Does cancer research focus on areas of importance to patients?

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Influence of Long-Term Zinc Administration on Spatial Learning and Exploratory Activity in Rats

Abstract

Animal brain contains a significant amount of zinc, which is a cofactor for more than 300 enzymes. Moreover, it provides the basis for functioning of more than 2000 transcription factors, and it is necessary for memory formation and learning processes in the brain. The aim of this study was to investigate the effect of zinc supplementation on behavior in 3-month-old rats. For this purpose, the Morris water maze paradigm, hole-board, and T-maze were used. Wistar rats received a solution of ZnSO₄ in drinking water at the doses of 16 mg/kg (Zn16 group) and 32 mg/kg (Zn32 group). In rats pretreated with the lower dose of zinc, the improvement of the mean escape latency was observed in comparison to the control group and Zn32 group. During memory task, both ZnSO₄-supplemented groups showed an increase in crossings over the previous platform position. Furthermore, the exploratory activity in Zn16 group was improved in comparison to Zn32 and control group. In the brains of zinc-supplemented rats, we observed the higher content of zinc, both in the hippocampus and the prefrontal cortex. Hippocampal zinc level correlated positively with the mean annulus crossings of the Zn16 group during the probe trial. These findings show that the long-term administration of ZnS0₄ can improve learning, spatial memory, and exploratory activity in rats.

Graphical Abstract

Improvement of spatial learning, memory, and exploratory behavior

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Effect of Different Selenium Supplementation Levels on Oxidative Stress, Cytokines, and Immunotoxicity in Chicken Thymus

Abstract

This study assessed the effects of different selenium (Se) supplementation levels on oxidative stress, cytokines, and immunotoxicity in chicken thymus. A total of 180 laying hens (1 day old; Mianyang, China) were randomly divided into 4 groups (n = 45). The chickens were maintained either on a basic diet (control group) containing 0.2 mg/kg Se, a low-supplemented diet containing 5 mg/kg Se, a medium-supplemented diet containing 10 mg/kg Se, or a high-supplemented diet containing 15 mg/kg Se for 15, 30, and 45 days, respectively. Over the entire experimental period, serum and thymus samples were collected and used for the detection of the experimental index. The results indicated that the antioxidative enzyme activities and messenger RNA (mRNA) levels of antioxidative enzymes, IFN-γ and IL-2 in the thymus, and the content of IFN-γ and IL-2 in the serum of excessive-Se-treated chickens at all time points (except for the 5 mg/kg Se supplement group at 15 days) were significantly decreased (P < 0.05) compared to the corresponding control groups. Interestingly, a significantly increase (P < 0.05) in the content of IFN-γ was observed in the serum and thymus in the 5 mg/kg Se supplement group at 15 and 30 days compared to the corresponding control groups. In histopathological examination, the thymus tissue from excessive-Se-treated chickens revealed different degrees of cortex drop, incrassation of the medulla, and degeneration of the reticular cells. These results suggested that the excessive Se could result in a decrease in immunity, an increase in oxidative damage, and a series of clinical pathology changes, such as cortex drop, incrassation of the medulla, and degeneration of the reticular cells.

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Excessive Selenium Supplementation Induced Oxidative Stress and Endoplasmic Reticulum Stress in Chicken Spleen

Abstract

Excessive selenium (Se) intake is harmful for animals and humans. The aim of the present study was to examine the effect of long-term excessive Se supplementation on oxidative stress and endoplasmic reticulum (ER) stress-related injuries in chicken spleen. A total of 180 1-day-old chickens were randomly divided into four groups with different Se dietary contents (0.2 mg/kg Se, 5 mg/kg Se, 10 mg/kg Se, or 15 mg/kg Se) for 45 days. Then, the levels of antioxidative enzymes, GPx, SOD, and MDA as well as the expression levels of GRP78, ARF6, caspase 3, caspase 12, and Bcl 2 in the spleen were determined at days 15, 30, and 45, respectively. The results showed that excessive Se treatment decreased the activities of GPx and SOD (P < 0.05) but increased the levels of MDA (P < 0.05) in a dose- and time-dependent manner. In addition, the ER stress genes GRP78 and ATF6 were highly expressed (P < 0.05), and the apoptosis genes caspase 3 and caspase 12 were increased, but Bcl 2 was decreased by Se treatment (P < 0.05). Correlation analysis showed that there was a high correlation between these biomarkers, which indicated that ER stress and ER stress-related apoptosis were correlated with oxidative stress. These results showed the important role of oxidative stress and ER stress in Se-related immune injuries in chicken.

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nMET, a new target in recurrent cancer.

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nMET, a new target in recurrent cancer.

Curr Cancer Drug Targets. 2016 Jan 4;

Authors: Xie Y, Istayeva S, Chen Z, Tokay T, Zhumadilov Z, Wu D, Hortelano G, Zhang J

Abstract
Membranous Met is classically identified with its role in cancer metastases, while nuclear Met is associated with a more invasive, aggressive and proliferative form of cancer. Full-length Met or N-terminal transmembrane domain cleaved Met can translocate into nucleus in a cell growth and pH dependent but ligand-dependent (full length Met) and -independent (cleaved Met) manner. nMET may play greater essential roles in cancer recurrence than membranous Met. For example in prostate cancer, it has been found that androgen receptor (AR) may inhibit the expression of membranous Met so anti-androgen based prostate cancer therapy may promote the expression of nuclear Met (nMET). We recently found a novel nMET/SOX9/β-Catenin/AR pathway in relapsed prostate cancer which may contribute to the formation of the feedback loop of AR reactivation via MET/nMET. Emerging evidence suggests the possibility of nMET as a prognostic marker in relapsed cancer. This review summarizes recent findings about nMET and its unique role in recurrent cancer.

PMID: 26728040 [PubMed - as supplied by publisher]

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ROLES OF INTERFERON REGULATORY FACTORS IN CHRONIC MYELOID LEUKEMIA.

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ROLES OF INTERFERON REGULATORY FACTORS IN CHRONIC MYELOID LEUKEMIA.

Curr Cancer Drug Targets. 2016 Jan 4;

Authors: Manzella L, Tirrò E, Pennisi MS, Massimino M, Stella S, Romano C, Vitale SR, Vigneri P

Abstract
The Interferon Regulatory Factor (IRF) family consists of multiple transcription factors involved in the regulation of a variety of biological processes. Originally identified as transcriptional regulators of the type I interferon system, IRFs play a pivotal role in adaptive immunity, cell growth, differentiation and tumorigenesis. Hence, understanding IRF biology has important implications in the host response to cancer development and progression. Many lines of evidence suggest that different IRFs are involved in the pathogenesis of Chronic Myeloid Leukemia (CML), a myeloproliferative disorder caused by the BCR-ABL oncoprotein. BCR-ABL displays constitutive tyrosine kinase activity that favors cell proliferation, inhibits apoptosis and allows cell survival even in the absence of proper adhesion to the extracellular matrix. Different BCR-ABL tyrosine kinase inhibitors are currently available for CML treatment. These drugs are able to generate eight year CML-specific overall survival rates >90%, only a minority of patients will achieve molecular responses compatible with drug discontinuation. Thus, there is an unmet need for additional therapeutic targets that may lead to the cure of most patients diagnosed with CML. A growing body of evidence has suggested a role for both IRF4 and IRF8 in the pathogenesis of CML. Furthermore, IRF1 is consistently deleted at one or both alleles in patients with leukemia and myelodysplasia. Finally, we have recently demonstrated that IRF5 is a target of BCR-ABL kinase activity and reduces CML cell proliferation. In this article, we provide an update on the current knowledge of the role of the IRFs in CML.

PMID: 26728039 [PubMed - as supplied by publisher]

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Immune-related adverse events with immune checkpoint blockade: a comprehensive review

Publication date: February 2016
Source:European Journal of Cancer, Volume 54
Author(s): J.M. Michot, C. Bigenwald, S. Champiat, M. Collins, F. Carbonnel, S. Postel-Vinay, A. Berdelou, A. Varga, R. Bahleda, A. Hollebecque, C. Massard, A. Fuerea, V. Ribrag, A. Gazzah, J.P. Armand, N. Amellal, E. Angevin, N. Noel, C. Boutros, C. Mateus, C. Robert, J.C. Soria, A. Marabelle, O. Lambotte
Cancer immunotherapy is coming of age; it has prompted a paradigm shift in oncology, in which therapeutic agents are used to target immune cells rather than cancer cells. The first generation of new immunotherapies corresponds to antagonistic antibodies that block specific immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. Targeting these checkpoints in patients living with cancer had led to long-lasting tumour responses. By unbalancing the immune system, these new immunotherapies also generate dysimmune toxicities, called immune-related adverse events (IRAEs) that mainly involve the gut, skin, endocrine glands, liver, and lung but can potentially affect any tissue. In view of their undisputed clinical efficacy, anti-CTLA-4 and anti-PD-1 antibodies are entering in the routine oncological practice, and the number of patients exposed to these drugs will increase dramatically in the near future. Although steroids can be used to treat these IRAEs, the associated immunosuppression may compromise the antitumour response. Oncologists must be ready to detect and manage these new types of adverse events. This review focuses on the mechanisms of IRAE generation, putative relationship between dysimmune toxicity and antitumour efficacy, as a basis for management guidelines.



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