Vectibix® (panitumumab) is a FDA approved drug (BLA-125147) indicated as a single agent for the treatment of EGFR-expressing metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy regimens. Approval is based on progression-free survival; no data demonstrate an improvement in disease-related symptoms or increased survival.. DRUG DESCRIPTION Vectibix® (panitumumab) is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). Panitumumab has an approximate molecular weight of 147 kDa. Panitumumab is produced in genetically engineered mammalian (Chinese Hamster Ovary) cells.. Panitumumab will be given on this study at 6 mg/kg, IV over 1 hr ...
Any continuous-dosing (i.e. daily dosing, every-other-day dosing, Monday-Wednesday-Friday dosing, weekly etc.) of systemic anti-cancer treatment for which the recover period is not known, or investigational drugs (i.e. targeted agents) within a duration of ≤ 5 half lives of the agent and their active metabolites (if any ...
Purpose: Although cetuximab, an anti-EGF receptor (EGFR) monoclonal antibody, is an effective treatment for patients with KRAS wild-type metastatic colorectal cancer (mCRC), its clinical use is limited by onset of resistance.. Experimental Design: We characterized two colorectal cancer models to study the mechanisms of acquired resistance to cetuximab.. Results: Following chronic treatment of nude mice bearing cetuximab-sensitive human GEO colon xenografts, cetuximab-resistant GEO (GEO-CR) cells were obtained. In GEO-CR cells, proliferation and survival signals were constitutively active despite EGFR inhibition by cetuximab treatment. Whole gene expression profiling identified a series of genes involved in the hepatocyte growth factor (HGF)-MET-dependent pathways, which were upregulated in GEO-CR cells. Furthermore, activated, phosphorylated MET was detected in GEO-CR cells. A second colorectal cancer cell line with acquired resistance to cetuximab was obtained (SW48-CR). Inhibition of MET ...
This study investigated the efficacy and tolerability of gimeracil/oteracil/tegafur + cetuximab + irinotecan in patients with KRAS wild-type metastatic
Merck Serono, a division of Merck KGaA,Darmstadt,Germany has announced that new data presented today at the 35th Congressof the European Society for Medical Oncology (ESMO) have shown that patients with KRAS wild-type metastatic colorectal cancer (mCRC) who experienced early tumor shrinkage (within 8 weeks) during 1st line Erbitux® (cetuximab) based treatment lived a median of […]. ...
Thank you for sharing this Molecular and Cellular Biology article.. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.. ...
Somatic genetic mutation in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene has been linked to poor prognosis and resistance to various targeted therapeutics in Non Small Cell Lung Cancer (NSCLC). Therapeutic strategies that target tumors harboring these mutations represent an unmet medical need. In this study, we investigated the relationship between antifolate sensitivity and KRAS mutation/amplification status in NSCLC.. Human NSCLC cell lines (KRAS wild type, KRAS mutant non-amplified and KRAS mutant amplified) were treated with Methotrexate (MTX) or Pemetrexed (PEM) and assayed for proliferation after 72h. In these studies, 5 out of 7 KRASwt (wildtype) cells and all KRASmut (mutant) amplified cells showed resistance to MTX treatment (IC50 ,10μM). In contrast, growth of all KRASmut non-amplified cell lines studied was inhibited with MTX treatment (IC50 ,100nM). Similar effects were observed for PEM in this study. Interrogation of the NCI Developmental Therapeutics ...
Design To show a HR advantage of 0.6 in progression-free survival (PFS) for FCGR2A-HH versus the rest and FCGR3A-VV versus the rest, with an 80% power, 80 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type (KRAS-WT) and 52 KRAS-WT patients are required, respectively. This leads to a total sample size of 952 and 619 patients, respectively. Samples were collected from 1123 mCRC patients from 15 European centres treated with cetuximab alone or in combination with chemotherapy. Fc gamma receptor (FCGR) status was centrally genotyped. Two additional externally genotyped series were included. ...
KRAS - KRAS mutant (Q61R), Myc-DDK-tagged ORF clone of Homo sapiens v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), transcript variant b as transfection-ready DNA available for purchase from OriGene - Your Gene Company.
Ras is a family of related proteins which is expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells (cellular signal transduction). Ras is the prototypical member of the Ras superfamily of proteins, which are all related in 3D structure and regulate diverse cell behaviours. When Ras is switched on by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation and survival. Mutations in ras genes can lead to the production of permanently activated Ras proteins. As a result, this can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. The 3 Ras genes in humans (HRas, KRas, and NRas) are the most common oncogenes in human cancer; ...
Kras: | |GTPase KRas| also known as |V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog| a... World Heritage Encyclopedia, the aggregation of the largest online encyclopedias available, and the most definitive collection ever assembled.
The morphological features of tumors are closely related to their growth patterns [8]. Polypoid tumors are believed to exhibit a predominantly vertical growth pattern, rather than a horizontal growth pattern, while non-polypoid tumors are believed to exhibit the opposite pattern, resulting in horizontal growth. Although there are some reports that LSTs have distinct biological characteristics compared to polypoid tumors [9, 10], the mechanism by which the LST conformation is generated remains unknown.. LSTs are believed to have distinct characteristics in terms of histological and genetic features [11]. Several molecular characteristics of LSTs have been described, including alteration of the adenomatous polyposis coli (APC) gene or β-catenin [12-14] affecting the WNT/APC/β-catenin signaling pathway, mutation of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) [12, 15-20]. However, the molecular background of LSTs has remained largely unknown [19, 21]. Most of these studies have ...
TY - JOUR. T1 - Sensitivity of wild type and mutant ras alleles to Ras specific exchange factors. T2 - Identification of factor specific requirements. AU - Nielsen, Klaus Hvid. AU - Gredsted, Lars. AU - Broach, James R.. AU - Willumsen, Berthe Marie. PY - 2001/4/19. Y1 - 2001/4/19. N2 - We have investigated the productive interaction between the four mammalian Ras proteins (H-, N-, KA- and KB-Ras) and their activators, the mammalian exchange factors mSos1, GRF1 and GRP, by using a modified Saccharomyces cerevisiae whose growth is dependent on activation of a mammalian Ras protein by its activator. All four mammalian Ras proteins were activated with similar efficiencies by the individual exchange factors. The H-Ras mutant V103E, which is competent for membrane localization, nucleotide binding, intrinsic and stimulated GTPase activity as well as intrinsic exchange, was defective for activation by all factors tested, suggesting that the integrity of this residue is necessary for catalyzed exchange. ...
Determination of fatty acid acquisition routes in an isogenic model with either Akt or Ras pathway activation demonstrated that Akt induces de novo fatty acid synthesis, whereas Ras decreases it. This was most evident for the mono-unsaturated fatty acid oleate (C18:1), of which 96% was produced de novo in Akt-driven cells but only 57% in Ras-driven cells. We confirmed that Akt pathway activation leads to elevated levels of stearoyl-CoA desaturase 1 (SCD1), a key enzyme in the synthesis of oleate, and that Ras pathway activation leads to increased uptake of exogenous lipids. We hypothesized that SCD1 inhibition would therefore be particularly toxic to the Akt-driven cells. We confirmed that Akt activated cells were significantly more sensitive to SCD1 inhibition than those with Ras activation. Growth of Ras-driven cells was unaffected by SCD1 inhibition for multiple doublings, after which the cells stopped growing. We found that growth inhibition coincided with depletion of lysolipids in the ...
Cellular signaling downstream of Ras is highly diversified and may involve many different effector molecules. A potential candidate is AF6 which was originally identified as a fusion to ALL-1 in acute myeloid leukemia. In the present work the interaction between Ras and AF6 is characterized and compared with other effectors. The binding characteristics are quite similar to Raf and RalGEF, i.e. nucleotide dissociation as well as GTPase-activating protein activity are inhibited, whereas the intrinsic GTPase activity of Ras is unperturbed by AF6 binding. Particularly, the dynamics of interaction are similar to Raf and RalGEF with a lifetime of the Ras. AF6 complex in the millisecond range. As probed by 31P NMR spectroscopy one of two major conformational states of Ras is stabilized by the interaction with AF6. Looking at the affinities of AF6 to a number of Ras mutants in the effector region, a specificity profile emerges distinct from that of other effector molecules. This finding may be useful in ...
The RAS/ERK pathway has been intensely studied for about three decades, not least because of its role in human pathologies. ERK activation is observed in the majority of human cancers; in about one-third of them, it is driven by mutational activation of pathway components. The pathway is arguably one of the best targets for molecule-based pharmacological intervention, and several small-molecule inhibitors are in clinical use. Genetically engineered mouse models have greatly contributed to our understanding of signaling pathways in development, tissue homeostasis, and disease. In the specific case of the RAS/ERK pathway, they have revealed unique biological roles of structurally and functionally similar proteins, new kinase-independent effectors, and unsuspected relationships with other cascades. This short review summarizes the contribution of mouse models to our current understanding of the pathway. ...
Alternative Name. HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog; HRAS1; GTPase HRas; p21ras; H-Ras- 1; p19 H-RasIDX protein; c-has/bas p21 protein; transforming protein p21; Ha-Ras1 proto-oncoprotein; c-ras-Ki-2 activated oncogene; GTP- and GDP-binding peptide B; transformation gene: oncogene HAMSV; Ras family small GTP binding protein H-Ras; CTLO; HAMSV; K-RAS; N-RAS; RASH1; C-HRAS; H-RASIDX; C-BAS/HAS; C-HA-RAS1;. ...
Alternative Name. HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog; HRAS1; GTPase HRas; p21ras; H-Ras- 1; p19 H-RasIDX protein; c-has/bas p21 protein; transforming protein p21; Ha-Ras1 proto-oncoprotein; c-ras-Ki-2 activated oncogene; GTP- and GDP-binding peptide B; transformation gene: oncogene HAMSV; Ras family small GTP binding protein H-Ras; CTLO; HAMSV; K-RAS; N-RAS; RASH1; C-HRAS; H-RASIDX; C-BAS/HAS; C-HA-RAS1;. ...
Ras proteins are members of a superfamily of small GTPases that are involved in many aspects of cell growth control. The ras p21 protooncogene products, H-ras, K-ras, and N-ras, transmit signals from growth factor receptors to a cascade of protein kinases that begins with the Raf protooncogene product, and leads to alterations in transcription factors and cell cycle proteins in the nucleus. This cascade is controlled at several points: Ras p21 proteins are regulated by GAPs and by exchange factors, whose activities are altered by growth factor receptor activation (Boguski and McCormick, 1993: Nature 366:643-654). Transmission of signals from Ras to Raf is regulated by the Ras-related protein Rap1 (a protein capable of reverting cell transformation) and by cAMP. Other aspects of Ras p21 regulation will be discussed, including the existence of RasGDl proteins that inhibit GDP dissociation from Ras, and may thus regulate the level of active Ras in the cell. The role of Ras in activation of Raf ...
Standard faecal occult blood testing for colorectal cancer has the benefit of being non-invasive, however, there are problems with sensitivity (tumours may bleed intermittently or not at all) and specificity. Since DNA is continuously released into the faecal stream there is potential for developing new screening tests to detect mutations in tumour DNA. KRAS mutations in tumours can be detected in stools some patients with colorectal cancer. Detection of KRAS mutations alone may be limited as theses occur in less than half of all colorectal cancers and may occur in pancreatic hyperplasia and other non-malignant conditions. However, research into developing tests for multiple DNA alterations, including KRAS, may offer great potential for new non-invasive screening for colorectal cancer with high levels of sensitivity and specificity ...
The mutant forms of KRas, NRas and HRas drive the initiation and progression of a number of human cancers, but less is known about the role of WT (wild-type) Ras alleles and isoforms in cancer. We used zinc-finger nucleases targeting HRas and NRas to modify both alleles of these genes in the mutant KRas-driven Hec1A endometrial cancer cell line, which normally expresses WT copies of these genes. The disruption of either WT isoform of Ras compromised growth-factor-dependent signalling through the ERK (extracellular-signal-regulated kinase) pathway. In addition, the disruption of HRas hindered the activation of Akt and subsequent downstream signalling. This was associated with decreased proliferation, increased apoptosis and decreased anchorage-independent growth in the HRas-disrupted cells. However, xenograft tumour growth was not significantly affected by the disruption of either NRas or HRas. As expected, deleting the mutant allele of KRas abolished tumour growth, whereas deletion of the ...
Why is it so difficult to design a drug for RAS? Well, RAS proteins are small GTPases that cycle between an "on" state when bound to a small intracellular molecule called GTP, and an "off" state when GTP is hydrolyzed to GDP. When RAS is "on", it is communicating with a multitude of downstream proteins that drive cellular proliferation and survival - two key functions that are necessary for normal cell growth, but must be tightly regulated. However, when RAS is mutated, it is chronically bound to GTP and in the "on" state. This hyperactive mutant RAS signaling promotes tumor initiation and maintenance, and it allows these corrupted cells to continue proliferating under conditions of DNA damage and metabolic stress. Researchers have attempted to design small molecules that disrupt GTP binding and inhibit activation of RAS, but because the affinity of RAS for GTP is so strong, so far, it has been impossible to generate a compound that can inhibit GTP-binding and RAS signaling.. To circumvent the ...
This trial investigated the efficacy and tolerability of cetuximab + irinotecan + S 1 as a first-line treatment in patients with KRAS wild-type metastatic
Certain KRAS gene mutations are often present in patients with colon, lung and pancreas cancer. Therapeutic antibodies Erbitux® and Vectibix ® are only effective treatment options in patients without KRAS gene mutations. This poster describes how compact sequencing technology can be used as a fast and cost effective alternative to established PCR methods.
UT Southwestern Medical Center cancer researchers have found a molecule that selectively and irreversibly interferes with the activity of a mutated cancer gene common in 30 percent of tumors.
Technology Networks is an internationally recognised publisher that provides access to the latest scientific news, products, research, videos and posters.
The catalytic p110 subunits of class 1 phosphoinositide 3-kinases (PI3Ks) have a conserved Ras binding domain (RBD), and an interaction has been noted between Ras guanosine triphosphatase (GTPase) and p110 PI3K in vitro and in overexpression systems. However, the biological relevance of this putative regulatory input has been unclear. Two groups now report a physiological role for Ras interactions with PI3K in flies and mouse neutrophils. Orme et al. created transgenic flies carrying a Dp110 (the only Drosophila p110) with mutations in the RBD that did not interact with Ras (either Ras1 or Ras2) but was otherwise biochemically normal. This Dp110RBD rescued flies from lethal deletion of Dp110; however, the rescued flies were smaller and females exhibited reduced fecundity, laying 60% fewer eggs. Dp110RBD flies also had decreased activation of Akt in response to insulin in the brain and imaginal discs and decreased basal Akt activation in the ovaries. Although the interaction with Ras does not ...
Background Receptor tyrosine kinases (RTKs) participate in a multitude of signaling pathways, some of them via the small G-protein Ras. An important component in the activation of Ras is Son of sevenless (SOS), which catalyzes the nucleotide exchange on Ras. Principal Findings We can now demonstrate that the activation of Ras requires, in addition, the essential participation of ezrin, radixin and/or moesin (ERM), a family of actin-binding proteins, and of actin. Disrupting either the interaction of the ERM proteins with co-receptors, down-regulation of ERM proteins by siRNA, expression of dominant-negative mutants of the ERM proteins or disruption of F-actin, abolishes growth factor-induced Ras activation. Ezrin/actin catalyzes the formation of a multiprotein complex consisting of RTK, co-receptor, Grb2, SOS and Ras. We also identify binding sites for both Ras and SOS on ezrin; mutations of these binding sites destroy the interactions and inhibit Ras activation. Finally, we show that the formation of
Large-scale tumor DNA sequencing campaigns have shown that activating RAS mutations are among the most common drivers of cancer. It is, therefore, not surprising that RAS sits at the epicenter of multiple signal transduction pathways that control cell survival and growth. A primary working hypothesis in our lab is that not all RAS mutations function in the same way and that mutation-specific tailored strategies will be required. To this end we are determined to characterize and understand the unique properties of specific mutant RAS isoforms. So far our work has shed new light on how KRAS G13D, a major cause of colorectal cancer, becomes activated and provided rationalle for new treatment strategies to address other RAS mutations (MCR, 2015). In a related effort we are developing small molecule inhibitors for KRAS G12C, the most common RAS mutation in lung cancer. RAS signaling is contingent upon RAS binding to GTP. Designing small-molecules that compete for the GTP-binding site may seem like an ...
Buy Dabur Ras-Rasayan with Gold and Pearl - Chaturmukh Ras, Jaimangal Ras, Mahalaxmivilas Ras, Vrihat Purnachandra Ras, Yogendra Ras.
Here, we have shown that altering the function of Gab1 and SHP-2 modulates the levels of active Ras/MAPK in epidermal cells in association with changes in growth and differentiation. Differentiation induced by dominant-negative Gab1 and SHP-2 mutants is abolished by active Ras, indicating that Gab1/SHP-2 actions in this process may reside upstream of Ras, consistent with prior biochemical data (Itoh et al., 2000; Shi et al., 2000; Cunnick et al., 2002). Duration of MAPK signaling is important in generating different biologic outcomes, but major cell type differences exist in signaling by Ras and its effectors (Shields et al., 2000). We observed that Gab1 and SHP-2 overexpression prolong the persistence of active epidermal MAPK in response to EGF stimulation, consonant with prior observations in fibroblasts and transformed cell lines. However, dominant-negative Gab1 and SHP-2 fail to block MAPK induction in response to strong EGF stimulation, underscoring the contribution of other elements such ...
More than 30% of all human cancers contain activating mutations of the small G‐protein RAS. As a result of this, RAS has been intensely studied and many efforts have been made to identify pathways that sustain RAS‐driven transformation [1]. Recent studies have indicated that the transcription factor GATA2 is one of these partners in crime, but a mechanistic link between RAS and GATA2 had not been identified [2]. A paper in this issue of EMBO reports closes this gap showing that GATA2 can be activated by p38 in RAS‐transformed cells [3].. See also: KR Katsumara et al (September 2014) ...
Purpose KRAS oncogene testing is recommended in all patients with metastatic colorectal cancer due to its impact on treatment selection, but we do not know if KRAS genotype affects extent or pattern...
KRAS gene mutations have long been known to cause cancer, and about one in three of solid tumours have KRAS mutations or mutations in the KRAS pathway.
A Ras homolog member I (ARHI). ARHI (A Ras homolog member I) is a member of the Ras family with several unique structural and functional properties. ARHI is expressed in normal human ovarian and breast tissue, but its expression is decreased or eliminated in breast and ovarian cancer. ARHI contains an N-terminal extension of 34 residues (human) that is required to retain its tumor suppressive activity. Unlike most other Ras family members, ARHI is maintained in the constitutively active (GTP-bound) state in resting cells and has modest GTPase activity. ARHI inhibits STAT3 (signal transducers and activators of transcription 3), a latent transcription factor whose abnormal activation plays a critical role in oncogenesis. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of ...
Oncogenic activation of RAS isoforms by mutation is a highly recurrent phenomenon in human tumors. Although mutant RAS is an attractive target for therapy, efforts to develop pharmacologic inhibitors have thus far been unsuccessful. This has led to efforts focused on inhibiting KRAS-dependent transformation by targeting downstream effector pathways. Although more than 10 families of RAS effector proteins have been identified (4), there is strong evidence that at least three of these, the RAF, PI3K, and the RAL exchange factors, play predominant roles in mediating its transforming effects (5-8). This suggests that multiple effector pathways downstream of RAS must be blocked to achieve a therapeutic effect. Indeed, recent research has identified that dual inhibition of both the MEK (downstream of RAF) and PI3K kinase effector pathways is essential to cause the regression of genetically engineered KRAS mutant tumors in mice (18). However, in human cancer cell lines, our results show that at least a ...
Complete information for RRAS2 gene (Protein Coding), RAS Related 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for RRAS gene (Protein Coding), RAS Related, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Vascular networks develop from a growing vascular front that responds to VEGF and other guidance cues. Angiogenesis is required for normal tissue function, but, under conditions of stress, inappropriate vascularization can lead to disease. Therefore, inhibition of angiogenic sprouting may prevent neovascularization in patients with blinding neovascular eye diseases, including macular degeneration. VEGF antagonists have therapeutic benefits but also can elicit off-target effects. Here, we found that the Ras pathway, which functions downstream of a wide range of cytokines including VEGF, is active in the growing vascular front of developing and pathological vascular networks. The endogenous Ras inhibitor p120RasGAP was expressed predominately in quiescent VEGF-insensitive endothelial cells and was ectopically downregulated in multiple neovascular models. MicroRNA-132 negatively regulated p120RasGAP expression. Experimental delivery of α-miR-132 to developing mouse eyes disrupted tip cell Ras ...
Results: Of the 66 pts, 41 (62%) pts had wild-type (WT) KRAS and 25 (38%) pts harbored a KRAS mutation (codon 12 & 13). In the mutant KRAS group, 6 pts had SD (24%) and 19 pts had PD (76%) as their best OR; there were no responses. In the WT KRAS population, the PR rate was 12% (95% CI: 2 to 22), the SD rate was 54% (95% CI: 38 to 69), and the PD rate was 34% (95% CI: 20 to 49). The association between KRAS mutation status and lack of response to panitumumab was statistically significant (Fishers exact test, p = 0.003). From a Cox PH model, the hazard ratio for WT:mutant KRAS was 0.6 (95% CI: 0.34 to 0.95) for PFS and 0.5 (95% CI: 0.29 to 0.91) for OS. ...
SAN DIEGO, July 3, 2012 /PRNewswire/ -- Trovagene to Study Trans-Renal KRAS Mutation Detection in Pancreatic Cancer. Study will compare detection of KRAS...
SUKHDARSHAN PHARMACY PVT. LTD. - Manufacturer of Giloy Papita Ras in Rai Industrial, Sonipat, Haryana, India. Get deals on Giloy Papita Ras at Tradeindia.
This gene encodes a member of the Ras family of small GTPases. These membrane-associated proteins function as signal transducers in multiple processes including cell growth and differentiation, and dysregulation of Ras signaling has been associated with many types of cancer. The encoded protein may play a role in the tumor necrosis factor-alpha and MAP kinase signaling pathways. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011 ...
Of the three ras genes, kras is most frequently mutated in human cancer. Ras proteins are highly homologous but differ extensively in their C-terminal hypervari...
Interestingly, in a third category of models, ERK reactivation was minimal but viability was still unaffected suggesting that ERK activity is uncoupled from viability control in these cells.. Overall, we observe a range of effects of KRAS G12C inhibition on downstream signaling dynamics and the change in major downstream signals observed are not sufficient to explain the viability outcome. While KRAS has been shown to activate PI3K at least is some contexts, ARS1620-driven loss of KRAS-GTP resulted in suppression of p-AKT only in 3 of 12 cell lines studied (LU65, NCI-H358, and NCI-H23). Thus, we show that the PI3K pathway is not under the sole control of mutant KRAS in KRAS G12C NSCLC models, and perhaps tumors, as shown previously in colorectal models (22).. Overall, these results suggest that KRAS does not uniformly control prosurvival signals across KRAS G12C cell lines. To more finely resolve the dynamic signaling response throughout the pathway, we used densitometry quantification across ...
The RAS oncogene is the most elusive cancer therapy target yet identified. Mutant KRAS (mut-KRAS) is the predominant oncogenic form of RAS, and is present in 17...
BIOC Biocept Inc Biocepts Target Selector™ ctDNA Platform Demonstrates Single Copy Detection for EGFR, BRAF, and KRAS Mutations; Study Resu...
(2013) Schokoroy et al. PLoS ONE. Background:The ErbB receptors, Ras proteins and nucleolin are major contributors to malignant transformation. The pleiotropic protein nucleolin can bind to both Ras protein and ErbB receptors. Previously, we have demonstrated a crosstalk between Ras, nucleolin an...
If you engineer chemical differences in what you think are important regions of a protein, you can determine how vital these regions really are to the function of the protein," Adams said. "This allows you to determine the important aspects of proteins that need to be targeted for therapeutic purposes.". The first new study will be based on a finding in Adams laboratory - that a single mutation in the Ras protein decreases the flexibility of an important interaction. The new study will focus on simple experiments to determine how the decreased flexibility interferes with the proteins ability to do its job. "We made a mutation in an important region of our Ras protein known to be vital for the proper interaction of cell signaling regulatory proteins, and the mutation seemed to reduce the flexibility of the protein," Adams said. "We have preliminary data that shows that this one mutation causes a decrease in an important protein-protein interaction," one that interferes with the proteins ...
Exclusive to Global Medical Discovery (new Significance Statement and figure). Ras regulates SCF-beta-TrCP activity and specificity via its effector NORE1A