Adjuvant dabrafenib and trametinib for patients with resected BRAF -mutated melanoma: DESCRIBE-AD real-world retrospective observational study.

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF - V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice.

Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial.

Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the "on-off" schedule.

Autoimmune Responses in Oncology: Causes and Significance.

Specific anti-tumor immune responses have proven to be pivotal in shaping tumorigenesis and tumor progression in solid cancers. These responses can also be of an autoimmune nature, and autoantibodies can sometimes be present even before the onset of clinically overt disease. Autoantibodies can be generated due to mutated gene products, aberrant expression and post-transcriptional modification of proteins, a pro-immunogenic milieu, anti-cancer treatments, cross-reactivity of tumor-specific lymphocytes, epitope spreading, and microbiota-related and genetic factors.

Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays.

Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response.

Value of PD-L1, PD-1, and CTLA-4 Expression in the Clinical Practice as Predictors of Response to Nivolumab and Ipilimumab in Monotherapy in Patients With Advanced Stage Melanoma.

Background: The introduction of immune checkpoint inhibitors (ICI) has improved the survival outcomes of patients with advanced melanoma. To date, only a few studies have evaluated the immunohistochemical (IHC) expression of PD-1 and CTLA-4 in tumor-infiltrating lymphocytes (TILs) as predictive markers of response to ICI, most of them in the context of clinical trials. Moreover, the predictive value of PD-L1 in melanoma cells in the response to immunotherapy is unclear.

Relevance of Reference Centers in Sarcoma Care and Quality Item Evaluation: Results from the Prospective Registry of the Spanish Group for Research in Sarcoma (GEIS).

Background: Reference centers (RCs) are a key point for improving the survival of patients with soft-tissue sarcomas (STS). The aim of this study was to evaluate selected items in the management of patients with STS, comparing results between RC and local hospitals (LHs).

Materials And Methods: Diagnostic and therapeutic data from patients diagnosed between January 2004 and December 2011 were collected.

Radiotracer estimates of benthic activity effects on trace metal diffusion into mangrove sediments.

Potential influences of the whole benthic organisms' activity (i.e., coupled faunal and microbial effects) on (58)Co, (51)Cr and (65)Zn diffusion into surface mangrove sediment layers (0-6 cm depth) were evaluated in 36 h experiments.

Pseudoephedrine inhibits T-cell activation by targeting NF-κB, NFAT and AP-1 signaling pathways.

Pseudoephedrine (PSE) is a stereoisomer of ephedrine that is commonly used as a nasal decongestant in combination with other anti-inflammatory drugs for the symptomatic treatment of some common pathologies such as common cold. Herein, we describe for the first time the effects of PSE on T-cell activation events. We found that PSE inhibits interleukin-2 (IL-2) and tumor necrosis factor (TNF) alpha-gene transcription in stimulated Jurkat cells, a human T-cell leukemia cell line.

Genotype of the CYBA promoter -930A/G, polymorphism C677T of the MTHFR and APOE genotype in patients with hypertensive disorders of pregnancy: an observational study.

Background And Objective: Hypertensive disorders of pregnancy could be favoured by polymorphisms in genes affecting vascular physiology. The aim of our work was to study several variants in the genes regulating oxidative stress, plasma lipids metabolism and endothelial function (observational study).

Material And Methods: We studied the -930A/G polymorphism of the CYBA gene promoter, the apolipoprotein E (APOE) genotype and the methylene-tetrahydrofolate reductase (MTHFR) gene C677T polymorphism in 134 healthy pregnant women, 266 pregnant with non-proteinuric hypertension (NPH) and 184 patients with preeclampsia (PE).

Human recombinant erythropoietic agents do not induce changes in circulating levels of endoglin and vascular endothelial growth factor in anemic cancer patients.

The correlation of erythropoietin (EPO) receptor levels with angiogenesis and progression in some cancers has suggested that EPO could acts directly as an angiogenic factor. The purpose of this study was to assess the effect of treatment with human recombinant erythropoietic (rHuEPO) agents in cancer patients with chemotherapy-induced anaemia on endoglin and vascular endothelial growth factor (VEGF) circulating levels as a possible marker of angiogenesis. Endoglin and VEGF were measured in serum samples from 25 cancer patients with chemotherapy-induced anemia before and after 3-4 weeks of treatment with rHuEPO.

The oxidation-reduction state of serum proteins in multiple sclerosis patients: effect of interferon beta-1b.

The concentration of reduction equivalents in serum was studied in a cohort of healthy individuals, in a group of multiple sclerosis (MS) patients undergoing treatment with interferon beta-1b and another group of MS patients who refused treatment with interferon beta-1b. Two classes of sulfhydryl groups were detectable in serum: (1) the uncovered sulfhydryls, accessible to the oxidation-reduction substrate 5,5-dithiobis-(-2-nitrobenzoic acid) (DTNB); and (2) the hidden sulfhydryls that required previous heat denaturation of serum proteins to become accessible to DTNB. The concentration of the reduced form of both the uncovered- and hidden-type of sulfhydryls was higher in the serum of MS patients than in healthy individuals.

Receptor-independent mechanisms are involved in the priming of neutrophil's oxidase by vasoactive intestinal peptide.

Vasoactive intestinal peptide (VIP) primed the respiratory burst of human neutrophils induced by phorbol myristate acetate (PMA) and by the chemotactic peptide N-formyl-Met-Leu-Phe (fMLP). The sigmoidal-shaped curve of the priming effect of VIP differs for both agonist since the Hill coefficient was close to three in the case of neutrophil activation by fMLP whereas the corresponding value for PMA was close to one. The priming effect of VIP was enhanced when neutrophils were stimulated by FMLP in the presence of sphinganine, a protein kinase C inhibitor, at concentrations which almost abolished the response to PMA.

Vasoactive intestinal peptide inhibits fMLP-induced respiratory burst in human lymphocytes.

N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) induced in lymphocytes the production of reactive oxygen intermediates in a process which was inhibited by the presence of Vasoactive Intestinal Peptide (VIP) in a dose-dependent response at VIP concentrations in the range 10(-10)-10(-7) M. The dissociation constant for the high-affinity receptors of VIP agrees with the ID50 of the activation of adenylate cyclase which are close to 0.2 nM VIP, whereas the ID50 for the inhibition by VIP of fMLP-induced chemiluminescence approaches to 5 nM VIP.