tbuckley/cabot-search huggingface dataset:
Dendritic cells-based vaccine to inhibit triple-negative breast cancer cells proliferation.
Authors: Yong Huang, Meijun Long, Jun An, Mi Tang, Renbin Liu
Journal: Journal of Clinical Oncology (2016)

e12566 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited effective treatment options. New therapeutic approaches are urgently needed to improve the prognosis of TNBC. We studied the character of Runx2 gene in breast cancer and whether the Runx2-dendritic cell (DC) vaccine can induce specific antitumor effect on triple negative breast cancer in vitro. Methods: The expression of Runx2 in triple negative breast cancer，non-triple negative breast cancer and normal breast cells were analyzed by RT-PCR，immunocytochemistry and westernblot. DC were isolated and cultured from peripheral blood of healthy donors, the surface maker CD11c, CD80, CD86 and HLA-DR were analyzed with flow cytometry. Runx2 lentivirus were prepared to infect DC and divided in transfected group, negative group and blank group. Fluorescence microscope, PCR and Westernblot tested its transfection efficiency of all groups. DC and T cells were cultured together to induce CTL, ELISA was used to detect the secretion of IL-12 and IFN-γ. The killing ability of CTL were calculated by MTT. Results: PCR results shown the ΔCT value of Runx2 in MDA –MB -231,MCF7 and MCF10A were 10.37±0.61, 11.86±0.59, 12.97±0.06（P < 0.05）respectively. Both immunocytochemistry and westernblot showed Runx2 were strongly positive in MDA –MB -231, but weaker in MCF7 and MCF10A.In this study, Runx2-lentivirus were prepared and transfected DC. Rich green flurescent confirmed that the Runx2 gene were successfully turned into mature DC .Then the transfected DC were co-cultured with T cells, and the secretion of IL-12、IFN-γ（pg/ml）were measured as 170.33±5.03、517.15±5.88. While the secretion of IL-12、IFN-γ were 72.30±3.05、171.57±1.37（P < 0.05）in non-transfected group. And the killing ratio of cytotoxic T cells of transfected group on triple negative breast cancer was 60.02±3.51 compared with 25.57±3.64（P < 0.05）of the control group. Conclusions: Runx2 maybe a new target for triple negative breast cancer treatment. Runx2 can transduce DC successfully and the vaccine induce specific CTL and strong cytotoxicity against triple negative breast cancer.
Risk factors associated with mortality among women with breast cancer in Haiti.
Authors: Joseph Bernard, Garvey Rama Pascal, Sarah Cassandra Raymond, Vincent DeGennaro
Journal: Journal of Clinical Oncology (2017)

e13069 Background: According to recent estimations of GLOBOCAN 2012, breast cancer is the 2 nd most common cancer among Haitian women. This study aims to describe the epidemiology of breast cancer at a Haitian hospital and to determine the factors associated with mortality. Methods: A retrospective chart review was conducted on women treated for breast cancer at the Innovating Health International Cancer Center, in Port-au-Prince, Haiti. All charts with complete information from 2014 and 2015 were included. Charts were reviewed to collect key variables related to breast cancer. Odds ratios were calculated and Mantel-Haenszel Chi-square test was used to identify the factors associated with mortality. Results: Among the 289 charts reviewed, 275 were selected for this study. The mean age is 51.82 years-old [20 - 100]. 81.1% of the patients had stage III or IV breast cancer at their first consultation. 92% of the women were diagnosed with invasive ductal carcinoma. Of the 165 cases tested for hormone receptor status, 54.5% were ER-positive, 31.5% were triple negative and 12.1% were HER2-enriched. The mortality rate is 24.4%. The odds of dying from breast cancer was significantly higher among women who had their menarche before 15 years old [Odds Ratio (OR) = 4.2; P = 0.02], stage III or IV breast cancer (OR = 3.7; P = 0.01), triple-negative or HER2-positive breast cancer (OR = 2.5; P = 0.01). Mortality was significantly lower among women who benefited from hormone therapy (OR = 0.22; P &lt; 0.01). Conclusions: Breast cancer is often diagnosed at late stages in Haiti, which increases mortality. Women with ER-positive breast cancer survive significantly more than those with HER2-positive or triple-negative breast cancer, mainly due to the availability of hormone therapy and the absence of trastuzumab. A national awareness and screening program has to be implemented to educate Haitian women on breast cancer and increase early diagnosis. As an essential medicine in oncology according to the World Health Organization (WHO), biosimilar trastuzumab needs to be available to increase the survival of patients with HER2-positive breast cancer.
From class waivers to precision medicine in paediatric oncology
Authors: Andrew D J Pearson, Stefan M Pfister, Andre Baruchel, Jean-Pierre Bourquin, Michela Casanova, Louis Chesler, François Doz, Angelika Eggert, Birgit Geoerger, David T W Jones, Pamela R Kearns, Jan J Molenaar, Bruce Morland, Gudrun Schleiermacher, Johannes H Schulte, Josef Vormoor, Lynley V Marshall, C Michel Zwaan, Gilles Vassal
Journal: The Lancet Oncology (2017)
Examining Provisions Related to Consent in the Revised Common Rule
Authors: Jeremy Sugarman
Journal: The American Journal of Bioethics (2017)

The long-standing overarching policy governing research with human subjects conducted and supported by most federal agencies and departments in the United States, known as the Common Rule, has recently been revised, with most requirements slated to become effective in 2018. Although there are multiple alterations to the current regulations, some of the most significant changes aim to enhance consent for research. While some of the particular provisions in this regard will be easy to apply and promise to help meet this goal, others may be more challenging to implement despite their intuitive appeal. In this article, I examine some of the provisions in the revised Common Rule that relate to consent: (1) new required consent elements; (2) the goal of comprehension in the consent process; (3) consent forms; and (4) broad consent. By raising issues about these provisions now and suggesting possible ways to overcome their potential shortfalls, the hope is that future efforts can be taken to help clarify and appropriately implement them.
Association of Concussion With Abnormal Menstrual Patterns in Adolescent and Young Women
Authors: Meredith L. Snook, Luke C. Henry, Joseph S. Sanfilippo, Anthony J. Zeleznik, Anthony P. Kontos
Journal: JAMA Pediatrics (2017)

Brain injury may interrupt menstrual patterns by altering hypothalamic-pituitary-ovarian axis function. Investigators have yet to evaluate the association of concussion with menstrual patterns in young women.To compare abnormal menstrual patterns in adolescent and young women after a sport-related concussion with those after sport-related orthopedic injuries to areas other than the head (nonhead).This prospective cohort study of adolescent and young women with a sport-related concussion (n = 68) or a nonhead sport-related orthopedic injury (n = 61) followed up participants for 120 days after injury. Patients aged 12 to 21 years who presented within 30 days after a sport-related injury to a concussion or sports medicine clinic at a single academic center were eligible. Menstrual patterns were assessed using a weekly text message link to an online survey inquiring about bleeding episodes each week. The first patient was enrolled on October 14, 2014, and follow-up was completed on January 24, 2016. Inclusion criteria required participants to be at least 2 years postmenarche, to report regular menses in the previous year, and to report no use of hormonal contraception.Sport-related concussion or nonhead sport-related orthopedic injury.Abnormal menstrual patterns were defined by an intermenstrual interval of less than 21 days (short) or more than 35 days (long) or a bleeding duration of less than 3 days or more than 7 days.A total of 1784 survey responses were completed of the 1888 text messages received by patients, yielding 487 menstrual patterns in 128 patients (mean [SD] age, 16.2 [2.0] years). Of the 68 patients who had a concussion, 16 (23.5%) experienced 2 or more abnormal menstrual patterns during the study period compared with 3 of 60 patients (5%) who had an orthopedic injury. Despite similar gynecologic age, body mass index, and type of sports participation between groups, the risk of 2 or more abnormal menstrual bleeding patterns after injury was significantly higher among patients with concussion than among those with an orthopedic injury (odds ratio, 5.85; 95% CI, 1.61-21.22).Adolescent and young women may have increased risk of multiple abnormal menstrual patterns after concussion. Because abnormal menstrual patterns can have important health implications, monitoring menstrual patterns after concussion may be warranted in this population. Additional research is needed to elucidate the relationship between long-term consequences of concussion and the function of the hypothalamic-pituitary-ovarian axis.
All patients with metal-on-metal hip implants should undergo tests, says MHRA
Authors: Deborah Cohen
Journal: BMJ (2017)

All patients with metal-on-metal hip implants are advised to have blood tests and either plain radiographs or scans, under new guidance by the Medicines and Healthcare Products Regulatory Agency (MHRA).1

Concerns have been repeatedly raised about these devices, and the regulator previously recommended in 2012 that symptomatic patients or those with particular types of implants should undergo tests.

Over 50 000 UK patients have had metal-on-metal hip replacements fitted. The MHRA said that the majority currently have well functioning hips but that some patients will develop progressive soft tissue reactions to the wear debris …
PEG, 45 Months' Experience from a District General Hospital (DGH)
Authors: A Koulaouzidis, D Nicolaides, E Said, S Kadis, JN Singh, AA Saeed
Journal: Endoscopy (2006)

Aims: To check current practice and determine early (within 4 weeks) and mid-term (within 8 weeks) and overall mortality post-Percutaneous Endoscopic Gastrostomy (PEG) insertion.
Prognostic Value of End of Treatment FDG-PET Scan in T-Cell Lymphoma, a 20-Year Single Institution Study
Authors: Enrico Derenzini, Angela Gueli, Safaa Ramadan, Anna Vanazzi, Simona Sammassimo, Federica Gigli, Niccolo' Frungillo, Riccardo Bruna, Alberto Agazzi, Alberto De Crescenzo, Rocco Pastano, Laura L Travaini, Chiara Grana, Laszlo Daniele, William Arcese, Corrado Tarella
Journal: Blood (2016)
Phase 1 study of CB-839, a small molecule inhibitor of glutaminase (GLS) in combination with paclitaxel (Pac) in patients (pts) with triple negative breast cancer (TNBC).
Authors: Angela DeMichele, James J. Harding, Melinda L. Telli, Pamela N. Munster, Rana McKay, Othon Iliopoulos, Keith W. Orford, Mark K. Bennett, James Walter Mier, Taofeek Kunle Owonikoko, Manish R. Patel, Richard D. Carvajal, Funda Meric-Bernstam, Jeffrey R. Infante
Journal: Journal of Clinical Oncology (2016)

1011 Background: CB-839 is a first-in-class highly selective inhibitor of GLS, a key enzyme in the utilization of glutamine by many cancer cells. TNBC is very glutaminolytic, with high GLS expression and a high glutamate:glutamine ratio, and highly dependent on glutamine for growth. CB-839 has selective activity in most in vitro and in vivo TNBC preclinical models tested. CX-839-001 is an ongoing Phase 1 basket trial of CB-839 as monotherapy and in combination with approved agents. BID dosing of CB-839 with meals provided optimal PK and tolerability and achieved robust inhibition of GLS in blood and tumors. After achieving strong GLS inhibition with acceptable toxicity and observing a TNBC patient (pt) with a 23% reduction in tumor burden on study for >18 months, a combination arm testing CB-839 with Pac (Pac-CB) for TNBC was opened. Methods: Patients with metastatic TNBC received escalating doses of CB-839 (400-800 BID) in combination with a fixed weekly Pac dose (80 mg/kg on Days 1, 8, 15 of 28 day cycle). Upon demonstration of safety and tolerability of the 600 mg BID CB-839 dose, an expansion cohort of taxane-naïve TNBC pts was opened (n=14). Results: Twelve pts have received Pac-CB during the dose escalation; 7 pts at 400 mg BID, 4 at 600 mg BID and 1 at 800 mg BID. These patients have been heavily pretreated (3 median prior therapies for adv/met disease), including 7 pts that have received a prior taxane (3 in the adv/met setting). The combination has been well tolerated with only one DLT to date (G4 neutropenia at 400 mg BID). Among 11 efficacy-evaluable TNBC pts on the Pac-CB treatment, 2 pts have achieved partial response (PR) and 4 pts have achieved stable disease (SD). Both pts with PRs had received prior Pac, including one pt that progressed on Pac without achieving a response. Three of the 4 SD pts remain on study for 2.9+, 7.1+, and 8.8+ months. Conclusions: The Pac-CB combination has been well tolerated with only 1 DLT to date; expansion at the CB-839 dose of 600 mg BID is in progress. Preliminary activity has been demonstrated with 2 PRs in the first 8 pts enrolled, even in the setting of prior progression on paclitaxel. Updated data on the expansion cohort will be presented. Clinical trial information: NCT02071862.
Abstract 182: Characterization of Electrophysiological and Conduction Parameters of the Heart in Trpm4-deficient Mice
Authors: Griet Jacobs, Miklos Kecskes, Rudi Vennekens
Journal: Circulation Research (2015)

TRPM4 is a Ca2+-activated non-selective cation channel that belongs to the family of the Transient Receptor Potential (TRP) ion channels. Importantly, TRPM4 is impermeable for Ca2+ and is involved in different Ca2+-dependent cell functions, such as exocytosis, contraction and cell death. Trpm4 is known to be expressed in atrial and ventricular cardiomyocytes. The interest in the functional role of TRPM4 in the heart has risen further by the discovery of Trpm4 mutations that are linked to cardiac conduction disorders, including Progressive Familial Heart Block type I (PFHBI) and Brugada Syndrome. Both gain-of-function and loss-of-function mutation were described in patients with cardiac conduction diseases. Recently, our group showed that TRPM4 plays a role during the late repolarization phase of the action potential in murine ventricular cardiomyocytes and that deletion of the Trpm4 gene leads to shorter ventricular action potentials. To characterize if deletion of Trpm4 has an effect on the conduction properties of the heart, an in depth electrophysiological study was performed in living mice. An octapolar catheter was inserted into the right atrium and ventricle of the heart to measure intracardial electrograms. The atrial-His (AH) and His-ventricular (HV) intervals were calculated and no differences were found between WT and Trpm4-deficient mice. Additionally, more detailed conduction parameters of the heart were determined by use of programmed electrical stimulation (PES) protocols. Sinus node recovery time (SNRT) was not different between WT and Trpm4-deficient mice. Effective refractory period of atrium (AERP), AV node (AVNERP) and ventricle (VERP) were in the same range in WT and Trpm4-deficient mice. Wenckebach periodicity, the parameter for AV nodal conduction, was also not different between WT and Trpm4-deficient mice. These results suggest that deletion of Trpm4 has no effects on the conduction properties of the murine heart.
The Intensive Care Trial for Critically Ill Onco-Haematologic Patients: The Need for Response Criteria at 5 Days of Full Treatment to Separate Good Risk Patients and Avoid Futile Intensive Care Interventions
Authors: Silvia Monsalvo, Belen Sevillano, Andrew Innes, Maialen Lasa, Laura Skinner, Richard Stumpfle, Syed Altaf, Eva Yebra, Donald MacDonald, Dragana Milojkovic, Aristeidis Chaidos, Ian H Gabriel, Stephen J Brett, Robert Broomhead, Parind Patel, Umeer Waheed, Jiri Pavlu, Renuka Palanicawandar, Edward Kanfer, Richard M Szydlo, Jane F. Apperley, Eduardo Olavarria
Journal: Blood (2016)
Selective Inhibition of Nuclear Cytoplasmic Transport As a New Treatment Paradigm in Myelofibrosis
Authors: Dongqing Yan, Srinivas K. Tantravahi, Anthony D. Pomicter, Anna Senina, Kevin C. Gantz, Hannah M. Redwine, Josef T. Prchal, Sabina Swierczek, Phillip M. Clair, Anna M. Eiring, Erkan Baloglu, Thomas O'Hare, Michael W. Deininger
Journal: Blood (2016)
Abstract 309: Two SoxD Family Transcription Factors Influence Heart Function at Baseline and After Cardiac Overload
Authors: Nadine Beetz, Daniel Quiat, Rhonda Bassel-Duby, Eric N Olson
Journal: Circulation Research (2013)

Background: Sox6, a member of the SoxD family of transcription factors, has recently been established as a mediator of the actions of MyomiRs miR-208b and 499 in skeletal muscle. Sox6 suppresses the expression of slow skeletal muscle genes and its deletion promotes skeletal muscle fiber switching in mice. However, the role of Sox6 in the heart remains elusive. Given the importance of MyomiRs in regulating cardiac stress responses and the regulation of Sox6 by MyomiRs in the heart, we postulate that Sox6 is a central regulator of cardiac hypertrophy and heart failure. Results: Because of functional redundancy of Sox6 and Sox5 in multiple tissues, Sox6 fl/fl mice were crossbred with Sox5 fl/fl mice and mice expressing CRE recombinase under the control of the alphaMHC gene promoter to obtain Sox5 fl/fl / Sox6 fl/fl /CRE+ ( Sox5/6 cKO) animals or CRE- controls. Sox5/6 cKO animals were viable and born at expected Mendelian ratios. At baseline, Sox5/6 cKO mice did not show any signs of hypertrophy or cardiac failure as assessed by echocardiography at the age of 9 weeks. While cardiac size and heart function measured by echocardiography was unaltered in mice aged 4-5 months, cardiac catheterization revealed significant decreases in contractility in Sox5/6 cKO animals. In addition, qPCR analysis of hearts showed increased expression of slow myosin Myh7 and Nppa , a marker of cardiac stress, in Sox5/6 cKO animals compared to controls. Following cardiac pressure overload for 3 weeks by transverse aortic constriction (TAC), significant decreases in cardiac function, as measured by echocardiography, were apparent in Sox5/6 cKO compared to control mice. Sox5/6 cKO mice subjected to TAC also showed signs of cardiac failure such as increased wet lung weight. Conclusion: Cardiac-specific deletion of Sox6 and Sox5 lead to reduction of cardiac function at baseline and exacerbated susceptibility to the development of cardiac failure after cardiac pressure overload. The contribution of each individual transcription factor to the observed phenotypes is currently being investigated.
Plerixafor As a Salvage Regimen to Mobilize Allogeneic Stem Cells in Healthy Volunteers (NCT01954914)
Authors: Kristina Hoelig, Helmuth Schmidt, Gero Hütter, Michael Kramer, Raphael Teipel, Kristin Zimmer, Matthias Blechschmidt, Tigran Torosian, Rainer Ordemann, Frank Kroschinsky, Alexander H. Schmidt, Martin Bornhäuser, Gerhard Ehninger, Johannes Schetelig
Journal: Blood (2016)
Cellular functions and pathways affected by PCGEM1, a prostate-specific gene associated with African-American prostate cancer patients
Authors: Gyorgy Petrovics, Lakshmi Ravindranath, Jesse P. Street, Mazen Makarem, Wei Zhang, Isabell A. Sesterhenn, Leon Sun, Judd W. Moul, Shiv Srivastava
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4021 

PCGEM1 is a novel class of prostate specific, androgen regulated gene that lacks protein-coding capacity, and may function as a non-coding RNA riboregulator. Evaluation of PCGEM1 expression in laser microdissected paired normal and tumor cells of 90 prostate cancer (CaP) patients revealed significantly elevated PCGEM1 expression levels in CaP cells of African- American patients (p=0.0002), suggesting potential roles for PCGEM1 in CaP biology. The objective of this study was to determine the cell biologic functions of PCGEM1 . LNCaP cells overexpressing PCGEM1 exhibited a marked growth advantage compared to vector control both in cell proliferation and in colony formation assays. Stably transfected LNCaP cells overexpressing PCGEM1 were used to assess biochemical mechanisms underlying its cell growth promoting effects. The effect of PCGEM1 overexpression in LNCaP cells on the phosphorylation state of key proteins involved in cellular pathways related to cell cycle, cell proliferation, and apoptosis was assayed. Protein lysates from exponentially growing cells were subjected to Western blotting and assayed using a panel of 36 phospho-specific antibodies. In LNCaP cells overexpressing PCGEM1 , a significant increase in phosphorylation of three out of 36 proteins, Rb(Ser807/811), GSK3beta(Ser9), and p38MAPK(Thr180/Tyr182) was detected. The phosphorylation of specific sites on these key signaling proteins induce specific downstream events currently under investigation in our laboratory. We conclude that overexpression of PCGEM1 promotes cell proliferation/colony formation of LNCaP cells and the underlying mechanisms may involve at least three different major pathways: the Rb, GSK3beta and p38MAPK pathways. These novel observations warrant future studies aimed at PCGEM1 functions, and its potential as therapeutic/biomarker target of CaP development especially in African-American patients.
Tumor Specific Glycosylated CD43 Is a Novel and Highly Specific Target for Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Marijn A. Gillissen, Martijn Kedde, Greta de Jong, Etsuko Yasuda, Sophie E. Levie, Arjen Q. Bakker, Marie Jose Kersten, Paul Hensbergen, Tim Beaumont, Pauline M. van Helden, Hergen Spits, Mette D. Hazenberg
Journal: Blood (2016)
Impact of Recombination on the Base Composition of Bacteria and Archaea
Authors: Louis-Marie Bobay, Howard Ochman
Journal: Molecular Biology and Evolution (2017)

The mutational process in bacteria is biased toward A and T, and most species are GC-rich relative to the mutational input to their genome. It has been proposed that the shift in base composition is an adaptive process-that natural selection operates to increase GC-contents-and there is experimental evidence that bacterial strains with GC-rich versions of genes have higher growth rates than those strains with AT-rich versions expressing identical proteins. Alternatively, a nonadaptive process, GC-biased gene conversion (gBGC), could also increase the GC-content of DNA due to the mechanistic bias of gene conversion events during recombination. To determine what role recombination plays in the base composition of bacterial genomes, we compared the spectrum of nucleotide polymorphisms introduced by recombination in all microbial species represented by large numbers of sequenced strains. We found that recombinant alleles are consistently biased toward A and T, and that the magnitude of AT-bias introduced by recombination is similar to that of mutations. These results indicate that recombination alone, without the intervention of selection, is unlikely to counteract the AT-enrichment of bacterial genomes.