다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Tumor-associated macrophages: from mechanisms to therapy.

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

The somatic genomic landscape of glioblastoma

A complex network of chemokines and their receptors influences the development of primary tumours and metastases. New information about the biological role of chemokines in these processes is providing insights into host–tumour interactions, such as the role of the leukocyte infiltrate, and into the mechanisms that determine the metastatic potential and site-specific spread of cancer cells. Chemokine-receptor antagonists are showing promise in animal models of inflammation and autoimmune disease. Could manipulating the local chemokine network have therapeutic benefits in malignant disease?

Cancer and the chemokine network

https://www.cell.com/trends/neurosciences/pdf/S0166-2236(09)00153-2.pdf

Molecular dissection of reactive astrogliosis and glial scar formation.

Active inflammation increases the heterogeneity of MRI texture in mice with relapsing experimental allergic encephalomyelitis

Erratum: Human astrocytes are resistant to fas ligand and tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis (Journal of Neuroscience (March 22, 2006) (3299-3308))

Combination of Hydroxychloroquine and Indapamide Attenuates Neurodegeneration in Models Relevant to Multiple Sclerosis

It has been estimated that cerebrospinal fluid (CSF) contains approximately 80 proteins that significantly increase or decrease in response to various clinical conditions. Here we have evaluated the CSF protein PrPC (cellular prion protein) for possible increases or decreases following spinal cord injury. The physiological function of PrPC is not yet completely understood; however, recent findings suggest that PrPC may have neuroprotective properties. Our results show that CSF PrPC is decreased in spinal cord injured patients 12 hours following injury and is absent at 7 days. Given that normal PrPC has been proposed to be neuroprotective we speculate that the decrease in CSF PrPC levels may influence neuronal cell survival following spinal cord injury.

Reduction of PrP(C) in human cerebrospinal fluid after spinal cord injury.

Excessive inflammation within the CNS is injurious, but an immune response is also required for regeneration. Macrophages and microglia adopt different properties depending on their microenvironment, and exposure to IL4 and IL13 has been used to elicit repair. Unexpectedly, while LPS-exposed macrophages and microglia killed neural cells in culture, the addition of LPS to IL4/IL13-treated macrophages and microglia profoundly elevated IL10, repair metabolites, heparin binding epidermal growth factor trophic factor, antioxidants, and matrix-remodeling proteases. In C57BL/6 female mice, the generation of M(LPS/IL4/IL13) macrophages required TLR4 and MyD88 signaling, downstream activation of phosphatidylinositol-3 kinase/mTOR and MAP kinases, and convergence on phospho-CREB, STAT6, and NFE2. Following mouse spinal cord demyelination, local LPS/IL4/IL13 deposition markedly increased lesional phagocytic macrophages/microglia, lactate and heparin binding epidermal growth factor, matrix remodeling, oligodendrogenesis, and remyelination. Our data show that a prominent reparative state of macrophages/microglia is generated by the unexpected integration of pro- and anti-inflammatory activation cues. The results have translational potential, as the LPS/IL4/IL13 mixture could be locally applied to a focal CNS injury to enhance neural regeneration and recovery.SIGNIFICANCE STATEMENT The combination of LPS and regulatory IL4 and IL13 signaling in macrophages and microglia produces a previously unknown and particularly reparative phenotype devoid of pro-inflammatory neurotoxic features. The local administration of LPS/IL4/IL13 into spinal cord lesion elicits profound oligodendrogenesis and remyelination. The careful use of LPS and IL4/IL13 mixture could harness the known benefits of neuroinflammation to enable repair in neurologic insults.

V. Wee Yong

Papers

Active inflammation increases the heterogeneity of MRI texture in mice with relapsing experimental allergic encephalomyelitis

Erratum: Human astrocytes are resistant to fas ligand and tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis (Journal of Neuroscience (March 22, 2006) (3299-3308))

Combination of Hydroxychloroquine and Indapamide Attenuates Neurodegeneration in Models Relevant to Multiple Sclerosis

Reduction of PrP(C) in human cerebrospinal fluid after spinal cord injury.

Harnessing the Benefits of Neuroinflammation: Generation of Macrophages/Microglia with Prominent Remyelinating Properties.