Direct Identification of an HPV-16 Tumor Antigen from Cervical Cancer Biopsy Specimens

Persistent infection with high-risk human papilloma viruses (HPV) is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile, and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altered epithelium, we exploited Poisson detection mass spectrometry (MS3) to identify those epitopes and inform future T cell-based vaccine design. Nine cervical cancer biopsies from HPV-16 positive HLA-A*02 patients were obtained, histopathology determined, and E7 oncogene PCR-amplified from tumor DNA and sequenced. Conservation of E7 oncogene coding segments was found in all tumors. MS3 analysis of HLA-A*02 immunoprecipitates detected E711–19 peptide (YMLDLQPET) in seven of the nine tumor biopsies. The remaining two samples were E711–19 negative and lacked the HLA-A*02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A*02 alleles. Thus, the conserved E711–19 peptide is a dominant HLA-A*02 binding tumor antigen in HPV-16 transformed cervical squamous and adenocarcinomas. Findings that a minority of HLA-A*02:01 tumors lack expression of both E711–19 and a peptide from a thioreductase important in processing of cysteine-rich proteins like E7 underscore the value of physical detection, define a potential additional tumor escape mechanism and have implications for therapeutic cancer vaccine development

Promoter methylation analysis of IDH genes in human gliomas

Mutations in isocitrate dehydrogenase (IDH) -1 or -2 are found in the majority of WHO grade II and III astrocytomas and oligodendrogliomas, and secondary glioblastomas. Almost all described mutations are heterozygous missense mutations affecting a conserved arginine residue in the substrate binding site of IDH1 (R132) or IDH2 (R172). But the exact mechanism of IDH mutations in neoplasia is not understood. It has been proposed that IDH mutations impart a ‘toxic gain of function’ to the mutant protein, however a dominant-negative effect of mutant IDH has also been described, implying that IDH may function as a tumour suppressor gene. As most, if not all, tumour suppressor genes are inactivated by epigenetic silencing, in a wide variety of tumours, we asked if IDH1 or IDH2 carry the epigenetic signature of a tumour suppressor by assessing cytosine methylation at their promoters. Methylation was quantified in 68 human brain tumours, including both IDH-mutant and IDH wildtype, by bisulfite pyrosequencing. In all tumours examined, CpG methylation levels were less than 8%. Our data demonstrate that inactivation of IDH function through promoter hypermethylation is not common in human gliomas and other brain tumours. These findings do not support a tumour suppressor role for IDH genes in human gliomas

Antrodia Camphorata increases insulin secretion and protects from apoptosis in MIN6 cells

Antrodia camphorata (A. camphorata) is a Taiwanese-specific fungus which has been used clinically to treat hypertension, immune- and liver-related diseases and cancer, however it has never been studied in Type II Diabetes (T2DM). Hyperglycaemia in T2DM causes endoplasmic reticulum (ER) stress, leading to β-cell dysfunction. During chronic ER stress, misfolded proteins accumulate and initiate β-cell apoptosis. Moreover, β-cell dysfunction leads to defect in insulin secretion, which is the key process in the development and progression of T2DM. Therefore, the aim of the present study was to examine the effects of A. camphorata on insulin secretion and ER stress-induced apoptosis in a mouse β-cell line, MIN6, and their underlying mechanisms. We demonstrated that the ethanolic extract of A. camphorata increased glucose-induced insulin secretion dose-dependently through peroxisome proliferator-activated receptor-γ (PPAR-γ) pathway, and upregulated genes that were involved in insulin secretion, including PPAR-γ, glucose transporter-2 (GLUT-2) and glucokinase. Furthermore, A. camphorata slightly increased cell proliferation, as well as protected from ER stress-induced apoptosis in MIN6 cells. In conclusion, this study provided evidences that A. camphorata might have anti-diabetic effects and could be a novel drug for T2DM

Fifty Most Cited Articles for Femoroacetabular Impingement and Hip Arthroscopy

Growing awareness of femoroacetabular impingement (FAI) and recent innovations in management has resulted in hip arthroscopy becoming one of the fastest-growing orthopaedic subspecialties. The purpose of this study was to identify the 50 most cited articles related to the topic of FAI and hip arthroscopy and to analyze their characteristics.The overall number of citations within these articles ranged from 99 to 820. Citation density ranged from 4.41 to 74.55. Seven countries produced these articles with the majority attributed to the United States (n=26) and Switzerland (n=18). Clinical studies made up more than half of the top articles (n=27). The JBJS level of evidence most commonly encountered was level IV (n=24) while the remaining articles were level III (n=3). No randomized controlled trials or non-randomized controlled trials were encountered in this search. The level of evidence was not significantly correlated with the overall number of citations, publication year, or citation density. The current top 50 list provides orthopaedic surgeons interested in hip arthroscopy with anup-to-date core list of the most cited articles in the scientific literature and represents a foundation to use to develop their knowledge regarding hip arthroscopy and FAI