Increased fatty acid synthase expression in prostate biopsy cores predicts higher Gleason score in radical prostatectomy specimen

BACKGROUND: Fatty acid synthase (FAS) is highly expressed in various types of cancer, and elevated expression of FAS has been suggested to be a predictor of tumor aggressiveness and poor prognosis. We examined whether FAS expression in prostate biopsy cores could predict the pathological characteristics of radical prostatectomy (RP) specimens. METHODS: Paraffin-embedded prostate biopsy cores, obtained from 102 patients who subsequently underwent RP, were immunostained with polyclonal anti-FAS antibody. The staining intensity was categorized into non-staining, weak, moderate, and strong. Tumors with moderate or strong immunostaining were considered to show high FAS expression, and other tumors were considered to show low FAS expression. The relation between the FAS expression status in biopsy cores and pathological parameters in RP specimens was analyzed. RESULTS: The FAS expression in the biopsy cores of 64 of the 102 tumors (63%) was high, whereas it was low in the biopsy cores of the other 38 tumors (37%). High FAS expression was significantly associated with Gleason Score (GS) ≥ 7 in RP specimens (p< 0.0001). In multivariable logistic regression analyses, GS ≥7 in biopsy cores (p <0.0001), higher preoperative PSA (p = 0.0194), and high FAS expression (p = 0.0004) were independent predictors of GS ≥ 7 in the RP specimen. CONCLUSIONS: Increased FAS expression in prostate biopsy cores could be a novel parameter for predicting higher GS in RP specimens. The treatment strategy for patients with high FAS expression in prostate biopsy cores should be carefully determined

Photodynamic therapy for pulmonary mucoepidermoid carcinoma

Pulmonary mucoepidermoid carcinoma (PMEC) are rare, accounting for 0.1–0.2% of all malignant lung tumors. Furthermore, endobronchial lesions are rare and are more commonly found in the segmental or lobar bronchi. We present, to the best of our knowledge, the first case of successful treatment with photodynamic therapy (PDT) for PMEC. A 77-year-old male presented with cough and hemosputum for 4 months. Chest computed tomography showed a mass in the right intermediate bronchus. Endobronchial biopsy revealed a diagnosis of PMEC. An optimal surgical technique to preserve respiratory function was desirable as most of the tumor emerged from the bronchial glands in the central airways and was of low-grade type. Hence, PDT was performed. Repeat bronchoscopies were performed 5 years after the PDT and showed no evidence of tumor recurrence. PDT is more likely to be effective for low-grade PMECs that are visible on bronchoscopy

Detection of changes in the structure and distribution map of triacylglycerol in fatty liver model by MALDI-SpiralTOF

Matrix-assisted laser desorption/ionisation spiral orbit-type time-of-flight mass spectrometry (MALDI-SpiralTOF) can analyse lipid profiles and characterise lipid structure. Imaging mass spectrometry (IMS) also provides distribution maps of selected m/z values. Here, we investigated triacylglycerol (TG) structure and distribution using these technologies to estimate mouse fatty liver. The distribution and intensity of the most intense mass spectrum ion was indicated by IMS at m/z 881.7 (52:2). Analysis using MS/MS showed a structural change between liver TG and dietary TG. These findings suggest that MALDI-SpiralTOF is a powerful tool for clinical screening and estimating fatty liver

Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates

Insulin balls, localized insulin amyloids formed at subcutaneous insulin-injection sites in patients with diabetes, cause poor glycemic control owing to impairments in insulin absorption. Our previous study has shown that some insulin balls are cytotoxic, but others are not, implying amyloid polymorphism. Interestingly, the patient with toxic insulin balls had been treated with antibiotic minocycline, suggesting a possible relationship between toxicity of insulin balls and minocycline. However, the direct effect of minocycline on the structure and cytotoxicity of the insulin amyloid is still unclear. Herein, we demonstrated that that minocycline at physiological concentrations induced degradation of insulin amyloids formed from human insulin and insulin drug preparations used for diabetes patients. Interestingly, the process involved the initial appearance of the toxic species, which subsequently changed into less-toxic species. It is also shown that the structure of the toxic species was similar to that of sonicated fragments of human insulin amyloids. Our study shed new light on the clarification of the revelation of insulin balls and the development of the insulin analogs for diabetes therapy.ISSN:2045-232

Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates

Insulin balls, localized insulin amyloids formed at subcutaneous insulin-injection sites in patients with diabetes, cause poor glycemic control owing to impairments in insulin absorption. Our previous study has shown that some insulin balls are cytotoxic, but others are not, implying amyloid polymorphism. Interestingly, the patient with toxic insulin balls had been treated with antibiotic minocycline, suggesting a possible relationship between toxicity of insulin balls and minocycline. However, the direct effect of minocycline on the structure and cytotoxicity of the insulin amyloid is still unclear. Herein, we demonstrated that that minocycline at physiological concentrations induced degradation of insulin amyloids formed from human insulin and insulin drug preparations used for diabetes patients. Interestingly, the process involved the initial appearance of the toxic species, which subsequently changed into less-toxic species. It is also shown that the structure of the toxic species was similar to that of sonicated fragments of human insulin amyloids. Our study shed new light on the clarification of the revelation of insulin balls and the development of the insulin analogs for diabetes therapy

Insulin amyloid polymorphs: implications for iatrogenic cytotoxicity

Amyloid specific fluorescent probes are becoming an important tool for studies of disease progression and conformational polymorphisms in diseases related to protein misfolding and aggregation such as localized and systemic amyloidosis. Herein, it is demonstrated that using the amyloid specific fluorescent probes pFTAA and benzostyryl capped benzothiadiazole BTD21, structural polymorphisms of insulin amyloids are imaged in localized insulin-derived amyloid aggregates formed at subcutaneous insulin-injection sites in patients with diabetes. It is also found that pFTAA and BTD21 could discriminate structural polymorphisms of insulin amyloids, so called fibrils and filaments, formed in vitro. In addition, it is shown that insulin drug preparations used for treating diabetes formed various types of amyloid aggregates that can be assessed and quantified using pFTAA and BTD21. Interestingly, incubated pFTAA-positive insulin preparation aggregates show cytotoxicity while BTD21-positive aggregates are less toxic. From these observations, a variety of amyloid polymorphic structures with different cytotoxicities formed both in vivo and in vitro by various insulin preparations are proposed.Funding Agencies|JSPS KAKENHIMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [19H02527, 17K08708, 15K08597]; Ehime University Research Unit; Swedish Research CouncilSwedish Research Council [2015-05868, 2015-04521, 2019-04405]</p

Insulin amyloid polymorphs: implications for iatrogenic cytotoxicity†

Amyloid specific fluorescent probes are becoming an important tool for studies of disease progression and conformational polymorphisms in diseases related to protein misfolding and aggregation such as localized and systemic amyloidosis. Herein, it is demonstrated that using the amyloid specific fluorescent probes pFTAA and benzostyryl capped benzothiadiazole BTD21, structural polymorphisms of insulin amyloids are imaged in localized insulin-derived amyloid aggregates formed at subcutaneous insulin-injection sites in patients with diabetes. It is also found that pFTAA and BTD21 could discriminate structural polymorphisms of insulin amyloids, so called fibrils and filaments, formed in vitro. In addition, it is shown that insulin drug preparations used for treating diabetes formed various types of amyloid aggregates that can be assessed and quantified using pFTAA and BTD21. Interestingly, incubated pFTAA-positive insulin preparation aggregates show cytotoxicity while BTD21-positive aggregates are less toxic. From these observations, a variety of amyloid polymorphic structures with different cytotoxicities formed both in vivo and in vitro by various insulin preparations are proposed

Up-Regulation of Antioxidant Proteins in the Plasma Proteome during Saturation Diving: Unique Coincidence under Hypobaric Hypoxia.

Saturation diving (SD) is one of the safest techniques for tolerating hyperbaric conditions for long durations. However, the changes in the human plasma protein profile that occur during SD are unknown. To identify differential protein expression during or after SD, 65 blood samples from 15 healthy Japanese men trained in SD were analyzed by two-dimensional fluorescence difference gel electrophoresis. The expression of two proteins, one 32.4 kDa with an isoelectric point (pI) of 5.8 and the other 44.8 kDa with pI 4.0, were elevated during SD to 60, 100, and 200 meters sea water (msw). The expression of these proteins returned to pre-diving level when the SD training was completed. The two proteins were identified using in-gel digestion and mass spectrometric analysis; the 32.4 kDa protein was transthyretin and the 44.8 kDa protein was alpha-1-acid glycoprotein 1. Oxidation was detected at methionine 13 of transthyretin and at methionine 129 of alpha-1-acid glycoprotein 1 by tandem mass spectrometry. Moreover, haptoglobin was up-regulated during the decompression phase of 200 msw. These plasma proteins up-regulated during SD have a common function as anti-oxidants. This suggests that by coordinating their biological effects, these proteins activate a defense mechanism to counteract the effects of hyperbaric-hyperoxic conditions during SD