AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie(XTSJ) decoction on gastric cancer stem-like cells(GCSCs). METHODS: The gastric cancer cell line MKN-45 line was selected and sorted...AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie(XTSJ) decoction on gastric cancer stem-like cells(GCSCs). METHODS: The gastric cancer cell line MKN-45 line was selected and sorted by FACS using the cancer stem cell marker CD44; the stemness of these cells was checked in our previous study. In an in vitro study, the expression of Notch-1, Hes1, Vascular endothelial growth factor(VEGF), and Ki-67 in both CD44-positive gastric cancer stem-like cells(GCSCs) and CD44-negative cells was measured by Western blot. The effect of XTSJ serum on cell viability and on the above markers was measured by MTT assay and Western blot, respectively. In an in vivo study, the ability to induce angiogenesis and maintenance of GCSCs in CD44-positive-MKN-45- and CD44-negative-engrafted mice were detected by immunohistochemical staining using markers for CD34 and CD44, respectively. The role of XTSJ decoction in regulating the expression of Notch-1, Hes1, VEGF and Ki-67 was measured by Western blot and real-time polymerase chain reaction.RESULTS: CD44+ GCSCs showed more cell proliferation and VEGF secretion than CD44-negative cells in vitro, which were accompanied by the high expression of Notch-1 and Hes1 and positively associated with tumor growth(GCSCs vs CD44-negative cells, 2.72 ± 0.25 vs 1.46 ± 0.16, P < 0.05) and microvessel density(MVD)(GCSCs vs CD44-negative cells, 8.15 ± 0.42 vs 3.83 ± 0.49, P < 0.001) in vivo. XTSJ decoction inhibited the viability of both cell types in a dose-dependent manner in vitro. Specifically, a significant difference in the medium-(82.87% ± 6.53%) and high-dose XTSJ groups(77.43% ± 7.34%) was detected at 24 h in the CD44+ GCSCs group compared with the saline group(95.42% ± 5.76%) and the low-dose XTSJ group(90.74% ± 6.57%)(P < 0.05). However, the efficacy of XTSJ decoction was reduced in the CD44- groups; significant differences were only detected in the high-dose XTSJ group at 48 h(78.57% ± 6.94%) and 72 h(72.12% ± 7.68%) when compared with the other CD44- groups(P < 0.05). Notably, these differences were highly consistent with the Notch-1, Hes1, VEGF and Ki-67 expression in these cells. Similarly, in vivo, XTSJ decoction inhibited tumor growth in a dose-dependent manner. A significant difference was observed in the medium(1.76 ± 0.15) and high-dose XTSJ(1.33 ± 0.081) groups compared with the GCSCs control group(2.72 ± 0.25) and the low-dose XTSJ group(2.51 ± 0.25)(P < 0.05). We also detected a remarkable decrease of MVD in the medium-(7.10 ± 0.60) and high-dose XTSJ(5.99 ± 0.47) groups compared with the GCSC control group(8.15 ± 0.42) and the low-dose XTSJ group(8.14 ± 0.46)(P < 0.05). Additionally, CD44 expression was decreased in these groups [medium-(4.43 ± 0.45) and high-dose XTSJ groups(3.56 ± 0.31) vs the GCSC control(5.96 ± 0.46) and low dose XTSJ groups(5.91 ± 0.38)](P < 0.05). The significant differences in Notch-1, Hes1, VEGF and Ki-67 expression highly mirrored the results of XTSJ decoction in inhibiting tumor growth, MVD and CD44 expression.CONCLUSION: Notch-1 may play an important role in regulating the proliferation of GCSCs; XTSJ decoction could attenuate tumor angiogenesis, at least partially, by inhibiting Notch-1.展开更多
Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC p...Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC patients remains very poor.Thus,a suitable therapeutic strategy for GC is important for prolonging survival.Both tumor cells themselves and the tumor microenvironment play an important role in tumorigenesis,including angiogenesis,inflammation,immunosuppression and metastasis.Importantly,these cells contribute to gastric carcinogenesis by altering the angiogenic phenotype switch.The development,relapse and spreading of tumors depend on new vessels that provide the nutrition,growth factors and oxygen required for continuous tumor growth.Therefore,a state of tumor dormancy could be induced by blocking tumor-associated angiogenesis.Recently,several antiangiogenic agents have been identified,and their potential for the clinical management of GC has been tested.Here,we provide an up-to-date summary of angiogenesis and the angiogenic factors associated with tumor progression in GC.We also review antiangiogenic agents with a focus on the anti-vascular endothelial growth factor receptor(VEGFR)-mediated pathway for endothelial cell growth and their angiogenesis ability in GC.However,most antiangiogenic agents have reported no benefit to overall survival(OS)compared to chemotherapy alone in local or advanced GC.In phase III clinical trials,only ramucirumab(anti-VEGFR blocker)and apatinib(VEGFR-TKI blocker)have reported an improved median overall response rate and prolonged OS and progression-free survival outcomes as a 2 nd-line agent combined with chemotherapy treatment in advanced GC.By providing insights into the molecular mechanisms of angiogenesis associated with tumor progression in GC,this review will hopefully aid the optimization of antiangiogenesis strategies for GC therapy in combination with chemotherapy and adjuvant treatment.展开更多
In this editorial,we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer.Cancer of the pancreas remains one of the deadliest cancer types.The highest incidence and mortality...In this editorial,we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer.Cancer of the pancreas remains one of the deadliest cancer types.The highest incidence and mortality rates of pancreatic cancer are found in developed countries.Trends of pancreatic cancer incidence and mortality vary considerably worldwide.A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease.Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche.In this editorial,we highlight the foundational studies that have driven our understanding of these processes.In our experimental center,we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer.We focused on the role of mast cells(MCs).MCs contain pro-angiogenic factors,including tryptase,that are associated with increased angiogenesis in various tumors.In this editorial,we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue.The assessment includes the density of c-Kit receptor-positive MCs,the density of tryptase-positive MCs,the area of tryptasepositive MCs,and angiogenesis in terms of microvascularization density.展开更多
Objective:To investigate the anti-angiogenic effect of tea polyphenols(TPS)on breast cancer and normal tissues in a mouse model.Methods:Breast cancer was successfully implanted into 48 BALB/c mice,which were then rand...Objective:To investigate the anti-angiogenic effect of tea polyphenols(TPS)on breast cancer and normal tissues in a mouse model.Methods:Breast cancer was successfully implanted into 48 BALB/c mice,which were then randomly divided into a TP oral gavage group,a TP local injection group,a ginsenoside Rg3 group,and a model control group according to a random number table.The tumor inhibitory rates of each group were calculated,while microvessel density(MVD)and the expression of vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),and tissue inhibitor of metalloproteinase(TIMP-2)were detected by immunohistochemistry.Results:TPs could inhibit the growth of breast cancer xenografts in the mouse model.The tumor inhibition rates of the TP oral gavage and TP local injection groups were 37.43%and 40.94%,respectively.Compared with the model control group,MVD and VEGF and bFGF expression was downregulated(all P<.05),whereas TIMP-2 expression was elevated in the TP oral gavage and TP local injection groups(P=.015 and P=.032).TPs showed no significant effect on MVD and VEGF and TIMP-2 expression in the heart,brain,and kidney of the mouse model.Conclusion:TPs can restrict the growth of breast cancer by specifically inhibiting the angiogenesis of breast tumor tissue while having little effect on the normal tissue of important organs including the heart,brain,and kidney.展开更多
AIM: To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS: Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma ...AIM: To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS: Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups. Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested, the tumor volumes were determined, and the expressions of CD34, VEGF and FIk-1 were examined by immunohistochemical method. RESULTS: Tumor volume was significantly inhibited in the endostatin group (84.17%) and tumor weight was significantly inhibited in the endostatin group (0.197±0.049) compared to the control group (1.198±0.105) (F=22.56, P=0.001), microvessel density (MVD) was significantly decreased in the treated group (31.857±3.515) compared to the control group (100.143±4.290) (F=151.62, P<0.001). Furthermore, the expression of FIk-1 was significantly inhibited in the treated group (34.29%) compared to the control group (8.57%) (x^2=13.745, P=0.001). However no significant decrease was observed in the expression of vascular endothelial growth factor (VEGF) between these two groups (x^2=0.119, P=0.730). CONCLUSION: Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/FIk-1 pathway. This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.展开更多
Mast cells(MCs), located ubiquitously near blood vessels, are descended from CD34+ hematopoietic stem cells. Initially, although their role has been well defined in hypersensitivity reactions, the discovery of their s...Mast cells(MCs), located ubiquitously near blood vessels, are descended from CD34+ hematopoietic stem cells. Initially, although their role has been well defined in hypersensitivity reactions, the discovery of their sharing in both innate and adaptive immunity has allowed to redefine their crucial interplay on the regulatory function between inflammatory and tumor cells through the release of mediators granule-associated(mainly tryptase and vascular endothelial growth factor). In particular, in several animal and human malignancies it has been well demonstrated that activated c-Kit receptor(c-KitR) and tryptase(an agonist of the proteinase-activated receptor-2) take pivotal part in tumor angiogenesis after the MCs activation, contributing to tumor cells invasion and metastasis. In this review, we focused on crucial MCs density(MCD) role in colorectal cancer(CRC) development and progression angiogenesis-mediated; then, we will analyze the principal studies that have focused on MCD as possible prognostic factor. Finally, we will consider a possible role of MCD as novel therapeutic target mainly by c-KitR tyrosine kinase inhibitors(imatinib, masitinib) and tryptase inhibitors(gabexate and nafamostat mesylate) with the aim to prevent CRC progression.展开更多
Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide.At the time of diagnosis,more than 20%of patients already have metastatic disease.In the la...Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide.At the time of diagnosis,more than 20%of patients already have metastatic disease.In the last 20 years,the natural course of the disease has changed due to major changes in the management of metastatic disease such as the advent of novel surgical and local therapy approaches as well as the introduction of novel chemotherapy drugs and targeted agents such as anti-epidermal growth factor receptor,anti-BRAF and antiangiogenics.Angiogenesis is a complex biological process of new vessel formation from existing ones and is an integral component of tumor progression supporting cancer cells to grow,proliferate and metastasize.Many molecules are involved in this proangiogenic process,such as vascular endothelial growth factor and its receptors on endothelial cells.A well-standardized methodology that is applied to assess angiogenesis in the tumor microenvironment is microvascular density by using immunohistochemistry with antibodies against endothelial CD31,CD34 and CD105 antigens.Even smaller molecules,such as the micro-RNAs,which are small non-coding RNAs,are being studied for their usefulness as surrogate biomarkers of angiogenesis and prognosis.In this review,we will discuss recent advances regarding the investigation of angiogenesis,the crosstalk between elements of the immune microenvironment and angiogenesis and how a disorganized tumor vessel network affects the trafficking of CD8+T cells in the tumor bed.Furthermore,we will present recent data from clinical trials that combine antiangiogenic therapies with immune checkpoint inhibitors in colorectal cancer.展开更多
基金Supported by Project of Experimental Animal Research(the Science and Technology Commission of Shanghai),No.13140901803
文摘AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie(XTSJ) decoction on gastric cancer stem-like cells(GCSCs). METHODS: The gastric cancer cell line MKN-45 line was selected and sorted by FACS using the cancer stem cell marker CD44; the stemness of these cells was checked in our previous study. In an in vitro study, the expression of Notch-1, Hes1, Vascular endothelial growth factor(VEGF), and Ki-67 in both CD44-positive gastric cancer stem-like cells(GCSCs) and CD44-negative cells was measured by Western blot. The effect of XTSJ serum on cell viability and on the above markers was measured by MTT assay and Western blot, respectively. In an in vivo study, the ability to induce angiogenesis and maintenance of GCSCs in CD44-positive-MKN-45- and CD44-negative-engrafted mice were detected by immunohistochemical staining using markers for CD34 and CD44, respectively. The role of XTSJ decoction in regulating the expression of Notch-1, Hes1, VEGF and Ki-67 was measured by Western blot and real-time polymerase chain reaction.RESULTS: CD44+ GCSCs showed more cell proliferation and VEGF secretion than CD44-negative cells in vitro, which were accompanied by the high expression of Notch-1 and Hes1 and positively associated with tumor growth(GCSCs vs CD44-negative cells, 2.72 ± 0.25 vs 1.46 ± 0.16, P < 0.05) and microvessel density(MVD)(GCSCs vs CD44-negative cells, 8.15 ± 0.42 vs 3.83 ± 0.49, P < 0.001) in vivo. XTSJ decoction inhibited the viability of both cell types in a dose-dependent manner in vitro. Specifically, a significant difference in the medium-(82.87% ± 6.53%) and high-dose XTSJ groups(77.43% ± 7.34%) was detected at 24 h in the CD44+ GCSCs group compared with the saline group(95.42% ± 5.76%) and the low-dose XTSJ group(90.74% ± 6.57%)(P < 0.05). However, the efficacy of XTSJ decoction was reduced in the CD44- groups; significant differences were only detected in the high-dose XTSJ group at 48 h(78.57% ± 6.94%) and 72 h(72.12% ± 7.68%) when compared with the other CD44- groups(P < 0.05). Notably, these differences were highly consistent with the Notch-1, Hes1, VEGF and Ki-67 expression in these cells. Similarly, in vivo, XTSJ decoction inhibited tumor growth in a dose-dependent manner. A significant difference was observed in the medium(1.76 ± 0.15) and high-dose XTSJ(1.33 ± 0.081) groups compared with the GCSCs control group(2.72 ± 0.25) and the low-dose XTSJ group(2.51 ± 0.25)(P < 0.05). We also detected a remarkable decrease of MVD in the medium-(7.10 ± 0.60) and high-dose XTSJ(5.99 ± 0.47) groups compared with the GCSC control group(8.15 ± 0.42) and the low-dose XTSJ group(8.14 ± 0.46)(P < 0.05). Additionally, CD44 expression was decreased in these groups [medium-(4.43 ± 0.45) and high-dose XTSJ groups(3.56 ± 0.31) vs the GCSC control(5.96 ± 0.46) and low dose XTSJ groups(5.91 ± 0.38)](P < 0.05). The significant differences in Notch-1, Hes1, VEGF and Ki-67 expression highly mirrored the results of XTSJ decoction in inhibiting tumor growth, MVD and CD44 expression.CONCLUSION: Notch-1 may play an important role in regulating the proliferation of GCSCs; XTSJ decoction could attenuate tumor angiogenesis, at least partially, by inhibiting Notch-1.
基金Supported by the Ministry of Science and Technology,Taiwan,No.MOST 106-2320-B-255-005 and No.MOST 107-2320-B-255-003Chang Gung Medical Research Foundation,Taoyuan,Taiwan,No.CMRPF1G0011,No.CMRPF1G0251,No.CMRPF1I0031,No.CMRPF1H0051,and No.CMRPF1I0041Chang Gung University of Science and Technology,Taoyuan,Taiwan,No.ZRRPF3H0131
文摘Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC patients remains very poor.Thus,a suitable therapeutic strategy for GC is important for prolonging survival.Both tumor cells themselves and the tumor microenvironment play an important role in tumorigenesis,including angiogenesis,inflammation,immunosuppression and metastasis.Importantly,these cells contribute to gastric carcinogenesis by altering the angiogenic phenotype switch.The development,relapse and spreading of tumors depend on new vessels that provide the nutrition,growth factors and oxygen required for continuous tumor growth.Therefore,a state of tumor dormancy could be induced by blocking tumor-associated angiogenesis.Recently,several antiangiogenic agents have been identified,and their potential for the clinical management of GC has been tested.Here,we provide an up-to-date summary of angiogenesis and the angiogenic factors associated with tumor progression in GC.We also review antiangiogenic agents with a focus on the anti-vascular endothelial growth factor receptor(VEGFR)-mediated pathway for endothelial cell growth and their angiogenesis ability in GC.However,most antiangiogenic agents have reported no benefit to overall survival(OS)compared to chemotherapy alone in local or advanced GC.In phase III clinical trials,only ramucirumab(anti-VEGFR blocker)and apatinib(VEGFR-TKI blocker)have reported an improved median overall response rate and prolonged OS and progression-free survival outcomes as a 2 nd-line agent combined with chemotherapy treatment in advanced GC.By providing insights into the molecular mechanisms of angiogenesis associated with tumor progression in GC,this review will hopefully aid the optimization of antiangiogenesis strategies for GC therapy in combination with chemotherapy and adjuvant treatment.
文摘In this editorial,we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer.Cancer of the pancreas remains one of the deadliest cancer types.The highest incidence and mortality rates of pancreatic cancer are found in developed countries.Trends of pancreatic cancer incidence and mortality vary considerably worldwide.A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease.Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche.In this editorial,we highlight the foundational studies that have driven our understanding of these processes.In our experimental center,we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer.We focused on the role of mast cells(MCs).MCs contain pro-angiogenic factors,including tryptase,that are associated with increased angiogenesis in various tumors.In this editorial,we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue.The assessment includes the density of c-Kit receptor-positive MCs,the density of tryptase-positive MCs,the area of tryptasepositive MCs,and angiogenesis in terms of microvascularization density.
基金National Natural Science Foundation of China(30472280)and Independent innovation project of Capital Medical Development Research Fund/Traditional Chinese Medicine(SF-2009-III-13).
文摘Objective:To investigate the anti-angiogenic effect of tea polyphenols(TPS)on breast cancer and normal tissues in a mouse model.Methods:Breast cancer was successfully implanted into 48 BALB/c mice,which were then randomly divided into a TP oral gavage group,a TP local injection group,a ginsenoside Rg3 group,and a model control group according to a random number table.The tumor inhibitory rates of each group were calculated,while microvessel density(MVD)and the expression of vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),and tissue inhibitor of metalloproteinase(TIMP-2)were detected by immunohistochemistry.Results:TPs could inhibit the growth of breast cancer xenografts in the mouse model.The tumor inhibition rates of the TP oral gavage and TP local injection groups were 37.43%and 40.94%,respectively.Compared with the model control group,MVD and VEGF and bFGF expression was downregulated(all P<.05),whereas TIMP-2 expression was elevated in the TP oral gavage and TP local injection groups(P=.015 and P=.032).TPs showed no significant effect on MVD and VEGF and TIMP-2 expression in the heart,brain,and kidney of the mouse model.Conclusion:TPs can restrict the growth of breast cancer by specifically inhibiting the angiogenesis of breast tumor tissue while having little effect on the normal tissue of important organs including the heart,brain,and kidney.
基金Supported by the Key Technologies Research and Development Program of Heilongjiang Province During the 9th Five-Year Plan Period,No.G99C 19-5
文摘AIM: To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS: Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups. Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested, the tumor volumes were determined, and the expressions of CD34, VEGF and FIk-1 were examined by immunohistochemical method. RESULTS: Tumor volume was significantly inhibited in the endostatin group (84.17%) and tumor weight was significantly inhibited in the endostatin group (0.197±0.049) compared to the control group (1.198±0.105) (F=22.56, P=0.001), microvessel density (MVD) was significantly decreased in the treated group (31.857±3.515) compared to the control group (100.143±4.290) (F=151.62, P<0.001). Furthermore, the expression of FIk-1 was significantly inhibited in the treated group (34.29%) compared to the control group (8.57%) (x^2=13.745, P=0.001). However no significant decrease was observed in the expression of vascular endothelial growth factor (VEGF) between these two groups (x^2=0.119, P=0.730). CONCLUSION: Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/FIk-1 pathway. This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.
文摘Mast cells(MCs), located ubiquitously near blood vessels, are descended from CD34+ hematopoietic stem cells. Initially, although their role has been well defined in hypersensitivity reactions, the discovery of their sharing in both innate and adaptive immunity has allowed to redefine their crucial interplay on the regulatory function between inflammatory and tumor cells through the release of mediators granule-associated(mainly tryptase and vascular endothelial growth factor). In particular, in several animal and human malignancies it has been well demonstrated that activated c-Kit receptor(c-KitR) and tryptase(an agonist of the proteinase-activated receptor-2) take pivotal part in tumor angiogenesis after the MCs activation, contributing to tumor cells invasion and metastasis. In this review, we focused on crucial MCs density(MCD) role in colorectal cancer(CRC) development and progression angiogenesis-mediated; then, we will analyze the principal studies that have focused on MCD as possible prognostic factor. Finally, we will consider a possible role of MCD as novel therapeutic target mainly by c-KitR tyrosine kinase inhibitors(imatinib, masitinib) and tryptase inhibitors(gabexate and nafamostat mesylate) with the aim to prevent CRC progression.
文摘Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide.At the time of diagnosis,more than 20%of patients already have metastatic disease.In the last 20 years,the natural course of the disease has changed due to major changes in the management of metastatic disease such as the advent of novel surgical and local therapy approaches as well as the introduction of novel chemotherapy drugs and targeted agents such as anti-epidermal growth factor receptor,anti-BRAF and antiangiogenics.Angiogenesis is a complex biological process of new vessel formation from existing ones and is an integral component of tumor progression supporting cancer cells to grow,proliferate and metastasize.Many molecules are involved in this proangiogenic process,such as vascular endothelial growth factor and its receptors on endothelial cells.A well-standardized methodology that is applied to assess angiogenesis in the tumor microenvironment is microvascular density by using immunohistochemistry with antibodies against endothelial CD31,CD34 and CD105 antigens.Even smaller molecules,such as the micro-RNAs,which are small non-coding RNAs,are being studied for their usefulness as surrogate biomarkers of angiogenesis and prognosis.In this review,we will discuss recent advances regarding the investigation of angiogenesis,the crosstalk between elements of the immune microenvironment and angiogenesis and how a disorganized tumor vessel network affects the trafficking of CD8+T cells in the tumor bed.Furthermore,we will present recent data from clinical trials that combine antiangiogenic therapies with immune checkpoint inhibitors in colorectal cancer.
