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      Effects of Social Isolation on Ehrlich Tumor Growth and Tumor Leukocyte Infiltration in Mice: Evidence of Participation of the Submaxillary Salivary Gland

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          Objective: Considering previous studies on stress and Ehrlich tumor growth from our laboratory and also known cell growth and behavior-related properties of submaxillary salivary gland products, we studied the effects of stress by social isolation, in combination or not with sialectomy (submaxillary gland ablation), on growth and leukocyte infiltration into Ehrlich adenocarcinomas. Methods: 5 × 10<sup>7</sup> tumor cells/ml were inoculated into the footpads of mice and tumor growth was evaluated by measuring paw thickness on alternate days. Ten days after inoculation, tumors were harvested and processed for immunocytochemical analysis of tumor-infiltrating leukocytes (TIL) and nerve-like growth factor (NGF)/epidermal growth factor (EGF)-positive tumor cells. T and B lymphocyte, NK cell and macrophage percentages were calculated. Results: Sialectomy slightly reduced tumor growth and caused a significant increase in NK cell infiltration of tumors (p < 0.05). Social isolation caused a highly significant enhancement of both tumor growth (p ≤ 0.05) and percentage of macrophages infiltrating tumors (p < 0.05). Sialectomized isolated animals showed few significant changes in tumor growth rate (p ≤ 0.05), but presented increased percentages of NK cells, macrophages and B lymphocytes (p < 0.05). A reduction in the percentage of NGF+ tumor cells was also observed (p < 0.05). All of these effects were seen only in 8-month-old mice, but not in younger animals. Conclusion: A possible link between salivary gland factors, tumor growth and TIL patterns was considered, suggesting that growth factors may modulate tumor leukocyte infiltration as well as tumor growth rate.

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          Nerve growth factor is mitogenic for cancerous but not normal human breast epithelial cells.

          We show here that nerve growth factor (NGF), the archetypal neurotrophic factor, is able to stimulate the proliferation of breast cancer cells (MCF-7 and MDA-MB-231 cell lines), although it is unable to stimulate growth of normal breast epithelial cells (NBEC). This stimulation induced cells in the G0 phase to reenter the cell cycle, as well as shortening cell cycle duration. Immunoblotting experiments revealed that both the two cancer cell lines and the NBEC express high affinity (p140(trk)) and low affinity (p75) NGF receptors. Inhibition of the NGF growth-promoting effect by the drugs K-252a and PD98059 indicated that activation of Trk-tyrosine kinase activity and the mitogen-activated protein kinase cascade are necessary to obtain the mitogenic effect. Activation of mitogen-activated protein kinase can be detected in breast cancer cells after 10 min of NGF stimulation, whereas no change was detected in NBEC. These results demonstrate that NGF is a mitogenic factor for human breast cancer cells and that it might constitute a new regulator of breast tumor growth.
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            “Isolation stress” revisited: Isolation-rearing effects depend on animal care methods

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              Nerve growth factor: a neurotrophin with activity on cells of the immune system.

               L. Aloe,  M Simone,  F Properzi (2016)
              Numerous studies published in the last two decades provide evidence that nerve growth factor (NGF), a polypeptide originally discovered because of its neurotrophic activity, acts on a variety of cells of the immune system, including mast cells, eosinophils, and B and T lymphocytes. NGF has been shown to increase during inflammatory responses, autoimmune disorders, parasitic infections, and allergic diseases. Moreover, stress, which is characterized also by activation of a variety of immune cells, causes a significant increase in basal plasma NGF levels. Recently published studies reveal that hematopoietic progenitor cells seem to be able to produce and/or respond to NGF. We report these data and discuss the hypothesis of the possible implication of NGF on the functional activities of immune cells.

                Author and article information

                S. Karger AG
                May 2002
                28 May 2002
                : 9
                : 6
                : 313-318
                aLaboratory of Veterinary Pathology, Faculdade de Medicina Veterinária, Universidade de Santo Amaro, bDepartment of Immunology, Instituto de Ciências Biomédicas, cDepartment of Pathology, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, dLaboratory of Pathology, Instituto de Ciências da Saúde, Universidade Paulista, São Paulo, Brasil
                59388 Neuroimmunomodulation 2001;9:313–318
                © 2002 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 4, References: 28, Pages: 6
                Original Paper


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