Search results for " Cancer"
showing 10 items of 6120 documents
Microenvironmental Th9 and Th17 lymphocytes induce metastatic spreading in lung cancer.
2020
Immune microenvironment plays a critical role in lung cancer control versus progression and metastasis. In this investigation, we explored the effect of tumor-infiltrating lymphocyte subpopulations on lung cancer biology by studying in vitro cocultures, in vivo mouse models, and human lung cancer tissue. Lymphocyte conditioned media (CM) induced epithelial-mesenchymal transition (EMT) and migration in both primary human lung cancer cells and cell lines. Correspondingly, major accumulation of Th9 and Th17 cells was detected in human lung cancer tissue and correlated with poor survival. Coculturing lung cancer cells with Th9/Th17 cells or exposing them to the respective CM induced EMT in canc…
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy
2019
Supplemental Digital Content is available in the text.
Interactions between immune challenges and cancer cells proliferation: timing does matter!
2015
Using first a theoretical framework, we show that repeated short immune challenges could impact the accumulation of cancerous cells through continuous perturbation of immune system efficiency. We discuss for a new indirect role for infectious disease in cancer progression.
Are Long Noncoding RNAs New Potential Biomarkers in Gastrointestinal Stromal Tumors (GISTs)? The Role of H19 and MALAT1
2019
Long noncoding RNAs (lncRNAs) are emerging as key regulators of genetic and epigenetic networks, and their deregulation may underlie complex diseases, such as carcinogenesis. Several studies described lncRNA alterations in patients with solid tumors. In particular, HOTAIR upregulation has been associated with tumor aggressiveness, metastasis, and poor survival in gastrointestinal stromal tumor (GIST) patients. We analyzed expression levels of other lncRNAs, H19 and MALAT1, in FFPE tissue specimens from 40 surgically resected and metastatic GIST patients, using real-time PCR analysis. H19 and MALAT1 were both upregulated in 50% of GIST patients. MALAT1 lncRNA expression levels seem to be cor…
Integrated analysis of colorectal cancer microRNA datasets: Identification of microRNAs associated with tumor development
2018
Colorectal cancer (CRC) is one of the leading cause of cancer death worldwide. Currently, no effective early diagnostic biomarkers are available for colorectal carcinoma. Therefore, there is a need to discover new molecules able to identify pre-cancerous lesions. Recently, microRNAs (miRNAs) have been associated with the onset of specific pathologies, thus the identification of miRNAs associated to colorectal cancer may be used to detect this pathology at early stages. On these bases, the expression levels of miRNAs were analyzed to compare the miRNAs expression levels of colorectal cancer samples and normal tissues in several miRNA datasets. This analysis revealed a group of 19 differentia…
Targeting BRAF and RAS in Colorectal Cancer
2021
Simple Summary In colorectal cancer, mutations of the KRAS and BRAF genes are quite common and can contribute to the activation of cell signaling pathways that lead to cell proliferation and differentiation. These processes promote cancer growth, and in some cases, they may cause cells to develop resistance to certain types of treatment, notably EGFR inhibitors. We summarize recent knowledge regarding the effects of KRAS and BRAF mutations in the setting of colorectal cancer and discuss the new therapies under development. Abstract Colorectal cancer (CRC) is still one of the most frequent forms of cancer in the world in terms of incidence. Around 40% of CRC patients carry a mutation of the …
CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC
2019
Abstract Although EGFR mutant–selective tyrosine kinase inhibitors (TKI) are clinically effective, acquired resistance can occur by reactivating ERK. We show using in vitro models of acquired EGFR TKI resistance with a mesenchymal phenotype that CXCR7, an atypical G protein-coupled receptor, activates the MAPK–ERK pathway via β-arrestin. Depletion of CXCR7 inhibited the MAPK pathway, significantly attenuated EGFR TKI resistance, and resulted in mesenchymal-to-epithelial transition. CXCR7 overexpression was essential in reactivation of ERK1/2 for the generation of EGFR TKI–resistant persister cells. Many patients with non–small cell lung cancer (NSCLC) harboring an EGFR kinase domain mutatio…
Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma
2016
Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. We show that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, is expressed at low levels, possibly owing to epigenetic silencing. In LAC cells including the cancer stem cell compartment, we show that GLI1 is activated noncanonically by MAPK/ERK signaling. Different mechanisms can trigger the MAPK/ERK/GLI1 cascade including KRAS mutation and stimulation of NRP2 by VEGF produced by the cancer cells themselves in an autocrin…
Autocrine CCL5 Effect Mediates Trastuzumab Resistance by ERK Pathway Activation in HER2-Positive Breast Cancer.
2020
Abstract HER2-positive breast cancer is currently managed with chemotherapy in combination with specific anti-HER2 therapies, including trastuzumab. However, a high percentage of patients with HER2-positive tumors do not respond to trastuzumab (primary resistance) or either recur (acquired resistance), mostly due to molecular alterations in the tumor that are either unknown or undetermined in clinical practice. Those alterations may cause the tumor to be refractory to treatment with trastuzumab, promoting tumor proliferation and metastasis. Using continued exposure of a HER2-positive cell line to trastuzumab, we generated a model of acquired resistance characterized by increased expression …
Therapeutic resistance in breast cancer cells can result from deregulated EGFR signaling
2020
The epidermal growth factor receptor (EGFR) interacts with various downstream molecules including phospholipase C (PLC)/protein kinase C (PKC), Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/GSK-3, Jak/STAT and others. Often these pathways are deregulated in human malignancies such as breast cancer. Various therapeutic approaches to inhibit the activity of EGFR family members including small molecule inhibitors and monoclonal antibodies (MoAb) have been developed. A common problem with cancer treatments is the development of drug-resistance. We examined the effects of a conditionally-activated EGFR (v-Erb-B:ER) on the resistance of breast cancer cells to commonly used chemotherapeutic drugs such as doxorub…