The initiation and progression of cancer not only involves genetic abnormalities, but also epigenetic alterations, such as DNA methylation and histone modifications. Epigenetics refers to the heritable changes that do...The initiation and progression of cancer not only involves genetic abnormalities, but also epigenetic alterations, such as DNA methylation and histone modifications. Epigenetics refers to the heritable changes that do not involve any structural changes in the target gene, i.e., DNA sequence and protein sequence. Thus, these epigenetic aberrations are potentially reversible, allowing the malignant cells to revert to a state with more normal characteristics. The use of epigenetics is emerging as an effective and promising approach to treat cancer. Epigenetic drugs, which target two well- known epigenetic pathways, namely, DNA methyltransferases and histone deacetylases, are already being applied for the cancer treatment. In the current study, an overview regarding the under-standing of epigenetic alterations in the development of cancer and the current state of epigenetic drug discovery is provided.展开更多
Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for L...Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.展开更多
G-quadruplex secondary structures are four-stranded globular nucleic acid structures form in the specific DNA and RNA G-rich sequences with biological significance such as human telomeres,oncogene-promoter regions,rep...G-quadruplex secondary structures are four-stranded globular nucleic acid structures form in the specific DNA and RNA G-rich sequences with biological significance such as human telomeres,oncogene-promoter regions,replication initiation sites,and 5′and 3′-untranslated(UTR)regions.The non-canonical G-quadruplex secondary structures can readily form under physiologically relevant ionic conditions and are considered to be new molecular target for cancer therapeutics.This review discusses the essential progress in our lab related to the structures and functions of biologically relevant DNA G-quadruplexes in human gene promoters and telomeres,and the opportunities presented for the development of G-quadruplex-targeted smallmolecule drugs.展开更多
Sphingosine-1-phosphate(S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival,cell proliferation, cell migration, angiogenesis and many other cellular processes. S1 P ...Sphingosine-1-phosphate(S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival,cell proliferation, cell migration, angiogenesis and many other cellular processes. S1 P either activates S1 P receptors(S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1 P signaling and its pathogenic roles in diseases as well as in developing modulators of S1 P signaling, including S1 P agonists, S1 P antagonists and sphingosine kinase(SphK) inhibitors.Ceramide and S1 P have been defined as reciprocal regulators of cell fate, and S1 P signaling has been shown to be crucial for the pathogenesis of various diseases, including autoimmune diseases, inflammation and cancer; therefore, targeting S1 P signaling may curtail the process of pathogenesis and serve as a potential therapeutic target for the treatment of these diseases. In this review, we describe recent advances in our understanding of S1 P signaling in cancer development(particularly in inflammationassociated cancer) as well as in innate and adaptive immunity, and we also discuss modulators of S1 P signaling in cancer treatment.展开更多
Mitochondria are the power plants of the cell and play key roles in activating the apoptotic pathway in cancer cells,which are readily susceptible to cytotoxic reactive oxygen species and temperature elevations.Herein...Mitochondria are the power plants of the cell and play key roles in activating the apoptotic pathway in cancer cells,which are readily susceptible to cytotoxic reactive oxygen species and temperature elevations.Herein,we develop a"nanomissile"that targets mitochondria to enhance tumor treatment effects by facilitating mitochondrial dysfunction and releasing cytochrome C to activate the apoptotic pathway of cancer cells under 650-nm laser irradiation.Porphyringrafted polydopamine nanomaterial(PTPF-MitP)is designed as a nanomissile,with integrated O;-evolving photodynamic therapy and moderate photothermal therapy,which can selectively deliver to the mitochondria through a targeting unit,MitP.The cytotoxicity of PTPF-MitP to human lung tumor cells is twice as high as that of PTPF that does not have mitochondrial targeting units.In addition,it represents a realtime visualization and highly efficient treatment for tumor sites in vivo.This development represents a viable strategy for cancer therapy.展开更多
文摘The initiation and progression of cancer not only involves genetic abnormalities, but also epigenetic alterations, such as DNA methylation and histone modifications. Epigenetics refers to the heritable changes that do not involve any structural changes in the target gene, i.e., DNA sequence and protein sequence. Thus, these epigenetic aberrations are potentially reversible, allowing the malignant cells to revert to a state with more normal characteristics. The use of epigenetics is emerging as an effective and promising approach to treat cancer. Epigenetic drugs, which target two well- known epigenetic pathways, namely, DNA methyltransferases and histone deacetylases, are already being applied for the cancer treatment. In the current study, an overview regarding the under-standing of epigenetic alterations in the development of cancer and the current state of epigenetic drug discovery is provided.
基金J. Chad Brenner received funding from NIH (Grants No. U01DE025184 and P30: CA046592 S1)Andrew C. Birkeland and Rebecca Hoesli received support from University of Michigan Otolaryngology Resident Research (Grant No. T32DC005356)Megan L. Ludwig was supported by NIH (Grant No. T-32-GM007315)
文摘Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.
文摘G-quadruplex secondary structures are four-stranded globular nucleic acid structures form in the specific DNA and RNA G-rich sequences with biological significance such as human telomeres,oncogene-promoter regions,replication initiation sites,and 5′and 3′-untranslated(UTR)regions.The non-canonical G-quadruplex secondary structures can readily form under physiologically relevant ionic conditions and are considered to be new molecular target for cancer therapeutics.This review discusses the essential progress in our lab related to the structures and functions of biologically relevant DNA G-quadruplexes in human gene promoters and telomeres,and the opportunities presented for the development of G-quadruplex-targeted smallmolecule drugs.
基金financial support from the National Natural Science Foundation of China(91229204)the Major Project of the Chinese National Programs for Fundamental Research and Development(2015CB910304)
文摘Sphingosine-1-phosphate(S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival,cell proliferation, cell migration, angiogenesis and many other cellular processes. S1 P either activates S1 P receptors(S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1 P signaling and its pathogenic roles in diseases as well as in developing modulators of S1 P signaling, including S1 P agonists, S1 P antagonists and sphingosine kinase(SphK) inhibitors.Ceramide and S1 P have been defined as reciprocal regulators of cell fate, and S1 P signaling has been shown to be crucial for the pathogenesis of various diseases, including autoimmune diseases, inflammation and cancer; therefore, targeting S1 P signaling may curtail the process of pathogenesis and serve as a potential therapeutic target for the treatment of these diseases. In this review, we describe recent advances in our understanding of S1 P signaling in cancer development(particularly in inflammationassociated cancer) as well as in innate and adaptive immunity, and we also discuss modulators of S1 P signaling in cancer treatment.
基金supported by the National Natural Science Foundation of China(21705117,22174110,21904095 and 22004089)the Elite Scholar Program of Tianjin University(2019XRG-0065)+2 种基金the Program of Tianjin Science and Technology Major Project and Engineering(19ZXYXSY00090)the Program for Chang Jiang Scholars and Innovative Research Team,Ministry of Education,China(IRT-16R61)the Special Fund Project for the Central Government to Guide Local Science and Technology Development(2020)。
文摘Mitochondria are the power plants of the cell and play key roles in activating the apoptotic pathway in cancer cells,which are readily susceptible to cytotoxic reactive oxygen species and temperature elevations.Herein,we develop a"nanomissile"that targets mitochondria to enhance tumor treatment effects by facilitating mitochondrial dysfunction and releasing cytochrome C to activate the apoptotic pathway of cancer cells under 650-nm laser irradiation.Porphyringrafted polydopamine nanomaterial(PTPF-MitP)is designed as a nanomissile,with integrated O;-evolving photodynamic therapy and moderate photothermal therapy,which can selectively deliver to the mitochondria through a targeting unit,MitP.The cytotoxicity of PTPF-MitP to human lung tumor cells is twice as high as that of PTPF that does not have mitochondrial targeting units.In addition,it represents a realtime visualization and highly efficient treatment for tumor sites in vivo.This development represents a viable strategy for cancer therapy.
