keyword
MENU ▼
Read by QxMD icon Read
search

K-ras

keyword
https://www.readbyqxmd.com/read/29163826/hdac-inhibitors-enhance-neratinib-activity-and-when-combined-enhance-the-actions-of-an-anti-pd-1-immunomodulatory-antibody-in-vivo
#1
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134654/pten-loss-and-activation-of-k-ras-and-%C3%AE-catenin-cooperate-to-accelerate-prostate-tumourigenesis
#2
Matthew T Jefferies, Adam C Cox, Boris Y Shorning, Valerie Meniel, David Griffiths, Howard G Kynaston, Matthew J Smalley, Alan R Clarke
Aberrant phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) and WNT signalling are emerging as key events in the multistep nature of prostate tumourigenesis and progression. Here, we report a compound prostate cancer murine model in which these signalling pathways cooperate to produce a more aggressive prostate cancer phenotype. Using Cre-LoxP technology and the probasin promoter, we combined the loss of Pten (Pten(fl/fl) ), to activate the PI3K signalling pathway, with either dominant stabilized β-catenin [Catnb(+/lox(ex3)) ] or activated K-RAS (K-Ras(+/V12) ) to aberrantly activate WNT and MAPK signalling, respectively...
December 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29133460/elevated-hur-in-pancreas-promotes-a-pancreatitis-like-inflammatory-microenvironment-that-facilitates-tumor-development
#3
Weidan Peng, Narumi Furuuchi, Ludmila Aslanukova, Yu-Hung Huang, Samantha Z Brown, Wei Jiang, Sankar Addya, Vikalp Vishwakarma, Erika Peters, Jonathan R Brody, Dan A Dixon, Janet A Sawicki
Human antigen R (ELAVL1, HuR) is perhaps the best-characterized RNA-binding protein. Through its overexpression in various tumor types, HuR promotes post-transcriptional regulation of target genes in multiple core signaling pathways associated with tumor progression. The role of HuR overexpression in pancreatic tumorigenesis is unknown and led us to explore the consequences of HuR overexpression using a novel transgenic mouse model that has a >2-fold elevation of pancreatic HuR expression. Histologically, HuR overexpressing pancreas displays a fibro-inflammatory response and other pathological features characteristic of chronic pancreatitis...
November 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29129563/da-raf-a-dominant-negative-antagonist-of-the-ras-erk-pathway-is-a-putative-tumor-suppressor
#4
Emiri Kanno, Osamu Kawasaki, Kazuya Takahashi, Kazunori Takano, Takeshi Endo
Activating mutations of RAS genes, particularly KRAS, are detected with high frequency in human tumors. Mutated Ras proteins constitutively activate the ERK pathway (Raf-MEK-ERK phosphorylation cascade), leading to cellular transformation and tumorigenesis. DA-Raf1 (DA-Raf) is a splicing variant of A-Raf and contains the Ras-binding domain (RBD) but lacks the kinase domain. Accordingly, DA-Raf antagonizes the Ras-ERK pathway in a dominant-negative fashion and suppresses constitutively activated K-Ras-induced cellular transformation...
November 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29126425/hdac7-promotes-lung-tumorigenesis-by-inhibiting-stat3-activation
#5
Yubin Lei, Lingling Liu, Shujing Zhang, Shicheng Guo, Xiaoqing Li, Jiucun Wang, Bo Su, Yuchao Fang, Xiaofeng Chen, Hengning Ke, Wufan Tao
BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. However, the molecular mechanisms underlying lung cancer development have not been fully understood. The functions of histone deacetylases (HDACs), a class of total eighteen proteins (HDAC1-11 and SIRT1-7 in mammals) that deacetylate histones and non-histone proteins, in cancers are largely unknown. METHODS: Hdac7 (+/-)/K-Ras mice and HDAC7-depleted human lung cancer cell lines were used as models for studying the function of Hdac7 gene in lung cancer...
November 10, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29120102/deciphering-lipid-codes-k-ras-as-a-paradigm
#6
REVIEW
Yong Zhou, John F Hancock
The cell plasma membrane (PM) is a highly dynamic and heterogeneous lipid environment, driven by complex hydrophobic and electrostatic interactions among the hundreds of types of lipid species. Although the biophysical processes governing lipid lateral segregation in the cell PM have been established in vitro, biological implications of lipid heterogeneity are poorly understood. Of particular interest is how membrane proteins potentially utilize transient spatial clustering of PM lipids to regulate function...
November 9, 2017: Traffic
https://www.readbyqxmd.com/read/29119228/macropinocytosis-mtorc1-and-cellular-growth-control
#7
REVIEW
Sei Yoshida, Regina Pacitto, Ken Inoki, Joel Swanson
The growth and proliferation of metazoan cells are driven by cellular nutrient status and by extracellular growth factors. Growth factor receptors on cell surfaces initiate biochemical signals that increase anabolic metabolism and macropinocytosis, an actin-dependent endocytic process in which relatively large volumes of extracellular solutes and nutrients are internalized and delivered efficiently into lysosomes. Macropinocytosis is prominent in many kinds of cancer cells, and supports the growth of cells transformed by oncogenic K-Ras...
November 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29118162/does-mutated-k-ras-oncogene-attenuate-the-effect-of-sulindac-in-colon-cancer-chemoprevention
#8
Photini F S Rice, Kevin G Ehrichs, Mykella S Jones, Hwudarw Chen, Chiu-Hsieh Hsu, Edward R Abril, Raymond B Nagle, David G Besselsen, Jennifer K Barton, Natalia A Ignatenko
The non-steroidal anti-inflammatory drug (NSAID) Sulindac has been successfully used alone or in combination with other agents to suppress colon tumorigenesis in patients with genetic predisposition, and also showed its efficacy in prevention of sporadic colon adenomas. At the same time, some experimental and clinical reports suggest that a mutant K-RAS oncogene may negate Sulindac anti-tumor efficacy. To directly assess Sulindac activity at suppressing premalignant lesions carrying K-RAS mutation, we utilized a novel mouse model with an inducible colon-specific expression of the mutant K-ras oncogene (K-ras G12D)...
November 8, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29104470/critical-role-of-p53-and-k-ras-in-the-diagnosis-of-early-colorectal-cancer-a-one-year-single-center-analysis
#9
Hui-Ying Lu, Ri-Tian Lin, Guang-Xi Zhou, Tian-Ming Yu, Zhan-Ju Liu
Background: Colorectal cancer (CRC) is strongly associated with colorectal polyps, which has become the third most common cancer in China. In the present study, we revealed the susceptible population and risk factors of colorectal polyps, and analyzed the expression of Ki-67, p53 and K-ras in the intestinal mucosa of patients with colorectal polyps in order to explore their significance in the detection and prognosis of CRC at an early stage. Materials and Methods: Total 801 cases of colorectal polyps were collected during endoscopic resection including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD)...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29090098/akt1-and-akt3-but-not-akt2-through-interaction-with-dna-pkcs-stimulate-proliferation-and-post-irradiation-cell-survival-of-k-ras-mutated-cancer-cells
#10
Mahmoud Toulany, Julia Maier, Mari Iida, Simone Rebholz, Marina Holler, Astrid Grottke, Manfred Jüker, Deric L Wheeler, Ulrich Rothbauer, H Peter Rodemann
Akt1 through the C-terminal domain interacts with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and stimulates the repair of DNA double-strand breaks (DSBs) in K-RAS-mutated (K-RASmut) cells. We investigated the interactions of distinct domain(s) of DNA-PKcs in binding to full-length Akt1. Similarly, we analyzed potential interactions of DNA-PKcs with Akt2 and Akt3. Finally the effect of Akt isoforms in cell proliferation and tumor growth was tested. We demonstrated that Akt1 preferentially binds to the N-terminal domain of DNA-PKcs using pull-down studies with distinct eGFP-tagged DNA-PKcs fragments that were expressed by plasmids in combination with mCherry-tagged full-length Akt isoforms...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29059163/molecular-genetics-and-cellular-events-of-k-ras-driven-tumorigenesis
#11
REVIEW
G G Jinesh, V Sambandam, S Vijayaraghavan, K Balaji, S Mukherjee
Cellular transformation and the accumulation of genomic instability are the two key events required for tumorigenesis. K-Ras (Kirsten-rat sarcoma viral oncogene homolog) is a prominent oncogene that has been proven to drive tumorigenesis. K-Ras also modulates numerous genetic regulatory mechanisms and forms a large tumorigenesis network. In this review, we track the genetic aspects of K-Ras signaling networks and assemble the sequence of cellular events that constitute the tumorigenesis process, such as regulation of K-Ras expression (which is influenced by miRNA, small nucleolar RNA and lncRNA), activation of K-Ras (mutations), generation of reactive oxygen species (ROS), induction of DNA damage and apoptosis, induction of DNA damage repair pathways and ROS detoxification systems, cellular transformation after apoptosis by the blebbishield emergency program and the accumulation of genomic/chromosomal instability that leads to tumorigenesis...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29042709/derivation-and-basic-characterization-of-colorectal-carcinoma-primary-cell-lines
#12
Lukas Krbal, Jiri Soukup, Stanislav John, Veronika Hanusova
BACKGROUND: Colorectal carcinoma is one of the most common malignancies in western countries. Among different approaches to its research, primary cancer cell lines can play an important role. AIM: The main purposes of this study were: 1) to establish an effective and reproducible method of colorectal cancer cell isolation and cultivation from primary tumours and lymph node metastases and 2) to elucidate the biological features of the tumours favouring successful cell cultivation...
October 17, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/29040282/colorectal-carcinoma-tumour-budding-and-podia-formation-in-the-xenograft-microenvironment
#13
Friedrich Prall, Claudia Maletzki, Maja Hühns, Mathias Krohn, Michael Linnebacher
Tumour budding and podia formation are well-appreciated in surgical pathology as an aggressive invasion phenotype of colorectal carcinoma cells that is attained in the microenvironment of the invasive margin. In this study, we addressed how tumour budding and podia formation feature in xenografts. Primary colorectal carcinomas (N = 44) of various molecular types (sporadic standard type, high-degree microsatellite-unstable, CpG island methylator phenotype) were transplanted subcutaneously into T and B cell-deficient NSG mice, making possible immunohistochemistry with routine surgical pathology antibodies...
2017: PloS One
https://www.readbyqxmd.com/read/29038336/the-k-ras-n-ras-and-h-ras-isoforms-unique-conformational-preferences-and-implications-for-targeting-oncogenic-mutants
#14
Jillian A Parker, Carla Mattos
Ras controls a multitude of cellular signaling processes, including cell proliferation, differentiation, and apoptosis. Deregulation of Ras cycling often promotes tumorigenesis and various other developmental disorders, termed RASopothies. Although the structure of Ras has been known for many decades, it is still one of the most highly sought-after drug targets today, and is often referred to as "undruggable." At the center of this paradoxical protein is a lack of understanding of fundamental differences in the G domains between the highly similar Ras isoforms and common oncogenic mutations, despite the immense wealth of knowledge accumulated about this protein to date...
October 16, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29033317/ras-binder-induces-a-modified-switch-ii-pocket-in-gtp-and-gdp-states
#15
Daniel R Gentile, Manoj K Rathinaswamy, Meredith L Jenkins, Steven M Moss, Braden D Siempelkamp, Adam R Renslo, John E Burke, Kevan M Shokat
Covalent inhibitors of K-Ras(G12C) have been reported that exclusively recognize the GDP state. Here, we utilize disulfide tethering of a non-natural cysteine (K-Ras(M72C)) to identify a new switch-II pocket (S-IIP) binding ligand (2C07) that engages the active GTP state. Co-crystal structures of 2C07 bound to H-Ras(M72C) reveal binding in a cryptic groove we term S-IIG. In the GppNHp state, 2C07 binding to a modified S-IIP pushes switch I away from the nucleotide, breaking the network of polar contacts essential for adopting the canonical GTP state...
September 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29024814/anti-tumor-effects-of-nvp-bkm120-alone-or-in-combination-with-mek162-in-biliary-tract-cancer
#16
Ling Jin, Mei-Hua Jin, Ah-Rong Nam, Ji-Eun Park, Ju-Hee Bang, Do-Youn Oh, Yung-Jue Bang
There are currently no clinically validated therapeutic targets for biliary tract cancer (BTC). Despite promising results in other cancers, compounds targeting the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, alone or in combination with Ras/Raf/MEK pathway inhibitors, have not been evaluated in BTC. Here, we examined the effects of a pan-PI3K inhibitor (BKM120) with or without a MEK inhibitor (MEK162), on eight human BTC cell lines carrying mutations in K-Ras and/or the PI3K catalytic subunit, PI3KCA...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28977864/gene-polymorphisms-in-the-pi3k-akt-mtor-signaling-pathway-contribute-to-prostate-cancer-susceptibility-in-chinese-men
#17
Ting Liu, Abulajiang Gulinaer, Xiaoli Shi, Feng Wang, Hengqing An, Wenli Cui, Qiaoxin Li
In this hospital-based case-control study of 413 prostate cancer (PCa) cases and 807 cancer-free controls, we investigated the role of functional single nucleotide polymorphisms (SNPs) of pivotal genes in the PI3K/AKT/mTOR pathway. We genotyped 17 SNPs in mTOR, Raptor, AKT1, AKT2, PTEN, and K-ras and found that 4 were associated with PCa susceptibility. Among the variants, the homozygote variant CC genotype of mTOR rs17036508 C>T were associated with higher PCa risk than the wild TT genotypes (adjusted OR = 3...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975450/low-frequency-of-tert-promoter-mutations-in-a-series-of-well-differentiated-follicular-patterned-thyroid-neoplasms
#18
A Proietti, C Sartori, E Macerola, N Borrelli, G Materazzi, P Vitti, F Basolo
The diagnostic and clinical approaches to follicular-patterned thyroid neoplasms often create dilemmas for pathologist and clinicians. The molecular analysis of these tumors could be a useful tool to overcome diagnostic limitations. The most frequent molecular alterations are point mutations of RAS family genes. Nevertheless, other molecular markers should be taken into account for their prognostic role, as BRAF mutations and the recently described telomerase reverse transcriptase (TERT) promoter mutation. We investigated the prevalence and the possible role of TERT promoter, BRAF, and RAS mutations in a series of low-risk well-differentiated follicular-patterned thyroid neoplasms...
October 3, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28971839/simultaneous-k-ras-activation-and-keap1-deletion-cause-atrophy-of-pancreatic-parenchyma
#19
Shin Hamada, Tooru Shimosegawa, Keiko Taguchi, Tatsuhide Nabeshima, Masayuki Yamamoto, Atsushi Masamune
The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response, such as growth promotion and chemoresistance of cancer cells. Nrf2 is constitutively activated in most cancer cells. However, the activation of Nrf2 together with oncogenic mutations does not always result in cancer promotion. K-ras(LSL-G12D/+)::p53(LSL-R172H/+)::Pdx-1-Cre (KPC) mice are an established model of pancreatic cancer, which specifically express mutants of both K-ras and p53 in the pancreas by using Pdx-1-Cre...
September 28, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28969083/additional-k-ras-mutation-analysis-and-plectin-1-staining-improve-the-diagnostic-accuracy-of-pancreatic-solid-mass-in-eus-guided-fine-needle-aspiration
#20
Joo Kyung Park, Woo Hyun Paik, Byeong Jun Song, Ji Kon Ryu, Min A Kim, Jin Myung Park, Sang Hyub Lee, Yong-Tae Kim
BACKGROUND: One of the major genetic alterations in pancreatic ductal adenocarcinoma (PDAC) is the point mutation of K-ras gene. Plectin-1 was also recently identified as PDAC specific biomarker. The aim of this study was to investigate the improvement of diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) by using additional K-ras mutation analysis and Plectin-1 staining in patients with pancreatic mass. METHODS: A total of 85 study patients with pancreatic mass underwent EUS-FNA and the final diagnoses were as follows; PDACs: 70 patients, pancreas neuroendocrine tumor: 4, metastasis to pancreas: 5, autoimmune pancreatitis: 3, chronic pancreatitis: 1, tuberculous lymphadenitis: 1, pseudocyst: 1...
September 8, 2017: Oncotarget
keyword
keyword
59308
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"