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Nathan Goodyear

Artesunate interacts with Vitamin D receptor to reverse mouse model of sepsis-induced i... - 0 views

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    To be read
Nathan Goodyear

The Role of Toll-Like Receptor 4 in Infectious and Noninfectious Inflammation - 0 views

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    To be read
Nathan Goodyear

Interleukin‐2 enhances the natural killer cell response to Herceptin‐coated H... - 1 views

  • administration of low‐dose IL‐2 results in expansion of a CD3– / CD56+ NK cell population in patients with advanced cancer
  • approximately 20 % will overexpress theHer2 / neu proto‐oncogene
  • In breast cancer, Her2 / neu overexpression is associated with a worse histologicalgrade, decreased relapse‐free and overall survival periods, and altered sensitivity to chemotherapeutic regimens
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  • NK cells are large granular lymphocytes that comprise approximately 10 % of circulating lymphocytes
  • all human NK cells express the CD56 antigen
  • treatment with various concentrations of IL‐2 in vivo may induce distinct functions within the NK cell compartment and, therefore, may have profound effects on NK cell‐mediated cytotoxicity
  • CD56bright
  • CD56dim
  • We show here that ADCC conducted by NK cells in vitro is enhanced by IL‐2 activation and is critically dependent on interactions between FcγRIII on NK cells and Herceptin‐coated tumor targets
  • administration of low‐dose IL‐2 to patients results in the marked expansion of a CD56+ population of immune effectors with the ability to lyse antibody‐coated cancer targets
  • NK cells represented only 7 % of lymphocytes prior to therapy but comprised over 50 % of the population after 10 weeks of low‐dose IL‐2
  • These data suggest that the enhanced ADCC seen following the expansion of NK cells with low‐dose IL‐2 is likely due to an increase in the overall number of NK cells
  • co‐administration of IL‐2 with rhu4D5 mAb will enhance activation of NK cell effector functions
  • Stimulation of NK cells with IL‐2 resulted in a significant increase in the lysis of rhu4D5‐coated targets
  • We have shown that costimulation with IL‐2 plus rhu4D5 results in significant production of IFN‐γ by NK cells with concomitant up‐regulation of cell‐surface activation and adhesion molecules
  • It has been previously demonstrated that continuous low‐dose IL‐2 can expand a CD56+ lymphocyte population, and we have now shown that this cell population is a potent mediator of ADCC against rhu4D5 mAb‐coated Her2 / neu+ targets
  • These results suggest that administration of low‐dose IL‐2 can be used to expand NK cell numbers, while higher doses may be used to enhance their cytolytic capacity in the setting of mAb therapy
  • we have demonstrated that NK cell lysis of Her2 / neu+ breast cancer cell lines in the presence of rhu4D5 mAb is markedly enhanced following stimulation with IL‐2
  • we have presented evidence that administration of low‐dose IL‐2 in vivo results in the expansion of a potent NK cell effector population
  • Our experiments suggest that NK cells costimulated with IL‐2 and immobilized IgG can secrete potent immunomodulatory cytokines which may serve to potentiate the anti‐tumor immune response.
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    low dose IL-2 found to expand NK levels in conjuction in with herceptin in HER-2 positive breast cancer cell lines.
Nathan Goodyear

Role of IL-2 in cancer immunotherapy: OncoImmunology: Vol 5, No 6 - 1 views

  • IL-2 is one of the key cytokines with pleiotropic effects on the immune system
  • IL-2 as “T-cell growth factor”
  • approved for the treatment of metastatic renal cell carcinoma (1992) and later for metastatic melanoma (1998) by FDA
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  • It is produced predominately by antigen-simulated CD4+ T cells, while it can also be produced by CD8+ cells, natural killer (NK) cells, and activated dendritic cells (DC)
  • IL-2 is an important factor for the maintenance of CD4+ regulatory T cells
  • plays a critical role in the differentiation of CD4+ T cells into a variety of subsets
  • It can promote CD8+ T-cell and NK cell cytotoxicity activity, and modulate T-cell differentiation programs in response to antigen, promoting naive CD4+ T-cell differentiation into T helper-1 (Th1) and T helper-2 (Th2) cells while inhibiting T helper-17 (Th17) differentiation
  • Of note, Tregs, which act to dampen the immune response, constitutively express high levels of α chain
  • IL-2Rα is unique to IL-2 and is expressed by a number of immune cells including T regulatory cells (Treg), activated CD4+ and CD8+T cells, B cells, mature DCs, endothelial cells
  • some investigators evaluated the efficacy of regimens containing low-dose IL-2
  • IL-2 can promote the activation and cell growth of T and NK cells
  • Unfortunately, not all of patients would benefit from targeted therapy and nearly all patients who initially respond to targeted inhibitors inevitably develop acquired resistance to the treatment
  • IL-2 also stimulates T-regulatory cells that constitutively express CTLA-4 and can suppress immune reactions. Hence, IL-2 might enhance antitumor reactivity in the presence of CTLA-4 blockade
  • both HD and low-dose IL-2 therapy preferentially induce the expansion of CD4+CD25+Foxp3+ Treg and the Treg level remains elevated after each cycle of HD IL-2 therapy
  • Due to rapid elimination and metabolism via the kidney, IL-2 has a short serum half-life of several minutes
  • HD IL-2-induced severe toxicities including vascular leak syndrome (VLS), pulmonary edema, hypotension, and heart toxicities
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    Great historical and functional role of IL-2 in the fight against cancer.
Nathan Goodyear

Forecasting the cytokine storm following systemic interleukin (IL)-2 administration - 0 views

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    To be read
Nathan Goodyear

Suppression of chemotherapy-induced cytokine/lipid mediator surge and ovarian cancer by... - 0 views

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    COX2 inhibition to slow/block chemotherapy induced metastasis.
Nathan Goodyear

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 pa... - 0 views

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    To be read
Nathan Goodyear

Nutrients | Free Full-Text | Effect of Probiotics on Metabolic Outcomes in Pregnant Wom... - 0 views

  • The gut microbial composition is altered during pregnancy
  • probiotic supplements may contribute to the maintenance of bacterial diversity and glucose homeostasis in individuals with metabolic disturbances
  • Assessment of four randomized controlled trials in this review involving 288 pregnant women with GDM found that a 6–8 week probiotic intervention did not improve FBG or LDL-cholesterol levels
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  • probiotic supplementation in women with GDM was associated with significant reductions in insulin resistance
  • One proposed method is by the production of short chain fatty acids (SCFAs), generated as a by-product of bacterial fermentation of dietary fibers. SCFAs act as an energy source for intestinal cells and have been found to regulate the production of hormones effecting energy intake and expenditure such as leptin and grehlin
  • Another hypothesized mechanism of SCFA action includes reducing gastrointestinal permeability by upregulating transcription of tight junction proteins, enhancing production of Glucagon-like peptide-2 (GLP-2) which promotes crypt cell proliferation, and reducing inflammation in colonic epithelial cells by increasing PPAR-gamma activation
  • Maintenance of the integrity of the gut barrier minimizes the concentration of lipopolysaccharide (LPS) in circulation
  • LPS is a structural component of gram negative bacterial cell walls, which induces an immune-cell response upon absorption into the human bloodstream, stimulating proinflammatory cytokine production and the onset of insulin resistance and hyperglycemia
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    Review (4 studies) found that 6-8 weeks of probiotic therapy of pregnant women with gestational diabetes improved insulin resistance.
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Nathan Goodyear

Curcumin abrogates LPS-induced proinflammatory cytokines in RAW 264.7 macrophages. Evid... - 0 views

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    Curcumin is a potent inhibitor of LPS induced inflammation in cell line. Particularily, PGE2, IL-6, and TNF-alpha were inhibited in a dose dependent manner form 5microM to 30 microM.
Nathan Goodyear

Chemotherapy induces tumor immune evasion by upregulation of programmed cell ... - 0 views

  • upregulation of glycolysis in cancer cells, with subsequent exhaustion of glucose in the microenvironment, leading to the death of T cells from starvation
  • PD‐L1 expression promotes the production of interleukin 10, a cytokine involved in the death of activated T cells
  • PD‐L1 expression in tumor tissue might lead to T‐cell exhaustion and unresponsiveness
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  • PD‐L1 on cancer cells could induce T‐cell apoptosis through
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    Chemotherapy found to increase PD-L1 expression in vitro and in vivo studies.
Nathan Goodyear

Antitumor immunity of low-dose cyclophosphamide: changes in T cells and cytokines TGF-b... - 0 views

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    Low dose cytoxan effects both local and systemic immune system.
Nathan Goodyear

Zinc deficiency induces production of the proinflammatory cytokines IL-1β and... - 0 views

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    Zinc deficiency results in increase in IL-1B, TNF-alpha, and IL-6
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