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showing 10 items of 642 documents
Molecular, Biological and Structural Features of VL CDR-1 Rb44 Peptide, Which Targets the Microtubule Network in Melanoma Cells
2019
Microtubules are important drug targets in tumor cells, owing to their role in supporting and determining the cell shape, organelle movement and cell division. The complementarity-determining regions (CDRs) of immunoglobulins have been reported to be a source of anti-tumor peptide sequences, independently of the original antibody specificity for a given antigen. We found that, the anti-Lewis B mAb light-chain CDR1 synthetic peptide Rb44, interacted with microtubules and induced depolymerization, with subsequent degradation of actin filaments, leading to depolarization of mitochondrial membrane-potential, increase of ROS, cell cycle arrest at G2/M, cleavage of caspase-9, caspase-3 and PARP, …
Multiple Myeloma-Derived Extracellular Vesicles Induce Osteoclastogenesis through the Activation of the XBP1/IRE1α Axis
2020
Bone disease severely affects the quality of life of over 70% of multiple myeloma (MM) patients, which daily experience pain, pathological fractures, mobility issues and an increased mortality. Recent data have highlighted the crucial role of the endoplasmic reticulum-associated unfolded protein response (UPR) in malignant transformation and tumor progression
Intratumoral Heterogeneity and Longitudinal Changes in Gene Expression Predict Differential Drug Sensitivity in Newly Diagnosed and Recurrent Gliobla…
2020
Background: Inevitable recurrence after radiochemotherapy is the major problem in the treatment of glioblastoma, the most prevalent type of adult brain malignancy. Glioblastomas are notorious for a high degree of intratumor heterogeneity manifest through a diversity of cell types and molecular patterns. The current paradigm of understanding glioblastoma recurrence is that cytotoxic therapy fails to target effectively glioma stem cells. Recent advances indicate that therapy-driven molecular evolution is a fundamental trait associated with glioblastoma recurrence. There is a growing body of evidence indicating that intratumor heterogeneity, longitudinal changes in molecular biomarkers and spe…
Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications
2019
Chronic inflammatory cell death is a major risk factor for the development of diverse cancers including liver cancer. Herein, disruption of the hepatic microenvironment as well as the immune cell composition are major determinants of malignant transformation and progression in hepatocellular carcinomas (HCC). Considerable research efforts have focused on the identification of predisposing factors that promote induction of an oncogenic field effect within the inflammatory liver microenvironment. Among the most prominent factors involved in this so-called inflammation-fibrosis-cancer axis is the NF-κB pathway. The dominant role of this pathway for malignant transformation and progression…
The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk.
2021
Simple Summary Hyaluronan is a main glycosaminoglycan in extracellular matrix with an important role in breast cancer progression. Alterations in its synthesis and size may affect tu-mour growth and metastasis. Communication between stromal and breast cancer cells consists of the secretion of factors that provoke a series of cell signalling that influence cell fate and tis-sue microenvironment, by favouring tumour cell survival and motility. Here, we present the c10orf118 protein expressed in high amounts by breast tumour cells as a new regulator in hya-luronan synthesis. This protein is found both in Golgi and secreted in the extracellular matrix, whereas its role is still unknown. The sec…
A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?
2021
Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved. Genetic studies have so far highlighted a major role of gene variants promoting fat deposition in the liver (PNPLA3 rs738409
The phospholipase DDHD1 as a new target in colorectal cancer therapy
2018
Background Our previous study demonstrates that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability, and that this effect is associated with the downregulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on the contribution of DDHD1 in neurological disorders, there is no information on its role in cancer. This study investigates the role of DDHD1 in colon cancer. Methods DDHD1 siRNAs and an overexpression vector were transfected into colorectal cancer and normal cells to downregulate or upregulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the functional…
AKT3 Expression in Mesenchymal Colorectal Cancer Cells Drives Growth and Is Associated with Epithelial-Mesenchymal Transition
2021
Simple Summary Colorectal cancer can be subdivided into four distinct subtypes that are characterised by different clinical features and responses to therapies currently used in the clinic to treat this disease. One of those subtypes, called CMS4, is associated with a worse prognosis and poor response to therapies compared to other subtypes. We therefore set out to explore what proteins are differentially expressed and used in CMS4 to find potential new targets for therapy. We found that protein AKT3 is highly expressed in CMS4, and that active AKT3 inhibits a protein that stalls growth of cancer cells (p27KIP1). We can target AKT3 with inhibitors which leads to strongly reduced growth of c…
Perspective: Cancer Patient Management Challenges During the COVID-19 Pandemic
2020
On March 11, 2020, the WHO has declared the coronavirus disease 2019 (COVID-19) a global pandemic. As the last few months have profoundly changed the delivery of health care in the world, we should recognize the effort of numerous comprehensive cancer centers to share experiences and knowledge to develop best practices to care for oncological patients during the COVID-19 pandemic. Patients as well as physicians must be aware of all these constraints and profound social, personal, and medical challenges posed by the tackling of this deadly disease in everyday life in order to adjust to such a completely novel scenario. This review will discuss facing the challenges and the current approaches…
Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms
2020
Frontiers in oncology 10, 1338 (2020). doi:10.3389/fonc.2020.01338