Nervous System Cancer Models
Organized and edited by William A. Weiss1, and Ken Aldape2, with
contributions from Abhijit Guha3, Mark Israel4, David Louis5, Eric C.
Holland6, Andrea I. McClatchey7 , Anat O. Stemmer-Rachamimov5,Terry Van
Dyke8 and Cynthia Wetmore9.
1Univ of CA, San Francisco, CA
2MD Anderson Cancer Center, Houston TX
3MSc, MD, FRCS(C), FACS
Associate Prof. Neurosurgery, Univ. Health Network
Toronto, Ontario, Canada
4Norris Cotton Cancer Center, Dartmouth Medical School, Hanover NH
5Molecular Neuro-Oncology Laboratory, CNY6
Massachusetts General Hospital
Charlestown, MA
6Dept of Cell Biology, Neurolgical Surger and Neurology,
Memorial Sloan Kettering Cancer Center, New York
7
Harvard Medical School
8
UNC Chapel Hill
9
Mayo clinic
Welcome to the MMHCC Web site for Cancers of the Nervous System.
As you enter the site you will find an introductory section providing background
information on cancers of the nervous system, a general overview of current
methods for diagnosis and treatment, descriptions of commonly occurring
molecular alterations, existing murine models for many tumors, and a
section on preclinical developmental therapeutics.
Overview of Nervous System Tumors
1.1 Gliomas
General comments
Primary nervous system neoplasms are not among the most common tumors, but some of them
are among the most lethal. The prognosis for patients with glioblastoma, the most
important of the primary brain tumors, remains at approximately 1 year despite
aggressive surgery, radio- and chemotherapy. More needs to be understood about
these neoplasms in order to design effective therapies. This short overview will
focus on classification of nervous system tumors. It is not meant to be an exhaustive,
list but rather will highlight selected neoplasms considered most important and relevant
to the MMHCC. Additional information on these and other nervous system neoplasms can
be obtained in one of several authoritative texts.
The parenchyma of the central nervous system (CNS) is composed primarily of neurons
and glia. In turn, the glia is composed of 3 cell types: astrocytes, oligodendrocytes
and ependyma. While neoplasms can arise from either the neuronal or glial components
of the CNS, the glial tumors (gliomas) are by far more important both in terms of
frequency and clinical aggressiveness. The most common gliomas are those derived
from astrocytes and oligodendrocytes. From a practical point of view, the most
important initial distinction is to separate diffuse from circumscribed gliomas.
Diffuse gliomas, which are most common in the hemispheres of adults, cannot be cured
by surgical excision. Such tumors are divided histologically into astrocytomas,
oligodendrogliomas and oligo-astrocytomas; either of these three subtypes can transform
into the most malignant form, glioblastoma. On the other hand, circumscribed gliomas,
although also a diverse group, can often be excised in their entirety and thereby cured.
Diffuse cerebral gliomas are graded by histological criteria to provide estimates of
their behavior. The WHO divides these tumors into low-grade (grade II), anaplastic
(grade III) and glioblastoma (grade IV). Low-grade tumors have a relatively homogeneous
appearance on macroscopic examination, often appearing somewhat more tan and soft than
the surrounding normal brain. Because of their diffuse nature, the tumor margins are ill defined, merging imperceptibly with the adjacent white and gray matter. Cystic change may occur, but is less common than in circumscribed types of glioma. There may be grossly visible extension along the ventricular walls and into the ventricles, as well as along the pial surface and into the subarachnoid space. Anaplastic gliomas in general display more heterogeneity macroscopically, with darker regions indicating higher cellularity and vascularity. Finally, glioblastoma appears highly heterogeneous, with yellow zones of necrosis and red regions of hemorrhage in most cases. Macroscopic multifocality is not uncommon in glioblastomas, particularly at autopsy, but this almost always represents spread of a single tumor, rather than true multiple primary gliomas. Spread in this fashion along white matter tracts may be prominent. A curious variant of diffuse glioma is gliomatosis cerebri, in which tumor cells infiltrate throughout the central nervous system without forming conspicuous masses.
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