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https://www.readbyqxmd.com/read/28329682/the-swi-snf-protein-pbrm1-restrains-vhl-loss-driven-clear-cell-renal-cell-carcinoma
#1
Amrita M Nargund, Can G Pham, Yiyu Dong, Patricia I Wang, Hatice U Osmangeyoglu, Yuchen Xie, Omer Aras, Song Han, Toshinao Oyama, Shugaku Takeda, Chelsea E Ray, Zhenghong Dong, Mathieu Berge, A Ari Hakimi, Sebastien Monette, Carl L Lekaye, Jason A Koutcher, Christina S Leslie, Chad J Creighton, Nils Weinhold, William Lee, Satish K Tickoo, Zhong Wang, Emily H Cheng, James J Hsieh
PBRM1 is the second most commonly mutated gene after VHL in clear cell renal cell carcinoma (ccRCC). However, the biological consequences of PBRM1 mutations for kidney tumorigenesis are unknown. Here, we find that kidney-specific deletion of Vhl and Pbrm1, but not either gene alone, results in bilateral, multifocal, transplantable clear cell kidney cancers. PBRM1 loss amplified the transcriptional outputs of HIF1 and STAT3 incurred by Vhl deficiency. Analysis of mouse and human ccRCC revealed convergence on mTOR activation, representing the third driver event after genetic inactivation of VHL and PBRM1...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28328183/seroprevalence-of-bartonella-species-coxiella-burnetii-and-toxoplasma-gondii-among-patients-with-hematological-malignancies-a-pilot-study-in-romania
#2
C J Messinger, E S Gurzau, E B Breitschwerdt, C I Tomuleasa, S J Trufan, M M Flonta, R G Maggi, I B Neagoe, P M Rabinowitz
Patients receiving immunosuppressive cancer treatments in settings where there is a high degree of human-animal interaction may be at increased risk for opportunistic zoonotic infections or reactivation of latent infections. We sought to determine the seroprevalence of selected zoonotic pathogens among patients diagnosed with haematologic malignancies and undergoing chemotherapeutic treatments in Romania, where much of the general population lives and/or works in contact with livestock. A convenience sample of 51 patients with haematologic cancer undergoing chemotherapy at a referral clinic in Cluj-Napoca, Romania, was surveyed regarding animal exposures...
March 22, 2017: Zoonoses and Public Health
https://www.readbyqxmd.com/read/28327998/3rd-eso-esmo-international-consensus-guidelines-for-advanced-breast-cancer-abc-3
#3
F Cardoso, A Costa, E Senkus, M Aapro, F André, C H Barrios, J Bergh, G Bhattacharyya, L Biganzoli, M J Cardoso, L Carey, D Corneliussen-James, G Curigliano, V Dieras, N El Saghir, A Eniu, L Fallowfield, D Fenech, P Francis, K Gelmon, A Gennari, N Harbeck, C Hudis, B Kaufman, I Krop, M Mayer, H Meijer, S Mertz, S Ohno, O Pagani, E Papadopoulos, F Peccatori, F Penault-Llorca, M J Piccart, J Y Pierga, H Rugo, L Shockney, G Sledge, S Swain, C Thomssen, A Tutt, D Vorobiof, B Xu, L Norton, E Winer
No abstract text is available yet for this article.
February 19, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327965/carbon-dating-cancer-defining-the-chronology-of-metastatic-progression-in-colorectal-cancer
#4
H Lote, I Spiteri, L Ermini, A Vatsiou, A Roy, A McDonald, N Maka, M Balsitis, N Bose, M Simbolo, A Mafficini, A Lampis, J C Hahne, F Trevisani, Z Eltahir, G Mentrasti, C Findlay, Eaj Kalkman, M Punta, B Werner, S Lise, A Aktipis, C Maley, M Greaves, C Braconi, J White, M Fassan, A Scarpa, A Sottoriva, N Valeri
Background: HASH(0x34f2da0) Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but lack of chronological references makes dating the exact onset of tumours very challenging. Patients and Methods: HASH(0x35e8198) Here we describe the case of a colorectal cancer patient presenting with synchronous lung metastasis and metachronous thyroid, chest wall and urinary tract metastases over the course of five years...
February 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327934/pazopanib-or-placebo-in-completely-resected-stage-i-nsclc-patients-results-of-the-phase-ii-ifct-0703-trial
#5
B Besse, J Mazières, L Ribassin-Majed, F Barlesi, J Bennouna, R Gervais, L Moreau, H Berard, D Debieuvre, O Molinier, D Moro-Sibilot, P J Souquet, S Jacquot, L Petit, H Lena, J P Pignon, B Lacas, F Morin, B Milleron, G Zalcman, J C Soria
Background: Adjuvant treatment in resected stage I non-small cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/β. We explored the feasibility and efficacy of adjuvant pazopanib in this population. Patients and methods: In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/d (P800) for 6 months with a two-step Fleming design...
February 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327917/fifth-ovarian-cancer-consensus-conference-of-the-gynecologic-cancer-intergroup-first-line-interventions
#6
A Karam, J A Ledermann, J-W Kim, J Sehouli, K Lu, C Gourley, N Katsumata, R A Burger, B-H Nam, M Bacon, C Ng, J Pfisterer, R L M Bekkers, A Casado Herráez, A Redondo, H Fujiwara, N Gleeson, O Rosengarten, G Scambia, J Zhu, A Okamoto, G Stuart, K Ochiai
The consensus statements regarding first-line therapies in women with ovarian cancer, reached at the Fifth Ovarian Cancer Consensus Conference held in Tokyo, Japan, in November 2015 are reported. Three topics were reviewed and the following statements are recommended: (i) Surgery: the subgroups that should be considered in first-line ovarian cancer clinical trials should be (a) patients undergoing primary debulking surgery and (b) patients receiving neo-adjuvant chemotherapy. The amount of residual disease following surgery should further stratify patients into those with absent gross residual disease and others...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28325472/dosimetric-comparison-between-treatment-plans-of-patients-treated-with-low-dose-rate-vs-high-dose-rate-interstitial-prostate-brachytherapy-as-monotherapy-initial-findings-of-a-randomized-clinical-trial
#7
T Major, C Polgár, K Jorgo, G Stelczer, P Ágoston
PURPOSE: The aim of this study was to compare the dosimetry of intraoperative dose plans of prostate cancer patients treated with low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (BT). METHODS AND MATERIALS: A randomized clinical trial was initiated at our institution to compare the results and side effects of LDR and HDR BT as monotherapy in the treatment of early, organ-confined prostate cancer patients. Eighty-seven patients were randomly assigned to receive HDR afterloading BT with one fraction of 19 Gy or permanent LDR (125)I seed BT with 145 Gy...
March 15, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28325287/cholesterol-containing-nuclease-resistant-sirna-accumulates-in-tumors-in-a-carrier-free-mode-and-silences-mdr1-gene
#8
Ivan V Chernikov, Daniil V Gladkikh, Mariya I Meschaninova, Alya G Ven'yaminova, Marina A Zenkova, Valentin V Vlassov, Elena L Chernolovskaya
Chemical modifications are an effective way to improve the therapeutic properties of small interfering RNAs (siRNAs), making them more resistant to degradation in serum and ensuring their delivery to target cells and tissues. Here, we studied the carrier-free biodistribution and biological activity of a nuclease-resistant anti-MDR1 cholesterol-siRNA conjugate in healthy and tumor-bearing severe combined immune deficiency (SCID) mice. The attachment of cholesterol to siRNA provided its efficient accumulation in the liver and in tumors, and reduced its retention in the kidneys after intravenous and intraperitoneal injection...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325282/dna-aptamers-for-the-characterization-of-histological-structure-of-lung-adenocarcinoma
#9
Galina S Zamay, Tatiana I Ivanchenko, Tatiana N Zamay, Valentina L Grigorieva, Yury E Glazyrin, Olga S Kolovskaya, Irina V Garanzha, Andrey A Barinov, Alexey V Krat, Gleb G Mironov, Ana Gargaun, Dmitry V Veprintsev, Sergey S Bekuzarov, Andrey K Kirichenko, Ruslan A Zukov, Marina M Petrova, Andrey A Modestov, Maxim V Berezovski, Anna S Zamay
Nucleic acid aptamers are becoming popular as molecular probes for identification and imaging pathology and, at the same time, as a convenient platform for targeted therapy. Recent studies have shown that aptamers may be effectively used for tumor characterization and as commercially available monoclonal antibodies. Here we present three DNA aptamers binding to whole transformed lung cancer tissues, including tumor cells, connective tissues, and blood vessels. Protein targets have been revealed using affinity purification followed by mass spectrometry analyses, and they have been validated using a panel of correspondent antibodies and 3D imaging of tumor tissues...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325259/vitamin-d-analogues-potential-use-in-cancer-treatment
#10
REVIEW
Michael J Duffy, Alyson Murray, Naoise C Synnott, Norma O'Donovan, John Crown
The vitamin D receptor (VDR) is a member of the thyroid-steroid family of nuclear transcription factors. Following binding of the active form of vitamin D, i.e., 1,25(OH)2D3 (also known as calcitriol) and interaction with co-activators and co-repressors, VDR regulates the expression of several different genes. Although relatively little work has been carried out on VDR in human cancers, several epidemiological studies suggest that low circulating levels of vitamin D are associated with both an increased risk of developing specific cancer types and poor outcome in patients with specific diagnosed cancers...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323271/a-serological-biopsy-using-five-stomach-specific-circulating-biomarkers-for-gastric-cancer-risk-assessment-a-multi-phase-study
#11
Huakang Tu, Liping Sun, Xiao Dong, Yuehua Gong, Qian Xu, Jingjing Jing, Roberd M Bostick, Xifeng Wu, Yuan Yuan
OBJECTIVES: We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers-pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)-for identifying high-risk individuals and predicting risk of developing gastric cancer (GC). METHODS: Among 12,112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-phase study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis...
March 21, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28322970/gold-nanoparticles-radiations-and-the-immune-system-current-insights-into-the-physical-mechanisms-and-the-biological-interactions-of-this-new-alliance-towards-cancer-therapy
#12
REVIEW
Nikolaos M Dimitriou, George Tsekenis, Evangelos C Balanikas, Athanasia Pavlopoulou, Melina Mitsiogianni, Theodora Mantso, George Pashos, Andreas G Boudouvis, Ioannis N Lykakis, Georgios Tsigaridas, Mihalis I Panayiotidis, Vassilios Yannopapas, Alexandros G Georgakilas
Considering both cancer's serious impact on public health and the side effects of cancer treatments, strategies towards targeted cancer therapy have lately gained considerable interest. Employment of gold nanoparticles (GNPs), in combination with ionizing and non-ionizing radiations, has been shown to improve the effect of radiation treatment significantly. GNPs, as high-Z particles, possess the ability to absorb ionizing radiation and enhance the deposited dose within the targeted tumors. Furthermore, they can convert non-ionizing radiation into heat, due to plasmon resonance, leading to hyperthermic damage to cancer cells...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28320945/three-dimensional-culture-system-identifies-a-new-mode-of-cetuximab-resistance-and-disease-relevant-genes-in-colorectal-cancer
#13
Cunxi Li, Bhuminder Singh, Ramona Graves-Deal, Haiting Ma, Alina Starchenko, William H Fry, Yuanyuan Lu, Yang Wang, Galina Bogatcheva, Mohseen P Khan, Ginger L Milne, Shilin Zhao, Gregory Daniel Ayers, Nenggan Li, Huaying Hu, Mary Kay Washington, Timothy J Yeatman, Oliver G McDonald, Qi Liu, Robert J Coffey
We previously reported that single cells from a human colorectal cancer (CRC) cell line (HCA-7) formed either hollow single-layered polarized cysts or solid spiky masses when plated in 3D in type-I collagen. To begin in-depth analyses into whether clonal cysts and spiky masses possessed divergent properties, individual colonies of each morphology were isolated and expanded. The lines thus derived faithfully retained their parental cystic and spiky morphologies and were termed CC (cystic) and SC (spiky), respectively...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28318871/changes-in-health-related-quality-of-life-of-oral-cancer-patients-treated-with-curative-intent-experience-of-a-developing-country
#14
J G Doss, W M N Ghani, I A Razak, Y H Yang, S N Rogers, R B Zain
This study aimed to assess changes in oral cancer patients' health-related quality of life (HRQOL) and the impact of disease stage on HRQOL scores. HRQOL data were collected from seven hospital-based centres using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) version 4.0 instrument. The independent samples t-test, χ(2) test, and paired samples t-test were used to analyse the data. A total of 300 patients were recruited. The most common oral cancer sub-site was tongue and floor of mouth (42...
March 16, 2017: International Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28318083/dienophile-modified-mannosamine-derivatives-for-metabolic-labeling-of-sialic-acids-a-comparative-study
#15
Jeremias E G A Dold, Jessica Pfotzer, Anne-Katrin Späte, Valentin Wittmann
Sialic acids play an important role in numerous cell adhesion processes and sialylation levels are known to be altered under certain pathogenic conditions such as cancer. Metabolic glycoengineering with mannosamine derivatives is a convenient way to introduce non-natural chemical reporter groups into sialylated glycoconjugates offering the opportunity to label sialic acids using bioorthogonal ligation chemistry. The labeling intensity not only depends on the rate of the ligation reaction but also on the extent to which the natural sialic acids are replaced by the modified ones, i...
March 20, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28317934/dek-is-required-for-homologous-recombination-repair-of-dna-breaks
#16
Eric A Smith, Boris Gole, Nicholas A Willis, Rebeca Soria, Linda M Starnes, Eric F Krumpelbeck, Anil G Jegga, Abdullah M Ali, Haihong Guo, Amom R Meetei, Paul R Andreassen, Ferdinand Kappes, Lisa M Privette Vinnedge, Jeremy A Daniel, Ralph Scully, Lisa Wiesmüller, Susanne I Wells
DEK is a highly conserved chromatin-bound protein whose upregulation across cancer types correlates with genotoxic therapy resistance. Loss of DEK induces genome instability and sensitizes cells to DNA double strand breaks (DSBs), suggesting defects in DNA repair. While these DEK-deficiency phenotypes were thought to arise from a moderate attenuation of non-homologous end joining (NHEJ) repair, the role of DEK in DNA repair remains incompletely understood. We present new evidence demonstrating the observed decrease in NHEJ is insufficient to impact immunoglobulin class switching in DEK knockout mice...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317088/phase-i-trial-of-the-oral-smoothened-inhibitor-sonidegib-in-combination-with-paclitaxel-in-patients-with-advanced-solid-tumors
#17
A Stathis, D Hess, R von Moos, K Homicsko, G Griguolo, M Joerger, M Mark, C J Ackermann, S Allegrini, C V Catapano, A Xyrafas, M Enoiu, S Berardi, P Gargiulo, C Sessa
Purpose To establish a recommended phase II dose (RP2D) for the oral smoothened inhibitor sonidegib in combination with paclitaxel; secondary objectives include evaluation of safety, tolerability, markers of Hedgehog (Hh) signaling and preliminary antitumor activity. Methods Patients with advanced solid tumors were enrolled in cohorts of escalating sonidegib dose levels (400mg, 600mg and 800mg orally, once daily on days 1-28) in combination with paclitaxel 80 mg/m(2) on days 1, 8 and 15 in 4-weekly cycles. Dose-limiting toxicities (DLTs) were assessed using CTCAE v4...
March 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28314751/identification-of-glycopeptides-as-post-translationally-modified-neoantigens-in-leukemia
#18
Stacy A Malaker, Sarah A Penny, Lora G Steadman, Paisley T Myers, Justin Loke, Manoj Raghavan, Dina L Bai, Jeffery Shabanowitz, Donald Hunt, Mark Cobbold
Leukemias are highly immunogenic but have a low mutational load, providing few mutated peptide targets. Thus, the identification of alternative neoantigens is a pressing need. Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues...
March 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28314589/fgfr2-mutations-are-associated-with-poor-outcomes-in-endometrioid-endometrial-cancer-an-nrg-oncology-gynecologic-oncology-group-study
#19
Yvette W Jeske, Shamshad Ali, Sara A Byron, Feng Gao, Robert S Mannel, Rahel G Ghebre, Paul A DiSilvestro, Shashikant B Lele, Michael L Pearl, Amy P Schmidt, Heather A Lankes, Nilsa C Ramirez, Golnar Rasty, Matthew Powell, Paul J Goodfellow, Pamela M Pollock
PURPOSE: Activating FGFR2 mutations have been identified in ~10% of endometrioid endometrial cancers (ECs). We have previously reported that mutations in FGFR2 are associated with shorter disease free survival (DFS) in stage I/II EC patients. Here we sought to validate the prognostic importance of FGFR2 mutations in a large, multi-institutional patient cohort. METHODS: Tumors were collected as part of the GOG 210 clinical trial "Molecular Staging of Endometrial Cancer" where samples underwent rigorous pathological review and had more than three years of detailed clinical follow-up...
March 14, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28303452/should-genetic-testing-be-offered-for-children-the-perspectives-of-adolescents-and-emerging-adults-in-families-with-li-fraumeni-syndrome
#20
Melissa A Alderfer, Robert B Lindell, Claire I Viadro, Kristin Zelley, Jessica Valdez, Belinda Mandrell, Carol A Ford, Kim E Nichols
Whether children should be offered genetic testing for cancer risk is much debated but young voices are rarely heard in these conversations. The current study explored perspectives of genetic testing held by adolescents and emerging adults in families with Li Fraumeni syndrome (LFS). Twelve 12- to 25-year-olds in families with LFS completed qualitative interviews for this study. All believed that testing should be offered for children but many qualified this statement saying parental approval would be needed and testing should be optional...
March 16, 2017: Journal of Genetic Counseling
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