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https://www.readbyqxmd.com/read/29238628/intraprostatic-fiducials-compared-with-bony-anatomy-and-skin-marks-for-image-guided-radiation-therapy-of-prostate-cancer
#1
Juliette Moreau, Julian Biau, Jean-Louis Achard, Ivan Toledano, Charles Benhaim, Fabrice Kwiatkowski, Geneviève Loos, Michel Lapeyre
Purpose Prostate motion occurs during radiotherapy for localized prostate cancer. We evaluated the input of intraprostatic fiducials for image-guided radiation therapy and compared it with bony anatomy and skin marks. Methods Eleven patients were implanted with three fiducial markers in the prostate. Daily sets of orthogonal kV-kV images were compared with digitally reconstructed radiography. Data were recorded for skin marks, bony anatomy, and fiducial markers. The variations were analyzed along three principal axes (left-right: LR, superoinferior: SI, and anteroposterior: AP)...
October 12, 2017: Curēus
https://www.readbyqxmd.com/read/29229169/acute-kidney-injury-in-children
#2
REVIEW
Scott M Sutherland, David M Kwiatkowski
Acute kidney injury (AKI) has become one of the more common complications seen among hospitalized children. The development of a consensus definition has helped refine the epidemiology of pediatric AKI, and we now have a far better understanding of its incidence, risk factors, and outcomes. Strategies for diagnosing AKI have extended beyond serum creatinine, and the most current data underscore the diagnostic importance of oliguria as well as introduce the concept of urinary biomarkers of kidney injury. As AKI has become more widespread, we have seen that it is associated with a number of adverse consequences including longer lengths of stay and greater mortality...
November 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29224250/multiple-autologous-bone-marrow-derived-cd271-mesenchymal-stem-cell-transplantation-overcomes-drug-resistant-epilepsy-in-children
#3
Olga Milczarek, Danuta Jarocha, Anna Starowicz-Filip, Stanislaw Kwiatkowski, Bogna Badyra, Marcin Majka
There is a need among patients suffering from drug-resistant epilepsy (DRE) for more efficient and less toxic treatments. The objective of the present study was to assess the safety, feasibility, and potential efficacy of autologous bone marrow cell transplantation in pediatric patients with DRE. Two females and two males (11 months to 6 years) were enrolled and underwent a combined therapy consisting of autologous bone marrow nucleated cells (BMNCs) transplantation (intrathecal: 0.5 × 109 ; intravenous: 0...
December 10, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29221145/subependymal-giant-cell-astrocytomas-in-tuberous-sclerosis-complex-have-consistent-tsc1-tsc2-biallelic-inactivation-and-no-braf-mutations
#4
Anika Bongaarts, Krinio Giannikou, Roy J Reinten, Jasper J Anink, James D Mills, Floor E Jansen, G M Wim Spliet, Willfred F A den Dunnen, Roland Coras, Ingmar Blümcke, Werner Paulus, Theresa Scholl, Martha Feucht, Katarzyna Kotulska, Sergiusz Jozwiak, Anna Maria Buccoliero, Chiara Caporalini, Flavio Giordano, Lorenzo Genitori, Figen Söylemezoğlu, José Pimentel, Mark Nellist, Antoinette Y N Schouten-van Meeteren, Anwesha Nag, Angelika Mühlebner, David J Kwiatkowski, Eleonora Aronica
Subependymal giant cell astrocytomas (SEGAs) are rare, low-grade glioneuronal brain tumors that occur almost exclusively in patients with tuberous sclerosis complex (TSC). Though histologically benign, SEGAs can lead to serious neurological complications, including hydrocephalus, intractable seizures and death. Previous studies in a limited number of SEGAs have provided evidence for a biallelic two-hit inactivation of either TSC1 or TSC2, resulting in constitutive activation of the mechanistic target of rapamycin complex 1 pathway...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217530/the-impact-of-smoking-and-tp53-mutations-in-lung-adenocarcinoma-patients-with-targetable-mutations-the-lung-cancer-mutation-consortium-lcmc2
#5
Dara L Aisner, Lynette M Sholl, Lynne Berry, Michael Rossi, Heidi Chen, Junya Fujimoto, Andre L Moreira, Suresh Ramalingam, Liza C Villaruz, Gregory A Otterson, Eric B Haura, Katerina Politi, Bonnie S Glisson, Jeremy Cetnar, Edward Garon, Joan Schiller, Saiama Waqar, Lecia V Sequist, Julie R Brahmer, Yu Shyr, Kelly Kugler, Ignacio Ivan Wistuba, Bruce E Johnson, John D Minna, Mark G Kris, Paul A Bunn, David J Kwiatkowski
PURPOSE Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas. PATIENTS AND METHODS Sixteen U.S. institutions enrolled 1367 lung cancer patients in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and immunohistochemistry...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29211316/the-efficacy-of-prostate-specific-antigen-screening-impact-of-key-components-in-the-erspc-and-plco-trials
#6
Harry J de Koning, Roman Gulati, Sue M Moss, Jonas Hugosson, Paul F Pinsky, Christine D Berg, Anssi Auvinen, Gerald L Andriole, Monique J Roobol, E David Crawford, Vera Nelen, Maciej Kwiatkowski, Marco Zappa, Marcos Luján, Arnauld Villers, Tiago M de Carvalho, Eric J Feuer, Alex Tsodikov, Angela B Mariotto, Eveline A M Heijnsdijk, Ruth Etzioni
BACKGROUND: The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that prostate-specific antigen (PSA) screening significantly reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval, 0.69-0.91). The US Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated no such reduction but had a wide 95% CI (rate ratio for prostate cancer mortality, 1.09; 95% CI, 0.87-1.36). Standard meta-analyses are unable to account for key differences between the trials that can impact the estimated effects of screening and the trials' point estimates...
December 6, 2017: Cancer
https://www.readbyqxmd.com/read/29206810/mglur5-modulation-of-behavioral-and-epileptic-phenotypes-in-a-mouse-model-of-tuberous-sclerosis-complex
#7
Elyza Kelly, Samantha M Schaeffer, Sameer C Dhamne, Jonathan O Lipton, Lothar Lindemann, Michael Honer, Georg Jaeschke, Chloe E Super, Stephen Ht Lammers, Meera E Modi, Jill L Silverman, John R Dreier, David J Kwiatkowski, Alexander Rotenberg, Mustafa Sahin
Drugs targeting metabotropic glutamate receptor 5 (mGluR5) have therapeutic potential in autism spectrum disorders (ASD), including Tuberous Sclerosis Complex (TSC). The question whether inhibition or potentiation of mGluR5 could be beneficial depends, among other factors, on the specific indication. To facilitate the development of mGluR5 treatment strategies, we tested the therapeutic utility of mGluR5 negative and positive allosteric modulators (an mGluR5 NAM and PAM) for TSC, using a mutant mouse model with neuronal loss of Tsc2 that demonstrates disease-related phenotypes including behavioral symptoms of ASD and epilepsy...
December 5, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29206326/assessing-the-influence-of-isoflurane-anesthesia-on-cardiac-metabolism-using-hyperpolarized-1-13-c-pyruvate
#8
Jonas Steinhauser, Patrick Wespi, Grzegorz Kwiatkowski, Sebastian Kozerke
Isoflurane is a frequently used anesthetic in small-animal dissolution dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) studies. Although the literature suggests interactions with mitochondrial metabolism, the influence of the compound on cardiac metabolism has not been assessed systematically to date. In the present study, the impact of low versus high isoflurane concentration was examined in a crossover experiment in healthy rats. The results revealed that cardiac metabolism is modulated by isoflurane concentration, showing increased [1-13 C]lactate and reduced [13 C]bicarbonate production during high isoflurane relative to low isoflurane dose [average differences: +16% [1-13 C]lactate/total myocardial carbon, -22% [13 C]bicarbonate/total myocardial carbon; +51% [1-13 C]lactate/[13 C]bicarbonate]...
December 5, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/29184052/notch-transactivates-rheb-to-maintain-the-multipotency-of-tsc-null-cells
#9
Jun-Hung Cho, Bhaumik Patel, Santosh Bonala, Sasikanth Manne, Yan Zhou, Surya K Vadrevu, Jalpa Patel, Marco Peronaci, Shanawaz Ghouse, Elizabeth P Henske, Fabrice Roegiers, Krinio Giannikou, David J Kwiatkowski, Hossein Mansouri, Maciej M Markiewski, Brandon White, Magdalena Karbowniczek
Differentiation abnormalities are a hallmark of tuberous sclerosis complex (TSC) manifestations; however, the genesis of these abnormalities remains unclear. Here we report on mechanisms controlling the multi-lineage, early neuronal progenitor and neural stem-like cell characteristics of lymphangioleiomyomatosis (LAM) and angiomyolipoma cells. These mechanisms include the activation of a previously unreported Rheb-Notch-Rheb regulatory loop, in which the cyclic binding of Notch1 to the Notch-responsive elements (NREs) on the Rheb promoter is a key event...
November 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/29183003/direct-hyperpolarization-of-micro-and-nanodiamonds-for-bioimaging-applications-considerations-on-particle-size-functionalization-and-polarization-loss
#10
Grzegorz Kwiatkowski, Fabian Jähnig, Jonas Steinhauser, Patrick Wespi, Matthias Ernst, Sebastian Kozerke
Due to the inherently long relaxation time of 13C spins in diamond, the nuclear polarization enhancement obtained with dynamic nuclear polarization can be preserved for a time on the order of about one hour, opening up an opportunity to use diamonds as a new class of long-lived contrast agents. The present communication explores the feasibility of using 13C spins in directly hyperpolarized diamonds for MR imaging including considerations for potential in vivo applications.
November 21, 2017: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/29133320/effect-of-an-intensive-3-week-preoperative-home-rehabilitation-programme-in-patients-with-chronic-obstructive-pulmonary-disease-eligible-for-lung-cancer-surgery-a-multicentre-randomised-controlled-trial
#11
Hélène Laurent, Géraud Galvaing, Emilie Thivat, Emmanuel Coudeyre, Sylvie Aubreton, Ruddy Richard, Fabrice Kwiatkowski, Frederic Costes, Marc Filaire
INTRODUCTION: Surgery is the standard curative treatment for lung cancer but is only possible in patients with local tumour and preserved exercise capacity. Improving fitness before surgery can reduce postoperative complications and mortality. However, preoperative rehabilitation remains difficult to implement for several reasons. We aim to investigate the effectiveness of an intensive 3-week home-based preoperative exercise training programme on hospital discharge ability, postoperative complications and physical performance in patients with chronic obstructive pulmonary disease (COPD) who are eligible for lung cancer surgery...
November 12, 2017: BMJ Open
https://www.readbyqxmd.com/read/29128923/fluid-overload-independent-of-acute-kidney-injury-predicts-poor-outcomes-in-neonates-following-congenital-heart-surgery
#12
Kenneth E Mah, Shiying Hao, Scott M Sutherland, David M Kwiatkowski, David M Axelrod, Christopher S Almond, Catherine D Krawczeski, Andrew Y Shin
BACKGROUND: Fluid overload (FO) is common after neonatal congenital heart surgery and may contribute to mortality and morbidity. It is unclear if the effects of FO are independent of acute kidney injury (AKI). METHODS: This was a retrospective cohort study which examined neonates (age < 30 days) who underwent cardiopulmonary bypass in a university-affiliated children's hospital between 20 October 2010 and 31 December 2012. Demographic information, risk adjustment for congenital heart surgery score, surgery type, cardiopulmonary bypass time, cross-clamp time, and vasoactive inotrope score were recorded...
November 11, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29111781/cognitive-disorders-in-a-patient-with-an-arachnoid-cyst-of-the-sylvian-fissure-and-improvement-after-surgical-treatment-case-description
#13
Karolina Kwiatkowska, Agata Hałabuda, Justyna Rybus, Stanisław Kwiatkowski
Arachnoid cysts cause a wide spectrum of clinical symptoms. Often it is difficult to clearly establish the relation between the presence of an arachnoid cyst and problems reported by the patient, which may, although not necessarily, be due to chronically elevated intracranial pressure. In recent years, increasing attention is paid to cognitive disorders accompanying arachnoid cysts, such as memory disorders, attention disorders, or language function disorders. This article presents a case of an 11-year-old patient, treated at the University Children's Hospital in Cracow for an arachnoid cyst, located in the left middle cranial fossa...
November 7, 2017: Applied Neuropsychology. Child
https://www.readbyqxmd.com/read/29110722/molecular-markers-for-artemisinin-and-partner-drug-resistance-in-natural-plasmodium-falciparum-populations-following-increased-insecticide-treated-net-coverage-along-the-slope-of-mount-cameroon-cross-sectional-study
#14
Tobias O Apinjoh, Regina N Mugri, Olivo Miotto, Hanesh F Chi, Rolland B Tata, Judith K Anchang-Kimbi, Eleanor M Fon, Delphine A Tangoh, Robert V Nyingchu, Christopher Jacob, Roberto Amato, Abdoulaye Djimde, Dominic Kwiatkowski, Eric A Achidi, Alfred Amambua-Ngwa
BACKGROUND: Drug resistance is one of the greatest challenges of malaria control programmes, with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy (ACT) partner drugs critical to elimination efforts. Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon. METHODS: Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through cross-sectional surveys from May 2013 to March 2014 along the slope of mount Cameroon...
November 6, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/29100407/tert-promoter-status-and-gene-copy-number-gains-effect-on-tert-expression-and-association-with-prognosis-in-breast-cancer
#15
Mathilde Gay-Bellile, Lauren Véronèse, Patricia Combes, Eleonore Eymard-Pierre, Fabrice Kwiatkowski, Marie-Mélanie Dauplat, Anne Cayre, Maud Privat, Catherine Abrial, Yves-Jean Bignon, Marie-Ange Mouret-Reynier, Philippe Vago, Frédérique Penault-Llorca, Andrei Tchirkov
Upregulation of the telomerase reverse transcriptase (TERT) gene in human cancers leads to telomerase activation, which contributes to the growth advantage and survival of tumor cells. Molecular mechanisms of TERT upregulation are complex, tumor-specific and can be clinically relevant. To investigate these mechanisms in breast cancer, we sequenced the TERT promoter, evaluated TERT copy number changes and assessed the expression of the MYC oncogene, a known transcriptional TERT regulator, in two breast cancer cohorts comprising a total of 122 patients...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29056426/mtorc1-couples-nucleotide-synthesis-to-nucleotide-demand-resulting-in-a-targetable-metabolic-vulnerability
#16
Alexander J Valvezan, Marc Turner, Amine Belaid, Hilaire C Lam, Spencer K Miller, Molly C McNamara, Christian Baglini, Benjamin E Housden, Norbert Perrimon, David J Kwiatkowski, John M Asara, Elizabeth P Henske, Brendan D Manning
The mechanistic target of rapamycin complex 1 (mTORC1) supports proliferation through parallel induction of key anabolic processes, including protein, lipid, and nucleotide synthesis. We hypothesized that these processes are coupled to maintain anabolic balance in cells with mTORC1 activation, a common event in human cancers. Loss of the tuberous sclerosis complex (TSC) tumor suppressors results in activation of mTORC1 and development of the tumor syndrome TSC. We find that pharmacological inhibitors of guanylate nucleotide synthesis have selective deleterious effects on TSC-deficient cells, including in mouse tumor models...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29054992/suppression-of-adaptive-responses-to-targeted-cancer-therapy-by-transcriptional-repression
#17
Maria Rusan, Kapsok Li, Yvonne Li, Camilla L Christensen, Brian J Abraham, Nicholas Kwiatkowski, Kevin A Buczkowski, Bruno Bockorny, Ting Chen, Shuai Li, Kevin Rhee, Haikuo Zhang, Wankun Chen, Hideki Terai, Tiffany Tavares, Alan L Leggett, Tianxia Li, Yichen Wang, Tinghu Zhang, Tae-Jung Kim, Sook-Hee Hong, Neermala Poudel-Neupane, Michael Silkes, Tenny Mudianto, Li Tan, Takeshi Shimamura, Matthew Meyerson, Adam J Bass, Hideo Watanabe, Nathanael S Gray, Richard A Young, Kwok-Kin Wong, Peter S Hammerman
Acquired drug resistance is a major factor limiting the effectiveness of targeted cancer therapies. Targeting tumors with kinase inhibitors induces complex adaptive programs that promote the persistence of a fraction of the original cell population, facilitating the eventual outgrowth of inhibitor-resistant tumor clones. We show that the addition of a newly identified CDK7/12 inhibitor, THZ1, to targeted therapy enhances cell killing and impedes the emergence of drug-resistant cell populations in diverse cellular and in vivo cancer models...
October 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29053628/antioxidant-defence-oxidative-stress-and-oxidative-damage-in-saliva-plasma-and-erythrocytes-of-dementia-patients-can-salivary-age-be-a-marker-of-dementia
#18
Magdalena Choromańska, Anna Klimiuk, Paula Kostecka-Sochoń, Karolina Wilczyńska, Mikołaj Kwiatkowski, Natalia Okuniewska, Napoleon Waszkiewicz, Anna Zalewska, Mateusz Maciejczyk
Oxidative stress plays a crucial role in dementia pathogenesis; however, its impact on salivary secretion and salivary qualities is still unknown. This study included 80 patients with moderate dementia and 80 healthy age- and sex-matched individuals. Salivary flow, antioxidants (salivary peroxidase, catalase, superoxide dismutase, uric acid and total antioxidant capacity), and oxidative damage products (advanced oxidation protein products, advanced glycation end products (AGE), 8-isoprostanes, 8-hydroxy-2'-deoxyguanosine and total oxidant status) were estimated in non-stimulated and stimulated saliva, as well as in plasma and erythrocytes...
October 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29029388/rapamycin-induced-mir-21-promotes-mitochondrial-homeostasis-and-adaptation-in-mtorc1-activated-cells
#19
Hilaire C Lam, Heng-Jia Liu, Christian V Baglini, Harilaos Filippakis, Nicola Alesi, Julie Nijmeh, Heng Du, Alicia Llorente Lope, Katherine A Cottrill, Adam Handen, John M Asara, David J Kwiatkowski, Issam Ben-Sahra, William M Oldham, Stephen Y Chan, Elizabeth P Henske
mTORC1 hyperactivation drives the multi-organ hamartomatous disease tuberous sclerosis complex (TSC). Rapamycin inhibits mTORC1, inducing partial tumor responses; however, the tumors regrow following treatment cessation. We discovered that the oncogenic miRNA, miR-21, is increased in Tsc2-deficient cells and, surprisingly, further increased by rapamycin. To determine the impact of miR-21 in TSC, we inhibited miR-21 in vitro. miR-21 inhibition significantly repressed the tumorigenic potential of Tsc2-deficient cells and increased apoptosis sensitivity...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028633/acute-kidney-injury-in-congenital-heart-disease
#20
Katja M Gist, David M Kwiatkowski, David S Cooper
PURPOSE OF REVIEW: Acute kidney injury (AKI) is associated with significant morbidity and mortality in patients with congenital heart disease undergoing cardiac surgery or in pediatric patients with congestive heart failure. RECENT FINDINGS: This review describes the definition and various manifestations of AKI, the impact of biomarkers on the diagnosis of AKI, the importance of fluid overload as a consequence of AKI and its long-term impact. SUMMARY: There are novel biomarkers for AKI detection that should facilitate early recognition and intervention to prevent or attenuate the effects of AKI and fluid overload...
October 11, 2017: Current Opinion in Cardiology
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