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Table 1 Examples of U251 human tumor cell genes that constitute beneficial responses (A) or undesirable responses (B) to metronomic CPA treatment

From: Transcriptional profiling provides insights into metronomic cyclophosphamide-activated, innate immune-dependent regression of brain tumor xenografts

A. Beneficial responses
Gene U251 (day 12) U251 (day 18) Pro-tumor or Anti-tumor Activities References
Fold change p-value Fold change p-value
LUM 8.7 1.3E-06 14.1 1.7E-14 Inhibits tumor cell migration and invasion [112]
SSTR2 5.5 7.5E-23 5.9 0 Inhibits glioma proliferation [113]
IFNB1 5.5 9.3E-37 5.9 2.5E-43 Pro-apoptotic, anti-proliferative, anti-angiogenic factor; inhibits accumulation of pro-angiogenic tumor-associated neutrophils [114,115]
ZBP1 4.8 0 5.6 0 DNA sensor; activates IRFs, NFkB, and innate immunity; interferon-inducible [116-118]
XAF1 2.8 2.2E-35 5.5 0 Interferon-inducible, pro-apoptotic [119]
IFIT3 4.0 1.7E-37 5.3 7.8E-42 Interferon-inducible, pro-apoptotic [120]
DMBT1 3.3 7.0E-15 5.0 0 Tumor suppressor down-regulated in glioblastoma [121]
DDX58 2.8 6.5E-43 4.5 0 Induces interferon-I, activates apoptosis [122]
TNFSF4/OX40L 2.3 2.5E-08 3.5 2.8E-31 Increases adhesion of activated T cells at tumor site [123]
CXCL2/MIP2 −4.6 3.8E-14 −3.1 1.3E-09 Up-regulated in temozolomide-resistant glioma [124]
CXCR4 −3.6 7.4E-38 −5.0 2.0E-26 Promotes angiogenesis in glioma [125,126]
LGR5 −4.7 3.8E-43 −5.3 1.2E-39 Marker for poor prognosis in glioblastoma [127]
IL8/CXCL8 −7.6 1.5E-11 −5.5 1.1E-24 Proinflammatory cytokine; increases tumor angiogenesis, invasion and metastasis; interferon-inducible [128]
B.B. Undesirable responses
Gene U251 (day 12) U251 (day 18) Pro-tumor or Anti-tumor Activities References
Fold change p-value Fold change p-value
MMP13 10.1 1.1E-11 15.4 0 Promotes tumor cell proliferation and invasion [129]
CEACAM1 5.9 4.7E-29 13.2 7.7E-29 Immune-inhibitory adhesion molecule; interferon-inducible [94]
LAMP3/CD208 6.4 1.5E-30 9.6 0 Promotes metastases [130]
EREG 6.5 2.3E-25 8.5 0 Binds EGFR and induces glioma cell growth [95]
IDO1 4.8 0 6.5 0 Immunosuppressive in human glioblastoma; interferon-inducible [96]
ACP5 4.5 2.3E-33 5.0 7.2E-39 Pro-metastatic factor [131]
  1. Shown are fold-change values (fold increases or decreases in expression compared to drug-free controls) and associated p-values derived from microarray analyses for U251 tumors analyzed on day 12 and day 18 after initial CPA treatment.