In vivo antitumor effect of proteoglycan fraction from Agaricus brasiliensis does not depend on the production of antitumor antibodies / O efeito antitumoral in vivo da fração proteoglicana de Agaricus brasiliensis não depende da produção de anticorpos antitumorais

Polysaccharides isolated from the edible mushroom Agaricus brasiliensis were previously shown to have antitumor, antiproliferative, and immunomodulatory activity. Here, we evaluated the in vivo effect of the acid-treated fraction from A. brasiliensis (ATF) on the subcutaneous growth of Ehrlich tumor cells (EHR) and on the production of tumor-specific antibodies. Mice (n=10) were inoculated with 2 × 106 EHR and injected subcutaneously in the tumor inoculum region with 0.1 mL ATF or saline. Control (tumor-free) group received ATF or saline. Treatments were carried out for 7, 14, or 30 days, with three consecutive doses and an interval of 4 days between the first and last doses, being repeated until the end of each experimental period.  Histopathological analysis shows the infiltration of mononuclear and polymorphonuclear cells into the tumor site of all tumor-bearing mice. Tumor stimulated the influx of polymorphonuclear cells in the early stages, especially at 7 days, while the influx of mononuclear cells was higher in the final stages, at 14 and 30 days in all animals, independently of the treatment with ATF. Treatment of animals for 30 days reduced the tumor weight in 30% but we did not find a correlation with the antitumor antibody production since both treated and untreated mice were able to produce them

The Effect of Annealing Temperatures After Thermomechanical Process to the Corrosion Behavior of Ni3(si,ti) in Sulfate Solution

The corrosion behaviour of the intermetallic compounds Ni3(Si,Ti) (L12: single phase), has been investigated using an immersion test, polarization method, scanning electron microscope in 0.5 kmol/m3 H2SO4 solution at 303 K. Moreover, the corrosion behaviour of austenitic stainless steel type 304 was studied under the same experimental conditions as reference. It was found that the intergranular attack and uniform attack were observed on Ni3(Si,Ti) after thermomechanical and annealing processes (1173K and 1273K) respectively in the immersion test. From the immersion test and polarization curves, all annealed Ni3(Si,Ti) had less corrosion resistance compared to type 304. In addition, Ni3(Si,Ti) was difficult to form a stable passive film, but not for type 304

The environment-induced cracking of as-annealed Ni3(Si,Ti) and Ni3(Si,Ti) with 2Mo in sodium chloride solutions

Accepted manuscript version. The final publication is available at Springer via http://doi.org/10.1186/s40712-015-0046-7.Background The environment-induced cracking (EIC) of as-annealed Ni3(Si,Ti) and Ni3(Si,Ti) with 2Mo has been researched as functions of applied stress, chloride ion concentration, test temperature, and pH. Methods The investigation of EIC was carried out by applying a constant method in NaCl solutions. Results The EIC susceptibility of both intermetallic compounds increased with increasing test temperature and Cl− ion concentration and increased with decreasing pH. The fracture surface morphologies of Ni3(Si,Ti) was intergranular while Ni3(Si,Ti) with 2Mo was a mixture of intergranular and transgranular, and the relationship between log t f (time to failure) and log l ss (steady-state elongation rate) became the identical straight line irrespective of applied stress, chloride ion concentration, test temperature, and pH, which means that l ss becomes a relevant parameter for predicting t f. The EIC susceptibility of Ni3(Si,Ti) with 2Mo was lower than that of Ni3(Si,Ti), which showed the advantageous effect of Mo. Conclusions From the results acquired, EIC of both the compounds was indicated to take place by hydrogen embrittlement (HE)

The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al

Quaternionic potentials in non-relativistic quantum mechanics

We discuss the Schrodinger equation in presence of quaternionic potentials. The study is performed analytically as long as it proves possible, when not, we resort to numerical calculations. The results obtained could be useful to investigate an underlying quaternionic quantum dynamics in particle physics. Experimental tests and proposals to observe quaternionic quantum effects by neutron interferometry are briefly reviewed.Comment: 21 pages, 16 figures (ps), AMS-Te

Proteomic profile of KSR1-regulated signalling in response to genotoxic agents in breast cancer

Kinase suppressor of Ras 1 (KSR1) has been implicated in tumorigenesis in multiple cancers, including skin, pancreatic and lung carcinomas. However, our recent study revealed a role of KSR1 as a tumour suppressor in breast cancer, the expression of which is potentially correlated with chemotherapy response. Here, we aimed to further elucidate the KSR1-regulated signalling in response to genotoxic agents in breast cancer. Stable isotope labelling by amino acids in cell culture (SILAC) coupled to high-resolution mass spectrometry (MS) was implemented to globally characterise cellular protein levels induced by KSR1 in the presence of doxorubicin or etoposide. The acquired proteomic signature was compared and GO-STRING analysis was subsequently performed to illustrate the activated functional signalling networks. Furthermore, the clinical associations of KSR1 with identified targets and their relevance in chemotherapy response were examined in breast cancer patients. We reveal a comprehensive repertoire of thousands of proteins identified in each dataset and compare the unique proteomic profiles as well as functional connections modulated by KSR1 after doxorubicin (Doxo-KSR1) or etoposide (Etop-KSR1) stimulus. From the up-regulated top hits, several proteins, including STAT1, ISG15 and TAP1 are also found to be positively associated with KSR1 expression in patient samples. Moreover, high KSR1 expression, as well as high abundance of these proteins, is correlated with better survival in breast cancer patients who underwent chemotherapy. In aggregate, our data exemplify a broad functional network conferred by KSR1 with genotoxic agents and highlight its implication in predicting chemotherapy response in breast cancer

P-MAPA and interleukin-12 reduce cell migration/invasion and attenuate the toll-like receptor-mediated inflammatory response in ovarian cancer SKOV-3 cells : a preliminary study

Immunotherapies have emerged as promising complementary treatments for ovarian cancer (OC), but its effective and direct role on OC cells is unclear. This study examined the combinatory effects of the protein aggregate magnesium–ammonium phospholinoleate–palmitoleate anhydride, known as P-MAPA, and the human recombinant interleukin-12 (hrIL-12) on cell migration/invasion, apoptosis, toll-like receptor (TLR)-mediated inflammation, and cytokine/chemokine profile in human OC cell line SKOV-3. P-MAPA and IL-12 showed cancer cell toxicity under low doses after 48 h. Although apoptosis/necrosis and the cell cycle were unchanged by the treatments, P-MAPA enhanced the sensitivity to paclitaxel (PTX) and P-MAPA associated with IL-12 significantly reduced the migratory potential and invasion capacity of SKOV-3 cells. P-MAPA therapy reduced TLR2 immunostaining and the myeloid differentiation factor 88 (MyD88), but not the TLR4 levels. Moreover, the combination of P-MAPA with IL-12 attenuated the levels of MyD88, interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB p65). The IL-12 levels were increased and P-MAPA stimulated the secretion of cytokines IL-3, IL-9, IL-10, and chemokines MDC/CCL22 and, regulated on activation, normal T cells expressed and secreted (RANTES)/CCL5. Conversely, combination therapy reduced the levels of IL-3, IL-9, IL-10, MDC/CCL22, and RANTES/CCL5. Collectively, P-MAPA and IL-12 reduce cell dynamics and effectively target the TLR-related downstream molecules, eliciting a protective effect against chemoresistance. P-MAPA also stimulates the secretion of anti-inflammatory molecules, possibly having an immune response in the OC microenvironment2515CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP401040/2016-00708/20182019/00906-6; 2016/03993-9We would like to give a special thanks to Farmabrasilis-Brazil, FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, grant numbers: 2019/00906-6 and 2016/03993-9), CAPES (grant number: 0708/2018), and CNPq (grant number: 401040/2016-0) by providing financial suppor

Time and cell-dependent effects of endocytosis inhibitors on the internalization of biomolecule markers and nanomaterials

Endocytosis is an essential function of cells, with key roles in the internalisation of nutrients, signal molecules and also drugs. Endocytic processes are therefore widely investigated in the context of drug delivery, and inhibitors of endocytic pathways have been used to provide information regarding uptake mechanisms of drug carrier materials. Here we describe studies in which two established inhibitors of clathrin dependent and independent endocytosis, chlorpromazine and methyl‐β‐cyclodextrin respectively, were employed to probe endocytic pathways of three cell lines chosen to represent tumour‐relevant or associated phenotypes: 3 T3 (fibroblasts), HCT 116 (colon cancer) and MGLVA‐1 (gastric cancer). For clathrin mediated endocytosis the data highlight that chlorpromazine inhibition of transferrin internalization, via clathrin dependent endocytosis, is cell and time dependent. We also show that inhibition of uptake is transient with a resumption of transferrin internalization after a maximal inhibition period. The same endocytosis inhibitors were used to probe the internalization of 50 and 100 nm carboxylated polystyrene nanoparticles (C‐PS‐NPs) as model drug delivery carriers. Flow cytometry data indicated that internalisation of C‐PS‐NPs varied considerably with the incubation time of cells with chlorpromazine or methyl‐β‐cyclodextrin, and that the effects were also markedly cell‐line dependent. These data highlight that the effects of endocytosis inhibitors on the internalisation pathways even of relatively simple nanoparticles are complex and interdependent. We suggest that mechanistic investigations of the endocytic processes which govern practical applications of nanoparticles for diagnostic and therapeutic applications should be considered on a cell, time and concentration basis