The immunology of renal cell carcinoma Díaz-Montero, C Marcela; Rini, Brian I; Finke, James H
Nature reviews. Nephrology,
12/2020, Letnik:
16, Številka:
12
Journal Article
Recenzirano
Renal cell carcinoma (RCC) is the most common type of kidney cancer and comprises several subtypes with unique characteristics. The most common subtype (~70% of cases) is clear-cell RCC. RCC is ...considered to be an immunogenic tumour but is known to mediate immune dysfunction in large part by eliciting the infiltration of immune-inhibitory cells, such as regulatory T cells and myeloid-derived suppressor cells, into the tumour microenvironment. Several possible mechanisms have been proposed to explain how these multiple tumour-infiltrating cell types block the development of an effective anti-tumour immune response, including inhibition of the activity of effector T cells and of antigen presenting cells via upregulation of suppressive factors such as checkpoint molecules. Targeting immune suppression using checkpoint inhibition has resulted in clinical responses in some patients with RCC and combinatorial approaches involving checkpoint blockade are now standard of care in patients with advanced RCC. However, a substantial proportion of patients do not benefit from checkpoint blockade. The identification of reliable biomarkers of response to checkpoint blockade is crucial to facilitate improvements in the clinical efficacy of these therapies. In addition, there is a need for the development of other immune-based strategies that address the shortcomings of checkpoint blockade, such as adoptive cell therapies.
Chemical gardens and clock reactions are two of the best‐known demonstration reactions in chemistry. Until now these have been separate categories. We have discovered that a chemical garden confined ...to two dimensions is a clock reaction involving a phase change, so that after a reproducible and controllable induction period it explodes.
Chemical gardens and clock reactions are two of the best‐known demonstration reactions in chemistry. Until now these have been separate categories. We have discovered that a chemical garden confined to two dimensions is a clock reaction involving a phase change, so that after a reproducible and controllable induction period it explodes.
Although the polymorphism of calcium carbonate is well known, and its polymorphs—calcite, aragonite, and vaterite—have been highly studied in the context of biomineralization, polyamorphism is a much ...more recently discovered phenomenon, and the existence of more than one amorphous phase of calcium carbonate in biominerals has only very recently been understood. Here we summarize what is known about polyamorphism in calcium carbonate as well as what is understood about the role of amorphous calcium carbonate in biominerals. We show that consideration of the amorphous forms of calcium carbonate within the physical notion of polyamorphism leads to new insights when it comes to the mechanisms by which polymorphic structures can evolve in the first place. This not only has implications for our understanding of biomineralization, but also of the means by which crystallization may be controlled in medical, pharmaceutical, and industrial contexts.
Coming in to form: A summary is given of what is known about polyamorphism in calcium carbonate as well as the role of amorphous calcium carbonate in biomineralization. The amorphous forms of calcium carbonate within the physical notion of polyamorphism lead to new insights when it comes to the mechanisms by which polymorphic structures can evolve. This also has implications beyond biomineralization.
Despite their significant potential, catalytic asymmetric reactions of olefins with formaldehyde are rare and metal-free approaches have not been previously disclosed. Here we describe an ...enantioselective intermolecular Prins reaction of styrenes and paraformaldehyde to form 1,3-dioxanes, using confined imino-imidodiphosphate (iIDP) Brønsted acid catalysts. Isotope labeling experiments and computations suggest a concerted, highly asynchronous addition of an acid-activated formaldehyde oligomer to the olefin. The enantioenriched 1,3-dioxanes can be transformed into the corresponding optically active 1,3-diols, which are valuable synthetic building blocks.
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Malignant bone tumors are aggressive neoplasms which arise from bone tissue or as a result of metastasis. The most prevalent types of cancer, such as breast, prostate, and lung ...cancer, all preferentially metastasize to bone, yet the role of the bone niche in promoting cancer progression remains poorly understood. Tissue engineering has the potential to bridge this knowledge gap by providing 3D in vitro systems that can be specifically designed to mimic key properties of the bone niche in a more physiologically relevant context than standard 2D culture. Elucidating the crucial components of the bone niche that recruit metastatic cells, support tumor growth, and promote cancer-induced destruction of bone tissue would support efforts for preventing and treating these devastating malignancies. In this review, we summarize recent efforts focused on developing in vitro 3D models of primary bone cancer and bone metastasis using tissue engineering approaches. Such 3D in vitro models can enable the identification of effective therapeutic targets and facilitate high-throughput drug screening to effectively treat bone cancers.
Biomaterials-based 3D culture have been traditionally used for tissue regeneration. Recent research harnessed biomaterials to create 3D in vitro cancer models, with demonstrated advantages over conventional 2D culture in recapitulating tumor progression and drug response in vivo. However, previous work has been largely limited to modeling soft tissue cancer, such as breast cancer and brain cancer. Unlike soft tissues, bone is characterized with high stiffness and mineral content. Primary bone cancer affects mostly children with poor treatment outcomes, and bone is the most common site of cancer metastasis. Here we summarize emerging efforts on engineering 3D bone cancer models using tissue engineering approaches, and future directions needed to further advance this relatively new research area.
Lowland Maya civilization flourished in the tropical region of the Yucatan peninsula and environs for more than 2500 years (~1000 BCE to 1500 CE). Known for its sophistication in writing, art, ...architecture, astronomy, and mathematics, Maya civilization still poses questions about the nature of its cities and surrounding populations because of its location in an inaccessible forest. In 2016, an aerial lidar survey across 2144 square kilometers of northern Guatemala mapped natural terrain and archaeological features over several distinct areas. We present results from these data, revealing interconnected urban settlement and landscapes with extensive infrastructural development. Studied through a joint international effort of interdisciplinary teams sharing protocols, this lidar survey compels a reevaluation of Maya demography, agriculture, and political economy and suggests future avenues of field research.
In gold nanoparticle-enhanced radiotherapy, intravenously administered nanoparticles tend to accumulate in the tumor tissue by means of the so-called permeability and retention effect and upon ...irradiation with x-rays, the nanoparticles release a secondary electron field that increases the absorbed dose that would otherwise be obtained from the interaction of the x-rays with tissue alone. The concentration of the nanoparticles in the tumor, number of nanoparticles per unit of mass, which determines the total absorbed dose imparted, can be measured via magnetic resonance or computed tomography images, usually with a resolution of several millimeters. Using a tumor vasculature model with a resolution of 500 nm, we show that for a given concentration of nanoparticles, the dose enhancement that occurs upon irradiation with x-rays greatly depends on whether the nanoparticles are confined to the tumor vasculature or have already extravasated into the surrounding tumor tissue. We show that, compared to the reference irradiation with no nanoparticles present in the tumor model, irradiation with the nanoparticles confined to the tumor vasculature, either in the bloodstream or attached to the inner blood vessel walls, results in a two to three-fold increase in the absorbed dose to the whole tumor model, with respect to an irradiation when the nanoparticles have already extravasated into the tumor tissue. Therefore, it is not enough to measure the concentration of the nanoparticles in a tumor, but the location of the nanoparticles within each volume element of a tumor, be it inside the vasculature or the tumor tissue, needs to be determined as well if an accurate estimation of the resultant absorbed dose distribution, a key element in the success of a radiotherapy treatment, is to be made.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome ...in Escherichia coli knockout mutants of cobB, the only known sirtuin‐like deacetylase, and patZ, the best‐known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identified and differentially quantified. Nearly 65% of these proteins are related to metabolism. The global activity of CobB contributes to the deacetylation of a large number of substrates and has a major impact on physiology. Apart from the regulation of acetyl‐CoA synthetase, we found that CobB‐controlled acetylation of isocitrate lyase contributes to the fine‐tuning of the glyoxylate shunt. Acetylation of the transcription factor RcsB prevents DNA binding, activating flagella biosynthesis and motility, and increases acid stress susceptibility. Surprisingly, deletion of patZ increased acetylation in acetate cultures, which suggests that it regulates the levels of acetylating agents. The results presented offer new insights into functional roles of protein acetylation in metabolic fitness and global cell regulation.
Synopsis
An integrated analysis of proteomic, transcriptomic and metabolic flux data reveals functional roles of protein acetylation in E. coli. Acetylation regulates protein function directly, by modulating metabolic enzyme activity, or indirectly by affecting transcriptional regulators.
Protein acetylation is analyzed under four different growth conditions and is found to be highly context‐dependent.
The global activity of the lysine deacetylase CobB contributes to the deacetylation of a large number of substrates and affects physiology and metabolism.
Acetylation of the transcription factor RcsB prevents DNA binding, impairs flagella biosynthesis and motility and increases acid stress susceptibility.
Deletion of the lysine acetyltransferase patZ increases acetylation in acetate cultures, suggesting that PatZ regulates the levels of acetylating agents.
An integrated analysis of proteomic, transcriptomic and metabolic flux data reveals functional roles of protein acetylation in E. coli. Acetylation regulates protein function directly, by modulating metabolic enzyme activity, or indirectly by affecting transcriptional regulators.
This work reports on the tribological and surface hardness modifications of ultrahigh molecular weight polyethylene (UHMWPE) and polyether ether ketone (PEEK) after plasma immersion dual ion ...implantation of nitrogen, oxygen and helium ions at constant energy and fluence. The results show that the hardness and wear rate can be improved in both polymers by an appropriate combination of the bombarding ions. Wear tests were carried out on modified UHMWPE and PEEK against CoCrMo and Al2O3 counter materials, in an adult bovine serum (ABS) medium at 37°C. In particular, the dual bombardment with nitrogen and oxygen in a 3:1 ion fluence ratio provides the highest wear rate reduction on both polymers when sliding against CoCrMo. In the case of the test against Al2O3, the averaged low wear rates were obtained using He/N ion fluencies of 3:1. More specifically, the wear performance of plasma treated PEEK is superior to this shown by UHMWPE.
•UHMWPE and PEEK polymers were compared for biomedical applications.•Influence of implantation of helium, oxygen and nitrogen gases have been studied.•Ion implantation was used for implantation of gases into UHMWPE and PEEK.•UHMWPE and PEEK were studied vs CoCr and Al2O3 in wear rate tests.•Helium implantation is interesting for wear rate reduction on UHMWPE and PEEK.
From Chemical Gardens to Chemobrionics Barge, Laura M.; Cardoso, Silvana S. S.; Cartwright, Julyan H. E. ...
Chemical reviews,
08/2015, Letnik:
115, Številka:
16
Journal Article
Recenzirano
Odprti dostop
The results of a study on chemobrionics, with an emphasis on chemical-garden-type systems, are presented.
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