were associated with lymph node metastasis:large tumor size, undifferentiated histologic type and submucosal invasion. No statistical relationship was found for age, sex, tumor location, gross type, or DNA ploidy in multivariate analysis. The 5-year survival rate was 94.2% for those without lymph node metastasis and 87.3% for those with lymph node metastasis, and the difference was significant (P<0.05).CONCLUSION: In patients with EGC, the survival rate of patients with positive lymph nodes is significantly worse than that of patients with no lymph node metastasis. Therefore,a standard D2 lymphadenectomy should be performed in patients at high risk of lymph node metastasis: large tumor size, undifferentiated histologic type and submucosal invasion.
基金This study was supported by grants from the Key Project of Medical Science from Jiangsu Province (RC2003100)the Project of Medical Science from Department of Health, Jiangsu Province (H200523), China.
文摘BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost importance. Circulating diagnostic and prognostic biomarkers could be used in proper postoperative treatment of patients at an early stage of HCC development. This review summarizes recent studies of the specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. DATA SOURCES: An English-language literature search was conducted using MEDLINE (June 1998 to Spetember 2006) on researches of some valuable specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. RESULTS: Hepatoma tissues can synthesize various tumor-related proteins, polypeptides, and isoenzymes, such as alpha-fetoprotein (AFP), hepatoma-specific gamma-glutamyl transpeptidase (HS-GGT), etc, and then secrete into blood. The valuable early diagnostic and prognostic biomarkers could predict the development an metastases of HCC. Recent researches have confirmed that circulating hepatoma-specific AFP subfraction, transforming growth factor (TGF)-beta 1, HS-GGT, and free insulin-like growth factor (IGF)-II may be more specific markers than total AFP level for early diagnosis for HCC. The circulating genetic markers such as AFP-mRNA, TGF-beta 1-mRNA, IGF-II-mRNA, etc from peripheral blood mononuclear cells of HCC patients have been most extensively used in monitoring distal metastasis or postoperative recurrence of HCC. CONCLUSIONS: Hepatoma tissues synthesize and secrete valuable molecular markers into blood. The analyses of circulating hepatoma-specific biomarkers are useful to early diagnosis of HCC or monitoring metastasis or postoperative recurrence of HCC.
文摘Objectives To determine the pre-therapeutic serum level of vascular endothelial growth factor (VEGF) in patients with hepatocellular carcinoma (HCC) and to elucidate the relation between the serum level and clinical characteristics and metastasis of HCC. Methods One-hundred and fifteen HCC patients, 40 patients with benign liver lesions, and 30 healthy control subjects were included in this study. The serum VEGF level was measured with the quantitative sandwich enzyme linked immunosorbent assay (ELISA, R&D systems). Results The serum VEGF levels in the HCC group (465.62±336.24 pg/ml) was significantly elevated as compared with those in patients with benign liver lesions (159.54±120.58 pg/ml) and those in normal controls (123.53±51.84 pg/ml). The VEGF levels were not significantly different between the patients with benign liver lesions and the normal controls. The serum VEGF levels showed a positive rate of 77.4%, 25%, and 3.3% in the HCC patients, benign liver lesion patients and normal controls, respectively. In the 115 HCC patients, the serum VEGF levels in patients with portal vein (PV) emboli (n=26, 582.76±441.89 pg/ml), with metastasis (n=43, 548.29±438.57 pg/ml) or with large HCC lesions (≥5 cm in diameter) (n=69, 554.43±369.99 pg/ml) were significantly higher than those without PV-emboli (n=89, 431.39±292.84 pg/ml), without metastasis (n=72, 416.24±247.27 pg/ml) or with small HCC lesions (n=42, 328.67±227.47 pg/ml). The serum VEGF levels in stage Ⅰ, Ⅱ, Ⅲ, Ⅳa and Ⅳb HCC patients were 340.6 pg/ml, 451.55±307.84 pg/ml, 397.44±257.18 pg/ml, 486.10±397.73 pg/ml and 647.93±344.56 pg/ml, respectively. Conclusion The pre-therapeutic serum VEGF levels in HCC patients appear to reflect the disease’s potential activity of vascular invasion and metastasis.
文摘Objective To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).Methods Seventy-six NSCLC samples were stained for VEGF-C, VEGFR-3 and CD34 with immunohistochemical methods. Assessment of lymphatic vessel density (LVD) and microvessel density (MVD) was performed. The expressions of VEGF-C in 24 fresh NSCLC samples were determined with Western blot assay.Results Of the 76 NSCLC cases, 55 were VEGF-C positive and 40 were VEGFR-3 positive in cancer cells. A significant positive correlation was found between VEGF-C expression and VEGFR-3 expression in cancer cells (P<0.05). VEGF-C expression was negatively associated with differentiation of tumor cells (P<0.05). VEGF-C expression and VEGFR-3 expression were positively associated with lymph node metastasis and lymphatic invasion (P<0.05). LVD was positively related to VEGF-C expression, lymph node metastasis, lymphatic invasion and clinical stage (P<0.05). There was a significant correlation between LVD and MVD (R=0.732, P<0.05). Patients with positive VEGF-C expression had worse outcomes than those with negative VEGF-C expression (P<0.01).Conclusions In NSCLC, VEGF-C and VEGFR-3 are related to the lymphangiogenesis, angiogenesis, and occurrence and development of lung cancers. VEGF-C expression could be a useful predictor of poor prognosis in NSCLC.
文摘AIM To investigate the predictors forrecurrence or metastasis of HCC,and toevaluate the effect of antiangiogenic therapy onthe growth of transplantable human HCC in nudemice.METHODS RT-PCR was used to measure theexpression of matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)in 56 pairs of nontumorous liver andtumor samples.Sixty blood samples from humanHCC were examined by nested RT-PCR to find outAFP mRNA.Recombinant human endostatin andpolyclonal antibody against VEGF wereadministered to treat human HCC transplanted innude mice.RESULTS Thirty of 56 HCC samples showedstronger expression of MMP-9 in tumoroustissues than in nontumorous tissues.Fifteen ofthe 26 patients with relative expression level ofMMP-9 more than 0.34 developed tumorrecurrence or metastasis,whereas only 7 of 30patients with relative expression level less than0.34 developed tumor recurrence(P【0.05).There was no significant difference in therelative expression level of VEGF betweenpatients with postoperative recurrence ormetastasis and those without recurrence.AFPmRNA was detectable in 53.3% of patients withHCC.The sensitivity and specificity of AFPmRNA as a marker to detect hematogenousdissemination of HCC cells was 81.8% and84.4%,respectively.Recombinant human endostatin and polyclonal antibody against VEGFinhibited the growth of transplantable HCC innude mice by 52.2% and 45.7%,respectively.CONCLUSION MMP-9 expression in HCCcorrelates with the postoperative recurrence ormetastasis of HCC.Patients with high level ofMMP-9 expression in HCC are susceptible tometastasis.AFP mRNA could serve as anindicator of hematogenous spreading of HCCcells in circulation and a predictor of recurrenceor metastasis of HCC.Antiangiogenesis may bean adjuvant therapy for HCC.
文摘The TGFβ signaling pathway is conserved from flies to humans and has been shown to regulate such diverse pro- cesses as cell proliferation, differentiation, motility, adhesion, organization, and programmed cell death. Both in vitro and in vivo experiments suggest that TGF[~ can utilize these varied programs to promote cancer metastasis through its effects on the tumor microenvironment, enhanced invasive properties, and inhibition of immune cell function. Recent clinical evidence demonstrating a link between TGFβ signaling and cancer progression is fostering interest in this signaling pathway as a therapeutic target. Anti-TGFβ therapies are currently being developed and tested in pre- clinical studies. However, targeting TGFβ carries a substantial risk as this pathway is implicated in multiple homeostatic processes and is also known to have tumor-suppressor functions. Additionally, clinical and experimental results show that TGFβ has diverse and often conflicting roles in tumor progression even within the same tumor types. The development of TGFβ inhibitors for clinical use will require a deeper understanding of TGFβ signaling, its consequences, and the contexts in which it acts.
文摘Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bidirectional interactions between tumor cells and cells that make up bone result in a selective advantage for tumor growth and can lead to bone destruction or new bone matrix deposition. This review discusses our current understanding of the molecu- lar components and mechanisms that are responsible for those interactions.
