Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

n/

Biostimulants promoting growth of Vicia faba L. seedlings: inulin coated ZnO nanoparticles

In the present contribution, inulin coated ZnO nanoparticles (ZnO@inu NPs) were investigated for their potential application on crop production systems, by appraisal of their biostimulating effects on Vicia faba L (faba bean). Naked and coated ZnO NPs were synthesized according to purposely implemented eco-friendly protocols and characterized with multiple techniques to determine their crystallographic phase, average particle size, and degree of coating. Faba beans were grown in culture medium supplemented with NPs at 50 or 100 mg kg−1, using ZnO NPs alone, inulin alone, a mixture of the two, or ZnO@inu NPs. Seed germination rate and biometric evaluations on seedlings were carried out, together with Zn localization in the plant tissues. cellular and molecular effects were ascertained by analyses of photosynthetic pigments, cytotoxicity, genotoxicity, viability, induction of oxidative stress and tissue damage, antioxidant response, and modulation of gene expression. these combined studies indicated a potential role of ZnO@inu NPs in promoting growth and development of V. faba seedlings, acting at a post-germinative phase, probably by stimulating the stem cell mitosis. Finally, inulin as a coating agent for the ZnO NPs favored the bioavailability and adsorption of the nanomaterials into the plant tissues, without altering their bioactivity but mitigating any adverse side effect. Graphical Abstract: [Figure not available: see fulltext.]

Broadening the repertoire of melanoma-associated T-cell epitopes

Immune therapy has provided a significant breakthrough in the treatment of metastatic melanoma. Despite the remarkable clinical efficacy and established involvement of effector CD8 T cells, the knowledge of the exact peptide-MHC complexes recognized by T cells on the tumor cell surface is limited. Many melanoma-associated T-cell epitopes have been described, but this knowledge remains largely restricted to HLA-A2, and we lack understanding of the T-cell recognition in the context of other HLA molecules. We selected six melanoma-associated antigens (MAGE-A3, NY-ESO-1, gp100, Mart1, tyrosinase and TRP-2) that are frequently recognized in patients with the aim of identifying novel T-cell epitopes restricted to HLA-A1, -A3, -A11 and -B7. Using in silico prediction and in vitro confirmation, we identified 127 MHC ligands and analyzed the T-cell responses against these ligands via the MHC multimer-based enrichment of peripheral blood from 39 melanoma patients and 10 healthy donors. To dissect the T-cell reactivity against this large peptide library, we used combinatorial-encoded MHC multimers and observed the T-cell responses against 17 different peptide-MHC complexes in the patient group and four in the healthy donor group. We confirmed the processing and presentation of HLA-A3-restricted T-cell epitopes from tyrosinase (TQYESGSMDK) and gp100 (LIYRRRLMK) and an HLA-A11-restricted T-cell epitope from gp100 (AVGATKVPR) via the cytolytic T-cell recognition of melanoma cell lines and/or K562 cells expressing the appropriate antigen and HLA molecule. We further found T-cell reactivity against two of the identified sequences among tumor-infiltrating lymphocytes from melanoma patients, suggesting a potential clinical relevance of these sequences. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-015-1664-x) contains supplementary material, which is available to authorized users

Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model

Combining different types of immune therapies might benefit certain patients. Here, the authors develop an autologous immune-humanized melanoma mouse model that allows the preclinical assessment of cancer cell–T cell interactions from each individual patient and the benefits of immunotherapies combinations

Stability and enzymatic studies with omeprazole: hydroxypropyl-β-cyclodextrin

The original publication is available at www.springerlink.com. A publicação original está disponível em www.springerlink.comOmeprazole (OME) exhibits low stability to light, heat and humidity. In stress conditions OME stability should improve under inclusion complex form with hydroxypropyl-b-cyclodextrin (HPbCD). Stability of OME, its physical mixture (PM) with HPbCD and OME:HPbCD inclusion complex was assessed during 60 days. The inclusion complexes were prepared by kneading and freezedrying techniques and characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). A molecular modelling was also held to predict the most probable tridimensional conformation of inclusion complex OME:HPbCD. The inhibitory activity of free and complexed OME on selected enzymes, namely, papain (protease model of the proton pump) and acetylcholinesterase (enzyme present in cholinergic neurons and also involved in Alzheimer’s disease) was compared. The results obtained show that HPbCD do not protect against OME degradation, in any prepared powder, in the presence of light, heat and humidity. This may indicate that the reactive group of OME is not included in the HPbCD cavity. This fact is supported by molecular modelling data, which demonstrated that 2-pyridylmethyl group of OME is not included into the cyclodextrin cavity. In relation to enzymatic assays it was observed that free OME and OME in the binary systems showed identical inhibitory activity on papain and acethylcolinesterase, concluding that HPbCD do not affect OME activity on these two enzymes

Collagen density regulates the activity of tumor-infiltrating T cells

The number of reads per kilobase per million mapped (RPKM) for all RefSeq annotated genes. (XLSX 5563 kb

Comparison of efficacy in patients with metastatic melanoma treated with ipilimumab and nivolumab who did or did not discontinue treatment due to immune-related adverse events:A real-world data study

SIMPLE SUMMARY: This retrospective study of real-world patients with metastatic melanoma shows that discontinuing treatment with combination immunotherapy due to adverse events does not result in a poorer outcome compared to patients that did not discontinue due to toxicity. This is important knowledge for clinicians and patients, as discontinuing treatment may cause great anxiety for patients because they believe that it may limit the response. ABSTRACT: Immune-related adverse events (irAEs) are very prevalent when treating patients with ipilimumab and nivolumab in combination, and 30–40% of patients discontinue the treatment for this reason. It is of high clinical relevance to investigate the consequences of discontinuing the treatment early since combination therapy with ipilimumab and nivolumab is the first line of treatment for many patients with metastatic melanoma. In this follow-up study, with real-world data from the nationwide DAMMED database, we investigated whether there was a difference in progression-free survival (PFS) and overall survival (OS) for patients who discontinued or did not discontinue treatment within the first four doses of treatment due to irAEs. In total, 448 patients were treated with ipilimumab and nivolumab. Of these, 133 patients discontinued due to irAEs in the induction phase. Using the Cox proportional hazards model, there was no significant difference in PFS when comparing the group that discontinued with the group that did not discontinue. The group that discontinued had a significantly longer OS than the group that received the full length of treatment. Therefore, we conclude that there is no significant negative impact on efficacy for patients who discontinue due to irAEs in the induction phase of combination immunotherapy for metastatic melanoma