Gene expression profiling unveils the temporal dynamics of CIGB-300-regulated transcriptome in AML cell lines.

Background: Protein kinase CK2 activity is implicated in the pathogenesis of various hematological malignancies like Acute Myeloid Leukemia (AML) that remains challenging concerning treatment. This kinase has emerged as an attractive molecular target in therapeutic. Antitumoral peptide CIGB-300 blocks CK2 phospho-acceptor sites on their substrates but it also binds to CK2α catalytic subunit.

CIGB-300 Anticancer Peptide Differentially Interacts with CK2 Subunits and Regulates Specific Signaling Mediators in a Highly Sensitive Large Cell Lung Carcinoma Cell Model.

Large cell lung carcinoma (LCLC) is one form of NSCLC that spreads more aggressively than some other forms, and it represents an unmet medical need. Here, we investigated for the first time the effect of the anti-CK2 CIGB-300 peptide in NCI-H460 cells as an LCLC model. NCI-H460 cells were highly sensitive toward CIGB-300 cytotoxicity, reaching a peak of apoptosis at 6 h.

CIGB-300-Regulated Proteome Reveals Common and Tailored Response Patterns of AML Cells to CK2 Inhibition.

Protein kinase CK2 is a highly pleiotropic and ubiquitously expressed Ser/Thr kinase with instrumental roles in normal and pathological states, including neoplastic phenotype in solid tumor and hematological malignancies. In line with previous reports, CK2 has been suggested as an attractive prognostic marker and molecular target in acute myeloid leukemia (AML), a blood malignant disorder that remains as an unmet medical need. Accordingly, this work investigates the complex landscape of molecular and cellular perturbations supporting the antileukemic effect exerted by CK2 inhibition in AML cells.

Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection.

Coronaviruses constitute a global threat to the human population; therefore, effective pan-coronavirus antiviral drugs are required to tackle future re-emerging virus outbreaks. Protein kinase CK2 has been suggested as a promising therapeutic target in COVID-19 owing to the in vitro antiviral activity observed after both pharmacologic and genetic inhibition of the enzyme. Here, we explored the putative antiviral effect of the anti-CK2 peptide CIGB-325 on bovine coronavirus (BCoV) infection using different in vitro viral infected cell-based assays.

Targeting of Protein Kinase CK2 in Acute Myeloid Leukemia Cells Using the Clinical-Grade Synthetic-Peptide CIGB-300.

Protein kinase CK2 has emerged as an attractive therapeutic target in acute myeloid leukemia (AML), an advent that becomes particularly relevant since the treatment of this hematological neoplasia remains challenging. Here we explored for the first time the effect of the clinical-grade peptide-based CK2 inhibitor CIGB-300 on AML cells proliferation and viability. CIGB-300 internalization and subcellular distribution were also studied, and the role of B23/nucleophosmin 1 (NPM1), a major target for the peptide in solid tumors, was addressed by knock-down in model cell lines.

Treatment with an Anti-CK2 Synthetic Peptide Improves Clinical Response in COVID-19 Patients with Pneumonia. A Randomized and Controlled Clinical Trial.

The instrumental role of CK2 in the SARS-CoV-2 infection has pointed out this protein kinase as promising therapeutic target in COVID-19. Anti-SARS-CoV-2 activity has been reported by CK2 inhibitors ; however, no anti-CK2 clinical approach has been investigated in COVID-19. This trial aimed to explore the safety and putative clinical benefit of CIGB-325, an anti-CK2 peptide previously assessed in cancer patients.

Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945.

Casein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosphoproteome of two cell lines representing major AML subtypes.

Postmortem Findings in Patient with Guillain-Barré Syndrome and Zika Virus Infection.

Postmortem examination results of a patient with Guillain-Barré syndrome and confirmed Zika virus infection revealed demyelination of the sciatic and cranial IV nerves, providing evidence of the acute demyelinating inflammatory polyneuropathy Guillain-Barré syndrome variant. Lack of evidence of Zika virus in nervous tissue suggests that pathophysiology was antibody mediated without neurotropism.

The role of postexercise measurements in the diagnosis of peripheral arterial disease in HIV-infected patients.

Peripheral arterial disease (PAD) is a marker of atherosclerosis, which is not well studied in the population with human immunodeficiency virus (HIV). We prospectively enrolled HIV-infected patients who had normal resting ankle-brachial index (rABI) readings. All participants performed either a treadmill walking test (TT) or pedal plantar flexion test (PFT).

Development of diagnostic criteria for serious non-AIDS events in HIV clinical trials.

Purpose: Serious non-AIDS (SNA) diseases are important causes of morbidity and mortality in the HAART era. We describe development of standard criteria for 12 SNA events for Endpoint Review Committee (ERC) use in START, a multicenter international HIV clinical trial.

Methods: SNA definitions were developed based upon the following: (1) criteria from a previous trial (SMART), (2) review of published literature, (3) an iterative consultation and review process with the ERC and other content experts, and (4) evaluation of draft SNA criteria using retrospectively collected reports in another trial (ESPRIT).

Viral load and CD4+ cell count as risk factors for prolonged QT interval in HIV-infected subjects: a cohort-nested case-control study in an outpatient population.

Background: QTc interval prolongation is a serious ECG finding which has frequently been reported in HIV-infected patients, but associated risk factors have not been determined in this population.

Methods: Data were collected from the charts of a cohort of 135 consecutive HIV-infected patients from our HIV outpatient clinic. The cohort was divided into two groups, patients with prolonged QTc and those with normal QTc interval.

Does the handling time of unrefrigerated human fecal specimens impact the detection of Clostridium difficile toxins in a hospital setting?

Background: The stability of Clostridium difficile toxins is an important factor in determining the accuracy of the enzyme immunoassay (EIA). The Centers for Disease Control has stated that C. difficile toxins may become undetectable in unrefrigerated stool specimens within 2 h after collection.

Kodamaea ohmeri fungemia in an immunocompetent patient treated with micafungin: case report and review of the literature.

Kodamaea (Pichia) ohmeri is an unusual yeast-form fungus that has recently been identified as an important etiology of fungemia, endocarditis, cellulitis, funguria and peritonitis in immunocompromised patients. We report a case of K. ohmeri fungemia in a 34-year-old hospitalized patient with thrombophlebitis.

Eosinopenia: Is it a good marker of sepsis in comparison to procalcitonin and C-reactive protein levels for patients admitted to a critical care unit in an urban hospital?

Introduction: The role of eosinopenia as a marker of sepsis has recently been evaluated. The aim of our study was to test the value of eosinopenia as a diagnostic marker of sepsis in comparison to procalcitonin and C-reactive protein levels.

Methods: A prospective study of critically ill adult patients admitted to the medical intensive care unit at an urban hospital.

Impact of adding maraviroc to antiretroviral regimens in patients with full viral suppression but impaired CD4 recovery.

We reviewed the effect of adding maraviroc on CD4 cell counts in nine patients on antiretroviral therapy with full viral suppression but impaired CD4 cell recovery. There were no significant differences in changes in CD4 cell count, percentage of CD4 cells, or in the ratio of CD4/CD8 cells at 30 days and 25 weeks of maraviroc therapy. Plasma endotoxin levels measured in four patients before and during maraviroc treatment also showed no significant differences.

Determination of the underlying cause of death in three multicenter international HIV clinical trials.

Purpose: Describe processes and challenges for an Endpoint Review Committee (ERC) in determining and adjudicating underlying causes of death in HIV clinical trials.

Method: Three randomized HIV trials (two evaluating interleukin-2 and one treatment interruption) enrolled 11,593 persons from 36 countries during 1999-2008. Three ERC members independently reviewed each death report and supporting source documentation to assign underlying cause of death; differences of opinion were adjudicated.

Comparison of prognostic importance of latest CD4+ cell count and HIV RNA levels in patients with advanced HIV infection on highly active antiretroviral therapy.

Unlabelled: The comparative prognostic importance of latest plasma HIV RNA levels (viral loads) and CD4+ cell counts among patients prescribed highly active antiretroviral therapy (HAART) has not been well characterized.

Method: We assessed the prognostic value of latest CD4+ cell counts and latest viral loads for progression to AIDS or death and explored their interaction among 432 HIV-infected persons with advanced HIV who were prescribed a protease inhibitor (PI) as their first HAART regimen.

Results: Pre-HAART median CD4+ cell count and viral load were 41 cells/mm3 and 126,331 copies/mL, respectively.

CD4(+) cell count increase predicts clinical benefits in patients with advanced HIV disease and persistent viremia after 1 year of combination antiretroviral therapy.

The relationship between 12-month CD4(+) cell count response and clinical outcome (AIDS-defining event or death) in a subset of 228 patients with a human immunodeficiency virus load >400 copies/mL despite receiving combination antiretroviral therapy as part of a larger randomized trial was defined by use of Cox models. The 12-month CD4(+) cell count responses were divided into 5 categories, ranging from decrease or no change (29% of patients) to a > or =100-cell/mm(3) increase (27% of patients). There was a lower risk of clinical progression for each incremental increase in CD4(+) cell count response.

Prevalence of GB virus type C in urban Americans infected with human immunodeficiency virus type 1.

GBV-C virus infection has been linked to improved clinical outcome in HIV-1 co-infected individuals. The epidemiology of GBV-C has, thus far, been limited to the gay male, HIV+ population. Here we describe the prevalence of antibodies against GBV-C envelope glycoprotein E2 and GBV-C viremia in an HIV+ inner city population.

A randomized clinical trial comparing nelfinavir and ritonavir in patients with advanced HIV disease (CPCRA 042/CTN 102).

Purpose: To compare the long-term clinical efficacy and toxicity of initial strategies of nelfinavir (NFV) or ritonavir (RTV) in patients with CD4+ cells below 200/mm3.

Method: This was an open-label randomized multicenter trial (CPCRA, CTN). Patients were naïve to protease inhibitor use except for hard gel saquinavir.

Prevalence and characteristics of hepatitis C virus coinfection in a human immunodeficiency virus clinical trials group: the Terry Beirn Community Programs for Clinical Research on AIDS.

The baseline prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection among 2705 patients enrolled in HIV clinical trials in the Community Programs for Clinical Research on AIDS (CPCRA) was 16.6%. For men, multivariate logistic regression showed that the baseline prevalence of HIV-HCV coinfection was positively associated with history of injection drug use, older age, antiretroviral therapy naive status, African American or Latino ethnicity, and no history of having sex with men.