Comparative response to PDT with methyl-aminolevulinate and temoporfin in cutaneous and oral squamous cell carcinoma cells.

Cutaneous and Head and Neck squamous cell carcinoma (CSCC, HNSCC) are among the most prevalent cancers. Both types of cancer can be treated with photodynamic therapy (PDT) by using the photosensitizer Temoporfin in HNSCC and the prodrug methyl-aminolevulinate (MAL) in CSCC. However, PDT is not always effective.

Panorama of the Intracellular Molecular Concert Orchestrated by Actinoporins, Pore-Forming Toxins from Sea Anemones.

Actinoporins (APs) are soluble pore-forming proteins secreted by sea anemones that experience conformational changes originating in pores in the membranes that can lead to cell death. The processes involved in the binding and pore-formation of members of this protein family have been deeply examined in recent years; however, the intracellular responses to APs are only beginning to be understood. Unlike pore formers of bacterial origin, whose intracellular impact has been studied in more detail, currently, we only have knowledge of a few poorly integrated elements of the APs' intracellular action.

Sticholysin II shows similar immunostimulatory properties to LLO stimulating dendritic cells and MHC-I restricted T cell responses of heterologous antigen.

Induction of CD8 T cell responses against tumor cells and intracellular pathogens is an important goal of modern vaccinology. One approach of translational interest is the use of liposomes encapsulating pore-forming proteins (PFPs), such as Listeriolysin O (LLO), which has shown efficacy at priming strong and sustained CD8 T cell responses. Recently, we have demonstrated that Sticholysin II (StII), a PFP from the sea anemone Stichodactyla helianthus, co-encapsulated into liposomes with ovalbumin (OVA) was able to stimulate, antigen presenting cells, antigen-specific CD8 T cells and anti-tumor activity in mice.

Selection on individuals of introduced species starts before the actual introduction.

Biological invasion is a global problem with large negative impacts on ecosystems and human societies. When a species is introduced, individuals will first have to pass through the invasion stages of uptake and transport, before actual introduction in a non-native range. Selection is predicted to act during these earliest stages of biological invasion, potentially influencing the invasiveness and/or impact of introduced populations.

Differences in adrenocortical responses between urban and rural burrowing owls: poorly-known underlying mechanisms and their implications for conservation.

The hypothalamus-pituitary-adrenal/interrenal (HPA) axis of vertebrates integrates external information and orchestrates responses to cope with energy-demanding and stressful events through changes in circulating glucocorticoid levels. Urbanization exposes animals to a wide variety of ever-changing stimuli caused by human activities that may affect local wildlife populations. Here, we empirically tested the hypothesis that urban and rural owls () show different adrenocortical responses to stress, with urban individuals showing a reduced HPA-axis response compared to rural counterparts to cope with the high levels of human disturbance typical of urban areas.

Trabectedin for reversing platinum resistance and resensitization to platinum in patients with recurrent ovarian cancer.

Aims: We evaluated trabectedin in patients with platinum-resistant/refractory and partially platinum-sensitive recurrent ovarian cancer and the outcomes after reintroduction of platinum.

Methods: Twenty-seven patients (platinum-resistant/refractory n = 24/PPS; n = 3) treated with trabectedin were retrospectively analyzed.

Results: Trabectedin resulted in an objective response rate (ORR) of 18.

Corticosterone implants produce stress-hyporesponsive birds.

In birds, the use of corticosterone (Cort) implants is a frequent tool aimed at simulating systemic elevations of this hormone and studying effects on biological traits (e.g. physiology, morphology, behavior).

Dengue Virus Induces Increased Activity of the Complement Alternative Pathway in Infected Cells.

Severe dengue virus (DENV) infection is associated with overactivity of the complement alternative pathway (AP) in patient studies. Here, the molecular changes in components of the AP during DENV infection were investigated. mRNA for factor H (FH), a major negative regulator of the AP, was significantly increased in DENV-infected endothelial cells (EC) and macrophages, but, in contrast, production of extracellular FH protein was not.

Magnetic core mesoporous silica nanoparticles doped with dacarbazine and labelled with 99mTc for early and differential detection of metastatic melanoma by single photon emission computed tomography.

Cancer is responsible for more than 12% of all causes of death in the world, with an annual death rate of more than 7 million people. In this scenario melanoma is one of the most aggressive ones with serious limitation in early detection and therapy. In this direction we developed, characterized and tested in vivo a new drug delivery system based on magnetic core-mesoporous silica nanoparticle that has been doped with dacarbazine and labelled with technetium 99 m to be used as nano-imaging agent (nanoradiopharmaceutical) for early and differential diagnosis and melanoma by single photon emission computed tomography.

Indirect calculation of monoclonal antibodies in nanoparticles using the radiolabeling process with technetium 99 metastable as primary factor: Alternative methodology for the entrapment efficiency.

The use of monoclonal antibodies (Mab) in the current medicine is increasing. Antibody-drug conjugates (ADCs) represents an increasingly and important modality for treating several types of cancer. In this area, the use of Mab associated with nanoparticles is a valuable strategy.

Biophysical and biochemical strategies to understand membrane binding and pore formation by sticholysins, pore-forming proteins from a sea anemone.

Actinoporins constitute a unique class of pore-forming toxins found in sea anemones that are able to bind and oligomerize in membranes, leading to cell swelling, impairment of ionic gradients and, eventually, to cell death. In this review we summarize the knowledge generated from the combination of biochemical and biophysical approaches to the study of sticholysins I and II (Sts, StI/II), two actinoporins largely characterized by the Center of Protein Studies at the University of Havana during the last 20 years. These approaches include strategies for understanding the toxin structure-function relationship, the protein-membrane association process leading to pore formation and the interaction of toxin with cells.

Damage of eukaryotic cells by the pore-forming toxin sticholysin II: Consequences of the potassium efflux.

Pore-forming toxins (PFTs) form holes in membranes causing one of the most catastrophic damages to a target cell. Target organisms have evolved a regulated response against PFTs damage including cell membrane repair. This ability of cells strongly depends on the toxin concentration and the properties of the pores.

Lifetime variation in feather corticosterone levels in a long-lived raptor.

In long-lived animals, the challenges that threaten individual homeostasis, and the way they are dealt with, are expected to vary in an age-related manner, encompassing the progressive selection of superior phenotypes and the acquisition and improvement of key skills (e.g. foraging, breeding and fighting abilities).

Effects of Ontogeny, Diel Rhythms, and Environmental Variation on the Adrenocortical Physiology of Semialtricial Black Kites (Milvus migrans).

We examined whether hypothalamic-pituitary-adrenal axis activity in the nestlings of a semialtricial raptor, the black kite (Milvus migrans), varied with advancing age, throughout the day, and in response to a number of socioecological factors presumed to affect allostatic load. Both baseline corticosterone (CORT) titers and maximum CORT levels during 30 min of handling and restraint augmented across all sampled ages, suggesting that nestlings' energetic demands and capacity to respond to perturbations increase progressively throughout development. CORT secretion also peaked in the early morning, reached minimum levels in the central hours of the day, and increased again before dusk, suggesting a possible role of CORT in the regulation of activity-inactivity patterns.

CD69 expression potentially predicts response to bendamustine and its modulation by ibrutinib or idelalisib enhances cytotoxic effect in chronic lymphocytic leukemia.

Clinical responses to bendamustine in chronic lymphocytic leukemia (CLL) are highly heterogeneous and no specific markers to predict sensitivity to this drug have been reported. In order to identify biomarkers of response, we analyzed the in vitro activity of bendamustine and the gene expression profile in primary CLL cells. We observed that mRNA expression of CD69 (CD69) and ITGAM (CD11b) constitute the most powerful predictor of response to bendamustine.

Links between fear of humans, stress and survival support a non-random distribution of birds among urban and rural habitats.

Urban endocrine ecology aims to understand how organisms cope with new sources of stress and maintain allostatic load to thrive in an increasingly urbanized world. Recent research efforts have yielded controversial results based on short-term measures of stress, without exploring its fitness effects. We measured feather corticosterone (CORTf, reflecting the duration and amplitude of glucocorticoid secretion over several weeks) and subsequent annual survival in urban and rural burrowing owls.

Evaluation of a novel multiplex RT-qPCR assay for the quantification of leukemia-associated BCR-ABL1 translocation.

Although monitoring of BCR-ABL1 translocation has become an established practice in the management of chronic myeloid leukemia (CML), the detection limit of the BCR-ABL1 transcripts needs more standardization. The aim of the present study was to evaluate the clinical performances of a novel assay for the quantification of BCR-ABL1 fusion transcripts (e13a2 and e14a2) and ABL1 in a single reaction. This assay is based on the real-time reverse transcription polymerase chain reaction (RT-qPCR) in multiplex format.

Lapatinib plus trastuzumab in pretreated human epidermal growth factor receptor 2-positive metastatic breast cancer.

Background: Dual human epidermal growth factor receptor 2 (HER2) blockade has been preclinically and clinically assessed in HER2-overexpressing metastatic breast cancer (mBC) with encouraging results.

Patients And Methods: This is a descriptive retrospective study of trastuzumab plus lapatinib activity in patients with HER2-overexpressing mBC from two centers. The primary endpoints were to assess objective response rate (ORR) and toxicity.

Clonal evolution in chronic lymphocytic leukemia: analysis of correlations with IGHV mutational status, NOTCH1 mutations and clinical significance.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder characterized with highly variable clinical course. The most common chromosomal abnormalities in CLL, using conventional and molecular cytogenetics, are trisomy 12, del(13)(q14), del(11)(q22-23), del(17)(p13), and del(6)(q21). Whereas the prognostic marker such as IGHV mutational status remains stable during course of the diseases, chromosomal aberrations may be acquired over time.

Characterization and adequacy of the use of radiotherapy and its trend in time.

Background And Purpose: Characterization of radiotherapy activity and its trend over time. Gathering of parameters for future planning of our resources, applicable to similar population areas. Performing a clinical audit of appropriate use of radiotherapy.

The two component adjuvant IC31® potentiates the protective immunity induced by a dengue 2 recombinant fusion protein in mice.

Here we evaluated the suitability of the synthetic adjuvant IC31® to potentiate the protective capacity of PD5 protein (domain III of the envelope protein of dengue 2 virus fused to the carrier protein P64k). Unlike Alum, PD5 mixed with IC31® induced complete protection against virus challenge in mice and increased IFN-γ secretion after in vitro re-stimulation. The induced antibody response was highly specific to the homologous serotype and showed both IgG1 and IgG2a subtypes.

Phage-displayed antibody fragments recognizing dengue 3 and dengue 4 viruses as tools for viral serotyping in sera from infected individuals.

The current study shows the usefulness of dengue-3- and dengue-4-specific phage-displayed antibody fragments as tools for viral detection and serotyping in sera from infected individuals. C6/36 HT cells were inoculated with acute-phase sera from patients, and supernatants were collected daily and analyzed by ELISA using phage-displayed antibody fragments as serotype-specific detector reagents. Serotyping of most samples was possible as early as two to three days postinoculation.