PET imaging and in silico analyses to support personalized treatment in oncology

Over the last decades many molecules and key pathways in cancer were identified, which facilitated a shift in anticancer drug development from DNA-damaging chemotherapy to a more personalized approach with targeted antibody therapeutics including antibody-drug conjugates (ADC) and bispecific T-cell engagers (BiTEs). A major challenge in oncology is to identify those patients that will benefit from targeted antibody therapeutics. Eventually this should lead to ‘personalized medicine’ in which a specific drug is used to treat a tumor with specific molecular or genetic characteristics in a specifically selected patient. Therefore, it is important to assess tumor selective expression of molecular targets, which is usually done by immunohistochemistry (IHC), but there may also be a role for molecular PET imaging in selecting patients and predicting tumor responses. This thesis provides an overview of molecular PET imaging with antibodies in cancer patients. Moreover, results from a first-in-human PET study using a BiTE as tracer were published. With a plethora of targeted agents becoming available to treat patients with cancer, broad knowledge concerning frequency of target expression across tumor types is of importance to fully exploit therapeutic options. Performing large-scale, golden standard, IHC analyses for many drug targets is time-consuming and demands many resources. Therefore we used functional genomic mRNA profiling instead to predict target overexpression rates for the proteoglycan “glypican 3” and for 59 ADC targets across 60 tumor types and subtypes

Epithelial Ovarian Cancer

Epithelial ovarian cancer generally presents at an advanced stage and is the most common cause of gynaecological cancer death. Treatment requires expert multidisciplinary care. Population-based screening has been ineffective, but new approaches for early diagnosis and prevention that leverage molecular genomics are in development. Initial therapy includes surgery and adjuvant therapy. Epithelial ovarian cancer is composed of distinct histological subtypes with unique genomic characteristics, which are improving the precision and effectiveness of therapy, allowing discovery of predictors of response such as mutations in breast cancer susceptibility genes BRCA1 and BRCA2, and homologous recombination deficiency for DNA damage response pathway inhibitors or resistance (cyclin E1). Rapidly evolving techniques to measure genomic changes in tumour and blood allow for assessment of sensitivity and emergence of resistance to therapy, and might be accurate indicators of residual disease. Recurrence is usually incurable, and patient symptom control and quality of life are key considerations at this stage. Treatments for recurrence have to be designed from a patient's perspective and incorporate meaningful measures of benefit. Urgent progress is needed to develop evidence and consensus-based treatment guidelines for each subgroup, and requires close international cooperation in conducting clinical trials through academic research groups such as the Gynecologic Cancer Intergroup.status: publishe

Po Wan Sioe

From Penghidoepan Series, Taon ka II, No. 8, 15 Augustus 192

Some aerospace applications of estimation theory

Electrical Engineering, Mathematics and Computer Scienc

Port\u27s Banana terminal is operational

Gulfport, Mississippi banana terminal is operational, 1963. View of automated conveyor belt carrying banana stems from the ship\u27s compartment to loading ramps and storage sheds.https://scholarsjunction.msstate.edu/mss-rand-papers/1280/thumbnail.jp

Relacje między aktywnością dehydrogenaz i fosfataz a zawartością wielopierścieniowych węglowodorów aromatycznych w glebach miejskich

The humus horizons of soils in 12 park gardens located in cities of eastern and south Poland and Upper Silesia were the objects of study. Gardens situated in city centres and suburbs were included in the test. The location of park gardens and the related intensity of anthropogenic pressure were factors significantly affecting the activity of dehydrogenases and phos-phatases, and the PAH content in the studied urban soils. The relationship between the dehydrogenase and phosphatases activity and the PAH content in soils varied, depending on the location of the park gardens, which shows that it is deter-mined mostly by the condition of the environment, as shaped by the intensity of anthropogenic pressure.Obiektami badań były poziomy próchniczne gleb 12 parków zlokalizowanych na obszarze Górnego Śląska i miast południowej i wschodniej Polski. Badaniami objęto jednocześnie parki położone w centrach miast oraz na przedmieściach. Lokalizacja ogrodów parkowych i związana z nią intensywność presji antropogenicznej była czynnikiem wpływającym istotnie na aktywność dehydrogenaz i fosfataz oraz zawartość WWA w badanych glebach miejskich. Relacje między aktywnością dehydrogenaz i fosfataz a zawartością WWA w glebach miały zróżnicowany charakter w zależności od lokalizacji ogrodów parkowych, co świadczy, że są one determinowane głównie stanem środowiska kształtowanego intensywnością presji antropogenicznej

The reliability of the clinical examination in predicting hemodynamic status in acute febrile illness in a tropical, resource-limited setting

Introduction The clinical examination alone is widely considered unreliable when assessing fluid responsiveness in critically ill patients. Little evidence exists on the performance of the clinical examination to predict other hemodynamic derangements or more complex hemodynamic states. Materials and methods Patients with acute febrile illness were assessed on admission, both clinically and per non-invasive hemodynamic measurement. Correlations between clinical signs and hemodynamics patterns were analyzed, and the predictive capacity of the clinical signs was examined. Results Seventy-one patients were included; the most common diagnoses were bacterial sepsis, scrub typhus and dengue infection. Correlations between clinical signs and hemodynamic parameters were only statistically significant for Cardiac Index (r=0.75, p-value <0.01), Systemic Vascular Resistance Index (r=0.79, p-value <0.01) and flow time corrected (r=0.44, p-value 0.03). When assessing the predictive accuracy of clinical signs, the model identified only 62% of hemodynamic states correctly, even less if there was more than one hemodynamic abnormality. Discussion The clinical examination is not reliable to assess a patient's hemodynamic status in acute febrile illness. Fluid responsiveness, cardiodepression and more complex hemodynamic states are particularly easily missed