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41.
Stefanie A. Khler Lisa Brandl Pamela L. Strissel Laura Gloßner Arif B. Ekici Miriam Angeloni Fulvia Ferrazzi Veronika Bahlinger Arndt Hartmann Matthias W. Beckmann Markus Eckstein Reiner Strick 《International journal of molecular sciences》2022,23(18)
Methylene blue (MB) is a dye used for histology with clinical importance and intercalates into nucleic acids. After MB staining of formalin fixed paraffin embedded (FFPE) muscle invasive bladder cancer (MIBC) and normal urothelium, specific regions could be microdissected. It is not known if MB influences RNA used for gene expression studies. Therefore, we analyzed MIBC using five different RNA isolation methods comparing patient matched FFPE and fresh frozen (FF) tissues pre-stained with or without MB. We demonstrate a positive impact of MB on RNA integrity with FF tissues using real time PCR with no interference of its chemical properties. FFPE tissues showed no improvement of RNA integrity, which we propose is due to formalin induced nucleotide crosslinks. Using direct multiplex RNA hybridization the best genes for normalization of MIBC and control tissues were identified from 34 reference genes. In addition, 5SrRNA and 5.8SrRNA were distinctive reference genes detecting <200 bp fragments important for mRNA analyses. Using these normalized RNAs from MB stained MIBC and applying multiplex RNA hybridization and mRNA sequencing, a minimal gene expression panel precisely identified luminal and basal MIBC tumor subtypes, important for diagnosis, prognosis and chemotherapy response. 相似文献
42.
Ramona Erber Steffen Spoerl Andreas Mamilos Rosemarie Krupar Arndt Hartmann Matthias Ruebner Juergen Taxis Mareike Wittenberg Torsten E. Reichert Gerrit Spanier Silvia Spoerl 《International journal of molecular sciences》2022,23(1)
Oral cancer often presents with aggressive behavior and a high risk of recurrence and metastasis. For oral squamous cell carcinoma (OSCC), which is the most frequent histological subtype, therapy strategies include surgery, radiation therapy, chemotherapy, immune checkpoint inhibitors, and EGFR inhibitors. Recently, a Trop-2 antibody-drug conjugate (ADC) has been approved in the United States of America for the treatment of advanced triple-negative breast cancer. However, this ADC has also been tested in other solid tumors including head & neck squamous cell carcinoma. The prognostic impact of Trop-2 has already been reported for several cancers. We studied the prognostic influence of Trop-2 protein expression on OSCC patients’ survival. The cohort comprised n = 229 OSCC patients with available archived tumor tissue and corresponding non-neoplastic oral mucosa tissue. Using immunohistochemistry, we investigated Trop-2 expression in both the central and peripheral regions of each tumor and in corresponding non-neoplastic oral mucosa. In patients suffering from OSCC with combined high central and low peripheral Trop-2 expression, five-year overall survival (OS) was 41.2%, whereas 55.6% of OSCC patients who presented lower central and/or higher peripheral tumoral Trop-2 expression were alive after five years (p = 0.075). In multivariate Cox regression, the expression pattern of high central tumoral and lower peripheral Trop-2 expression was significantly correlated with impaired OS (HR = 1.802, 95%-CI: 1.134–2.864; p = 0.013) and recurrence-free survival (RFS) (HR = 1.633, 95%-CI: 1.042–2.560; p = 0.033), respectively, when adjusting for co-variables. Hence, Trop-2 may serve as an independent prognostic biomarker in OSCC. In subsequent studies, the pathophysiological meaning of downregulated Trop-2 expression in the OSCC periphery has to be analyzed. 相似文献
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Michal Becker-Cohen Ari Zimran Tama Dinur Maayan Tiomkin Claudia Cozma Arndt Rolfs David Arkadir Elena Shulman Orly Manor Ora Paltiel Gilad Yahalom Daniela Berg Shoshana Revel-Vilk 《International journal of molecular sciences》2022,23(20)
Carriers of GBA1 gene variants have a significant risk of developing Parkinson’s disease (PD). A cohort study of GBA carriers between 40–75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40–74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7–33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14–32%), Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2–26.4%), smell assessment (12.4%, 95% CI 6.6–20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7–19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as “abnormal”. Then we calculated the percentage of “abnormal” tests for each subject; the median (range) was 4.55 (0–43.5%). Twenty-two subjects had more than 15% “abnormal” tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD. 相似文献
44.
Nicola Mitwasi Claudia Arndt Liliana R. Loureiro Alexandra Kegler Frederick Fasslrinner Nicole Berndt Ralf Bergmann Vaclav Ho&#x;ej&#x;í Claudia Rssig Michael Bachmann Anja Feldmann 《International journal of molecular sciences》2022,23(9)
Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies. 相似文献
45.
Ramona Erber Miriam Angeloni Robert Sthr Michael P. Lux Daniel Ulbrich-Gebauer Enrico Pelz Agnes Bankfalvi Kurt W. Schmid Robert F. H. Walter Martina Vetter Christoph Thomssen Doris Mayr Frederick Klauschen Peter Sinn Karl Sotlar Katharina Stering Albrecht Stenzinger Marius Wunderle Peter A. Fasching Matthias W. Beckmann Oliver Hoffmann Rainer Kimmig Nadia Harbeck Rachel Wuerstlein Fulvia Ferrazzi Arndt Hartmann 《International journal of molecular sciences》2022,23(15)
In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B. 相似文献
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49.
Arndt Bode 《Informatik-Spektrum》2004,38(7):309
Zusammenfassend lässt sich de lege lata jedenfalls festhalten, dass Softwareagenten mangels Rechtspersönlichkeit und Geschäftsfähigkeit keine eigenen Willenserklärungen abgeben und damit nicht nach Stellvertretungsrecht behandelt werden können.
Prof. Dr. Peter Sester, s. S. 311 相似文献
50.
Reviews the book, Gifted at risk: Poetic portraits by Jean Sunde Peterson (2009). In this book, Peterson utilizes subjective personal introspection, or autoethnography, to render poems and essays about her years in gifted education and in counseling gifted students. As complementary constructions, each one of Peterson’s reflections about a particular case includes a poem and an essay. As arts-based research in education, each entry is from Peterson’s own impressions and memories about a specific gifted student, whom she taught or counseled. For anyone who works with adolescents and emerging adults who are gifted, Peterson’s book will be an informative resource. It does not stand alone as a textbook to introduce topics about giftedness, as it lacks explicit definitions, citations, and references. However, together with one or two more thorough treatments of giftedness research, it will do well. Counselors will come back to its pages numerous times as they work with gifted students. It will be a resource for them to reflect about the struggles and triumphs of gifted life—with highs and lows being realistically recounted. Its coverage—from moving toward good decisions, to suicide attempts and suffering abuse, to an eye toward “developmental task accomplishment”, is broad. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献