tbuckley/cabot-search huggingface dataset:
Ccl22 Diverts T Regulatory Cells and Controls the Growth of Melanoma
Authors: Jared Klarquist, Kristen Tobin, Peyman Farhangi Oskuei, Steven W. Henning, Manuel F. Fernandez, Emilia R. Dellacecca, Flor C. Navarro, Jonathan M. Eby, Shilpak Chatterjee, Shikhar Mehrotra, Joseph I. Clark, I. Caroline Le Poole
Journal: Cancer Research (2016)

T regulatory cells (Treg) avert autoimmunity, but their increased levels in melanoma confer a poor prognosis. To explore the basis for Treg accumulation in melanoma, we evaluated chemokine expression in patients. A 5-fold increase was documented in the Treg chemoattractants CCL22 and CCL1 in melanoma-affected skin versus unaffected skin, as accompanied by infiltrating FoxP3+ T cells. In parallel, there was an approximately two-fold enhancement in expression of CCR4 in circulating Treg but not T effector cells. We hypothesized that redirecting Treg away from tumors might suppress autoimmune side effects caused by immune checkpoint therapeutics now used widely in the clinic. In assessing this hypothesis, we observed a marked increase in skin Treg in mice vaccinated with Ccl22, with repetitive vaccination sufficient to limit Treg accumulation and melanoma growth in the lungs of animals challenged by tumor cell injection, whether using a prevention or treatment protocol design. The observed change in Treg accumulation in this setting could not be explained by Treg conversion. Overall, our findings offered a preclinical proof of concept for the potential use of CCL22 delivered by local injection as a strategy to enhance the efficacious response to immune checkpoint therapy while suppressing its autoimmune side effects. Cancer Res; 76(21); 6230-40. ©2016 AACR.
Do nanoparticles have a future in dermal drug delivery?
Authors: Alexa Patzelt, Wing Cheung Mak, Sora Jung, Fanny Knorr, Martina C. Meinke, Heike Richter, Eckart Rühl, Kwan Yee Cheung, Ngo Bich Nga Nathalie Tran, Jürgen Lademann
Journal: Journal of Controlled Release (2016)
P3-123: Clinical and genetic predictors of response and survival in patients with gefitinib treated non-small cell lung carcinoma
Authors: In-Jae Oh, Jung-Hwan Lim, Dong-Ryeol Chae, Jin-Young Ju, Gye-Jung Cho, Kyu-Sik Kim, Yu-Il Kim, Sung-Chul Lim, Young-Chul Kim, Kyung-Ok Park, Sun-Mi Back
Journal: Journal of Thoracic Oncology (2007)
HE3235, a synthetic adrenal hormone disease-modifying agent, in castrate resistant prostate cancer (CRPC): Results of phase I/II clinical trial.
Authors: R. B. Montgomery, M. J. Morris, C. J. Ryan, D. R. Stickney, J. M. Frincke, C. L. Reading, J. Sarantopoulos, H. I. Scher
Journal: Journal of Clinical Oncology (2010)

4674 Background: HE3235 (17α-ethynyl-5α-androstane-3α, 17ß-diol), an androstanediol analog, showed activity in preclinical CRPC models. HE3235 decreased AR expression in LNCaP cells in vitro, and suppressed growth and tumoral androgen synthesis in CRPC LuCaP 35V xenografts. HE3235 inhibits the conversion of d-cholesterol to d-pregnenolone independent of CYP 17 inhibition. We previously reported preliminary results of this ongoing phase I/II dose escalation trial guided by safety, tolerance and pharmacokinetics, which is now completed (Montgomery et al, ASCO GU Symposium 2010 Abstr 235). Methods: Men with CRPC and an ECOG PS of ≤ 2 who progressed either radiographically or biochemically following at least one taxane-containing chemotherapy regimen are eligible. HE3235 is given orally, BID, in cohorts of 3-6 pts. Dose cohorts were 10, 20, 30, 50, 100, 200 and 350 mg or higher until MTD observed. Subjects are treated on 28-day cycles until toxicity or disease progression. Scans to assess progression are obtained every 2 cycles. A grant from the DoD supported PCCTC sites. Results: To date 32 subjects have completed ≥1 cycle with a total of 98 cycles at doses of 10 (n=4), 20 (n=12), 30 (n=5), 50 (n=3), 100 (n=3), 200 (n=3) and 350 mg/day (n=2). PK was dose proportional with a T1/2 of 10-14 hours. HE3235 was well tolerated with 16.4% of all adverse events grade 3 or 4 toxicity with 1% treatment related. Median time to progression is currently 20 weeks (IQR 8, 24) for all evaluable subjects (≥ 2 cycles) in the 10-200 mg cohorts. PSA kinetics were similar to pre-clinical models showing an initial 69% median increase during cycle 1 followed by a 16% decline during cycle 2 with an attenuated 45% progression over cycles 3 and 4 consistent with the properties of a disease modifying agent. Conclusions: HE3235 is a novel, orally delivered agent with clinical activity in advanced CRPC patients. It is well tolerated and has an AUC linear to dose. Based on the safety and activity observed, the trial continues to accrue an expansion cohort at 100 mg/day of patients with chemotherapy-naïve CRPC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hollis-Eden Pharmaceuticals Hollis-Eden Pharmaceuticals
Review of<i>Walsh and Hoyt’s Clinical Neuro-Ophthalmology</i>
Authors: Joshua Pasol, Byron L. Lam
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
A randomized, multicenter, double-blind, placebo-controlled study of the Bruton tyrosine kinase inhibitor, ibrutinib, versus placebo in combination with nab-paclitaxel and gemcitabine in the first-line treatment of patients with metastatic pancreatic adenocarcinoma (RESOLVE).
Authors: Margaret A. Tempero, Lisa M Coussens, Lawrence Fong, Robert Manges, Priyanka Singh, Yunfeng Li, George W. Cole, Danelle Frances James, Josep Tabernero
Journal: Journal of Clinical Oncology (2016)

TPS483 Background: Advanced pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and short survival. Nab-paclitaxel/gemcitabine (Nab-P/GCB) is a preferred regimen for front-line treatment. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (ibr) shows antitumor activity in preclinical PDAC models, in part, due to modulation of the tumor microenvironment. Ibr treatment inhibits mast-cell degranulation and decreases tumor-associated inflammation and desmoplasia with simultaneous enhanced presence and activity of cytotoxic T cells in tumors (Affara et al, Cancer Cell, 2014; Masso-Valles et al, Cancer Res, 2015). This randomized trial will evaluate the efficacy of ibr in combination with Nab-P/GCB. Methods: The randomized, multicenter, double-blind RESOLVE trial (NCT02436668; PCYC-1137-CA) will compare ibr vs. placebo in combination with Nab-P/GCB in approximately 320 patients with untreated metastatic PDAC. Key eligibility criteria include histologically confirmed metastatic PDAC; stage IV diagnosis within 6 weeks of randomization; adequate hematologic, hepatic, and renal function; and Karnofsky performance score ≥ 70. Key exclusion criteria include prior therapies (chemotherapy for primary PDAC, BTK inhibitor, or radiotherapy), neuroendocrine or acinar pancreatic carcinoma, known brain or leptomeningeal disease, and history of stroke or intracranial hemorrhage &lt; 6 months prior to enrollment. Patients will be randomized to oral ibr (560 mg) or matched placebo given daily in combination with Nab-P (125 mg/m 2 ) and GCB (1,000 mg/m 2 ) on days 1, 8, and 15 of a 28-day cycle until disease progression or treatment is no longer tolerated. A safety run-in phase will evaluate the ibr combination prior to the randomization portion of the study. The primary endpoint is progression-free survival; secondary endpoints include overall survival and safety. Enrollment in the trial has been initiated. Clinical trial information: NCT02436668.
Surveillance of the Middle East respiratory syndrome (MERS) coronavirus (CoV) infection in healthcare workers after contact with confirmed MERS patients: incidence and risk factors of MERS-CoV seropositivity
Authors: C.-J. Kim, W.S. Choi, Y. Jung, S. Kiem, H.Y. Seol, H.J. Woo, Y.H. Choi, J.S. Son, K.-H. Kim, Y.-S. Kim, E.S. Kim, S.H. Park, J.H. Yoon, S.-M. Choi, H. Lee, W.S. Oh, S.-Y. Choi, N.-J. Kim, J.-P. Choi, S.Y. Park, J. Kim, S.J. Jeong, K.S. Lee, H.C. Jang, J.Y. Rhee, B.-N. Kim, J.H. Bang, J.H. Lee, S. Park, H.Y. Kim, J.K. Choi, Y.-M. Wi, H.J. Choi
Journal: Clinical Microbiology and Infection (2016)
P2-237: Pemetrexed as second-line treatment in advanced NSCLC patients: results on 160 patients in a multi-institutional analysis
Authors: Alessandra Bearz, Isabella Garassino, Raffaele Cavina, Adolfo Favaretto, Massimo Boccalon, Renato Talamini, Armando Santoro, Umberto Tirelli
Journal: Journal of Thoracic Oncology (2007)
Medicaid and Children’s Hospitals—A Vital but Strained Double Helix for Children’s Health Care
Authors: Matthew M. Davis, Kristin Kan
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
FGF23 and Nutritional Metabolism
Authors: Lindsay R. Pool, Myles Wolf
Journal: Annual Review of Nutrition (2017)

The discovery of fibroblast growth factor 23 (FGF23) has provided a more complete understanding of the regulation of phosphate and mineral homeostasis in health and in chronic kidney disease. It has also offered new insights into stratification of risk of cardiovascular events and death among patients with chronic kidney disease and the general population. In this review, we provide an overview of FGF23 biology and physiology, summarize clinical outcomes that have been associated with FGF23, discuss potential mechanisms for these observations and their public health implications, and explore clinical and population health interventions that aim to reduce FGF23 levels and improve public health.
Frontal fibrosing alopecia: there is no statistically significant association with leave-on facial skin care products and sunscreens: reply from the authors
Authors: N. Aldoori, K. Dobson, C.R. Holden, A.J. McDonagh, M. Harries, A.G. Messenger
Journal: British Journal of Dermatology (2016)

We did not perform a matched one-to-one comparison between FFA subjects and controls, we compared two groups with similar ages. The only continuous variable was age. The responses to the questions posed were categorical. We therefore maintain that a Fisher's exact test rather than a McNemar's test was an appropriate method for analyzing the results.
Improvement of Quality of Response with Ibrutinib Plus Bendamustine/Rituximab Vs Placebo Plus Bendamustine/Rituximab for Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Authors: Paula Cramer, Asher Chanan-Khan, Graeme Fraser, Fatih Demirkan, Rodrigo Santucci Silva, Halyna Pylypenko, Sebastian Grosicki, Ann Janssens, Andre Goy, Jiri Mayer, Marie Sarah Dilhuydy, Javier Loscertales, Nancy L. Bartlett, Abraham Avigdor, Simon Rule, Steven Sun, Charles Phelps, Michelle Mahler, Mariya Salman, Michael Schaffer, Sriram Balasubramanian, Angela Howes, Michael Hallek
Journal: Blood (2015)
PWE-021 Whole gut transit scintigraphy with a liquid-phase meal in patients with chronic gastrointestinal symptoms
Authors: L I Sonoda, M Y Halim, D R Parry-Jones, S Middleton, K K Balan
Journal: Gut (2010)

<h3>Introduction</h3> Functional gastrointestinal symptoms are common in the general population. Whole gut transit scintigraphy (WGTS) has been available to investigate patients with functional gastrointestinal symptoms for several years but the technique has not been widely utilised. The aim of this study was to review our experience of doing a liquid-phase WGTS in patients with functional gastrointestinal problems and determine its clinical usefulness. <h3>Methods</h3> 56 patients (14 males, mean age 43 years) with functional upper and lower GI symptoms had undergone WGTS using 111In-DTPA in water and a dual-headed gamma camera over a 5-year-period. Gastric emptying (GE) analysis was done using time-activity curves. Small bowel transit (SBT) was determined by the time taken for 10% of total abdominal counts to reach the caecum. Geometric centre (GC) of activity was used to determine colonic transit (CT) time. <h3>Result</h3> Presenting symptoms were constipation (n=27), diarrhoea (n=14) and dyspepsia (n=15). WGTS confirmed the diagnosis in 63% patients with constipation. 26% patients with constipation also had a delayed GE and SBT. 30% patients with constipation and 29% with diarrhoea had normal colonic transit. Only 29% of diarrhoea patients seemed to have a rapid CT. More than 50% patients with dyspepsia had normal GE, SBT and CT whereas 40% of them had a delayed CT and SBT. <h3>Conclusion</h3> WGTS appears to have a useful role in patients with symptoms of chronic constipation. In patients with diarrhoea, WGTS helps to elucidate its true cause. The procedure helps the clinician explain the symptoms and focus on a particular region of the GI tract for further investigation.
Transdifferentiation Requires iNOS Activation
Authors: Shu Meng, Gang Zhou, Qilin Gu, Palas K. Chanda, Frank Ospino, John P. Cooke
Journal: Circulation Research (2016)

We have previously shown that innate immunity is necessary for transdifferentiation of fibroblasts to endothelial cells. A major signaling molecule involved in innate immunity is inducible nitric oxide synthase (iNOS). Accordingly, we hypothesized that iNOS-generated nitric oxide (NO) might enhance transdifferentiation.To elucidate the role of NO in epigenetic plasticity during transdifferentiation.We exposed the BJ fibroblasts to transdifferentiation formulation that included endothelial growth factors and innate immune activator polyinosinic:polycytidylic acid to induce endothelial cells. Generation of transdifferentiated endothelial cells was associated with iNOS expression and NO elaboration. In the absence of polyinosinic:polycytidylic acid, or in the presence of antagonists of NFκB (nuclear factor kappa B) or iNOS activity, NO synthesis and induce endothelial cell generation was reduced. Furthermore, genetic knockout (in murine embryonic fibroblasts) or siRNA knockdown (in BJ fibroblasts) of iNOS nearly abolished transdifferentiation, an effect that could be reversed by iNOS overexpression. Notably, polyinosinic:polycytidylic acid induced nuclear localization of iNOS, and its binding to, and nitrosylation of, the epigenetic modifier ring finger protein 1A (RING1A) as assessed by immunostaining, Co-IP, and mass spectrometry. Nitrosylation of RING1A reduced its binding to chromatin and reduced global levels of repressive histone marker H3K27 trimethylation. Overexpression of a mutant form of RING1A (C398A) lacking the nitrosylation site almost abrogated transdifferentiation.Overall, our data indicate that during transdifferentiation, innate immune activation increases iNOS generation of NO to S-nitrosylate RING1A, a key member of the polycomb repressive complex. Nitrosylation of RING1A reduces its binding to chromatin and decreases H3K27 trimethylation level. The release of epigenetic repression by nitrosylation of RING1A is critical for effective transdifferentiation.
P0021 : Altering transplanted cell engraftment and proliferation in the liver through paracrine signaling with cotransplantation of liver sinusoidal endothelial cells and hepatocytes in mice
Authors: S. Merlin, K. Bellofatto, E. Berishvili, B. Joseph, R. Badhe, S. Gupta, A. Follenzi
Journal: Journal of Hepatology (2015)
Patterns of care, prognosis, and survival of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib.
Authors: A. Italiano, A. Cioffi, R. G. Maki, P. Schoffski, P. Rutkowski, A. Le Cesne, F. Duffaud, A. Adenis, N. Isambert, E. Bompas, J. Blay, P. G. Casali, P. Coco, D. R. D'Adamo, M. L. Keohan, M. Toulmonde, C. Antonescu, M. Debiec-Rychter, J. Coindre, B. Bui Nguyen
Journal: Journal of Clinical Oncology (2011)

10044 Background: Data regarding the management and outcome of metastatic GIST patients (pts) refractory to 1st line imatinib (I) and 2nd sunitinib (S) are limited. Methods: Eleven institutions participated in this retrospective study. A preliminary analysis based on the data from 176 pts treated in 9 institutions is presented in this abstract. Final analysis will be presented at the meeting. Results: Median age was 57 years (range 18-84). Median progression free-survival (PFS) on 1st line I and 2nd line S were 22.4 months (mo) (95% CI: 19.2-26.2) and 8.2 mo (95% CI: 6-10.4), respectively. Pts who were treated with 3rd or 4th line sorafenib (vs other treatment) had significantly higher PFS, although improvement in overall survival (OS) was observed in 4th line only. On univariate analysis, age, performance status ≥2, haemoglobin <10g/dl, albumin < 35g/l and primary mutation on exon 11 or 9 (versus wild-type or PDGFRα mutation) were significantly associated with inferior OS. On multivariate analysis, albumin level (HR=2.2, 95% CI 1.1–4.4; p = 0.03) and mutational status (HR=4.1, 95% CI 1.4–11.9; p = 0.01) were the sole independent predictors of poor OS. Conclusions: This collaborative study is the largest one focusing on the management and survival of GIST patients refractory to I and S. Pts more likely to carry secondary mutations seem to have the worst outcome. Rechallenge with I is associated with limited clinical benefit, but appears superior to best supportive care. Sorafenib may provide the best treatment option in case of clinical trial ineligibility, given these data. Treatment N PFS OS Median (months) 95% CI P value Median (months) 95% CI P value 3rd-line setting 157 3.6 [3.0-4.2] - 9.5 [7.7-11.4] - Imatinib (I) 23 3.6 p = 0.001 9.9 p < 0.0001 I + other agent (not “ib”) 26 2.7 8.6 Nilotinib (N) 26 3.9 13.6 Sorafenib 54 6.1 11.3 Other 10 2.5 9.1 Best supportive care (BSC) 18 2.1 2.3 4th line setting 104 2.5 [1.9-3.0] - 5.1 [3.6-6.7] - I 18 4.9 p = 0.008 7.4 p < 0.0001 I + other agent (not “ib”) 13 1.9 5.5 N 14 3.8 5.4 Sorafenib 14 7.5 11.5 Other 20 1.8 8.2 BSC 25 1.6 1.6 5th line setting 45 2.6 [1.7-3.6] - 4.4 [2.7-6.0] - 6th line setting 18 1.4 [0.6-2.2] - 2.8 [1.4-4.2] -
Changes in Overall Diet Quality and Subsequent Type 2 Diabetes Risk: Three U.S. Prospective Cohorts
Authors: Sylvia H. Ley, An Pan, Yanping Li, JoAnn E. Manson, Walter C. Willett, Qi Sun, Frank B. Hu
Journal: Diabetes Care (2016)

OBJECTIVE Recent public health recommendations emphasize adopting a healthful dietary pattern, but evidence is scarce on whether incremental diet quality changes have an impact on long-term diabetes prevention. We aim to evaluate diet quality changes during a 4-year period and subsequent 4-year type 2 diabetes incidence. RESEARCH DESIGN AND METHODS Participants of prospective cohorts, the Nurses’ Health Study (NHS), NHS II, and the Health Professionals Follow-up Study, who were free of diabetes at baseline (n = 124,607), were observed for ≥20 years. Diet quality, reflected by the Alternate Healthy Eating Index (AHEI) score, was assessed every 4 years to calculate changes. RESULTS We documented 9,361 cases of type 2 diabetes during 2,093,416 person-years of follow-up. A &amp;gt;10% decrease in AHEI score over 4 years was associated with a higher subsequent diabetes risk (pooled hazard ratio 1.34 [95% CI 1.23–1.46]) with multiple adjustment, whereas a &amp;gt;10% increase in AHEI score was associated with a lower risk (0.84 [0.78–0.90]). Greater improvement in diet quality was associated with lower diabetes risk across baseline diet quality status (P for trend ≤ 0.001 for low, medium, or high initial diet quality) and baseline BMI (P for trend ≤ 0.01 for BMI &amp;lt;25, 25–29, or 30 kg/m2). Changes in body weight explained 32% (95% CI 24–41) of the association between AHEI changes (per 10% increase) and diabetes risk. CONCLUSIONS Improvement in overall diet quality is associated with a lower risk of type 2 diabetes, whereas deterioration in diet quality is associated with a higher risk. The association between diet quality changes and diabetes risk is only partly explained by body weight changes.
Synaptopodin Is a Coincidence Detector of Tyrosine versus Serine/Threonine Phosphorylation for the Modulation of Rho Protein Crosstalk in Podocytes
Authors: Lisa Buvall, Hanna Wallentin, Jonas Sieber, Svetlana Andreeva, Hoon Young Choi, Peter Mundel, Anna Greka
Journal: Journal of the American Society of Nephrology (2016)

Tyrosine and serine/threonine signal-transduction pathways influence many aspects of cell behavior, including the spatial and temporal regulation of the actin cytoskeleton. However, little is known about how input from diverse tyrosine and serine/threonine kinases is integrated to control Rho protein crosstalk and actin remodeling, which are critically important in podocyte health and disease. Here we unveil the proteolytically-regulated, actin organizing protein synaptopodin as a coincidence detector of tyrosine versus serine/threonine phosphorylation. We show that serine/threonine and tyrosine kinases duel for synaptopodin stability versus degradation. EGFR/Src-mediated tyrosine phosphorylation of synaptopodin in podocytes promotes binding to the serine/threonine phosphatase calcineurin. This leads to the loss of 14-3-3 binding, resulting in synaptopodin degradation, Vav2 activation, enhanced Rac1 signaling, and ultimate loss of stress fibers. Our studies reveal how synaptopodin, a single proteolytically-controlled protein, integrates antagonistic tyrosine versus serine/threonine phosphorylation events for the dynamic control of the actin cytoskeleton in podocytes.