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Targeting innate sensing in the tumor microenvironment to improve immunotherapy

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Cellular & Molecular Immunology 2020年第1期17卷 13-26页

作者： Zhida Liu Yang-Xin Fu Department of Pathology UT Southwestern Medical CenterDallasTX 75235USA Department of Immunology UT Southwestern Medical CenterDallasTX 75235USA

The innate immune sensing pathways play critical roles in the defense against pathogen infection,but their roles in cancer immunosurveillance and cancer therapies are less *** propose that defective innate immune sensing inside the tumor microenvironment might limit T-cell responses to immunotherapy.A recent mechanistic understanding of conventional therapies revealed that both innate immune sensing and T-cell responses are essential for optimal antitumor efficacy.T-cell-based immunotherapy,particularly immune checkpoint blockade,has achieved great success in reactivating antitumor immune responses to lead to tumor regression,but only in a small fraction of ***,incorporating conventional therapy that can increase innate sensing and immunotherapy should lead to promising strategies for cancer ***,we review the innate sensing pathways related to cancer initiation/progression and therapies,summarize the recent key findings in innate immune sensing related to conventional therapies,evaluate current combination strategies,and highlight the potential issues of combinational therapies in terms of antitumor efficacy and toxicities.

关键词： Innate immune sensing Conventional therapy Immunotherapy

Hippo signaling and epithelial cell plasticity in mammalian liver development, homeostasis, injury and disease

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Science China(Life Sciences) 2019年第12期62卷 1609-1616页

作者： Randy L.Johnson Department of Cancer Biology University of Texas MD Anderson Cancer Center

A traditional view of cellular differentiation is unidirectional: progenitor cells adopt specific fates in response to environmental cues resulting in deployment of cell-specific gene expression programs and acquisition of unique differentiated cellular properties such as production of structural and functional proteins that define individual cell types. In both development and in tissue repair stem and progenitor cells are thought to both self-renew to maintain the pool of precursors and to expand to give rise to transient amplifying and differentiated cell types. Recently, however, it has become appreciated that differentiated cell types can be reprogrammed to adopt progenitor and stem cell properties. In the case of epithelial cells in the mammalian liver, hepatocytes and biliary epithelial cells there is a significant degree of plasticity between these lineages that has been implicated in mechanisms of tissue repair and in liver pathologies such as cancer. Recent studies have highlighted the role of Hippo signaling, an emerging growth control and tumor suppressor pathway, in regulating epithelial cell plasticity in the mammalian liver and in this review, the role of cellular plasticity and Hippo signaling in regulating normal and abnormal tissue responses in the mammalian liver will be discussed.

关键词： liver homeostasis plasticity regeneration cancer Hippo pathway

The exploration of N6-deoxyadenosine methylation in mammalian genomes

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Protein & Cell 2021年第10期12卷 756-768页

作者： Xuwen Li Zijian Zhang Xinlong Luo Jacob Schrier Andrew D.Yang Tao P.Wu Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Medical Scientist Training Program Baylor College of MedicineHoustonTX 77030USA Huffington Center on Aging Baylor College of MedicineHoustonTX 77030USA Dan L Duncan Comprehensive Cancer Center Baylor College of MedicineHoustonTX 77030USA

N^(6)-methyladenine(N^(6)-mA,m^(6)dA,or 6mA),a prevalent DNA modification in prokaryotes,has recently been identified in higher eukaryotes,including *** 6mA has been well-studied in prokaryotes,the function and regulatory mechanism of 6mA in eukaryotes are still poorly *** studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes,from transposable-element suppression to environmental stress ***,we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes,predominantly mammals.

关键词： DNA N^(6)-methyladenine(6mA) mammalian DNA modification norvcanonical mammalian DNA methylation

Temperature-sensitive polymeric nanogels encapsulating withβ-cyclodextrin and ICG complex for high-resolution deep-tissue ultrasound-switchable fluorescence imaging

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Nano Research 2020年第4期13卷 1100-1110页

作者： Ruilin Liu Tingfeng Yao Yang Liu Shuai Yu Liqin Ren Yi Hong Kytai T.Nguyen Baohong Yuan Ultrasound and Optical Imaging Laboratory Department of Bioengineeringthe University of Texas at ArlingtonArlingtonTX 76019USA Joint Biomedical Engineering Program the University of Texas at Arlington and the University of Texas Southwestern Medical CenterDallasTX 75390USA Department of Bioengineering the University of Texas at ArlingtonArlingtonTX 76019USA

One of the thorny problems currently impeding the applications of the fluorescence imaging technique is the poor spatial resolution in deep ***-switchable fluorescence(USF)imaging is a novel imaging tool that has recently been explored to possibly surmount the above-mentioned ***,αβ-cyclodextrin/indocyanine green(ICG)complex-encapsulated poly(N-isopropylacrylamide)(PNIPAM)nanogel was synthesized and studied for ex vivo/in vivo deep tissue/high-resolution near infrared USF(NIR-USF)*** be specific,our results revealed that the average diameter of the as-prepared nanogels was significantly decreased to-32 nm from-335 nm compared to the reported ICG-PNIPAM ***,the excitation/emission characteristics of the ICG itself in present nanogels were almost completely retained,and the resultant nanogel exhibited high physiological stability and positive *** particular,the signal-to-noise ratio of the USF image for the PNIPAM/P-cyclodextrin/ICG nanogel(33.01±2.42 dB)was prominently higher than that of the ICG-PNIPAM nanoparticles(18.73±0.33 dB)in 1.5-cm-thick chicken breast *** NIR-USF imaging in 3.5-cm-thick chicken breast tissues was achieved using this new *** e x v iv o NIR-USF imaging of the mouse liver was also successfully *** experiments showed that the present nanogels were able to be effectively accumulated into U87 tumor-bearing mice via enhanced permeability and retention effects,and the high-resolution NIR-USF imaging of in v ivo tumor was efficiently *** metabolism and in vivo biodistribution of the nanogels were ***,the results suggest that the current nanogel is a highly promising NIR-USF probe for deep tissue and high-resolution USF imaging.

关键词： deep tissue imaging high-resolution ultrasound-switchable NIR fluorescence imaging in vivo imaging

Beta-adrenergic signaling on neuroendocrine differentiation, angiogenesis, and metastasis in prostate cancer progression

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Asian Journal of Andrology 2019年第3期21卷 253-259页

作者： Yicheng Zhao Wenliang Li Texas Therapeutics Institute Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at Houston Houston TX 77030 USA Graduate School of Biomedical Sciences University of Texas Health Science Center at Houston Houston TX 77030 USA Division of Oncology Department of Internal Medicine and Memorial Herman Cancer Center University of Texas Health Science Center at Houston Houston TX 77030 USA

Prostate cancer is a complex, heterogeneous disease that mainly affects the older male population with a high-mortality rate. The mechanisms underlying prostate cancer progression are still incompletely understood. Beta-adrenergic signaling has been shown to regulate multiple cellular processes as a mediator of chronic stress. Recently, beta-adrenergic signaling has been reported to affect the development of aggressive prostate cancer by regulating neuroendocrine differentiation, angiogenesis, and metastasis. Here, we briefly summarize and discuss recent advances in these areas and their implications in prostate cancer therapeutics. We aim to provide a better understanding of the contribution of beta-adrenergic signaling to the progression of aggressive prostate cancer.

关键词： angiogenesis beta-adrenergic signaling pathway metastasis neuroendocrine differentiation prostate cancer

DNA mismatch repair in trinucleotide repeat instability

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Science China(Life Sciences) 2017年第10期60卷 1087-1092页

作者： Jinzhen Guo Luping Chen Guo-Min Li Department of Radiation Oncology University of Texas Southwestern Medical Center Department of Biochemistry and Molecular Medicine Norris Comprehensive Cancer Center University of Southern California Keck School of Medicine

Trinucleotide repeat expansions cause over 30 severe neuromuscular and neurodegenerative disorders, including Huntington's disease, myotonic dystrophy type 1, and fragile X syndrome. Although previous studies have substantially advanced the understanding of the disease biology, many key features remain unknown. DNA mismatch repair(MMR) plays a critical role in genome maintenance by removing DNA mismatches generated during DNA replication. However, MMR components,particularly mismatch recognition protein MutSβ and its interacting factors MutLα and MutLγ, have been implicated in trinucleotide repeat instability. In this review, we will discuss the roles of these key MMR proteins in promoting trinucleotide repeat instability.

关键词： DNA mismatch repair trinucleotide repeat instability neurodegenerative diseases MutSβ

Surface-ligand effect on radiosensitization of ultrasmall luminescent gold nanoparticles

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Journal of Innovative Optical Health Sciences 2016年第4期9卷 66-73页

作者： Xingya Jiang Bujie Du Mengxiao Yu Xun Jia Jie Zheng Department of Chemistry and Biochemistry The University of Texas at Dallas 800 W.Campbell Rd. RichardsonTX 75080USA Department of Radiation Oncology The University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard DallasTX 75390USA

Gold nanoparticles(AuNPs)could serve as pot ential radiother apy sensitizers because of their exceptional biocompatibility and high.Z material nature;however,since in vitro and in vivo behaviors of AuNPs are determined not only by their particle size but also by their surface chemistries,whether surface ligands can affect their radiosensitization has seldom been investi-gated in the radiosensitization of *** conducting head-to-head comparison on radio-sensitization of two kinds of ultrasmall(~2 nm)near-infrared(NIR)emitting AuNPs that are coated with zwitterionic glutathione and neutr al polyethylene glyol(PEG)ligands,respectively,we found that zwitterionic glut athione coated AuNPs(GS-AuNPs)can reduce survival rates of MCF-7 cells under irr adiation of clinically used megavoltage photon beam at low dosage of~2.25 *** the other hand,PEG-AuNPs can serve as a radiation-protecting agent and enabled MCF-7 cells more resistant to the irradiation,clearly indicating the key role of surface cheistry in radiosensitization of *** detailed studies suggested that such difference was inde-pendent of cellular uptake and its eficiency,but might be related to the ligand-induced difference in photoelectron generation and/or inter actions between AuNPs and X-ray triggered reactive oxygen species(ROS).

关键词： Gold nanoparticles surface-ligand cell uptake radiosensitizer radiation-protecting

Long non-coding RNAs regulation of therapeutic resistance

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Cancer Drug Resistance 2019年第3期2卷 550-567页

作者： Susan Tsang Tajhal Patel Jason T.Yustein Integrative Molecular and Biomedical Sciences Program Baylor College of MedicineHoustonTX 77030USA Department of Pediatrics Texas Children’s Cancer CenterBaylor College of MedicineHoustonTX 77030USA.

Non-protein coding RNAs have emerged as a regulator of cell signaling and cancer progression through regulation of cell proliferation,metastatic burden,and cancer stem cell capacity.A subtype of non-protein coding RNA is long non-protein coding RNA(lncRNA).Besides their aforementioned roles in cancer cell biology,dysregulation of lncRNAs contribute to resistance to therapeutic treatments.A couple of important therapeutic classes are chemotherapy and targeted/hormone *** review highlights the variety of malignancies affected by lncRNA dysregulation and the underlying mechanism causing therapeutic resistance.

关键词： Long non-protein coding RNA cancer chemotherapeutic resistance target therapeutics hormone therapy and microRNA sponge

Synthesis of cobalt, palladium, and rhenium nanoparticles

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Tungsten 2020年第3期2卷 261-288页

作者： Shahab Ranjbar Bahadori Ryan Hart Yao‑Wu Hao Department of Materials Science and Engineering University of Texas at ArlingtonArlingtonTX 76019USA

Over the past decade,metal nanoparticles(MNPs)have attracted extensive attention due to their unique physiochemical properties that make them highly applicable in various fields such as chemical sensing,energy storage,catalysis,medicine,and environmental *** physiochemical properties depend drastically on the MNP size and morphology,which are largely determined by their synthesis *** on MNPs predominantly focused on coinage metals(Au,Ag and Cu),but in the last decade research on metals with a relatively high melting temperature such as Pd,Co,and Re has seen rapid increases,mainly driven by their potential applications as *** paper presents the recent advances on different synthesis techniques of Co,Pd,and Re nanoparticles,their resulting nanostructures,as well as existing and potential applications.

关键词： Nanotechnology Co nanoparticle Pd nanoparticle Re nanoparticle Nanoparticle synthesis