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https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#1
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212542/two-stage-genome-wide-association-study-identifies-a-novel-susceptibility-locus-associated-with-melanoma
#2
Katherine J Ransohoff, Wenting Wu, Hyunje G Cho, Harvind C Chahal, Yuan Lin, Hong-Ji Dai, Christopher I Amos, Jeffrey E Lee, Jean Y Tang, David A Hinds, Jiali Han, Qingyi Wei, Kavita Y Sarin
Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211936/reduction-of-cyclophosphamide-dose-for-patients-with-subset-2-low-risk-rhabdomyosarcoma-is-associated-with-an-increased-risk-of-recurrence-a-report-from-the-soft-tissue-sarcoma-committee-of-the-children-s-oncology-group
#3
David O Walterhouse, Alberto S Pappo, Jane L Meza, John C Breneman, Andrea Hayes-Jordan, David M Parham, Timothy P Cripe, James R Anderson, William H Meyer, Douglas S Hawkins
BACKGROUND: Failure-free survival (FFS) and overall survival (OS) rates were found to improve on Intergroup Rhabdomyosarcoma Study (IRS) IV (IRS-IV) compared with IRS-III for patients with subset 2 (IRS stage 1, group III nonorbit or stage 3, group I/II) low-risk embryonal rhabdomyosarcoma with the addition of cyclophosphamide (total cumulative cyclophosphamide dose of 26.4 g/m(2) ) to the combination of vincristine and dactinomycin (VAC). The goal of Children's Oncology Group ARST0331 for subset 2 low-risk patients was to reduce the total cumulative cyclophosphamide dose without compromising FFS...
February 17, 2017: Cancer
https://www.readbyqxmd.com/read/28211886/a-novel-approach-for-the-identification-of-efficient-combination-therapies-in-primary-human-acute-myeloid-leukemia-specimens
#4
I Baccelli, J Krosl, G Boucher, I Boivin, V-P Lavallée, J Hébert, S Lemieux, A Marinier, G Sauvageau
Appropriate culture methods for the interrogation of primary leukemic samples were hitherto lacking and current assays for compound screening are not adapted for large-scale investigation of synergistic combinations. In this study, we report a novel approach that efficiently distills synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens. In single-dose experiments and under culture conditions preserving leukemia stem cell activity, our strategy considerably reduces the number of tests needed for the identification of promising compound combinations...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211448/cx-5461-is-a-dna-g-quadruplex-stabilizer-with-selective-lethality-in-brca1-2-deficient-tumours
#5
Hong Xu, Marco Di Antonio, Steven McKinney, Veena Mathew, Brandon Ho, Nigel J O'Neil, Nancy Dos Santos, Jennifer Silvester, Vivien Wei, Jessica Garcia, Farhia Kabeer, Daniel Lai, Priscilla Soriano, Judit Banáth, Derek S Chiu, Damian Yap, Daniel D Le, Frank B Ye, Anni Zhang, Kelsie Thu, John Soong, Shu-Chuan Lin, Angela Hsin Chin Tsai, Tomo Osako, Teresa Algara, Darren N Saunders, Jason Wong, Jian Xian, Marcel B Bally, James D Brenton, Grant W Brown, Sohrab P Shah, David Cescon, Tak W Mak, Carlos Caldas, Peter C Stirling, Phil Hieter, Shankar Balasubramanian, Samuel Aparicio
G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition. Exposure to CX-5461, and its related drug CX-3543, blocks replication forks and induces ssDNA gaps or breaks...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28211093/gsskat-rapid-gene-set-analysis-and-multiple-testing-correction-for-rare-variant-association-studies-using-weighted-linear-kernels
#6
Nicholas B Larson, Shannon McDonnell, Lisa Cannon Albright, Craig Teerlink, Janet Stanford, Elaine A Ostrander, William B Isaacs, Jianfeng Xu, Kathleen A Cooney, Ethan Lange, Johanna Schleutker, John D Carpten, Isaac Powell, Joan E Bailey-Wilson, Olivier Cussenot, Geraldine Cancel-Tassin, Graham G Giles, Robert J MacInnis, Christiane Maier, Alice S Whittemore, Chih-Lin Hsieh, Fredrik Wiklund, William J Catolona, William Foulkes, Diptasri Mandal, Rosalind Eeles, Zsofia Kote-Jarai, Michael J Ackerman, Timothy M Olson, Christopher J Klein, Stephen N Thibodeau, Daniel J Schaid
Next-generation sequencing technologies have afforded unprecedented characterization of low-frequency and rare genetic variation. Due to low power for single-variant testing, aggregative methods are commonly used to combine observed rare variation within a single gene. Causal variation may also aggregate across multiple genes within relevant biomolecular pathways. Kernel-machine regression and adaptive testing methods for aggregative rare-variant association testing have been demonstrated to be powerful approaches for pathway-level analysis, although these methods tend to be computationally intensive at high-variant dimensionality and require access to complete data...
February 16, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28206967/calcium-regulatory-proteins-as-modulators-of-chemotherapy-in-human-neuroblastoma
#7
Ana-Maria Florea, Elizabeth Varghese, Jennifer E McCallum, Safa Mahgoub, Irfan Helmy, Sharon Varghese, Neha Gopinath, Steffen Sass, Fabian J Theis, Guido Reifenberger, Dietrich Büsselberg
Neuroblastoma (NB) is a pediatric cancer treated with poly-chemotherapy including platinum complexes (e.g. cisplatin (CDDP), carboplatin), DNA alkylating agents, and topoisomerase I inhibitors (e.g. topotecan (TOPO)). Despite aggressive treatment, NB may become resistant to chemotherapy. We investigated whether CDDP and TOPO treatment of NB cells interacts with the expression and function of proteins involved in regulating calcium signaling. Human neuroblastoma cell lines SH-SY5Y, IMR-32 and NLF were used to investigate the effects of CDDP and TOPO on cell viability, apoptosis, calcium homeostasis, and expression of selected proteins regulating intracellular calcium concentration ([Ca2+]i)...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205160/non-fermentative-gram-negative-rods-bacteremia-in-children-with-cancer-a-14-year-single-center-experience
#8
D Averbuch, C Avaky, M Harit, P Stepensky, I Fried, T Ben-Ami, V Temper, Y Peled, H Troen, R Masarwa, W Abu Ahmad, M Weintraub, S Revel-Vilk, D Engelhard
PURPOSE: Data on non-fermentative Gram-negative rods (NFGNR) bacteremia in children with malignancies are limited. The aim of this study was to present clinical picture, antimicrobial susceptibility pattern, risk factors for resistance and outcome in NFGNR bacteremia in children with cancer. METHODS: All episodes of NFGNR bacteremia occurring during 2001-2014 in children with cancer in a tertiary-care hospital were retrospectively analyzed. Pseudomonas and Acinetobacter spp...
February 15, 2017: Infection
https://www.readbyqxmd.com/read/28205047/pre-diagnosis-insulin-like-growth-factor-i-and-risk-of-epithelial-invasive-ovarian-cancer-by-histological-subtypes-a-collaborative-re-analysis-from-the-ovarian-cancer-cohort-consortium
#9
Jennifer Ose, Helena Schock, Elizabeth M Poole, Matti Lehtinen, Kala Visvanathan, Kathy Helzlsouer, Julie E Buring, I-Min Lee, Anne Tjønneland, Marie-Christine Boutron-Ruault, Antonia Trichopoulou, Amalia Mattiello, N Charlotte Onland-Moret, Elisabete Weiderpass, María-José Sánchez, Annika Idahl, Ruth C Travis, Sabina Rinaldi, Melissa A Merritt, Nicolas Wentzensen, Shelley S Tworoger, Rudolf Kaaks, Renée T Fortner
PURPOSE: Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results. METHODS: We pooled and harmonized data from 6 case-control studies nested within the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis IGF-I concentrations and subsequent risk of EOC...
February 16, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28204995/dalteparin-or-vitamin-k-antagonists-to-prevent-recurrent-venous-thromboembolism-in-cancer-patients-a-patient-level-economic-analysis-for-france-and-austria
#10
George Dranitsaris, Lesley G Shane, Jean-Philippe Galanaud, Gunar Stemer, Philippe Debourdeau, Seth Woodruff
BACKGROUND: International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146-53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs...
February 15, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28202353/the-potential-clinical-promise-of-multimodality-metronomic-chemotherapy-revealed-by-preclinical-studies-of-metastatic-disease
#11
Robert S Kerbel, Yuval Shaked
We present a rationale for further clinical development and assessment of metronomic chemotherapy on the basis of unexpected results obtained in translational mouse models of cancer involving treatment of advanced metastatic disease. Historically, mouse cancer therapy models have been dominated by treating established primary tumors or early stage low volume microscopic disease. Treatment of primary tumors is also almost always the case when using genetically engineered mouse models (GEMMS) of cancer or patient-derived xenografts (PDXs)...
February 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28200088/mri-assessment-and-outcomes-in-patients-receiving-neoadjuvant-chemotherapy-only-for-primary-rectal-cancer-longterm-results-from-the-gemcad-0801-trial
#12
U B Patel, G Brown, I Machado, J Santos-Cores, C Pericay, E Ballesteros, A Salud, M Isabel-Gil, C Montagut, J Maurel, J Ramón-Ayuso, C Fernandez-Martos
No abstract text is available yet for this article.
February 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28200038/comprehensive-evaluation-of-published-gene-expression-prognostic-signatures-for-biomarker-based-lung-cancer-clinical-studies
#13
H Tang, S Wang, G Xiao, J Schiller, V Papadimitrakopoulou, J Minna, I I Wistuba, Y Xie
No abstract text is available yet for this article.
February 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28198370/smac-mimetics-synergize-with-immune-checkpoint-inhibitors-to-promote-tumour-immunity-against-glioblastoma
#14
Shawn T Beug, Caroline E Beauregard, Cristin Healy, Tarun Sanda, Martine St-Jean, Janelle Chabot, Danielle E Walker, Aditya Mohan, Nathalie Earl, Xueqing Lun, Donna L Senger, Stephen M Robbins, Peter Staeheli, Peter A Forsyth, Tommy Alain, Eric C LaCasse, Robert G Korneluk
Small-molecule inhibitor of apoptosis (IAP) antagonists, called Smac mimetic compounds (SMCs), sensitize tumours to TNF-α-induced killing while simultaneously blocking TNF-α growth-promoting activities. SMCs also regulate several immunomodulatory properties within immune cells. We report that SMCs synergize with innate immune stimulants and immune checkpoint inhibitor biologics to produce durable cures in mouse models of glioblastoma in which single agent therapy is ineffective. The complementation of activities between these classes of therapeutics is dependent on cytotoxic T-cell activity and is associated with a reduction in immunosuppressive T-cells...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28196063/long-term-results-and-recurrence-patterns-from-scope-1-a-phase-ii-iii-randomised-trial-of-definitive-chemoradiotherapy-cetuximab-in-oesophageal-cancer
#15
T Crosby, C N Hurt, S Falk, S Gollins, J Staffurth, R Ray, J A Bridgewater, J I Geh, D Cunningham, J Blazeby, R Roy, T Maughan, G Griffiths, S Mukherjee
BACKGROUND: The SCOPE-1 study tested the role of adding cetuximab to conventional definitive chemoradiotherapy (dCRT), and demonstrated greater toxicity and worse survival outcomes. We present the long-term outcomes and patterns of recurrence. METHODS: SCOPE-1 was a phase II/III trial in which patients were randomised to cisplatin 60 mg m(-2) (day 1) and capecitabine 625 mg m(-2) bd (days 1-21) for four cycles +/- cetuximab 400 mg m(-2) day 1 then by 250 mg m(-2) weekly...
February 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28195671/trachycladines-and-analogues-synthesis-and-anti-cancer-activity-evaluation
#16
Zisis V Peitsinis, Achilleas G Mitrakas, Eirini A Nakiou, Dafni A Melidou, Dimitra Kalamida, Christos Kakouratos, Michael I Koukourakis, Alexandros E Koumbis
The synthesis of four new analogues of marine nucleoside trachycladine A was accomplished via direct regio- and stereoselective Vorbrüggen glycosylations of 2,6-dichloropurine and 2-chloropurine with a D-ribose derived chiron. Naturally occurring trachycladines (A and B) and a series of analogues were examined for their cytotoxic activity against a number of cancer cell lines (glioblastoma, lung and cervical cancer). Parent trachycladine A and two analogues (the diacetate of 2,6-dichloropurine derivative and N-cyclopropyl trachycladine A) were found to result in a significant reduction of cell viability, with the latter exhibiting a stronger effect...
February 14, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28195261/immunohistochemical-evaluation-of-mismatch-repair-proteins-in-colorectal-carcinoma-the-aifeg-gipad-proposal
#17
A Remo, M Fassan, G Lanza
Microsatellite instability (MSI) is a hypermutable phenotype that usually arises from either a germline mutation in components of the mismatch repair (MMR) machinery (i.e. hMLH1, MSH2, MSH6 and PMS2) in patients with Lynch syndrome (LS) or somatic hypermethylation of the hMLH1 promoter in sporadic carcinomas. In all colorectal cancers (CRC) is possible to identify the MMR deficiency through protein expression by immunoistochemistry (IHC). Recently, the predictive role of MMR deficiency in reduced chemotherapy benefit and the introduction of universal screening for Lynch syndrome suggest to include MMR testing into routine clinical practice...
September 2016: Pathologica
https://www.readbyqxmd.com/read/28195142/a-genome-wide-association-study-yields-five-novel-thyroid-cancer-risk-loci
#18
Julius Gudmundsson, Gudmar Thorleifsson, Jon K Sigurdsson, Lilja Stefansdottir, Jon G Jonasson, Sigurjon A Gudjonsson, Daniel F Gudbjartsson, Gisli Masson, Hrefna Johannsdottir, Gisli H Halldorsson, Simon N Stacey, Hannes Helgason, Patrick Sulem, Leigha Senter, Huiling He, Sandya Liyanarachchi, Matthew D Ringel, Esperanza Aguillo, Angeles Panadero, Enrique Prats, Almudena Garcia-Castaño, Ana De Juan, Fernando Rivera, Li Xu, Lambertus A Kiemeney, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Hoskuldur Kristvinsson, Romana T Netea-Maier, Thorvaldur Jonsson, Jose I Mayordomo, Theo S Plantinga, Hannes Hjartarson, Jon Hrafnkelsson, Erich M Sturgis, Unnur Thorsteinsdottir, Thorunn Rafnar, Albert de la Chapelle, Kari Stefansson
The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with Pcombined<3 × 10(-8)): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28194687/fecal-incontinence-and-radiation-dose-on-anal-sphincter-in-patients-with-locally-advanced-rectal-cancer-larc-treated-with-preoperative-chemoradiotherapy-a-retrospective-single-institutional-study
#19
F Arias, C Eito, G Asín, I Mora, K Cambra, F Mañeru, B Ibáñez, L Arbea, A Viudez, I Hernández, J I Arrarás, M Errasti, M Barrado, M Campo, I Visus, S Flamarique, M A Ciga
BACKGROUND: The objective of the study is to determine the correlations among the variables of dose and the sphincter function (SF) in patients with locally advanced rectal cancer treated with preoperative capecitabine/radiotherapy followed by low anterior resection (LAR) + TME. METHODS: We retrospectively reviewed 92 consecutive patients with LARC treated at our center with LAR from 2006 and more than 2 years free from disease. We re-contoured the anal sphincters (AS) of patients with the help of the radiologist...
February 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28194568/t1-colon-cancer-in-the-era-of-screening-risk-factors-and-treatment
#20
F Bianco, S De Franciscis, A Belli, A Falato, R Fusco, D F Altomare, A Amato, C R Asteria, A Avallone, G A Binda, L Boccia, P Buzzo, M Carvello, C Coco, P Delrio, P De Nardi, M Di Lena, A Failla, F La Torre, M La Torre, M Lemma, P Luffarelli, G Manca, I Maretto, F Marino, A Muratore, A Pascariello, S Pucciarelli, D Rega, V Ripetti, G Rizzo, A Serventi, A Spinelli, F Tatangelo, E D L Urso, G M Romano
BACKGROUND: The aim of this study was to identify risk factors for lymph node positivity in T1 colon cancer and to carry out a surgical quality assurance audit. METHODS: The sample consisted of consecutive patients treated for early-stage colon lesions in 15 colorectal referral centres between 2011 and 2014. The study investigated 38 factors grouped into four categories: demographic information, preoperative data, indications for surgery and post-operative data...
February 13, 2017: Techniques in Coloproctology
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