Expression und Regulation von CD276/ B7-H3 auf Blasentumorlinien und somatischen Urothelzellen

Das Harnblasenkarzinom zählt zu den häufigsten Krebsarten weltweit. Fast alle Harnblasenkarzinome sind Urothelzellkarzinome. Etwa die Hälfte der Fälle in Deutschland gehören zur prognostisch schlechteren Gruppe der invasiven Harnblasenkarzinome. Diese Tumoren müssen aufgrund ihrer größeren Ausbreitung potenziell intensiver therapiert werden. Ein wichtiger Baustein einer solchen Therapie kann eine Immuntherapie sein. Aktuell stehen hier für das Urothelzellkarzinom vor allem PD-1-Inhibitoren zu Verfügung. Wie PD-1 gehört auch CD276 zur immunmodularischen B7-Familie. Zielsetzung dieser Arbeit war es, das Expressionsverhalten von CD276 sowie dessen Regulation auf Urothelkarzinomzellen und auf somatischen Urothelzellkulturen zu untersuchen und so dieses potenziell therapeutisch relevante Molekül auf Urothelzellen besser verstehen zu können. Es wurden Zellkulturversuche und Immunfluoreszenzfärbungen von Gewebeproben durchgeführt, um die Expression von CD276 sowohl auf Zellebene als auch im gesamten histologischen Kontext beurteilen zu können. Die grundsätzliche Expression von CD276 war in den untersuchten Zellen sehr heterogen. Ebenso zeigte sich ein variables Bild bei einem Vergleich der Expression auf Transkriptebene, Proteinebene und auf der Zelloberfläche. Unter verschiedenen Triggerfaktoren wie Hypoxie, LPS, PMA und Ionomycin, FSL-1 und Mycoplasmen zeigte sich keine Änderung der Expression von CD276 auf Tumorzelllinien und somatischen Urothelzellkulturen. Die Auswertung der Immunfluoreszenz war erschwert durch die uneinheitlichen Auswertungsstrategien bereits publizierter Untersuchungen anderer Arbeitsgruppen. In dieser Arbeit konnte kein Zusammenhang der Expression von CD276 mit dem Ausbreitungsstadium des Tumors oder seines Differenzierungsgrads gezeigt werden. Eine signifikant erhöhte Expression von CD276 zeigte sich dagegen in Proben eines Patienten, der einige Zeit zuvor eine BCG-Instillation erhalten hatte. Weitere Studien sind nötig, um die Ergebnisse zu überprüfen und die Expression von CD276 auf Urothelkarzinomzellen zu erforschen

Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario.

BACKGROUND Two-dose COVID-19 vaccination often results in poor humoral response rates in patients with hematologic malignancies (HMs); yet responses to COVID-19 booster vaccines and the risk of COVID-19 infection post-booster are mostly uncertain. METHODS We included 200 outpatients with HMs and predominantly lymphoid neoplasms (96%, 191/200) in our academic center and reported on the humoral responses, which were assessed by measurement of anti-spike IgG antibodies in peripheral blood as early as 14 days after mRNA-based prime-boost vaccination, as well as factors hampering booster efficacy. Previous basic (double) immunization was applied according to the local recommendations with mRNA- and/or vector-based vaccines. We also report on post-booster COVID-19 breakthrough infections that emerged in the Omicron era and the prophylaxis strategies that were applied to poor and non-responders to booster vaccines. RESULTS A total of 55% (110/200) of the patients achieved seroconversion (i.e., anti-spike protein IgG antibody titer > 100 AU/mL assessed in median 48 days after prime-boost vaccination) after prime-boost vaccination. Multivariable analyses revealed age, lymphocytopenia, ongoing treatment and prior anti-CD20 B-cell depletion to be independent predictors for booster failure. With each month between anti-CD20-mediated B-cell depletion and booster vaccination, the probability of seroconversion increased by approximately 4% (p < 0.001) and serum-antibody titer (S-AbT) levels increased by 90 AU/mL (p = 0.011). Notably, obinutuzumab treatment was associated with an 85% lower probability for seroconversion after prime-boost vaccination compared to rituximab (p = 0.002). Of poor or non-responders to prime-boost vaccination, 41% (47/114) underwent a second booster and 73% (83/114) underwent passive immunization. COVID-19 breakthrough infections were observed in 15% (29/200) of patients after prime-boost vaccination with predominantly mild courses (93%). Next to seroconversion, passive immunization was associated with a significantly lower risk of COVID-19 breakthrough infections after booster, even in vaccine non-responders (all p < 0.05). In a small proportion of analyzed patients with myeloid neoplasms (9/200), the seroconversion rate was higher compared to those with lymphoid ones (78% vs. 54%, accordingly), while the incidence rate of COVID-19 breakthrough infections was similar (22% vs. 14%, respectively). Following the low frequency of myeloid neoplasms in this study, the results may not be automatically applied to a larger cohort. CONCLUSIONS Patients with HMs are at a high risk of COVID-19 booster vaccine failure; yet COVID-19 breakthrough infections after prime-boost vaccination are predominantly mild. Booster failure can likely be overcome by passive immunization, thereby providing immune protection against COVID-19 and attenuating the severity of COVID-19 courses. Further sophistication of clinical algorithms for preventing post-vaccination COVID-19 breakthrough infections is urgently needed

Clinical Post-SARS-CoV-2 Infection Scenarios in Vaccinated and Non-Vaccinated Cancer Patients in Three German Cancer Centers: A Retrospective Analysis.

COVID-19 vaccines have become an integral element in the protection of cancer patients against SARS-CoV-2. To date, there are no direct comparisons of the course of COVID-19 infection in cancer patients between the pre- and post-vaccine era. We analyzed SARS-CoV-2 infections and their impact on cancer in COVID-19 vaccinated and non-vaccinated patients from three German cancer centers. Overall, 133 patients with SARS-CoV-2 were enrolled in pre- and post-vaccine eras: 84 non-vaccinated and 49 vaccinated, respectively. A mild course of COVID-19 was documented more frequently in vaccinated patients (49% vs. 29%), while the frequency of severe and critical courses occurred in approximately one-half of the non-vaccinated patients (22% vs. 42%, p = 0.023). Particularly, patients with hematologic neoplasms benefited from vaccination in this context (p = 0.031). Admissions to intermediate- and intensive-care units and the necessity of non-invasive and invasive respiratory support were reduced by 71% and 50% among vaccinated patients, respectively. The median length of admission was 11 days for non-vaccinated and 5 days for vaccinated patients (p = 0.002). COVID-19 mortality was reduced by 83% in vaccinated patients (p = 0.046). Finally, the median time from SARS-CoV-2 infection to restarting cancer therapy was 12 and 26 days among vaccinated and non-vaccinated groups, respectively (p = 0.002). Although this study does not have enough power to perform multivariate analyses to account for confounders, it provides data on COVID-19 in non-vaccinated and vaccinated cancer patients and illustrates the potential benefits of COVID-19 vaccines for these patients

COVID-19: Effect on the Well-being of the United States

The purpose of this thesis is to look into COVID-19 and attempt to identify what effect the pandemic has had on the overall well-being of the United States. This information will be collected in a literature review format where the current research will be cross-referenced and analyzed to identify the physical and mental health state of society. After observing the various reports and studies covering the pandemic, it is clear to see that there has been a sharp decline in the overall mental and physical health of the nation. This has been the result of lockdowns, isolation, economic downturn, and the large social transition that has occurred over the past 2 years. This study helped clarify that the general public of the United States has decreased in health, but it showed points of resilience that point in the direction of the population making a recovery. It is unclear how long it will take the United States to return to normal levels of physical and mental health, but being able to identify and now address the problem is a step in the direction of returning towards pre-pandemic wellness

Cotton, Cattle and Commerce: Differing Economic Development Paths as an Explanatory Factor for Divergent Political Outcomes in the United States and Argentina

(Statement of Responsibility) by Christian Reitnauer(Thesis) Thesis (B.A.) -- New College of Florida, 2019RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE(Bibliography) Includes bibliographical references.This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.Faculty Sponsor: Hicks, Barbar

COVID-19: Effect on the Well-being of the United States

The purpose of this thesis is to look into COVID-19 and attempt to identify what effect the pandemic has had on the overall well-being of the United States. This information will be collected in a literature review format where the current research will be cross-referenced and analyzed to identify the physical and mental health state of society. After observing the various reports and studies covering the pandemic, it is clear to see that there has been a sharp decline in the overall mental and physical health of the nation. This has been the result of lockdowns, isolation, economic downturn, and the large social transition that has occurred over the past 2 years. This study helped clarify that the general public of the United States has decreased in health, but it showed points of resilience that point in the direction of the population making a recovery. It is unclear how long it will take the United States to return to normal levels of physical and mental health, but being able to identify and now address the problem is a step in the direction of returning towards pre-pandemic wellness

Europa an der Saar? Tele-Saar & EUROPE 1 – Zwei Sender zwischen lokaler und europäischer Öffentlichkeit

„Europa an der Saar? Tele-Saar & EUROPE 1 – Zwei Sender zwischen lokaler und europäischer Öffentlichkeit“ ist die Synthese zweier Seminar-Arbeiten von Patrick Hinsberger und Steffen Reitnauer. Die Suche nach einer europäischen Öffentlichkeit am Ende des zweiten Weltkriegs führt sie ins Saarland, wo es der französischen Militärregierung in der Nachkriegszeit gelingt die ersten privaten, kommerziellen Medienangebote zu etablieren und damit Pionierarbeit bei der Verbreitung des Mediums Fernsehen in Europa geleistet haben. Dabei stellt sich heraus, dass der Fernsehsender Tele-Saar und der Rundfunksender Europe 1 weniger das Instrument politischer Vorgaben als vielmehr das Ergebnis transnationalen Ambitionen war und die Vernetzung einzelner lokaler Medienöffentlichkeiten zum Ziel hatte. Fraglich bleibt, ob dies den Initiatoren tatsächlich gelungen ist

Characterization of the expression pattern for a putative toxin in black widow silk glands

Studies have shown that Latrodectus hesperus, black widow spiders, produce silks that illustrate remarkable strength and toughness that can be compared to steel. The ultimate goal, in the future, is to decipher the exact primary sequence for the silk protein so that it may be mass produced and integrated into many beneficial products, such as bullet-proof vests or a new type of medical suture. Using the silk could not only make our industrial products stronger, more elastic, cheaper, but also biodegradable, which would reduce much waste produced from non-bio-degradable products and be environmentally friendly.However, there has been an interesting discovery in recent years regarding black widow spider silk. Our lab has recently discovered that there may be neurotoxin proteins present in black widow spider silk-producing glands. This was discovered when researchers where analyzing the components that constitute black widow silk. However the glands that are responsible for producing toxins are located in glands near the fangs of the spider in the cephalic region, by the head. The glands that are responsible for producing silk are in the abdominal region of the spider, clearly away from where toxin proteins are produced.For our research we have decided to confirm if toxin proteins are being produced in web glands. We have selected to study the tubuliform gland, aggregate gland, major ampullate gland, and minor ampullate glands to look for the expression of toxin RNAs where they are not typically expressed. We have designed an experiment where we have created primers that use real time PCR to amplify the mRNA sequences in each of the glands. Using this analysis, we will examine whether some recently identified putative toxin proteins are expressed in silk-producing glands. Results will be discussed