Ursolic acid(UA),a natural pentacyclic triterpenoid,possesses widespread biological and pharmacological activities.However,drawbacks such as low bioavailability,poor targeting and rapid metabolism greatly hinder its f...Ursolic acid(UA),a natural pentacyclic triterpenoid,possesses widespread biological and pharmacological activities.However,drawbacks such as low bioavailability,poor targeting and rapid metabolism greatly hinder its further clinical application.Recently,with the development of nanotechnology,various UA nanosystems have emerged as promising strategies for effective cancer therapy.This article reviews various types of UA-based nanodelivery systems,primarily with emphasis placed on novel UA-based carrier-free nanodrugs,which are considered to be innovative methods for cancer therapy.Moreover,this review presents carrier-free nano-drugs that co-assembled of UA and photosensitizers that displayed synergistic antitumor performance.Finally,the article also describes the development and challenges of UA nanosystems for future research in this field.Overall,the information presented in this review will provide new insight into the rational utilization of nano-drugs in cancer therapy.展开更多
Objective: Cancer metastasis remains the primary cause of cancer-related death worldwide.In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells tha...Objective: Cancer metastasis remains the primary cause of cancer-related death worldwide.In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma cells.The purpose of this study was to identify the roles of KCTD12 in cancer metastasis.Methods: The Cancer Genome Atlas(TCGA) datasets were used to evaluate the relationship between KCTD12 and skin cutaneous melanoma(SKCM) prognosis.The effects of endogenous KCTD12 on biological behaviors were examined using the MTT assay.The impacts of KCTD12 on melanoma stemness were explored using spheroid formation assay.KCTD12 knockout A375 cells were generated to confirm the inhibitory effect of KCTD12 on CD271, and a mouse metastatic model was used to determine the impact of KCTD12 on melanoma metastasis in vivo.Results: KCTD12 levels were lower in lung metastatic cells than in paired parental melanoma cells, and low KCTD12 expression indicated a poor prognosis in SKCM.Cancer metastasis-related capacities were higher in lung metastatic cells than in parental melanoma cells.Moreover, KCTD12 knockdown enhanced tumor growth and metastasis both in vitro and in vivo.Mechanistically, the interaction between KCTD12 and CD271 might be responsible for the stemness transformation after KCTD12 knockdown.Conclusions: This study identifies for the first time the role of the interaction between KCTD12 and CD271 in inducing melanoma cell stemness transformation.Moreover, KCTD12 repression enhances melanoma cell growth, adhesion, migration and invasion.展开更多
Objective:Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied,but there is a lack of effective strategies and drugs for the treatment of tumor metastases.Here,we descri...Objective:Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied,but there is a lack of effective strategies and drugs for the treatment of tumor metastases.Here,we describe a functional product based on a combination of compounds,which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases,improving anti-cancer treatment,and enhancing immunity and antioxidant capacity.Our designed combination,named MVBL,consists of four inexpensive compounds:L-selenium-methylselenocysteine(MSC),D-α-tocopheryl succinic acid(VES),β-carotene(β-Ca),and L-lysine(Lys).Methods:The effects of MVBL on cell viability,cell cycle,cell apoptosis,cell migration,cell invasion,reactive oxygen species(ROS),and paclitaxel(PTX)-combined treatment were studied in vitro.The inhibition of tumor metastasis,antioxidation,and immune enhancement capacity of MVBL were determined in vivo.Results:MVBL exhibited higher toxicity to tumor cells than to normal cells.It did not significantly affect the cell cycle of cancer cells,but increased their apoptosis.Wound healing,adhesion,and transwell assays showed that MVBL significantly inhibited tumor cell migration,adhesion,and invasion.MVBL sensitized MDA-MB-231 breast cancer cells to PTX,indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs.In mice,experimental data showed that MVBL inhibited tumor metastasis,prolonged their survival time,and enhanced their antioxidant capacity and immune function.Conclusions:This study revealed the roles of MVBL in improving immunity and antioxidation,preventing tumor growth,and inhibiting metastasis in vitro and in vivo.MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.展开更多
Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenes...Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.展开更多
Dear Editor,Cancer metastasis,dissemination of cancer cells from primary tumors to distant sites,attributes to 90%cancer-related death.1 Although the targeted therapies,bio-nanomaterial-based target delivery,and the c...Dear Editor,Cancer metastasis,dissemination of cancer cells from primary tumors to distant sites,attributes to 90%cancer-related death.1 Although the targeted therapies,bio-nanomaterial-based target delivery,and the consequent adoption of the so-called personalized medicine have obtained notable achievements in some cancers,significant problems still exist with these approaches.2 There are hardly any cancer therapeutic agents that can interfere with metastasized cancer.In recent times,we proposed a novel concept,namely cancer metastasis chemoprevention,which is different from the existing cancer chemotherapy and cancer chemoprevention.Cancer metastasis chemoprevention aims at safely preventing circulating tumor cells(CTCs)and related molecules from gemmating into the metastatic tissues.The strategy does not intend to kill cancer cells as cancer chemotherapy does,nor to aimlessly prevent cancers from carcinogenesis as cancer chemoprevention does.展开更多
Dear Editor,Metastasis is the cause of most fatalities in cancer patients and remains the phenomenon poorly understood mechanistically. Deciphering of the regulatory networks underlying the cancer cell metastasis is u...Dear Editor,Metastasis is the cause of most fatalities in cancer patients and remains the phenomenon poorly understood mechanistically. Deciphering of the regulatory networks underlying the cancer cell metastasis is urgently needed. Nucleolar protein 7 (NOL7) has been reported to function as a tumor suppressor in cervical cancer.1 Our current study reveals a novel tumor-promoting capacity of NOL7 in melanoma. We first detected that NOL7 expression is upregulated in metastatic melanoma as compared with its expression at the primary site through isobaric tag for relative and absolute quantitation proteomic screening, further confirming this finding with the analysis of NOL7 protein and messenger RNA (mRNA) levels (Supplementary Fig. S1). Importantly, NOL7 expression increased with the disease progression from benign nevus to primary melanoma and further to metastatic melanoma (Fig. 1a and Supplementary Fig. S1d). Previous studies have shown that melanoma is commonly associated with the amplification of the chromosome region 6p, particularly 6p21–23, where the NOL7 gene resides, and that this region frequently undergoes heterozygous loss in cervical cancer.2 It might therefore be predicted that NOL7 exhibits a different expression pattern and plays different roles in melanoma and cervical cancer.展开更多
The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into law.The cancer crusade costs trillions with disappointing returns,teasing the possibility of...The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into law.The cancer crusade costs trillions with disappointing returns,teasing the possibility of a new breakthrough.Cure for cancer post-metastases still seems tantalisingly out of reach.Once metastasized,cancer-related death is extremely difficult,if not impossible,to be reversed.Here we present cancer pre-metastasis chemoprevention strategy that can prevent circulating tumour cells(CTCs)from initiating metastases safely and effectively,and is disparate from the traditional cancer chemotherapy and cancer chemoprevention.Deep learning of the biology of CTCs and their disseminating organotropism,complexity of their adhesion to endothelial niche reveals that if the adhesion of CTCs to their metastasis niche(the first and the most important part in cancer metastatic cascade)can be pharmaceutically interrupted,the lethal metastatic cascade could be prevented from getting initiated.We analyse the key inflammatory and adhesive factors contributing to CTC adhesion/germination,provide pharmacological fundamentals for abortifacients to intervene CTC adhesion to the distant metastasis sites.The adhesion/inhibition ratio(AIR)is defined for selecting the best cancer metastasis chemopreventive candidates.The successful development of such new therapeutic modalities for cancer metastasis chemoprevention has great potential to revolutionise the current ineffective post-metastasis treatments.展开更多
In the process of collating the raw data,the authors noticed one inadvertent mistake in Fig.1 that need to be corrected.1 The correct data are provided as follows.The key findings of the article are not affected by th...In the process of collating the raw data,the authors noticed one inadvertent mistake in Fig.1 that need to be corrected.1 The correct data are provided as follows.The key findings of the article are not affected by these corrections.展开更多
基金supported by the National Natural Science Foundation of China(81972832,81472767)Scientific Research Training Program for Undergraduate of Fuzhou University(25055,25068)。
文摘Ursolic acid(UA),a natural pentacyclic triterpenoid,possesses widespread biological and pharmacological activities.However,drawbacks such as low bioavailability,poor targeting and rapid metabolism greatly hinder its further clinical application.Recently,with the development of nanotechnology,various UA nanosystems have emerged as promising strategies for effective cancer therapy.This article reviews various types of UA-based nanodelivery systems,primarily with emphasis placed on novel UA-based carrier-free nanodrugs,which are considered to be innovative methods for cancer therapy.Moreover,this review presents carrier-free nano-drugs that co-assembled of UA and photosensitizers that displayed synergistic antitumor performance.Finally,the article also describes the development and challenges of UA nanosystems for future research in this field.Overall,the information presented in this review will provide new insight into the rational utilization of nano-drugs in cancer therapy.
基金supported by grants from the Ministry of Science and Technology of China (Grant No.2015CB931804)National Natural Science Foundation of China (Grant No.U1505225, 81773063, 81273548, 81571802)+1 种基金the Natural Science Foundation of Fujian Province (Grant No.2016J06020)Fujian Development and Reform Commission project (Grant No.829054)
文摘Objective: Cancer metastasis remains the primary cause of cancer-related death worldwide.In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma cells.The purpose of this study was to identify the roles of KCTD12 in cancer metastasis.Methods: The Cancer Genome Atlas(TCGA) datasets were used to evaluate the relationship between KCTD12 and skin cutaneous melanoma(SKCM) prognosis.The effects of endogenous KCTD12 on biological behaviors were examined using the MTT assay.The impacts of KCTD12 on melanoma stemness were explored using spheroid formation assay.KCTD12 knockout A375 cells were generated to confirm the inhibitory effect of KCTD12 on CD271, and a mouse metastatic model was used to determine the impact of KCTD12 on melanoma metastasis in vivo.Results: KCTD12 levels were lower in lung metastatic cells than in paired parental melanoma cells, and low KCTD12 expression indicated a poor prognosis in SKCM.Cancer metastasis-related capacities were higher in lung metastatic cells than in parental melanoma cells.Moreover, KCTD12 knockdown enhanced tumor growth and metastasis both in vitro and in vivo.Mechanistically, the interaction between KCTD12 and CD271 might be responsible for the stemness transformation after KCTD12 knockdown.Conclusions: This study identifies for the first time the role of the interaction between KCTD12 and CD271 in inducing melanoma cell stemness transformation.Moreover, KCTD12 repression enhances melanoma cell growth, adhesion, migration and invasion.
基金the National Natural Science Foundation of China(Nos.81961138017 and 81703555)the Natural Science Foundation of Fujian Province(Nos.2021J011046 and 2020J01859)+4 种基金the Young and Middle-aged Teacher Education Research Project of Fujian Province(No.JAT200412)the Science and Technology Planning Projects of Fuzhou(No.2021S094)the Science and Technology Planning Projects of Fuzhou Institute of Oceanography(No.2021F08)the Belt&Road Program(No.KXPT-2021-3,CAST)the Ministry of Science and Technology of China(No.2015CB931804)。
文摘Objective:Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied,but there is a lack of effective strategies and drugs for the treatment of tumor metastases.Here,we describe a functional product based on a combination of compounds,which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases,improving anti-cancer treatment,and enhancing immunity and antioxidant capacity.Our designed combination,named MVBL,consists of four inexpensive compounds:L-selenium-methylselenocysteine(MSC),D-α-tocopheryl succinic acid(VES),β-carotene(β-Ca),and L-lysine(Lys).Methods:The effects of MVBL on cell viability,cell cycle,cell apoptosis,cell migration,cell invasion,reactive oxygen species(ROS),and paclitaxel(PTX)-combined treatment were studied in vitro.The inhibition of tumor metastasis,antioxidation,and immune enhancement capacity of MVBL were determined in vivo.Results:MVBL exhibited higher toxicity to tumor cells than to normal cells.It did not significantly affect the cell cycle of cancer cells,but increased their apoptosis.Wound healing,adhesion,and transwell assays showed that MVBL significantly inhibited tumor cell migration,adhesion,and invasion.MVBL sensitized MDA-MB-231 breast cancer cells to PTX,indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs.In mice,experimental data showed that MVBL inhibited tumor metastasis,prolonged their survival time,and enhanced their antioxidant capacity and immune function.Conclusions:This study revealed the roles of MVBL in improving immunity and antioxidation,preventing tumor growth,and inhibiting metastasis in vitro and in vivo.MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.
基金the National Natural Science Foundation of China(Grant No.:82360542)Jiangxi Provincial Natural Science Foundation,China(Grant Nos.:20224BAB214030 and 20224BAB216072)+2 种基金Doctoral Startup Fund of Gannan Medical University,China(Grant Nos.:QD202136 and QD202132)Science and Technology Planning Projects of Fuzhou,China(Grant No.:2021FZR0101)the Natural Science Foundation of Fujian Province,China(Grant No.:2022YZ0104).
文摘Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.
基金supported by the Natural Science Foundation of China(81961138017,81773063,U1505225,81703555,and 81801849).
文摘Dear Editor,Cancer metastasis,dissemination of cancer cells from primary tumors to distant sites,attributes to 90%cancer-related death.1 Although the targeted therapies,bio-nanomaterial-based target delivery,and the consequent adoption of the so-called personalized medicine have obtained notable achievements in some cancers,significant problems still exist with these approaches.2 There are hardly any cancer therapeutic agents that can interfere with metastasized cancer.In recent times,we proposed a novel concept,namely cancer metastasis chemoprevention,which is different from the existing cancer chemotherapy and cancer chemoprevention.Cancer metastasis chemoprevention aims at safely preventing circulating tumor cells(CTCs)and related molecules from gemmating into the metastatic tissues.The strategy does not intend to kill cancer cells as cancer chemotherapy does,nor to aimlessly prevent cancers from carcinogenesis as cancer chemoprevention does.
基金This work was supported by the grants from the National Natural Science Foundation of China(81961138017,81773063,and U1505225)Ministry of Science and Technology of China(2015CB931804)Young and Middle-aged Teacher Education Research Project of Fujian Province,JAT190623。
文摘Dear Editor,Metastasis is the cause of most fatalities in cancer patients and remains the phenomenon poorly understood mechanistically. Deciphering of the regulatory networks underlying the cancer cell metastasis is urgently needed. Nucleolar protein 7 (NOL7) has been reported to function as a tumor suppressor in cervical cancer.1 Our current study reveals a novel tumor-promoting capacity of NOL7 in melanoma. We first detected that NOL7 expression is upregulated in metastatic melanoma as compared with its expression at the primary site through isobaric tag for relative and absolute quantitation proteomic screening, further confirming this finding with the analysis of NOL7 protein and messenger RNA (mRNA) levels (Supplementary Fig. S1). Importantly, NOL7 expression increased with the disease progression from benign nevus to primary melanoma and further to metastatic melanoma (Fig. 1a and Supplementary Fig. S1d). Previous studies have shown that melanoma is commonly associated with the amplification of the chromosome region 6p, particularly 6p21–23, where the NOL7 gene resides, and that this region frequently undergoes heterozygous loss in cervical cancer.2 It might therefore be predicted that NOL7 exhibits a different expression pattern and plays different roles in melanoma and cervical cancer.
基金NSFC 81961138017,81773063,82202355 and 3220422101Belt&Road Program,CAST and (2021FZR0101)Natural Science Foundation of Fujian Province(2021J05210,2021J011046).
文摘The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into law.The cancer crusade costs trillions with disappointing returns,teasing the possibility of a new breakthrough.Cure for cancer post-metastases still seems tantalisingly out of reach.Once metastasized,cancer-related death is extremely difficult,if not impossible,to be reversed.Here we present cancer pre-metastasis chemoprevention strategy that can prevent circulating tumour cells(CTCs)from initiating metastases safely and effectively,and is disparate from the traditional cancer chemotherapy and cancer chemoprevention.Deep learning of the biology of CTCs and their disseminating organotropism,complexity of their adhesion to endothelial niche reveals that if the adhesion of CTCs to their metastasis niche(the first and the most important part in cancer metastatic cascade)can be pharmaceutically interrupted,the lethal metastatic cascade could be prevented from getting initiated.We analyse the key inflammatory and adhesive factors contributing to CTC adhesion/germination,provide pharmacological fundamentals for abortifacients to intervene CTC adhesion to the distant metastasis sites.The adhesion/inhibition ratio(AIR)is defined for selecting the best cancer metastasis chemopreventive candidates.The successful development of such new therapeutic modalities for cancer metastasis chemoprevention has great potential to revolutionise the current ineffective post-metastasis treatments.
文摘In the process of collating the raw data,the authors noticed one inadvertent mistake in Fig.1 that need to be corrected.1 The correct data are provided as follows.The key findings of the article are not affected by these corrections.
