Search results for "Neoplasms"
showing 10 items of 7988 documents
CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells.
2017
ObjectiveCancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies.DesignTo discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients. Candidate predictive biomarkers of efficacy were identified by integrating genomic, reverse-phase protein mic…
Requirements Analysis and Specification for a Molecular Tumor Board Platform Based on cBioPortal
2020
Clinicians in molecular tumor boards (MTB) are confronted with a growing amount of genetic high-throughput sequencing data. Today, at German university hospitals, these data are usually handled in complex spreadsheets from which clinicians have to obtain the necessary information. The aim of this work was to gather a comprehensive list of requirements to be met by cBioPortal to support processes in MTBs according to clinical needs. Therefore, oncology experts at nine German university hospitals were surveyed in two rounds of interviews. To generate an interview guideline a scoping review was conducted. For visual support in the second round, screenshot mockups illustrating the requirements …
Development of a method to determine axitinib, lapatinib and afatinib in plasma by micellar liquid chromatography and validation by the European Medi…
2017
A method based on micellar liquid chromatography to quantify the tyrosine kinase inhibitors axitinib, lapatinib and afatinib in plasma is reported. The sample pretreatment was a simple 1/5-dilution in a pure micellar solution, filtration and direct injection, without requiring extraction or purification steps. The three drugs were resolved from the matrix in 17 min, using an aqueous solution of 0.07 M sodium dodecyl sulfate – 6.0% 1-pentanol, buffered at pH 7 with 0.01 M phosphate salt as mobile phase, running under isocratic mode at 1 mL/min through a C18 column. The detection was performed by absorbance at 260 nm. An accurate mathematical relationship was established between the retention…
Exosomal HSP60: a potentially useful biomarker for diagnosis, assessing prognosis, and monitoring response to treatment.
2017
Introduction: Cell-to-cell communication is imperative for life and it is mediated by sending and receiving information via the secretion and subsequent receptor-mediated detection of biological molecules. Exosomes (EXs) secreted from cells to the extracellular environment play an important role in intercellular communication in normal and pathological conditions. Areas covered: New evidence indicates that tumor cells-derived EXs contribute to cancer progression through the modulation of tumor microenvironment. The exosomal heat shock protein 60 (HSP60) is very likely a key player in intercellular cross-talk, particularly during the progress of diseases, such as cancer. Many studies have fo…
The B-cell receptor in control of tumor B-cell fitness: Biology and clinical relevance
2019
Surface expression of a functional B cell antigen receptor (BCR) is essential for the survival and proliferation of mature B cells. Most types of B-cell lymphoproliferative disorders retain surface BCR expression, including B-cell non-Hodgkin lymphomas (B-NHL) and chronic lymphocytic leukemia (CLL). Targeting BCR effectors in B-NHL cell lines in vitro has indicated that this signaling axis is crucial for malignant B cell growth. This has led to the development of inhibitors of BCR signaling, which are currently used for the treatment of CLL and several B-NHL subtypes. Recent studies based on conditional BCR inactivation in a MYC-driven mouse B-cell lymphoma model have revisited the role of …
The Role of p53 Signaling in Colorectal Cancer.
2021
Simple Summary The transcription factor p53 is a crucial tumor suppressor that regulates diverse cellular responses to protect against cancer development. Deactivating p53 signaling either by altering p53 regulators or by p53 mutations occurs frequently in human colorectal carcinoma (CRC). Forty-three percent of CRCs harbor p53 mutations that reduce wild-type p53 tumor suppressor activity and often provide neo-morphic functions, which contribute to tumorigenesis. In this review, we summarize wild-type p53 signaling, how it can be deregulated in CRC, and the functional and phenotypical effects of p53 mutations. We also discuss current therapeutic strategies of targeting p53. Abstract The tra…
Calcified Spinal Meningioma: A Lurking Danger
2017
Tumors of the spine with an intradural location have an incidence ranging from 3 to 10 per 100,000 persons per year, and intradural extramedullary tumors account for two thirds of all intraspinal neoplasms. Among these, spinal meningiomas account for 25%–46% of all spinal cord tumors. They develop from the arachnoid cells that differentiate from neural crest cells and, like cerebral meningioma, they have a slow-growing behavior. Although spinal meningiomas are not uncommon, calcified spinal meningioma is rare in spinal location. Calcified meningioma manifests with extensive matrix and tends to infiltrate the surrounding structures. It exhibits a growth pattern limited by an incompletely dev…
Role of MUC1 in idiopathic pulmonary fibrosis: mechanistic insights
2017
Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible form of fibrotic interstitial lung disease. MUC1, a membrane-bound O-glycoprotein, is considered as oncogenic molecule by altering signaling pathways involved in cellular processes related to IPF. In previous studies we have observed an up-regulation of MUC1 and its phosphorylated forms in IPF lung tissue. However the exact participation of MUC1 in IPF is currently unknown. Objective: To analyze the mechanism of MUC1-induced lung fibrosis in different cellular and animal models of IPF. Methods: The intracellular mechanism of MUC1 was evaluated by western blot, immunoprecipation and immunofluorescence …
Differentiating cancer cells reveal early large-scale genome regulation by pericentric domains.
2021
Abstract Finding out how cells prepare for fate change during differentiation commitment was our task. To address whether the constitutive pericentromere-associated domains (PADs) may be involved, we used a model system with known transcriptome data, MCF-7 breast cancer cells treated with the ErbB3 ligand heregulin (HRG), which induces differentiation and is used in the therapy of cancer. PAD-repressive heterochromatin (H3K9me3), centromere-associated-protein-specific, and active euchromatin (H3K4me3) antibodies, real-time PCR, acridine orange DNA structural test (AOT), and microscopic image analysis were applied. We found a two-step DNA unfolding after 15–20 and 60 min of HRG treatment, re…
Advanced mechanotherapy: Biotensegrity for governing metastatic tumor cell fate via modulating the extracellular matrix.
2021
Mechano-transduction is the procedure of mechanical stimulus translation via cells, among substrate shear flow, topography, and stiffness into a biochemical answer. TAZ and YAP are transcriptional coactivators which are recognized as relay proteins that promote mechano-transduction within the Hippo pathway. With regard to healthy cells in homeostasis, mechano-transduction regularly restricts proliferation, and TAZ and YAP are totally inactive. During cancer development a YAP/TAZ - stimulating positive response loop is formed between the growing tumor and the stiffening ECM. As tumor developments, local stromal and cancerous cells take advantage of mechanotransduction to enhance proliferatio…