Epstein-Barr virus (EBV) causes malignant carcinomas including B cell lymphomas accompanied by the systemic inflammation. Previously, we observed that phosphatidylserine (PS)-exposing subset of extracellular vesicles (EVs) secreted from an EBV strain Akata-transformed lymphoma (Akata EVs) convert surrounding phagocytes into tumor-associated macrophages (TAMs) via induction of inflammatory response, which is in part mediated by EBV-derived micro RNAs. However, it is still unclear about EV-carried other potential inflammatory factors associated with TAM formation in EBV lymphomas. To this end, we sought to explore proteomic and phospholipidomic profiles of PS-exposing EVs derived from EBV-transformed lymphomas. Mass spectrometric analysis revealed that several immunomodulatory proteins including integrin αLβ2 and fibroblast growth factor 2 (FGF2) were highly expressed in PS-exposing Akata EVs compared with another EBV strain B95-8-transformed lymphoma-derived counterparts which significantly lack TAM-inducing ability. Pharmacological inhibition of either integrin αLβ2 or FGF2 hampered cytokine induction in monocytic cultured cells elicited by PS-exposing Akata EVs, suggesting the involvement of these proteins in EV-mediated TAM induction in EBV lymphomas. In addition, phospholipids containing precursors of immunomodulatory lipid mediators were also enriched in PS-exposing Akata EVs compared with B95-8 counterparts. Phospholipidomic analysis of fractionated Akata EVs by density gradient centrifugation further demonstrated that PS-exposing Akata EVs might be identical to certain Akata EVs in low density fractions containing exosomes. Therefore, we concluded that a variety of immunomodulatory cargo molecules in a certain EV subtype are presumably conducive to the development of EBV lymphomas.
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Bioimaging with fluorescent probes is used as an invaluable tool in a biomedical field both in vivo and in vitro. However, organic dyes have some problems such as photo-breaching and cytotoxicity due to short wavelength with high quantum energy. Recently, a new approach using rare-earth-doped ceramic nanophosphors (RED-CNP) shows that fluorescence from RED-CNP in both visible (upconversion) and near infrared (NIR) wavelength region under NIR excitation is available for bioimaging. In order to efficiently introduce the RED-CNP into cancer cells, in this study we have developed a lipid nano-particles of liposome-encapsulated erbium (Er) ion-doped Y2O3 (lipo-Y2O3). Cationic lipo-Y2O3 could clearly visualize the intracellular region of human hepatocellular carcinoma Huh-7 cells by a fluorescence microscope measurements equipped with near-infrared excitation source scanning. The results imply that the lipo-Y2O3 would potentially be useful material for imaging of cancer cells. The embedded Y2O3 in the liposome having cancer-specific ligands and/or antibodies on its surface should have a great potential for cancer cell imaging in general in living subjects.
We report our three cases of intestinal tuberculosis in which none showed respiratory symptoms. Case 1 : A male of 60's. Lower abdominal pain was persistent for a month and fecal occult blood tests were positive. Type 2 colonic cancer of the cecum was doubted by colonoscopy (CS) in the local doctor and he was introduced to our hospital. CS revealed ulceration and stenosis at the ileocecal area. Biopsy of the ulceration showed granulomatous lesion and lead to diagnosis of tuberculosis. Chest X-ray showed lung lesions as well. Case 2 : A male of 50's. Because persistent diarrhea for three weeks later evolves to right lower abdominal pain and vomiting, he was admitted. CS showed ulceration of the terminal ileum and ileocecal valve. Biopsy of the ulceration showed granulomatous lesion and lead to diagnosis. Sputum was positive for tubercle bacilli and lead to diagnosis of lung and intestinal tuberculosis. Case 3 : A female of 30's. Abdominal pain and diarrhea repeated for a year and CS was performed. The intestine from terminal ileum to sigmoid colon showed skipping lesions of circular ulcers. Ileocecal biopsy showed Tb-PCR positive and lung lesion were suspected on chest X-ray. There were all of three cases ulcerative lesions on the ileocecal area, and tubercle bacilli were able to be detected.
