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  • 1
    In: Biophysical Journal, Elsevier BV, Vol. 106, No. 2 ( 2014-01), p. 593a-
    Type of Medium: Online Resource
    ISSN: 0006-3495
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
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    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Public Library of Science (PLoS) ; 2010
    In:  PLoS Computational Biology Vol. 6, No. 6 ( 2010-6-24), p. e1000828-
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  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2163-2163
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2163-2163
    Abstract: Heregulin (HRG) is a soluble growth factor involved in the control of proliferation, survival, invasion, and differentiation of normal and malignant mammary epithelial cells. HRG binds its receptor, HER3, leading to activation of the HER2-HER3 heterodimer, which acts as an oncogenic factor in breast cancers. Pharmacological inhibitors to HER2 are currently being used in the clinic to treat HER2-positive breast cancer, however, they are associated with resistance after one year of therapy. A more comprehensive understanding of the signaling network downstream of HRG, in HER2-positive breast cancer cells, will be crucial for further development of inhibitors that do not elicit resistance. This study assessed HRG signaling in the HER2-positive breast cancer cell lines BT474 and SKBR3. The RSK (p90 ribosomal S6 Kinase) pathway was activated in an ERK-dependent manner. HRG stimulation increased phosphorylation of RSK at S380, T359, and S363. HRG stimulated the phosphorylation of CREB (cAMP Response-Element Binding Protein), an established substrate of RSK, at S133 and this was blocked by pharmacological inhibition of RSK. HRG induced the expression of c-FOS in an RSK-dependent manner. These data demonstrate that RSK has an important role in transducing HRG signaling to the gene expression program and suggest that inhibitors of RSK may be useful in the treatment of HER2-positive breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2163. doi:1538-7445.AM2012-2163
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 4
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 208, No. 9 ( 2022-05-01), p. 2085-2097
    Abstract: Asthma is a common and ubiquitous chronic respiratory disease that is associated with airway inflammation and hyperreactivity resulting in airway obstruction. It is now accepted that asthma is controlled by a combination of host genetics and environment in a rather complex fashion; however, the link between sensing of the environment and development and exacerbation of allergic lung inflammation is unclear. Human populations expressing cosegregating D299G and T399I polymorphisms in the TLR4 gene are associated with a decreased risk for asthma in adults along with hyporesponsiveness to inhaled LPS, the TLR4 ligand. However, these data do not account for other human genetic or environmental factors. Using a novel mouse strain that expresses homologous human TLR4 polymorphisms (TLR4-single nucleotide polymorphism [SNP]), we directly tested the effect of these TLR4 polymorphisms on in vivo responses to allergens using two models of induction. We report that intact TLR4 is required for allergic inflammation when using the OVA and LPS model of induction, as cellular and pathological benchmarks were diminished in both TLR4-SNP and TLR4-deficent mice. However, in the more clinically relevant model using house dust mite extract for induction, responses were enhanced in the TLR4-SNP mice, as evidenced by greater levels of eosinophilic inflammation, Th2 cytokine production, and house dust mite–specific IgG1 production compared with wild-type mice; however, mucus production and airway hyperreactivity were not affected. These results suggest that the TLR4 polymorphic variants (genes) interact differently with the allergic stimulation (environment).
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2022
    detail.hit.zdb_id: 1475085-5
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  • 5
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2018
    In:  The Journal of Immunology Vol. 200, No. 1_Supplement ( 2018-05-01), p. 52.12-52.12
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 200, No. 1_Supplement ( 2018-05-01), p. 52.12-52.12
    Abstract: Infection with the protozoan parasite, Giardia, produces symptoms associated with intestinal distress, but does not induce intestinal inflammation. Long-term sequellae of this infection include malnutrition, Irritable Bowel Syndrome and Chronic Fatigue Syndrome. Previous work indicates that T-cells are critical for clearance of this parasite; however, it is unclear which cells are responsible for the activation of T-cells. As such, our goal was to examine the contribution of myeloid cells to Giardia immunity as possible T-cell activators, effector cells and/or immune regulators. Small intestinal lamina propria cells were isolated from Giardia-infected wild-type or CCR2 deficient mice. Flow cytometry was used to determine cell phenotypes and to monitor cytokine response. EdU labeling was used to examine in situ proliferation of resident macrophages. Lastly, wild-type mice were treated with an anti-CSF1R monoclonal antibody to deplete macrophage populations. Flow cytometry demonstrated that CD11b+, F4/80+, CD11cint, MHCII+, Ly6Cint, CX3CR1int cells accumulate in the small intestine and express ARG1 and NOS2 during infection. Intracellular cytokine staining revealed an increase in IL-10 with a concurrent decrease in TNF-α. Macrophage accumulation was the same in wild-type and CCR2-deficient mice, and EdU labeling suggested in situ proliferation of resident macrophages rather than recruitment of inflammatory monocytes. Mice treated with anti-CSF1R eliminated the parasites as well as control mice. This study demonstrates that macrophages with a regulatory phenotype accumulate in the small intestine during Giardia infections and may explain why intestinal inflammation is not present during Giardia infections.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2018
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  • 6
    Online Resource
    Online Resource
    Wiley ; 2020
    In:  Current Protocols in Microbiology Vol. 57, No. 1 ( 2020-06)
    In: Current Protocols in Microbiology, Wiley, Vol. 57, No. 1 ( 2020-06)
    Abstract: Giardia lamblia is a protozoan parasite that is found ubiquitously throughout the world and is a major contributor to diarrheal disease. Giardia exhibits a biphasic lifestyle existing as either a dormant cyst or a vegetative trophozoite. Infections are typically initiated through the consumption of cyst‐contaminated water or food. Giardia was first axenized in the 1970s and can be readily maintained in a laboratory setting. Additionally, Giardia is one of the few protozoans that can be induced to complete its complete lifecycle using laboratory methods. In this article, we outline protocols to maintain Giardia and induce passage through its lifecycle. We also provide protocols for infecting and quantifying parasites in an animal infection model. © 2020 Wiley Periodicals LLC. Basic Protocol 1 : In vitro maintenance and growth of Giardia trophozoites Basic Protocol 2 : In vitro encystation of Giardia cysts Basic Protocol 3 : In vivo infections using Giardia trophozoites
    Type of Medium: Online Resource
    ISSN: 1934-8525 , 1934-8533
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 7
    Online Resource
    Online Resource
    Elsevier BV ; 2003
    In:  Frontiers in Neuroendocrinology Vol. 24, No. 3 ( 2003-7), p. 181-199
    In: Frontiers in Neuroendocrinology, Elsevier BV, Vol. 24, No. 3 ( 2003-7), p. 181-199
    Type of Medium: Online Resource
    ISSN: 0091-3022
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2003
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    SSG: 12
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  • 8
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 4 ( 2014-12-08)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2014
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  • 9
    Online Resource
    Online Resource
    Elsevier BV ; 2015
    In:  Biophysical Journal Vol. 108, No. 2 ( 2015-01), p. 614a-
    In: Biophysical Journal, Elsevier BV, Vol. 108, No. 2 ( 2015-01), p. 614a-
    Type of Medium: Online Resource
    ISSN: 0006-3495
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 1477214-0
    SSG: 12
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  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P1-17-06-P1-17-06
    Abstract: Background: Aromatase inhibitors (AIs) are part of standard endocrine therapy for hormone receptor (HR)-positive breast cancer (BC) and are used in both adjuvant and metastatic settings. Since AIs work by inhibiting the conversion of androgens to estrogen in peripheral adipose tissue, the higher levels of estrogen in obese patients may lead to incomplete inhibition by AIs and influence their efficacy. A retrospective analysis of the ABCSG-12 trial found that overweight premenopausal patients with early-stage BC treated with anastrozole had a 60% increased risk of disease recurrence and more than doubling in risk of death compared with normal weight patients on anastrozole. Similarly, an exploratory analysis from the ATAC trial found that in post-menopausal women with early-stage BC, overall recurrence rates were lower in patients randomized to anastrozole versus tamoxifen but in women with body mass index (BMI) & gt; 30, there was no significant difference in disease recurrence between anastrozole and tamoxifen. While these findings raise concern for the efficacy of adjuvant AI therapy in obese patients with early-stage BC, this has not yet been demonstrated in the metastatic setting. The aim of this study was to determine the impact of BMI on efficacy of AIs in patients with metastatic HR-positive BC. Methods: We performed a retrospective chart review of all female patients with metastatic HR-positive BC on an AI in first- or second-line settings and seen at our academic institution between 2001-2020. The primary endpoint was progression-free survival (PFS), defined as the time from start of AI to disease progression or death from any cause. PFS was compared across BMI groups using Kaplan-Meier curves and log-rank tests. Cox proportional hazards regression model was used for univariate and multivariate analyses. Results: We identified 219 patients who had received an AI in the first- or second-line settings for metastatic HR-positive BC and with documented information on BMI. The median age was 59 with 45% of patients White, 29% African American, 16% Hispanic/Latino, 5.5% Asian and remainder other/unknown. 32% (71) had HER-2 positive disease. 82% (179) were on an AI in the first-line setting. Overall, 53% were on letrozole, 42% on anastrozole and 5.5% on exemestane. Of the 219 patients, 56% (123) had a low BMI (defined as & lt; 27 kg/m2) and 44% (96) had a high BMI (≥ 27 kg/m2; based on the Breast Cancer Weight Loss [BWEL] trial). The median PFS was 21.9 months (95% CI, 14.5 to 28.4) in the low BMI group versus 20.2 months (95% CI, 14.3 to 27.5) in the high BMI group with no statistically significant difference (p =0.73). There were 8 (6.5%) deaths in the low BMI group and 7 (7.3%) deaths in the high BMI group. Multivariate cox regression model did not demonstrate any significant impact of BMI on PFS when adjusting for age, race/ethnicity, HER2 status, type of AI, line of therapy, drug partner and type of metastatic disease (HR =0.91, 95% CI =0.64 to 1.30, p =0.6 for high BMI group). Subgroup analysis of patients on an AI in the first line setting also did not show a significant difference in PFS with median PFS 19.3 and 18 months in the low and high BMI groups, respectively. Conclusions: In patients on an AI for metastatic HR-positive breast cancer, there was no statistically significant difference in PFS in patients with low versus high BMI. While BMI influences efficacy of AIs in the adjuvant setting, our results demonstrate that in the metastatic setting, BMI does not significantly impact the efficacy of AIs among our patient population. This discrepancy could be due to other differences in disease characteristics that make complete aromatase inhibition more important in the adjuvant setting when disease burden is the lowest. Additional larger studies are needed to confirm this finding. Citation Format: Rima Patel, Zhiqiang Li, Brittney S. Zimmerman, Marc Y. Fink, Jason D. Wells, Xiang Zhou, Kristin L. Ayers, Arielle Redfern, Scott Newman, Rong Chen, William K. Oh, Amy Tiersten. Impact of body mass index on the efficacy of aromatase inhibitors in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-06.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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