Definition and Independent Validation of a Proteomic-Classifier in Ovarian Cancer

Simple Summary: The heterogeneity of epithelial ovarian cancer and its associated molecular biological characteristics are continuously integrated in the development of therapy guidelines. In a next step, future therapy recommendations might also be able to focus on the patient's systemic status, not only the tumor's molecular pattern. Therefore, new methods to identify and validate host-related biomarkers need to be established. Using mass spectrometry, we developed and independently validated a blood-based proteomic classifier, stratifying epithelial ovarian cancer patients into good and poor survival groups. We also determined an age dependence of the prognostic performance of this classifier and its association with important biological processes. This work highlights that, just like molecular markers of the tumor itself, the systemic condition of a patient (partly reflected in proteomic patterns) also influences survival and therapy response and could therefore be integrated into future processes of therapy planning. Abstract: Mass-spectrometry-based analyses have identified a variety of candidate protein biomarkers that might be crucial for epithelial ovarian cancer (EOC) development and therapy response. Comprehensive validation studies of the biological and clinical implications of proteomics are needed to advance them toward clinical use. Using the Deep MALDI method of mass spectrometry, we developed and independently validated (development cohort: n = 199, validation cohort: n = 135) a blood-based proteomic classifier, stratifying EOC patients into good and poor survival groups. We also determined an age dependency of the prognostic performance of this classifier, and our protein set enrichment analysis showed that the good and poor proteomic phenotypes were associated with, respectively, lower and higher levels of complement activation, inflammatory response, and acute phase reactants. This work highlights that, just like molecular markers of the tumor itself, the systemic condition of a patient (partly reflected in proteomic patterns) also influences survival and therapy response in a subset of ovarian cancer patients and could therefore be integrated into future processes of therapy planning

Characteristics of Patients in SPCG-15-A Randomized Trial Comparing Radical Prostatectomy with Primary Radiotherapy plus Androgen Deprivation Therapy in Men with Locally Advanced Prostate Cancer

Background: There is no high-grade evidence for surgery as primary treatment for locally advanced prostate cancer. The SPCG-15 study is the first randomized trial comparing surgical treatment with radiotherapy. Objective: To describe the baseline characteristics of the first 600 randomized men in the SPCG-15 study. The study will compare mortality and functional outcomes. Design, setting, and participants: This study is a Scandinavian prospective, open, multicenter phase III randomized clinical trial aiming to randomize 1200 men. Intervention: Radical prostatectomy with or without consecutive radiotherapy (experimental) and radiotherapy with neoadjuvant androgen deprivation therapy (standard of care). Outcome measurements and statistical analysis: Cause-specific survival, metastasis-free survival, overall survival, and patient-reported bowel function, sexual health, and lower urinary tract symptoms were measured. Results and limitations: The distribution of characteristics was similar in the two study arms. The median age was 67 yr (range 45-75 yr). Among the operated men, 36% had pT3a stage of disease and 39% had pT3b stage. International Society of Urological Pathology grades 2, 3, 4, and 5 were prevalent in 21%, 35%, 7%, and 27%, respectively. Half of the men (51%) in the surgery arm had no positive lymph nodes. The main limitation is the pragmatic design comparing the best available practice at each study site leading to heterogeneity of treatment regimens within the study arms. Conclusions: We have proved that randomization between surgery and radiotherapy for locally advanced prostate cancer is feasible. The characteristics of the study population demonstrate a high prevalence of advanced disease, well-balanced comparison groups, and a demography mirroring the Scandinavian population of men with prostate cancer at large. Patient summary: This study, which has recruited >600 men, compares radiotherapy with surgery for prostate cancer, and an analysis at the time of randomization indicates that the study will be informative and generalizable to most men with locally advanced but not metastasized prostate cancer. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.Peer reviewe

Focus: Implementing participation - Advancement of social services in analog and digital spaces

Digitale Informations- und Kommunikationstechnologien gewinnen als fester Bestandteil zunehmend Bedeutung in den alltäglichen Lebenswelten einer wachsenden Zahl von Menschen. Ihre Entwicklung und selbstverständliche Nutzung schreiten in einem immer rasanteren Tempo voran; die vielfältigen Anwendungsmöglichkeiten adressieren längst alle Lebensbereiche. Während der Digitalisierung von Kommunikationsprozessen zuweilen demokratisierende Kräfte zugesprochen werden, scheint eine kritische Reflexion möglicher Potentiale und Auswirkungen digitaler Informations- und Kommunikationstechnologien auf Teilhabedynamiken in unterschiedlichen Lebensbereichen dringend erforderlich. Die Autorinnen und Autoren möchten mit dieser SI:SO-Schwerpunktausgabe einen Beitrag zu einer kritischen Reflexion digitaler Innovationen und ihrer Auswirkungen auf die zukünftige Gestaltung sozialer Dienste leisten. Mit der zweisprachigen Ausgabe ist zudem die Hoffnung verbunden, diesen Beitrag auch einem europäischen und weltweiten Publikum zugänglich zu machen.Digital information and communications technologies are becoming an increasingly important part in everyday life of a growing number of people. Their development and natural use are progressing even faster with a wide range of possible applications addressing all areas of life. While the digitization of communication processes is sometimes said to have democratizing forces, critical reflection on the potential and impact of digital information and communication technologies on participation dynamics in different areas of life seems urgently needed. The Authors would like to contribute to a critical reflection on digital innovations and their impact on the future design of social services. The bilingual edition further aims to make this contribution accessible to a European and global audience

Patient-derived xenograft (PDX) models in basic and translational breast cancer research

Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research

Molecular and cytological characterization of the global Musa germplasm collection provides insights into the treasure of banana diversity

© 2016, The Author(s). Bananas (Musa spp.) are one of the main fruit crops grown worldwide. With the annual production reaching 144 million tons, their production represents an important contribution to the economies of many countries in Asia, Africa, Latin-America and Pacific Islands. Most importantly, bananas are a staple food for millions of people living in the tropics. Unfortunately, sustainable banana production is endangered by various diseases and pests, and the breeding for resistant cultivars relies on a far too small base of genetic variation. Greater diversity needs to be incorporated in breeding, especially of wild species. Such work requires a large and thoroughly characterized germplasm collection, which also is a safe depository of genetic diversity. The largest ex situ Musa germplasm collection is kept at the International Transit Centre (ITC) in Leuven (Belgium) and currently comprises over 1500 accessions. This report summarizes the results of systematic cytological and molecular characterization of the Musa ITC collection. By December 2015, 630 accessions have been genotyped. The SSR markers confirmed the previous morphological based classification for 84% of ITC accessions analyzed. The remaining 16% of the genotyped entries may need field verification by taxonomist to decide if the unexpected classification by SSR genotyping was correct. The ploidy level estimation complements the molecular data. The genotyping continues for the entire ITC collection, including newly introduced accessions, to assure that the genotype of each accession is known in the largest global Musa gene bank. Open Access ispartof: Biodiversity and Conservation vol:26 issue:4 pages:801-824 status: publishe

Target—effector interaction in the natural killer cell system: Isolation of target structures

A sensitive target binding assay has recently been shown to detect natural killer (NK) cells in the mouse. Preincubation of NK cells with detergent-solubilized cell-surface proteins of YAC lymphoma cells prevented subsequent binding to intact YAC targets. The NK target structures (NK-TS) consisted of three molecular species tentatively assigned molecular weights of 130,000, 160,000, and 240,000 based on electrophoretic mobility in sodium dodecyl sulfate/polyacrylamide gels. Moloney cell surface antigen (MCSA), gp71, p30, H-2, and NK-TS were localized in distinct fractions of gels. The NK-TS bound to concanavalin A-Sepharose columns and could be eluted with the specific sugar, suggesting that the target structures may be glycosylated. NK-TS molecules could not be detected in gels of NK-insensitive target cells such as P815, A9HT, YWA, or EL-4. The quantity obtained from the gels varied directly with the NK sensitivity of YAC which is more sensitive when grown in vitro than when grown in vivo. The NK-TS molecules specifically inhibited the binding of NK cells but not alloimmune T cells to their appropriate targets. Additional NK-sensitive tumor cells also expressed some or all of the target molecules exhibited by YAC. Some of these structures shared specificities in the case of MPC-11 or were unique in the case of Molt-4 and K562, as shown by cross-inhibition studies. These results suggest that NK-sensitive cell lines express distinct target structures with possible relevance to natural tumor resistance

A Pilot Study on the Influence of Maternal Attachment Representations on Maternal Heart Rate Mediated by Perceived Stress

Past findings have suggested that there is a link between attachment representations and reactions towards stress (subjective and physiological). The aim of this study was to examine the mediating effect of perceived stress on the association between attachment representation and physiological changes, specifically heart rate. As part of a long-term study investigating the transgenerational transmission of childhood maltreatment, n = 163 mothers participated in multiple assessments. The Adult Attachment Projective Picture System (AAP) was used to measure maternal attachment representation, categorizing individuals as securely or insecurely attached. Perceived daily stress was assessed using the Perceived Stress Scale 14 (PSS-14), and maternal baseline heart rate (HR) was measured via electrocardiography during a laboratory visit. The results revealed that the representation of secure attachment had a significant reducing effect on both the mother’s perceived daily stress and heart rate. Furthermore, the association between secure attachment representation and heart rate was mediated by perceived stress. This study emphasizes the role of attachment representation in maternal well-being, highlighting its impact on stress and physiological responses

Maternal sensitivity modulates child’s parasympathetic mode and buffers sympathetic activity in a free play situation

Background Behavioral and physiological (self-)regulation in early life is crucial for the understanding of childhood development and adjustment. The autonomic nervous system (ANS) is a main player in the regulative system and should therefore be modulated by the quality of interactive behavior of the caregiver. We experimentally investigated the ANS response of 18–36-month-old children in response to the quality of maternal behavior during a mother–child-interacting paradigm. Method Eighty mothers and their children came to our laboratory and took part in an experimental paradigm, consisting of three episodes: a resting phase (E1), a structured play phase (E2), and a free play situation (E3) between mothers and their child. Children’s and mother’s heart rate (HR), the sympathetic nervous system (SNS) activity via the pre-ejection period (PEP) and the left ventricular ejection time (LVET), and the parasympathetic nervous system (PNS) activity via the respiratory sinus arrhythmia (RSA) were continuously measured by an electrocardiogram. Maternal sensitivity of interactive behavior was assessed by using the Emotional Availability (EA) Scales. Results Children of mothers with insensitive behavior had a significantly lower RSA at baseline, showed a lack of RSA withdrawal during structured and free play, and had shorter LVET across all episodes compared to children of sensitive mothers. Conclusion Our findings depict the influence of low-quality maternal interaction on the child’s ANS regulation, in calm and more stressful play situations. The overall higher SNS mode with impaired PNS reactivity may negatively influence child’s ANS homoeostasis, which may result in a long-term impact on mental and physical wellbeing. Further, the maternal sensitivity may function as a buffer for the stress response of their child. These results could serve as a basis for the development of appropriate psychoeducational programs for mothers of low sensitivity in their interaction with the child

Definition and Independent Validation of a Proteomic-Classifier in Ovarian Cancer

Mass-spectrometry-based analyses have identified a variety of candidate protein biomarkers that might be crucial for epithelial ovarian cancer (EOC) development and therapy response. Comprehensive validation studies of the biological and clinical implications of proteomics are needed to advance them toward clinical use. Using the Deep MALDI method of mass spectrometry, we developed and independently validated (development cohort: n = 199, validation cohort: n = 135) a blood-based proteomic classifier, stratifying EOC patients into good and poor survival groups. We also determined an age dependency of the prognostic performance of this classifier, and our protein set enrichment analysis showed that the good and poor proteomic phenotypes were associated with, respectively, lower and higher levels of complement activation, inflammatory response, and acute phase reactants. This work highlights that, just like molecular markers of the tumor itself, the systemic condition of a patient (partly reflected in proteomic patterns) also influences survival and therapy response in a subset of ovarian cancer patients and could therefore be integrated into future processes of therapy planning.status: publishe