The clonal evolution of metastatic colorectal cancer.

Tumor heterogeneity and evolution drive treatment resistance in metastatic colorectal cancer (mCRC). Patient-derived xenografts (PDXs) can model mCRC biology; however, their ability to accurately mimic human tumor heterogeneity is unclear. Current genomic studies in mCRC have limited scope and lack matched PDXs.

Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer.

Pancreatic cancer (PC) mobilizes myeloid cells from the bone marrow to the tumor where they promote tumor growth and proliferation. Cancer stem cells (CSCs) are a population of tumor cells that are responsible for tumor initiation. Aldehyde dehydrogenase-1 activity in PC identifies CSCs, and its activity has been correlated with poor overall prognosis in human PC.

Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis.

Purpose: To determine the role of the CCL2/CCR2 axis and inflammatory monocytes (CCR2(+)/CD14(+)) as immunotherapeutic targets in the treatment of pancreatic cancer.

Experimental Design: Survival analysis was conducted to determine if the prevalence of preoperative blood monocytes correlates with survival in patients with pancreatic cancer following tumor resection. Inflammatory monocyte prevalence in the blood and bone marrow of patients with pancreatic cancer and controls was compared.

His36Pro point-mutated proteolipid protein retained in the endoplasmic reticulum of oligodendrocytes in the shaking pup.

The shaking pup (shp) is a canine mutation that affects the myelin protein proteolipid protein (PLP) and its smaller and less abundant isoform, DM20, with proline replacing histidine(36), resulting in a severe myelin deficiency in the central nervous system. We present evidence that the mutation leads to disrupted trafficking of the shp PLP/DM20 within oligodendrocytes. Immunohistochemical studies revealed significantly reduced levels of PLP/DM20 and other major myelin components such as myelin basic protein (MBP), myelin associated glycoprotein (MAG), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in shp myelin.

Suppression of activated microglia promotes survival and function of transplanted oligodendroglial progenitors.

To evaluate the functional consequence of microglial activation in vivo, oligodendroglial progenitors were transplanted into the spinal cord of Long Evans shaker, a myelin mutant rat in which myelin defects are associated with progressive microglial activation. Cells grafted into neonatal rats at the initiation of gliosis successfully myelinated axons. However, cells transplanted during peak microglial activation did not lead to myelination due to death of the grafted cells within 3 days after transplantation.

Mutations in the rat myelin basic protein gene are associated with specific alterations in other myelin gene expression.

The Long Evans shaker (les) rat is a myelin basic protein (MBP) mutant that exhibits severe central nervous system (CNS) dysmyelination. We used a combination of immunohistochemistry, immunoblot and Northern blot analyses to determine the effect of MBP deficits on the expression of other CNS myelin genes in this mutant. Immunohistochemistry revealed a marked reduction in all major myelin proteins and differences in their intracellular distribution.

Inhibition of autoimmune encephalomyelitis by a tetracycline.

We have explored the use of minocycline, a tetracycline with antiinflammatory properties, to treat chronic relapsing-remitting experimental allergic encephalomyelitis, an animal model of multiple sclerosis. Therapeutic treatment with minocycline dramatically suppresses ongoing disease activity and limits disease progression. Disease suppression is associated with immune deviation in the periphery and with suppression of the inflammatory cascade in the central nervous system.