Metastatic breast cancer （MBC） is characterized by a combination of tumor growth, proliferation and metastatic progression and is typically managed with palliative intent. The benefit of standard systemic therapies ...Metastatic breast cancer （MBC） is characterized by a combination of tumor growth, proliferation and metastatic progression and is typically managed with palliative intent. The benefit of standard systemic therapies is relatively limited and the disease is considered incurable suggesting the need to investigate the biological drivers of the various phases of the metastatic process in order to improve the selection of molecularly driven therapies. The detection, enumeration and molecular analysis of circulating tumor cells （CTCs） provide an intriguing opportunity to advance this knowledge. CTCs enumerated by the Food and Drugs Administration-cleared CellSearchTM system are an independent prognostic factor of progression- free survival （PFS） and overall survival （OS） in MBC patients. Several published papers demonstrated the poor prognosis for MBC patients that presented basal CTC count _〉5 in 7.5 mL of blood. Therefore, the enumeration of CTCs during treatment for MBC provides a tool with the ability to predict progression of disease earlier than standard timing of anatomical assessment using conventional radiological tests. During the metastatic process cancer cells exhibit morphological and phenotypic plasticity undergoing epithelial- mesenchymal transition （EMT）. This important phenomenon is associated with down regulation of epithelial marker （e.g., EpCAM） with potential limitations in the applicability of current CTCs enrichment methods. Such observations translated in a number of investigations aimed at improving our capabilities to enumerate and perform molecular characterization of CTCs. Theoretically, the phenotypic analysis of CTCs can represent a ＂liquid＂ biopsy of breast tumor that is able to identify a new potential target against the metastatic disease and advance the development and monitoring of personalized therapies.展开更多
Tumor budding, defined as a small number of cancer cells observed in pathology sections detached from the main tumor mass, is a common phenomenon in cancer. It issuggested that cells in buds are in the process of acti...Tumor budding, defined as a small number of cancer cells observed in pathology sections detached from the main tumor mass, is a common phenomenon in cancer. It issuggested that cells in buds are in the process of actively moving away from the primary tumor in the first step of metastasis. Tumor budding has been observed in a variety of carcinomas and is best studied in colorectal cancers where it portends poor prognosis. More recently, tumor budding was found to be of prognostic significance in other cancers including breast cancer. Tumor budding in breast cancer is associated with other adverse pathologic factors, such as larger tumor size and lymphovascular invasion, but may have additional independent prognostic value. In the future, standardization of the quantification criteria for tumor budding may further aid in its adoption as a prognostic marker.展开更多
Metastasis-associated in colon cancer-1(MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in ca...Metastasis-associated in colon cancer-1(MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer(GC), MACC1 has been shown to be involved in oncogenesis and t umor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelialto-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry(VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment.展开更多
Long non-coding RNAs(lnc RNAs), a newly discovered class of nc RNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that ...Long non-coding RNAs(lnc RNAs), a newly discovered class of nc RNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that lnc RNAs are involved in diverse physiological and pathophysiological processes, such as cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. Aberrant expression of lnc RNAs frequently occurs in gastrointestinal cancer and plays emerging roles in cancer metastasis. In this review, we focus on and outline the regulatory functions of recently identified metastasis-associated lnc RNAs, and evaluate the p o t e n t i a l r o l e s o f l n c R N A s a s n o v e l d i a g n o s t i c biomarkers and therapeutic targets in gastrointestinal cancer.展开更多
Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in c...Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in cancer metastasis and recurrence.Although clinical applications have been challenging owing to the difficulties of CTC identification,recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment.Furthermore,CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis.A number of clinical studies have already been carried out on the basis of CTC technology.Nevertheless,the clinical utility of CTCs is still unknown in gastric cancer.In this review,we elaborate on the latest advances of CTC research in gastric cancer.展开更多
Circulating tumor cells(CTCs)have become a blistering topic of discussion for oncologists because of their tremendous potential in the diagnosis and treatment of cancer.Over the past few years,they have been doled wit...Circulating tumor cells(CTCs)have become a blistering topic of discussion for oncologists because of their tremendous potential in the diagnosis and treatment of cancer.Over the past few years,they have been doled with quite an amount of research in this area understanding that CTCs are shed from tumors and circulate in the bloodstream.This process can also occur at an early stage of cancer.The major limitation in isolation of CTCs is their availability in limited numbers.Hence,many techniques have been developed and are under continuous improvement to enhance their effi cacy of CTC isolation and enumeration.They have shown their potentiality to not just indicate the presence of a tumor but also to provide us with its core information.They have also proven to be useful in detecting minor subgroups of cells present in the primary tissue which might eventually be the cause of treatment resistance or relapse of the disease.Hence,detecting and characterizing CTCs can defi nitely become an inevitable step in treating solid tumor malignancies.In this review,we have tried to comprehend the basics of CTCs including isolation,detection,characterization,and molecular mechanism of their circulation in the blood stream.We have mostly focused on the signifi cance of CTCs in diagnosis and therapies of four most common types of cancers,namely,breast,prostate,lung,and colorectal.This review provides the coverage of most of the advancements with regards to different tumor malignancies and their probable use in predicting outcomes of the disease to realize the concept of personalized medicine.展开更多
缺氧是肿瘤微环境的主要特点,通过缺氧诱导因子(hypoxia-inducible factor,HIF)激活众多靶基因,从而影响肿瘤的代谢、增殖、凋亡、侵袭转移、耐药等多个方面。上皮细胞间质化(epithelial to mesenchymal transition,EMT)是肿瘤发生侵袭...缺氧是肿瘤微环境的主要特点,通过缺氧诱导因子(hypoxia-inducible factor,HIF)激活众多靶基因,从而影响肿瘤的代谢、增殖、凋亡、侵袭转移、耐药等多个方面。上皮细胞间质化(epithelial to mesenchymal transition,EMT)是肿瘤发生侵袭转移的重要起始过程,缺氧亦是EMT的诱发因素之一并可通过多条信号转导通路包括TGF-β,Notch,Wnt/β-catenin等调节EMT。研究缺氧诱导EMT的机制并阻断其进程,可成为治疗肿瘤的新靶点。展开更多
文摘Metastatic breast cancer （MBC） is characterized by a combination of tumor growth, proliferation and metastatic progression and is typically managed with palliative intent. The benefit of standard systemic therapies is relatively limited and the disease is considered incurable suggesting the need to investigate the biological drivers of the various phases of the metastatic process in order to improve the selection of molecularly driven therapies. The detection, enumeration and molecular analysis of circulating tumor cells （CTCs） provide an intriguing opportunity to advance this knowledge. CTCs enumerated by the Food and Drugs Administration-cleared CellSearchTM system are an independent prognostic factor of progression- free survival （PFS） and overall survival （OS） in MBC patients. Several published papers demonstrated the poor prognosis for MBC patients that presented basal CTC count _〉5 in 7.5 mL of blood. Therefore, the enumeration of CTCs during treatment for MBC provides a tool with the ability to predict progression of disease earlier than standard timing of anatomical assessment using conventional radiological tests. During the metastatic process cancer cells exhibit morphological and phenotypic plasticity undergoing epithelial- mesenchymal transition （EMT）. This important phenomenon is associated with down regulation of epithelial marker （e.g., EpCAM） with potential limitations in the applicability of current CTCs enrichment methods. Such observations translated in a number of investigations aimed at improving our capabilities to enumerate and perform molecular characterization of CTCs. Theoretically, the phenotypic analysis of CTCs can represent a ＂liquid＂ biopsy of breast tumor that is able to identify a new potential target against the metastatic disease and advance the development and monitoring of personalized therapies.
文摘Tumor budding, defined as a small number of cancer cells observed in pathology sections detached from the main tumor mass, is a common phenomenon in cancer. It issuggested that cells in buds are in the process of actively moving away from the primary tumor in the first step of metastasis. Tumor budding has been observed in a variety of carcinomas and is best studied in colorectal cancers where it portends poor prognosis. More recently, tumor budding was found to be of prognostic significance in other cancers including breast cancer. Tumor budding in breast cancer is associated with other adverse pathologic factors, such as larger tumor size and lymphovascular invasion, but may have additional independent prognostic value. In the future, standardization of the quantification criteria for tumor budding may further aid in its adoption as a prognostic marker.
文摘Metastasis-associated in colon cancer-1(MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer(GC), MACC1 has been shown to be involved in oncogenesis and t umor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelialto-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry(VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment.
基金Supported by the National Natural Science Foundation of China,No.81272762 and No.81201635the Guangdong Natural Science Funds for Distinguished Young Scholar,No.S20120011334
文摘Long non-coding RNAs(lnc RNAs), a newly discovered class of nc RNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that lnc RNAs are involved in diverse physiological and pathophysiological processes, such as cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. Aberrant expression of lnc RNAs frequently occurs in gastrointestinal cancer and plays emerging roles in cancer metastasis. In this review, we focus on and outline the regulatory functions of recently identified metastasis-associated lnc RNAs, and evaluate the p o t e n t i a l r o l e s o f l n c R N A s a s n o v e l d i a g n o s t i c biomarkers and therapeutic targets in gastrointestinal cancer.
文摘Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in cancer metastasis and recurrence.Although clinical applications have been challenging owing to the difficulties of CTC identification,recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment.Furthermore,CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis.A number of clinical studies have already been carried out on the basis of CTC technology.Nevertheless,the clinical utility of CTCs is still unknown in gastric cancer.In this review,we elaborate on the latest advances of CTC research in gastric cancer.
文摘Circulating tumor cells(CTCs)have become a blistering topic of discussion for oncologists because of their tremendous potential in the diagnosis and treatment of cancer.Over the past few years,they have been doled with quite an amount of research in this area understanding that CTCs are shed from tumors and circulate in the bloodstream.This process can also occur at an early stage of cancer.The major limitation in isolation of CTCs is their availability in limited numbers.Hence,many techniques have been developed and are under continuous improvement to enhance their effi cacy of CTC isolation and enumeration.They have shown their potentiality to not just indicate the presence of a tumor but also to provide us with its core information.They have also proven to be useful in detecting minor subgroups of cells present in the primary tissue which might eventually be the cause of treatment resistance or relapse of the disease.Hence,detecting and characterizing CTCs can defi nitely become an inevitable step in treating solid tumor malignancies.In this review,we have tried to comprehend the basics of CTCs including isolation,detection,characterization,and molecular mechanism of their circulation in the blood stream.We have mostly focused on the signifi cance of CTCs in diagnosis and therapies of four most common types of cancers,namely,breast,prostate,lung,and colorectal.This review provides the coverage of most of the advancements with regards to different tumor malignancies and their probable use in predicting outcomes of the disease to realize the concept of personalized medicine.
文摘缺氧是肿瘤微环境的主要特点,通过缺氧诱导因子(hypoxia-inducible factor,HIF)激活众多靶基因,从而影响肿瘤的代谢、增殖、凋亡、侵袭转移、耐药等多个方面。上皮细胞间质化(epithelial to mesenchymal transition,EMT)是肿瘤发生侵袭转移的重要起始过程,缺氧亦是EMT的诱发因素之一并可通过多条信号转导通路包括TGF-β,Notch,Wnt/β-catenin等调节EMT。研究缺氧诱导EMT的机制并阻断其进程,可成为治疗肿瘤的新靶点。
