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https://www.readbyqxmd.com/read/28915640/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#1
Shu-Yan Han, Wei Zhao, Hai-Bo Han, Hong Sun, Dong Xue, Yan-Na Jiao, Xi-Ran He, Shan-Tong Jiang, Ping-Ping Li
Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904816/regulation-of-hnrnpa1-by-micrornas-controls-the-mir-18a-k-ras-axis-in-chemotherapy-resistant-ovarian-cancer
#2
Cristian Rodriguez-Aguayo, Paloma Del C Monroig, Roxana S Redis, Emine Bayraktar, Maria I Almeida, Cristina Ivan, Enrique Fuentes-Mattei, Mohammed H Rashed, Arturo Chavez-Reyes, Bulent Ozpolat, Rahul Mitra, Anil K Sood, George A Calin, Gabriel Lopez-Berestein
The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is still unclear. Here we demonstrate a regulatory circuit involving oncogenic and tumor-suppressor miRNAs and an RNA-binding protein in a chemotherapy-resistant ovarian cancer model. We identified and characterized miR-15a-5p and miR-25-3p as negative regulators of hnRNPA1 expression, which is required for the processing of miR-18a-3p, an inhibitor of the K-RAS oncogene...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28903430/resveratrol-inhibits-age-dependent-spontaneous-tumorigenesis-by-sirt1-mediated-post-translational-modulations-in-the-annual-fish-nothobranchius-guentheri
#3
Tingting Liu, Long Ma, Zhaodi Zheng, Fenglin Li, Shan Liu, Yingbo Xie, Guorong Li
Resveratrol, SIRT1 activator, inhibits carcinogenesis predominantly performed in transgenic animal models, orthotopic cancers of nude mice or different cancer cell lines, but its effects during process of spontaneous tumors using vertebrate models remain untested. Spontaneous liver neoplasm is an age-related disease and is inhibited by resveratrol in the annual fish Nothobranchius guentheri, which indicates that the fish can act as an excellent model to study spontaneous tumorigenesis. Totally, 175 fish were fed with resveratrol and another 175 fish for controls...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901317/k-ras-mutation-and-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-treatment-in-patients-with-nonsmall-cell-lung-cancer
#4
Bin Zhou, Congrong Tang, Jie Li
OBJECTIVE: The aim of this study was to evaluate the relationship between k-RAS gene mutation and the resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in patients with nonsmall-cell lung cancer (NSCLC). METHODS: Forty-five pathologies confirmed NSCLC patients who received EGFR-TKI (Gefitinib) treatment were retrospectively included in this study. The mutation of codon 12 and 13, located in exon1 and exon 2 of k-RAS gene were examined by polymerase chain reaction (PCR) and DAN sequencing in tumor samples of the included 45 NSCLC patients...
2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28881608/anti-tumor-efficacy-of-theliatinib-in-esophageal-cancer-patient-derived-xenografts-models-with-epidermal-growth-factor-receptor-egfr-overexpression-and-gene-amplification
#5
Yongxin Ren, Jianming Zheng, Shiming Fan, Linfang Wang, Min Cheng, Dongxia Shi, Wei Zhang, Renxiang Tang, Ying Yu, Longxian Jiao, Jun Ni, Haibin Yang, Huaqing Cai, Fang Yin, Yunxin Chen, Feng Zhou, Weihan Zhang, Weiguo Qing, Weiguo Su
Targeted therapy is not yet approved for esophageal cancer (EC). In this study, we first evaluated EGFR gene and protein expression in 70 Chinese EC patient tumor samples collected during surgery. We then established 23 patient-derived EC xenograft (PDECX) models and assessed the efficacy of theliatinib, a potent and highly selective EGFR inhibitor currently in Phase I clinical study, in 9 PDECX models exhibiting various EGFR expression levels. Immunohistochemical analysis showed that 50 patient tumor samples (71...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28863262/spatiotemporal-analysis-of-k-ras-plasma-membrane-interactions-reveals-multiple-high-order-homo-oligomeric-complexes
#6
Suparna Sarkar-Banerjee, Abdallah Sayyed-Ahmad, Priyanka Prakash, Kwang-Jin Cho, M Neal Waxham, John F Hancock, Alemayehu A Gorfe
Self-assembly of plasma membrane-associated Ras GTPases has major implications to the regulation of cell signaling. However, the structural basis of homo-oligomerization and the fractional distribution of oligomeric states remained undetermined. We have addressed these issues by deciphering the distribution of dimers and higher-order oligomers of K-Ras4B, the most frequently mutated Ras isoform in human cancers. We focused on the constitutively active G12V K-Ras and two of its variants, K101E and K101C/E107C, which respectively destabilize and stabilize oligomers...
September 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28858737/ginkgo-biloba-l-leaf-extract-offers-multiple-mechanisms-in-bridling-n-methylnitrosourea-mediated-experimental-colorectal-cancer
#7
Hanaa H Ahmed, Hanan S El-Abhar, Elsayed Abdul Khalik Hassanin, Noha F Abdelkader, Mohamed B Shalaby
In Egypt, colorectal cancer (CRC) is the 6th cancer in both gender and CRC rates are high in subjects under 40 years of age. This study goaled to determine the development of CRC using relevant biochemical markers and to elucidate the potent mechanism of Ginkgo biloba L. leaf extract in retrogression of experimental CRC. Adult male Sprague-Dawley rats were administered N-methylnitrosourea (N-MNU; 2mg in 0.5ml water/rat) intrarectally thrice a week for five weeks to induce CRC, followed by treatment with either 5-fluorouracil (5-FU; 12...
August 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28846108/runx3-plays-a-critical-role-in-restriction-point-and-defense-against-cellular-transformation
#8
X-Z Chi, J-W Lee, Y-S Lee, I Y Park, Y Ito, S-C Bae
The restriction (R)-point decision is fundamental to normal differentiation and the G1-S transition, and the decision-making machinery is perturbed in nearly all cancer cells. The mechanisms underlying the cellular context-dependent R-point decision remain poorly understood. We found that the R-point was dysregulated in Runx3(-/-)mouse embryonic fibroblasts (MEFs), which formed tumors in nude mice. Ectopic expression of Runx3 restored the R-point and abolished the tumorigenicity of Runx3(-/-)MEFs and K-Ras-activated Runx3(-/-)MEFs (Runx3(-/-);K-Ras(G12D/+))...
August 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28844705/resectable-pancreatic-head-adenocarcinoma-is-r0-resection-an-illusion-genetic-evaluation-of-venous-resection-margin-affirmed-unrecognized-disease
#9
O Turrini, M Gilabert, J Ewald, V Moutardier, J-R Delpero, J-L Iovanna
PURPOSE: To assess the K-ras gene mutation in the histologically negative venous margin of a pancreaticoduodenectomy (PD) specimen and its impact on survival. METHOD: From 2007 to 2010, 22 patients underwent R0 PD for resecable pancreatic adenocarcinoma. All specimens were stained and the portal vein (PV) bed was identified by blue ink; a 2mm(3) sample (including the blue ink) was cut from a microscopic free-tumor block. DNA was extracted and assessed by quantitative real time polymerase chain reaction to detect the K-ras gene mutation...
August 22, 2017: Journal of Visceral Surgery
https://www.readbyqxmd.com/read/28827765/opposite-feedback-from-mtorc1-to-h-ras-and-k-ras4b-downstream-of-srebp1
#10
Itziar M D Posada, Benoit Lectez, Farid A Siddiqui, Christina Oetken-Lindholm, Mukund Sharma, Daniel Abankwa
As a major growth factor transducer, Ras is an upstream activator of mTORC1, which further integrates nutrient and energy inputs. To ensure a contextual coupling of cell division via Ras/MAPK-signalling and growth via mTORC1-signalling, feedback loops from one pathway back to the other are required. Here we describe a novel feedback from mTORC1, which oppositely affects oncogenic H-ras- and K-ras-signalling output, and as a consequence stemness properties of tumourigenic cells. Amino acid stimulation of mTORC1 increases the processed form of SREBP1, a major lipidome regulator...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28825637/superoxide-dismutases-in-pancreatic-cancer
#11
REVIEW
Justin G Wilkes, Matthew S Alexander, Joseph J Cullen
The incidence of pancreatic cancer is increasing as the population ages but treatment advancements continue to lag far behind. The majority of pancreatic cancer patients have a K-ras oncogene mutation causing a shift in the redox state of the cell, favoring malignant proliferation. This mutation is believed to lead to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and superoxide overproduction, generating tumorigenic behavior. Superoxide dismutases (SODs) have been studied for their ability to manage the oxidative state of the cell by dismuting superoxide and inhibiting signals for pancreatic cancer growth...
August 19, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28790854/hypermethylation-of-secreted-frizzled-related-proteins-predicts-poor-prognosis-in-non-m3-acute-myeloid-leukemia
#12
Hong Guo, Ting-Juan Zhang, Xiang-Mei Wen, Jing-Dong Zhou, Ji-Chun Ma, Cui An, Wei Zhang, Zi-Jun Xu, Jiang Lin, Jun Qian
OBJECTIVE: Secreted frizzled-related proteins (SFRPs) as Wnt signaling antagonists have been found to be dysregulated by promoter hypermethylation in several cancers including acute myeloid leukemia (AML). This study aimed to investigate the methylated status of SFRPs promoter region and its clinical relevance in Chinese non-M3 AML patients. METHODS: SFRPs methylation in 139 primary non-M3 AML patients was determined using methylation-specific real-time quantitative polymerase chain reaction...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28766076/multicenter-analysis-of-risk-factors-for-anastomotic-leakage-after-middle-and-low-rectal-cancer-resection-without-diverting-stoma-a-retrospective-study-of-319-consecutive-patients
#13
Wei Zhang, Zheng Lou, Qizhi Liu, Ronggui Meng, Haifeng Gong, Liqiang Hao, Peng Liu, Ge Sun, Jun Ma, Wei Zhang
PURPOSE: The purpose of this study was to evaluate the risk factors for anastomotic leakage (AL) after anterior resection for middle and low rectal cancer in order to help surgeons to decide which patients could benefit from a diverting stoma. METHODS: Data on 319 patients having a middle and low rectal cancer resection with anastomosis between May 2011 and October 2015 from two hospitals were included in the study. The analysis included the following variables: patient-related variables (gender, age, diabetes mellitus, ASA score, preoperative radiochemotherapy, body mass index, blood hemoglobin, and serum albumin level), tumor-related variables (K-ras status, distance of tumor from the anal verge, histopathologic grade, pathological T stage, pathological N stage, pathological M stage, TNM stage, and tumor size), and surgery-related variables (laparoscopic or open surgery, blood loss, and operative time)...
August 2, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28765579/inhibition-of-akt1-signaling-promotes-invasion-and-metastasis-of-non-small-cell-lung-cancer-cells-with-k-ras-or-egfr-mutations
#14
Guanhua Rao, Mariaelena Pierobon, In-Kyu Kim, Wei-Hsun Hsu, Jianghong Deng, Yong-Wha Moon, Emanuel F Petricoin, Yu-Wen Zhang, Yisong Wang, Giuseppe Giaccone
Accumulating evidence supports a role of the PI3K-AKT pathway in the regulation of cell motility, invasion and metastasis. AKT activation is known to promote metastasis, however under certain circumstances, it also shows an inhibitory activity on metastatic processes, and the cause of such conflicting results is largely unclear. Here we found that AKT1 is an important regulator of metastasis and down-regulation of its activity is associated with increased metastatic potential of A549 cells. Inhibition of AKT1 enhanced migration and invasion in KRAS- or EGFR-mutant non-small cell lung cancer (NSCLC) cells...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28764929/inhibition-of-aurora-kinase-a-induces-necroptosis-in-pancreatic-carcinoma
#15
Yangchun Xie, Shan Zhu, Meizuo Zhong, Minghua Yang, Xiaofan Sun, Jinbao Liu, Guido Kroemer, Michael Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Induction of non-apoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2...
July 29, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28764863/cellular-expression-in-vitro-and-in-vivo-confirmation-of-gaec1-oncogenic-properties-in-colon-cancer
#16
Riajul Wahab, Vinod Gopalan, Farhadul Islam, Robert A Smith, Bin Qiao, Alfred K Lam
GAEC1 (Gene amplified in esophageal cancer 1) alterations have oncogenic properties in oesophageal squamous cell carcinomas and frequent amplifications of the gene were noted in colorectal adenocarcinomas. However, the subcellular localization and expression of GAEC1 at the protein level have never been reported in human cancer cells. The present study aimed to investigate whether GAEC1 is differentially expressed in different stages of colon cancer and to elucidate its underlying cellular and molecular mechanism in colon cancer progression...
July 26, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28755079/pancreatic-adenocarcinoma-with-a-germline-pten-p-arg234gln-mutation
#17
Sunao Uemura, Hiroyuki Matsubayashi, Yoshimi Kiyozumi, Katsuhiko Uesaka, Yusuke Yamamoto, Keiko Sasaki, Masato Abe, Kenichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi
A minor fraction of pancreatic ductal adenocarcinoma (PDAC) develops in association with germline mutations of the genes responsible for inherited cancer syndromes. However, the PDAC that has a germline PTEN mutation has not received much attention. Genome-wide whole exome sequencing was performed on germline and somatic DNA from an 82-year-old woman who had developed a solid pancreatic cancer but did not show characteristic findings of PTEN hamartoma tumor syndromes (PHTS). Histology of the resected pancreatic tumor showed unique PDAC findings of primarily dendriform structures and dense fibrous tissue, accompanied by multiple pancreatic intraepithelial neoplasias in the vicinity...
July 28, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28743497/molecular-interaction-between-k-ras-and-h-rev107-in-the-ras-signaling-pathway
#18
Chang Woo Han, Mi Suk Jeong, Se Bok Jang
Ras proteins are small GTPases that serve as master moderators of a large number of signaling pathways involved in various cellular processes. Activating mutations in Ras are found in about one-third of cancers. H-REV107, a K-Ras binding protein, plays an important role in determining K-Ras function. H-REV107 is a member of the HREV107 family of class II tumor suppressor genes and a growth inhibitory Ras target gene that suppresses cellular growth, differentiation, and apoptosis. Expression of H-REV107 was strongly reduced in about 50% of human carcinoma cell lines...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28742845/evaluation-of-k-ras-and-p53-expression-in-pancreatic-adenocarcinoma-using-the-cancer-genome-atlas
#19
Liming Lu, Jingchun Zeng
Genetic alterations in K-ras and p53 are thought to be critical in pancreatic cancer development and progression. However, K-ras and p53 expression in pancreatic adenocarcinoma have not been systematically examined in The Cancer Genome Atlas (TCGA) Data Portal. Information regarding K-ras and p53 alterations, mRNA expression data, and protein/protein phosphorylation abundance was retrieved from The Cancer Genome Atlas (TCGA) databases, and analyses were performed by the cBioPortal for Cancer Genomics. The mutual exclusivity analysis showed that events in K-ras and p53 were likely to co-occur in pancreatic adenocarcinoma (Log odds ratio = 1...
2017: PloS One
https://www.readbyqxmd.com/read/28740607/crystal-structure-of-a-human-k-ras-g12d-mutant-in-complex-with-gdp-and-the-cyclic-inhibitory-peptide-krpep-2d
#20
Satoshi Sogabe, Yusuke Kamada, Masanori Miwa, Ayumu Niida, Tomoya Sameshima, Masahiro Kamaura, Kazuko Yonemori, Shigekazu Sasaki, Jun-Ichi Sakamoto, Kotaro Sakamoto
The Ras proteins play roles in cell differentiation, proliferation, and survival. Aberrant signaling through Ras-mediated pathways in tumor cells occurs as a result of several types of mutational damage, which most frequently affects the amino acids G12, G13, and Q61. Recently, KRpep-2d was identified as a K-Ras(G12D) selective inhibitory peptide against the G12D mutant of K-Ras, which is a key member of the Ras protein family and an attractive cancer therapeutic target. In this study, the crystal structure of the human K-Ras(G12D) mutant was determined in complex with GDP and KRpep-2d at 1...
July 13, 2017: ACS Medicinal Chemistry Letters
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