tbuckley/cabot-search huggingface dataset:
Generation of a functional mammary gland from a single stem cell
Authors: Mark Shackleton, François Vaillant, Kaylene J. Simpson, John Stingl, Gordon K. Smyth, Marie-Liesse Asselin-Labat, Li Wu, Jane E. Visvader, Geoffrey J. Lindeman
Journal: Cancer Research (2006)

4839   The mammary gland can be functionally regenerated in mice by serial transplantation of epithelial fragments, providing evidence for the existence of self-renewing, multipotential mammary stem cells (MaSCs). Recently the concept has emerged that MaSCs play a central role in breast tumorigenesis. However, the identity and purification of MaSC has proved elusive due to the lack of defined markers. Using specific cell surface markers and flow cytometry, we have identified a distinct subpopulation that is enriched for MaSCs, demonstrated by transplantation into cleared mammary fat pads at limiting dilution. Remarkably, a single mammary epithelial cell from this population, carrying the lacZ transgene, was found to generate a complete mammary gland in vivo. These cells contributed to both the luminal and myoepithelial lineages in transplanted virgin mammary glands, and extensive lobuloalveolar units were generated during pregnancy. Serial transplantation of the clonal outgrowths also yielded complete mammary glands, confirming that the cells were capable of self-renewal. These data establish that single cells from the enriched population have multipotential and self-renewing capacity, a hallmark of stem cells. It will be of interest to determine whether the stem cell is a target of transformation mammary tumorigenesis models.
WITHDRAWN: Phytochemical investigation and antihyperglycemic activity of leaves of Aegle marmelos (L.) Correa
Authors: Soe Sandar Phyo, Win Myint, Khine Khine Lwin, Aye Kyi, Myint Myint Than
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
Genesis of a KPC-producing Klebsiella pneumoniae after in vivo transfer from an imported Greek strain
Authors: F Barbier, E Ruppé, P Giakkoupi, L Wildenberg, J C Lucet, A Vatopoulos, M Wolff, A Andremont
Journal: Eurosurveillance (2010)

We document here the in vivo transfer of blaKPC-2 between intensive care unit-acquired and a commensal strain of K. pneumoniae in a French patient after his repatriation from Greece. This first report of in vivo transfer of a blaKPC-2 between two K. pneumoniae strains raises further concerns about the spread of carbapenem resistance among Enterobacteriaceae.
Phase I Single (SAD) and Multiple Ascending Dose (MAD) Studies of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of AG-348, a First-in-Class Allosteric Activator of Pyruvate Kinase-R, in Healthy Subjects
Authors: Hua Yang, Elizabeth Merica, Yue Chen, Marvin Cohen, Ronald Goldwater, Collin Hill, Hyeryun Kim, Penelope Kosinski, Charles Kung, Bruce Silver, Luke Utley, Sam Agresta
Journal: Blood (2014)
The potential for a concerted system for the rapid monitoring of excess mortality throughout Europe
Authors: M Kanieff, G Rago, G Minelli, T Lamagni, O Sadicova, J Šelb, A Vantarakis, S Conti
Journal: Eurosurveillance (2010)

We present the results of a survey conducted in the context of the project European Monitoring of Excess Mortality for Public Health Action (EuroMOMO), which is being conducted to develop a routine public health mortality monitoring system for the timely detection of excess deaths related to public health threats in Europe. The survey was conducted in 32 European countries using two questionnaires on: i) the existing and planned mortality monitoring systems, and ii) the routine collection of mortality data. Nine existing mortality monitoring systems were identified in seven countries (Belgium, Germany, France (two systems), Italy (two systems), Portugal, Spain, and Switzerland), as well as several systems that were in a pilot or planning state. Each system is described in detail. The results will be used for the subsequent phases of EuroMOMO, in particular for identifying the minimum requirements for the planned European system and for selecting countries to be included in the project's pilot phase.
Brief Report: Pulmonary Function Tests: High Rate of False‐Negative Results in the Early Detection and Screening of Scleroderma‐Related Interstitial Lung Disease
Authors: Yossra A. Suliman, Rucsandra Dobrota, Dörte Huscher, Thi D. L. Nguyen‐Kim, Britta Maurer, Suzana Jordan, Rudolf Speich, Thomas Frauenfelder, Oliver Distler
Journal: Arthritis & Rheumatology (2015)

Objective Validated methods for the screening and early diagnosis of systemic sclerosis (SSc; scleroderma)–related interstitial lung disease (ILD) are needed. The aim of this study was to evaluate the performance of pulmonary function tests (PFTs) compared with that of high‐resolution computed tomography (HRCT) of the chest for the detection of SSc‐related ILD in clinical practice, and to identify predictors of lung involvement that is functionally occult but significant on HRCT. Methods Prospectively enrolled patients with SSc were assessed according to the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trial and Research standards. The assessment included PFTs and HRCT. The HRCT images were evaluated in a blinded manner by 2 experienced radiologists. The performance parameters of PFTs for the diagnosis of SSc‐related ILD were calculated. Predictors of significant ILD as determined by HRCT in patients with normal forced vital capacity (FVC) values were identified through logistic regression. Results Among the 102 patients, 64 (63.0%) showed significant ILD on HRCT, while only 27 (26.0%) had an FVC &lt;80% of predicted, and 54 (53.0%) had a decrease in the results of at least 1 PFT. Forty (62.5%) of 64 patients with significant ILD on HRCT had a normal FVC value, translating into a high false‐negative rate. Notably, 5 of 40 patients with a normal FVC value had severe, functionally occult lung fibrosis; in 2 of these patients, the results of all of the PFTs were within normal limits. Patients with normal FVC values despite evidence of fibrosis on HRCT more frequently had anti–Scl‐70 antibodies and diffuse SSc and less frequently had anticentromere antibodies (ACAs) compared with patients with both normal FVC values and normal HRCT results. Conclusion The derived evidence‐based data reveal a high risk of missing significant SSc‐related ILD when relying solely on PFTs. More comprehensive screening algorithms for early detection are warranted. In particular, additional imaging investigations for the early detection of SSc‐related ILD should be considered in ACA‐negative patients with normal FVC values.
525. A Novel Shuttle Vector Approach To Identify Genes Involved in Hematopoietic Stem Cell Disorders Using Vector-Mediated Genotoxicity
Journal: Molecular Therapy (2013)

Here we report a novel retroviral shuttle vector approach to perform mutagenesis screens to identify genes and gene networks involved in the development of hematopoietic stem cell disorders (HSCs). Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders that are characterized by dysplasia that often progress to acute myeloid leukemia (AML). However, little is known about the mechanisms of disease progression. Several mutations in the transcription factor AML1 (RUNX1) have been identified, and account for 15%40% of MDS-refractory anemia. Our goal is to identify genes activated by vector-mediated genotoxicity in transplanted HSCs that collaborate with AML1 to promote MDS and progression to AML. The genes and gene networks identified in our screen may be used as therapeutic targets or biomarkers for detection and treatment of these HSC disorders. In addition, our approach has the potential to identify genes and gene networks involved in other stem cell disorders.
Toxin producing Vibrio cholerae O75 outbreak, United States, March to April 2011
Authors: TJ M Onifade, R Hutchinson, K Van Zile, D Bodager, R Baker, C Blackmore
Journal: Eurosurveillance (2011)

The Florida Department of Health, Florida, United States, is investigating a Vibrio cholerae O75 outbreak. Ten cases with disease onsets from 23 March to 13 April 2011, presented with gastrointestinal symptoms of diarrhoea, nausea, vomiting, cramps, chills, and/or fever, after consuming raw or lightly cooked oysters harvested from Apalachicola Bay, Florida. Symptoms were milder than those during outbreaks of epidemic (serogroup O1 and O139) Vibrio cholerae; no case required rehydration treatment or hospitalisation.
Elevated potassium levels suppress T cell activation within tumors
Authors: Robert L Eil, Rahul Roychoudhuri, David Clever, Shashank Patel, Madhu Sukumar, Jenny H Pan, Douglas Palmer, Christopher A Klebanoff, Nicholas P Restifo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Tumors progress in immunocompetent hosts despite the ability of the adaptive immune system to recognize cancer cells. Ion gradients regulate T cell function but their role in intratumoral immune responses is unexplored. We found that the concentration of K+ was strikingly elevated
Shifting paradigms for ischaemic preconditioning: AUTHOR'S RETROSPECTIVE
Authors: G. L. Semenza
Journal: Cardiovascular Research (2012)

This editorial refers to an article by Z. Cai et al . [11][1] published in Cardiovascular Research in 2008 (see [Box 1][2]). It is accompanied by an editorial by G. Heusch, pp. 214–215, this issue, as part of this Spotlight on Landmark Papers in Cardiovascular Research . 

One of the most intensively studied phenomena in cardiovascular research is ischaemic preconditioning (IPC), the observation that exposure of the heart to several short (e.g. 5 min) cycles of ischaemia (I5) and reperfusion (R5) will protect against injury caused by a subsequent prolonged (e.g. 30 min) episode of ischaemia (I30) followed by reperfusion.1 The onset of cardioprotection is immediately following the IPC stimulus and lasts for only several hours,1 but is followed by a second window of cardioprotection with the onset ∼24 h after IPC and lasting for several days thereafter.2,3

Based on thousands of research studies spanning two decades, a dominant paradigm was established that acute- or early-phase cardioprotection was rapid but short-lived because it involved transient post-translational modifications of existing proteins, whereas delayed or late-phase cardioprotection was slower to develop but longer lasting because it involved de novo synthesis of mRNAs and their translation into proteins. A remarkably long list of signal transduction pathways, biochemical reactions, and gene products have been implicated in the response of the heart to IPC.4–6 For several molecular targets, the paradigm holds: the activity of the protein is regulated during the acute phase of protection, whereas expression of the protein is regulated during the late phase.

It is conventional wisdom that the IPC stimulus-response pathway is centred in cardiomyocytes. Indeed, some investigators have attempted to develop reductionist cell culture models in which cardiomyocytes are exposed to oxygen and glucose deprivation for various lengths of time,7 although others in the …

 [1]: #ref-11
 [2]: #F2
Ammonia produces pathological changes in human hepatic stellate cells and is a target for therapy of portal hypertension
Authors: Rajiv Jalan, Francesco De Chiara, Vairappan Balasubramaniyan, Fausto Andreola, Varun Khetan, Massimo Malago, Massimo Pinzani, Rajeshwar P. Mookerjee, Krista Rombouts
Journal: Journal of Hepatology (2015)
Novel Small-Molecule Inhibitors Targeting Complement Factor D for Therapy of Paroxysmal Nocturnal Hemoglobinuria
Authors: B. Paul Morgan, Jane Thanassi, Steven Podos, Avinash Phadke, Venkat Gadhachanda, Godwin Pais, Akihiro Hashimoto, Qiuping Wang, Dawei Chen, Xiangzhu Wang, Atul Agarwal, Milind Deshpande, Yongqing Huang, Jason Wiles, Mingjun Huang
Journal: Blood (2014)
Prognostic Tests for Estrogen Receptor–Positive Breast Cancer
Authors: Jee Ye Kim, Seung-il Kim, Soonmyung Paik
Journal: JAMA Oncology (2015)

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 Oncology 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 Oncology journal
Mechanistic Investigation of Bone Marrow Suppression Associated with Palbociclib and its Differentiation from Cytotoxic Chemotherapies
Authors: Wenyue Hu, Tae Sung, Bart A. Jessen, Stephane Thibault, Martin B. Finkelstein, Nasir K. Khan, Aida I. Sacaan
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Palbociclib (PD-0332991) is the first selective cyclin-dependent kinase (CDK) 4/6 inhibitor approved for metastatic breast cancer. Hematologic effects, especially neutropenia, are dose-limiting adverse events for palbociclib in humans. Experimental Design: Reversible hematologic effects and bone marrow hypocellularity have been identified in toxicology studies in rats and dogs after palbociclib treatment. To understand the mechanism by which the hematologic toxicity occurs, and to further differentiate it from the myelotoxicity caused by cytotoxic chemotherapeutic agents, an in vitro assay using human bone marrow mononuclear cells (hBMNC) was utilized. Results: This work demonstrated that palbociclib-induced bone marrow suppression occurred through cell-cycle arrest, with no apoptosis at clinically relevant concentrations, was not lineage-specific, and was reversible upon palbociclib withdrawal. In contrast, treatment with chemotherapeutic agents (paclitaxel and doxorubicin) resulted in DNA damage and apoptotic cell death in hBMNCs. In the presence or absence of the antiestrogen, palbociclib-treated hBMNCs did not become senescent and resumed proliferation following palbociclib withdrawal, consistent with pharmacologic quiescence. The breast cancer cells, MCF-7, conversely, became senescent following palbociclib or antiestrogen treatment with additive effects in combination and remained arrested in the presence of antiestrogen. Conclusions: Palbociclib causes reversible bone marrow suppression, clearly differentiating it from apoptotic cell death caused by cytotoxic chemotherapeutic agents. This study also distinguished the cell-cycle arresting action of palbociclib on normal bone marrow cells from the senescent effects observed in breast cancer cells. These results shed light on the mechanism and support risk management of palbociclib-induced bone marrow toxicity in the clinic. Clin Cancer Res; 22(8); 2000–8. ©2015 AACR.
Virus-specific CD8+ T cells infiltrate melanoma lesions and retain function despite high PD-1 expression
Authors: Dan A Erkes, Toktam Mohgbeli, Christopher M Snyder
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts It is well known that CD8+ T cell infiltration of tumors is correlated with positive patient prognosis. Because of this, many viral vaccine vectors have been created to induce expansion and infiltration of tumor-specific CD8+ T cells. Cytomegalovirus (CMV) is a herpes virus that
Quantitative molecular analysis of MCM6 and MCM7 and their association with HPV E6 and E7 mRNA expression, viral load and physical status in invasive cervical carcinoma
Authors: Hewei Li, Melisa D. Harrison, Patricia L. Avissar, Douglas P. Malinowski
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

918 

Objective: This study aimed to determine the association of minichromosome maintenance proteins MCM6 and MCM7 expression with human papillomavirus (HPV) E6 and E7 mRNA expression levels, viral load and physical status in invasive cervical carcinoma. Methods: Thirty four pairs of cervical carcinoma and matched adjacent normal cervical epithelium specimens were obtained as fresh-frozen tissues. All clinical specimens were obtained with patient consent and under IRB approval. Samples were analyzed for HPV presence by PCR analysis and DNA sequencing of the L1 amplicon. mRNA expression of MCM6, MCM7, HPV E6 and E7 was analyzed by TaqMan real-time RT-PCR assay. HPV E2 and E6 DNA copy numbers were quantified by TaqMan real-time PCR assay. HPV viral load was represented by the copy number of E6 DNA per genome. Physical status was determined by the ratio between the DNA copy number of E2 and E6. Correlation of variables was statistically analyzed using Spearman's correlation method. Results: All 34 cervical carcinoma specimens were positive for high-risk HPV DNA. 32 of them infected with HPV16, HPV18 or both were analyzed. Our results showed a wide variation in expression patterns of HPV E6 and E7 mRNA (from 0.01 to 48.83) and in viral load of HPV16 and HPV18 (0.2-163 copies per genome and 3-8365 copies per genome, respectively). Mixed episomal and integrated forms of viral physical status were detected in all tumor samples with E2/E6 ratios ranged from 0.001 to 0.91. In contrast, MCM6 and MCM7 displayed consistent over-expression in the carcinoma samples with a 3.3-3.5 fold increase of mRNA relative to the matched normal cervical epithelium controls. MCM6 and MCM7 mRNA expression levels were not strongly correlated with either E6/E7 expression (R=0.481, P  0.5). In addition, our previous study observed consistent elevated expression of MCM6 and MCM7 proteins in the same cohort of cervical carcinoma and cervical intraepithelial neoplasia (CIN) 2+ tissues, as evidenced by Western blot and immunohistochemistry assays (H Li, et al., Proc Amer Assoc Cancer Res 2005;46:4886). Conclusions: In the present panel of cervical specimens, elevated expression levels of MCM6 and MCM7 mRNA are not well correlated with expression levels of HPV E6 and E7 mRNA, viral load and physical status. Together with our previous findings at the protein level, MCM6 and MCM7 appear to be more reliable molecular biomarkers to identify high-grade lesions and cervical carcinoma within cervical biopsy specimens, than HPV parameters.
Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial
Authors: Anna Wilkins, Helen Mossop, Isabel Syndikus, Vincent Khoo, David Bloomfield, Chris Parker, John Logue, Christopher Scrase, Helen Patterson, Alison Birtle, John Staffurth, Zafar Malik, Miguel Panades, Chinnamani Eswar, John Graham, Martin Russell, Peter Kirkbride, Joe M O'Sullivan, Annie Gao, Clare Cruickshank, Clare Griffin, David Dearnaley, Emma Hall
Journal: The Lancet Oncology (2015)

Patient-reported outcomes (PROs) might detect more toxic effects of radiotherapy than do clinician-reported outcomes. We did a quality of life (QoL) substudy to assess PROs up to 24 months after conventionally fractionated or hypofractionated radiotherapy in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial.
Rapidly controlled outbreak of Serratia marcescens infection/colonisations in a neonatal intensive care unit, Pescara General Hospital, Pescara, Italy, April 2011
Authors: E Polilli, G Parruti, P Fazii, D D’Antonio, D Palmieri, C D’Incecco, A Mangifesta, G Garofalo, L Del Duca, C D’Amario, M Scimia, V Cortesi, V Fortunato
Journal: Eurosurveillance (2011)

In April 2011, an outbreak of Serratia marcescens infection/colonisations occurred in the neonatal intensive care unit of Pescara General Hospital. Rapid microbiological investigations lead to identification of five cases of likely cross-transmission from a neonate hospitalised for S. marcescens sepsis: four infections and one neonate colonised post-mortem. Two low birth weight neonates died. The environmental investigation detected S. marcescens from two soap dispensers. Strict hygiene measures lead to early interruption of the outbreak, without recurrences to date.
Management of Nonvariceal Upper Gastrointestinal Bleeding
Journal: Annals of Internal Medicine (2010)

Objective:�Toprovideanoverviewofmanagementof� nonvaricealuppergastrointestinalbleeding�(NVUGIB). •� Methods:�Literaturereviewinthecontextofaclinical� case. •� Results:� NVUGIBisacommoncondition,� withap- proximately� 30%� to� 50%� ofcasesattributableto� pepticulcerdisease.�Endoscopyisthecornerstone�
Correspondence
Authors: Moses S. Elisaf
 *, Sonia Athina P. Karabina, Alexandros D. Tselepis
Journal: Cardiovascular Research (1998)

We have read with great interest the recently published patients with microvascular angina than in the control paper by Miwa et al. on HDL abnormalities observed in subjects (p,0.05),implying an increase in larger HDL patients with variant angina [1].The authors noticed that particles.Interestingly, the HDL particles appeared to be high HDL cholesterol /ApoA1 levels associated with low larger in patients with microvascular angina as compared HDL cholesterol and ApoA1 levels were characteristic in to controls both in the smoking and in the non smoking patients with variant angina, in whose HDL particles were subpopulations.large, cholesterol-rich and possibly malfunctioning.Since Thus, despite the absence of lower HDL cholesterol similar to variant angina altered endothelial-mediated levels, patients with microvascular angina, as well as vasomotion of coronary arteries is also observed in the patients with CAD, exhibit larger HDL particles, which, microvasculature of patients with microvascular angina along with the other lipid derangements observed in this [2,3], such HDL abnormalities could have also played a population, could contribute to the existing functional role in its pathogenesis.Recently we have studied the lipid abnormalities.profile of patients with microvascular angina in comparison with patients with coronary artery disease (CAD) and normal subjects [4].By contrast to the findings References observed in patients with variant angina, HDL cholesterol and ApoA1 levels in microvascular angina patients did not