Genetic and immune landscape evolution in MMR-deficient colorectal cancer.

Mismatch repair-deficient (MMRd) colorectal cancers (CRCs) have high mutation burdens, which make these tumours immunogenic and many respond to immune checkpoint inhibitors. The MMRd hypermutator phenotype may also promote intratumour heterogeneity (ITH) and cancer evolution. We applied multiregion sequencing and CD8 and programmed death ligand 1 (PD-L1) immunostaining to systematically investigate ITH and how genetic and immune landscapes coevolve.

[Neonatal ophthalmia caused by Herpes Simplex Virus type I].

Unlabelled: There are different etiologies of neonatal ophthalmia such as viral ones. Among them, the Herpes simplex virus, both type I and II, is particularly relevant due to its potential severity. It is a rare, in frequent entity, but with a high rate of morbidity and mortality without appropriate diagnosis and management.

Pre-therapeutic efficacy of the CDK inhibitor dinaciclib in medulloblastoma cells.

Medulloblastoma (MB) is the most common aggressive paediatric brain tumour and, despite the recent progress in the treatments of MB patients, there is still an urgent need of complementary or alternative therapeutic options for MB infants. Cyclin Dependent Kinase inhibitors (CDKi) are at the front-line of novel targeted treatments for multiple cancers and the CDK4/6 specific inhibitor palbociclib has been pre-clinically identified as an effective option for MB cells. Herein, we identified the pan-CDKi dinaciclib as a promising alternative to palbociclib for the suppression of MB cells proliferation.

Differential Role of Circulating microRNAs to Track Progression and Pre-Symptomatic Stage of Chronic Heart Failure: A Pilot Study.

(1)Background: Chronic heart failure (CHF) contributes to the overall burden of cardiovascular disease. Early identification of at-risk individuals may facilitate the targeting of precision therapies. Plasma microRNAs are promising circulating biomarkers for their implications with cardiac pathologies.

Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition.

A subset of lung adenocarcinomas is driven by the EML4-ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on-target mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resistance, we found that EML4-ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib.

A Specific Circulating MicroRNA Cluster Is Associated to Late Differential Cardiac Response to Doxorubicin-Induced Cardiotoxicity .

Background: Cardiotoxicity is a detrimental side effect of the anticancer drug doxorubicin (DOX), characterized by progressive heart dysfunction. Circulating microRNAs (miRNAs) are recognized as potential biomarkers of cardiac disease; thus, we aimed to investigate their association with late cardiotoxicity in an animal model of disease.

Methods: Twenty C57BL/6 female mice were administered with 24 mg/kg cumulative dose of DOX or saline during 2 weeks, followed by a recovery period of one month (T42).

Plasmatic and chamber-specific modulation of cardiac microRNAs in an acute model of DOX-induced cardiotoxicity.

Background: Doxorubicin (DOX) is a chemotherapeutic drug limited in its usefulness by an adverse side effect, cardiotoxicity. The mechanisms leading to this detrimental occurrence are not completely clear, and lately many authors focused their attention on the possible role of microRNAs (miRNAs), small regulators of cardiovascular functions, in this phenomenon. Notably, these molecules recently emerged also as potential circulating biomarkers of several cardiac diseases.

miRNAs in bone metastasis.

Bone metastasis is one of the most common forms of metastasis from a number of different primary carcinomas. MicroRNAs (miRNAs) are short, endogenous RNAs that negatively regulate gene expression to control essential pathways, including those involved in bone organogenesis and homeostasis. As these pathways are often hijacked during bone metastasis, it is not surprising that miRNAs can also influence bone metastasis formation.

Community-acquired pneumonia by Legionella pneumophila serogroups 1-6 in Brazil.

A prospective cohort study of adult patients hospitalized due to community-acquired pneumonia was carried out for 1 year in a Brazilian university general hospital to detect the incidence of community-acquired pneumonia by Legionella pneumophila serogroups 1-6. During a whole year, a total of 645 consecutive patients who were hospitalized due to a initial presumptive diagnosis of respiratory disease by ICD-10 (J00-J99), excluding upper respiratory diseases, were screened to detect the patients with community-acquired pneumonia. Fifty-nine consecutive patients hospitalized due to community-acquired pneumonia between July 19, 2000 and July 18, 2001, were included in the study.

Immunological patterns during regular intensive training in athletes: quantification and evaluation of a preventive pharmacological approach.

The effects of regular intensive exercise training on immune system homeostasis and the potential value of treatment with an immunostimulating agent were assessed in this randomized, double-blind, placebo-controlled, parallel-group study. A total of 60 athletes were studied over a 3-month period of regular intensive physical activity. After 1 and 3 months there were significant decreases in the immunoglobulin levels in the whole athlete population compared with baseline values.

[Photoplethysmography as a means of early diagnosis of changes in the microcirculation of children and adolescents with type I diabetes. Preliminary study].

Recent progress in non invasive diagnostic techniques for the study of the microcirculation, evoked a great interest in the screening of the patients with a diabetic microangiopathy. The authors, in this paper, wanted to evaluate the usefulness of photoplethysmography in the study of the microcirculation in children affected by type I diabetes; this technique was proposed as very reliable, non invasive and easily repeatable. 42 diabetic patients, with an age from 6 to 18 years, and a group of 12 healthy subjects of the same age, as a control group, were considered.

Autoimmunity and B-cell dysfunction in chronic proliferative disorders of large granular lymphocytes/natural killer cells.

Clinical and laboratory findings of B-cell immune dysfunction were evaluated in ten patients with a large granular lymphocyte/natural killer cell proliferative disease (LGL/NK-PD). Increased immunoglobulin synthesis with autoantibody formation was documented: polyclonal hypergammaglobulinaemia (six patients), neutrophil autoantibody (one patient), antinuclear antibody (one patient), and rheumatoid factor (five patients). In addition, serum beta 2-microglobulin level was raised in seven patients, a benign monoclonal gammopathy was detected in one, and concurrent B-type hairy cell leukemia in another.

Investigation of chronic lymphocytosis in adults.

Thirteen cases of idiopathic chronic lymphocytosis are the subject of this report. Patients showed a lymphocyte count between 4 and 15 X 10(9)/L for at least six months, marrow lymphocytosis not exceeding 25%, absence of lymphomegaly and hepatosplenomegaly, and no associated infections, immune, or neoplastic disease. Morphologic examination of smears revealed a lymphocytosis of large granular lymphocytes in five.

Effect of 3-hydroxy-3-methylglutaric acid administration on bile lipid composition in humans.

The effects of the lipid-lowering agent 3-hydroxy-3-methylglutaric acid (HMGA) on serum lipids and on biliary lipid composition were evaluated in a double-blind, placebo-controlled study in normolipidemic volunteers. After 4 weeks of HMGA administration (1 g three times a day orally) serum total cholesterol showed a significant decrease with regard to both pretreatment values and corresponding values of controls. The bile lipid molar percentage composition and the cholesterol saturation index showed no modification after HMGA and did not differ from the values obtained in the placebo group.