Prostate cancer progresses from an androgen-dependent to androgen-independent stage after androgen ablation therapy. Mitochondrial DNA plays a role in cell death and metastatic competence. Further, heteroplasmic largedeletion mitochondrial DNA is very common in prostate cancer. To investigate the role of mitochondrial DNA in androgen dependence of prostate cancers, we tested the changes of normal and deleted mitochondrial DNA in accordance with the progression of prostate cancer. We demonstrated that the androgen-independent cell line C4-2, established by inoculation of the androgen-dependent LNCaP cell line into castrated mice, has a greatly reduced amount of normal mitochondrial DNA and an accumulation of large-deletion DNA. Strikingly, the depletion of mitochondrial DNA from androgen-dependent LNCaP resulted in a loss of androgen dependence. Reconstitution of normal mitochondrial DNA to the mitochondrial DNAdepleted clone restored androgen dependence. These results indicate that mitochondrial DNA determines androgen dependence of prostate cancer cell lines. Further, mitochondrial DNA-deficient cells formed tumors in castrated athymic mice, whereas LNCaP did not. The accumulation of large deletion and depletion of mitochondrial DNA may thus play a role in the development of androgen independence, leading to progression of prostate cancers.
ObjectivesEvaluation of Helicobacter pylori infection status (non‐infection, past infection, current infection) has become important. This study aimed to determine the usefulness of the Kyoto classification of gastritis for diagnosing H. pylori infection status by endoscopy.MethodsIn this prospective study, 498 subjects were recruited. Seven well‐experienced endoscopists blinded to the history of eradication therapy performed the examinations. Endoscopic findings were assessed according to the Kyoto classification of gastritis: diffuse redness, regular arrangement of collecting venules (RAC), fundic gland polyp (FGP), atrophy, xanthoma, hyperplastic polyp, map‐like redness, intestinal metaplasia, nodularity, mucosal swelling, white and flat elevated lesion, sticky mucus, depressive erosion, raised erosion, red streak, and enlarged folds. We established prediction models according to a machine learning procedure and compared them with general assessment by endoscopists using the Kyoto classification of gastritis.ResultsSignificantly higher diagnostic odds were obtained for RAC (32.2), FGP (7.7), and red streak (4.7) in subjects with non‐infection, map‐like redness (12.9) in subjects with past infection, and diffuse redness (26.8), mucosal swelling (13.3), sticky mucus (10.2) and enlarged fold (8.6) in subjects with current infection. The overall diagnostic accuracy rate was 82.9% with the Kyoto classification of gastritis. The diagnostic accuracy of the prediction model was 88.6% for the model without H. pylori eradication history and 93.4% for the model with eradication history.ConclusionsThe Kyoto classification of gastritis is useful for diagnosing H. pylori infection status based on endoscopic findings. Our prediction model is helpful for novice endoscopists. (UMIN000016674).
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