E-cadherin-Fc chimera protein matrix enhances cancer stem-like properties and induces mesenchymal features in colon cancer cells.

Cancer stem cells (CSC) are a subpopulation of tumor cells with properties of high tumorigenicity and drug resistance, which lead to recurrence and poor prognosis. Although a better understanding of CSC is essential for developing cancer therapies, scarcity of the CSC population has hindered such analyses. The aim of the present study was to elucidate whether the E-cadherin-Fc chimera protein (E-cad-Fc) enhances cancer stem-like properties because studies show that soluble E-cadherin stimulates human epithelial growth factor receptor (EGFR) and downstream signaling pathways that are reported to play a crucial role in CSC. For this purpose, we used ornithine decarboxylase (ODC)-degron-transduced (Degron(+)) KM12SM cells as a CSC model that retains relatively low CSC properties. Compared to cultures without E-cad-Fc treatment, we found that E-cad-Fc treatment further suppressed proteasome activity and largely enhanced cancer stem-like properties of ODC-degron-transduced KM12SM cells. These results include increased expression of stem cell markers Lgr5, Bmi-1, SOX9, CD44, and CD44v9, aldehyde dehydrogenase (ALDH), and enhancement of robust spheroid formation, and chemoresistance to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP). These effects could be attributed to activation of the EGFR pathway as identified by extensive phosphorylation of EGFR, ERK, PI3K, AKT, and mTOR. In SW480 cells, E-cad-Fc matrix induced some CSC markers such as CD44v9 and ALDH. We also found that E-cad-Fc matrix showed high efficiency of inducing mesenchymal changes in colon cancer cells. Our data suggest that the E-cad-Fc matrix may enhance CSC properties such as enhancement of chemoresistance and sphere formation.

Partial Acquisition of Spectral Projections Accelerates Four-dimensional Spectral-spatial EPR Imaging for Mouse Tumor Models: A Feasibility Study.

PURPOSE: Our study aimed to accelerate the acquisition of four-dimensional (4D) spectral-spatial electron paramagnetic resonance (EPR) imaging for mouse tumor models. This advancement in EPR imaging should reduce the acquisition time of spectroscopic mapping while reducing quality degradation for mouse tumor models. PROCEDURES: EPR spectra under magnetic field gradients, called spectral projections, were partially measured. Additional spectral projections were later computationally synthesized from the measured spectral projections. Four-dimensional spectral-spatial images were reconstructed from the post-processed spectral projections using the algebraic reconstruction technique (ART) and assessed in terms of their image qualities. We applied this approach to a sample solution and a mouse Hs766T xenograft model of human-derived pancreatic ductal adenocarcinoma cells to demonstrate the feasibility of our concept. The nitroxyl radical imaging agent 2H,15N-DCP was exogenously infused into the mouse xenograft model. RESULTS: The computation code of 4D spectral-spatial imaging was tested with numerically generated spectral projections. In the linewidth mapping of the sample solution, we achieved a relative standard uncertainty (standard deviation/| mean |) of 0.76 µT/45.38 µT = 0.017 on the peak-to-peak first-derivative EPR linewidth. The qualities of the linewidth maps and the effect of computational synthesis of spectral projections were examined. Finally, we obtained the three-dimensional linewidth map of 2H,15N-DCP in a Hs766T tumor-bearing leg in vivo. CONCLUSION: We achieved a 46.7% reduction in the acquisition time of 4D spectral-spatial EPR imaging without significantly degrading the image quality. A combination of ART and partial acquisition in three-dimensional raster magnetic field gradient settings in orthogonal coordinates is a novel approach. Our approach to 4D spectral-spatial EPR imaging can be applied to any subject, especially for samples with less variation in one direction.

Tetrapotassium [mu(2)-N-carboxylato-D-penicillaminato(3-)-5:6kappa(2)S:S][mu(2)-D-penicillaminato(1-)-2:3kappa(2)S:S]tetrakis[mu(2)-D-penicillaminato(2-)]-1:2kappa(3)N,S:S;1:6kappa(3)N,S:S;3:4kappa(3)S:N,S;4:5kappa(3)N,S:S-2,3,5,6-tetragold(I)-1,4-dinickel(II) ethanol monosolvate decahydrate.

In the crystal structure of the title compound, K(4)[Au(4)Ni(2)(C(6)H(8)NO(4)S)(C(5)H(9)NO(2)S)(4)(C(5)H(10)NO(2)S)].C(2)H(6)O.10H(2)O, (I), two planar [Ni(C(5)H(9)NO(2)S)(2)](2-) units are spanned by [Au(2)(C(5)H(10)NO(2)S)](+) and [Au(2)(C(6)H(8)NO(4)S)](-) linkers through S atoms, forming an S:S-bridged Au(I)(4)Ni(II)(2) hexanuclear complex anion. One of six organic ligands in the complex anion is a carbamino derivative of D-penicillamine (3-mercaptovaline) and the others are deprotonated D-penicillamines. Each complex anion binds to nine K(+) ions through six carboxylate and one carbamino groups to construct a three-dimensional structure.

In-vitro proliferation assay with recycled ascitic cancer cells in malignant pleural mesothelioma: A case report.

BACKGROUND: We report the first case, to the best of our knowledge, of massive ascites due to recurrent malignant pleural mesothelioma that was controlled using KM-cell-free and concentrated ascites reinfusion therapy (KM-CART). The tumor cells derived via KM-CART were utilized secondarily in an in vitro cell growth assay using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) to investigate anticancer drug susceptibility. CASE SUMMARY: A 56-year-old man presented with recurrent malignant mesothelioma with massive ascites; more than 4000 mL of ascitic fluid was removed, filtered, and concentrated using KM-CART, and the cell-free ascitic fluid was reinfused into the patient to improve quality of life. Cancer cells isolated secondarily in an in vitro proliferation assay using CD-DST exhibited low sensitivity to pemetrexed and high sensitivity to gemcitabine. Treatment with gemcitabine maintained stable disease for 4 mo. CONCLUSION: The combination of KM-CART and CD-DST may be a promising treatment option for malignant ascites associated with malignant mesothelioma.