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The recombinant antibodies AQ806, AS739, AT693, AU197 and AU734 detect by flow cytometry the spike S protein from SARS-CoV-2.

Long-chain n-3 PUFA (n-3 LCPUFA) are known to reduce blood pressure (BP), heart rate and vagal tone, but potential stress-mitigating effects of n-3 LCPUFA are not well investigated. We explored the effects of oily fish consumption on long-term stress and the stress response in schoolchildren. Healthy 8–9-year-old children were randomised to receive about 300 g/week of oily fish or poultry for 12 weeks (199 randomised, 197 completing). At baseline and endpoint, we measured erythrocyte n-3 LCPUFA, hair cortisol and the response to a 1-min cold pressor test (CPT) on saliva cortisol, BP and continuous electrocardiogram recordings. Post-intervention hair cortisol did not differ between the groups, but sex-specificity was indicated (Psex × group = 0·074, boys: −0·9 (95 % CI −2·9, 1·0) ng/g, girls: 0·7 (95 % CI −0·2, 1·6) ng/g). Children in the fish group tended to be less prone to terminate CPT prematurely (OR 0·20 (95 % CI 0·02, 1·04)). Mean heart beat interval during CPT was 18·2 (95 % CI 0·3, 36·6) ms longer and high frequency power increased (159 (95 % CI 29, 289) ms2) in the fish v. poultry group. The cardiac autonomic response in the 10 min following CPT was characterised by a sympathetic peak followed by a parasympathetic peak, which was most pronounced in the fish group. This exploratory study does not support a strong effect of oily fish consumption on stress but indicates that oily fish consumption may increase vagal cardiac tone during the physiological response to CPT. These results warrant further investigation.

Un yaourt avec votre morphine ? Selon une étude parue en juin 2019 dans la revue scientifique PNAS, la morphine altère le microbiote intestinal, ce qui réduit son effet analgésique. La prise de probiotiques atténue cette accoutumance à la morphine.

The recombinant antibodies AS739, AT693, AU197 and AU734 detect by western blot the spike S protein from SARS-CoV-2.

Micro, Small and Medium-sized Enterprises plays a vital role in a country’s economy. However, in the Philippines, they only contribute 25% of the country’s total gross value added. This is because of the challenges faced by the entrepreneurs, one of which is poor inventory management. This paper focuses on the current inventory process of Family Milk Tea, a family owned, beverage business in the Philippines. Current process shows loss of sales due to stockout and additional charges due to overstocking. Aside from this, tracking of sales is done manually through writing or typing in a work sheet using Microsoft Excel. This result to inaccuracy in terms of inventory and sales report. As a solution, Seiton, a mobile application will be used to alleviate the problem. Due to mobile phone’s universality, this makes Seiton an ideal tool in integrating conveniency and effectivity of Inventory Management System.

There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)���positive and HPV���negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue���saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV���positive and HPV���negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer���testis antigens, 5 cancer���retina antigens and 8 oncogenes) and 29 HPV���antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV���positive and 209 HPV���negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c���myc, LAGE���1, MAGE���A1, ���A3, ���A4, NY���ESO���1, SpanX���a1 and p53. AR to MAGE���A3, MAGE���A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ���10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue���sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV���positive and HPV���negative HNSCC. �� In Copyright http://rightsstatements.org/vocab/InC/1.0/, What's new? Head and neck squamous cell carcinoma remains a deadly disease but new immunotherapeutic approaches are underexplored. Here the authors tested for antibody responses against human antigens to characterize the expression of such antigens in tumors positive or negative for human papillomavirus (HPV). Antibody responses were significantly different in prevalence and pattern based on HPV���status in a large patient cohort. The authors urge independent confirmation of their results but point out that multiplex serology of tumor antigens could be a promising strategy to identify immunotherapeutic targets based on HPV status., publishedVersion

Background The transcription factor NF-κB drives neoplastic progression of many cancers including primary brain tumors (glioblastoma [GBM]). Precise therapeutic modulation of NF-κB activity can suppress central oncogenic signaling pathways in GBM, but clinically applicable compounds to achieve this goal have remained elusive. Methods In a pharmacogenomics study with a panel of transgenic glioma cells, we observed that NF-κB can be converted into a tumor suppressor by the non-psychotropic cannabinoid cannabidiol (CBD). Subsequently, we investigated the anti-tumor effects of CBD, which is used as an anticonvulsive drug (Epidiolex) in pediatric neurology, in a larger set of human primary GBM stem-like cells (hGSC). For this study, we performed pharmacological assays, gene expression profiling, biochemical, and cell-biological experiments. We validated our findings using orthotopic in vivo models and bioinformatics analysis of human GBM datasets. Results We found that CBD promotes DNA binding of the NF-κB subunit RELA and simultaneously prevents RELA phosphorylation on serine-311, a key residue that permits genetic transactivation. Strikingly, sustained DNA binding by RELA-lacking phospho-serine 311 was found to mediate hGSC cytotoxicity. Widespread sensitivity to CBD was observed in a cohort of hGSC defined by low levels of reactive oxygen species (ROS), while high ROS content in other tumors blocked CBD-induced hGSC death. Consequently, ROS levels served as a predictive biomarker for CBD-sensitive tumors. Conclusions This evidence demonstrates how a clinically approved drug can convert NF-κB into a tumor suppressor and suggests a promising repurposing option for GBM therapy.

Purpose of review Cryoglobulins (CG) are immunoglobulins that precipitate in the cold, and dissolve at 37°C. In vivo, in cold exposed tissues and organs, they can induce vasculitis and occlusive vasculopathy after deposition on vascular endothelium under low temperature and high concentration conditions. Clinical manifestations are cutaneous (purpura, ulcers, vasomotor symptoms, and livedo reticularis), rheumatological (arthralgia and arthritis), and peripheral neuropathy (paresthesia and pain in the lower limbs). In profound organs such as the kidneys, CG deposition is less temperature-dependent, favored by local protein and anion concentrations, and can lead to glomerulonephritis. This review will focus on cryoglobulinemic vasculitis and vascular lesion, and their diagnosis. Recent findings The mechanisms of vascular lesions of pathogenic CG in function of CG type and their characteristics are better defined. Optimal conditions for CG detection are critical. The importance of looking for underlying diseases, especially hepatitis C virus status in mixed CG, is reminded. Summary A decision diagram for CG vasculitis diagnosis based on clinical and biological parameters is proposed.

Background Cryoglobulins (CG) are immunoglobulins which precipitate at low temperature. The analysis of IgG subclass composition of CG is poorly reported. The aim of this study was to determine the subclasses of IgG-containing type I and mixed type II and III CG in relation to clinical manifestations. Methods Out of a previous series of 1675 patients, inclusion criteria were a cryoprecipitate > 1 mL and a total IgG > 300 mg/L. IgG subclasses were quantified by immunoturbidimetry, rheumatoid factor (RF), and C4 by immunonephelometry. Clinical parameters were collected from hospital charts. Results CG samples from 86 patients were included, 10 type I CG and 76 mixed CG. Type I CG subclasses were IgG1 (6/10) and IgG2/IgG3 (4/10), never IgG4. IgG subclass in type II vs. III CG were 73.3 ± 15.2% vs. 52.5 ± 20.7% for IgG1 (p

Background: Apathy is a prevalent behavioral syndrome of Huntington disease (HD) that can result in severe loss of function for the individual with HD and substantial caregiver distress. Research-based evidence of apathy is characterized by methodological differences, and there is a deficiency in the evidence concerning the subtypes of apathy.Objective: To characterize apathy in premanifest and motor-manifest HD gene expansion carriers and controls using the Short Problem Behaviors Assessment for Huntington’s Disease (PBA–s) and the Lille Apathy Rating Scale (LARS).Method: We included 82 HD gene expansion carriers (premanifest and motor manifest) and 32 controls (Mini-Mental State Examination score ≥24 and Montreal Cognitive Assessment score ≥19) in the study. We quantified apathy using the PBA–s and the LARS and performed correlation analyses between the global LARS score and motor function, cytosine-adenine-guanine repeat length, cytosine-adenine-guanine Age Product score, and neuropsychiatric and cognitive symptoms.Results: The motor-manifest HD gene expansion carriers scored significantly higher than the controls on the global score and the Intellectual Curiosity and Action Initiation subscales of the LARS. Apathy was present in 28% of the HD gene expansion carriers (including 7 premanifest). The apathetic participants had a significantly higher motor score, significantly higher scores on the neuropsychiatric instruments, and significantly lower cognitive scores compared with the controls.Conclusion: Apathy is a frequent syndrome that is found in individuals with HD. Apathy has a specific expression, with symptoms such as reduced initiation, voluntary actions, and interests, that might be related to the underlying neuropathology. Apathy is related to disease progression, neuropsychiatric symptoms, and cognitive impairments.

This article explores the relationship between media coverage of chemical hazards, scientific understandings of chemical risk, and policy change in the USA at the state level from 1990 to 2010. We observe that media coverage compounded by scientific development, especially in relation to a greater understanding of chemical hazards and approaches to its management, affected public perception of health and environmental risk, aiding in a shift of expectations about necessary levels of statutory protection from the states. We also note the emergence of effective framings of chemical risk around impacts on vulnerable populations, such as children, where media attention and policy action created important coalitions of support. The resulting increased state-, county-, and city-level policy action eventually led to support and momentum policy change at the federal level. This study helps to clarify how media attention to chemical hazards may play an important role in influencing eventual policy responses and risk management approaches.

With the increasing number of COVID-19 cases in the Philippines, universities are coming up with different ways on how to continue education online for the incoming school year. But this only poses a huge challenge, where many students have no access to education resources. Mapua University recognized this problem and offered an option to its students to choose whether to have a fully online term or a blend of online and face-to-face classes (blended learning). The study aims to determine the maximum number of IE-EMG students allowed to attend face-to-face classes for the 1st quarter of A.Y. 2020-2021, where blended learning is opted to be implemented as the learning mode of delivery. An integer programming model is designed to help the beneficiaries of this study with assigning courses and class schedules for blended learning to IE students of the IE-EMG department while observing IATF protocols and the university's guidelines. An optimal solution was obtained using Excel's solver tool, where Max Z is equal to 135, this suggests that the faculty members should limit the total number of IE-EMG students that will attend face-to-face classes every week to 135. The obtained solution could be used by the faculty members of the department as a guide in arranging the class schedules of the students.

Cliënttevredenheid wordt beschouwd als een belangrijke indicator van de kwaliteit van de jeugdhulp die kinderen en jongeren ontvangen. Om deze te meten voor 9-12 jarige kinderen die gespecialiseerde jeugdhulp in groepsverband ontvangen, is de SMILEY 9-12 ontwikkeld. Het instrument, bestaande uit 24 items in de vorm van visueel analoge schaaltjes (VAS), brengt op zes domeinen de ervaringen van kinderen in kaart: informatieverstrekking, behandelomgeving, expertise hulpverleners, relatie met hulpverlener, voortgang hulpverlening en behandeluitkomsten. De SMILEY 9-12 is op constructvaliditeit en betrouwbaarheid getest in een sample van 594 kinderen die hulp ontvingen van 20 verschillende jeugdhulporganisaties in Nederland. Toepassing van Mokken Schaalanalyse voor Polytome items (MSP) resulteerde in een finale versie met 18 items, die als een matig sterke (H=0.43) en betrouwbare (Rho=0.91) schaal kan worden beschouwd om cliënttevredenheid bij kinderen te meten. Deze versie toont ‘steekproef onafhankelijkheid’ voor kenmerken als leeftijd, sekse, hulpfase, type ontvangen hulpverlening, en wijze van afname (groepsgewijs vs. individueel). Kinderen die in groepsverband ambulante hulp of dagbehandeling krijgen blijken (iets) meer tevreden te zijn dan kinderen in residentiële zorg. We gaan aan het eind van dit artikel in op de implicaties van onze bevindingen voor de praktijk van de jeugdhulp en het toekomstig onderzoek.

The current opioid epidemic necessitates a better understanding of human addiction neurobiology to develop efficacious treatment approaches. Here, we perform genome-wide assessment of chromatin accessibility of the human striatum in heroin users and matched controls. Our study reveals distinct neuronal and non-neuronal epigenetic signatures, and identifies a locus in the proximity of the gene encoding tyrosine kinase FYN as the most affected region in neurons. FYN expression, kinase activity and the phosphorylation of its target Tau are increased by heroin use in the post-mortem human striatum, as well as in rats trained to self-administer heroin and primary striatal neurons treated with chronic morphine in vitro. Pharmacological or genetic manipulation of FYN activity significantly attenuates heroin self-administration and responding for drug-paired cues in rodents. Our findings suggest that striatal FYN is an important driver of heroin-related neurodegenerative-like pathology and drug-taking behavior, making FYN a promising therapeutic target for heroin use disorder., Epigenetic mechanisms have emerged as contributors to the molecular impairments caused by exposure to environmental factors such as abused substances. Here the authors perform epigenetic profiling of the striatum and identify the tyrosine kinase FYN is an important driver of neurodegenerative-like pathology and drug-taking behaviour.

SARS-CoV2 virus affects the immune system at multiple sites.1 Severe cases with a cytokine storm show massive defects of all T cell subsets with lymphopenia. B cells are rather hyper-reactive, suggesting defective regulation from T cells and patients with severe forms produce higher levels of antivirus antibodies.2 However, the production of high affinity and protective antibodies requires a fine tuning of the interactions between viral-specific T and B cells. Defects of such regulation can lead to changes in immunoglobulin (Ig) production, with reduction of their protective properties, and induction of autoreactive and possibly pathogenic antibodies through tolerance loss. Serum protein electrophoresis is a simple way to look at Ig heterogeneity. Profiles can show polyclonal hypergammaglobulinaemia, oligoclonality with several small spikes or monoclonality with single M-spike. From 3 March to 30 April 2020, 136 patients tested PCR-positive …

Age-related loss of muscle mass and strength is widely attributed to limitation in the capacity of muscle resident satellite cells to perform their myogenic function. This idea contains two notions that have not been comprehensively evaluated by experiment. First, it entails the idea that we damage and lose substantial amounts of muscle in the course of our normal daily activities. Second, it suggests that mechanisms of muscle repair are in some way exhausted, thus limiting muscle regeneration. A third option is that the aged environment becomes inimical to the conduct of muscle regeneration. In the present study we used our established model of human muscle xenografting to test whether muscle samples taken from cadavers, of a range of ages, maintained their myogenic potential after being transplanted into immunodeficient mice. We find no measurable difference in regeneration across the range of ages investigated up to 78 years of age. Moreover, we report that satellite cells maintained their myogenic capacity even when muscles were grafted 11 days postmortem in our model. We conclude that the loss of muscle mass with increasing age is not attributable to any intrinsic loss of myogenicity and is most likely a reflection of progressive and detrimental changes in the muscle micro-environment such as to disfavor the myogenic function of these cells.

Pathological angiogenesis contributes to morbidity in a number of diseases including cancer, diabetic retinopathy and the neovascular form of age-related macular degeneration, leading to significant efforts to develop effective anti-angiogenic therapeutics for these conditions. The field is dominated by inhibitors of vascular endothelial growth factor (VEGF), yet angiogenesis can also be driven and modified by other factors. We have previously demonstrated that leucine-rich alpha-2-glycoprotein 1 (LRG1) contributes to abnormal vessel growth by activating a TGFß switch. Here we report the development and characterisation of a function-blocking fully humanised IgG4 and its Fab fragment, that bind to LRG1 with high affinity and specificity and inhibit vascular leakage in the mouse model of laser-induced choroidal neovascularisation. In summary, we have developed a therapeutic antibody that targets a VEGF-independent signalling axis, which may be effective in a number of conditions either as monotherapy or in combination with other vascular targeted therapies.

Cryoglobulins (CGs) are cold precipitating immunoglobulins, and hepatitis C virus (HCV) infection is its most common cause. The purpose of the study was to determine the contribution of HCV in a large cohort of CG. Biological characteristics and specificity of CGs in HCV patients were compared to non-HCV subjects. Cryoglobulin analysis included isotype, clonality, concentration, and rheumatoid factor (RF) in cryoprecipitate and serum complement and RF. This study is an extension of the study carried out on a cohort of 13,439 patients tested for CGs from all medical units, in which 1,675/13,439 (12.5%) patients had a CG, and 680/1,675 (40.6%) had HCV serology or viral load determination (HCV RNA). Among these 680 CG patients tested for HCV, 325 of 680 (47.8%) HCV patients (272 HCV RNA+ and 45 HCV RNA− patients) were compared to 355/680 (52.2%) non-HCV subjects. After a positive detection of CG, HCV status was determined only for 37.7% (256/680) of patients, allowing the diagnosis of a previously unknown HCV infection for 39.8% (102/256). Concentration of HCV RNA+ CGs (median = 80.5 mg/L) was significantly higher than that of HCV RNA− CG (median = 50.5 mg/L, p = 0.001) and HCV− CG (median = 32 mg/L, p < 0.0001). There was no difference of median CG concentration between HCV RNA− patients and non-HCV subjects. Rheumatoid factor titer was significantly higher in type II CG compared to type III CG in HCV RNA+ patients (254 ± 720 vs. 15 ± 21 IU/mL, p < 0.0001) and non-HCV subjects (333 ± 968 vs. 16.8 ± 26 IU/mL, p = 0.0004). Complement functional activity CH50 was lower in HCV RNA+ patients (36 ± 24 U/mL) and in HCV RNA− patients (32 ± 21 U/mL) than in non-HCV subjects (50 ± 25 U/mL, p = 0.001 and p = 0.004). In conclusion, HCV infection and treatment influence CG characteristics. It is essential, and far from always tested, to determine the HCV status of patients with mixed CG, and conversely to search for CG in patients with HCV infection.

Research suggests that personality may change due to important life events, such as psychotherapy, and that personality and attitudes may predict treatment progress. Longitudinal data in a community mental health clinic showed positive changes in Emotional Stability, Hope, Gratitude, and Motivation during the course of psychotherapy. The static approach relating baseline personality and attitudes to treatment progress did not yield fruitful results. The dynamic approach was more effective, in which we treated personality and attitudes as malleable and used changes in these variables as predictors of progress. Treatment progress correlated with an increase in Emotional Stability. Positive changes in general life attitudes (Hope, Gratitude, Quality of Life) more so than therapy-specific attitudes (Motivation, Working Alliance) predicted symptom reduction.

Cryoglobulins (CGs) are cold precipitating immunoglobulins, and hepatitis C virus (HCV) infection is its most common cause. The purpose of the study was to determine the contribution of HCV in a large cohort of CG. Biological characteristics and specificity of CGs in HCV patients were compared to non-HCV subjects. Cryoglobulin analysis included isotype, clonality, concentration, and rheumatoid factor (RF) in cryoprecipitate and serum complement and RF. This study is an extension of the study carried out on a cohort of 13,439 patients tested for CGs from all medical units, in which 1,675/13,439 (12.5%) patients had a CG, and 680/1,675 (40.6%) had HCV serology or viral load determination (HCV RNA). Among these 680 CG patients tested for HCV, 325 of 680 (47.8%) HCV patients (272 HCV RNA+ and 45 HCV RNA− patients) were compared to 355/680 (52.2%) non-HCV subjects. After a positive detection of CG, HCV status was determined only for 37.7% (256/680) of patients, allowing the diagnosis of a previously unknown HCV infection for 39.8% (102/256). Concentration of HCV RNA+ CGs (median = 80.5 mg/L) was significantly higher than that of HCV RNA− CG (median = 50.5 mg/L, p = 0.001) and HCV− CG (median = 32 mg/L, p < 0.0001). There was no difference of median CG concentration between HCV RNA− patients and non-HCV subjects. Rheumatoid factor titer was significantly higher in type II CG compared to type III CG in HCV RNA+ patients (254 ± 720 vs. 15 ± 21 IU/mL, p < 0.0001) and non-HCV subjects (333 ± 968 vs. 16.8 ± 26 IU/mL, p = 0.0004). Complement functional activity CH50 was lower in HCV RNA+ patients (36 ± 24 U/mL) and in HCV RNA− patients (32 ± 21 U/mL) than in non-HCV subjects (50 ± 25 U/mL, p = 0.001 and p = 0.004). In conclusion, HCV infection and treatment influence CG characteristics. It is essential, and far from always tested, to determine the HCV status of patients with mixed CG, and conversely to search for CG in patients with HCV infection.

There have been dramatic changes worldwide in the attitudes toward and consumption of recreational and medical cannabis. Cannabinoid receptors, which mediate the actions of cannabis, are abundantly expressed in brain regions known to mediate neural processes underlying reward, cognition, emotional regulation and stress responsivity relevant to addiction vulnerability. Despite debates regarding potential pathological consequences of cannabis use, cannabis use disorder is a clinical diagnosis with high prevalence in the general population and that often has its genesis in adolescence and in vulnerable individuals associated with psychiatric comorbidity, genetic and environmental factors. Integrated information from human and animal studies is beginning to expand insights regarding neurobiological systems associated with cannabis use disorder, which often share common neural characteristics with other substance use disorders, that could inform prevention and treatment strategies.

OBJECTIVE Enhanced Recovery After Surgery (ERAS) protocols have rapidly gained popularity in multiple surgical specialties and are recognized for their potential to improve patient outcomes and decrease hospitalization costs. However, they have only recently been applied to spinal surgery. The goal in the present work was to describe the development, implementation, and impact of an Enhanced Recovery After Spine Surgery (ERASS) protocol for patients undergoing elective spine procedures at an academic community hospital. METHODS A multidisciplinary team, drawing on prior publications and spine surgery best practices, collaborated to develop an ERASS protocol. Patients undergoing elective cervical or lumbar procedures were prospectively enrolled at a single tertiary care center; interventions were standardized across the cohort for pre-, intra-, and postoperative care using standardized order sets in the electronic medical record. Protocol efficacy was evaluated by comparing enrolled patients to a historic cohort of age- and procedure-matched controls. The primary study outcomes were quantity of opiate use in morphine milligram equivalents (MMEs) on postoperative day (POD) 1 and length of stay. Secondary outcomes included frequency and duration of indwelling urinary catheter use, discharge disposition, 30-day readmission and reoperation rates, and complication rates. Multivariable linear regression was used to determine whether ERASS protocol use was independently predictive of opiate use on POD 1. RESULTS In total, 97 patients were included in the study cohort and were compared with a historic cohort of 146 patients. The patients in the ERASS group had lower POD 1 opiate use than the control group (26 ± 33 vs 42 ± 40 MMEs, p < 0.001), driven largely by differences in opiate-naive patients (16 ± 21 vs 38 ± 36 MMEs, p < 0.001). Additionally, patients in the ERASS group had shorter hospitalizations than patients in the control group (51 ± 30 vs 62 ± 49 hours, p = 0.047). On multivariable regression, implementation of the ERASS protocol was independently predictive of lower POD 1 opiate consumption (β = −7.32, p < 0.001). There were no significant differences in any of the secondary outcomes. CONCLUSIONS The authors found that the development and implementation of a comprehensive ERASS protocol led to a modest reduction in postoperative opiate consumption and hospital length of stay in patients undergoing elective cervical or lumbar procedures. As suggested by these results and those of other groups, the implementation of ERASS protocols may reduce care costs and improve patient outcomes after spine surgery.

Vascular dysfunction contributes to the pro-oncogenic tumor microenvironment and impedes the delivery of therapeutics. Normalizing of the tumor vasculature has therefore become a potential therapeutic objective. We previously reported that the secreted glycoprotein, leucine-rich α-2-glycoprotein 1 (LRG1), contributes to the formation of pathogenic neovascularization. Here we show that in mouse models of cancer, Lrg1 is induced in tumor endothelial cells. We demonstrate that the expression of LRG1 impacts on tumor progression as Lrg1 deletion or treatment with a LRG1 function-blocking antibody inhibited tumor growth and improved survival. Inhibition of LRG1 increased endothelial cell pericyte coverage and improved vascular function resulting in significantly enhanced efficacy of cisplatin chemotherapy, adoptive T-cell therapy and immune checkpoint inhibition (anti-PD1) therapy. With immunotherapy, LRG1 inhibition led to a significant shift in the tumor microenvironment from being predominantly immune silent (cold) to immune active (hot). LRG1 therefore drives vascular abnormalization and its inhibition represents a novel and effective means of improving the efficacy of cancer therapeutics.