Ratio of healthy cells to tumor cells in brain tumor
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Several studies demonstrated that the CXCR4/CXCL12 axis is involved in tumor cell proliferation, angiogenesis, invasion, and metastasis in malignant gliomas as well as in other brain tumors. Brain tumor cell lines, primary tumors, and metastases have high concentrations of CXCR4 receptors compared to normal brain parenchyma (Rempel, Dudas, Ge, & Gutierrez, 2000; Rubin et al., 2003; Sehgal, Keener, Boynton, Warrick, & Murphy, 1998; Woerner, Warrington, Kung, Perry, & Rubin, 2005). Expression analysis using cDNA expression arrays revealed that CXCR4 is overexpressed in 57% of primary glioblastoma multiforme tumor tissues and in 88% of glioblastoma cell lines analyzed (Sehgal et al., 1998). CXCR4 and CXCL12 expression varies in glioma cells with low-grade tumors expressing intermediate level of CXCR4 and CXCL12 and advanced gliomas expressing higher levels of CXCR4 (Gagliardi et al., 2014; Rempel et al., 2000). The invading regions of glioblastomas and satellite tumors, which are the primary reason for recurrence, are also known to express high levels of CXCR4 (Zagzag et al., 2008). As such, CXCR4 expression is considered a prognostic marker in gliomas. In addition, patients with CXCR4-positive glioblastoma multiforme exhibited poorer postoperative life expectancy when compared to patients with CXCR4-negative tumors.
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