A negative-solvatochromic fluorescent probe for visualizing intracellular distributions of fatty acid metabolites.

Metabolic distribution of fatty acid to organelles is an essential biological process for energy homeostasis as well as for the maintenance of membrane integrity, and the metabolic pathways are strictly regulated in response to environmental stimuli. Herein, we report a fluorescent fatty acid probe, which bears an azapyrene dye that changes its absorption and emission features depending on the microenvironment polarity of the organelle into which it is transported. Owing to the environmental sensitivity of this dye, the distribution of the metabolically incorporated probe in non-polar lipid droplets, medium-polarity membranes, and the polar aqueous regions, can be visualized in different colors. Based on density scatter plots of the fluorophore, we demonstrate that the degradation of triacylglycerols in lipid droplets occurs predominantly via lipolysis rather than lipophagy in nutrition-starved hepatocytes. This tool can thus be expected to significantly advance our understanding of the lipid metabolism in living organisms.

Pro-tumoral behavior of omental adipocyte-derived fibroblasts in tumor microenvironment at the metastatic site of ovarian cancer.

Adipocyte-rich omentum offers "good soil" for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro coculturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon coculturing with O-ADF. Additionally, exogenous transforming growth factor-ß1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/ß-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks.

Effects of Amino Group Substitution on the Photophysical Properties and Stability of Near-Infrared Fluorescent P-Rhodamines.

A series of phosphine oxide-bridged rhodamines (P-rhodamines) bearing various acyclic and cyclic amine moieties, including dimethyl- and diethylamine, azetidine, pyrrolidine and 7-azabicyclo[2,2,1]heptane (7ABH), have been synthesized. The photophysical properties as well as chemical and photostability of these dyes have been studied in detail. Among these dyes, the 7ABH-substituted dye shows stronger fluorescence in the near-infrared (NIR) region, relative to the other P-rhodamines. This dye could be applied to live-cell imaging, wherein lysosomes were selectively stained in a pH-independent manner. It was also found that the ring fusion of the amine moieties gives rise to remarkably redshifted spectra, with absorption and emission maxima at 770 and 820 nm, respectively, spectrally close to that of indocyanine green (ICG). Importantly, the ring-fused P-rhodamines showed much higher photostability than ICG, indicative of their promising utility as the NIR-emissive dyes.

[A case of radiation therapy successfully treated liver and lung tumors arising from postoperative cecum cancer].

The patient was an 85-year-old man who underwent a rt-hemicolectomy, cholecystectomy and choledocholithotomy for cecum cancer and bile duct stone. The tumor was a well differentiated adenocarcinoma, type 2 in the Japanese classification of colorectal carcinoma. The tumor was considered to be in stage II (ss, ly2, v0, n (-), P0, H0, M (-)). He did not receive any adjuvant chemotherapy. After 2 years and 3 months from the surgery, an abdominal MRI and an abdominal CT scan revealed a 30 mm hepatic nodule lesion. We diagnosed with liver metastasis of the cecum cancer. The patient refused both surgery and radio-frequency ablation therapy. We chose radiotherapy for liver metastasis. He was given a total dose of 50 Gy/25 fractions. After 3 months from the radiotherapy, the tumor was reduced gradually and tumor marker (CEA) was normalized. The disease was diagnosed as CR because no tumors were detected. There has been no liver recurrence. But after 4 years and 6 months from the surgery, 20 mm lung nodules in rt-lower lung were revealed by chest X-ray. Once more, we chose radiotherapy for lung tumor. He was given a total dose of 66 Gy/33 fractions. At present, the tumor was reduced gradually. There has been no recurrence since his irradiation. If the case was made a good choice, radiation therapy appears to be effective for liver and lung tumors from the colorectal cancer.