Identification of a novel biomarker-CCL5 using antibody microarray for colorectal cancer
PATHOLOGY RESEARCH AND PRACTICE
Authors: Chen, Mingxia; Yang, Xiaoqing; Yang, Min; Zhang, Wei; Li, Lei; Sun, Qing
Abstract
Purpose: To screen novel candidate biomarkers in primary colorectal cancer (CRC), and indentify their clinical valuation in progress of colorectal cancer. Methods: By using antibody microarray, 274 target proteins in tissue samples from primary colorectal cancer patients were detected. Among differently expressed proteins in CRC tissues, As promising candidate biomarker, RANTES/CCL5 was validated by enzyme-linked immunosorbentassay and immunohistochemistry (IHC), and the clinical significance of CCL5 was analyzed. Results: Totally, 25 differentially expressed proteins were indentified between colorectal cancers and matched normal mucosa. CCL5 expression was significantly associated with adverse pathological progress, apt to lymph node metastasis and higher T stage. Conclusions: CCL5 may contribute to promoting tumor growth, and CCL5 is a promising target that may help in understanding the pathogenesis of CRC.
Methylprednisolone Reduces Persistent Post-ischemic Inflammation in a Rat Hypoxia-Ischemia Model of Perinatal Stroke
TRANSLATIONAL STROKE RESEARCH
Authors: Altamentova, Svetlana; Rumajogee, Prakasham; Hong, James; Beldick, Stephanie R.; Park, Sei Joon; Yee, Albert; Fehlings, Michael G.
Abstract
In perinatal stroke, the initial injury results in a chronic inflammatory response caused by the release of proinflammatory cytokines, gliosis and microglia activation. This chronic and ongoing inflammatory response exacerbates the brain injury, often resulting in encephalopathy and cerebral palsy (CP). Using a neonatal rat model of hypoxia-ischemia (HI) at postnatal day (P)7, we demonstrated that chronic inflammation is persistent and continues into the tertiary phase of perinatal stroke and can be attenuated by the administration of methylprednisolone sodium-succinate (MPSS, 30 mg/kg), a US Food and Drug Administration (FDA) approved anti-inflammatory agent. The inflammatory response was assessed by real-time quantitative PCR and ELISA for markers of inflammation (CCL3, CCL5, IL18 and TNF alpha). Structural changes were evaluated by histology (LFB/H&E), while cellular changes were assessed by Iba-1, ED1, GFAP, NeuN, Olig2 and CC1 immunostaining. Functional deficits were assessed with the Cylinder test and Ladder Rung Walking test. MPSS was injected 14 days after HI insult to attenuate chronic inflammation. In neonatal conditions such as CP, P21 is a clinically relevant time-point in rodents, corresponding developmentally to a 2-year-old human. Administration of MPSS resulted in reduced structural damage (corpus callosum, cortex, hippocampus, striatum), gliosis and reactive microglia and partial restoration of the oligodendrocyte population. Furthermore, significant behavioural recovery was observed. In conclusion, we demonstrated that administration of MPSS during the tertiary phase of perinatal stroke results in attenuation of the chronic inflammatory response, leading to pathophysiological and functional recovery. This work validates the high clinical impact of MPSS to treat neonatal conditions linked to chronic inflammation.