Proteomics Analyses of Small Extracellular Vesicles of Aqueous Humor: Identification and Validation of GAS6 and SPP1 as Glaucoma Markers.

Cataracts and glaucoma account for a high percentage of vision loss and blindness worldwide. Small extracellular vesicles (sEVs) are released into different body fluids, including the eye's aqueous humor. Information about their proteome content and characterization in ocular pathologies is not yet well established.

Discovery of CDC42 Inhibitors with a Favorable Pharmacokinetic Profile and Anticancer In Vivo Efficacy.

We previously reported trisubstituted pyrimidine lead compounds, namely, ARN22089 and ARN25062, which block the interaction between CDC42 with its specific downstream effector, a PAK protein. This interaction is crucial for the progression of multiple tumor types. Such inhibitors showed anticancer efficacy in vivo.

Hamartoma of mature cardiac myocytes presenting as a polypoid epicardial tumor in the interatrial groove and with gene fusions by copy number anomalies of chromosome 7.

Hamartoma of mature cardiac myocytes (HMCM) is an extremely rare cardiac tumor characterized by benign growth of differentiated mature striated cardiac myocytes, and usually involves the ventricular myocardium. We describe the case of a 15-year-old female who presented with a short history of atrial fibrillation and a polypoid epicardial tumor that was attached to the interatrial groove by a short pedicle. The resected specimen showed features consistent with HMCM.

Management of High-Risk Neuroblastoma with Soft-Tissue-Only Disease in the Era of Anti-GD2 Immunotherapy.

Neuroblastoma presents with two patterns of disease: locoregional or systemic. The poor prognostic risk factors of locoregional neuroblastoma (LR-NB) include age, or amplification, 11q, histology, diploidy with or mutations, and aberrations. Anti-GD2 immunotherapy has significantly improved the outcome of high-risk (HR) NB and is mostly effective against osteomedullary minimal residual disease (MRD), but less so against soft tissue disease.

POTEE promotes breast cancer cell malignancy by inducing invadopodia formation through the activation of SUMOylated Rac1.

The small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial-mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1-SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1-SUMO1.

NCAPH Drives Breast Cancer Progression and Identifies a Gene Signature that Predicts Luminal A Tumor Recurrence.

Despite their generally favorable prognosis, luminal A tumors paradoxically pose the highest ten-year recurrence risk among breast cancers. From those that relapse, a quarter of them do it within five years after diagnosis. Identifying such patients is crucial, as long-term relapsers could benefit from extended hormone therapy, whereas early relapsers may require aggressive treatment.

EpiGe: A machine-learning strategy for rapid classification of medulloblastoma using PCR-based methyl-genotyping.

Molecular classification of medulloblastoma is critical for the treatment of this brain tumor. Array-based DNA methylation profiling has emerged as a powerful approach for brain tumor classification. However, this technology is currently not widely available.

Naxitamab Combined with Granulocyte-Macrophage Colony-Stimulating Factor as Consolidation for High-Risk Neuroblastoma Patients in First Complete Remission under Compassionate Use-Updated Outcome Report.

Naxitamab is an anti-GD2 antibody approved for the treatment of relapsed/refractory HR-NB. We report the survival, safety, and relapse pattern of a unique set of HR-NB patients consolidated with naxitamab after having achieved first CR. Eighty-two patients were treated with 5 cycles of GM-CSF for 5 days at 250 μg/m/day (-4 to 0), followed by GM-CSF for 5 days at 500 μg/m/day (1-5) and naxitamab at 3 mg/kg/day (1, 3, 5), on an outpatient basis.

MIF/CXCR4 signaling axis contributes to survival, invasion, and drug resistance of metastatic neuroblastoma cells in the bone marrow microenvironment.

Background: The bone marrow (BM) is the most common site of dissemination in patients with aggressive, metastatic neuroblastoma (NB). However, the molecular mechanisms underlying the aggressive behavior of NB cells in the BM niche are still greatly unknown. In the present study, we explored biological mechanisms that play a critical role in NB cell survival and progression in the BM and investigated potential therapeutic targets.

Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study.

Introduction: The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) has been widely used in a two-dose schedule. We assessed whether a third dose of the homologous or a different vaccine could boost immune responses.

Methods: RHH-001 is a phase 4, participant masked, two centre, safety and immunogenicity study of Brazilian adults (18 years and older) in São Paulo or Salvador who had received two doses of CoronaVac 6 months previously.

The rye transcription factor ScSTOP1 regulates the tolerance to aluminum by activating the ALMT1 transporter.

Plants have evolved different mechanisms to increase their tolerance to aluminum (Al) toxicity and low pH in the soil. The Zn finger transcription factor SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1) plays an essential role in the adaptation of plants to Al and low pH stresses. In this work, we isolated the ScSTOP1 gene from rye (Secale cereale L.

nAChRs gene expression and neuroinflammation in APPswe/PS1dE9 transgenic mouse.

An evaluation of the APPswe/PS1dE9 transgenic AD mouse, presenting with the toxic Aβ1-42 deposition found in human AD, allowed us to characterize time-dependent changes in inflammatory and cholinergic markers present in AD. Astrogliosis was observed in cortex and hippocampus, with cellular loss occurring in the same areas in which Aβ plaques were present. In this setting, we found early significantly elevated levels of IL-1β and TNFα gene expression; with the hippocampus showing the highest IL-1β expression.

Targeted therapy for pediatric low-grade glioma.

Purpose: Pediatric low-grade gliomas are the most frequent brain tumors in children. The standard approach for symptomatic unresectable tumors is chemotherapy. Recently, key molecular alterations/pathways have been identified and targeted drugs developed and tested in clinical trials.

AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity.

Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel-the MYC pathway and the cyclin D-cyclin-dependent kinase (CDK)-retinoblastoma protein (RB) pathway. Both MYC and the cyclin D-CDK-RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability.

Prognostic value of patient-derived xenograft engraftment in pediatric sarcomas.

The goals of this work were to identify factors favoring patient-derived xenograft (PDX) engraftment and study the association between PDX engraftment and prognosis in pediatric patients with Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma. We used immunodeficient mice to establish 30 subcutaneous PDX from patient tumor biopsies, with a successful engraftment rate of 44%. Age greater than 12 years and relapsed disease were patient factors associated with higher engraftment rate.

Unraveling the adult cell progeny of early postnatal progenitor cells.

NG2-glia, also referred to as oligodendrocyte precursor cells or polydendrocytes, represent a large pool of proliferative neural cells in the adult brain that lie outside of the two major adult neurogenic niches. Although their roles are not fully understood, we previously reported significant clonal expansion of adult NG2-cells from embryonic pallial progenitors using the StarTrack lineage-tracing tool. To define the contribution of early postnatal progenitors to the specific NG2-glia lineage, we used NG2-StarTrack.

Stromal SNAI2 Is Required for ERBB2 Breast Cancer Progression.

SNAI2 overexpression appears to be associated with poor prognosis in breast cancer, yet it remains unclear in which breast cancer subtypes this occurs. Here we show that excess SNAI2 is associated with a poor prognosis of luminal B HER2/ERBB2 breast cancers in which SNAI2 expression in the stroma but not the epithelium correlates with tumor proliferation. To determine how stromal SNAI2 might influence HER2 tumor behavior, -deficient mice were crossed with a mouse line carrying the protooncogene to generate HER2/ERBB2 breast cancer.

Comparative analysis of the drug-drug interaction between immunosuppressants, safety and efficacy of rifabutin from rifampicin-based Anti-TB treatment in living donor liver transplant recipients with active tuberculosis.

Background: The Interaction between anti-tuberculous and immunosuppressive drugs which may increase the risk of graft rejections is a major challenge in managing transplant recipients with tuberculosis (TB). Instead of rifampicin (RFM), most guidelines recommended the use of rifabutin (RFB) because of its reduced capacity to induce immunosuppressant metabolism while maintaining the same efficacy as RFM against TB. However, there has been no available data directly comparing the outcome of RFB from RFM-based anti-TB regimens in liver transplant patients with TB.

Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--The BRACE CORONA Trial.

Angiotensin-converting enzyme-2 (ACE2) expression may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain.

Spontaneous renal pelvic perforation in a patient with advanced lung cancer receiving avastin (bevacizumab). About a case.

Bevacizumab is a monoclonalantibody used as a targeted therapy in blocking vascularendothelial growth factor in different types of oncologicaland non-oncological diseases. It has demonstratedsurvival benefits in the treatment of many types of malignanttumors, including lung cancer. As all drugs have adverseeffects, one of the most uncommon being gastrointestinalperforation and few cases of ureteral stenosis.

Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1.

Post-translational modifications directly control protein activity and, thus, they represent an important means to regulate the responses of cells to different stimuli. Protein SUMOylation has recently been recognised as one such modification, and it has been associated with various diseases, including different types of cancer. However, the precise way that changes in SUMOylation influence the tumorigenic properties of cells remains to be fully clarified.

[Serum cellular inflammatory markers in the diagnosis of prostate cancer.].

Unlabelled: Prostate cancer (PCa) is one of the most frequent neoplasms in the masculine sex, which has multiple etiological factors, inflammation is one of them.

Objective: To determine the role of different inflammatory markers in the diagnosis of PCa in first prostatic biopsies.

Methods: This is a prospective study evaluating neutrophil/ lymphocyte (NLR), neutrophil/monocyte (NMR) and platelet/lymphocyte (PLR) ratios of 78 patients with suspected PCa due to PSA alteration and/or abnormal digital rectal examination, and its correlation with twelve-cylinder biopsy result.