Search results for " KRAS"

Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?

2010

An important molecular target for metastatic CRC treatment is the epidermal growth factor receptor (EGFR). Many potential biomarkers predictive of response to anti-EGFR monoclonal antibodies (cetuximab and panitumumab) have been retrospectively evaluated, including EGFR activation markers and EGFR ligands activation markers. With regard to the "negative predictive factors" responsible for primary or intrinsic resistance to anti-EGFR antibodies a lot of data are now available. Among these, KRAS mutations have emerged as a major predictor of resistance to panitumumab or cetuximab in the clinical setting and several studies of patients receiving first and subsequent lines of treatment have sho…

Cetuximab plus FOLFOX-4 in untreated patients with advanced colorectal cancer: a Gruppo Oncologico dell'Italia Meridionale Multicenter phase II study.

2010

<i>Objectives:</i> FOLFOX-4 and FOLFIRI are considered equivalent in terms of activity and efficacy as first-line chemotherapy in metastatic colorectal cancer (mCRC). The monoclonal antibody (mAb) cetuximab showed intrinsic activity as a single agent in mCRC and was approved in combination with CPT-11 for patients who failed previous CPT-11-based treatment. The purpose of this phase II study was to evaluate the activity and safety of FOLFOX-4 plus cetuximab in untreated mCRC patients. <i>Methods:</i> Untreated patients with measurable metastatic disease and expressing epidermal growth factor receptor (EGFR) received cetuximab at a loading dose of 400 mg/m<sup>2…

The prevalent KRAS exon 2 c.35 G > A mutation in metastatic colorectal cancer patients: a biomarker of worse prognosis and potential benefit of bevac…

2015

Bevacizumab-containing chemotherapy differently predict increased efficacy in KRAS exon 2 mutant and wild-type metastatic colorectal cancer (MCRC) patients. Mutant compared to wild-type status did not significantly affect progression-free survival (PFS) and overall survival (OS) in patients fit for first line bevacizumab-containing FIr-B/FOx regimen, and after progression. In patients unfit for intensive regimens, mutant status significantly affected PFS, while not OS. Codon 12 KRAS mutations differentially affect GTPase function, and confer worse clinical behaviour. Prognostic relevance of the prevalent c.35 G. >. A KRAS mutation was retrospectively evaluated. Fit c.35 G. >. A mutant patie…

1,2,4-Amino-triazine derivatives as pyruvate dehydrogenase kinase inhibitors: Synthesis and pharmacological evaluation

2023

: Among the different hallmarks of cancer, deregulation of cellular metabolism turned out to be an essential mechanism in promoting cancer resistance and progression. The pyruvate dehydrogenase kinases (PDKs) are well known as key regulators in cells metabolic process and their activity was found to be overexpressed in different metabolic alerted types of cancer, including the high aggressive pancreatic ductal adenocarcinoma (PDAC). To date few PDK inhibitors have been reported, and the different molecules developed are characterized by structural chemical diversity. In an attempt to find novel classes of potential PDK inhibitors, the molecular hybridization approach, which combine two or m…

Zvaigžņotā Debess: 2009, Pavasaris (203)

2009

Contents: E.R.Mustel, President of the Astronomical Council of the USSR Academy of Sciences. Congratulations to Editorial Board of “Zvaigžņotā debess” ; Z.Alksne. Gould’s Belt ; I.Daube. At the Radioastrophysical Observatory of the Latvian Academy of Sciences ; Z.Alksne, A.Alksnis. Lopsided Galaxies ; A.Alksnis. HII Region Gum 29 – a Stellar Nursery ; D.Docenko. On Collision of Asteroid 2008 TC3 with the Earth ; V.Lapoška. On „Leap Second” ; I.Vilks, M.Gills. Beginning of the International Year of Astronomy in Paris: Impressions by Latvian Delegates ; J.Jaunbergs. Equatorial Ridge on Iapetus ; M.Sudārs. Space Shuttle Is Not Likely to Retire Next Year ; I.Vilks. Planet Satellite Names in Lat…

The Long and Winding Road to Useful Predictive Factors for Anti-EGFR Therapy in Metastatic Colorectal Carcinoma: The KRAS/BRAF Pathway

2010

Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with metastatic colorectal carcinoma. Among patients not carrying activating mutations in the KRAS gene, only a limited number will experience tumor response to these therapeutic agents. The role of BRAF mutations in determining resistance to this treatment is emerging through preclinical and clinical studies. Standardization and validation of laboratory mutation analysis is needed to allow an optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Clinical single-arm and randomized studies were conducted both in first-line and refractory settings to evaluate…

Latvijas arheologu atskaites sesija par 2016.-2017.gada izrakumu rezultātiem: referātu tēzes

2018

Admissible perturbations of alpha-psi-pseudocontractive operators: convergence theorems

2015

In the last decades, the study of convergence of fixed point iterative methods has received an increasing attention, due to their performance as tools for solving numerical problems. As a consequence of this fact, one can access to a wide literature on iterative schemes involving different types of operators; see [2, 4, 5]. We point out that fixed point iterative approximation methods have been largely applied in dealing with stability and convergence problems; see [1, 6]. In particular, we refer to various control and optimization questions arising in pure and applied sciences involving dynamical systems, where the problem in study can be easily arranged as a fixed point problem. Then, we …

Application of the LISS Lyapunov-Krasovskii small-gain theorem to autonomously controlled production networks with time-delays

2010

Accepted version of a paper published by IEEE. (c) 2010 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works Published version: http://dx.doi.org/10.1109/SYSTOL.2010.5676085 In this paper we consider general autonomously controlled production networks. A production network consists of geographically distributed plants, which are connected by transport routes such that transportation times (time-delays) …

Kultūrvēsturisko pilsētbūvniecības ansambļu saglabāšana: Slokas centra piemērs

2018

Sloka pēdējās desmitgadēs ir piedzīvojusi nopietnas sociālas izmaiņas ar ietekmi uz tās pilsētvidi. Mūsdienu situācija, atrodoties Jūrmalas pilsētas nomalē, ne vienmēr ir labvēlīga, lai tajā arī turpmāk varētu būt nozīmīgi pakalpojumu centri un pastāvīgajiem iedzīvotājiem paredzēts dzīvojamais fonds, dzīvojamā apkaime. Vietizpētei izvēlētais Slokas centrs piesaista ar tajā vēl joprojām esošajām un saskatāmajām pilsētvides vērtībām: cilvēku vajadzībām un ģeogrāfiskajam novietojumam atbilstošu un plānotu vidi, publiski pieejamu Lielupes krastmalu. Darbā sniegta šī brīža situācijas dokumentācija un analīze, veidots salīdzinājums ar līdzīgiem apdzīvotu vietu piemēriem, lai parādītu, ka arī šāda…