Search results for "KRAS"

KRAS: one actor, many potential roles in diagnosis

2014

Plasma cell-free DNA in diagnostic KRAS mutation testing

2015

Epidermaalisen kasvutekijän reseptorin (EGFR) monoklonaalisia vasta-aineita (mAb) käytetään apuna metastaattisen kolorektaalisyövän (mCRC) hoidossa. Aktivoivat mutaatiot KRAS- ja NRAS-onkogeeneissä tekevät syöpäsolut vastustuskykyisiksi anti-EGFR-vasta-aineille, ja tästä syystä tuumorit tulee genotyypittää ennen hoidon aloittamista. Kudosbiopsian ottaminen on kuitenkin invasiivinen toimenpide, eikä näyte välttämättä edusta kattavasti syövän kaikkien solupopulaatioiden geneettisiä muutoksia. Verenkierron solunulkoisen DNA:n (cfDNA) on havaittu sisältävän maligneista soluista lähtöisin olevia onkogeenisiä mutaatioita, ja se voi olla hyvä vaihtoehtoinen tuumoriperäisen DNA:n lähde. Kehitimme j…

Distinct biological effects are observed in HT-29 colorectal carcinoma cells induced to express K-RASG12V or K-RASG13D

2015

ANALISI DEI MECCANISMI ATTRAVERSO CUI RAS REGOLA LA PROLIFERAZIONE E L’APOPTOSI IN CELLULE DI ADENOCARCINOMA COLORETTALE HT-29

2014

RAS is a family of small proteins with GTPase activity that regulate proliferation, differentiation and apoptosis in all cell types. The three major isoforms of RAS (H-, K- and N-RAS) differ only in the last 25 amino acids which are the site of different post-translational modifications that lead to diverse subcellular localization and efficiency of activation of alternative pathways of signal transduction. This might explain, at least in part, the different biological effects of the RAS isoforms in the cells. RAS mutations are a common event in tumorigenesis and in colorectal carcinomas the mutations in K-RAS are more frequent than mutations in H-RAS. In almost all cases, the genetic alter…

To be or not to be heavier: The role of dermal bones in the buoyancy of the Late Triassic temnospondyl amphibian Metoposaurus krasiejowensis.

2022

Stereospondyli are a clade of large aquatic temnospondyls known to have evolved a large dermal pectoral girdle. Among the Stereospondyli, metoposaurids in particular possess large interclavicles and clavicles relative to the rest of the postcranial skel-eton. Because of the large size of these dermal bones, it was first proposed that they served as ballast during hydrostatic buoyancy control which assisted metoposaurids to live a bottom-dwelling mode of life. However, a large bone need not necessarily be heavy, for which determining the bone compactness becomes crucial for under-standing any such adaptation in these dermal bones. Previous studies on the evolu-tion of bone adaptations to aqu…

Fixed point iterative schemes for variational inequality problems

2018

In a wide class of evolutionary processes, the problem of computing the solutions of an initial value problem is encountered. Here, we consider projected dynamical systems in the sense of \cite{Daniele} and references therein. Precisely, a projected dynamical system is an operator which solves the initial value problem: \begin{equation}\label{PDS}\frac{dx(t)}{dt}= \Pi_{\mathbb{K}}\left(x(t),-F(x(t))\right), \quad x(0)=x_0 \in \mathbb{K}, \, t \in [0,+\infty[,\tag{P}\end{equation} where $\mathbb{K}$ is a convex polyhedral set in $\mathbb{R}^n$, $F: \mathbb{K} \to \mathbb{R}^n$ and $\Pi_{\mathbb{K}}: \mathbb{R} \times \mathbb{K} \to \mathbb{R}^n$ is given as follows $\Pi_{\mathbb{K}}(x,-F(x))…

Driver mutations and differential sensitivity to targeted therapies: a new approach to the treatment of lung adenocarcinoma

2010

The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as "driver mutations". These are responsible for both the initiation and maintenance of the malignancy. The epidermal growth factor receptor (EGFR) pathway is the main regulator of cell function and cancer development. It has a widely defined role in the occurrence of driver mutations. Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma. In th…

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

2014

Abstract: Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal-epithelial transition factor (MET) amplification, epithelial-mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current…

Loss of p53 Attenuates the Contribution of IL-6 Deletion on Suppressed Tumor Progression and Extended Survival in Kras-Driven Murine Lung Cancer

2013

Interleukin-6 (IL-6) is involved in lung cancer tumorigenesis, tumor progression, metastasis, and drug resistance. Previous studies show that blockade of IL-6 signaling can inhibit tumor growth and increase drug sensitivity in mouse models. Clinical trials in non-small cell lung cancer (NSCLC) reveal that IL-6 targeted therapy relieves NSCLC-related anemia and cachexia, although other clinical effects require further study. We crossed IL-6(-/-) mice with Kras(G12D) mutant mice, which develop lung tumors after activation of mutant Kras(G12D), to investigate whether IL-6 inhibition contributes to tumor progression and survival time in vivo. Kras(G12D); IL-6(-/-) mice exhibited increased tumor…

Cell of origin markers identify different prognostic subgroups of lung adenocarcinoma

2018

Strong prognostic markers able to stratify lung adenocarcinoma (ADC) patients are lacking. We evaluated whether a six-immunohistochemical markers panel (TTF1, SP-A, Napsin A, MUC5AC, CDX2 and CK5), defining the putative neoplastic “cell of origin,” allows to identify prognostic subgroups among lung ADC. We screened a large cohort of ADC specimens (2003–2013) from Torino Institutional Repository identifying: (i) marker positivity by immunohistochemistry, (ii) main morphological appearance by light microscopy, (iii) presence of “hotspot” mutations of candidate genes by Sequenom technology. To evaluate possible predictors of survival and time to recurrence, uni- and multivariable-adjusted comp…