tbuckley/cabot-search huggingface dataset:
Milk intake and mammographic density in premenopausal women.
Authors: Yunan Han, Xiaoyu Zong, Diane Elizabeth Eapen, Yize Li, Graham A. Colditz, Adetunji Toriola
Journal: Journal of Clinical Oncology (2018)

1569 Background: Mammographic density (MD), which reflects the amount of epithelial and stromal tissues in relation to adipose tissue in the breast, is a strong risk factor for breast cancer. Although diet is associated with breast cancer risk, studies evaluating the associations of adult diet with MD have mainly reported null associations. Few studies have, however, investigated the associations of dairy intake with MD, with conflicting results. Therefore, we investigated the associations of milk intake with MD in premenopausal women. Methods: We recruited 375 premenopausal women, with no history of cancer, who had routine screening mammography at the Breast Health Center, Washington University in St. Louis in 2016. We used Volpara to measure MD: volumetric percent density (VPD), dense volume (DV) and non-dense volume (NDV). In addition to known breast cancer risk factors, all participants completed a detailed questionnaire on milk intake (skim milk and 1%/2% milk were categorized into 4 groups: < once/week, once/week, 2-6 times/week, ≥once/day; whole and soy milk were categorized into 2 groups: < once/week, ≥once/week, because fewer women consumed them). We used multivariable linear regression models (adjusted for age, body mass index (BMI), parity, oral contraceptive use, family history of breast cancer, race) to evaluate the associations between milk intake and log transformed VPD, DV and NDV. Beta coefficients (β) were evaluated and back transformed for easier interpretation. Results: The mean age was 47.5 years (range: 32-58 years), mean VPD was 9.48%, mean DV was 80.69 cm3, and mean NDV was 1079 cm3. Compared with women who drank 1%/2% milk < once/week, VPD was 20% (p-value = 0.003) lower in the once/week group, 14% (p-value = 0.047) lower in the 2-6 times/week group, and 12% (p-value = 0.144) lower in the ≥once/day group. NDV was 19% (p-value = 0.039) lower among women who drank soy milk ≥once/week compared with women who drank < once/week. There were no associations of skim and whole milk with MD. Conclusions: We observed that 1%/2% milk intake was inversely associated with VPD, while soy milk intake was inversely associated with NDV. Further studies on how 1%/2% and soy milk intake impact MD are needed, as this could have implications in breast cancer prevention.
High Prevalence of Hepatic Fibrosis, Measured by Elastography, in a Population-Based Study of Mexican Americans
Authors: Gordon P. Watt, Miryoung Lee, Jen-Jung Pan, Michael B. Fallon, Rohit Loomba, Laura Beretta, Joseph B. McCormick, Susan P. Fisher-Hoch
Journal: Clinical Gastroenterology and Hepatology (2018)
Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort
Authors: Jonathan Huang, Brenda Eskenazi, Riana Bornman, Stephen Rauch, Jonathan Chevrier
Journal: Environmental Health Perspectives (2018)

Background: Indoor residual spraying (IRS) of insecticides, conducted in low- and middle-income countries to control malaria, may result in high exposure to dichlorodiphenyltrichloroethane (DDT), its breakdown product dichlorodiphenyldichloroethylene (DDE), or pyrethroids. Animal studies suggest in utero exposure to these chemicals may increase childhood infection frequency. Objectives: We investigated associations between maternal DDT/E and pyrethroid metabolite concentration and child infection associations in an IRS setting in which susceptibility factors are common and infections are leading causes of child morbidity and mortality. Methods: Using gas chromatography–mass spectrometry, we measured serum DDT/E and urinary pyrethroid metabolite concentrations in peripartum samples from 674 women participating in the Venda Health Examination of Mother, Babies and their Environment (VHEMBE) study. Counts of persistent child fevers, otitis media, and severe sore throat between 1 and 2 y of age were ascertained from maternal interviews. Associations between DDT/E and pyrethroid metabolite concentrations and infections were estimated using zero-inflated Poisson regression. We estimated relative excess risks due to interaction (RERI) with poverty, maternal energy intake, and maternal HIV status. Results: Concentrations of DDT/E, particularly p,p′-DDE, were associated with higher rates of persistent fevers [IRR=1.21 (95% CI: 1.01, 1.46)], for a 10-fold increase in p,p′-DDE). This association was stronger among children from households below versus above the South African food poverty line [IRR=1.31 (95% CI: 1.08, 1.59) vs. IRR=0.93 (95% CI: 0.69, 1.25), respectively] and for children whose mothers had insufficient versus sufficient caloric intake during pregnancy [IRR=1.30 (95% CI: 1.07, 1.58) vs. IRR=0.96 (95% CI: 0.72, 1.28), respectively]. Conclusions: In utero IRS insecticide exposure may increase childhood infection rates. This was particularly apparent among children from poorer households or whose mothers had low energy intake during pregnancy. https://doi.org/10.1289/EHP2657
Adipocyte-Derived Lipids Mediate Melanoma Progression via FATP Proteins
Authors: Maomao Zhang, Julie S. Di Martino, Robert L. Bowman, Nathaniel R. Campbell, Sanjeethan C. Baksh, Theresa Simon-Vermot, Isabella S. Kim, Pearce Haldeman, Chandrani Mondal, Vladimir Yong-Gonzales, Mohsen Abu-Akeel, Taha Merghoub, Drew R. Jones, Xiphias Ge Zhu, Arshi Arora, Charlotte E. Ariyan, Kivanç Birsoy, Jedd D. Wolchok, Katherine S. Panageas, Travis Hollmann, Jose Javier Bravo-Cordero, Richard M. White
Journal: Cancer Discovery (2018)

Advanced, metastatic melanomas frequently grow in subcutaneous tissues and portend a poor prognosis. Though subcutaneous tissues are largely composed of adipocytes, the mechanisms by which adipocytes influence melanoma are poorly understood. Using in vitro and in vivo models, we find that adipocytes increase proliferation and invasion of adjacent melanoma cells. Additionally, adipocytes directly transfer lipids to melanoma cells, which alters tumor cell metabolism. Adipocyte-derived lipids are transferred to melanoma cells through the FATP/SLC27A family of lipid transporters expressed on the tumor cell surface. Among the six FATP/SLC27A family members, melanomas significantly overexpress FATP1/SLC27A1. Melanocyte-specific FATP1 expression cooperates with BRAFV600E in transgenic zebrafish to accelerate melanoma development, an effect that is similarly seen in mouse xenograft studies. Pharmacologic blockade of FATPs with the small-molecule inhibitor Lipofermata abrogates lipid transport into melanoma cells and reduces melanoma growth and invasion. These data demonstrate that stromal adipocytes can drive melanoma progression through FATP lipid transporters and represent a new target aimed at interrupting adipocyte-melanoma cross-talk.Significance: We demonstrate that stromal adipocytes are donors of lipids that mediate melanoma progression. Adipocyte-derived lipids are taken up by FATP proteins that are aberrantly expressed in melanoma. Inhibition of FATPs decreases melanoma lipid uptake, invasion, and growth. We provide a mechanism for how stromal adipocytes drive tumor progression and demonstrate a novel microenvironmental therapeutic target. Cancer Discov; 8(8); 1006-25. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 899.
AB0189 3d skin organoid mimicking systemic sclerosis generated by patient-derived induced pluripotent stem cells: ‘disease in a dish’ and development of animal model
Authors: J.-W. Kim, Y. Kim, J. Kim, M.-J. Park, E. Kwon, J. Lee, S.-K. Kwok, J.H. Ju, S.-H. Park
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is a rare autoimmune disease characterised by vasculopathy and fibrosis of various organs including skin. Although SSc has high morbidity and mortality, evidences for disease modifying treatment are still lacking due to difficulties in performing clinical trials. Patient-specific induced pluripotent stem cells (iPSCs), which can differentiate into various cell types, are used in 3D organoid formation. <h3>Objectives</h3> We generated 3D skin organoid model from SSc-derived iPSCs by differentiating them into keratinocytes and fibroblasts. SSc-mimicking 3D skin organoid can be used in studies for disease modelling and drug screening. <h3>Methods</h3> Peripheral blood mononuclear cells (PBMCs) from patients with SSc were reprogrammed to iPSCs. SSc-derived iPSCs differentiated into keratinocytes and fibroblasts <i>in vitro</i>. Expression of markers for iPSCs, keratinocytes, and fibroblasts were determined by reverse transcription polymerase chain reaction (RT-PCR) analysis and immunofluorescence assay (IFA). 3D skin organoid using iPSC-derived differentiation cell line was generated by 3D culture system. Histologic analysis was performed on 3D skin organoid. SSc-derived 3D skin organoid was applied to SCID skin defect mice. Histologic analysis was also performed on SCID skin graft model. <h3>Results</h3> SSc-derived iPSCs formed colonies that resemble embryonic stem cells. Alkaline phosphatase staining showed undifferentiated state of iPSCs. Expression of iPSC markers was increased on SSc-iPSCs. Differentiated keratinocytes and fibroblasts from iPSCs highly expressed their markers for keratinocytes and fibroblasts, respectively. Dermis of SSc-derived 3D skin organoid was thicker and denser than that derived from healthy control. Epidermis and dermis of SCID skin graft model were thickened in those derived from SSc compared to those derived from healthy control. <h3>Conclusions</h3> Patient-derived 3D skin organoid and animal model well represented the characteristics of SSc. These models can serve as useful research tools to understand the disease and screen new drugs for SSc. <h3>Disclosure of Interest</h3> None declared
Predicting Survival From Large Echocardiography and Electronic Health Record Datasets
Authors: Manar D. Samad, Alvaro Ulloa, Gregory J. Wehner, Linyuan Jing, Dustin Hartzel, Christopher W. Good, Brent A. Williams, Christopher M. Haggerty, Brandon K. Fornwalt
Journal: JACC. Cardiovascular imaging (2018)
Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor
Authors: Camilla L. Christensen, Nicholas Kwiatkowski, Brian J. Abraham, Julian Carretero, Fatima Al-Shahrour, Tinghu Zhang, Edmond Chipumuro, Grit S. Herter-Sprie, Esra A. Akbay, Abigail Altabef, Jianming Zhang, Takeshi Shimamura, Marzia Capelletti, Jakob B. Reibel, Jillian D. Cavanaugh, Peng Gao, Yan Liu, Signe R. Michaelsen, Hans S. Poulsen, Amir R. Aref, David A. Barbie, James E. Bradner, Rani E. George, Nathanael S. Gray, Richard A. Young, Kwok-Kin Wong
Journal: Cancer Cell (2015)
Impact of Suicidal Ideation on Long-Term Cardiac Outcomes in Patients with Acute Coronary Syndrome: Sex-Specific Differences
Authors: Jae-Min Kim, Robert Stewart, Hee-Joon Lee, Hee-Ju Kang, Kyung-Yeol Bae, Sung-Wan Kim, Il-Seon Shin, Min-Chul Kim, Young Joon Hong, Youngkeun Ahn, Myung Ho Jeong, Jin-Sang Yoon
Journal: Psychotherapy and Psychosomatics (2018)
Who regulates whom: ZNF341 is an additional player in the STAT3/T <sub>H</sub> 17 song
Authors: Avery August
Journal: Science Immunology (2018)

Deficiency of ZNF341, a transcription factor featuring 12 Cys2His2 zinc fingers that regulates the expression and autoinduction of STAT3 (signal transducer and activator of transcription 3), results in hyper–immunoglobulin E syndrome and defective T helper 17 cell differentiation in humans.
AB0326 Matrix metalloproteinase-3 is a good predictor for joint destruction only in male patients with rheumatoid arthritis
Authors: Y. Yamada, K. Inui, T. Okano, K. Orita, Y. Sugioka, K. Mamoto, T. Koike, M. Tada, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Serum level of matrix metalloproteinase-3 (MMP-3) is elevated by synovial inflammation. It destroys articular cartilage such as proteoglycans so that it has been used as a clinical biomarker of joint destruction in patients with rheumatoid arthritis (RA). <h3>Objectives</h3> The purpose of this study is to investigate a relation between radiographic progression, MMP-3 and other factors such as ultrasonography (US) findings. <h3>Methods</h3> 259 patients (213 women) with RA were enrolled in this study. Their baseline data such as age, sex, disease duration, use of glucocorticoid (GC) or DMARDs, disease activity (DAS28), laboratory data (MMP-3, CRP, RF and ACPA), and the Power Doppler (PD) score at digits and wrists by US were collected. The modified total Sharp score (mTSS), erosion score (ERN) and joint space narrowing (JSN) were examined at baseline and 1 year. Their changes from baseline to 1 year (Δ) were calculated. Relationship between baseline MMP-3 and other variables was examined. Predictors for joint destruction was investigated by multiple regression. Statistical analysis was separated by sex because upper limit of MMP-3 is different between men and women. <h3>Results</h3> MMP-3 showed no correlations with GC use, DAS28, CRP or mTSS. MMP-3 was correlated with ΔmTSS and ΔJSN only in men, but PD score only in women (table 1). Multiple regression analysis revealed that MMP-3 was correlated independently with ΔmTSS only in men, whereas PD score was correlated independently with ΔmTSS in women. PD score, but not MMP-3, could predict joint destruction at 1 year in women (table 2). <h3>Conclusions</h3> The baseline MMP-3 was a good predictor for joint destruction at 1 year only in male patients with RA. On the other hand, the baseline PD score was a useful predictor for joint destruction only in female patients with RA. <h3>Disclosure of Interest</h3> None declared
Macular and Optic Nerve Head Vessel Density and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma
Authors: Sasan Moghimi, Linda M. Zangwill, Rafaella C. Penteado, Kyle Hasenstab, Elham Ghahari, Huiyuan Hou, Mark Christopher, Adeleh Yarmohammadi, Patricia Isabel C. Manalastas, Takuhei Shoji, Christopher Bowd, Robert N. Weinreb
Journal: Ophthalmology (2018)
HEYL, an overexpressed gene in breast cancer, functions as a novel negative regulator of TGF-β pathway
Authors: Liangfeng Han, Ji Shin Lee, Tsuyoshi Mori, Huiping Zhang, Goran Landberg, Anne Kallioniemi, Pedram Argani, Saraswati Sukumar
Journal: Cancer Research (2008)

5201   In this study, we characterized the expression and investigated the function of HEYL, a basic helix-loop-helix (bHLH) transcription repressor, as a novel oncogene in breast cancer. HEYL was previously identified by our laboratory as an overexpressed tumor endothelial cell marker by SAGE analysis of purified endothelial cells from normal breast and invasive ductal carcinomas. Quantitative RT-PCR and immunohistochemical analysis (IHC) showed that HEYL was overexpressed frequently (16-30%) in breast carcinomas. Even stronger expression was detected in carcinoma cells compared to tumor endothelial cells, but minimal to no expression was detectable in normal epithelial cells. IHC of tissue microarrays showed that high HEYL expression correlates with poor survival in patients with ER-negative breast cancer. Neither gene amplification nor mutation accounted for the overexpression of HEYL. Rather, we found that activated Notch was capable of upregulating HEYL expression in breast cancer cells. Studying the downstream effects, we found that HEYL was a transforming oncogene in NIH3T3 cells, which formed tumors in immunodeficient mice. Stable overexpression of HEYL in Hs578T cells increased proliferation in vitro and facilitated rapid tumor cell growth in vivo. Deciphering the pathway by which HEYL promoted cell growth led to the confirmation of a direct interaction of HEYL with Smad3 through use of GST pull-down, biomolecular complementary fluorescence, and co-localization assays, as well as the mapping of interactions sites through deletion analysis. This interaction led to competition with the TGF-beta pathway, repressing the effects of TGF-beta in PAI- and p15 promoter-, and Smad binding element-linked-luciferase assays. Further, both PAI and p15 mRNA levels were repressed in HEYL-overexpressing cells. The precise mechanism of HEYL-mediated interference with Smad3 activity is under investigation. In summary, HEYL may be an important negative regulator of TGF-beta pathway, particularly at the early stages of breast oncogenesis.
Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer
Authors: P.D. Bonomi, D. Gandara, F.R. Hirsch, K.M. Kerr, C. Obasaju, L. Paz-Ares, C. Bellomo, J.D. Bradley, P.A. Bunn Jr, M. Culligan, J.R. Jett, E.S. Kim, C.J. Langer, R.B. Natale, S. Novello, M. Pérol, S.S. Ramalingam, M. Reck, C.H. Reynolds, E.F. Smit, M.A. Socinski, D.R. Spigel, J.F. Vansteenkiste, H. Wakelee, N. Thatcher
Journal: Annals of Oncology (2018)

Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs.Randomized trials of EGFR-directed mAbs cetuximab and necitumumab in combination with chemotherapy, immunotherapy, or antiangiogenic therapy in patients with advanced NSCLC, including SqCLC, were searched in the literature. Results of associations of potential biomarkers and outcomes were summarized.Data from phase III clinical trials indicate that patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein (H-score of ≥200) and/or gene copy numbers of EGFR (e.g. ≥40% cells with ≥4 EGFR copies as detected by fluorescence in situ hybridization; gene amplification in ≥10% of analyzed cells) derive greater therapeutic benefits from EGFR-directed mAbs. Biomarker data are limited for EGFR mAbs used in combination with immunotherapy and are absent when used in combination with antiangiogenic agents.Therapy with EGFR-directed mAbs in combination with chemotherapy is associated with greater clinical benefits in patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein and/or have increased EGFR gene copy number. These data support validating the role of these as biomarkers to identify those patients who derive the greatest clinical benefit from EGFR mAb therapy. However, data on biomarkers for EGFR-directed mAbs combined with immunotherapy or antiangiogenic agents remain limited.
Clinical outcomes of patients on check point inhibitor therapy who receive routine vaccinations.
Authors: Erin Lynn Schenk
Journal: Journal of Clinical Oncology (2017)

e14597 Background: Routine vaccination reduces preventable illness and infection in cancer patients even while undergoing therapy. Increasingly, patients with advanced malignancies receive check point inhibitors (CPI) and, with tumor response, can remain on therapy for extended periods of time. These agents promote tumor clearance by impeding a normal route of immune regulation which can result in autoimmunity. To the best of our knowledge, clinical outcomes for patients on CPI therapy who receive routine vaccinations have not been studied. Methods: The medical records of patients who received CPI therapy at Mayo Clinic in Rochester, Minnesota from March 25, 2011 to August 25, 2015 were reviewed for type and date of immunizations, CPI duration, adverse events (AE) at least possibly related to therapy, and survival from start of CPI. Patients who received &gt; 1 dose of pembrolizumab or nivolumab were included in analysis. Patients were excluded if no follow up was done at our institution. Results: One hundred and eight patients were included in the analysis. Most patients received CPI therapy for metastatic melanoma (n = 71) or non-small cell lung cancer (n = 23). A total of 53 routine vaccinations were administered to 30 patients while on CPI therapy. Eighteen patients received a single vaccination. Annual influenza vaccination was most frequently administered (n = 38) followed by pneumococcal vaccines (n = 9). AEs were reported in 17/30 vaccinated patients and in 22/78 non-vaccinated patients (p = 0.004). In the vaccinated cohort, 11 patients experienced AEs after immunization and was not significantly different from the non-vaccinated patients (p = 0.265). For both cohorts, thyroid, rash, and pneumonitis were the most common AEs. Grade 3 AEs occurred with similar frequency between the 2 groups. Patients in the vaccinated cohort received more cycles of therapy (median 20.5 vs 6 cycles, p &lt; 0.001). Median survival of patients who were not vaccinated was 503 days and median survival was not reached in the vaccinated group (p = 0.005). Conclusions: Routine vaccination of patients receiving CPI therapy did not significantly increase number or severity of adverse events. Routine vaccination did not reduce patient benefit from CPIs.
A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors
Authors: Mariano J. Alvarez, Prem S. Subramaniam, Laura H. Tang, Adina Grunn, Mahalaxmi Aburi, Gabrielle Rieckhof, Elena V. Komissarova, Elizabeth A. Hagan, Lisa Bodei, Paul A. Clemons, Filemon S. Dela Cruz, Deepti Dhall, Daniel Diolaiti, Douglas A. Fraker, Afshin Ghavami, Daniel Kaemmerer, Charles Karan, Mark Kidd, Kyoung M. Kim, Hee C. Kim, Lakshmi P. Kunju, Ülo Langel, Zhong Li, Jeeyun Lee, Hai Li, Virginia LiVolsi, Roswitha Pfragner, Allison R. Rainey, Ronald B. Realubit, Helen Remotti, Jakob Regberg, Robert Roses, Anil Rustgi, Antonia R. Sepulveda, Stefano Serra, Chanjuan Shi, Xiaopu Yuan, Massimo Barberis, Roberto Bergamaschi, Arul M. Chinnaiyan, Tony Detre, Shereen Ezzat, Andrea Frilling, Merten Hommann, Dirk Jaeger, Michelle K. Kim, Beatrice S. Knudsen, Andrew L. Kung, Emer Leahy, David C. Metz, Jeffrey W. Milsom, Young S. Park, Diane Reidy-Lagunes, Stuart Schreiber, Kay Washington, Bertram Wiedenmann, Irvin Modlin, Andrea Califano
Journal: Nature Genetics (2018)