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Cns tumours and molecular therapies

Sarah Lapointe, Arie Perry, Nicholas A Butowski
Primary CNS tumours refer to a heterogeneous group of tumours arising from cells within the CNS, and can be benign or malignant. Malignant primary brain tumours remain among the most difficult cancers to treat, with a 5 year overall survival no greater than 35%. The most common malignant primary brain tumours in adults are gliomas. Recent advances in molecular biology have improved understanding of glioma pathogenesis, and several clinically significant genetic alterations have been described. A number of these (IDH, 1p/19q codeletion, H3 Lys27Met, and RELA-fusion) are now combined with histology in the revised 2016 WHO classification of CNS tumours...
August 4, 2018: Lancet
András Marosi, Lucie Dufkova, Barbara Forró, Orsolya Felde, Károly Erdélyi, Jana Širmarová, Martin Palus, Václav Hönig, Jiří Salát, Réka Tikos, Miklós Gyuranecz, Daniel Růžek, Byron Martina, Penelope Koraka, Albert D M E Osterhaus, Tamás Bakonyi
Recent studies demonstrated that inhibitors of pro-inflammatory molecular cascades triggered by rabies infection in the central nervous system (CNS) can enhance survival in mouse model and that certain antiviral compounds interfere with rabies virus replication in vitro. In this study different combinations of therapeutics were tested to evaluate their effect on survival in rabies-infected mice, as well as on viral load in the CNS. C57Bl/6 mice were infected with Silver-haired bat rabies virus (SHBRV)-18 at virus dose approaching LD50 and LD100 ...
May 24, 2018: Vaccine
M Kopáčková, P Beránek, I Bydžovská, R Pytlík, J Soukup, M Mrhalová
OBJECTIVE: Presentation of a rare finding non-Hodgkin´s B-lymphoma of the ovary in a patient during caesarean section. DESIGN: Case report. SETTINGS: Department of Obstetrics and Gynaecology, Regional Hospital Liberec, a.s.; First Internal Clinic - Clinic of Hematology, First Faculty of Medicine and General University Hospital, Charles University in Prague; Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University in Praque and Motol University Hospital...
December 0: Ceská Gynekologie
J C Pickles, C Hawkins, T Pietsch, T S Jacques
Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours...
February 2018: Neuropathology and Applied Neurobiology
Peter Herhaus, Stefan Habringer, Tibor Vag, Katja Steiger, Julia Slotta-Huspenina, Carlos Gerngroß, Benedikt Wiestler, Hans-Jürgen Wester, Markus Schwaiger, Ulrich Keller
CXCR4 belongs to the family of chemokine receptors. Together with its sole known ligand CXCL12 (SDF-1alpha), it has a pivotal role during organogenesis and for homing of hematopoietic stem cells. CXCR4 is overexpressed in various malignancies, and this is often associated with poor prognosis. Therefore, molecular imaging of CXCR4 bears a great potential for diagnostics and selecting patients for CXCR4-directed therapies. The CXCR4-directed positron emission tomography (PET) tracer [(68)Ga]Pentixafor has been shown to visualize CXCR4 expression in various malignancies in vivo...
December 2017: EJNMMI Research
Soumen Khatua, Vijay Ramaswamy, Eric Bouffet
Ependymomas are the third commonest paediatric central nervous system (CNS) tumour, accounting for 6-12% of brain tumours in children. The management of these tumours has seen considerable changes over the last two decades, leading to a significant improvement in outcomes. However, despite advances in neurosurgical, neuroimaging and postoperative adjuvant therapy, management of these tumours remain challenging, and recurrence occurs in over 50% of cases, particularly when complete resection is not achieved prior to conformal radiotherapy...
January 2017: European Journal of Cancer
Waldemar Och, Kamil Kulbacki, Błażej Szostak, Beata Sikorska, Magdalena Zakrzewska, Tomasz Szmuda, Paweł P Liberski, Tomasz Budzisz
Meningiomas (MGs) are the most frequent primary tumours of the central nervous system (CNS) and exhibit a large spectrum of histological types and clinical phenotypes. The WHO classification of CNS tumours established strict diagnostic criteria of the benign (Grade 1), atypical (Grade 2) and anaplastic (Grade 3) subtypes. Combined with the resection rate, WHO grading has the most crucial role as the prognostic factor. Additionally, such biomarkers as Ki-67/MIB-1, progesterone receptors and phosphor-histone H3 were correlated with MG progression...
July 2016: Neurologia i Neurochirurgia Polska
Isabella Zhang, Nicholas G Zaorsky, Joshua D Palmer, Ranee Mehra, Bo Lu
The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance...
October 2015: Lancet Oncology
T Nakamura, K Tateishi, T Niwa, Y Matsushita, K Tamura, M Kinoshita, K Tanaka, S Fukushima, H Takami, H Arita, A Kubo, T Shuto, M Ohno, Y Miyakita, S Kocialkowski, T Sasayama, N Hashimoto, T Maehara, S Shibui, T Ushijima, N Kawahara, Y Narita, K Ichimura
AIMS: Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor-κB (NF-κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF-κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL. METHODS: We conducted the systematic sequencing of 21 genes relevant to the NF-κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation...
April 2016: Neuropathology and Applied Neurobiology
David A Reardon, Patrick Y Wen
Heterogeneity within and across tumours is increasingly recognized as a critical factor that limits therapeutic progress for many cancers. Key studies reported in 2014 describe previously unappreciated patterns of geographical and temporal heterogeneity for glioblastoma (the most-common primary CNS tumour in adults), with important implications for ongoing therapeutic studies evaluating molecular targeted therapies.
February 2015: Nature Reviews. Clinical Oncology
Ajay Patil, G V Sherbet
HER2 positive breast cancers have been shown to have a greater propensity to metastasise to the brain. This may be due to several reasons, including the creation of a "sanctuary-site" for tumour in the brain following trastuzumab therapy. Elucidating the mechanism of this phenomenon may aid the prevention or intervention and treatment of such metastases, but research is limited by the deficiency and diminished access of CNS tissue. However, CNS penetrable HER2 receptor antagonists such as lapatinib and intrathecal administration of trastuzumab might benefit patients, and are worthy of further investigation...
March 28, 2015: Cancer Letters
A Broniscer, R G Tatevossian, N D Sabin, P Klimo, J Dalton, R Lee, A Gajjar, D W Ellison
AIMS: A few case series in adults have described the characteristics of epithelioid glioblastoma (e-GB), one of the rarest variants of this cancer. We evaluated clinical, radiological, histological and molecular characteristics in the largest series to date of paediatric e-GB. METHODS: Review of clinical characteristics and therapy, imaging studies and histology was performed in patients younger than 22 years with e-GB seen at our institution over 15 years. Sequencing of hotspot mutations and fluorescence in situ hybridization of relevant genes were undertaken...
April 2014: Neuropathology and Applied Neurobiology
D La Torre, M Aguennouz, A Conti, M Giusa, G Raffa, R V Abbritti, A Germano', F F Angileri
Glioblastoma Multiforme (GBM) is the most common and lethal of human primary central nervous system (CNS) tumors. Due to the tumour's intrinsic clinical and molecular heterogeneity, choice of initial treatment, prediction of survival, stratification of patients, prediction and monitoring of response to therapy, represent some of the greatest challenges in the management of GBM patients. Patients, despite optimal surgery, radiation and chemotherapy, still have a median survival of 14-16 months. A reason for this dismal prognosis is because of the relative inaccuracy of current prognostic markers, so far based on clinical or pathological variables...
September 2011: Translational Medicine @ UniSa
Mercé Falip, Xavier Salas-Puig, Carlos Cara
Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs...
August 2013: CNS Drugs
Yael P Mossé, Megan S Lim, Stephan D Voss, Keith Wilner, Katherine Ruffner, Julie Laliberte, Delphine Rolland, Frank M Balis, John M Maris, Brenda J Weigel, Ashish M Ingle, Charlotte Ahern, Peter C Adamson, Susan M Blaney
BACKGROUND: Various human cancers have ALK gene translocations, amplifications, or oncogenic mutations, such as anaplastic large-cell lymphoma, inflammatory myofibroblastic tumours, non-small-cell lung cancer (NSCLC), and neuroblastoma. Therefore, ALK inhibition could be a useful therapeutic strategy in children. We aimed to determine the safety, recommended phase 2 dose, and antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma...
May 2013: Lancet Oncology
Elizabeth Harford-Wright, Kate M Lewis, Robert Vink
Despite recent advances in cancer treatment and diagnosis, the prognosis for patients with CNS tumours remains extremely poor. This is, in part, due to the difficulty in completely removing tumours surgically, and also because of the presence of the blood brain barrier, which can prevent the entry of chemotherapeutic agents typically used in cancer treatment. Despite the presence of the blood brain barrier, tumour cells are capable of entering and colonising the brain to form secondary brain tumours. Additionally, tumour related disruption of the blood brain barrier is associated with the clinical presentation of many patients, with accompanying increases in intracranial pressure due, in part, to the development of vasogenic oedema...
April 2013: Recent Patents on CNS Drug Discovery
Rupert Bartsch, Anna S Berghoff, Matthias Preusser
The incidence of brain metastases (BM) in breast cancer patients has increased over the last decade, presumably due to advances in systemic treatment. Today, breast cancer is the second most common cause of BM among all solid malignancies, second only to lung cancer; furthermore, it is the most common cause of leptomeningeal carcinomatosis. The HER2-positive subtype was consistently shown to have a higher risk for BM as compared with HER2-negative disease. More recently, however, it was shown that a similar incidence exists in triple-negative tumours...
February 2013: CNS Drugs
Damien Ricard, Ahmed Idbaih, François Ducray, Marion Lahutte, Khê Hoang-Xuan, Jean-Yves Delattre
Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas--the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials...
May 26, 2012: Lancet
Nikolai G Rainov, Volkmar Heidecke
Advances in medical and surgical treatments in the last two to three decades have resulted in quantum leaps in the overall survival of patients with many types of non-central nervous system (CNS) malignant disease, while survival of patients with malignant gliomas (WHO grades 3 and 4) has only moderately improved. Surgical resection, external fractionated radiotherapy and oral chemotherapy, during and after irradiation, remain the pillars of malignant glioma therapy and have shown significant benefits. However, numerous clinical trials with adjuvant agents, most of them administered systemically and causing serious complications and side effects, have not achieved a noteworthy extension of survival, or only with considerable deterioration in patients' quality of life...
February 2011: Sultan Qaboos University Medical Journal
Rafael Tabarés-Seisdedos, Nancy Dumont, Anaïs Baudot, Jose M Valderas, Joan Climent, Alfonso Valencia, Benedicto Crespo-Facorro, Eduard Vieta, Manuel Gómez-Beneyto, Salvador Martínez, John L Rubenstein
In the past 5 years, several leading groups have attempted to explain why individuals with Down's syndrome have a reduced risk of many solid tumours and an increased risk of leukaemia and testicular cancer. Niels Bohr, the Danish physicist, noted that a paradox could initiate progress. We think that the paradox of a medical disorder protecting against cancer could be formalised in a new model of inverse cancer morbidity in people with other serious diseases. In this Personal View, we review evidence from epidemiological and clinical studies that supports a consistently lower than expected occurrence of cancer in patients with Down's syndrome, Parkinson's disease, schizophrenia, diabetes, Alzheimer's disease, multiple sclerosis, and anorexia nervosa...
June 2011: Lancet Oncology
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