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https://www.readbyqxmd.com/read/28738565/zwitterionic-hydrophilic-interaction-liquid-chromatography-tandem-mass-spectrometry-with-hybridspe-precipitation-for-the-determination-of-intact-cisplatin-in-human-plasma
#1
Feifan Xie, Pieter Colin, Jan Van Bocxlaer
Cisplatin is a first-line chemotherapeutic for the treatment of a wide variety of cancers since its discovery in the 1960s. Although various techniques have been reported for the measurement of total platinum in biological matrices, such as inductively coupled plasma-mass spectrometry and derivatization procedures, a specific, sensitive and robust assay for the quantification of intact cisplatin is still lacking. Therefore, we present a rapid, selective, sensitive, and reliable UHPLC-MS/MS based method for the determination of intact cisplatin in human plasma in support of a Phase II clinical trial...
November 1, 2017: Talanta
https://www.readbyqxmd.com/read/28733441/molecular-screening-for-cancer-treatment-optimization-moscato-01-in-pediatric-patients-a-single-institutional-prospective-molecular-stratification-trial
#2
Anne Catherine Harttrampf, Ludovic Lacroix, Marc Deloger, Frederic Deschamps, Stéphanie Puget, Nathalie Auger, Philippe Vielh, Pascale Varlet, Zsofia Balogh, Samuel Abbou, Adrien Allorant, Dominique Valteau-Couanet, Sabine Sarnacki, Louise Galmiche, Guillaume Meurice, Véronique Minard-Colin, Jacques Grill, Laurence Brugières, Christelle Dufour, Nathalie Gaspar, Stefan Michiels, Gilles Vassal, Jean-Charles Soria, Birgit Geoerger
This single institutional feasibility study prospectively characterized genomic alterations in recurrent or refractory solid tumors of pediatric patients in order to select a targeted therapy.<br /><br />Experimental Design: Following treatment failure patients with signed consent and aged above 6 months, underwent tumor biopsy or surgical resection of primary or metastatic tumor site.  These newly acquired samples were analyzed by comparative genomic hybridization array, next generation sequencing for 75 target genes, whole exome and RNA sequencing...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28731777/induction-and-maintenance-adjuvant-mitomycin-c-topical-therapy-for-upper-tract-urothelial-carcinoma-tolerability-and-intermediate-term-outcomes
#3
Michael Metcalfe, Gavin Wagenheim, Lianchun Xiao, John Papadopoulos, Neema Navai, John W Davis, Jose A Karam, Ashish M Kamat, Christopher G Wood, Colin P Dinney, Surena F Matin
PURPOSE: Endoscopic management of upper tract urothelial carcinoma (UTUC) is associated with higher recurrences, which could be reduced by application of topical therapy. Adjuvant induction Bacillus Calmette-Guerin has shown inferior outcomes for UTUC compared to bladder cancer, and maintenance regimens for UTUC are unexplored. We report on the efficacy, safety, and tolerability of Mitomycin C (MMC) induction and maintenance adjuvant topical therapy for UTUC. MATERIALS AND METHODS: Patients with UTUC who received adjuvant topical therapy after complete endoscopic control of Ta/T1 tumors were retrospectively reviewed...
July 21, 2017: Journal of Endourology
https://www.readbyqxmd.com/read/28724986/core-shell-lipid-polymer-hybrid-nanoparticles-with-combined-docetaxel-and-molecular-targeted-therapy-for-the-treatment-of-metastatic-prostate-cancer
#4
Qi Wang, Heba Alshaker, Torsten Böhler, Shyam Srivats, Yimin Chao, Colin Cooper, Dmitri Pchejetski
Many prostate cancers relapse after initial chemotherapy treatment. Combining molecular and chemotherapy together with encapsulation of drugs in nanocarriers provides effective drug delivery and toxicity reduction. We developed core shell lipid-polymer hybrid nanoparticles (CSLPHNPs) with poly (lactic-co-glycolic acid) (PLGA) core and lipid layer containing docetaxel and clinically used inhibitor of sphingosine kinase 1 (SK1) FTY720 (fingolimod). We show for the first time that FTY720 (both free and in CSLPHNPs) re-sensitizes castrate resistant prostate cancer cells and tumors to docetaxel, allowing a four-fold reduction in effective dose...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720581/hit-ndrive-patient-specific-multi-driver-gene-prioritization-for-precision-oncology
#5
Raunak Shrestha, Ermin Hodzic, Thomas Sauerwald, Phuong Dao, Kendric Wang, Jake Yeung, Shawn Anderson, Fabio Vandin, Gholamreza Haffari, Colin C Collins, Cenk Sahinalp
Prioritizing molecular alterations that act as drivers of cancer remains a crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a computational method that integrates genomic and transcriptomic data to identify a set of patient-specific, sequence-altered genes, with sufficient collective influence over dysregulated transcripts. HIT'nDRIVE aims to solve the "random walk facility location" (RWFL) problem in a gene (or protein) interaction network, which differs from the standard facility location problem by its use of an alternative distance measure: "multi-hitting time", the expected length of the shortest random walk from any one of the set of sequence-altered genes to an expression-altered target gene...
July 18, 2017: Genome Research
https://www.readbyqxmd.com/read/28714471/progression-through-mitosis-promotes-parp-inhibitor-induced-cytotoxicity-in-homologous-recombination-deficient-cancer-cells
#6
Pepijn M Schoonen, Francien Talens, Colin Stok, Ewa Gogola, Anne Margriet Heijink, Peter Bouwman, Floris Foijer, Madalena Tarsounas, Sohvi Blatter, Jos Jonkers, Sven Rottenberg, Marcel A T M van Vugt
Mutations in homologous recombination (HR) genes BRCA1 and BRCA2 predispose to tumorigenesis. HR-deficient cancers are hypersensitive to Poly (ADP ribose)-polymerase (PARP) inhibitors, but can acquire resistance and relapse. Mechanistic understanding how PARP inhibition induces cytotoxicity in HR-deficient cancer cells is incomplete. Here we find PARP inhibition to compromise replication fork stability in HR-deficient cancer cells, leading to mitotic DNA damage and consequent chromatin bridges and lagging chromosomes in anaphase, frequently leading to cytokinesis failure, multinucleation and cell death...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28700433/data-set-for-the-reporting-of-carcinomas-of-the-cervix-recommendations-from-the-international-collaboration-on-cancer-reporting-iccr
#7
W Glenn McCluggage, Meagan J Judge, Isabel Alvarado-Cabrero, Máire A Duggan, Lars-Christian Horn, Pei Hui, Jaume Ordi, Christopher N Otis, Kay J Park, Marie Plante, Colin J R Stewart, Edwin K Wiredu, Brian Rous, Lynn Hirschowitz
A comprehensive pathologic report is essential for optimal patient management, cancer staging and prognostication. In many countries, proforma reports are used but the content of these is variable. The International Collaboration on Cancer Reporting is an alliance formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Partnership Against Cancer and the European Society of Pathology, for the purpose of developing standardized, evidence-based reporting data sets for each cancer site...
July 11, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28699269/determinants-of-short-and-long-term-outcomes-in-patients-undergoing-immediate-breast-reconstruction-following-neoadjuvant-chemotherapy
#8
Craig A Wengler, Stephanie A Valente, Zahraa AlHilli, Neil M Woody, Julia H Muntean, Jame Abraham, Rahul D Tendulkar, Risal Djohan, Colin O'Rourke, Joseph P Crowe, Stephen R Grobmyer
BACKGROUND: We evaluated oncologic outcomes and complications of skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) with immediate reconstruction (IR) after neoadjuvant chemotherapy (NAC) in patients with early-stage and locally advanced breast cancer (BC). METHODS: BC patients from 2000 to 2014 treated with NAC followed by SSM/NSM and IR were reviewed. Patient demographics, tumor characteristics, NAC response, complications, and recurrence were analyzed...
July 11, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28698647/identification-of-fbxl4-as-a-metastasis-associated-gene-in-prostate-cancer
#9
Elzbieta Stankiewicz, Xueying Mao, D Chas Mangham, Lei Xu, Marc Yeste-Velasco, Gabrielle Fisher, Bernard North, Tracy Chaplin, Bryan Young, Yuqin Wang, Jasmin Kaur Bansal, Sakunthala Kudahetti, Lucy Spencer, Christopher S Foster, Henrik Møller, Peter Scardino, R Tim Oliver, Jonathan Shamash, Jack Cuzick, Colin S Cooper, Daniel M Berney, Yong-Jie Lu
Prostate cancer is the most common cancer among western men, with a significant mortality and morbidity reported for advanced metastatic disease. Current understanding of metastatic disease is limited due to difficulty of sampling as prostate cancer mainly metastasizes to bone. By analysing prostate cancer bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.1-16.2, containing the FBXL4 gene, which was confirmed in larger series of bone metastases by fluorescence in situ hybridisation (FISH)...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697982/prostate-cancer-screening-in-a-new-era-of-genetics
#10
Heather H Cheng, Colin C Pritchard, Bruce Montgomery, Daniel W Lin, Peter S Nelson
Men who inherit pathogenic germline mutations in BRCA2 and BRCA1 are at increased risk of developing aggressive prostate cancer, and those with germline mutations in other DNA repair genes such as ATM, CHEK2, and MSH2/MSH6 may also have increased risks. Although clinically important, there is lack of specific guidance regarding management strategies for men at increased risk owing to germline mutation status or family history of aggressive prostate cancer. We review prostate cancer genetic risk factors and the ongoing IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) screening study...
May 31, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28697344/muc1-and-hif-1alpha-signaling-crosstalk-induces-anabolic-glucose-metabolism-to-impart-gemcitabine-resistance-to-pancreatic-cancer
#11
Surendra K Shukla, Vinee Purohit, Kamiya Mehla, Venugopal Gunda, Nina V Chaika, Enza Vernucci, Ryan J King, Jaime Abrego, Gennifer D Goode, Aneesha Dasgupta, Alysha L Illies, Teklab Gebregiworgis, Bingbing Dai, Jithesh J Augustine, Divya Murthy, Kuldeep S Attri, Oksana Mashadova, Paul M Grandgenett, Robert Powers, Quan P Ly, Audrey J Lazenby, Jean L Grem, Fang Yu, José M Matés, John M Asara, Jung-Whan Kim, Jordan H Hankins, Colin Weekes, Michael A Hollingsworth, Natalie J Sarkova, Aaron R Sasson, Jason B Fleming, Jennifer M Oliveto, Costas A Lyssiotis, Lewis C Cantley, Lyudmyla Berim, Pankaj K Singh
Poor response to cancer therapy due to resistance remains a clinical challenge. The present study establishes a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate (dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine through molecular competition. We also demonstrate that MUC1-regulated stabilization of hypoxia inducible factor-1α (HIF-1α) mediates such metabolic reprogramming...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28697131/patterns-of-care-for-locally-advanced-pancreatic-adenocarcinoma-using-the-national-cancer-database
#12
Arya Amini, Bernard L Jones, Priscilla Stumpf, Stephen Leong, Christopher H Lieu, Colin Weekes, S Lindsey Davis, Wells A Messersmith, William T Purcell, Debashis Ghosh, Tracey Schefter, Karyn A Goodman
OBJECTIVES: The role of radiotherapy (RT) in locally advanced pancreatic cancer (LAPC) is uncertain. This study examines patterns of care and survival outcomes of LAPC undergoing chemotherapy alone versus chemotherapy plus RT (C + RT). METHODS: The National Cancer Database was queried for nonmetastatic LAPC patients who received chemotherapy alone or C + RT. RESULTS: Of the 13,695 patients included, 5306 underwent chemotherapy alone and 4971, C + RT...
August 2017: Pancreas
https://www.readbyqxmd.com/read/28695300/new-fty720-docetaxel-nanoparticle-therapy-overcomes-fty720-induced-lymphopenia-and-inhibits-metastatic-breast-tumour-growth
#13
Heba Alshaker, Qi Wang, Shyam Srivats, Yimin Chao, Colin Cooper, Dmitri Pchejetski
PURPOSE: Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity...
July 10, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28694244/tumor-matrix-stiffness-promotes-metastatic-cancer-cell-interaction-with-the-endothelium
#14
Steven E Reid, Emily J Kay, Lisa J Neilson, Anne-Theres Henze, Jens Serneels, Ewan J McGhee, Sandeep Dhayade, Colin Nixon, John Bg Mackey, Alice Santi, Karthic Swaminathan, Dimitris Athineos, Vasileios Papalazarou, Francesca Patella, Álvaro Román-Fernández, Yasmin ElMaghloob, Juan Ramon Hernandez-Fernaud, Ralf H Adams, Shehab Ismail, David M Bryant, Manuel Salmeron-Sanchez, Laura M Machesky, Leo M Carlin, Karen Blyth, Massimiliano Mazzone, Sara Zanivan
Tumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro This facilitates N-cadherin-dependent cancer cell-endothelium interaction...
July 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28687117/-relapse-after-rhabdomyosarcoma-in-childhood-and-adolescence-impact-of-an-early-detection-on-survival
#15
Coralie Mallebranche, Matthieu Carton, Véronique Minard-Colin, Anne-Sophie Desfachelle, Angélique Rome, Hervé J Brisse, Véronique Mosseri, Estelle Thébaud, Isabelle Pellier, Hélène Boutroux, Virginie Gandemer, Nadège Corradini, Daniel Orbach
SUBJECT: Prognostic values of an early detection of a relapse after treatment of a localized rhabdomyosarcoma and the interest of performing systematic radiologic assessment after treatment have not yet been evaluated in Europe. MATERIAL AND METHODS: Modalities of relapse of 99 patients under 20 years of age, after an initially localized rhabdomyosarcoma, treated in 9 French centers ("Société française des cancers de l'enfant" consortium) have been analyzed...
July 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28678185/semi-quantitative-mass-spectrometry-in-aml-cells-identifies-new-non-genomic-targets-of-the-ezh2-methyltransferase
#16
Yordan Sbirkov, Colin Kwok, Amandeep Bhamra, Andrew J Thompson, Veronica Gil, Arthur Zelent, Kevin Petrie
Alterations to the gene encoding the EZH2 (KMT6A) methyltransferase, including both gain-of-function and loss-of-function, have been linked to a variety of haematological malignancies and solid tumours, suggesting a complex, context-dependent role of this methyltransferase. The successful implementation of molecularly targeted therapies against EZH2 requires a greater understanding of the potential mechanisms by which EZH2 contributes to cancer. One aspect of this effort is the mapping of EZH2 partner proteins and cellular targets...
July 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28669882/tumor-growth-model-of-ductal-carcinoma-from-in-situ-phase-to-stroma-invasion
#17
Olivier Gallinato, Thierry Colin, Olivier Saut, Clair Poignard
This paper aims at modeling breast cancer transition from the in situ stage -when the tumor is confined to the duct- to the invasive phase. Such a transition occurs thanks to the degradation of the duct membrane under the action of specific enzymes so-called matrix metalloproteinases (MMPs). The model consists of advection-reaction equations that hold in the duct and in the surrounding tissue, in order to describe the proliferation and the necrosis of the cancer cells in each subdomain. The divergence of the velocity is given by the increase of the cell densities...
September 21, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28666423/precision-oncology-using-a-limited-number-of-cells-optimization-of-whole-genome-amplification-products-for-sequencing-applications
#18
Shonan Sho, Colin M Court, Paul Winograd, Sangjun Lee, Shuang Hou, Thomas G Graeber, Hsian-Rong Tseng, James S Tomlinson
BACKGROUND: Sequencing analysis of circulating tumor cells (CTCs) enables "liquid biopsy" to guide precision oncology strategies. However, this requires low-template whole genome amplification (WGA) that is prone to errors and biases from uneven amplifications. Currently, quality control (QC) methods for WGA products, as well as the number of CTCs needed for reliable downstream sequencing, remain poorly defined. We sought to define strategies for selecting and generating optimal WGA products from low-template input as it relates to their potential applications in precision oncology strategies...
July 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28658624/hepatocyte-hyperproliferation-upon-liver-specific-co-disruption-of-thioredoxin-1-thioredoxin-reductase-1-and-glutathione-reductase
#19
Justin R Prigge, Lucia Coppo, Sebastin S Martin, Fernando Ogata, Colin G Miller, Michael D Bruschwein, David J Orlicky, Colin T Shearn, Jean A Kundert, Julia Lytchier, Alix E Herr, Åse Mattsson, Matthew P Taylor, Tomas N Gustafsson, Elias S J Arnér, Arne Holmgren, Edward E Schmidt
Energetic nutrients are oxidized to sustain high intracellular NADPH/NADP(+) ratios. NADPH-dependent reduction of thioredoxin-1 (Trx1) disulfide and glutathione disulfide by thioredoxin reductase-1 (TrxR1) and glutathione reductase (Gsr), respectively, fuels antioxidant systems and deoxyribonucleotide synthesis. Mouse livers lacking both TrxR1 and Gsr sustain these essential activities using an NADPH-independent methionine-consuming pathway; however, it remains unclear how this reducing power is distributed...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28655541/management-of-patients-with-advanced-prostate-cancer-the-report-of-the-advanced-prostate-cancer-consensus-conference-apccc-2017
#20
Silke Gillessen, Gerhardt Attard, Tomasz M Beer, Himisha Beltran, Alberto Bossi, Rob Bristow, Brett Carver, Daniel Castellano, Byung Ha Chung, Noel Clarke, Gedske Daugaard, Ian D Davis, Johann de Bono, Rodolfo Borges Dos Reis, Charles G Drake, Ros Eeles, Eleni Efstathiou, Christopher P Evans, Stefano Fanti, Felix Feng, Karim Fizazi, Mark Frydenberg, Martin Gleave, Susan Halabi, Axel Heidenreich, Celestia S Higano, Nicolas James, Philip Kantoff, Pirkko-Liisa Kellokumpu-Lehtinen, Raja B Khauli, Gero Kramer, Chris Logothetis, Fernando Maluf, Alicia K Morgans, Michael J Morris, Nicolas Mottet, Vedang Murthy, William Oh, Piet Ost, Anwar R Padhani, Chris Parker, Colin C Pritchard, Mack Roach, Mark A Rubin, Charles Ryan, Fred Saad, Oliver Sartor, Howard Scher, Avishay Sella, Neal Shore, Matthew Smith, Howard Soule, Cora N Sternberg, Hiroyoshi Suzuki, Christopher Sweeney, Matthew R Sydes, Ian Tannock, Bertrand Tombal, Riccardo Valdagni, Thomas Wiegel, Aurelius Omlin
BACKGROUND: In advanced prostate cancer (APC), successful drug development as well as advances in imaging and molecular characterisation have resulted in multiple areas where there is lack of evidence or low level of evidence. The Advanced Prostate Cancer Consensus Conference (APCCC) 2017 addressed some of these topics. OBJECTIVE: To present the report of APCCC 2017. DESIGN, SETTING, AND PARTICIPANTS: Ten important areas of controversy in APC management were identified: high-risk localised and locally advanced prostate cancer; "oligometastatic" prostate cancer; castration-naïve and castration-resistant prostate cancer; the role of imaging in APC; osteoclast-targeted therapy; molecular characterisation of blood and tissue; genetic counselling/testing; side effects of systemic treatment(s); global access to prostate cancer drugs...
June 24, 2017: European Urology
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