Metabolic stress induces a Wnt-dependent cancer stem cell-like state transition.

Reciprocal interactions between cancer cells and the tumor microenvironment drive multiple clinically significant behaviors including dormancy, invasion, and metastasis as well as therapy resistance. These microenvironment-dependent phenotypes share typical characteristics with cancer stem cells (CSC). However, it is poorly understood how metabolic stress in the confined tumor microenvironment contributes to the emergence and maintenance of CSC-like phenotypes. Here, we demonstrate that chronic metabolic stress (CMS) in a long-term nutrient deprivation induces a Wnt-dependent phenoconversion of non-stem cancer cells toward stem-like state and this is reflected in the transcriptome analysis. Addition of Wnt3a as well as transfection of dominant-negative Tcf4 establishes an obligatory role for the Wnt pathway in the acquisition of CSC-like characteristics in response to metabolic stress. Furthermore, systematic characterization for multiple single cell-derived clones and negative enrichment of CD44+/ESA+ stem-like cancer cells, all of which recapitulate stem-like cancer characteristics, suggest stochastic adaptation rather than selection of pre-existing subclones. Finally, CMS in the tumor microenvironment can drive a CSC-like phenoconversion of non-stem cancer cells through stochastic state transition dependent on the Wnt pathway. These findings contribute to an understanding of the metabolic stress-driven dynamic transition of non-stem cancer cells to a stem-like state in the tumor metabolic microenvironment.

Preparation of poly epsilon-caprolactone nanoparticles containing magnetite for magnetic drug carrier.

Magnetic poly epsilon-caprolactone (PCL) nanoparticles were prepared in a well shaped spherical form by the o/w emulsion method. The influence of some preparative variables on the size and surface property was investigated. Nanoparticles were smooth, well individualized and homogeneous in size. The presence of magnetite and its superparamagnetic characteristic were confirmed by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR) and vibrating sample magnetometer (VSM), respectively. The anti-cancer drug was encapsulated in the magnetic nanoparticle during preparation. A typical release behavior was observed for 30 days. In vitro experiment of magnetic susceptibility under external magnetic field demonstrated that the magnetic PCL nanoparticles have sufficient magnetic susceptibility for a potential magnetic drug carrier for targeted delivery.

Role of the inflamed synovial volume of the wrist in defining remission of rheumatoid arthritis with gadolinium-enhanced 3D-SPGR MR imaging.

The purpose of this study was to assess the role of inflamed synovial volume (ISV) in defining a state of remission in rheumatoid arthritis (RA) with contrast-enhanced, fat-suppression, three-dimensional (3D) gradient-recalled acquisition in the steady state with radiofrequency spoiling (SPGR) magnetic resonance (MR) imaging. Sixteen patients with RA (5 remission and 11 non-remission patients) were enrolled in this study. Contrast-enhanced, fat-suppression, 3D-SPGR MR imaging was performed before (n = 12) and after (n = 16) a mean 17 months of disease-modifying antirheumatic drugs (DMARDs). ISV was calculated by using a segmentation method. Statistical analysis of changes in ISVs and residual ISVs between the remission and the non-remission groups was performed. Intra- and inter-observer reproducibility was tested. Residual ISVs and relative changes in ISVs were 3.23 +/- 1.84 cm(3) and 51.4% (range 47.6-55.2%) in the remission group and 6.26 +/- 2. 03 cm(3)and 31.4% (range -73.5-53.5%) in the non-remission group. Both values were significantly different between the two groups (P < 0.05 and 0.05, respectively). Volume measurement showed high reproducibility: Intra- and inter-observer mean percentage errors were 5.04, 7.06, and 5.09%, respectively. Residual ISVs and relative changes in ISVs measured by MR imaging may provide objective and quantitative parameters in defining a state of remission in RA after therapy; however, the clinical utility of these measurements remains to be verified. J. Magn. Reson. Imaging 1999;10:202-208.

Colorectal mucinous carcinoma: findings on MRI.

PURPOSE: The purpose of this work was to define the characteristic MR features of colorectal mucinous carcinomas and to correlate the mucin pool with the signal intensity of this tumor. METHOD: MRI of 12 cases of pathologically proven colorectal carcinoma containing mucin was evaluated. We analyzed the signal intensity of tumor on T1- and T2-weighted MR images and correlated the area of intratumoral high signal intensity on T2-weighted images with the mucinous pool on the pathologic specimens. Two radiologists independently estimated the area of high signal intensity in the tumor on T2-weighted images and one pathologist estimated the amount of mucinous pool in the pathologic specimen. RESULTS: In 9 (75%) of 12 cases, focal or diffuse high signal intensity areas were detected on T2-weighted fast spin echo images. In seven cases in which mucin pools were seen macroscopically, partial (n = 3) or diffuse high signal intensity areas were noted on the T2-weighted images. Among the five cases in which microscopic mucinous pools were detected on the pathologic slides, three cases showed no high signal foci on MR images, and in the remaining two cases, high signal intensity areas were noted as small foci. CONCLUSION: Intratumoral high signal intensity on T2-weighted fast spin echo MR images occurs in mucinous carcinomas and correlates with the mucin pools on pathologic specimens.