Abstract Context Glioblastoma multiforme (GBM) is a malignant and aggressive primary brain tumor with a poor prognosis. This adverse prognosis is due to the tumor's tendency for advancement and recurrence caused by highly intrusive nature of the persisting GBM cells that actively escape from the main tumor mass into the surrounding normal brain tissue. On the basis of biomarker illustration, it can be classified into molecular subgroups. Aims (1) To determine the expression of IDH1, ATRX, p53, and Ki67 by immunohistochemistry, in a cohort of GBMs. (2) To determine whether altered protein expression of any of these growth-control genes in GBM will show association with patient survival. (3) To establish prognostically distinct molecular subgroups of GBM, irrespective of histopathological diagnosis. Results In this prospective observational study, 35 histologically diagnosed cases of glioblastoma were enrolled. The mean age at the time of presentation was 43.46 ± 17.25 years with a male:female ratio of 1.3:1. Of the 35 cases, microvascular proliferation was seen in 23 cases. Large foci of necrosis (>50%) were seen in 10 cases and 27 cases had mitotic count ≥ 5/high power field (HPF). Of 35 cases, 5 (14.3%) cases showed IDH1 immunopositivity and 30 (85.7%) cases were negative for IDH1. ATRX was retained in 24 (68.6%) cases, while it was lost in 11 (31.4%) cases. The p53 immunoexpression was seen in 31 (88.6%) cases, whereas p53 was negative in 4 (11.4%) cases. The overall median survival (OS) was 6 months. In two protein pairs, the three compositions were IDH1–/p53+ (74.3%), ATRX +/IDH1– (62.9%), and ATRX +/p53+ (57.1%). Combined three-protein immunohistochemical analysis revealed five different molecular variants. Also, 8.6% (3/35) of the samples had aberrant protein expression of all three proteins, i.e., ATRX–/p53 +/IDH1 + , while 11.4% (4/35) were wild-type protein expression group, i.e., ATRX +/p53–/IDH1–. Conclusion In patients with single protein expression, Kaplan–Meier survival analysis showed statistically better OS in IDH1 mutant glioblastomas. In cases with double protein pairs, IDH1/p53 revealed statistically significant association with better median OS. The survival analysis of patients with IDH1/ATRX/p53 protein combinations also denoted a better OS. Hence, GBM can be grouped into prognostically relevant subgroups using these protein expression signatures individually, as well as the combined protein expression signatures.

2023-07-01·European journal of nuclear medicine and molecular imaging

Somatostatin receptor activity assessed by ⁶⁸Ga-DOTATOC PET can preoperatively predict DAXX/ATRX loss of expression in well-differentiated pancreatic neuroendocrine tumors.

Article

作者: Gianolli, Luigi ; Falconi, Massimo ; Mapelli, Paola ; Andreasi, Valentina ; Bezzi, Carolina ; Schiavo Lena, Marco ; Picchio, Maria ; Baldassi, Francesco ; De Cobelli, Francesco ; Ghezzo, Samuele ; Canevari, Carla ; Partelli, Stefano ; Muffatti, Francesca ; Magnani, Patrizia

PURPOSETo evaluate the role of ⁶⁸Ga-DOTATOC PET parameters in predicting DAXX/ATRX loss of expression in patients with Pancreatic neuroendocrine tumors (PanNET) candidate to surgery.METHODSThis retrospective study included 72 consecutive patients with PanNET (January 2018-March 2022) who underwent to ⁶⁸Ga-DOTATOC PET for preoperative staging. Image analysis: qualitative assessment and extraction of SUVmax, SUV mean, somatostatin receptor density (SRD), and total lesion somatostatin receptor density (TLSRD) from primary PanNET. Radiological diameter and biopsy information (grade, Ki67) were collected. Loss of expression (LoE) of DAXX/ATRX was assessed by immunohistochemistry on surgical specimen. Student t-test, univariate and multivariate logistic regression and ROC curves have been used to investigate the predictive value of PET parameters on DAXX/ATRX LoE.RESULTSForty-two/72 patients had a G1, 28/72 a G2, and 2/72 a G3 PanNET. Seven/72 patients had DAXX LoE, 10/72 ATRX LoE, and 2/72 DAXX/ATRX LoE. SRD and TLSRD could predict DAXX LoE (p = 0.002, p = 0.018, respectively). By evaluating SRD in combination with radiological diameter, only SRD maintained statistical significance (multivariate logistic regression: p = 0.020, OR = 1.05), providing the best prediction (AUC-ROC = 79.01%; cut-off = 46.96; sensitivity = 77.78%; specificity = 88.89%). In the sub-analysis performed on 55 patients with biopsy availability, SRD demonstrated its role in providing useful and additional information (multivariate logistic regression: SRD p = 0.007; grade p = 0.040).CONCLUSIONSRD has a predictive role on DAXX LoE in PanNETs, with higher probability of LoE at increasing SRD values. SRD provides complementary/additional information to grade assessed on biopsy material, and the combined use of these approaches might support patients' management by preoperatively identifying subjects with more aggressive diseases.

2019-11-01·Current Research in Food Science

Antioxidant active packaging systems to extend the shelf life of sliced cooked ham

Article

作者: Lorenzo, José M ; Munekata, Paulo E S ; Domínguez, Rubén ; Bermúdez, Roberto ; Pateiro, Mirian ; Gagaoua, Mohammed ; Zhang, Wangang

The effectiveness of active packaging systems with green tea extract and oregano essential oil was checked for their use in sliced cooked ham. Three packaging systems were evaluated: i) control group without active film, ii) ATGT packed with active film of green tea extract (1%) and iii) ATRX with a mixture of green tea extract and oregano essential oil (1%). The evolution of microbiological, physicochemical (pH, aw, colour and lipid oxidation) and sensory attributes were analysed after 0, 7, 14 and 21 days of refrigerated storage. Microbial populations were below the limits established by the European Regulations (10⁶ UFC/g). The samples packed with ATGT showed the better antimicrobial activity against total viable counts (TVC) and lactic acid bacteria (BAL), while lower counts of Brochothrix thermosphacta was observed in ATRX film (1.48 vs. 1.78 and 2.59 UFC/g for ATRX vs. ATGT and CON, respectively). Regarding colour, low differences were found between the samples packaged with active and control films. Unlike L*, a* and b* parameters showed a progressive diminution throughout the storage in all batches, being the films that contained green tea (ATGT) were the ones that showed the less discolouration at the end of storage (8.86 vs. 8.63 and 7.50 for ATGT vs. CON and ATRX, respectively). The low fat content of this type of product and the use of anaerobic atmosphere for the packaging of cooked ham did not allow to show an antioxidant effect on lipid oxidation (values below 0.15 mg MDA/kg). Finally, the use of ATGT and ATRX did not suppose a modification of the sensorial attributes of the product, being acceptance scores under the acceptance limit during the whole display.

项与 aTRX(Oblique Therapeutics) 相关的新闻（医药）

2023-02-23

·GlobeNewswire-Health Care

Roche launches two new antibodies to identify key clinical mutations in patients with brain cancer

Recent advances in cancer genomics have deepened the medical community’s understanding of the molecular alterations in brain tumours, more precisely subclassifying patients into specific diagnoses. Understanding a patient's brain tumour mutation status in the IDH1 and ATRX genes enables more informed clinical decisions and may improve patient outcomes. The IDH1 R132H and ATRX antibodies are the latest additions to Roche’s neuropathology portfolio, which contains 29 biomarkers. Basel, 23 February 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today the launch of the IDH1 R132H (MRQ-67) Rabbit Monoclonal Primary Antibody and the ATRX Rabbit Polyclonal Antibody to identify mutation status in patients diagnosed with brain cancer. A brain tumour is formed when there is an abnormal growth of cells in the brain. There are two main types of cells in the brain: neurons, the communicators of the nervous system and glial cells, which support and protect neurons and maintain the body’s natural state of balance. Gliomas, brain tumours that develop from glial cells, are the most prevalent type of malignant brain tumours in adults.1 Gliomas that have mutations in the IDH1 and ATRX genes are biologically distinct from tumours that do not carry these mutations. Knowing a patient’s IDH1 and ATRX mutation status enables clinicians to provide personalised care to patients based on their specific tumour classification, including a more informed prognosis, the selection of targeted therapies and inclusion in clinical trials.2 “A patient's IDH1 status helps determine eligibility for clinical trials, which offers more treatment options, and may one day lead to potential targeted therapies for people fighting brain cancer,” said Matt Sause, CEO of Roche Diagnostics. Time is critical for patients fighting brain cancer. Patients diagnosed with glioblastoma, the most common brain cancer in adults, have an average survival rate of less than one year. Having an understanding of a glioma patient's mutation status will enable clinicians to quickly determine the optimum treatment path for that patient and help predict therapeutic outcomes. Immunohistochemistry is recommended by all major glioma practice guidelines for determining IDH1 R132H and ATRX mutation status.3-5 When compared to sequencing, identification of IDH1 R132H mutations via immunohistochemistry has been shown to be more accurate, rapid, accessible and cost effective.6 The IDH1 assay can also detect the IDH1 R132H mutation in acute myeloid leukaemia (AML). Roche’s IDH1 and ATRX assays are optimised and fully-automated on the BenchMark series of instruments. The two tests are now available in the US. They will likely be available in other non-CE markets later this year and in countries that accept the CE mark in 2024. About the IDH1 R132H (MRQ-67) Rabbit Monoclonal Antibody and the ATRX Rabbit Polyclonal AntibodyRoche’s IDH1 R132H (MRQ-67) Rabbit Monoclonal Antibody can detect the IDH1 R132H mutation in adult-type gliomas and in acute myeloid leukaemia (AML). When present, IDH1 R132H is associated with a relatively favourable prognosis and is important in patient stratification for clinical trials.2 IDH1 R132H immunohistochemistry is recommended by all major glioma clinical practice guidelines as the initial IDH testing modality.3-5 Roche’s ATRX Rabbit Polyclonal Antibody detects a mutation in the ATRX gene, providing significant diagnostic and prognostic information to clinicians. ATRX testing is considered “desirable” by the World Health Organization for IDH-mutant gliomas.3 About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. All trademarks used or mentioned in this release are protected by law.References[1] Finch, A. et al. Advances in Research of Adult Gliomas. Int J Mol Sci. 2021; 22(2):924.[2] Gritsch S, et al. Diagnostic, therapeutic, and prognostic implications of the 2021 World Health Organization classification of tumours of the central nervous system. Cancer. 2022 Jan 1;128(1):47-58.[3] WHO Classification of Tumours Editorial Board. Central nervous system tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2021. Accessed Feb 2 2022. (WHO classification of tumours series, 5th ed.; vol. 6). Available at: https://tumourclassification.iarc.who.int/chapters/45.[4] National Comprehensive Cancer Network Guidelines. Central Nervous System Cancers (Version 2.2022). https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. Accessed Oct 29 2022.[5] Weller, M. et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021;18,170-186.[6] IDH1/2 Mutations in Glioma: ESMO Biomarker Factsheet. European Society for Medical Oncology. Updated Nov 23 2016. Available at: https://oncologypro.esmo.org/education-library/factsheets-on-biomarkers/idh1-2-mutations-in-glioma. Accessed Jan 5 2023. Roche Group Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Nathalie AltermattPhone: +41 79 771 05 25 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74 Dr. Barbara von SchnurbeinPhone: +41 79 699 97 44 Sileia Urech Phone: +41 79 935 81 48 Attachment 23022023_MR_IDH1_en

临床研究免疫疗法

100 项与 aTRX(Oblique Therapeutics) 相关的药物交易

登录后查看更多信息