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https://www.readbyqxmd.com/read/28922791/targeting-hypoxia-to-improve-non-small-cell-lung-cancer-outcome
#1
Ahmed Salem, Marie-Claude Asselin, Bart Reymen, Alan Jackson, Philippe Lambin, Catharine M L West, James P B O'Connor, Corinne Faivre-Finn
Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance and poor survival. Hypoxia is an attractive therapeutic target, particularly in the context of radiotherapy, which is delivered to more than half of NSCLC patients. However, NSCLC hypoxia-targeted therapy trials have not yet translated into patient benefit. Recently, early termination of promising evofosfamide and tarloxotinib bromide studies due to futility highlighted the need for a paradigm shift in our approach to avoid disappointments in future trials...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922238/primary-central-nervous-system-lymphoma-time-for-diagnostic-biomarkers-and-biotherapies
#2
Louis Royer-Perron, Khê Hoang-Xuan, Agusti Alentorn
PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare cancer with a somber prognosis in older patients, which it affects predominantly. Only in recent years have molecular alterations characterizing PCNSL been thoroughly described. This opens possibilities for the use of targeted therapies. Developments in imaging and biomarkers have also great potential to help clinicians faced with diagnostic and prognostic uncertainties. RECENT FINDINGS: Several biomarkers for PCNSL, such as different microRNAs, which could be tested in cerebrospinal fluid and vitreous fluid, and IL-10, which has been shown to have excellent sensitivity and specificity in the cerebrospinal fluid, have emerged in the last years...
September 15, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28916879/a-score-combining-baseline-neutrophilia-and-primary-tumor-suvpeak-measured-from-fdg-pet-is-associated-with-outcome-in-locally-advanced-cervical-cancer
#3
Antoine Schernberg, Sylvain Reuze, Fanny Orlhac, Irène Buvat, Laurent Dercle, Roger Sun, Elaine Limkin, Alexandre Escande, Christine Haie-Meder, Eric Deutsch, Cyrus Chargari, Charlotte Robert
PURPOSE: We investigated whether a score combining baseline neutrophilia and a PET biomarker could predict outcome in patients with locally advanced cervical cancer (LACC). METHODS: Patients homogeneously treated with definitive chemoradiation plus image-guided adaptive brachytherapy (IGABT) between 2006 and 2013 were analyzed retrospectively. We divided patients into two groups depending on the PET device used: a training set (TS) and a validation set (VS). Primary tumors were semi-automatically delineated on PET images, and 11 radiomics features were calculated (LIFEx software)...
September 15, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#4
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28915670/prostate-cancer-diagnosis-using-epigenetic-biomarkers-3d-high-content-imaging-and-probabilistic-cell-by-cell-classifiers
#5
Darko Stefanovski, George Tang, Kolja Wawrowsky, Raymond C Boston, Nils Lambrecht, Jian Tajbakhsh
BACKGROUND: Prostate cancer (PCa) management can benefit from novel concepts/biomarkers for reducing the current 20-30% chance of false-negative diagnosis with standard histopathology of biopsied tissue. METHOD: We explored the potential of selected epigenetic markers in combination with validated histopathological markers, 3D high-content imaging, cell-by-cell analysis, and probabilistic classification in generating novel detailed maps of biomarker heterogeneity in patient tissues, and PCa diagnosis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915312/dce-and-dw-mri-as-early-imaging-biomarkers-of-treatment-response-in-a-preclinical-model-of-triple-negative-breast-cancer
#6
Stephanie L Barnes, Anna G Sorace, Jennifer G Whisenant, J Oliver McIntyre, Hakmook Kang, Thomas E Yankeelov
This work evaluates quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted MRI (DW-MRI) parameters as early biomarkers of response in a preclinical model of triple negative breast cancer (TNBC). The standard Tofts' model of DCE-MRI returns estimates of the volume transfer constant (K(trans) ) and the extravascular extracellular volume fraction (ve ). DW-MRI returns estimates of the apparent diffusion coefficient (ADC). Mice (n = 38) were injected subcutaneously with MDA-MB-231...
September 15, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28912459/iron-deposition-is-associated-with-differential-macrophage-infiltration-and-therapeutic-response-to-iron-chelation-in-prostate-cancer
#7
Avigdor Leftin, Huiyong Zhao, Mesru Turkekul, Elisa de Stanchina, Katia Manova, Jason A Koutcher
Immune cells such as macrophages are drivers and biomarkers of most cancers. Scoring macrophage infiltration in tumor tissue provides a prognostic assessment that is correlated with disease outcome and therapeutic response, but generally requires invasive biopsy. Routine detection of hemosiderin iron aggregates in macrophages in other settings histologically and in vivo by MRI suggests that similar assessments in cancer can bridge a gap in our ability to assess tumor macrophage infiltration. Quantitative histological and in vivo MRI assessments of non-heme cellular iron revealed that preclinical prostate tumor models could be differentiated according to hemosiderin iron accumulation-both in tumors and systemically...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28910821/vascular-disrupting-agent-in-pancreatic-and-hepatic-tumour-allografts-observations-of-location-dependent-efficacy-by-mri-microangiography-and-histomorphology
#8
Ting Yin, Yewei Liu, Ronald Peeters, Yuanbo Feng, Jie Yu, Uwe Himmelreich, Raymond Oyen, Yicheng Ni
BACKGROUND: Tumours growing in organs of different vascular environment could exhibit diverse responses to vascular disrupting agent (VDA). This study was aimed to identify in vivo imaging biomarkers for evaluation of pancreatic and hepatic tumours and comparison of their responses to a VDA Combretastatin A4 Phosphate (CA4P) using multiparametric MRI. METHODS: Male WAG/Rij rats were used for orthotopic pancreatic head tumour and hepatic tumour implantation; tumour growth was monitored by 3D isotropic MRI using a 3...
September 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28906339/multiparametric-magnetic-resonance-imaging-of-prostate-cancer-bone-disease-correlation-with-bone-biopsy-histological-and-molecular-features
#9
Raquel Perez-Lopez, Daniel Nava Rodrigues, Ines Figueiredo, Joaquin Mateo, David J Collins, Dow-Mu Koh, Johann S de Bono, Nina Tunariu
OBJECTIVES: The aim of this study was to correlate magnetic resonance imaging (MRI) of castration-resistant prostate cancer (CRPC) bone metastases with histological and molecular features of bone metastases. MATERIALS AND METHODS: Forty-three bone marrow biopsies from 33 metastatic CRPC (mCRPC) patients with multiparametric MRI and documented bone metastases were evaluated. A second cohort included 10 CRPC patients with no bone metastases. Associations of apparent diffusion coefficient (ADC), normalized b900 diffusion-weighted imaging (nDWI) signal, and signal-weighted fat fraction (swFF) with bone marrow biopsy histological parameters were evaluated using Mann-Whitney U test and Spearman correlations...
September 12, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28904817/ihc-based-subcellular-quantification-provides-new-insights-into-prognostic-relevance-of-flip-and-procaspase-8-in-non-small-cell-lung-cancer
#10
Ryan A Hutchinson, Helen G Coleman, Kathy Gately, Vincent Young, Siobhan Nicholson, Robert Cummins, Elaine Kay, Sean O Hynes, Philip D Dunne, Seedevi Senevirathne, Peter W Hamilton, Darragh G McArt, Daniel B Longley
In this study, we developed an image analysis algorithm for quantification of two potential apoptotic biomarkers in non-small-cell lung cancer (NSCLC): FLIP and procaspase-8. Immunohistochemical expression of FLIP and procaspase-8 in 184 NSCLC tumors were assessed. Individual patient cores were segmented and classified as tumor and stroma using the Definiens Tissue Studio. Subsequently, chromogenic expression of each biomarker was measured separately in the nucleus and cytoplasm and reported as a quantitative histological score...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28903399/phosphatidylcholine-specific-phospholipase-c-inhibition-reduces-her2-overexpression-cell-proliferation-and-in-vivo-tumor-growth-in-a-highly-tumorigenic-ovarian-cancer-model
#11
Luisa Paris, Franca Podo, Francesca Spadaro, Laura Abalsamo, Maria Elena Pisanu, Alessandro Ricci, Serena Cecchetti, Luisa Altabella, Maria Buoncervello, Ludmila Lozneanu, Marina Bagnoli, Carlo Ramoni, Silvana Canevari, Delia Mezzanzanica, Egidio Iorio, Rossella Canese
Antagonizing the oncogenic effects of human epidermal growth factor receptor 2 (HER2) with current anti-HER2 agents has not yet yielded major progress in the treatment of advanced HER2-positive epithelial ovarian cancer (EOC). Using preclinical models to explore alternative molecular mechanisms affecting HER2 overexpression and oncogenicity may lead to new strategies for EOC patient treatment. We previously reported that phosphatidylcholine-specific phospholipase C (PC-PLC) exerts a pivotal role in regulating HER2 overexpression in breast cancer cells...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902567/phase-ii-cancer-clinical-trials-for-biomarker-guided-treatments
#12
Sin-Ho Jung
The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomaker, whether the used biomarker is validated or not, and the study objectives. In this paper, we demonstrate the design and analysis of two phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint...
September 13, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28900512/aptavalve-gated-mesoporous-carbon-nanospheres-image-cellular-mucin-and-provide-on-demand-targeted-drug-delivery
#13
Chengyi Li, Min Qian, Shanshan Wang, Huilin Jiang, Yilin Du, Jianxin Wang, Weiyue Lu, Niren Murthy, Rongqin Huang
In this report, we present a mesoporous carbon nanosphere that can target drugs to tumors and image tumor biomarkers. A single-strand DNA (P0 aptamer) aptavalve was capped on the surface of doxorubicin-loaded oxide mesoporous carbon nanospheres (Dox-OMCN-P0) through π-π stacking for real-time imaging-guided on-demand targeting drug delivery. The Dox-OMCN-P0 could not only realize the detection of MUC1 tumor marker with a wide linear range (0.1 - 10.6 μmol/L) and a low detection limit (17.5 nmol) based on different apparatuses, but also achieve in-situ targeting imaging of cellular MUC1 concentration in vitro and in vivo via "off-on" fluorescence biosensing...
2017: Theranostics
https://www.readbyqxmd.com/read/28900220/diffusion-kurtosis-imaging-evaluating-epithelial-mesenchymal-transition-in-colorectal-carcinoma-xenografts-model-a-preliminary-study
#14
Huanhuan Liu, Wenbin Shen, Caiyuan Zhang, Yanfen Cui, Jinning Li, Tingting Zhang, Weibo Chen, Dengbin Wang
Epithelial-mesenchymal transition (EMT) plays an important role in aggravating invasiveness and metastatic behavior of colorectal cancer (CRC). Identification of EMT is important for structuring treatment strategy, but has not yet been studied by using noninvasive imaging modality. Diffusion kurtosis imaging (DKI) is an advanced diffusion weighted model that could reflect tissue microstructural changes in vivo. In this study, EMT was induced in CRC cells (HCT116) by overexpressing Snail1 gene. We aimed to investigate the value of DKI in identifying EMT in CRC and decipher the correlations between DKI-derived parameters and EMT biomarker E-cadherin and cell proliferative index Ki-67 expression...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898277/iron-imaging-reveals-tumor-and-metastasis-macrophage-hemosiderin-deposits-in-breast-cancer
#15
Avigdor Leftin, Nir Ben-Chetrit, Florian Klemm, Johanna A Joyce, Jason A Koutcher
Iron-deposition is a metabolic biomarker of macrophages in both normal and pathological situations, but the presence of iron in tumor and metastasis-associated macrophages is not known. Here we mapped and quantified hemosiderin-laden macrophage (HLM) deposits in murine models of metastatic breast cancer using iron and macrophage histology, and in vivo MRI. Iron MRI detected high-iron pixel clusters in mammary tumors, lung metastasis, and brain metastasis as well as liver and spleen tissue known to contain the HLMs...
2017: PloS One
https://www.readbyqxmd.com/read/28894575/genomic-imbalances-and-myb-fusion-in-synchronous-bilateral-adenoid-cystic-carcinoma-and-invasive-lobular-carcinoma-of-the-breast
#16
Anikó Kovács, Fredrik Persson, Marta Persson, Mattias K Andersson, Göran Stenman
The incidence of synchronous bilateral breast carcinomas (BBCs) has increased with a more frequent use of magnetic resonance imaging screening of the contralateral breast in women with newly diagnosed breast cancer. A total of 30% of all BBCs occur synchronously. In the present study, we describe a unique case of synchronous BBC in a 59-year-old previously healthy woman with no known family history of breast or ovarian cancer. At the time of diagnosis the patient had an invasive lobular carcinoma (ILC) in the right breast and an adenoid cystic carcinoma (ACC) in the left breast...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28891455/epigenetic-biomarkers-for-risk-assessment-of-particulate-matter-associated-lung-cancer
#17
Arpit Bhargava, Neha Bunkar, Aniket Aglawe, Kailash Chand Pandey, Rajnarayan Tiwari, Koel Chaudhury, Irina Yu Goryacheva, Pradyumna Kumar Mishra
BACKGROUND: Particulate matter directly emitted into the air by sources such as combustion processes and windblown dust, or formed in the atmosphere by transformation of emitted gases are the major contributors to air pollution that triggers a diverse array of human pathologies including lung cancer. The mortality in lung cancer is usually high as the disease is not symptomatic at its early treatable stage. Moreover, available methods for screening are costly and mainly rely on imaging techniques which lack sufficient sensitivity and specificity...
September 10, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28888199/chlorambucil-labelled-with-the-phenosafranin-scaffold-as-a-new-chemotherapeutic-for-imaging-and-cancer-treatment
#18
Beata Miksa, Malgorzata Sierant, Ewa Skorupska, Adam Michalski, Slawomir Kazmierski, Urszula Steinke, Artur Rozanski, Pawel Uznanski
Here we report the first of the phenosafranin-chlorambucil conjugate as a new type of a chemotherapeutic agent suitable for dual detection methods (spectrophotometric and fluorescence) in imaging systems and cancer treatment. The synthetic cationic dye (3,7-diamino-5-phenylphenazinium chloride) is used as a fluorescent light-triggered scaffold that acts as a carrier for an anti-cancer drug. The chlorambucil was attached covalently via amide bonds to the bifunctional fluorophore, which facilitates tracking with visible light...
September 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28886423/molecular-imaging-of-colorectal-tumors-by-targeting-colon-cancer-secreted-protein-2-ccsp-2
#19
Jaeil Kim, Eun-Ju Do, Helen Moinova, Sang Mun Bae, Ja Young Kang, Seung-Mo Hong, Stephen P Fink, Jinmyoung Joo, Young-Ah Suh, Se Jin Jang, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Jaewon Choe, Suk-Kyun Yang, Sanford D Markowitz, Sang-Yeob Kim, Seung-Jae Myung
A versatile biomarker for detecting colonic adenoma and colon cancer has yet to be developed. Colon cancer secreted protein-2 (CCSP-2) is a protein specifically expressed and secreted in colon adenomas and cancers. We developed a fluorescent imaging method based on CCSP-2 targeting for a more sensitive and specific detection of colorectal tumors. CCSP-2 expression was evaluated in human colon adenoma and colorectal specimens. Anti-CCSP-2 antibody was labeled with a near-infrared fluorescent dye, FPR-675, and molecular imaging of surgical human colorectal tumors was performed...
September 4, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28885890/qualitative-radiogenomics-association-between-oncotype-dx-test-recurrence-score-and-bi-rads-mammographic-and-breast-mr-imaging-features
#20
Genevieve A Woodard, Kimberly M Ray, Bonnie N Joe, Elissa R Price
Purpose To evaluate the association between Breast Imaging Reporting and Data System (BI-RADS) mammographic and magnetic resonance (MR) imaging features and breast cancer recurrence risk in patients with estrogen receptor-positive breast cancer who underwent the Oncotype DX assay. Materials and Methods In this institutional review board-approved and HIPAA-compliant protocol, 408 patients diagnosed with invasive breast cancer between 2004 and 2013 who underwent the Oncotype DX assay were identified. Mammographic and MR imaging features were retrospectively collected according to the BI-RADS lexicon...
September 8, 2017: Radiology
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