scholarly journals Metabolic landscapes in sarcomas

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Richard Miallot ◽  
Franck Galland ◽  
Virginie Millet ◽  
Jean-Yves Blay ◽  
Philippe Naquet
Keyword(s):  
Immune Responses ◽  
Metabolic Regulation ◽  
Large Scale ◽  
Soft Tissue Sarcomas ◽  
Genetic Alterations ◽  
Genetic History ◽  
Heterogeneous Tissue ◽  
Activation Pathways ◽  
Tissue Origin ◽  
Review Current

AbstractMetabolic rewiring offers novel therapeutic opportunities in cancer. Until recently, there was scant information regarding soft tissue sarcomas, due to their heterogeneous tissue origin, histological definition and underlying genetic history. Novel large-scale genomic and metabolomics approaches are now helping stratify their physiopathology. In this review, we show how various genetic alterations skew activation pathways and orient metabolic rewiring in sarcomas. We provide an update on the contribution of newly described mechanisms of metabolic regulation. We underscore mechanisms that are relevant to sarcomagenesis or shared with other cancers. We then discuss how diverse metabolic landscapes condition the tumor microenvironment, anti-sarcoma immune responses and prognosis. Finally, we review current attempts to control sarcoma growth using metabolite-targeting drugs.

scholarly journals An efficient direct screening system for microorganisms that activate plant immune responses based on plant–microbe interactions using cultured plant cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mari Kurokawa ◽  
Masataka Nakano ◽  
Nobutaka Kitahata ◽  
Kazuyuki Kuchitsu ◽  
Toshiki Furuya
Keyword(s):  
Immune Responses ◽  
Plant Defense ◽  
Pseudomonas Syringae ◽  
Large Scale ◽  
Plant Cells ◽  
Defense Responses ◽  
Root Tip ◽  
General Strategy ◽  
Plant Defense Responses ◽  
Microbe Interactions

AbstractMicroorganisms that activate plant immune responses have attracted considerable attention as potential biocontrol agents in agriculture because they could reduce agrochemical use. However, conventional methods to screen for such microorganisms using whole plants and pathogens are generally laborious and time consuming. Here, we describe a general strategy using cultured plant cells to identify microorganisms that activate plant defense responses based on plant–microbe interactions. Microbial cells were incubated with tobacco BY-2 cells, followed by treatment with cryptogein, a proteinaceous elicitor of tobacco immune responses secreted by an oomycete. Cryptogein-induced production of reactive oxygen species (ROS) in BY-2 cells served as a marker to evaluate the potential of microorganisms to activate plant defense responses. Twenty-nine bacterial strains isolated from the interior of Brassica rapa var. perviridis plants were screened, and 8 strains that enhanced cryptogein-induced ROS production in BY-2 cells were selected. Following application of these strains to the root tip of Arabidopsis seedlings, two strains, Delftia sp. BR1R-2 and Arthrobacter sp. BR2S-6, were found to induce whole-plant resistance to bacterial pathogens (Pseudomonas syringae pv. tomato DC3000 and Pectobacterium carotovora subsp. carotovora NBRC 14082). Pathogen-induced expression of plant defense-related genes (PR-1, PR-5, and PDF1.2) was enhanced by the pretreatment with strain BR1R-2. This cell–cell interaction-based platform is readily applicable to large-scale screening for microorganisms that enhance plant defense responses under various environmental conditions.

scholarly journals The features of host immune response with respect to microsatellite status of colorectal cancer

2007 ◽  
Vol 15 (1-2) ◽  
pp. 5-9
Author(s):  
Attila Fenyvesi
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Immune Responses ◽  
Continuous Production ◽  
Tumor Infiltrating Lymphocytes ◽  
Host Immune Response ◽  
Genetic Alterations ◽  
Clinicopathological Characteristics ◽  
Melting Point Analysis ◽  
Peritumoral Stroma

Background: The genetic alterations in colorectal cancer (CRC) progression are determined by two separate pathways, chromosomal and microsatellite instability (MSI). The CRCs with MSI have distinct clinicopathological characteristics with pronounced tumor-associated immune responses. The aim of our study was to investigate the intensity of host immune response in CRC tissue by comparing microsatellite stable (MSS) and instable tumors. Methods: The study was performed on CRC specimens from 28 patients with MSI and compared with 30 MSS tumors. The microsatellite status was evaluated with two markers by PCR and melting point analysis. The immunostaining with anti-CD3 pan-T cell antibody was used to quantify the number of tumor infiltrating lymphocytes. The lymphocytes in peritumoral stromal and the Crohn?s-like peritumoral reaction were counted on H&E slides. Results: No significant differences were found in the average number of lymphocytes in peritumoral stroma and in clinicopathological characteristics of CRCs. The conspicuous Crohn?s-like lymphoid reactions were present in 67.86% of CRCs with MSI versus 26.66% of MSS cases. The CRCs with MSI cases carried significantly higher numbers of tumor infiltrating T-lymphocytes (13.21 versus 7.47) (p<0.0001). Conclusion: The presences of peritumoral Crohn?s-like lymphoid and intraepithelial lymphocytic reaction were intensive markers for MSI in colorectal carcinomas in our study. The peculiar genetic instability in MSI tumors may lead to a continuous production of abnormal peptides, which act as neoantigens. They could induce specific antitumor immune responses effective in limiting tumor growth and spread. Abnormal peptides are potentially promising in immunotherapy advancing and in the design of a vaccine against colorectal tumors with MSI.

scholarly journals An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination

2021 ◽  
Vol 118 (45) ◽  
pp. e2110817118
Author(s):  
Dengning Xia ◽  
Rui Jin ◽  
Gaurav Byagathvalli ◽  
Huan Yu ◽  
Ling Ye ◽  
...  
Keyword(s):  
Immune Responses ◽  
Large Scale ◽  
Low Cost ◽  
Electrode Array ◽  
Dna Vaccination ◽  
Intradermal Injection ◽  
Antibody Responses ◽  
Transient Effects ◽  
Electric Pulses ◽  
High Electric Field Strength

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens with pandemic potential requires safe, protective, inexpensive, and easily accessible vaccines that can be developed and manufactured rapidly at a large scale. DNA vaccines can achieve these criteria, but induction of strong immune responses has often required bulky, expensive electroporation devices. Here, we report an ultra-low-cost (<1 USD), handheld (<50 g) electroporation system utilizing a microneedle electrode array (“ePatch”) for DNA vaccination against SARS-CoV-2. The low cost and small size are achieved by combining a thumb-operated piezoelectric pulser derived from a common household stove lighter that emits microsecond, bipolar, oscillatory electric pulses and a microneedle electrode array that targets delivery of high electric field strength pulses to the skin’s epidermis. Antibody responses against SARS-CoV-2 induced by this electroporation system in mice were strong and enabled at least 10-fold dose sparing compared to conventional intramuscular or intradermal injection of the DNA vaccine. Vaccination was well tolerated with mild, transient effects on the skin. This ePatch system is easily portable, without any battery or other power source supply, offering an attractive, inexpensive approach for rapid and accessible DNA vaccination to combat COVID-19, as well as other epidemics.

scholarly journals A Rapid Saliva Test for Monitoring Immune Protection against SARS-CoV-2 and its Variants

2021 ◽  
Author(s):  
Victoria SA. Momyer ◽  
Samantha Dixon ◽  
Q. John Liu ◽  
Brian Wee ◽  
Tiffany Y. Chen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Large Scale ◽  
Temporal Evolution ◽  
Data Driven ◽  
Small Scale ◽  
Non Invasive ◽  
Population Immunity ◽  
Detection Technology ◽  
Blood Drawing ◽  
Saliva Test

Given the ongoing transmission and emergence of SARS-Cov-2 variants globally, it is critical to have a timely assessment on individuals' immune responses as well as population immunity. Important questions such as the durability of COVID-19 immunity or the efficacy of vaccines require large datasets to generate meaningful insights. However, due to the complexity and relatively high-cost of many immunity assays and the needs for blood-drawing specialists, these assays were mostly limited to small-scale clinical studies. Our work demonstrated the potential of a non-invasive, inexpensive and data-driven solution for large-scale immunity surveillance and for predictive modeling of vaccine efficacy. Combining a proprietary saliva processing method and an ultra-sensitive digital detection technology, we were able to rapidly gather information regarding personalized immune response following infection or vaccination, monitor temporal evolution, and optimize predictive models for variant protection.

The ability to combine multiple mRNA antigens targeting multiple pathogens simultaneously, and the robust immune responses are confirmed in several clinical studies

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Immune Responses ◽  
Clinical Studies ◽  
Large Scale ◽  
Antigen Expression ◽  
Fine Tuning ◽  
Cold Chain ◽  
Disruptive Technology ◽  
Single Shot ◽  
Structural Components ◽  
Multiple Pathogens

In the last decade, great progress has been made on mRNA vaccines. MRNA vaccines that are well-tolerated and human immunogenic, stable and can be scaled up to hundreds of millions of doses have been produced with advancements in mRNA design, lipid nanoparticles (LNPs) composition and production techniques. The ability to combine multiple mRNA antigens in the same LNP, targeting multiple pathogens simultaneously, the lack of vector immunity, and the robust immune responses confirmed in several clinical studies make mRNA vaccines a disruptive technology that could change the development of vaccines in the coming years. Moreover, as mRNA was recently employed for large-scale vaccination applications, there is still plenty of room for refining and new advances.Ad-vector-based vaccines have also become promising immunization platforms. Ad vectors' structural components can be harnessed and modified for enhanced tropism, efficient transduction, and optimal antigen expression, and the structural components of Ad vaccine vectors can be harnessed and modified for enhanced tropism, effective transduction, and optimal antigen expression. Ad vectors can be readily created and mass-produced on a commercial basis, and their potency and stability make single-shot immunizations viable without using a frozen cold chain. Ad vectors' flexibility and promise for present and future vaccination applications is evidenced by their development against many illnesses.The use of biomaterials and engineering to improve vaccine delivery control has shown promise in boosting vaccination efficiency and fine-tuning the responses induced. Taken together, these vaccine science innovations have the potential to overcome many of the shortcomings in traditional vaccination technology, and they will almost probably play a crucial part in developing future known and novel disease vaccines.

scholarly journals NAD-Biosynthetic and Consuming Enzymes as Central Players of Metabolic Regulation of Innate and Adaptive Immune Responses in Cancer

2019 ◽  
Vol 10 ◽  
Author(s):  
Valentina Audrito ◽  
Antonella Managò ◽  
Federica Gaudino ◽  
Leonardo Sorci ◽  
Vincenzo Gianluca Messana ◽  
...  
Keyword(s):  
Immune Responses ◽  
Metabolic Regulation ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

scholarly journals Efficient Flow Synthesis of Human Antimicrobial Peptides

2020 ◽  
Vol 73 (4) ◽  
pp. 380
Author(s):  
John S. Albin ◽  
Bradley L. Pentelute
Keyword(s):  
Natural Products ◽  
Immune Responses ◽  
Antimicrobial Peptides ◽  
Large Scale ◽  
Flow Chemistry ◽  
Flash Chromatography ◽  
Reverse Phase ◽  
Vast Array ◽  
Host Immune Responses ◽  
Therapeutic Development

Organisms from all kingdoms of life have evolved a vast array of peptidic natural products to defend against microbes. These are known collectively as antimicrobial peptides (AMPs) or host defence peptides, reflecting their abilities not only to directly kill microbes, but also to modulate host immune responses. Despite decades of investigation, AMPs have yet to live up to their promise as lead therapeutics, a reality that reflects, in part, our incomplete understanding of these diverse agents in their various physiological contexts. Towards improving our understanding of AMP biology and the ways in which this can be best leveraged for therapeutic development, we are interested in large-scale comparisons of the antimicrobial and immunological activities of human AMPs, an undertaking that requires an efficient workflow for AMP synthesis and subsequent characterization. We describe here the application of flow chemistry and reverse-phase flash chromatography to the generation of 43AMPs, approaches that, when combined, significantly expedite synthesis and purification, potentially facilitating more systematic approaches to downstream testing and engineering.

scholarly journals Precision Oncology in Sarcomas: Divide and Conquer

2019 ◽  
pp. 1-16 ◽  
Author(s):  
Roberto Carmagnani Pestana ◽  
Roman Groisberg ◽  
Jason Roszik ◽  
Vivek Subbiah
Keyword(s):  
Next Generation Sequencing ◽  
Soft Tissue Sarcomas ◽  
Genetic Alterations ◽  
Divide And Conquer ◽  
Precision Oncology ◽  
Next Generation ◽  
Mesenchymal Tumors ◽  
Next Generation Sequencing Technology ◽  
Molecular Abnormalities ◽  
Generation Sequencing

Sarcomas are a heterogeneous group of rare malignancies that exhibit remarkable heterogeneity, with more than 50 subtypes recognized. Advances in next-generation sequencing technology have resulted in the discovery of genetic events in these mesenchymal tumors, which in addition to enhancing understanding of the biology, have opened up avenues for molecularly targeted therapy and immunotherapy. This review focuses on how incorporation of next-generation sequencing has affected drug development in sarcomas and strategies for optimizing precision oncology for these rare cancers. In a significant percentage of soft tissue sarcomas, which represent up to 40% of all sarcomas, specific driver molecular abnormalities have been identified. The challenge to evaluate these mutations across rare cancer subtypes requires the careful characterization of these genetic alterations to further define compelling drivers with therapeutic implications. Novel models of clinical trial design also are needed. This shift would entail sustained efforts by the sarcoma community to move from one-size-fits-all trials, in which all sarcomas are treated similarly, to divide-and-conquer subtype-specific strategies.

scholarly journals IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Fátima Rivera-Escalera ◽  
Jonathan J. Pinney ◽  
Laura Owlett ◽  
Hoda Ahmed ◽  
Juilee Thakar ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Responses ◽  
Large Scale ◽  
Myeloid Cells ◽  
Amyloid Plaque ◽  
Plaque Burden ◽  
Cytokine Signaling ◽  
Expression Of Genes ◽  
Adenoviral Transduction ◽  
Plaque Clearance

Abstract Background Neuroinflammation is thought to contribute to the pathogenesis of Alzheimer’s disease (AD), yet numerous studies have demonstrated a beneficial role for neuroinflammation in amyloid plaque clearance. We have previously shown that sustained expression of IL-1β in the hippocampus of APP/PS1 mice decreases amyloid plaque burden independent of recruited CCR2+ myeloid cells, suggesting resident microglia as the main phagocytic effectors of IL-1β-induced plaque clearance. To date, however, the mechanisms of IL-1β-induced plaque clearance remain poorly understood. Methods To determine whether microglia are involved in IL-1β-induced plaque clearance, APP/PS1 mice induced to express mature human IL-1β in the hippocampus via adenoviral transduction were treated with the Aβ fluorescent probe methoxy-X04 (MX04) and microglial internalization of fibrillar Aβ (fAβ) was analyzed by flow cytometry and immunohistochemistry. To assess microglial proliferation, APP/PS1 mice transduced with IL-1β or control were injected intraperitoneally with BrdU and hippocampal tissue was analyzed by flow cytometry. RNAseq analysis was conducted on microglia FACS sorted from the hippocampus of control or IL-1β-treated APP/PS1 mice. These microglia were also sorted based on MX04 labeling (MX04+ and MX04− microglia). Results Resident microglia (CD45loCD11b+) constituted > 70% of the MX04+ cells in both Phe- and IL-1β-treated conditions, and < 15% of MX04+ cells were recruited myeloid cells (CD45hiCD11b+). However, IL-1β treatment did not augment the percentage of MX04+ microglia nor the quantity of fAβ internalized by individual microglia. Instead, IL-1β increased the total number of MX04+ microglia in the hippocampus due to IL-1β-induced proliferation. In addition, transcriptomic analyses revealed that IL-1β treatment was associated with large-scale changes in the expression of genes related to immune responses, proliferation, and cytokine signaling. Conclusions These studies show that IL-1β overexpression early in amyloid pathogenesis induces a change in the microglial gene expression profile and an expansion of microglial cells that facilitates Aβ plaque clearance.

scholarly journals Progress in the Systemic Treatment of Advanced Soft-Tissue Sarcomas

1998 ◽  
Vol 5 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Scott H. Okuno ◽  
John H. Edmonson
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Systemic Treatment ◽  
Soft Tissue Sarcomas ◽  
Multimodality Treatment ◽  
Clinical Situation ◽  
Controlled Clinical Trials ◽  
Systemic Treatments ◽  
Review Current ◽  
Systemic Therapies

Background: Despite the plethora of chemotherapeutic remedies for advanced soft-tissue sarcomas, little evidence has developed to indicate that these efforts have been curative. No controlled comparison has yet proven that patients receiving multidrug regimens survive longer than those receiving doxorubicin alone. Methods: The authors review current systemic treatments and then discuss some investigational efforts now in progress. Also, they seek to demonstrate how the therapies currently available can be integrated with surgery and radiation therapy to accomplish more than might be anticipated from chemotherapy alone. Results: While working to develop better systemic therapies for advanced soft-tissue sarcomas, the integrated use of our best chemotherapy regimens in combination with selected surgical and radiotherapy efforts may provide patients with the best available therapy. Some recent observations involving the use of molgramostim plus chemotherapy have been intriguing. Conclusions: Progress in the systemic treatment of advanced soft-tissue sarcomas may be gradual, but it is real. Our daily challenge is to be certain that we offer each patient the best available multimodality treatment applicable to his or her clinical situation. Molgramostim should be made available for further study with chemotherapy in controlled clinical trials.

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