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https://www.readbyqxmd.com/read/28922417/lingering-single-strand-breaks-trigger-rad51-independent-homology-directed-repair-of-collapsed-replication-forks-in-the-polynucleotide-kinase-phosphatase-mutant-of-fission-yeast
#1
Arancha Sanchez, Mariana C Gadaleta, Oliver Limbo, Paul Russell
The DNA repair enzyme polynucleotide kinase/phosphatase (PNKP) protects genome integrity by restoring ligatable 5'-phosphate and 3'-hydroxyl termini at single-strand breaks (SSBs). In humans, PNKP mutations underlie the neurological disease known as MCSZ, but these individuals are not predisposed for cancer, implying effective alternative repair pathways in dividing cells. Homology-directed repair (HDR) of collapsed replication forks was proposed to repair SSBs in PNKP-deficient cells, but the critical HDR protein Rad51 is not required in PNKP-null (pnk1Δ) cells of Schizosaccharomyces pombe...
September 18, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28918971/-pulmonary-nocardiosis-with-cerebral-abscesses-mimicking-metastatic-lung-cancer-three-cases-and-a-review-of-literature
#2
A Fourrier, M Kerjouan, C Piau, P A Lentz, C Ricordel, H Léna, R Corre, B Desrues, S Jouneau
Nocardiosis is an infectious disease with wide range of clinical features, which can eventually lead to death. The agent responsible belongs to the genus Nocardia that includes about fifty different species. Nocardiosis occurs mainly in immunocompromised hosts. We report here three cases of disseminated nocardiosis misdiagnosed initially as cerebral metastatic lung cancer. These patients, including two immunocompetent hosts, presented with both pulmonary and cerebral lesions. In all three patients, the diagnosis was based on magnetic resonance imaging with diffusion sequence, apparent diffusion coefficient reconstruction and neurosurgical cerebral biopsies...
September 14, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28917291/intraoperative-raman-spectroscopy
#3
REVIEW
Michelle Brusatori, Gregory Auner, Thomas Noh, Lisa Scarpace, Brandy Broadbent, Steven N Kalkanis
Surgical excision of brain tumors provides a means of cytoreduction and diagnosis while minimizing neurologic deficit and improving overall survival. Despite advances in functional and three-dimensional stereotactic navigation and intraoperative MRI, delineating tissue in real time with physiologic confirmation is challenging. Raman spectroscopy has potential to be an important modality in the intraoperative evaluation of tissue during surgical resection. In vitro experimental studies have shown that this technique can be used to differentiate normal brain tissue from tissue with infiltrating cancer cells and dense cancerous masses with high specificity, indicating the feasibility of this method for in vivo application...
October 2017: Neurosurgery Clinics of North America
https://www.readbyqxmd.com/read/28916148/chemokine-receptor-directed-imaging-and-therapy
#4
REVIEW
Andreas K Buck, Antje Stolzenburg, Heribert Hänscheid, Andreas Schirbel, Katharina Lückerath, Margret Schottelius, Hans-Jürgen Wester, Constantin Lapa
The C - X - C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. The CXCR4/CXCL12 interplay can be disrupted by CXCR4 antagonists such as Plerixafor which are already in daily clinical use, i.e. for mobilization and subsequent harvesting of hematopoietic progenitor cells and stem cell transplantation. In a pathological condition, involvement in the process of metastasis and homing of cancer cells to a protective niche has been described, making CXCR4 an attractive target for imaging and treatment of malignant diseases...
September 12, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28915686/evaluation-on-efficacy-and-safety-of-the-addition-of-x-knife-therapy-to-gefitinib-in-nsclc-patients-with-symptomatic-brain-metastases
#5
Linbo Cai, Xiaoguang Qiu, Haihong Yang, Mingyao Lai, Changguo Shan, Weiping Hong, Juan Li, Longhui Luo, Ping Zhang, Lichao Wang
BACKGROUND: Stereotactic radiosurgery (SRS) is a widely used therapy for brain metastases(BMs) in Non-small cell lung cancer(NSCLC). However, its role in symptomatic patients with EGFR mutation remains unclear. We have retrospectively reviewed the clinical data of patients with symptomatic BMs whom received SRS as a salvage approach and concurrent gifitinib therapy. METHODS: Seven patients with primary NSCLC, symptomatic BMs, and EGFR mutation were identified in a retrospective review of patients treated with SRS using X-knife at Guangdong 999 Brain Hospital between 1 January 2012 and 31 August 2014...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28905151/the-role-of-the-neural-niche-in-brain-metastasis
#6
REVIEW
Reid Hoshide, Rahul Jandial
Cancers with neurologic metastasis are a burdensome affliction. As primary cancer care improves, the incidence of metastatic cancer increases as a result of prolonged survival time. Because of this, advances in the understanding of the mechanisms of metastasis are important for the development of continuing management strategies. Knowing how metastatic tumor cells engage, survive, and proliferate in the central nervous system (CNS) is an important first step in developing treatment paradigms. The neural niche is the soil of the CNS that accommodates tumor cells, is a microenvironment of cell signaling that exists between the tumor cell and the native neural cellular network...
September 13, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28902402/safety-net-versus-private-hospital-setting-for-brain-metastasis-patients-treated-with-radiosurgery-alone-disparities-in-follow-up-care-and-outcomes
#7
Kevin Diao, Yanqing Sun, Stella K Yoo, Cheng Yu, Jason C Ye, Nicholas Trakul, Richard L Jennelle, Paul E Kim, Gabriel Zada, John P Gruen, Eric L Chang
BACKGROUND: Stereotactic radiosurgery (SRS) alone is an increasingly accepted treatment for brain metastases, but it requires adherence to frequently scheduled follow-up neuroimaging because of the risk of distant brain metastasis. The effect of disparities in access to follow-up care on outcomes after SRS alone is unknown. METHODS: This retrospective study included 153 brain metastasis patients treated consecutively with SRS alone from 2010 through 2016 at an academic medical center and a safety-net hospital (SNH) located in Los Angeles, California...
September 13, 2017: Cancer
https://www.readbyqxmd.com/read/28901280/neuronal-and-extraneuronal-nicotinic-acetylcholine-receptors
#8
Michele Zoli, Susanna Pucci, Antonietta Vilella, Cecilia Gotti
Neuronal nicotinic acetylcholine receptors (nAChRs) belong to a super-family of Cys-loop ligand-gated ion channels that respond to endogenous acetylcholine (ACh) or other cholinergic ligands. These receptors are also the targets of drugs such as nicotine (the main addictive agent delivered by cigarette smoke) and are involved in a variety of physiological and pathophysiological processes. Numerous studies have shown that the expression and/or function of nAChRs is compromised in many neurological and psychiatric diseases...
September 11, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28898055/a-carbon-nanotube-optical-reporter-maps-endolysosomal-lipid-flux
#9
Prakrit V Jena, Daniel Roxbury, Thomas V Galassi, Leila Akkari, Christopher P Horoszko, David B Iaea, Januka Budhathoki-Uprety, Nina Pipalia, Abigail S Haka, Jackson D Harvey, Jeetain Mittal, Frederick R Maxfield, Johanna A Joyce, Daniel A Heller
Lipid accumulation within the lumen of endolysosomal vesicles is observed in various pathologies including atherosclerosis, liver disease, neurological disorders, lysosomal storage disorders, and cancer. Current methods cannot measure lipid flux specifically within the lysosomal lumen of live cells. We developed an optical reporter, composed of a photoluminescent carbon nanotube of a single chirality, that responds to lipid accumulation via modulation of the nanotube's optical band gap. The engineered nanomaterial, composed of short, single-stranded DNA and a single nanotube chirality, localizes exclusively to the lumen of endolysosomal organelles without adversely affecting cell viability or proliferation or organelle morphology, integrity, or function...
September 12, 2017: ACS Nano
https://www.readbyqxmd.com/read/28895098/recurrent-cerebral-attack-caused-by-thrombosis-in-the-pulmonary-vein-stump-in-a-patient-with-left-upper-lobectomy-on-anticoagulant-therapy-case-report-and-literature-review
#10
Takahito Nakano, Mayumi Inaba, Hiroyuki Kaneda
BACKGROUND: Thrombus formation in the pulmonary vein stump after pulmonary resection has recently been identified as a cause of systemic thrombosis including brain infarction. However, there is limited research focusing on the clinical course of pulmonary vein stump thrombus, and optimal treatment and prevention strategies of this important complication have not been established. CASE PRESENTATION: A 77-year-old woman was diagnosed with lung cancer of the left upper lobe, cT4N2M0, cStage IIIB...
September 11, 2017: Surgical Case Reports
https://www.readbyqxmd.com/read/28891034/rheb1-insufficiency-in-aged-male-mice-is-associated-with-stress-induced-seizures
#11
Qi Tian, Pavel Gromov, Joachim H Clement, Yingming Wang, Marc Riemann, Falk Weih, Xiao-Xin Sun, Mu-Shui Dai, Lev M Fedorov
The mechanistic target of rapamycin (mTOR), a protein kinase, is a central regulator of mammalian metabolism and physiology. Protein mTOR complex 1 (mTORC1) functions as a major sensor for the nutrient, energy, and redox state of a cell and is activated by ras homolog enriched in brain (RHEB1), a GTP-binding protein. Increased activation of mTORC1 pathway has been associated with developmental abnormalities, certain form of epilepsy (tuberous sclerosis), and cancer. Clinically, those mTOR-related disorders are treated with the mTOR inhibitor rapamycin and its rapalogs...
September 10, 2017: GeroScience
https://www.readbyqxmd.com/read/28890435/pain-control-in-thoracic-oncology
#12
Christine Peeters-Asdourian, Gilbert Massard, Paragi H Rana, Paul Van Houtte, Andrew P White, Bogdan Grigoriu, Dominique Lossignol, Mohammed Almalki, Jean Alexiou, Jean-Luc Engelholm, Jean-Paul Sculier
This review of pain management in lung cancer is based on the presentation of four cases of thoracic oncology patients with pain at various stages of their disease. The approach will be multidisciplinary, involving a thoracic oncologist, radiologist, thoracic and orthopaedic spine surgeon, radiation therapist, pain medicine specialist, and palliative care specialist. This multispecialty approach to the management of different painful presentations in thoracic oncology will demonstrate the complexity of each case and the improved patient outcomes which result from the involvement of different disciplines working in concert...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28889921/pd-1-checkpoint-inhibition-toxicities-and-management
#13
REVIEW
Andrew W Hahn, David M Gill, Neeraj Agarwal, Benjamin L Maughan
PURPOSE: With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others. MATERIALS AND METHODS: In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab...
September 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28886707/health-outcomes-of-non-nutritive-sweeteners-analysis-of-the-research-landscape
#14
REVIEW
Szimonetta Lohner, Ingrid Toews, Joerg J Meerpohl
BACKGROUND: Food products containing non-nutritive sweeteners (NNSs) instead of sugar have become increasingly popular in the last decades. Their appeal is obviously related to their calorie-free sweet taste. However, with the dramatic increase in their consumption, it is reasonable and timely to evaluate their potential health benefits and, more importantly, potential adverse effects. The main aim of this scoping review was to map the evidence about health outcomes possibly associated with regular NNS consumption by examining the extent, range, and nature of research activity in this area...
September 8, 2017: Nutrition Journal
https://www.readbyqxmd.com/read/28883237/chronic-intestinal-pseudo-obstruction-and-orthostatic-hypotension-associated-with-small-cell-lung-cancer-that-improved-with-tumor-reduction-after-chemoradiotherapy
#15
Yusuke Izumi, Takeshi Masuda, Yasushi Horimasu, Taku Nakashima, Shintaro Miyamoto, Hiroshi Iwamoto, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori
Chronic intestinal pseudo-obstruction (CIPO) is a rare disease with symptoms of ileus without obstruction. Most cases of CIPO are idiopathic, and CIPO as a paraneoplastic neurological syndrome (PNS) associated with small cell lung cancer (SCLC) is rare. A 63-year-old man was diagnosed with functional ileus and confined to bed due to orthostatic hypotension. Chest computed tomography revealed a right hilar mass suspected of being lung cancer. Based on detailed examinations, he was diagnosed with limited-stage SCLC...
September 6, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28881477/multimodal-quantitative-examination-of-nerve-function-in-colorectal-cancer-patients-prior-to-chemotherapy
#16
Tejaswi Kandula, Michelle A Farrar, Arun V Krishnan, Jenna Murray, Hannah C Timmins, David Goldstein, Cindy S-Y Lin, Matthew C Kiernan, Susanna B Park
INTRODUCTION: Given recent findings of subclinical sensory deficits in colorectal cancer patients prior to oxaliplatin treatment, the current study aimed to identify evidence of subclinical peripheral neuropathy on multimodal testing before chemotherapy commencement. METHODS: Clinical, functional and neurophysiological assessments were undertaken in 93 colorectal cancer patients prior to chemotherapy. RESULTS: There was no neurophysiological evidence of neuropathy, with 92/93 sural sensory values within normative reference values for age and no significant abnormalities detected in nerve conduction or nerve excitability studies...
September 7, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28880480/monoacylglycerol-signalling-and-abhd6-in-health-and-disease
#17
REVIEW
Pegah Poursharifi, Sri Ramachandra Murthy Madiraju, Marc Prentki
Lipid metabolism dysregulation underlies chronic pathologies such as obesity, diabetes and cancer. Besides their role in structure and energy storage, lipids are also important signalling molecules regulating multiple biological functions. Thus, understanding the precise lipid metabolism enzymatic steps that are altered in some pathological conditions is helpful for designing better treatment strategies. Several monoacylglycerol (MAG) species are only recently being recognized as signalling lipid molecules in different tissues...
September 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28876538/mikl%C3%A3-s-bodanszky-award-lecture-advances-in-the-selective-targeting-of-protein-phosphatase-1-and-phosphatase-2a-with-peptides
#18
REVIEW
Maja Köhn
Protein phosphatase-1 and phosphatase-2A are two ubiquitously expressed enzymes known to catalyze the majority of dephosphorylation reactions on serine and threonine inside cells. They play roles in most cellular processes and are tightly regulated by regulatory subunits in holoenzymes. Their misregulation and malfunction contribute to disease development and progression, such as in cancer, diabetes, viral infections, and neurological as well as heart diseases. Therefore, targeting these phosphatases for therapeutic use would be highly desirable; however, their complex regulation and high conservation of the active site have been major hurdles for selectively targeting them in the past...
October 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28873125/neurological-complications-associated-with-anti-programmed-death-1-pd-1-antibodies
#19
Justin C Kao, Bing Liao, Svetomir N Markovic, Christopher J Klein, Elie Naddaf, Nathan P Staff, Teerin Liewluck, Julie E Hammack, Paola Sandroni, Heidi Finnes, Michelle L Mauermann
Importance: Neurological complications are an increasingly recognized consequence of the use of anti-programmed death 1 (PD-1) antibodies in the treatment of solid-organ tumors, with an estimated frequency of 4.2%. To date, the clinical spectrum and optimum treatment approach are not established. Objective: To investigate the frequency, clinical spectrum, and optimum treatment approach to neurological complications associated with anti-PD-1 therapy. Design, Setting, and Participants: This single-center, retrospective cohort study was conducted from either September or December 2014 (the approval dates of the study drugs by the US Food and Drug Administration) to May 19, 2016...
September 5, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28870777/the-effects-of-late-toxicities-on-outcomes-in-long-term-survivors-of-ex-vivo-cd34-selected-allogeneic-hematopoietic-cell-transplantation
#20
Michael Scordo, Gunjan L Shah, Satyajit Kosuri, Diego Adrianzen Herrera, Christina Cho, Sean M Devlin, Molly A Maloy, Jimmy Nieves, Taylor Borrill, Scott T Avecilla, Richard C Meagher, Dean C Carlow, Richard J O'Reilly, Esperanza B Papadopoulos, Ann A Jakubowski, Guenther Koehne, Boglarka Gyurkocza, Hugo Castro-Malaspina, Roni Tamari, Miguel-Angel Perales, Sergio A Giralt, Brian C Shaffer
The late adverse events in long-term survivors after myeloablative conditioned allogeneic hematopoietic cell transplantation with ex-vivo CD34+ selection are not well characterized. Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, we assessed all grade ≥ 3 toxicities from the start conditioning to date of death, relapse, or last contact in 131 patients that survived > 1-year post-transplantation, identifying 285 individual toxicities among 17 organ-based toxicity groups...
September 1, 2017: Biology of Blood and Marrow Transplantation
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