Search results for "STK"

Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

2020

Background: Brain metastases (BM) have become a major challenge in patients with metastatic breast cancer. Methods: The aim of this analysis was to characterize patients with asymptomatic BM (n = 580) in the overall cohort of 2589 patients with BM from our Brain Metastases in Breast Cancer Network Germany (BMBC) registry. Results: Compared to symptomatic patients, asymptomatic patients were slightly younger at diagnosis (median age: 55.5 vs. 57.0 years, p = 0.01), had a better performance status at diagnosis (Karnofsky index 80&ndash

Comprehensive evaluation of coding region point mutations in microsatellite-unstable colorectal cancer

2018

Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI colorectal cancers (CRCs), however, also contain more point mutations than microsatellite-stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome-sequenced sporadic MSI CRCs and respective normals, and 12 whole-genome-sequenced sporadic MSI CR…

Predicting Prognosis of Breast Cancer Patients with Brain Metastases in the BMBC Registry—Comparison of Three Different GPA Prognostic Scores

2021

Several scores have been developed in order to estimate the prognosis of patients with brain metastases (BM) by objective criteria. The aim of this analysis was to validate all three published graded-prognostic-assessment (GPA)-scores in a subcohort of 882 breast cancer (BC) patients with BM in the Brain Metastases in the German Breast Cancer (BMBC) registry. The median age at diagnosis of BM was 57 years. All in all, 22.3% of patients (n = 197) had triple-negative, 33.4% (n = 295) luminal A like, 25.1% (n = 221) luminal B/HER2-enriched like and 19.2% (n = 169) HER2 positive like BC. Age ≥60 years, evidence of extracranial metastases (ECM), higher number of BM, triple-negative subtype and l…

Aurora-A Transcriptional Silencing and Vincristine Treatment Show a Synergistic Effect in Human Tumor Cells

2008

Aurora-A is a centrosome-associated serine/threonine kinase that is overexpressed in multiple types of human tumors. Primarily, Aurora-A functions in centrosome maturation and mitotic spindle assembly. Overexpression of Aurora-A induces centrosome amplification and G 2 /M cell cycle progression. Recently, it was observed that overexpression of Aurora-A renders cells resistant to cisplatin (CDDP)-, etoposide-, and paclitaxel-induced apoptosis.Our results indicate that already in initial stages of cancer progression Aurora-A overexpression could have a major role in inducing supernumerary centrosomes and aneuploidy, as shown by immunohistochemistry on tissue sections from various stages of hu…

La committenza gesuitica e la pittura a Palermo tra XVI e XVIII secolo

Il presente lavoro di ricerca mira ad approfondire e arricchire, mediante nuove acquisizioni, lo studio in merito alle opere pittoriche di committenza gesuitica custodite presso le fondazioni palermitane dell’Ordine: chiesa del Gesù a Casa Professa, Collegio Massimo dei Gesuiti, chiesa di San Stanislao Kostka e chiesa di San Francesco Saverio. A queste si aggiungono i dipinti di committenza della Compagnia trasferiti presso altre sedi. Ulteriore intento è quello di organizzare in maniera più organica la trattazione delle commissioni artistiche dell’Ordine a Palermo, che si presentava dispersiva e frammentaria. Tra i risultati più significativi si annovera il ritrovamento di un ciclo di affr…

Multisensory discourse resources : decolonizing ethnographic research practices

2020

Researchers have attempted to address the intersection of multisensory and multimodal discourse practices from an interactional perspective. This study argues for the value of experiential, non-interactional multisensory discourse resources and proposes a conceptual framework of multisensory discourse resources to bridge visual and family language ideology ethnography. A year-long ethnographic case study of three Nepalese families (immigrant and transmigrant), consisting of 150 h of observational data triangulated with qualitative interviews, posed two questions: (1) How do transnational families, in the homescape, use multisensory discourse resources to provide cultural, national, religiou…

Touring the magical North : Borealism and the indigenous Sámi in contemporary English-language children’s fantasy literature

2017

Discourses of exotic Lapland with its indigenous inhabitants, the Sámi, are widely circulated in the tourist industry and also surface in contemporary English-language children’s fantasy fiction. In contrast to the ‘self-orientalism’ of discourses of tourism, where places and people are represented as exotic to a tourist gaze, the portrayals of the North and its inhabitants gain different symbolic meanings in fictional texts produced by outsiders who rely on earlier texts – myths, fairy tales and anthropological accounts – rather than on their own lived experience of the North or indigeneity. This article applies the concept of Borealism to examine cross-cultural intertextuality and discou…

Glimmering utopias: 50 years of African film

2010

The history of African film began in the 1960s with the independence of the colonies. Despite all kinds of political and economic difficulties, numerous films have been made since then, featuring wide-ranging processes of consolidation, differentiation and transformation which were characteristic of post-colonial sub-Saharan Africa. However, these feature films should not merely be viewed as back references to specifically African problems. The glimmering fictions are imagination spaces. They preserve ideas about how the post-colonial circumstances should be approached. Seen from this perspective, the history of African film may be studied as a history of African utopias. Die Geschichte des…

Reimagining cultural memory of the arctic in the graphic narratives of Oqaluttuaq

2021

The Greenlandic oral story-telling tradition, Oqaluttuaq, meaning “history,” “legend,” and “narrative,” is recognized as an important entry point into Arctic collective memory. The graphic artist Nuka K. Godtfredsen and his literary and scientific collaborators have used the term as the title of graphic narratives published from 2009 to 2018, and focused on four moments or ‘snippets’ from Greenland’s history (from the periods of Saqqaq, late Dorset, Norse settlement, and European colonization). Adopting a fragmentary and episodic approach to historical narrativization, the texts frame the modern European presence in Greenland as one of multiple migrations to and settlements in the Artic, ra…

Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase as a target in LKB1 Mutant Lung Cancer

2013

Abstract The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non–small cell lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach to define novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers. High-throughput RNA interference screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase (DTYMK), which catalyzes dTTP biosynthesis, as synthetica…