tbuckley/cabot-search huggingface dataset:
Impact of Blood–Brain Barrier Integrity on Tumor Growth and Therapy Response in Brain Metastases
Authors: Matthias Osswald, Jonas Blaes, Yunxiang Liao, Gergely Solecki, Miriam Gömmel, Anna S. Berghoff, Laurent Salphati, Jeffrey J. Wallin, Heidi S. Phillips, Wolfgang Wick, Frank Winkler
Journal: Clinical Cancer Research (2016)

The role of blood-brain barrier (BBB) integrity for brain tumor biology and therapy is a matter of debate.We developed a new experimental approach using in vivo two-photon imaging of mouse brain metastases originating from a melanoma cell line to investigate the growth kinetics of individual tumor cells in response to systemic delivery of two PI3K/mTOR inhibitors over time, and to study the impact of microregional vascular permeability. The two drugs are closely related but differ regarding a minor chemical modification that greatly increases brain penetration of one drug.Both inhibitors demonstrated a comparable inhibition of downstream targets and melanoma growth in vitro In vivo, increased BBB permeability to sodium fluorescein was associated with accelerated growth of individual brain metastases. Melanoma metastases with permeable microvessels responded similarly to equivalent doses of both inhibitors. In contrast, metastases with an intact BBB showed an exclusive response to the brain-penetrating inhibitor. The latter was true for macro- and micrometastases, and even single dormant melanoma cells. Nuclear morphology changes and single-cell regression patterns implied that both inhibitors, if extravasated, target not only perivascular melanoma cells but also those distant to blood vessels.Our study provides the first direct evidence that nonpermeable brain micro- and macrometastases can effectively be targeted by a drug designed to cross the BBB. Small-molecule inhibitors with these optimized properties are promising agents in preventing or treating brain metastases in patients. Clin Cancer Res; 22(24); 6078-87. ©2016 AACRSee related commentary by Steeg et al., p. 5953.
Somatostatin Analogs as mainteinance therapy in heavily pretreated thymic epithelial tumors
Authors: G. Palmieri, M. Ottaviano, L. Nappi, P. Rescigno, M. Marino, L. Montella, M. Micillo, G. Palumbo, S. Del Vecchio, E. Matano, V. Damiano
Journal: Annals of Oncology (2015)
IκB kinaseα/β control biliary homeostasis and hepatocarcinogenesis in mice by phosphorylating the cell‐death mediator receptor‐interacting protein kinase 1
Authors: Christiane Koppe, Patricia Verheugd, Jérémie Gautheron, Florian Reisinger, Karina Kreggenwinkel, Christoph Roderburg, Luca Quagliata, Luigi Terracciano, Nikolaus Gassler, René H. Tolba, Yannick Boege, Achim Weber, Michael Karin, Mark Luedde, Ulf P. Neumann, Ralf Weiskirchen, Frank Tacke, Mihael Vucur, Christian Trautwein, Bernhard Lüscher, Christian Preisinger, Mathias Heikenwalder, Tom Luedde
Journal: Hepatology (2016)

The IκB‐Kinase (IKK) complex—consisting of the catalytic subunits, IKKα and IKKβ, as well as the regulatory subunit, NEMO—mediates activation of the nuclear factor κB (NF‐κB) pathway, but previous studies suggested the existence of NF‐κB‐independent functions of IKK subunits with potential impact on liver physiology and disease. Programmed cell death is a crucial factor in the progression of liver diseases, and receptor‐interacting kinases (RIPKs) exerts strategic control over multiple pathways involved in regulating novel programmed cell‐death pathways and inflammation. We hypothesized that RIPKs might be unrecognized targets of the catalytic IKK‐complex subunits, thereby regulating hepatocarcinogenesis and cholestasis. In this present study, mice with specific genetic inhibition of catalytic IKK activity in liver parenchymal cells (LPCs; IKKα/β LPC‐KO ) were intercrossed with RIPK1 LPC‐KO or RIPK3 −/− mice to examine whether RIPK1 or RIPK3 might be downstream targets of IKKs. Moreover, we performed in vivo phospho‐proteome analyses and in vitro kinase assays, mass spectrometry, and mutagenesis experiments. These analyses revealed that IKKα and IKKβ—in addition to their known function in NF‐κB activation—directly phosphorylate RIPK1 at distinct regions of the protein, thereby regulating cell viability. Loss of this IKKα/β‐dependent RIPK1 phosphorylation in LPCs inhibits compensatory proliferation of hepatocytes and intrahepatic biliary cells, thus impeding HCC development, but promoting biliary cell paucity and lethal cholestasis. Conclusions: IKK‐complex subunits transmit a previously unrecognized signal through RIPK1, which is fundamental for the long‐term consequences of chronic hepatic inflammation and might have potential implications for future pharmacological strategies against cholestatic liver disease and cancer. (H epatology 2016;64:1217‐1231)
<i>In Vitro</i> Effects of Lead on Gene Expression in Neural Stem Cells and Associations between Up-regulated Genes and Cognitive Scores in Children
Authors: Peter J. Wagner, Hae-Ryung Park, Zhaoxi Wang, Rory Kirchner, Yongyue Wei, Li Su, Kirstie Stanfield, Tomas R. Guilarte, Robert O. Wright, David C. Christiani, Quan Lu
Journal: Environmental Health Perspectives (2016)

Background:Lead (Pb) adversely affects neurodevelopment in children. Neural stem cells (NSCs) play an essential role in shaping the developing brain, yet little is known about how Pb perturbs NSC functions and whether such perturbation contributes to impaired neurodevelopment.Objectives:We aimed to identify Pb-induced transcriptomic changes in NSCs and to link these changes to neurodevelopmental outcomes in children who were exposed to Pb.Methods:We performed RNA-seq-based transcriptomic profiling in human NSCs treated with 1 μM Pb. We used qRT-PCR, Western blotting, ELISA, and ChIP (chromatin immunoprecipitation) to characterize Pb-induced gene up-regulation. Through interrogation of a genome-wide association study, we examined the association of gene variants with neurodevelopment outcomes in the ELEMENT birth cohort.Results:We identified 19 genes with significantly altered expression, including many known targets of NRF2—the master transcriptional factor for the oxidative stress response. Pb induced the expression of SPP1 (secreted phosphoprotein 1), which has known neuroprotective effects. We demonstrated that SPP1 is a novel direct NRF2 target gene. Single nucleotide polymorphisms (SNPs) (rs12641001) in the regulatory region of SPP1 exhibited a statistically significant association (p = 0.005) with the Cognitive Development Index (CDI).Conclusion:Our findings revealed that Pb induces an NRF2-dependent transcriptional response in neural stem cells and identified SPP1 up-regulation as a potential novel mechanism linking Pb exposure with neural stem cell function and neurodevelopment in children.Citation:Wagner PJ, Park HR, Wang Z, Kirchner R, Wei Y, Su L, Stanfield K, Guilarte TR, Wright RO, Christiani DC, Lu Q. 2017. In vitro effects of lead on gene expression in neural stem cells and associations between up-regulated genes and cognitive scores in children. Environ Health Perspect 125:721–729; http://dx.doi.org/10.1289/EHP265
Морфологічна діагностика ерозивного езофагіту при гастроезофагеальній рефлюксній хворобі
Authors: Yu.A. Haidar, L.M. Mosiychuk, N.Yu. Oshmianska 
Journal: GASTROENTEROLOGY (2016)

Досліджено біоптати стравоходу 79 хворих із клінічно підтвердженою гастроезофагеальною рефлюксною хворобою. За допомогою комп’ютерної морфометрії виміряно та проаналізовано ширину міжклітинних просторів плоского епітелію стравоходу, а також особливості міграції клітин запалення у випадках розвитку неерозивного, ерозивного й еозинофільного езофагіту залежно від тонуса сфінктера Одді та жовчного міхура.
High prevalence of bronchiectasis in patients with cartilage-hair hypoplasia
Authors: Svetlana Kostjukovits, Paula Klemetti, Anna Föhr, Merja Kajosaari, Helena Valta, Mervi Taskinen, Sanna Toiviainen-Salo, Outi Mäkitie
Journal: Journal of Allergy and Clinical Immunology (2016)
Second Report of Arab Leukemia Net (ALN) Registry for Chronic Myeloid Leukemia (CML) in the Middle East &amp;North Africa Region (AFME). Epidemiology of CML and Additional Chromosomal Abnormalities (ACAs) in Egypt, Multicenter Results
Authors: Mohamed osman Azzazi, Omar Fahmy, Mervat Mattar, Ashraf El Ghandour, Manal El Sorady, Samir Shehata, Yasser. El Nahass, Hani Hegab, Rasha Ibrahim, Rasha Magdy, Hend Ellithy, Mohammad Shazly, Rana Hussein Khaled, Mai Sameir, Mohab Elshaer
Journal: Blood (2014)
Sedation Interruption for Mechanically Ventilated Patients
Authors: Massimo Zambon, Pier Carlo Bergonzi, Sergio Colombo
Journal: JAMA (2013)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Psychosocial Adjustment and Perceived Risk Among Adolescent Girls From Families With <i>BRCA1/2</i> or Breast Cancer History
Authors: Angela R. Bradbury, Linda Patrick-Miller, Lisa A. Schwartz, Brian L. Egleston, Dare Henry-Moss, Susan M. Domchek, Mary B. Daly, Lisa Tuchman, Cynthia Moore, Paula K. Rauch, Rebecca Shorter, Kelsey Karpink, Colleen Burke Sands
Journal: Journal of Clinical Oncology (2016)

To evaluate the impact of breast cancer family history and maternal BRCA1/2 mutation on the psychosocial adjustment and perceived risk in girls age 11 to 19 years old.Girls age 11 to 19 years old with one or more relatives with breast cancer or a familial BRCA1/2 mutation (breast cancer family history [BCFH] positive, n = 208; n = 69 with BRCA1/2-positive mother), peers (BCFH negative, n = 112), and their mothers completed assessments of psychosocial adjustment, breast cancer-specific distress, and perceived risk of breast cancer.General psychosocial adjustment did not differ significantly between BCFH-positive and BCFH-negative girls, either by self-report or mother report, except for higher self-esteem among BCFH-positive girls (P = .01). BCFH-positive girls had higher breast cancer-specific distress than BCFH-negative girls (P < .001), but girls from BRCA1/2-positive families did not differ from other BCFH-positive peers. BCFH-positive girls were more likely to report themselves at increased self-risk for breast cancer in adulthood than BCFH-negative peers (74% v 33%, respectively; P ≤ .001). Girls from BRCA1/2-positive families were more likely than other BCFH-positive and BCFH-negative peers to report themselves at increased risk (P < .001). In all groups, perceived risk of breast cancer was associated with older age. Higher breast cancer-specific distress among adolescent girls was associated with higher self-perceived risk of breast cancer and higher maternal breast cancer-specific distress.Adolescent girls from BRCA1/2-positive and breast cancer families have higher self-esteem and do not have poorer psychosocial adjustment than peers. However, they do experience greater breast cancer-specific distress and perceived risk of breast cancer, particularly among older girls. Understanding the impact is important to optimize responses to growing up in families at familial and genetic risk for breast cancer, particularly given the debate over the genetic testing of children for cancer susceptibility in adulthood.
Biomarkers as potential predictors of pathologic complete response (pCR) in the NOAH trial of neoadjuvant trastuzumab in patients (pts) with HER2-positive locally advanced breast cancer (LABC)
Authors: L. Gianni, W. Eiermann, L. Pusztai, V. F. Semiglazov, B. Hoegel, A. Koehler, G. Manikhas, M. Bates, P. Valagussa, J. Baselga
Journal: Journal of Clinical Oncology (2008)

504 Background: The NOAH trial evaluated the addition of trastuzumab (H) to chemotherapy (CT) for pts with HER2-positive LABC. A significant improvement in pCR has been reported (Gianni. ASCO 2007; abs 532). Methods: 228 pts were randomized to receive 3 cycles of doxorubicin (60 mg/m2) and paclitaxel (150 mg/m2) q3w, 4 cycles of paclitaxel (175 mg/m2 q3w) and 3 cycles of CMF (C 600 mg/m2, M 40 mg/m2, F 600 mg/m2 d 1+8 q4w) with or without concomitant H (8 mg/kg loading dose then 6 mg/kg q3w for 1 year) before surgery. 171 (75%) core biopsies obtained before treatment were available for assays of c-Myc (by FISH), PTEN (by IHC) and IGF1R (by IHC) in addition to estrogen receptor (ER) and progesterone receptor (PgR). Results: The 171 pts with available biopsies were representative of the overall NOAH population, although with a lower incidence of ER+ tumors. Negative PgR status was strongly associated with pCR in the H group (51% vs 16% in PgR-positive tumors; p=0.008). Overall, 32 pts had c-Myc amplification (cut-off ratio >2). Of these, 11/21 (52%) H pts but only 1/11 (9%) CT pts had pCR. PTEN expression was not predictive of pCR after H but was associated with a higher pCR rate after CT alone (p=0.05). IGF1R membrane staining was significantly lower in H-treated pts with pCR than those with residual disease (24% vs 48%; p=0.05). In logistical regression analysis, PgR status and H treatment were significant predictors of pCR. In the H-treated group, PgR status (p=0.012) was the most significant predictor of pCR; ER and IGF1R membrane staining showed borderline significance (p=0.089 and p=0.075, respectively). Conclusions: PgR-negative status and c- Myc amplification are associated with higher pCR rates after addition of H compared to CT alone. Overexpression of membranous IGF1R is associated with a higher likelihood of residual disease after H-based CT. These results will be combined with those of ongoing studies of additional biomarkers (HER3, p95HER2 and HER2 homodimers) to define a multivariate residual disease predictor. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, Roche MGRM Genentech™ BioOncology, Roche Roche
Cost of Antihyperglycemic Medications in the United States—Reply
Authors: Xinyang Hua, William H. Herman, Philip Clarke
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Relative Risk of Cardiovascular Disease after Treatment for Aggressive Non-Hodgkin’s Lymphoma.
Authors: E. C. Moser, E. M. Noordijk, F. E. van Leeuwen, S. le Cessie, J. W. Baars, J. Thomas, P. Carde, M. van Glabbeke, J. H. Meerwaldt, J. C. Kluin-Nelemans
Journal: Blood (2005)
Cervical Cancer Screening Among Women Without a Cervix
Authors: Mona Saraiya, George F Sawaya
Journal: JAMA (2004)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Extracellular Matrix Invasion in Metastases and Angiogenesis: Commentary on the Matrigel “Chemoinvasion Assay”
Authors: Adriana Albini
Journal: Cancer Research (2016)

Invasive and metastatic cells must cross the basement membrane's extracellular matrix to disseminate to distant sites. Although in the eighties the concept was well established, no easy in vitro functional assay was available. Working in Hynda Kleinman's and George Martin's laboratory at NIH (Bethesda, MD), where the reconstituted basement membrane Matrigel was discovered, I had the intuition that Matrigel coating of migration filters could represent a valid tool to mimic in vitro biological matrix barriers. The "chemoinvasion assay" using Matrigel in Boyden blind-well chambers was developed in 1985-1986 and published in Cancer Research in 1987. It was a rapid and easy tool for studying invasion, a crucial step in cancer metastasis. Since its conception, the assay has been employed for studies on the metastatic process, angiogenesis, and for the screening of drugs that are potentially able to decrease cell invasion. It was adapted to be easily employed as a routine assay and commercialized. In that historical article, we also described the use of thick layers of Matrigel for the study of morphogenesis of invasive cells, a simple and visual assay, adaptable to reproduce collective cell migration in vitro To date, in its diverse optimized variants, the chemoinvasion assay is still widely used, contributing to novel data production. In the era of precision medicine and next-generation sequencing, the cheap, fast, and reproducible chemoinvasion assay may have further developments, including possible applications in the investigations on cancer stem cells, immunity and immune modulators, applications with siRNA silencing, selection of aggressive cell populations, and phenotypes and genetic evaluations. Cancer Res; 76(16); 4595-7. ©2016 AACR.See related article by Albini A et al., Cancer Res 1987;47:3239-45Visit the Cancer Research 75(th) Anniversary timeline.
Preoperative Frailty Assessment and Outcomes at 6 Months or Later in Older Adults Undergoing Cardiac Surgical Procedures
Authors: Dae Hyun Kim, Caroline A. Kim, Sebastian Placide, Lewis A. Lipsitz, Edward R. Marcantonio
Journal: Annals of Internal Medicine (2016)

Frailty assessment may inform surgical risk and prognosis not captured by conventional surgical risk scores.To evaluate the evidence for various frailty instruments used to predict mortality, functional status, or major adverse cardiovascular and cerebrovascular events (MACCEs) in older adults undergoing cardiac surgical procedures.MEDLINE and EMBASE (without language restrictions), from their inception to 2 May 2016.Cohort studies evaluating the association between frailty and mortality or functional status at 6 months or later in patients aged 60 years or older undergoing major or minimally invasive cardiac surgical procedures.2 reviewers independently extracted study data and assessed study quality.Mobility, disability, and nutrition were frequently assessed domains of frailty in both types of procedures. In patients undergoing major procedures (n = 18 388; 8 studies), 9 frailty instruments were evaluated. There was moderate-quality evidence to assess mobility or disability and very-low- to low-quality evidence for using a multicomponent instrument to predict mortality or MACCEs. No studies examined functional status. In patients undergoing minimally invasive procedures (n = 5177; 17 studies), 13 frailty instruments were evaluated. There was moderate- to high-quality evidence for assessing mobility to predict mortality or functional status. Several multicomponent instruments predicted mortality, functional status, or MACCEs, but the quality of evidence was low to moderate. Multicomponent instruments that measure different frailty domains seemed to outperform single-component ones.Heterogeneity of frailty assessment, limited generalizability of multicomponent frailty instruments, few validated frailty instruments, and potential publication bias.Frailty status, assessed by mobility, disability, and nutritional status, may predict mortality at 6 months or later after major cardiac surgical procedures and functional decline after minimally invasive cardiac surgery.National Institute on Aging and National Heart, Lung, and Blood Institute.