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https://www.readbyqxmd.com/read/28222901/pharmacotherapy-in-smoking-cessation-corticotropin-releasing-factor-receptors-as-emerging-intervention-targets
#1
REVIEW
Ioannis Sotiriou, Kleanthi Chalkiadaki, Christos Nikolaidis, Kyriaki Sidiropoulou, Ekaterini Chatzaki
Smoking represents perhaps the single most important health risk factor and a global contributor to mortality that can unquestionably be prevented. Smoking is responsible for many diseases, including various types of cancer, chronic obstructive pulmonary disease, coronary heart disease, peripheral vascular disease and peptic ulcer, while it adversely affects fetal formation and development. Since smoking habit duration is a critical factor for mortality, the goal of treatment should be its timely cessation and relapse prevention...
February 14, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28222225/daylight-photodynamic-therapy-vs-conventional-photodynamic-therapy-as-skin-cancer-preventive-treatment-in-patients-with-face-and-scalp-cancerization-an-intra-individual-comparison-study
#2
Elena Sotiriou, Demetrios Ioannides, Fotini Vrani, Elizabeth Lazaridou, Efstratios Vakirlis, Aimilios Lallas, Zoe Apalla
BACKGROUND: Individuals with medical history of non-melanoma skin cancers (NMSCs) usually develop multiple and/or recurrent malignant lesions around the site of the primary neoplasm. The latter represents the clinical expression of the "field cancerization" theory; supporting the presence of multiple malignant clones of dysplastic keratinocytes over the entire epithelium that potentially can progress into clinical lesions. Taking into consideration that the burden of NMSCs on public health and health-care cost is high, adequate control of recurrences and management of field change is challenging...
February 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28197375/tumor-infiltrating-lymphocyte-composition-organization-and-pd-1-pd-l1-expression-are-linked-in-breast-cancer
#3
Laurence Buisseret, Soizic Garaud, Alexandre de Wind, Gert Van den Eynden, Anais Boisson, Cinzia Solinas, Chunyan Gu-Trantien, Céline Naveaux, Jean-Nicolas Lodewyckx, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Denis Larsimont, Martine Piccart-Gebhart, John Stagg, Christos Sotiriou, Karen Willard-Gallo
The clinical relevance of tumor-infiltrating lymphocytes (TIL) in breast cancer (BC) has been clearly established by their demonstrated correlation with long-term positive outcomes. Nevertheless, the relationship between protective immunity, observed in some patients, and critical features of the infiltrate remains unresolved. This study examined TIL density, composition and organization together with PD-1 and PD-L1 expression in freshly collected and paraffin-embedded tissues from 125 patients with invasive primary BC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28151718/the-prognostic-role-of-androgen-receptor-in-patients-with-early-stage-breast-cancer-a-meta-analysis-of-clinical-and-gene-expression-data
#4
Ivana Bozovic-Spasojevic, Dimitrios Zardavas, Sylvain Brohée, Lieveke Ameye, Debora Fumagalli, Felipe Ades, Evandro De Azambuja, Yacine Bareche, Martine Piccart, Marianne Paesmans, Christos Sotiriou
: Androgen receptor (AR) expression has been observed in about 70% of breast cancer (BC) patients, but its prognostic role remains uncertain. METHODS: To assess the prognostic role of AR expression in early-stage BC we performed a meta-analysis of studies that evaluated the impact of AR at the protein and gene expression level on disease free survival (DFS) and/or overall survival (OS). Eligible studies were identified by systematic review of electronic databases using the MeSH-terms "breast neoplasm" and "androgen receptor" and were selected after a qualitative assessment based on the REMARK criteria...
November 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28031185/metadcn-meta-analysis-framework-for-differential-co-expression-network-detection-with-an-application-in-breast-cancer
#5
Li Zhu, Ying Ding, Cho-Yi Chen, Lin Wang, Zhiguang Huo, SungHwan Kim, Christos Sotiriou, Steffi Oesterreich, George C Tseng
MOTIVATION: Gene co-expression network analysis from transcriptomic studies can elucidate genegene interactions and regulatory mechanisms. Differential co-expression analysis helps further detect alterations of regulatory activities in case/control comparison. Co-expression networks estimated from single transcriptomic study is often unstable and not generalizable due to cohort bias and limited sample size. With the rapid accumulation of publicly available transcriptomic studies, co-expression analysis combining multiple transcriptomic studies can provide more accurate and robust results...
December 28, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27984746/mammalian-rad52-functions-in-break-induced-replication-repair-of-collapsed-dna-replication-forks
#6
Sotirios K Sotiriou, Irene Kamileri, Natalia Lugli, Konstantinos Evangelou, Caterina Da-Ré, Florian Huber, Laura Padayachy, Sebastien Tardy, Noemie L Nicati, Samia Barriot, Fena Ochs, Claudia Lukas, Jiri Lukas, Vassilis G Gorgoulis, Leonardo Scapozza, Thanos D Halazonetis
Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci...
December 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#7
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27760777/alternative-lengthening-of-human-telomeres-is-a-conservative-dna-replication-process-with-features-of-break-induced-replication
#8
Fani-Marlen Roumelioti, Sotirios K Sotiriou, Vasiliki Katsini, Maria Chiourea, Thanos D Halazonetis, Sarantis Gagos
Human malignancies overcome replicative senescence either by activating the reverse-transcriptase telomerase or by utilizing a homologous recombination-based mechanism, referred to as alternative lengthening of telomeres (ALT). In budding yeast, ALT exhibits features of break-induced replication (BIR), a repair pathway for one-ended DNA double-strand breaks (DSBs) that requires the non-essential subunit Pol32 of DNA polymerase delta and leads to conservative DNA replication. Here, we examined whether ALT in human cancers also exhibits features of BIR A telomeric fluorescence in situ hybridization protocol involving three consecutive staining steps revealed the presence of conservatively replicated telomeric DNA in telomerase-negative cancer cells...
December 2016: EMBO Reports
https://www.readbyqxmd.com/read/27737921/relevance-of-tumor-infiltrating-immune-cell-composition-and-functionality-for-disease-outcome-in-breast-cancer
#9
Rico D Bense, Christos Sotiriou, Martine J Piccart-Gebhart, John B A G Haanen, Marcel A T M van Vugt, Elisabeth G E de Vries, Carolien P Schröder, Rudolf S N Fehrmann
BACKGROUND: Not all breast cancer patients benefit from neoadjuvant or adjuvant therapy, resulting in considerable undertreatment or overtreatment. New insights into the role of tumor-infiltrating immune cells suggest that their composition, as well as their functionality, might serve as a biomarker to enable optimal patient selection for current systemic therapies and upcoming treatment options such as immunotherapy. METHODS: We performed several complementary unbiased in silico analyses on gene expression profiles of 7270 unrelated tumor samples of nonmetastatic breast cancer patients with known clinical follow-up...
January 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27684533/rna-sequencing-to-predict-response-to-neoadjuvant-anti-her2-therapy-a-secondary-analysis-of-the-neoaltto-randomized-clinical-trial
#10
Debora Fumagalli, David Venet, Michail Ignatiadis, Hatem A Azim, Marion Maetens, Françoise Rothé, Roberto Salgado, Ian Bradbury, Lajos Pusztai, Nadia Harbeck, Henry Gomez, Tsai-Wang Chang, Maria Antonia Coccia-Portugal, Serena Di Cosimo, Evandro de Azambuja, Lorena de la Peña, Paolo Nuciforo, Jan C Brase, Jens Huober, José Baselga, Martine Piccart, Sherene Loi, Christos Sotiriou
Importance: In neoadjuvant trials, treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancers with dual HER2 blockade resulted in increased pathologic complete response (pCR) rates compared with each targeted agent alone. Amplification and/or overexpression of HER2 currently remains the only biomarker for therapeutic decisions, but it is insufficient to explain the heterogeneous response to anti-HER2 agents. Objective: To investigate the ability of clinically and biologically relevant genes and gene signatures (GSs) measured by RNA sequencing to predict the efficacy of anti-HER2 agents...
September 29, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27672107/somatic-mutation-copy-number-and-transcriptomic-profiles-of-primary-and-matched-metastatic-estrogen-receptor-positive-breast-cancers
#11
D Fumagalli, T R Wilson, R Salgado, X Lu, J Yu, C O'Brien, K Walter, L Y Huw, C Criscitiello, I Laios, V Jose, D N Brown, F Rothé, M Maetens, D Zardavas, P Savas, D Larsimont, M J Piccart-Gebhart, S Michiels, M R Lackner, C Sotiriou, S Loi
BACKGROUND: Estrogen receptor-positive (ER+) breast cancers (BCs) constitute the most frequent BC subtype. The molecular landscape of ER+ relapsed disease is not well characterized. In this study, we aimed to describe the genomic evolution between primary (P) and matched metastatic (M) ER+ BCs after failure of adjuvant therapy. MATERIALS AND METHODS: A total of 182 ER+ metastatic BC patients with long-term follow-up were identified from a single institution. P tumor tissue was available for all patients, with 88 having matched M material...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27617288/portraying-breast-cancers-with-long-noncoding-rnas
#12
Olivier Van Grembergen, Martin Bizet, Eric J de Bony, Emilie Calonne, Pascale Putmans, Sylvain Brohée, Catharina Olsen, Mingzhou Guo, Gianluca Bontempi, Christos Sotiriou, Matthieu Defrance, François Fuks
Evidence is emerging that long noncoding RNAs (lncRNAs) may play a role in cancer development, but this role is not yet clear. We performed a genome-wide transcriptional survey to explore the lncRNA landscape across 995 breast tissue samples. We identified 215 lncRNAs whose genes are aberrantly expressed in breast tumors, as compared to normal samples. Unsupervised hierarchical clustering of breast tumors on the basis of their lncRNAs revealed four breast cancer subgroups that correlate tightly with PAM50-defined mRNA-based subtypes...
September 2016: Science Advances
https://www.readbyqxmd.com/read/27557300/70-gene-signature-as-an-aid-to-treatment-decisions-in-early-stage-breast-cancer
#13
RANDOMIZED CONTROLLED TRIAL
Fatima Cardoso, Laura J van't Veer, Jan Bogaerts, Leen Slaets, Giuseppe Viale, Suzette Delaloge, Jean-Yves Pierga, Etienne Brain, Sylvain Causeret, Mauro DeLorenzi, Annuska M Glas, Vassilis Golfinopoulos, Theodora Goulioti, Susan Knox, Erika Matos, Bart Meulemans, Peter A Neijenhuis, Ulrike Nitz, Rodolfo Passalacqua, Peter Ravdin, Isabel T Rubio, Mahasti Saghatchian, Tineke J Smilde, Christos Sotiriou, Lisette Stork, Carolyn Straehle, Geraldine Thomas, Alastair M Thompson, Jacobus M van der Hoeven, Peter Vuylsteke, René Bernards, Konstantinos Tryfonidis, Emiel Rutgers, Martine Piccart
BACKGROUND: The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. METHODS: In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online)...
August 25, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27524497/pold3-is-haploinsufficient-for-dna-replication-in-mice
#14
Matilde Murga, Emilio Lecona, Irene Kamileri, Marcos Díaz, Natalia Lugli, Sotirios K Sotiriou, Marta E Anton, Juan Méndez, Thanos D Halazonetis, Oscar Fernandez-Capetillo
The Pold3 gene encodes a subunit of the Polδ DNA polymerase complex. Pold3 orthologs are not essential in Saccharomyces cerevisiae or chicken DT40 cells, but the Schizosaccharomyces pombe ortholog is essential. POLD3 also has a specialized role in the repair of broken replication forks, suggesting that POLD3 activity could be particularly relevant for cancer cells enduring high levels of DNA replication stress. We report here that POLD3 is essential for mouse development and is also required for viability in adult animals...
September 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27454930/feasibility-study-of-endotag-1-a-tumor-endothelial-targeting-agent-in-combination-with-paclitaxel-followed-by-fec-as-induction-therapy-in-her2-negative-breast-cancer
#15
Michail Ignatiadis, Dimitrios Zardavas, Marc Lemort, Celine Wilke, Marie-Catherine Vanderbeeken, Veronique D'Hondt, Evandro De Azambuja, Andrea Gombos, Fabienne Lebrun, Lissandra Dal Lago, Fanny Bustin, Marion Maetens, Lieveke Ameye, Isabelle Veys, Stefan Michiels, Marianne Paesmans, Denis Larsimont, Christos Sotiriou, Jean-Marie Nogaret, Martine Piccart, Ahmad Awada
BACKGROUND: EndoTAG-1, a tumor endothelial targeting agent has shown activity in metastatic triple-negative breast cancer (BC) in combination with paclitaxel. METHODS: HER2-negative BC patients candidates for neoadjuvant chemotherapy were scheduled to receive 12 cycles of weekly EndoTAG-1 22mg/m2 plus paclitaxel 70mg/m2 followed by 3 cycles of FEC (Fluorouracil 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2) every 3 weeks followed by surgery. Primary endpoint was percent (%) reduction in Magnetic Resonance Imaging (MRI) estimated Gadolinium (Gd) enhancing tumor volume at the end of EndoTAG-1 plus paclitaxel administration as compared to baseline...
2016: PloS One
https://www.readbyqxmd.com/read/27289552/liquid-biopsy-based-clinical-research-in-early-breast-cancer-the-eortc-90091-10093-treat-ctc-trial
#16
REVIEW
Michail Ignatiadis, Brigitte Rack, Francoise Rothé, Sabine Riethdorf, Charles Decraene, Hervé Bonnefoi, Christian Dittrich, Carlo Messina, Melanie Beauvois, Elisabeth Trapp, Theodora Goulioti, Konstantinos Tryfonidis, Klaus Pantel, Madeline Repollet, Wolfgang Janni, Martine Piccart, Christos Sotiriou, Saskia Litiere, Jean-Yves Pierga
There is increasing evidence that breast cancer evolves over time under the selection pressure of systemic treatment. Today, treatment decisions in early breast cancer are based on primary tumour characteristics without considering the disease evolution. Chemoresistant micrometastatic disease is poorly characterised and thus it is not used in current clinical practice as a tool to personalise treatment approaches. The detection of chemoresistant circulating tumour cells (CTCs) has been shown to be associated with worse prognosis in early breast cancer...
August 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27177864/pik3ca-mutations-are-associated-with-reduced-pathological-complete-response-rates-in-primary-her2-positive-breast-cancer-pooled-analysis-of-967-patients-from-five-prospective-trials-investigating-lapatinib-and-trastuzumab
#17
S Loibl, I Majewski, V Guarneri, V Nekljudova, E Holmes, E Bria, C Denkert, C Schem, C Sotiriou, S Loi, M Untch, P Conte, R Bernards, M Piccart, G von Minckwitz, J Baselga
BACKGROUND: The predictive value of PIK3CA mutations in HER2 positive (HER2+) breast cancer treated with neoadjuvant anti-HER2 and chemotherapy has been reported, but the power for subgroup analyses was lacking. PATIENTS AND METHODS: We combined individual patient data from five clinical trials evaluating PIK3CA mutations and associations with pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Patients received either trastuzumab (T), lapatinib (L) or the combination T/L in addition to a taxane-based chemotherapy...
August 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27172896/loss-of-arid1a-activates-anxa1-which-serves-as-a-predictive-biomarker-for-trastuzumab-resistance
#18
Katrien Berns, Amir Sonnenblick, Annemiek Gennissen, Sylvain Brohée, E Marielle Hijmans, Bastiaan Evers, Debora Fumagalli, Christine Desmedt, Sibylle Loibl, Carsten Denkert, Patrick Neven, Wei Guo, Fan Zhang, Theo A Knijnenburg, Tjalling Bosse, Michiel S van der Heijden, Sanne Hindriksen, Wouter Nijkamp, Lodewyk F A Wessels, Heikki Joensuu, Gordon B Mills, Roderick L Beijersbergen, Christos Sotiriou, René Bernards
PURPOSE: Despite the substantial progress in the development of targeted anticancer drugs, treatment failure due to primary or acquired resistance is still a major hurdle in the effective treatment of most advanced human cancers. Understanding these resistance mechanisms will be instrumental to improve personalized cancer treatment. EXPERIMENTAL DESIGN: Genome-wide loss-of-function genetic screens were performed to identify genes implicated in resistance to HER2/PI3K/mTOR targeting agents in HER2(+) breast cancer cell lines...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27143638/consensus-on-precision-medicine-for-metastatic-cancers-a-report-from-the-map-conference
#19
C Swanton, J-C Soria, A Bardelli, A Biankin, C Caldas, S Chandarlapaty, L de Koning, C Dive, J Feunteun, S-Y Leung, R Marais, E R Mardis, N McGranahan, G Middleton, S A Quezada, J Rodón, N Rosenfeld, C Sotiriou, F André
Recent advances in biotechnologies have led to the development of multiplex genomic and proteomic analyses for clinical use. Nevertheless, guidelines are currently lacking to determine which molecular assays should be implemented in metastatic cancers. The first MAP conference was dedicated to exploring the use of genomics to better select therapies in the treatment of metastatic cancers. Sixteen consensus items were covered. There was a consensus that new technologies like next-generation sequencing of tumors and ddPCR on circulating free DNA have convincing analytical validity...
August 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27136393/the-topography-of-mutational-processes-in-breast-cancer-genomes
#20
Sandro Morganella, Ludmil B Alexandrov, Dominik Glodzik, Xueqing Zou, Helen Davies, Johan Staaf, Anieta M Sieuwerts, Arie B Brinkman, Sancha Martin, Manasa Ramakrishna, Adam Butler, Hyung-Yong Kim, Åke Borg, Christos Sotiriou, P Andrew Futreal, Peter J Campbell, Paul N Span, Steven Van Laere, Sunil R Lakhani, Jorunn E Eyfjord, Alastair M Thompson, Hendrik G Stunnenberg, Marc J van de Vijver, John W M Martens, Anne-Lise Børresen-Dale, Andrea L Richardson, Gu Kong, Gilles Thomas, Julian Sale, Cristina Rada, Michael R Stratton, Ewan Birney, Serena Nik-Zainal
Somatic mutations in human cancers show unevenness in genomic distribution that correlate with aspects of genome structure and function. These mutations are, however, generated by multiple mutational processes operating through the cellular lineage between the fertilized egg and the cancer cell, each composed of specific DNA damage and repair components and leaving its own characteristic mutational signature on the genome. Using somatic mutation catalogues from 560 breast cancer whole-genome sequences, here we show that each of 12 base substitution, 2 insertion/deletion (indel) and 6 rearrangement mutational signatures present in breast tissue, exhibit distinct relationships with genomic features relating to transcription, DNA replication and chromatin organization...
2016: Nature Communications
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