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https://www.readbyqxmd.com/read/28931215/berberine-could-inhibit-thyroid-carcinoma-cells-by-inducing-mitochondrial-apoptosis-g0-g1-cell-cycle-arrest-and-suppressing-migration-via-pi3k-akt-and-mapk-signaling-pathways
#1
Liang Li, Xingchun Wang, Rampersad Sharvan, Jingyang Gao, Shen Qu
Berberine, an important natural isoquinoline alkaloid from traditional Chinese medicine, is reported to exhibit multiple pharmacological properties, including anti-microbial, anti-diabetes, anti-obesity, anti-inflammatory and anti-carcinogenic activities. Although studies have shown that a wide range of carcinoma cells could be inhibited by berberine, few studies involved thyroid carcinoma. We therefore examined the effect of berberine on papillary thyroid carcinoma (PTC, the most common subtype) and anaplastic thyroid carcinoma (ATC, the most malignant and aggressive subtype)...
September 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28931069/methylation-associated-transcriptional-repression-of-elovl5-in-novel-colorectal-cancer-cell-lines
#2
Arnoud Boot, Jan Oosting, Jaap D H van Eendenburg, Peter J K Kuppen, Hans Morreau, Tom van Wezel
Genetic and epigenetic alterations mark colorectal cancer (CRC). Global hypomethylation is observed in nearly all CRC, but a distinct subset of CRC show the CpG Island Methylator Phenotype (CIMP). These tumors show DNA hypermethylation of a specific subset of CpG islands, resulting in transcriptional downregulation of nearby genes. Recently we reported the establishment of novel CRC cell lines derived from primary and metastatic CRC tissues. In this study we describe the DNA methylation profiling of these low passage CRC cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28928870/the-impact-of-microsatellite-instability-status-and-sidedness-of-the-primary-tumor-on-the-effect-of-cetuximab-containing-chemotherapy-in-patients-with-metastatic-colorectal-cancer
#3
Seung Tae Kim, Su-Jin Lee, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Ho Yeong Lim, Won Ki Kang, Young Suk Park
Background: Colorectal cancer (CRC) has been reconsidered as a heterogeneous disease. Among advances of genomic analysis in CRC, the sidedness of tumors (left-sided colon vs. right-sided colon) and microsatellite instability (MSI)-high (H) tumors have been highlighted. Methods: We analyzed 153 CRC patients who were available for evaluation of MSI status and had been treated with cetuximab-containing chemotherapy between April 2008 and January 2013. KRAS mutational status was available in all 153 patients, but BRAF mutational status was only available in 72 patients (47...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928829/braf-v600e-mutation-contributes-papillary-thyroid-carcinoma-and-hashimoto-thyroiditis-with-resistance-to-thyroid-hormone-a-case-report-and-literature-review
#4
Wanjia Xing, Xiaohong Liu, Qingqing He, Zongjing Zhang, Zhaoshun Jiang
Resistance to thyroid hormone (RTH) is a rare autosomal hereditary disorder characterized by increased serum thyroid hormone (TH) levels with unsuppressed or increased thyrotropin concentration. It remains unknown whether the coexistence of RTH with papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT) is incidental or whether it possesses a genetic or pathophysiological association. In the present study, a case of RTH with PTC and HT in an 11-year-old Chinese patient was examined and the clinical presentation of RTH with PTC was discussed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928360/tumor-associated-b-cells-induce-tumor-heterogeneity-and-therapy-resistance
#5
Rajasekharan Somasundaram, Gao Zhang, Mizuho Fukunaga-Kalabis, Michela Perego, Clemens Krepler, Xiaowei Xu, Christine Wagner, Denitsa Hristova, Jie Zhang, Tian Tian, Zhi Wei, Qin Liu, Kanika Garg, Johannes Griss, Rufus Hards, Margarita Maurer, Christine Hafner, Marius Mayerhöfer, Georgios Karanikas, Ahmad Jalili, Verena Bauer-Pohl, Felix Weihsengruber, Klemens Rappersberger, Josef Koller, Roland Lang, Courtney Hudgens, Guo Chen, Michael Tetzlaff, Lawrence Wu, Dennie Tompers Frederick, Richard A Scolyer, Georgina V Long, Manashree Damle, Courtney Ellingsworth, Leon Grinman, Harry Choi, Brian J Gavin, Margaret Dunagin, Arjun Raj, Nathalie Scholler, Laura Gross, Marilda Beqiri, Keiryn Bennett, Ian Watson, Helmut Schaider, Michael A Davies, Jennifer Wargo, Brian J Czerniecki, Lynn Schuchter, Dorothee Herlyn, Keith Flaherty, Meenhard Herlyn, Stephan N Wagner
In melanoma, therapies with inhibitors to oncogenic BRAF(V600E) are highly effective but responses are often short-lived due to the emergence of drug-resistant tumor subpopulations. We describe here a mechanism of acquired drug resistance through the tumor microenvironment, which is mediated by human tumor-associated B cells. Human melanoma cells constitutively produce the growth factor FGF-2, which activates tumor-infiltrating B cells to produce the growth factor IGF-1. B-cell-derived IGF-1 is critical for resistance of melanomas to BRAF and MEK inhibitors due to emergence of heterogeneous subpopulations and activation of FGFR-3...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28927801/design-synthesis-and-antitumor-activity-of-novel-sorafenib-derivatives-bearing-pyrazole-scaffold
#6
Min Wang, Shan Xu, Huajun Lei, Caolin Wang, Zhen Xiao, Shuang Jia, Jia Zhi, Pengwu Zheng, Wufu Zhu
Four series of Sorafenib derivatives bearing pyrazole scaffold (8a-m, 9a-c, 10a-e and 11a) were synthesized and characterized by NMR and MS. All of the target compounds were evaluated for the cytotoxicity against A549, HepG2, MCF-7, and PC-3 cancer cell lines and some selected compounds were further evaluated for the activity against VEGFR-2/KDR, BRAF, CRAF, c-Met, EGFR and Flt-3 kinases. Compounds 8b and 8i were more active than that of compounds 8h, 9a, especially the IC50 value of compounds 8b on VEGFR-2 kinase was 0...
September 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28927118/mutations-in-braf-codons-594-and-596-predict-good-prognosis-in-melanoma
#7
Xiaowen Wu, Junya Yan, Jie Dai, Meng Ma, Huan Tang, Jiayi Yu, Tianxiao Xu, Huan Yu, Lu Si, Zhihong Chi, Xinan Sheng, Chuanliang Cui, Yan Kong, Jun Guo
B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E is the most common kinase-activating mutation and is associated with poor prognosis in melanoma. However, the clinical significance of kinase-impairing mutations remains unclear. The present study aimed to analyze kinase-impairing mutations in BRAF codons 594 and 596 in non-Caucasian patients with melanoma and to investigate their possible clinical significance. To detect hotspot mutations, exon 15 of the BRAF gene was amplified using polymerase chain reaction in samples from 1,554 patients with melanoma...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926605/assessment-of-common-somatic-mutations-of-egfr-kras-braf-nras-in-pulmonary-non-small-cell-carcinoma-using-iplex%C3%A2-hs-a-new-highly-sensitive-assay-for-the-massarray%C3%A2-system
#8
Bobbie C Sutton, Ryan T Birse, Kevin Maggert, Tammy Ray, Jessica Hobbs, Amobi Ezenekwe, Jason Kazmierczak, Michael Mosko, Joan Kish, Andrew Bullock, Zonggao Shi, M Sharon Stack, Darryl Irwin
Increased early detection and personalized therapy for lung cancer have coincided with greater use of minimally invasive sampling techniques such as endobronchial ultrasound-guided biopsy (EBUS), endoscopic ultrasound-guided biopsy (EUS), and navigational biopsy, as well as thin needle core biopsies. As many lung cancer patients have late stage disease and other comorbidities that make open surgical procedures hazardous, the least invasive biopsy technique with the highest potential specimen yield is now the preferred first diagnostic study...
2017: PloS One
https://www.readbyqxmd.com/read/28926134/early-genetic-aberrations-in-patients-with-sporadic-colorectal-cancer
#9
Brooke R Druliner, Xiaoyang Ruan, Hugues Sicotte, Daniel O'Brien, Hongfang Liu, Jean-Pierre A Kocher, Lisa Boardman
Chromosome instability (CIN) is widely observed in both sporadic and hereditary colorectal cancer (CRC). Defects in APC and WNT signaling are primarily associated with CIN in hereditary CRC, but the genetic causes for CIN in sporadic CRC remain elusive. Using high-density SNP array and exome data from The Cancer Genome Atlas, we characterized loss of heterozygosity (LOH) and copy number variation (CNV) in the peripheral blood, normal colon and corresponding tumor tissue in 15 CRC patients with proficient mismatch repair (MMR) and 24 CRC patients with deficient MMR...
September 19, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28923882/mutational-profiling-of-acute-myeloid-leukemia-with-normal-cytogenetics-in-brazilian-patients-the-value-of-next-generation-sequencing-for-genomic-classification
#10
Thiago Rodrigo de Noronha, Miguel Mitne-Neto, Maria de Lourdes Chauffaille
Karyotype (KT) aberrations are important prognostic factors for acute myeloid leukemia (AML); however, around 50% of cases present normal results. Single nucleotide polymorphism array can detect chromosomal gains, losses or uniparental disomy that are invisible to KT, thus improving patients' risk assessment. However, when both tests are normal, important driver mutations can be detected by the use of next-generation sequencing (NGS). Fourteen adult patients with AML with normal cytogenetics were investigated by NGS for 19 AML-related genes...
September 18, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28923537/metagenomic-shotgun-sequencing-and-unbiased-metabolomic-profiling-identify-specific-human-gut-microbiota-and-metabolites-associated-with-immune-checkpoint-therapy-efficacy-in-melanoma-patients
#11
Arthur E Frankel, Laura A Coughlin, Jiwoong Kim, Thomas W Froehlich, Yang Xie, Eugene P Frenkel, Andrew Y Koh
This is the first prospective study of the effects of human gut microbiota and metabolites on immune checkpoint inhibitor (ICT) response in metastatic melanoma patients. Whereas many melanoma patients exhibit profound response to ICT, there are fewer options for patients failing ICT-particularly with BRAF-wild-type disease. In preclinical studies, specific gut microbiota promotes regression of melanoma in mice. We therefore conducted a study of the effects of pretreatment gut microbiota and metabolites on ICT Response Evaluation Criteria in Solid Tumors response in 39 metastatic melanoma patients treated with ipilimumab, nivolumab, ipilimumab plus nivolumab (IN), or pembrolizumab (P)...
September 14, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28923400/mitf-suppression-improves-the-sensitivity-of-melanoma-cells-to-a-braf-inhibitor
#12
Satoshi Aida, Yukiko Sonobe, Hiromi Tanimura, Nobuhiro Oikawa, Munehiro Yuhki, Hiroshi Sakamoto, Takakazu Mizuno
Microphthalmia-associated transcription factor (MITF) is expressed in melanomas and has a critical role in melanocyte development and transformation. Because inhibition of MITF inhibits cell growth in melanoma, MITF is a potential therapeutic target molecule. Here, we report the identification of CH6868398, which has a novel chemical structure and suppresses MITF expression at the protein level in melanoma cells. CH6868398 showed cell growth inhibition activity against MITF-dependent melanoma cells both with and without BRAF mutation and also exhibited anti-tumor efficacy in a melanoma xenograft model...
September 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28921907/dual-mapk-pi3k-pathway-inhibition-with-trametinib-and-gsk2141795-does-not-yield-clinical-benefit-in-metastatic-nras-mutant-and-wild-type-melanoma
#13
Alain P Algazi, Rosaura Esteve-Puig, Adi Nosrati, Brian Hinds, Adele Hobbs-Muthukumar, Prachi Nandoskar, Susana Ortiz-Urda, Paul B Chapman, Adil Daud
Aberrant MAPK and PI3K pathway signaling may drive the malignant phenotype in NRAS mutant and BRAF(WT) NRAS(WT) metastatic melanoma. To target these pathways NRAS mutant and BRAF(WT) NRAS(WT) patients received oral trametinib at 1.5 mg daily and GSK2141795 at 50 mg daily in a 2-cohort Simon 2-stage design. Participants had adequate end organ function and no more than 2 prior treatment regimens. Imaging assessments were performed at 8-week intervals. 10 NRAS mutant and 10 BRAF(WT) NRAS(WT) patients were enrolled...
September 16, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28921583/associations-of-alcohol-intake-smoking-physical-activity-and-obesity-with-survival-following-colorectal-cancer-diagnosis-by-stage-anatomic-site-and-tumor-molecular-subtype
#14
Harindra Jayasekara, Dallas R English, Andrew Haydon, Allison M Hodge, Brigid M Lynch, Christophe Rosty, Elizabeth J Williamson, Mark Clendenning, Melissa C Southey, Mark A Jenkins, Robin Room, John L Hopper, Roger L Milne, Daniel D Buchanan, Graham G Giles, Robert J MacInnis
The influence of lifestyle factors on survival following a diagnosis of colorectal cancer (CRC) is not well established. We examined associations between lifestyle factors measured before diagnosis and CRC survival. The Melbourne Collaborative Cohort Study collected data on alcohol intake, cigarette smoking and physical activity, and body measurements at baseline (1990-94) and wave 2 (2003-07). We included participants diagnosed to 31 August 2015 with incident stage I-III CRC within 10-years post exposure assessment...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28921484/reply-to-the-letter-by-s-sorscher-regarding-implications-of-braf-mutations-in-dmmr-colorectal-cancers
#15
REVIEW
R Cohen, T André
ᅟ.
September 18, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28921051/fine-particle-matters-induce-dna-damage-and-g2-m-cell-cycle-arrest-in-human-bronchial-epithelial-beas-2b-cells
#16
Jing Wu, Yanfeng Shi, Collins Otieno Asweto, Lin Feng, Xiaozhe Yang, Yannan Zhang, Hejing Hu, Junchao Duan, Zhiwei Sun
There is compelling evidence that exposure to particulate matter (PM) is linked to lung tumorigenesis. However, there is not enough experimental evidence to support the specific mechanisms of PM2.5-induced DNA damage and cell cycle arrest in lung tumorigenesis. In this study, we investigated the toxic effects and molecular mechanisms of PM2.5 on bronchial epithelial (BEAS-2B) cells. PM2.5 exposure reduced cell viability and enhanced LDH activity. The cell growth curves of BEAS-2B cells decreased gradually with the increase in PM2...
September 18, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28919012/braf-v600e-and-braf-inactivating-mutations-in-nsclc
#17
Rafael Rosell, Niki Karachaliou
No abstract text is available yet for this article.
September 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28919011/dabrafenib-plus-trametinib-in-patients-with-previously-untreated-braf-v600e-mutant-metastatic-non-small-cell-lung-cancer-an-open-label-phase-2-trial
#18
David Planchard, Egbert F Smit, Harry J M Groen, Julien Mazieres, Benjamin Besse, Åslaug Helland, Vanessa Giannone, Anthony M D'Amelio, Pingkuan Zhang, Bijoyesh Mookerjee, Bruce E Johnson
BACKGROUND: BRAF(V600E) mutation occurs in 1-2% of lung adenocarcinomas and acts as an oncogenic driver. Dabrafenib, alone or combined with trametinib, has shown substantial antitumour activity in patients with previously treated BRAF(V600E)-mutant metastatic non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of dabrafenib plus trametinib treatment in previously untreated patients with BRAF(V600E)-mutant metastatic NSCLC. METHODS: In this phase 2, sequentially enrolled, multicohort, multicentre, non-randomised, open-label study, adults (≥18 years of age) with previously untreated metastatic BRAF(V600E)-mutant NSCLC were enrolled into cohort C from 19 centres in eight countries within North America, Europe, and Asia...
September 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28918496/recurrent-papillary-craniopharyngioma-with-brafv600e-mutation-treated-with-neoadjuvant-targeted-therapy
#19
Elham Rostami, Petra Witt Nyström, Sylwia Libard, Johan Wikström, Olivera Casar-Borota, Olafur Gudjonsson
Craniopharyngiomas are histologically benign but locally aggressive tumors in the sellar region that may cause devastating neurological and endocrine deficits. They tend to recur following surgery with high morbidity; hence, postoperative radiotherapy is recommended following sub-total resection. BRAFV600E mutation is the principal oncogenic driver in the papillary variant of craniopharyngiomas. Recently, a dramatic tumor reduction has been reported in a patient with BRAFV600E mutated, multiply recurrent papillary craniopharyngioma using a combination therapy of BRAF inhibitor dabrafenib and MEK inhibitor trametinib...
September 16, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28918044/targeted-disruption-of-v600e-mutant-braf-gene-by-crispr-cpf1
#20
Meijia Yang, Heng Wei, Yuelong Wang, Jiaojiao Deng, Yani Tang, Liangxue Zhou, Gang Guo, Aiping Tong
BRAF-V600E (1799T > A) is one of the most frequently reported driver mutations in multiple types of cancers, and patients with such mutations could benefit from selectively inactivating the mutant allele. Near this mutation site, there are two TTTN and one NGG protospacer-adjacent motifs (PAMs) for Cpf1 and Cas9 CRISPR nucleases, respectively. The 1799T > A substitution also leads to the occurrence of a novel NGNG PAM for the EQR variant of Cas9. We examined the editing efficacy and selectivity of Cpf1, Cas9, and EQR variant to this mutation site...
September 15, 2017: Molecular Therapy. Nucleic Acids
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