Search results for "Tumor Burden"

β-Catenin Contributes to Lung Tumor Development Induced by EGFR Mutations

2014

Abstract The discovery of somatic mutations in EGFR and development of EGFR tyrosine kinase inhibitors (TKI) have revolutionized treatment for lung cancer. However, resistance to TKIs emerges in almost all patients and currently no effective treatment is available. Here, we show that β-catenin is essential for development of EGFR-mutated lung cancers. β-Catenin was upregulated and activated in EGFR-mutated cells. Mutant EGFR preferentially bound to and tyrosine phosphorylated β-catenin, leading to an increase in β-catenin–mediated transactivation, particularly in cells harboring the gefitinib/erlotinib-resistant gatekeeper EGFR-T790M mutation. Pharmacologic inhibition of β-catenin suppresse…

Multivalent DR5 peptides activate the TRAIL death pathway and exert tumoricidal activity.

2010

Abstract Ongoing clinical trials are exploring anticancer approaches based on signaling by TRAIL, a ligand for the cell death receptors DR4 and DR5. In this study, we report on the selective apoptotic effects of multivalent DR5 binding peptides (TRAILmim/DR5) on cancer cells in vitro and in vivo. Surface plasmon resonance revealed up to several thousand-fold increased affinities of TRAILmim/DR5-receptor complexes on generation of divalent and trivalent molecules, the latter of which was achieved with a conformationally restricted adamantane core. Notably, only multivalent molecules triggered a substantial DR5-dependent apoptotic response in vitro. In tumor models derived from human embryoni…

Patient prioritisation in HCC treatment: All (good) things come in threes.

2017

The Natural Fungal Metabolite Beauvericin Exerts Anticancer Activity In Vivo: A Pre-Clinical Pilot Study

2017

Recently, in vitro anti-cancer properties of beauvericin, a fungal metabolite were shown in various cancer cell lines. In this study, we assessed the specificity of this effect by comparing beauvericin cytotoxicity in malignant versus non-malignant cells. Moreover, we tested in vivo anticancer effects of beauvericin by treating BALB/c and CB-17/SCID mice bearing murine CT-26 or human KB-3-1-grafted tumors, respectively. Tumor size and weight were measured and histological sections were evaluated by Ki-67 and H/E staining as well as TdT-mediated-dUTP-nick-end (TUNEL) labeling. Beauvericin levels were determined in various tissues and body fluids by LC-MS/MS. In addition to a more pronounced …

High expression of QSOX1 reduces tumorogenesis, and is associated with a better outcome for breast cancer patients.

2012

International audience; ABSTRACT: INTRODUCTION: The gene quiescin/sulfhydryl oxidase 1, QSOX1, encodes an enzyme directed to the secretory pathway and excreted into the extracellular space. QSOX1 participates in the folding and stability of proteins and thus could regulate the biological activity of its substrates in the secretory pathway and/or outside the cell. The involvement of QSOX1 in oncogenesis has been studied primarily in terms of its differential expression in systemic studies. QSOX1 is overexpressed in prostate cancers and in pancreatic adenocarcinoma. In contrast, QSOX1 gene expression is repressed in endothelial tumors. In the present study, we investigated the role of QSOX1 i…

Veränderung des Schmeckvermögens bei Patienten mit Vestibularisschwannom

2014

Das Vestiularisschwannom ist ein gutartiger Tumor. Klinisch wird die Erkrankung durch die Kardinalsymptome einseitige Hörminderung, Tinnitus und Gleichgewichtsstörungen auffällig. Auf Grund der anatomischen Enge im Bereich des inneren Gehörganges kann es auch zu Affektionen des N.[for full text, please go to the a.m. URL]

MYC Activates Stem-like Cell Potential in Hepatocarcinoma by a p53-Dependent Mechanism

2014

Activation of c-MYC is an oncogenic hallmark of many cancers including liver cancer, and is associated with a variety of adverse prognostic characteristics. Despite a causative role during malignant transformation and progression in hepatocarcinogenesis, consequences of c-MYC activation for the biology of hepatic cancer stem cells (CSCs) are undefined. Here, distinct levels of c-MYC over-expression were established by using two dose-dependent tetracycline inducible systems in 4 hepatoma cell lines with different p53 mutational status. The CSCs were evaluated using side-population approach as well as standard in vitro and in vivo assays. Functional repression of p53 was achieved by lentivira…

The inhibitor of differentiation-1 (Id1) enables lung cancer liver colonization through activation of an EMT program in tumor cells and establishment…

2017

Abstract: Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1(-/-) mice) impaired liver colonization and increased survival of Id1 animals. Histologically, the presence of Idl in tumor cells of liver metastasis was responsible for liver colonization. Microarray analysis comparing liver tumor n…

Laparoscopic adrenalectomy for large adrenal masses: Single team experience

2014

Abstract Introduction Laparoscopic adrenalectomy is today considered the standard treatment for benign small adrenal tumors. An open question is the use of laparoscopy for large adrenal masses because of technical limitations and increased risk of malignancy. In this study we report our experience in laparoscopic adrenalectomy for adrenal masses larger than 6 cm. Methods Between January 2010 and December 2013 we performed 41 laparoscopic adrenalectomy. Fourteen of 41 patients (34,1%) were submitted to laparoscopic adrenalectomy for lesion >6 cm in size. All patients were submitted routinely to radiological and hormonal tests to indentify tumors characteristics. Results The patients treated …

Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis

2013

The mechanisms by which deregulated nuclear factor erythroid-2–related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1) signaling promote cellular proliferation and tumorigenesis are poorly understood. Using an integrated genomics and 13C-based targeted tracer fate association (TTFA) study, we found that NRF2 regulates miR-1 and miR-206 to direct carbon flux toward the pentose phosphate pathway (PPP) and the tricarboxylic acid (TCA) cycle, reprogramming glucose metabolism. Sustained activation of NRF2 signaling in cancer cells attenuated miR-1 and miR-206 expression, leading to enhanced expression of PPP genes. Conversely, overexpression of miR-1 and miR-206 decreased the exp…