CXC chemokine receptor type 4 (CXCR-4), the receptor for the chemokine stromal-derived factor 1 (SDF-1), has
been shown to mediate many of the processes essential for cancer progression
such as tumor cell proliferation, metastasis,
and angiogenesis. This gene encodes a CXC chemokine receptor specific for
stromal cell-derived factor-1. The protein has 7 transmembrane regions and is
located on the cell surface.
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| Biologic pathways and genetic features in neuroblastic tumors |
Dr. AlexCarlisle is a Neuroscientist in the Department of Neurosciences at Inova Fairfax Hospital and also oversees the Inova-GMU Neuroscience Translational Research Laboratory (INTR). One of his research focuses is biological and clinical association of CXCR4 with the development of peripheral neuroblastic tumors (pNT). Neuroblastoma is a disease in which malignant (cancer) cells form in nerve tissue of the adrenal gland, neck, chest, or spinal cord. It occurs mainly in infants and children, which accounts for 15% of pediatric cancer of the sympathetic nervous system. This kind of disease has a large degree of heterogeneity, which needs a variety of clinical and biological parameters to risk-assess and predict for improved prognostic and therapeutic targets.
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Neuroblastoma Stage 1 |
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Neuroblastoma Stage 4 |
The stage of the neuroblastoma is based on results of physical exams, imaging tests, and biopsies of the main tumor and other tissues, as well as the results of surgery. By the time neuroblastoma is diagnosed, the cancer is usually spread out to the lymph nodes, bones, bone marrow, liver, and skin. The severity of this disease ranges from stage 1 to stage 4s. Therefore, prognostic markers help predict whether the child’s outlook for cure is better or worse which would be predicted by the stage alone. One of the markers he talked about was MYCN oncogene, a gene that helps regulate cell growth. Hence, changes in oncogene could make cells grow and divide too rapidly, along with cancer cells. Neuroblastoma with rapid amplification of the MYCN oncogene tend to grow quickly and are less likely to mature, therefore, children who have this feature tend to have a worse prognosis than other children with Neuroblastoma.
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| HIV binding via cell surface receptors. |
The biological roles of CXCR4 consists of recruiting lymphocytes
into inflammatory sites, developing Neural Progenitor Cell migration during
embrogenesis, and it is also a co-receptor of HIV binding and fusion, and cancer progression in
growth metasis and angiogenesis. CRXC4 is known to be necessary for normal neuronal development because past research has shown
that the knockout mice of CXCR4 results showed in inflammation and malformation
of the dorsal ganglia.
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| A Model of Maturation in a Neuroblastoma. |
In the model for neuroblastoma maturation, undifferentiated or poorly differentiated triploid (3n) neuroblastoma cells recruit diploid (2n) Schwann cells and cause their proliferation. The diploid Schwann cells migrate into the tumor, where they suppress the proliferation of neuroblastoma cells and stimulate their differentiation into ganglionic cells. Fully mature tumors consist of highly differentiated ganglionic cells, mature neuroblasts, and numerous Schwann cells that form nerve bundles with axons.
References:
http://neuroscience.gmu.edu/people/acarlisl
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