Caveolin-1 is a risk factor for postsurgery metastasis in preclinical melanoma models

Melanomas are highly lethal skin tumours that are frequently treated by surgical resection. However, the efficacy of such procedures is often limited by tumour recurrence and metastasis. Caveolin-1 (CAV1) has been attributed roles as a tumour suppressor, although in late-stage tumours, its presence is associated with enhanced metastasis. The expression of this protein in human melanoma development and particularly how the presence of CAV1 affects metastasis after surgery has not been defined. CAV1 expression in human melanocytes and melanomas increases with disease progression and is highest in metastatic melanomas. The effect of increased CAV1 expression can then be evaluated using B16F10 murine melanoma cells injected into syngenic immunocompetent C57BL/6 mice or human A375 melanoma cells injected into immunodeficient B6Rag1−/− mice. Augmented CAV1 expression suppresses tumour formation upon a subcutaneous injection, but enhances lung metastasis of cells injected into the tail vein in both models. A procedure was initially developed using B16F10 melanoma cells in C57BL/6 mice to mimic better the situation in patients undergoing surgery. Subcutaneous tumours of a defined size were removed surgically and local tumour recurrence and lung metastasis were evaluated after another 14 days. In this postsurgery setting, CAV1 presence in B16F10 melanomas favoured metastasis to the lung, although tumour suppression at the initial site was still evident. Similar results were obtained when evaluating A375 cells in B6Rag1−/− mice. These results implicate CAV1 expression in melanomas as a marker of poor prognosis for patients undergoing surgery as CAV1 expression promotes experimental lung metastasis in two different preclinical models

Does native Trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection?

Indexación: Web of Science.Background: For several decades now an antagonism between Trypanosoma cruzi infection and tumor development has been detected. The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. Thus, recombinant TcCRT (rTcCRT) has important in vivo antiangiogenic and antitumor activities. However, the relevant question whether the in vivo antitumor effect of T. cruzi infection is indeed mediated by the native chaperone (nTcCRT), remains open. Herein, by using specific modified anti-rTcCRT antibodies (Abs), we have neutralized the antitumor activity of T. cruzi infection and extracts thereof, thus identifying nTcCRT as a valid mediator of this effect. Methods: Polyclonal anti-rTcCRT F(ab')(2) Ab fragments were used to reverse the capacity of rTcCRT to inhibit EAhy926 endothelial cell (EC) proliferation, as detected by BrdU uptake. Using these F(ab')(2) fragments, we also challenged the capacity of nTcCRT, during T. cruzi infection, to inhibit the growth of an aggressive mammary adenocarcinoma cell line (TA3-MTXR) in mice. Moreover, we determined the capacity of anti-rTcCRT Abs to reverse the antitumor effect of an epimastigote extract (EE). Finally, the effects of these treatments on tumor histology were evaluated. Results: The rTcCRT capacity to inhibit ECs proliferation was reversed by anti-rTcCRT F(ab')(2) Ab fragments, thus defining them as valid probes to interfere in vivo with this important TcCRT function. Consequently, during infection, these Ab fragments also reversed the in vivo experimental mammary tumor growth. Moreover, anti-rTcCRT Abs also neutralized the antitumor effect of an EE, again identifying the chaperone protein as an important mediator of this anti mammary tumor effect. Finally, as determined by conventional histological parameters, in infected animals and in those treated with EE, less invasive tumors were observed while, as expected, treatment with F(ab')(2) Ab fragments increased malignancy. Conclusion: We have identified translocated/externalized nTcCRT as responsible for at least an important part of the anti mammary tumor effect of the chaperone observed during experimental infections with T. cruzi.http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2764-

Fabrication and arc erosion behavior of Ag-SnO2-ZnO electrical contact materials

This study investigated the synthesis of Ag-SnO2-ZnO by powder metallurgy methods and their subsequent electrical contact behavior. The pieces of Lambda g-SnO2-ZnO were prepared by ball milling and hot pressing. The arc erosion behavior of the material was evaluated using homemade equipment. The microstructure and phase evolution of the materials were investigated through X-ray diffraction, energy-dispersive spectroscopy and scanning electron microscopy. The results showed that, although the mass loss of the Ag-SnO2-ZnO composite (9.08 mg) during the electrical contact test was higher than that of the commercial Ag-CdO (1.42 mg), its electrical conductivity remained constant (26.9 +/- 1.5% IACS). This fact would be related to the reaction of Zn2SnO4's formation on the material's surface via electric arc. This reaction would play an important role in controlling the surface segregation and subsequent loss of electrical conductivity of this type of composite, thus enabling the development of a new electrical contact material to replace the non-environmentally friendly Ag-CdO composite

Desarrollo de una gelatina hipocalórica, con fresa y rica en proteína.

Debido al grave problema de obesidad en México, la tendencia es a desarrollar productos con alto valor nutritivo, hipocalóricos y fáciles de consumir. El objetivo de este trabajo fue elaborar una gelatina hipocalórica y rica en proteínas, utilizando proteína de soya y fresas como fuente de antioxidantes. Se realizó la evaluación sensorial. Se le determinó la humedad y los lípidos (AOAC, 1990), se calculó la información nutrimental y el Puntaje Químico Corregido por la Digestibilidad verdadera (PDCAAS) de la proteína. Sensorialmente se logró una aceptación mayor al 75%. Por ración esta gelatina contiene 10.82 g de proteína con un PDCAAS de 94.25 %, y tan solo 121.88 kcal, adicionalmente contiene los antioxidantes de la fresa y no contiene azúcar. Se concluye que este es un producto con alto valor nutricio de fácil consumo, ideal para un desayuno o colación

Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens

SummaryBackgroundThe nasal vaccine candidate (NASVAC), comprising hepatitis B virus (HBV) surface (HBsAg) and core antigens (HBcAg), has been shown to be highly immunogenic in animal models.MethodsA phase I double-blinded, placebo-controlled randomized clinical trial was carried out in 19 healthy male adults with no serologic markers of immunity/infection to HBV. This study was aimed at exploring the safety and immunogenic profile of nasal co-administration of both HBV recombinant antigens. The trial was performed according to Good Clinical Practice guidelines. Participants ranged in age from 18 to 45 years and were randomly allocated to receive a mixture of 50μg HBsAg and 50μg HBcAg or 0.9% physiologic saline solution, as a placebo, via nasal spray in a five-dose schedule at 0, 7, 15, 30, and 60 days. A total volume of 0.5ml was administered in two dosages of 125μl per nostril. Adverse events were actively recorded 1h, 6h, 12h, 24h, 48h, 72h, 7 days and 30 days after each dose. Anti-HBs and anti-HBc titers were evaluated using corresponding ELISA kits at days 30 and 90.ResultsThe vaccine candidate was safe and well tolerated. Adverse reactions included sneezing (34.1%), rhinorrhea (12.2%), nasal stuffiness (9.8%), palate itching (9.8%), headache (9.8%), and general malaise (7.3%). These reactions were all self-limiting and mild in intensity. No severe or unexpected events were recorded during the trial. The vaccine elicited anti-HBc seroconversion in 100% of subjects as early as day 30 of the immunization schedule, while a seroprotective anti-HBs titer (≥10IU/l) was at a maximum at day 90 (75%). All subjects in the placebo group remained seronegative during the trial.ConclusionThe HBsAg–HBcAg vaccine candidate was safe, well tolerated and immunogenic in this phase I study in healthy adults. To our knowledge, this is the first demonstration of safety and immunogenicity for a nasal vaccine candidate comprising HBV antigens

Pseudoprogression and hyperprogression secondary to immunotherapy in lung cancer

BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) has undergone changes that have improved the prognosis of patients. With the advent of immunotherapy, it has been possible to prolong significantly the overall and progression-free survival as well as quality of life. Nevertheless, its use represents clinical challenges which may turn into adverse events, such as progression and pseudo-progression, which are uncontrolled and often deleterious immune responses that simulate tumoral progression, generate worsening of symptoms and performance status of patients and even may lead to non-cancer related death of patients. MATERIALS AND METHODS: We assessed 128 records (clinical trials, reports, meta-analyses) in order to provide an updated review of the treatment of NSCLC, current definitions proposed for pseudo and hyperprogression (which are not homogeneous so far), incidence, theories about their physiopathogenesis, importance of making a judicious diagnostic workup, imaging criteria as well as biochemical markers in order to predict their appearance, concluding with a brief discussion about the topic addressed. CONCLUSIONS: Since there is no definition or standardized diagnostic and imaging criteria, these entities are a topic of major interest in the area of oncologic immunotherapy, for which the following review has been generated

Antioxidant properties of soy-dairy milk blends fermented with probiotics

ABSTRACT Objective: Evaluate the effect of the substitution of cow milk with soy beverage on the antioxidant properties, physicochemical parameters, and sensory quality of the probiotic and conventional fermented beverages. Design/methodology/approach: Different combinations of soy beverage (T1=80%, T2=60%, T3=40%, and T4=20%) with cow milk (20%, 40%, 60%, and 80%, respectively) were fermented with either conventional or probiotic cultures. The antioxidant activity of fermented beverages was evaluated by DPPH method and the samples were also characterized for protein, fat, solids non-fat, density, and acidity. Sensory evaluation was done in order to determine the acceptability of the fermented beverages. Results: Overall, most treatments fermented with the probiotic culture showed higher (P<0.05) antioxidant capacity compared to those fermented with the conventional culture. In contrast, for both starter cultures, it was observed that the T1 treatment displayed the highest (P<0.05) antioxidant activity compared with the other treatments (T2, T3, and T4). Similarly, the treatment T1-probiotic culture was the most preferred, being the aroma and appearance, the sensory properties scored with the highest degree of liking. Study Limitations: Follow-up research is needed to identify the bioactive compounds responsible for antioxidant properties exhibited by fermented soy-dairy milk beverages. Findings/conclusions: Probiotic cultures can be used to generate soy-dairy milk fermented beverages with noticeable antioxidant and sensory properties.Objective: Evaluate the effect of the substitution of cow milk with soy beverage on the antioxidant properties, physicochemical parameters, and sensory quality of the probiotic and conventional fermented beverages.Design/methodology/approach: Different combinations of soy beverage (T1=80%, T2=60%, T3=40%, and T4=20%) with cow milk (20%, 40%, 60%, and 80%, respectively) were fermented with either conventional or probiotic cultures. The antioxidant activity of fermented beverages was evaluated by DPPH method and the samples were also characterized for protein, fat, solids non-fat, density, and acidity. Sensory evaluation was done in order to determine the acceptability of the fermented beverages.Results: Overall, most treatments fermented with the probiotic culture showed higher (P<0.05) antioxidant capacity compared to those fermented with the conventional culture. In contrast, for both starter cultures, it wasobserved that the T1 treatment displayed the highest (P<0.05) antioxidant activity compared with the other treatments (T2, T3, and T4). Similarly, the treatment T1-probiotic culture was the most preferred, being the aroma and appearance, the sensory properties scored with the highest degree of liking. Study Limitations: Follow-up research is needed to identify the bioactive compounds responsible for antioxidant properties exhibited by fermented soy-dairy milk beverages.Findings/conclusions: Probiotic cultures can be used to generate soy- dairy milk fermented beverages with noticeable antioxidant and sensory properties

Diversity in the Architecture of ATLs, a Family of Plant Ubiquitin-Ligases, Leads to Recognition and Targeting of Substrates in Different Cellular Environments

Ubiquitin-ligases or E3s are components of the ubiquitin proteasome system (UPS) that coordinate the transfer of ubiquitin to the target protein. A major class of ubiquitin-ligases consists of RING-finger domain proteins that include the substrate recognition sequences in the same polypeptide; these are known as single-subunit RING finger E3s. We are studying a particular family of RING finger E3s, named ATL, that contain a transmembrane domain and the RING-H2 finger domain; none of the member of the family contains any other previously described domain. Although the study of a few members in A. thaliana and O. sativa has been reported, the role of this family in the life cycle of a plant is still vague. To provide tools to advance on the functional analysis of this family we have undertaken a phylogenetic analysis of ATLs in twenty-four plant genomes. ATLs were found in all the 24 plant species analyzed, in numbers ranging from 20–28 in two basal species to 162 in soybean. Analysis of ATLs arrayed in tandem indicates that sets of genes are expanding in a species-specific manner. To get insights into the domain architecture of ATLs we generated 75 pHMM LOGOs from 1815 ATLs, and unraveled potential protein-protein interaction regions by means of yeast two-hybrid assays. Several ATLs were found to interact with DSK2a/ubiquilin through a region at the amino-terminal end, suggesting that this is a widespread interaction that may assist in the mode of action of ATLs; the region was traced to a distinct sequence LOGO. Our analysis provides significant observations on the evolution and expansion of the ATL family in addition to information on the domain structure of this class of ubiquitin-ligases that may be involved in plant adaptation to environmental stress