Hormone naive advanced prostate cancer is subdivided into two disease states： biochemical recurrence and traditional M 1 （metastatic） prostate cancer and characterized by no prior hormonal therapy or androgen depri...Hormone naive advanced prostate cancer is subdivided into two disease states： biochemical recurrence and traditional M 1 （metastatic） prostate cancer and characterized by no prior hormonal therapy or androgen deprivation therapy （ADT）. In biochemical recurrence/ prostate-specific antigen （PSA） recurrence, men should be risk-stratified based on their PSA doubling time, the Gleason score and the timing of the recurrence. In general, only men who are at high risk should be considered for early/immediate ADT although this is best done using shared decision with the patient. The type of ADT to be used in biochemical recurrence ranging from oral-only peripheral blockade （peripheral androgen deprivation） to complete hormonal therapy （combined androgen blockade [CAB]） remains in debate owing to lack of randomized controlled trials （RCT）. However, there is good RCT support for use of intermittent hormonal therapy （IHT）. There is also limited research on biomarker response （PSA and testosterone decline） to predict prognosis. On the other hand, in the setting of M1 hormone naive prostate cancer, there are many more RCT＇s to inform our decisions. CAB and gonadotrophin-releasing hormone antagonists perhaps provide a slight efficacy advantage while IHT may be slightly inferior with minimal M1 disease. The PSA nadir at 7 months after starting ADT is a powerful prognostic tool for M1 patients. There is growing recognition that serum testosterone （T） control while on ADT is linked to the development of castrate-resistant prostate cancer. Especially for a M 1 patient, maintaining a serum T below 20-30 ng d1-1 prolongs the response to ADT. Novel oral agents （abiraterone and enzalutamide） may soon find use in hormone naive disease and may alter the treatment landscape. Despite over 75 years of experience with ADT, many questions remain, and the field continues to evolve.展开更多
Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQare thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hosp...Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQare thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer （PCa） cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme.linked immunosorbent assay （ELISA） in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio （OR）： 0.66, 95% confidence interval （CI） =0.48-0.92] and increased plasma adiponectin levels （P= 0.036 and 0,043）, with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa （P=6.7 × 10-3）. ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.展开更多
Reprogramming of metabolism is a hallmark of tumors,which has been explored for therapeutic purposes.Prostate cancer(PCa),particularly advanced and therapy-resistant PCa,displays unique metabolic properties.Targeting ...Reprogramming of metabolism is a hallmark of tumors,which has been explored for therapeutic purposes.Prostate cancer(PCa),particularly advanced and therapy-resistant PCa,displays unique metabolic properties.Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes.Among the many nutrients,glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa.In addition to amino acid metabolism,glutamine is also widely involved in the synthesis of other macromolecules and biomasses.Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients.This review summarizes the metabolic landscape of PCa,with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa,and suggests novel therapeutic strategies.展开更多
The ability of epithelial cells to undergo phenotypic transitions during embryo-genesis, wound healing and malignant pro- gression is now widely accepted as a core biological process termed epithelialmesenchymal trans...The ability of epithelial cells to undergo phenotypic transitions during embryo-genesis, wound healing and malignant pro- gression is now widely accepted as a core biological process termed epithelialmesenchymal transition （EMT）. During cancer progression, the process of EMT has been associated with the acquisition of stemness properties, treatment resistance and metastatic progression, hallmarks of malig- nancy.展开更多
The neurovascular unit and stem cell therapy in ischemic stroke:Ischemic stroke,accounts for approximately 85% of all stroke incidents and is a major global health burden.It is the leading cause of disability and deat...The neurovascular unit and stem cell therapy in ischemic stroke:Ischemic stroke,accounts for approximately 85% of all stroke incidents and is a major global health burden.It is the leading cause of disability and death worldwide,posing immense societal and economic challenges due to the long-term care required for stro ke survivors and the significant healthcare costs associated with its treatment and management(Amarenco et al.,2009).展开更多
The treatment of metastatic renal cell carcinoma(RCC)and urothelial carcinoma(UC)remains a major challenge.Past research has implicated the immune system in tumor surveillance of both malignancies,leading to the appli...The treatment of metastatic renal cell carcinoma(RCC)and urothelial carcinoma(UC)remains a major challenge.Past research has implicated the immune system in tumor surveillance of both malignancies,leading to the application of immunotherapy agents for both cancers.Among them,the most promising agents are the checkpoint blockade drugs,such as antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),programmed death receptor 1(PD-1),and PD-1 ligand(PD-L1).In normal physiology,these immune checkpoints act as inhibitory signals to fine-tune the duration and strength of immune reactions,which is pivotal for maintaining self-tolerance.However,tumor cells also utilize immune checkpoint pathways to evade anti-tumor immune response,leading to disease progression and metastasis.Thus,there has been intense preclinical and clinical effort focused on the application of checkpoint inhibitors in metastatic RCC and UC.To date,nivolumab(anti-PD-1)and atezolizumab(anti-PD-L1)have been approved for the treatment of metastatic RCC and UC,respectively.Despite these successes,challenges remain in how to further improve response rates to immunotherapy and how to select patients that will benefit from this approach.In this report,we review existing data and research on immunotherapy in metastatic RCC and UC.展开更多
Cancer cells undergo metabolic reprogramming to support cell proliferation,growth,and dissemination.Alterations in lipid metabolism,and specifically the uptake and synthesis of fatty acids(FAs),comprise onewelldocumen...Cancer cells undergo metabolic reprogramming to support cell proliferation,growth,and dissemination.Alterations in lipid metabolism,and specifically the uptake and synthesis of fatty acids(FAs),comprise onewelldocumented aspect of this reprogramming.Recent studies have revealed an expanded range of roles played by FA in promoting the aggressiveness of cancer while simultaneously identifying new potential targets for cancer therapy.This article provides a brief review of these advances in our understanding of FA metabolism in cancer,highlighting both recent discoveries and the inherent challenges caused by the metabolic plasticity of cancer cells in targeting lipid metabolism for cancer therapy.展开更多
Alternative polyadenylation(APA)is a molecular process that generates diversity at the 3′end of RNA polymeraseⅡtranscripts from over 60%of human genes.APA is derived from the existence of multiple polyadenylation si...Alternative polyadenylation(APA)is a molecular process that generates diversity at the 3′end of RNA polymeraseⅡtranscripts from over 60%of human genes.APA is derived from the existence of multiple polyadenylation signals(PAS)within the same transcript,and results in the differential inclusion of sequence information at the 3′end.While APA can occur between two PASs allowing for generation of transcripts with distinct coding potential from a single gene,most APA occurs within the untranslated region(3′UTR)and changes the length and content of these non-coding sequences.APA within the 3′UTR can have tremendous impact on its regulatory potential of the mRNA through a variety of mechanisms,and indeed this layer of gene expression regulation has profound impact on processes vital to cell growth and development.Recent studies have particularly highlighted the importance of APA dysregulation in cancer onset and progression.Here,we review the current knowledge of APA and its impacts on mRNA stability,translation,localization and protein localization.We also discuss the implications of APA dysregulation in cancer research and therapy.展开更多
Objective: The DNA repair capacity (DRC) of tumor cells is an important contributor to resistance to radiation and platinum-based drugs. Because DRC may be affected by tumor cell metabolism, we measured DRC in lymphoc...Objective: The DNA repair capacity (DRC) of tumor cells is an important contributor to resistance to radiation and platinum-based drugs. Because DRC may be affected by tumor cell metabolism, we measured DRC in lymphocytes from patients with non-small-cell lung cancer (NSCLC) and compared the findings with the maximum standardized uptake value (SUVmax) on 18 F-fluorodeoxyglucose positron emission tomography (FDG PET) after (chemo)radiation therapy. Methods: This study included 151 patients with stage IA-IV NSCLC who had FDG PET at a single institution and donated blood samples before chemotherapy. We assessed the correlation of DRC, measured in peripheral T lymphocytes by a host-cell reac-tivation assay with SUVmax and their associations with overall survival (OS) time by hazards ratios calculated with a Cox pro-portional hazards regression model. Results: SUVmax of the primary tumor at diagnosis was inversely associated with lymphocyte DRC (r＝－0.175, P＝0.032), particularly among patients with advanced disease (r ＝ －0.218, P ＝ 0.015). However, △SUVmax of primary tumor was not significantly associated with DRC (r＝0.005, P＝0.968). SUVmax of regional lymph nodes at diagnosis (r＝－0.307, P＝0.0008) and after (chemo)radiation treatment (r＝－0.329, P＝0.034) and SUVmax of the primary tumor after (chemo)radiation treatment (r＝－0.253, P＝0.045) were also inversely associated with OS time. Conclusion: DRC was inversely associated with primary tumor SUVmax before treatment but not with △SUVmax after (chemo)radiation.展开更多
Colorectal cancer is a leading cause of cancer deaths.Most colorectal cancer patients eventually develop chemoresistance to the current standard-of-care therapies.Here,we used patient-derived colorectal cancer organoi...Colorectal cancer is a leading cause of cancer deaths.Most colorectal cancer patients eventually develop chemoresistance to the current standard-of-care therapies.Here,we used patient-derived colorectal cancer organoids to demonstrate that resistant tumor cells undergo significant chromatin changes in response to oxaliplatin treatment.Integrated transcriptomic and chromatin accessibility analyses using ATAC-Seq and RNA-Seq identified a group of genes associated with significantly increased chromatin accessibility and upregulated gene expression.CRISPR/Cas9 silencing of fibroblast growth factor receptor 1(FGFR1)and oxytocin receptor(OXTR)helped overcome oxaliplatin resistance.Similarly,treatment with oxaliplatin in combination with an FGFR1 inhibitor(PD166866)or an antagonist of OXTR(L-368,899)suppressed chemoresistant organoids.However,oxaliplatin treatment did not activate either FGFR1 or OXTR expression in another resistant organoid,suggesting that chromatin accessibility changes are patient-specific.The use of patient-derived cancer organoids in combination with transcriptomic and chromatin profiling may lead to precision treatments to overcome chemoresistance in colorectal cancer.展开更多
Human health is intimately connected and tied to the health of our environment and ecosystem,with only a very small fraction of the risk for chronic diseases explained by genetics alone.Companion animals are prone to ...Human health is intimately connected and tied to the health of our environment and ecosystem,with only a very small fraction of the risk for chronic diseases explained by genetics alone.Companion animals are prone to disease types that are shared with people,including cancers and endocrine disorders,reinforcing the thought that environmental factors contribute to the risks for chronic diseases.These factors include air and water pollution and the built environment.As such,there is increasing interest in pursuing research with companion animals,and specifically dogs,as sentinel species to inform comparative health assessments and identify risk factors for disease.Of the canine diseases for which environmental exposure research has been published,cancers have received the most attention.This review summarizes two main aspects of this comparative approach:(1)cancers that occur in dogs and which are similar to humans and(2)research investigating environmental exposures and health outcomes in dogs.The goal of this review is to highlight the diverse conditions in which pet dogs may provide unique perspectives and advantages to examine relationships between environmental exposures and health outcomes,with an emphasis on chemical pollution and cancer.Furthermore,this review seeks to raise awareness and stimulate discussion around the best practices for the use of companion animals as environmental health sentinels.展开更多
The delivery of lipid nanoparticle(LNP)-based mRNA therapeutics has captured the attention of the vaccine research community as an innovative and versatile tooi for treating a variety of human malignancies.mRNA vaccin...The delivery of lipid nanoparticle(LNP)-based mRNA therapeutics has captured the attention of the vaccine research community as an innovative and versatile tooi for treating a variety of human malignancies.mRNA vaccines are now in the limelight as an alternative to conventional vaccines owing to their high precision,low-cost,rapid manufacture,and superior safety profile.Multiple mRNA vaccine platforms have been developed to target several types of cancer,and many have demonstrated encouraging results in animal models and human trials.The effectiveness of these new mRNA vaccines depends on the efficacy and stability of the antigen(s)of interest generated and the reliability of their delivery to antigen-presenting cells(APCs),especially dendritic celis(DCs).In this review,we provide a detailed overview of mRNA vaccines and their delivery strategies and consider future directions and challenges in advancing and expanding this promising vaccine platform to widespread therapeutic use against cancer.展开更多
A broad understanding of the tumor immune landscape has led to a revolution of immune checkpoint inhibitors in the treatment of multiple cancer types.In genitourinary malignancies,immune checkpoint inhibitors have imp...A broad understanding of the tumor immune landscape has led to a revolution of immune checkpoint inhibitors in the treatment of multiple cancer types.In genitourinary malignancies,immune checkpoint inhibitors have improved outcomes for patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma;however,these treatments have not yet proven broadly beneficial for patients with metastatic prostate cancer.Numerous prospective trials are ongoing to further improve outcomes with immunotherapy combinations and for biomarker development to predict benefit from immune checkpoint inhibition.This perspective article highlights our current immunotherapy approaches in each of the genitourinary malignancies and the ongoing clinical trials that may inform our future treatments in renal,urothelial,and prostate cancers.展开更多
文摘Hormone naive advanced prostate cancer is subdivided into two disease states： biochemical recurrence and traditional M 1 （metastatic） prostate cancer and characterized by no prior hormonal therapy or androgen deprivation therapy （ADT）. In biochemical recurrence/ prostate-specific antigen （PSA） recurrence, men should be risk-stratified based on their PSA doubling time, the Gleason score and the timing of the recurrence. In general, only men who are at high risk should be considered for early/immediate ADT although this is best done using shared decision with the patient. The type of ADT to be used in biochemical recurrence ranging from oral-only peripheral blockade （peripheral androgen deprivation） to complete hormonal therapy （combined androgen blockade [CAB]） remains in debate owing to lack of randomized controlled trials （RCT）. However, there is good RCT support for use of intermittent hormonal therapy （IHT）. There is also limited research on biomarker response （PSA and testosterone decline） to predict prognosis. On the other hand, in the setting of M1 hormone naive prostate cancer, there are many more RCT＇s to inform our decisions. CAB and gonadotrophin-releasing hormone antagonists perhaps provide a slight efficacy advantage while IHT may be slightly inferior with minimal M1 disease. The PSA nadir at 7 months after starting ADT is a powerful prognostic tool for M1 patients. There is growing recognition that serum testosterone （T） control while on ADT is linked to the development of castrate-resistant prostate cancer. Especially for a M 1 patient, maintaining a serum T below 20-30 ng d1-1 prolongs the response to ADT. Novel oral agents （abiraterone and enzalutamide） may soon find use in hormone naive disease and may alter the treatment landscape. Despite over 75 years of experience with ADT, many questions remain, and the field continues to evolve.
文摘Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQare thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer （PCa） cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme.linked immunosorbent assay （ELISA） in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio （OR）： 0.66, 95% confidence interval （CI） =0.48-0.92] and increased plasma adiponectin levels （P= 0.036 and 0,043）, with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa （P=6.7 × 10-3）. ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.
基金This work was partially supported by the National Natural Science Foundation of China(No.81902611,No.82272886,and No.82200484)the Natural Science Foundation of Anhui Education Department(No.2022AH030118).
文摘Reprogramming of metabolism is a hallmark of tumors,which has been explored for therapeutic purposes.Prostate cancer(PCa),particularly advanced and therapy-resistant PCa,displays unique metabolic properties.Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes.Among the many nutrients,glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa.In addition to amino acid metabolism,glutamine is also widely involved in the synthesis of other macromolecules and biomasses.Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients.This review summarizes the metabolic landscape of PCa,with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa,and suggests novel therapeutic strategies.
文摘The ability of epithelial cells to undergo phenotypic transitions during embryo-genesis, wound healing and malignant pro- gression is now widely accepted as a core biological process termed epithelialmesenchymal transition （EMT）. During cancer progression, the process of EMT has been associated with the acquisition of stemness properties, treatment resistance and metastatic progression, hallmarks of malig- nancy.
基金supported by the NIH National Cancer Institute career development award(K25CA201545,to WL)。
文摘The neurovascular unit and stem cell therapy in ischemic stroke:Ischemic stroke,accounts for approximately 85% of all stroke incidents and is a major global health burden.It is the leading cause of disability and death worldwide,posing immense societal and economic challenges due to the long-term care required for stro ke survivors and the significant healthcare costs associated with its treatment and management(Amarenco et al.,2009).
文摘The treatment of metastatic renal cell carcinoma(RCC)and urothelial carcinoma(UC)remains a major challenge.Past research has implicated the immune system in tumor surveillance of both malignancies,leading to the application of immunotherapy agents for both cancers.Among them,the most promising agents are the checkpoint blockade drugs,such as antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),programmed death receptor 1(PD-1),and PD-1 ligand(PD-L1).In normal physiology,these immune checkpoints act as inhibitory signals to fine-tune the duration and strength of immune reactions,which is pivotal for maintaining self-tolerance.However,tumor cells also utilize immune checkpoint pathways to evade anti-tumor immune response,leading to disease progression and metastasis.Thus,there has been intense preclinical and clinical effort focused on the application of checkpoint inhibitors in metastatic RCC and UC.To date,nivolumab(anti-PD-1)and atezolizumab(anti-PD-L1)have been approved for the treatment of metastatic RCC and UC,respectively.Despite these successes,challenges remain in how to further improve response rates to immunotherapy and how to select patients that will benefit from this approach.In this report,we review existing data and research on immunotherapy in metastatic RCC and UC.
基金This work was supported by the Startup funds at Duke University School of Medicine to M.C.and the National Institutes of Health(Grants No.5R01CA205001-03 and 5R01CA200853-03)to J.H.
文摘Cancer cells undergo metabolic reprogramming to support cell proliferation,growth,and dissemination.Alterations in lipid metabolism,and specifically the uptake and synthesis of fatty acids(FAs),comprise onewelldocumented aspect of this reprogramming.Recent studies have revealed an expanded range of roles played by FA in promoting the aggressiveness of cancer while simultaneously identifying new potential targets for cancer therapy.This article provides a brief review of these advances in our understanding of FA metabolism in cancer,highlighting both recent discoveries and the inherent challenges caused by the metabolic plasticity of cancer cells in targeting lipid metabolism for cancer therapy.
文摘Alternative polyadenylation(APA)is a molecular process that generates diversity at the 3′end of RNA polymeraseⅡtranscripts from over 60%of human genes.APA is derived from the existence of multiple polyadenylation signals(PAS)within the same transcript,and results in the differential inclusion of sequence information at the 3′end.While APA can occur between two PASs allowing for generation of transcripts with distinct coding potential from a single gene,most APA occurs within the untranslated region(3′UTR)and changes the length and content of these non-coding sequences.APA within the 3′UTR can have tremendous impact on its regulatory potential of the mRNA through a variety of mechanisms,and indeed this layer of gene expression regulation has profound impact on processes vital to cell growth and development.Recent studies have particularly highlighted the importance of APA dysregulation in cancer onset and progression.Here,we review the current knowledge of APA and its impacts on mRNA stability,translation,localization and protein localization.We also discuss the implications of APA dysregulation in cancer research and therapy.
文摘Objective: The DNA repair capacity (DRC) of tumor cells is an important contributor to resistance to radiation and platinum-based drugs. Because DRC may be affected by tumor cell metabolism, we measured DRC in lymphocytes from patients with non-small-cell lung cancer (NSCLC) and compared the findings with the maximum standardized uptake value (SUVmax) on 18 F-fluorodeoxyglucose positron emission tomography (FDG PET) after (chemo)radiation therapy. Methods: This study included 151 patients with stage IA-IV NSCLC who had FDG PET at a single institution and donated blood samples before chemotherapy. We assessed the correlation of DRC, measured in peripheral T lymphocytes by a host-cell reac-tivation assay with SUVmax and their associations with overall survival (OS) time by hazards ratios calculated with a Cox pro-portional hazards regression model. Results: SUVmax of the primary tumor at diagnosis was inversely associated with lymphocyte DRC (r＝－0.175, P＝0.032), particularly among patients with advanced disease (r ＝ －0.218, P ＝ 0.015). However, △SUVmax of primary tumor was not significantly associated with DRC (r＝0.005, P＝0.968). SUVmax of regional lymph nodes at diagnosis (r＝－0.307, P＝0.0008) and after (chemo)radiation treatment (r＝－0.329, P＝0.034) and SUVmax of the primary tumor after (chemo)radiation treatment (r＝－0.253, P＝0.045) were also inversely associated with OS time. Conclusion: DRC was inversely associated with primary tumor SUVmax before treatment but not with △SUVmax after (chemo)radiation.
基金WethankDukeCenterforGenomicandComputational Biology sequencingcorefacilityforresearchsupport.This work wassupportedbyNIHNCIU01CA217514andU01 CA214300.
文摘Colorectal cancer is a leading cause of cancer deaths.Most colorectal cancer patients eventually develop chemoresistance to the current standard-of-care therapies.Here,we used patient-derived colorectal cancer organoids to demonstrate that resistant tumor cells undergo significant chromatin changes in response to oxaliplatin treatment.Integrated transcriptomic and chromatin accessibility analyses using ATAC-Seq and RNA-Seq identified a group of genes associated with significantly increased chromatin accessibility and upregulated gene expression.CRISPR/Cas9 silencing of fibroblast growth factor receptor 1(FGFR1)and oxytocin receptor(OXTR)helped overcome oxaliplatin resistance.Similarly,treatment with oxaliplatin in combination with an FGFR1 inhibitor(PD166866)or an antagonist of OXTR(L-368,899)suppressed chemoresistant organoids.However,oxaliplatin treatment did not activate either FGFR1 or OXTR expression in another resistant organoid,suggesting that chromatin accessibility changes are patient-specific.The use of patient-derived cancer organoids in combination with transcriptomic and chromatin profiling may lead to precision treatments to overcome chemoresistance in colorectal cancer.
文摘Human health is intimately connected and tied to the health of our environment and ecosystem,with only a very small fraction of the risk for chronic diseases explained by genetics alone.Companion animals are prone to disease types that are shared with people,including cancers and endocrine disorders,reinforcing the thought that environmental factors contribute to the risks for chronic diseases.These factors include air and water pollution and the built environment.As such,there is increasing interest in pursuing research with companion animals,and specifically dogs,as sentinel species to inform comparative health assessments and identify risk factors for disease.Of the canine diseases for which environmental exposure research has been published,cancers have received the most attention.This review summarizes two main aspects of this comparative approach:(1)cancers that occur in dogs and which are similar to humans and(2)research investigating environmental exposures and health outcomes in dogs.The goal of this review is to highlight the diverse conditions in which pet dogs may provide unique perspectives and advantages to examine relationships between environmental exposures and health outcomes,with an emphasis on chemical pollution and cancer.Furthermore,this review seeks to raise awareness and stimulate discussion around the best practices for the use of companion animals as environmental health sentinels.
基金supported by funding from the National Institutes of Health(R01CA266510 to M.C.)Department of Defense Prostate Cancer Research Program(W81XWH2010185 to M.C.).
文摘The delivery of lipid nanoparticle(LNP)-based mRNA therapeutics has captured the attention of the vaccine research community as an innovative and versatile tooi for treating a variety of human malignancies.mRNA vaccines are now in the limelight as an alternative to conventional vaccines owing to their high precision,low-cost,rapid manufacture,and superior safety profile.Multiple mRNA vaccine platforms have been developed to target several types of cancer,and many have demonstrated encouraging results in animal models and human trials.The effectiveness of these new mRNA vaccines depends on the efficacy and stability of the antigen(s)of interest generated and the reliability of their delivery to antigen-presenting cells(APCs),especially dendritic celis(DCs).In this review,we provide a detailed overview of mRNA vaccines and their delivery strategies and consider future directions and challenges in advancing and expanding this promising vaccine platform to widespread therapeutic use against cancer.
基金was supported by the National Institutes of Health(Grants No.5R01CA205001-03,5R01CA212403-02 and 5R01CA200853-03).
文摘A broad understanding of the tumor immune landscape has led to a revolution of immune checkpoint inhibitors in the treatment of multiple cancer types.In genitourinary malignancies,immune checkpoint inhibitors have improved outcomes for patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma;however,these treatments have not yet proven broadly beneficial for patients with metastatic prostate cancer.Numerous prospective trials are ongoing to further improve outcomes with immunotherapy combinations and for biomarker development to predict benefit from immune checkpoint inhibition.This perspective article highlights our current immunotherapy approaches in each of the genitourinary malignancies and the ongoing clinical trials that may inform our future treatments in renal,urothelial,and prostate cancers.
