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https://www.readbyqxmd.com/read/27922189/optimal-arac-cytotoxicity-to-aml-cells-requires-erk5-activity
#1
Ruifang Zheng, George P Studzinski
Cytarabine (AraC) has been the primary treatment agent for Acute Myeloid Leukemia (AML) in the past 30 years, but the precise mechanism of its action is not completely known. Here we assessed the role of ERK5 in AraC-induced cell death in AML cell lines HL60 and U937 using ERK5 inhibitors BIX02189 and XMD8-92. We report that inhibition of MEK5/ERK5 activity reduces AraC-induced cell death, DNA damage, the upregulated DNA damage biomarkers, and produced G2 phase cell cycle arrest. In addition, the pro-survival protein P-Bcl2 Ser70 was found to be associated with decreased AraC-induced cell death following XMD8-92 treatment, suggesting a regulatory role of ERK5 on Bcl2 phosphorylation...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27922049/identification-of-kiaa1199-as-a-biomarker-for-pancreatic-intraepithelial-neoplasia
#2
Han Na Suh, Sohee Jun, Ah-Young Oh, Mrinal Srivastava, Sunhye Lee, Cullen M Taniguchi, Songlin Zhang, Won Sup Lee, Junjie Chen, Bum-Joon Park, Jae-Il Park
Pancreatic cancer is one of the most aggressive cancers and has an extremely poor prognosis. Despite recent progress in both basic and clinical research, most pancreatic cancers are detected at an incurable stage owing to the absence of disease-specific symptoms. Thus, developing novel approaches for detecting pancreatic cancer at an early stage is imperative. Our in silico and immunohistochemical analyses showed that KIAA1199 is specifically expressed in human pancreatic cancer cells and pancreatic intraepithelial neoplasia, the early lesion of pancreatic cancer, in a genetically engineered mouse model and in human patient samples...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922044/from-tumour-heterogeneity-to-advances-in-precision-treatment-of-colorectal-cancer
#3
REVIEW
Cornelis J A Punt, Miriam Koopman, Louis Vermeulen
In recent years, the high heterogeneity of colorectal cancer (CRC) has become evident. Hence, biomarkers need to be developed that enable the stratification of patients with CRC into different prognostic subgroups and in relation to response to therapies, according to the distinctive tumour biology. Currently, only RAS-mutation status is used routinely as a negative predictive marker to avoid treatment with anti-EGFR agents in patients with metastatic CRC, and mismatch-repair status can guide the use of adjuvant chemotherapy in patients with early stage colon cancer...
December 6, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27922010/mek-inhibitors-block-growth-of-lung-tumours-with-mutations-in-ataxia-telangiectasia-mutated
#4
Michal Smida, Ferran Fece de la Cruz, Claudia Kerzendorfer, Iris Z Uras, Barbara Mair, Abdelghani Mazouzi, Tereza Suchankova, Tomasz Konopka, Amanda M Katz, Keren Paz, Katalin Nagy-Bojarszky, Markus K Muellner, Zsuzsanna Bago-Horvath, Eric B Haura, Joanna I Loizou, Sebastian M B Nijman
Lung cancer is the leading cause of cancer deaths, and effective treatments are urgently needed. Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma but directly targeting these with drugs remains challenging. Here we report that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27921315/imputing-estrogen-receptor-er-status-in-a-population-based-cancer-registry-a-sensitivity-analysis
#5
Rebecca Andridge, Anne-Michelle Noone, Nadia Howlader
Breast cancers are clinically heterogeneous based on tumor markers. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program provides baseline data on these tumor markers for reporting cancer burden and trends over time in the US general population. These tumor markers, however, are often prone to missing observations. In particular, estrogen receptor (ER) status, a key biomarker in the study of breast cancer, has been collected since 1992 but historically was not well-reported, with missingness rates as high as 25% in early years...
December 5, 2016: Statistics in Medicine
https://www.readbyqxmd.com/read/27921102/infrared-spectral-histopathology-using-haematoxylin-and-eosin-h-e-stained-glass-slides-a-major-step-forward-towards-clinical-translation
#6
Michael J Pilling, Alex Henderson, Jonathan H Shanks, Michael D Brown, Noel W Clarke, Peter Gardner
Infrared spectral histopathology has shown great promise as an important diagnostic tool, with the potential to complement current pathological methods. While promising, clinical translation has been hindered by the impracticalities of using infrared transmissive substrates which are both fragile and prohibitively very expensive. Recently, glass has been proposed as a potential replacement which, although largely opaque in the infrared, allows unrestricted access to the high wavenumber region (2500-3800 cm(-1))...
December 6, 2016: Analyst
https://www.readbyqxmd.com/read/27920576/hmmr-antisense-rna-1-a-novel-long-noncoding-rna-regulates-the-progression-of-basal-like-breast-cancer-cells
#7
Wei Liu, Jun Ma, Yong Cheng, Hongbo Zhang, Wengguang Luo, Hongyan Zhang
Recently, accumulating evidence has suggested that long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis and cancer progression. Hyaluronan-mediated motility receptor (HMMR) is an essential cancer-related gene in basal-like breast cancer (BLBC). In our study, HMMR antisense RNA 1 (HMMR-AS1) was analyzed in BLBC patients through polymerase chain reaction analysis. Here, we found that the expression of HMMR was positively correlated with HMMR-AS1 (RP11-80G.1). When HMMR-AS1 (RP11-80G.1) was knocked down, the expression of HMMR markedly reduced...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/27920368/use-of-the-concordance-index-for-predictors-of-censored-survival-data
#8
Adam R Brentnall, Jack Cuzick
The concordance index is often used to measure how well a biomarker predicts the time to an event. Estimators of the concordance index for predictors of right-censored data are reviewed, including those based on censored pairs, inverse probability weighting and a proportional-hazards model. Predictive and prognostic biomarkers often lose strength with time, and in this case the aforementioned statistics depend on the length of follow up. A semi-parametric estimator of the concordance index is developed that accommodates converging hazards through a single parameter in a Pareto model...
December 5, 2016: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/27920066/new-concepts-for-an-old-problem-the-diagnosis-of-endometrial-hyperplasia
#9
REVIEW
Peter A Sanderson, Hilary O D Critchley, Alistair R W Williams, Mark J Arends, Philippa T K Saunders
BACKGROUND: Endometrial hyperplasia (EH) is a uterine pathology representing a spectrum of morphological endometrial alterations. It is predominantly characterized by an increase in the endometrial gland-to-stroma ratio when compared to normal proliferative endometrium. The clinical significance of EH lies in the associated risk of progression to endometrioid endometrial cancer (EC) and 'atypical' forms of EH are regarded as premalignant lesions. Traditional histopathological classification systems for EH exhibit wide and varying degrees of diagnostic reproducibility and, as a consequence, standardized patient management can be challenging...
December 4, 2016: Human Reproduction Update
https://www.readbyqxmd.com/read/27920018/a-phase-ii-randomized-placebo-controlled-trial-of-oral-n-acetylcysteine-for-protection-of-melanocytic-nevi-against-uv-induced-oxidative-stress-in-vivo
#10
Pamela B Cassidy, Tong Liu, Scott R Florell, Matthew Honeggar, Sancy A Leachman, Kenneth M Boucher, Douglas Grossman
Oxidative stress plays a role in UV-induced melanoma, which may arise from melanocytic nevi. We investigated whether oral administration of the antioxidant N-acetylcysteine (NAC) could protect nevi from oxidative stress in vivo in the setting of acute UV exposure. The minimal erythemal dose (MED) was determined for 100 patients at increased risk for melanoma. Patients were randomized to receive a single dose (1,200 mg) of NAC or placebo, in double-blind fashion, and then one nevus was irradiated (1-2 MED) using a solar simulator...
December 5, 2016: Cancer Prevention Research
https://www.readbyqxmd.com/read/27919991/homotypic-interaction-of-stabilin-2-plays-a-critical-role-in-lymph-node-metastasis-of-tongue-cancer
#11
Myung Woul Han, Jong Cheol Lee, Seung-Yoon Park, Young Min Kim, Kyung-Ja Cho, Seong Who Kim, Myungjin Lee, Soon Yuhl Nam, In-San Kim, Sang Yoon Kim
BACKGROUND/AIM: Lymph node (LN) metastasis of solid types of tumors has important clinical significance and it is therefore critical to identify molecular biomarkers that would enable the selection of patients with LN metastases. PATIENTS AND METHODS: We evaluated the expression of stabilin-2 in primary oral tongue tumors and metastatic LNs using immunohistochemical staining. The correlation between risk factors and nodal metastasis was assessed and disease-free survival was analyzed...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919960/dancr-acts-as-a-diagnostic-biomarker-and-promotes-tumor-growth-and-metastasis-in-hepatocellular-carcinoma
#12
Xiang Ma, Xin Wang, Chao Yang, Zusen Wang, Bing Han, Liqun Wu, Likun Zhuang
BACKGROUND: Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is considered to be an oncogene in many cancer types. However, the role of DANCR in diagnosis and progression of hepatocellular carcinoma (HCC) is still unknown. PATIENTS AND METHODS: In this study, 146 participants including healthy volunteers (HVs) and patients with chronic hepatitis B (CHB), cirrhosis and HCC were recruited. RESULTS: Firstly, quantitative reverse transcription-PCR analysis showed that DANCR was up-regulated in tumor tissues and plasma of patients with HCC, and its expression was highly correlated with microvascular and liver capsule invasion of HCC...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919785/a-comparative-assessment-of-preclinical-chemotherapeutic-response-of-tumors-using-quantitative-non-gaussian-diffusion-mri
#13
Junzhong Xu, Ke Li, R Adam Smith, John C Waterton, Ping Zhao, Zhaohua Ding, Mark D Does, H Charles Manning, John C Gore
BACKGROUND: Diffusion-weighted MRI (DWI) signal attenuation is often not mono-exponential (i.e. non-Gaussian diffusion) with stronger diffusion weighting. Several non-Gaussian diffusion models have been developed and may provide new information or higher sensitivity compared with the conventional apparent diffusion coefficient (ADC) method. However the relative merits of these models to detect tumor therapeutic response is not fully clear. METHODS: Conventional ADC, and three widely-used non-Gaussian models, (bi-exponential, stretched exponential, and statistical model), were implemented and compared for assessing SW620 human colon cancer xenografts responding to barasertib, an agent known to induce apoptosis via polyploidy...
December 2, 2016: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/27918854/randomized-trial-testing-the-effects-of-eating-frequency-on-two-hormonal-biomarkers-of-metabolism-and-energy-balance
#14
Martine M Perrigue, Adam Drewnowski, Ching-Yun Wang, Xiaoling Song, Mario Kratz, Marian L Neuhouser
BACKGROUND: Eating frequency (EF) may influence obesity-related disease risk by attenuating postprandial fluctuations in hormones involved in metabolism, appetite regulation, and inflammation. MATERIALS/METHODS: This randomized crossover intervention trial tested the effects of EF on fasting plasma insulin-like growth factor-I (IGF-1) and leptin. Fifteen subjects (4 males, 11 females) completed two eucaloric intervention phases lasting 21 days each: low EF ("low-EF"; 3 eating occasions/day) and high EF ("high-EF"; 8 eating occasions/day)...
December 5, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27918846/soy-food-intake-and-biomarkers-of-breast-cancer-risk-possible-difference-in-asian-women
#15
Gertraud Maskarinec, Dan Ju, Yukiko Morimoto, Adrian A Franke, Frank Z Stanczyk
Soy foods may protect against breast cancer in Asian but not in Western populations. We examined if the levels of various markers of breast cancer risk and inflammation, as well as the effects of soy food consumption on these markers, differ between Asian and non-Asian premenopausal women in two soy intervention trials. One study randomized 220 women to a 2-yr intervention and the other one randomized 96 women in a crossover design to examine the effects of consumption of 2 daily soy servings on nipple aspirate fluid (NAF) volume; estrogens in serum, NAF, and urine; insulin-like growth factor-1 (IGF-1), IGF-binding protein 3, and inflammatory markers in serum; and mammographic densities...
December 5, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27918650/clinical-value-of-fully-automated-p16-ki-67-dual-staining-in-the-triage-of-hpv-positive-women-in-the-norwegian-cervical-cancer-screening-program
#16
Irene T Ovestad, Ingvild Dalen, Elisabeth Hansen, Janne L D Loge, Britt Mona Dybdahl, Marius B Dirdal, Pia Moltu, Jannicke M Berland
BACKGROUND: More accurate biomarkers in cervical cytology screening could reduce the number of women unnecessarily referred for biopsy. This study investigated the ability of p16/Ki-67 dual staining to predict high-grade cervical intraepithelial neoplasia (CIN) in human papillomavirus (HPV)-positive women from the Norwegian Cervical Cancer Screening Program. METHODS: Automated p16/Ki-67 dual staining was performed on liquid-based cytology samples from 266 women who were HPV-positive at their secondary screening...
December 5, 2016: Cancer
https://www.readbyqxmd.com/read/27918595/impact-of-sonic-hedgehog-pathway-expression-on-outcome-in-hpv-negative-head-and-neck-carcinoma-patients-after-surgery-and-adjuvant-radiotherapy
#17
Elisabeth Enzenhofer, Thomas Parzefall, Georg Haymerle, Sven Schneider, Lorenz Kadletz, Gregor Heiduschka, Johannes Pammer, Felicitas Oberndorfer, Fritz Wrba, Benjamin Loader, Matthäus Christoph Grasl, Christos Perisanidis, Boban M Erovic
INTRODUCTION: HPV positive patients suffering from head and neck cancer benefit from intensified radiotherapy when applied as a primary as well as an adjuvant treatment strategy. However, HPV negative patients treated with surgery and adjuvant radiotherapy lack validated prognostic biomarkers. It is therefore important to define prognostic biomarkers in this particular patient population. Especially, ´high-risk groups´ need to be defined in order to adapt treatment protocols. Since dysregulation of the sonic hedgehog pathway plays an important role in carcinogenesis, we aimed to assess whether members of the sonic hedgehog-signaling pathway may act as prognostic factors in patients with HPV negative head and neck squamous cell carcinoma...
2016: PloS One
https://www.readbyqxmd.com/read/27918237/gpx3-promoter-methylation-predicts-platinum-sensitivity-in-colorectal-cancer
#18
Lorraine Pelosof, Sashidhar Yerram, Todd Armstrong, Nina Chu, Ludmila Danilova, Breann Yanagisawa, Manuel Hidalgo, Nilofer Azad, James G Herman
Epigenetic control of gene expression is a major determinant of tumor phenotype and has been found to influence sensitivity to individual chemotherapeutic agents. Glutathione peroxidase 3 (GPX3, plasma glutathione peroxidase) is a key component of cellular antioxidant regulation and its gene has been reported to be methylated in specific tumor types. GPX3 role in oxidative damage has been associated with sensitivity to platinums in other tumors but its importance in colorectal cancer (CRC) has not been determined...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27918216/s100p-is-overexpressed-in-squamous-cell-and-adenosquamous-carcinoma-subtypes-of-endometrial-cancer-and-promotes-cancer-cell-proliferation-and-invasion
#19
Hongfei Jiang, Hang Hu, Fan Lin, Yoon Pin Lim, Yunfen Hua, Xiaomei Tong, Songying Zhang
S100P is known to affect tumor development and metastasis of various cancers, but its role in endometrial cancer is unclear. We reported that S100P expression was dramatically elevated in both endometrial squamous cell carcinoma and adenosquamous carcinoma, but not in adenocarcinoma and normal endometrial samples. Moreover, we revealed an oncogenic role of S100P promoting cell proliferation, invasion, and migration while reducing apoptosis, possibly via its upregulation and/or activation of receptors of advanced glycation end products and consequently the oncogenic PI3K-AKT and MAPK pathways...
November 25, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/27917920/transcriptome-and-long-noncoding-rna-sequencing-of-three-extracellular-vesicle-subtypes-released-from-the-human-colon-cancer-lim1863-cell-line
#20
Maoshan Chen, Rong Xu, Hong Ji, David W Greening, Alin Rai, Keiichi Izumikawa, Hideaki Ishikawa, Nobuhiro Takahashi, Richard J Simpson
Previously we reported that LIM1863 colorectal cancer (CRC) cells secrete three distinct extracellular vesicle subtypes - two subpopulations of exosomes (apical EpCAM-Exos and basolateral A33-Exos) and shed microvesicles (sMVs) - with distinct protein and miRNA signatures. Here, we extend our omics approach to understand the fundamental role of LIM1863-derived EVs by performing a comprehensive analysis of their mRNAs and long non-coding RNAs (lncRNAs) using RNA-Seq. We show that 2,389 mRNAs, 317 pseudogene transcripts, 1,028 lncRNAs and 206 short non-coding RNAs selectively distributed to (i...
December 5, 2016: Scientific Reports
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