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Parisa Fatourachi, Behnaz Faramarziyan Azimi Maragheh, Seyede Momeneh Mohammadi, Behnaz Valipour, Alireza Dehnad, Hojjatollah Nozad Charoudeh
Aim: In this study we attempt to indicate anti-carcinogenic influence of ether extracted metabolites of Streptomyces Levis sp. on gene expression in colon cancer. Background: Colon cancer is one of the most prevalent cancers worldwide. In recent decades, researchers have been seeking the treatment for cancer. Natural products are valuable compounds with fewer side effects in comparison to chemotherapy drugs. Methods: Secondary metabolites were extracted with the inoculation of bacterial sample in Mueller Hinton Broth...
2018: Gastroenterology and Hepatology From Bed to Bench
Shinya Fujie, Hiroyuki Matsubayashi, Hirotoshi Ishiwatari, Hiromasa Hazama, Takaaki Ito, Keiko Sasaki, Hiroyuki Ono
A 70-year-old man was referred to our hospital with exacerbation of diabetes. His blood tests showed elevated levels of serum IgG4 and HbA1c. Computed tomography of the pancreatic body demonstrated a weakly enhanced mass, 2 cm in size, with indistinct borders. Magnetic resonance cholangiopancreatography revealed a narrowing of the main pancreatic duct (MPD) at the pancreatic body, a markedly dilated upstream duct, and a slightly dilated downstream duct. Endoscopic ultrasonography demonstrated an iso-hypoechoic heterogeneous mass, protruding and spreading in the pancreatic duct...
March 2018: Journal of Gastrointestinal and Liver Diseases: JGLD
Alessandro Inno, Vincenzo Di Noia, Maurizio Martini, Ettore D'Argento, Mariantonietta Di Salvatore, Vincenzo Arena, Giovanni Schinzari, Armando Orlandi, Luigi Maria Larocca, Alessandra Cassano, Carlo Barone
Erlotinib is approved for the treatment of patients with EGFR mutation positive, metastatic NSCLC. It is also approved as second/third line therapy for EGFR mutation negative patients, but in this setting the benefit of erlotinib is modest and there is no validated biomarker for selecting EGFR wild-type patients who may benefit the most from the treatment. We retrospectively assessed EGFR and K-RAS mutational status, and EGFR, c-MET and IGF1-R expression in tumor samples of 72 patients with metastatic NSCLC treated with erlotinib after at least one prior line of chemotherapy, from 2008 to 2012...
March 20, 2018: Pathology Oncology Research: POR
F Roviello, K Polom, A D'Ignazio, V Pascale, D Marrelli
No abstract text is available yet for this article.
March 2018: European Journal of Cancer
Yibin Hao, Jianhua Zhang, Guoyong Shan, Ning Zhang, Wenwen Jin, Kejun Nan
Objective: to establish regulatory network of colorectal cancer involving p42.3 protein and to provide theoretical evidence for deep functional exploration of p42.3 protein in the onset and development of colorectal cancer. Methods: with protein similarity algorithm, reference protein set of p42.3 cell apoptosis was built according to structural features of p42.3. GO and KEGG databases were used to establish regulatory network of tumor cell apoptosis involving p42.3; meanwhile, the largest possible working pathway that involves p42...
December 2017: Saudi Journal of Biological Sciences
Zhen-Lu Li, Priyanka Prakash, Matthias Buck
Association of Raf kinase with activated Ras triggers downstream signaling cascades toward regulating transcription in the cells' nucleus. Dysregulation of Ras-Raf signaling stimulates cancers. We investigate the C-Raf RBD and CRD regions when bound to oncogenic K-Ras4B at the membrane. All-atom molecular dynamics simulations suggest that the membrane plays an integral role in regulating the configurational ensemble of the complex. Remarkably, the complex samples a few states dynamically, reflecting a competition between C-Raf CRD- and K-Ras4B- membrane interactions...
February 28, 2018: ACS Central Science
Lili Zhao, Xin Ni, Linlin Zhao, Yao Zhang, Dan Jin, Wei Yin, Dandan Wang, Wei Zhang
Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer. MicroRNAs have been increasingly implicated in NSCLC and may serve as novel therapeutic targets to combat cancer. Here we investigated the functional implication of miR-188 in NSCLC. We first analyzed miR-188 expression in both NSCLC clinical samples and cancer cell lines. Next we investigated its role in A549 and H2126 cells with cell proliferation, migration and apoptosis assays. To extend the in vitro study, we employed both xenograft model and LSL-K-ras G12D lung cancer model to examine the role of miR-188 in tumorigenesis...
March 12, 2018: Molecular Pharmaceutics
In Seok Yang, Sangwoo Kim
BACKGROUND: Aberrant mutations in KRAS play a critical role in tumor initiation and progression, and are a negative prognosis factor in lung adenocarcinoma (LUAD). RESULTS: Using genomic analysis for K-Ras isoforms (K-Ras4A and K-Ras4B) and large-scale multi-omics data, we inspected the overall survival (OS) and disease-free survival (DFS) of LUAD patients based on the abundance of transcript variants by analyzing RNA expression and somatic mutation data from The Cancer Genome Atlas (n = 516)...
February 19, 2018: BMC Bioinformatics
Yukihiro Akao, Minami Kumasaki, Haruka Shinohara, Nobuhiko Sugito, Yuki Kuranaga, Takuya Tsujino, Yuki Yoshikawa, Yukio Kitade
Despite considerable research on K-Ras inhibitors, none had been developed until now. We synthesized nuclease-resistant synthetic miR-143 (miR-143#12), which strongly silenced K-Ras, its effector signal molecules AKT and ERKs, and the K-Ras activator Sos1. We examined the anti-proliferative effect of miR-143#12 and the mechanism in human colon cancer DLD-1 cell (G13D) and other cell types harboring K-Ras mutations. Cell growth was markedly suppressed in a concentration-dependent manner by miR-143#12 (IC50 : 1...
March 2, 2018: Cancer Science
Yoko Sekita-Hatakeyama, Takeshi Nishikawa, Mao Takeuchi, Kouhei Morita, Maiko Takeda, Kinta Hatakeyama, Tokiko Nakai, Tomoko Uchiyama, Hiroe Itami, Tomomi Fujii, Akira Mitoro, Masayuki Sho, Chiho Ohbayashi
BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) technology is widely used for the diagnosis of pancreatic masses. However, in some cases, inadequate tissue volume or difficulty of morphological diagnosis are constraining factors for adequate cytopathological evaluation. K-ras mutation is the most frequently acquired genetic abnormality, occurring in approximately 90% of all patients with pancreatic ductal adenocarcinoma (PDAC). In the present study, the clinical utility of residual liquid-based cytology (LBC) specimens obtained using EUS-FNA for K-ras mutation analysis was evaluated...
2018: PloS One
Jinxing Hu, Yufei Han, Jingtao Wang, Yue Liu, Yanfang Zhao, Yajing Liu, Ping Gong
Based upon the modeling binding mode of marketed AZD9291 with T790M, a series of N-9-Diphenyl-9H-purin-2-amine derivatives were designed and synthesized with the purpose to overcome the drug resistance resulted from T790M/L858R double mutations. The most potent compound 23a showed excellent enzyme inhibitory activities and selectivity with nanomolar IC50 values for both the single T790M and double T790M/L858R mutant EGFRs, and was more than 8-fold selective for wild type EGFR. Compound 23a displayed strong antiproliferative activity against the H1975 non-small cell lung cancer (NSCLC) cells bearing T790M/L858R...
February 17, 2018: Bioorganic & Medicinal Chemistry
T Gambichler, I Rüddel, S Hessam, F G Bechara, E Stockfleth, L Schmitz
BACKGROUND: Koebnerized non-melanoma skin cancer following skin trauma represents a rare and obscure event. OBJECTIVES: To study molecularpathological parameters in koebnerized squamous cell carcinomas (K-SCCs) occurring after complete tumour removal. METHODS: We assessed two patients with multiple sclerosis who were on treatment with dimethylfumarate (DMF) preceded by long-term azathioprine therapy. Both patients rapidly developed several K-SCCs following histopathologically proven complete excision of cutaneous SCCs...
February 25, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Yu Li, Qiuyan Shi, Jiajia Shao, Yaping Yuan, Zhigang Yang, Shizhen Chen, Xin Zhou, Shijun Wen, Zhong-Xing Jiang
To improve the druggability of salinomycin, a 20-epi-amino-20-deoxysalinomycin derivatives library was synthesized with high efficacy from which a few salinomycin derivatives with high potency and selectivity were identified through comprehensive cytotoxicity assay, including a fluorine-19 magnetic resonance sensitive tool molecule. Using a K-ras cellular model, salinomycin and its derivatives showed different molecular mode of action from literature reports. These results would be valuable for developing salinomycin-based cancer therapy...
February 5, 2018: European Journal of Medicinal Chemistry
Laurence Booth, Jane L Roberts, Rumeesa Rais, John Kirkwood, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Andrew Poklepovic, Paul Dent
The irreversible ERBB1/2/4 inhibitor neratinib has been shown in vitro to rapidly reduce the expression of ERBB1/2/4 and RAS proteins via autophagic/lysosomal degradation. We have recently demonstrated that neratinib and valproate interact to suppress the growth of 4T1 mammary tumors but had not defined whether the [neratinib + valproate] drug combination, in a mouse, had altered the biology of the 4T1 cells. Exposure of 4T1 mammary tumors to [neratinib + valproate] for three days resulted, two weeks later, in tumors that expressed less ERBB1, K-RAS, N-RAS, indoleamine-pyrrole 2,3-dioxygenase (IDO-1), ornithine decarboxylase (ODC) and had increased Class I MHCA expression...
January 19, 2018: Oncotarget
Michael C Burns, Jennifer E Howes, Qi Sun, Andrew J Little, DeMarco V Camper, Jason R Abbott, Jason Phan, Taekyu Lee, Alex G Waterson, Olivia W Rossanese, Stephen W Fesik
K-RAS is mutated in approximately 30% of human cancers, resulting in increased RAS signaling and tumor growth. Thus, RAS is a highly validated therapeutic target, especially in tumors of the pancreas, lung and colon. Although directly targeting RAS has proven to be challenging, it may be possible to target other proteins involved in RAS signaling, such as the guanine nucleotide exchange factor Son of Sevenless (SOS). We have previously reported on the discovery of small molecules that bind to SOS1, activate SOS-mediated nucleotide exchange on RAS, and paradoxically inhibit ERK phosphorylation (Burns et al...
February 11, 2018: Analytical Biochemistry
Steffen Hanselmann, Patrick Wolter, Jonas Malkmus, Stefan Gaubatz
In this study, we investigated whether proteins that are involved in cytokinesis are potential targets for therapy of lung cancer. We find that the microtubule-associated protein PRC1 (protein required for cytokinesis 1), which plays a key role in organizing anti-parallel microtubule in the central spindle in cytokinesis, is overexpressed in lung cancer cell lines compared to normal cells. Increased expression of PRC1 is correlated with a poor prognosis of human lung adenocarcinoma patients. Lentiviral delivered, inducible RNAi of PRC1 demonstrated that proliferation of lung cancer cell lines strongly depends on PRC1...
January 12, 2018: Oncotarget
Roberto Serna-Blasco, Marta Sanz-Álvarez, Óscar Aguilera, Jesús García-Foncillas
RAS protein family members (KRAS4A, KRAS4B, HRAS and NRAS) function as GDP-GTP-regulated on-off switches, which regulate cytoplasmic-nuclear signaling networks ruling diverse normal cellular processes. Constitutive activating mutations in RAS genes are found in up to 30% of human cancers, and remarkably, the oncogenic Ras mutations and mutations in other components of Ras/MAPK signaling pathways seem to be mutually exclusive in most tumors, pointing out that deregulation of Ras-dependent signaling is an essential requirement for tumorigenesis...
February 9, 2018: Seminars in Cancer Biology
Shuai Li, Hyunbum Jang, Jian Zhang, Ruth Nussinov
K-Ras4B preferentially activates Raf-1. The high-affinity interaction of Ras-binding domain (RBD) of Raf with Ras was solved, but the relative position of Raf's cysteine-rich domain (CRD) in the Ras/Raf complex at the membrane and key question of exactly how it affects Raf signaling are daunting. We show that CRD stably binds anionic membranes inserting a positively charged loop into the amphipathic interface. Importantly, when in complex with Ras/RBD, covalently connected CRD presents the same membrane interaction mechanism, with CRD locating at the space between the RBD and membrane...
January 29, 2018: Structure
Yi-Jang Lin, Kevin M Haigis
K-Ras is the undisputed champion of oncogenes, yet our ability to interfere with its oncogenic function is hampered by insufficient mechanistic understanding. In this issue of Cell, Ambrogio and colleagues connect the ability of K-Ras to dimerize to the ability of wild-type K-Ras to limit the oncogenic properties of the mutant.
February 8, 2018: Cell
Gargi Maity, Inamul Haque, Arnab Ghosh, Gopal Dhar, Vijayalaxmi G Gupta, Sandipto Sarkar, Imaan Azeem, Douglas McGregor, Abhishek Choudhary, Donald R Campbell, Suman Kambhampati, Sushanta K Banerjee, Snigdha Banerjee
Myc-associated zinc-finger protein (MAZ) is a transcription factor with dual roles in transcription initiation and termination. Deregulation of MAZ expression is associated with the progression of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of action of MAZ in PDAC progression is largely unknown. Here, we present evidence that MAZ mRNA expression and protein levels are increased in human PDAC cell lines, tissue samples, a subcutaneous tumor xenograft in a nude mouse model, and spontaneous cancer in the genetically engineered PDAC mouse model...
February 6, 2018: Journal of Biological Chemistry
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