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https://www.readbyqxmd.com/read/28229086/rb-an-essential-player-in-adult-neurogenesis
#1
Bensun C Fong, Ruth S Slack
The fundamental mechanisms underlying adult neurogenesis remain to be fully clarified. Members of the cell cycle machinery have demonstrated key roles in regulating adult neural stem cell (NSC) quiescence and the size of the adult-born neuronal population. The retinoblastoma protein, Rb, is known to possess CNS-specific requirements that are independent from its classical role as a tumor suppressor. The recent study by Vandenbosch et al. has clarified distinct requirements for Rb during adult neurogenesis, in the restriction of proliferation, as well as long-term adult-born neuronal survival...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28229085/folate-receptor-alpha-is-more-than-just-a-folate-transporter
#2
Vineet Mohanty, M Rizwan Siddiqui, Tadanori Tomita, Chandra Shekhar Mayanil
Until recently folate receptor alpha (FRα) has only been considered as a folate transporter. However, a novel role of FRα as a transcription factor was reported by our lab. More recently our lab showed a novel pleiotropic role of FRα: (a) direct transcriptional activation of Oct4, Sox2, and Klf4 genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules. These observations beg a question: "Can a simple molecule such as folate be used to manipulate the production and/or differentiation of endogenous neural stem cells (NSCs), which may hold promise for future therapies?" Conditions such as spinal cord injury, motor neuron diseases, Alzheimer's disease and multiple sclerosis may benefit from increasing stem cell pool and promoting specific pathways of differentiation...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28221867/osimertinib-in-pretreated-t790m-positive-advanced-non-small-cell-lung-cancer-aura-study-phase-ii-extension-component
#3
James Chih-Hsin Yang, Myung-Ju Ahn, Dong-Wan Kim, Suresh S Ramalingam, Lecia V Sequist, Wu-Chou Su, Sang-We Kim, Joo-Hang Kim, David Planchard, Enriqueta Felip, Fiona Blackhall, Daniel Haggstrom, Kiyotaka Yoh, Silvia Novello, Kathryn Gold, Tomonori Hirashima, Chia-Chi Lin, Helen Mann, Mireille Cantarini, Serban Ghiorghiu, Pasi A Jänne
Purpose Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing ( EGFRm) and T790M resistance mutations. AURA (NCT01802632) is a phase I/II clinical trial to determine the dose, safety, and efficacy of osimertinib. This article reports the results from the phase II extension component. Patients and Methods Patients with EGFR-TKI-pretreated EGFRm- and T790M-positive advanced non-small-cell lung cancer (NSCLC) received once-daily osimertinib 80 mg...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28215459/leptomeningeal-metastases-presenting-exclusively-with-ocular-disturbance-in-34-patients-a-tertiary-care-cancer-hospital-experience
#4
Rory Richard Mayer, Benjamin Jay Frankfort, Ben A Strickland, James Matthew Debnam, Ian E McCutcheon, Morris D Groves, Jeffrey S Weinberg
Leptomeningeal disease (LMD) represents disseminated intracranial metastatic disease that requires early detection and initiation of therapy. Patients with LMD typically present with a variety of neurologic problems, including ocular disturbances. However, little is reported on LMD presenting exclusively with ocular-related disturbances in the absence of any other central nervous system (CNS) dysfunction. Our goal was to describe the workup for ocular disturbances in the setting of known cancer diagnosis. Retrospective case study utilizing prospectively collected database at a tertiary cancer care center for all patients with diagnosis of LMD between 2001 and 2009...
February 16, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28212424/risk-factors-for-central-nervous-system-tumors-in-children-new-findings-from-a-case-control-study
#5
Rebeca Ramis, Ibon Tamayo-Uria, Diana Gómez-Barroso, Gonzalo López-Abente, Antonio Morales-Piga, Elena Pardo Romaguera, Nuria Aragonés, Javier García-Pérez
BACKGROUND: Central nervous system tumors (CNS) are the most frequent solid tumor in children. Causes of CNS tumors are mainly unknown and only 5% of the cases can be explained by genetic predisposition. We studied the effects of environmental exposure on the incidence of CNS tumors in children by subtype, according to exposure to industrial and/or urban environment, exposure to crops and according to socio-economic status of the child. METHODS: We carried out a population-based case-control study of CNS tumors in Spain, covering 714 incident cases collected from the Spanish Registry of Childhood Tumors (period 1996-2011) and 4284 controls, individually matched by year of birth, sex, and autonomous region of residence...
2017: PloS One
https://www.readbyqxmd.com/read/28208698/advances-in-molecular-imaging-of-locally-delivered-targeted-therapeutics-for-central-nervous-system-tumors
#6
REVIEW
Umberto Tosi, Christopher S Marnell, Raymond Chang, William C Cho, Richard Ting, Uday B Maachani, Mark M Souweidane
Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28193095/intraocular-ependymoma-with-blood-filled-spaces
#7
Aditi Dewan, Ravindra Kumar Saran, Smriti Nagpal Gupta, Deepanjali Arya, Ruchi Goel
Intraocular glial lesions are rare and include retinal gliosis, hamartomas, and astrocytomas and rarely ependymomas. Ependymomas are slow-growing glial tumors preferentially arising in the central nervous system (CNS), occasionally presenting at sites outside the CNS, with only 2 cases of primary retinal ependymoma reported till date. We report herein the third such case of a 20-year-old male who presented with a painful blind eye. The enucleated specimen showed presence of a glial tumor with cells arranged in sheets as well as few true rosettes and pseudo-rosettes and an immunohistochemical profile similar to a classical ependymoma at usual sites in the CNS...
February 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28191622/embryonal-tumor-with-multilayered-rosettes-in-a-3-year-old-girl-case-report
#8
Aparna Govindan, Muralikrishnan Vp, Jacob Paul Alapatt
Embryonal tumor with multilayered rosettes(ETMR) is a new entity in the group of Primitive Neuroectodermal tumors of the central nervous system. It combines histopathological features of neuroblastoma and ependymoblastoma. This tumor occurs mostly in the first five years of life. A hallmark cytogenetic abnormality at the chromosome locus 19q13.42 has been identified. The authors report a case of ETMR in the parietooccipital region in a 3 year old girl who presented with features of raised intracranial tension...
January 8, 2017: Turkish Neurosurgery
https://www.readbyqxmd.com/read/28183697/safety-and-antitumor-activity-of-the-multi-targeted-pan-trk-ros1-and-alk-inhibitor-entrectinib-rxdx-101-combined-results-from-two-phase-1-trials-alka-372-001-and-startrk-1
#9
Alexander Drilon, Salvatore Siena, Sai-Hong Ignatius Ou, Manish Patel, Myung Ju Ahn, Jeeyun Lee, Todd M Bauer, Anna F Farago, Jennifer J Wheler, Stephen V Liu, Robert Doebele, Laura Giannetta, Giulio Cerea, Giovanna Marrapese, Michele Schirru, Alessio Amatu, Katia Bencardino, Laura Palmeri, Andrea Sartore-Bianchi, Angelo Vanzulli, Sara Cresta, Silvia Damian, Matteo Duca, Elena Ardini, Gang Li, Jason Christiansen, Karey Kowalski, Ann Johnson, Rupal Patel, David Luo, Edna Chow-Maneval, Zachary Hornby, Pratik S Multani, Alice T Shaw, Filippo G De Braud
Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two Phase 1 studies in patients with advanced or metastatic solid tumors, including patients with active CNS disease. Here we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the RP2D...
February 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28178709/neoplastic-meningitis-due-to-lung-breast-and-melanoma-metastases
#10
REVIEW
Emilie Le Rhun, Sophie Taillibert, Marc C Chamberlain
BACKGROUND: Neoplastic meningitis, a central nervous system (CNS) complication of cancer metastatic to the meninges and cerebrospinal fluid (CSF), is relevant to oncologists due to the impact of the disease on patient quality of life and survival rates. METHODS: A review of the literature of articles published in English was conducted with regard to neoplastic meningitis. RESULTS: The incidence of neoplastic meningitis is increasing because patients with cancer are surviving longer in part because of the use of novel therapies with poor CNS penetration...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28178376/treatment-trends-for-patients-with-brain-metastases-does-practice-reflect-the-data
#11
Kiri A Sandler, Narek Shaverdian, Ryan R Cook, Amar U Kishan, Christopher R King, Isaac Yang, Michael L Steinberg, Percy Lee
BACKGROUND: Published guidelines regarding the optimal treatment strategies for brain metastases focus on patients with ≤3 lesions. As delivery techniques for stereotactic radiosurgery (SRS) improve, radiation oncologists are increasingly using it for patients with >3 metastases. In the current study, the authors sought to characterize practice patterns among practitioners to identify areas of controversy. METHODS: A survey of practicing radiation oncologists was distributed via e-mail...
February 8, 2017: Cancer
https://www.readbyqxmd.com/read/28176655/epigenetics-in-clinical-management-of-children-and-adolescents-with-brain-tumors
#12
Andres Morales La Madrid, Mark W Kieran
Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages -not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the "classic" current therapeutic approaches...
February 3, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28174598/review-on-the-role-of-the-human-polyomavirus-jc-in-the-development-of-tumors
#13
REVIEW
Serena Delbue, Manola Comar, Pasquale Ferrante
Almost one fifth of human cancers worldwide are associated with infectious agents, either bacteria or viruses, and this makes the possible association between infections and tumors a relevant research issue. We focused our attention on the human Polyomavirus JC (JCPyV), that is a small, naked DNA virus, belonging to the Polyomaviridae family. It is the recognized etiological agent of the Progressive Multifocal Leukoencephalopathy (PML), a fatal demyelinating disease, occurring in immunosuppressed individuals...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28169156/posterior-reversible-encephalopathy-syndrome-associated-with-dose-adjusted-epoch-etoposide-prednisone-vincristine-cyclophosphamide-doxorubicin-chemotherapy
#14
Abby E Floeter, Amila Patel, Melinda Tran, Marc C Chamberlain, Paul C Hendrie, Ajay K Gopal, Ryan D Cassaday
INTRODUCTION: The purpose of our study was to identify the key risk factors for the development of posterior reversible encephalopathy syndrome (PRES) after administration of the combination chemotherapy regimen, DA-EPOCH (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin). MATERIALS AND METHODS: We performed a retrospective medical record review of patients receiving DA-EPOCH with or without rituximab (DA-EPOCH ± R) at our institution from July 2012 to September 2014...
January 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28152812/real-world-treatment-patterns-and-outcomes-in-her2-positive-mbc-patients-with-brain-metastasis-in-the-u-s-community-oncology-setting
#15
Eileen Fonseca, Bongin Yoo, Thomas Wilson, Hans-Peter Goertz, Catherine Lai
: 92 Background: Patients (pts) with HER2 positive (HER2+) metastatic breast cancer (MBC) have different patterns of disease and treatment (tx) from HER2 negative MBC. Brain metastasis (BM) frequently occurs and txs vary. METHODS: This retrospective study included adult HER2+ MBC pts from a community oncology network electronic health record (EHR) database and diagnosed between 2009-2011, with follow-up until 11/2014. Pts with other primary tumors were excluded...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28150132/nanomedicines-for-the-treatment-of-cns-diseases
#16
Jessica L Reynolds, Ram I Mahato
Targeting and delivering macromolecular therapeutics to the central nervous system (CNS) has been a major challenge. The blood-brain barrier (BBB) is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Therefore, much effort has been channelled into improving transport of therapeutics across the BBB and into the CNS including the use of nanoparticles. In this thematic issue, several reviews and original research are presented that address "Nanomedicines for CNS Diseases...
February 1, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28149758/defining-the-endpoints-how-to-measure-the-efficacy-of-drugs-that-are-active-against-central-nervous-system-metastases
#17
REVIEW
Alessandra Fabi, Antonello Vidiri
Brain metastases (BMs) are the most common cause of malignant central nervous system (CNS) tumors in adults. In the recent past, patients with BMs were excluded from clinical trials, but now, with the advent of new biological and immunological drugs, their inclusion is more common. In the last era response and progression criteria used across clinical trials have defined the importance to consider not only measurement changes of brain lesions but also the modification of parameters related to the metastases such as metabolism of tissue and its pathological features...
December 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28149756/anti-angiogenetic-therapies-for-central-nervous-system-metastases-from-non-small-cell-lung-cancer
#18
REVIEW
Consuelo Buttigliero, Valentina Bertaglia, Silvia Novello
Central nervous system (CNS) metastases are common in patients with advanced non-small cell lung cancer (NSCLC), occurring in 24% to 44% of patients in the course of their disease and confer significant morbidity and mortality. Systemic therapies have been deemed ineffective in brain metastases (BM) under the hypothesis that the blood-brain barrier (BBB) limits their delivery to the brain. Angiogenesis, which is mainly mediated by vascular endothelial growth factor (VEGF) pathway, is crucial for tumor survival, growth and invasion both in primary and metastatic brain lesions...
December 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28149160/immune-characteristics-study-of-ag490-a-signal-pathway-inhibitor-in-eae-model-mice
#19
Zhihua Zhao, Zhifeng Mao, Junjie Yin, Yaqing Shu, Wei Qiu, Zhengqi Lu, Xueqiang Hu
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination, axonal damage and progressive neurologic dysfunction in central nervous system (CNS). Many evidences show that B cells play an important role in the pathogenesis of MS. Follicular helper T cells (Tfh) secrete IL-21 to prompt the proliferation and differentiation of B cells in germinal center (GC) through clonal proliferation, somatic hypermutation, antibody class switching, antibody affinity maturation process. AG490 is a synthetic inhibitor to JAK-STAT signal pathway, which has been studied in inflammatory, tumor and autoimmune diseases...
February 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28138871/clinical-relevance-of-steroid-use-in-neuro-oncology
#20
REVIEW
K Ina Ly, Patrick Y Wen
BACKGROUND: Corticosteroids are commonly used in the management of primary central nervous system (CNS) tumors and CNS metastases to treat cancer- and treatment-related cerebral edema and improve neurologic function. However, they are also associated with significant morbidity and mortality, given their wide range of adverse effects. PURPOSE OF REVIEW: To review the mechanism of action, pharmacology, and toxicity profile of corticosteroids and to critically appraise the evidence that supports their use in neuro-oncologic practice based on the latest scientific and clinical data...
January 2017: Current Neurology and Neuroscience Reports
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