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Patrizia Ferroni, Francesca Santilli, Francesco Cavaliere, Paola Simeone, Leopoldo Costarelli, Rossella Liani, Romina Tripaldi, Silvia Riondino, Mario Roselli, Giovanni Davi, Fiorella Guadagni
The hypothesis that increased oxidative stress in breast cancer (BC) patients could induce enhanced lipid peroxidation, which, in turn, would contribute to platelet activation and poor clinical outcome is attractive. To address this issue, we investigated pre-surgical urinary 8-iso-prostaglandin (PG)F2α (marker of in vivo oxidative stress) and 11-dehydro-thromboxane (TX)B2 (marker of in vivo platelet activation) levels in patients with primary BC (n=115) compared with control women paired for co-morbidities and their association with patients' metabolic profile and clinical prognostic factors...
October 26, 2016: International Journal of Cancer. Journal International du Cancer
Ju Hui Jeong, Yong Jin Oh, Yunmee Lho, Sun You Park, Kwang-Hyeon Liu, Eunyoung Ha, Young Ho Seo
The molecular chaperone Hsp90 plays an important role in cancer cell survival and proliferation by regulating the maturation and stabilization of numerous oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 has emerged as an attractive therapeutic target for cancer treatment. In this study, the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors are described. Among the synthetic compounds, 6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl amide 19 exhibits a remarkable binding affinity to the N-terminus of Hsp90 in a fluorescence polarization (FP) binding assay (IC50 = 50...
October 18, 2016: European Journal of Medicinal Chemistry
Emad A Rakha, Devika Agarwal, Andrew R Green, Ibraheem Ashankyty, Ian O Ellis, Graham Ball, Mohammed A Alaskandarany
: Multigene assay is currently recommended for prognostic stratification of the clinically indeterminate group of breast cancer (BC) patients defined as lymph node (LN)-negative, oestrogen receptor (ER)-positive HER2-negative (LN-/ER+/HER2-) to determine the use of chemotherapy. However this cohort, comprising approximately 40% of BC, is not a homogeneous group and shows variable outcome. This study aims to determine the prognostic value of routinely assessed variables, singly and in combination, in the LN-/ER+/HER2- BC...
October 26, 2016: Histopathology
Barbara Bernardim, Pedro M S D Cal, Maria J Matos, Bruno L Oliveira, Nuria Martínez-Sáez, Inês S Albuquerque, Elizabeth Perkins, Francisco Corzana, Antonio C B Burtoloso, Gonzalo Jiménez-Osés, Gonçalo J L Bernardes
Maleimides remain the reagents of choice for the preparation of therapeutic and imaging protein conjugates despite the known instability of the resulting products that undergo thiol-exchange reactions in vivo. Here we present the rational design of carbonylacrylic reagents for chemoselective cysteine bioconjugation. These reagents undergo rapid thiol Michael-addition under biocompatible conditions in stoichiometric amounts. When using carbonylacrylic reagents equipped with PEG or fluorophore moieties, this method enables access to protein and antibody conjugates precisely modified at pre-determined sites...
October 26, 2016: Nature Communications
Filippo Pietrantonio, Claudio Vernieri, Giulia Siravegna, Alessia Mennitto, Rosa Berenato, Federica Perrone, Annunziata Gloghini, Elena Tamborini, Sara Lonardi, Federica Morano, Benedetta Picciani, Adele Busico, Chiara C Volpi, Antonia Martinetti, Francesca Battaglin, Ilaria Bossi, Alessio Pellegrinelli, Massimo Milione, Chiara Cremolini, Maria Di Bartolomeo, Alberto Bardelli, Filippo de Braud
Purpose Even if RAS-BRAF wild-type and HER2/MET negative mCRC patients frequently respond to anti-EGFR monoclonal antibodies, acquired resistance almost invariably occurs. Mechanisms of resistance to EGFR blockade include the emergence of KRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations. However, these findings derive from retrospective studies that analyzed one single resistance mechanism at a time; moreover, it is still unclear how molecular heterogeneity affects clonal evolution in patients...
October 25, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Henrik Møller, Katherine Henson, Margreet Lüchtenborg, John Broggio, Jackie Charman, Victoria H Coupland, Elizabeth Davies, Ruth H Jack, Richard Sullivan, Peter Vedsted, Kieran Horgan, Neil Pearce, Arnie Purushotham
BACKGROUND: In the re-organisation of cancer registration in England in 2012, a high priority was given to the recording of cancer stage and other prognostic clinical data items. METHODS: We extracted 86 852 breast cancer records for women resident in England and diagnosed during 2012-2013. Information on age, ethnicity, socio-economic status, comorbidity, tumour stage, grade, morphology and oestrogen, progesterone and HER2 receptor status was included. The two-year cumulative risk of death from any cause was estimated with the Kaplan-Meier method, and univariate and multivariate Cox proportional hazards regressions were used to estimate hazard ratios (HR) and their 95% confidence intervals (95% CI)...
October 25, 2016: British Journal of Cancer
Edgar Teddy Quispe-Soto, Gloria M Calaf
Global cancer burden increased to 14.1 million new cases in 2012; and breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed in 2012. Curcumin is the major bioactive ingredient extracted from the rhizome of the plant Curcuma longa (turmeric). Paclitaxel is a microtubule-stabilizing agent originally isolated from the bark of Taxus brevifolia. Curcumin and paclitaxel were evaluated with two human breast cancer cell lines as the luminal MCF-7 and the basal-like MDA-MB-231 that are either positive or negative for hormonal receptors estrogen receptor, progesterone receptor and HER2, respectively...
October 19, 2016: International Journal of Oncology
Arnaldo N S Silva, Jordy Coffa, Varsha Menon, Lindsay C Hewitt, Kakoli Das, Yohei Miyagi, Dan Bottomley, Hayley Slaney, Toru Aoyama, Wolfram Mueller, Tomio Arai, Iain B Tan, Niantao Deng, Xiu B Chan, Patrick Tan, Akira Tsuburaya, Kentaro Sakamaki, Jeremy D Hayden, Takaki Yoshikawa, Ilse Zondervan, Suvi Savola, Heike I Grabsch
OBJECTIVE: To establish the gene copy number status of receptor tyrosine kinase (RTK) and downstream signaling (DSS) genes genes in primary gastric cancer (primGC) and matched lymph node metastases (LNmet). BACKGROUND: Evidence suggests that coamplification between RTKs and DSSs and conversion between primGC and LNmet are associated with resistance to targeted therapy. METHODS: DNA from 237 Japanese primGC and 103 matched LNmet was analyzed using a newly developed multiplex ligation-dependent probe amplification (MLPA) probemix to investigate RTK (EGFR, HER2, FGFR2, and MET) and DSS (PIK3CA, KRAS, MYC, and CCNE1) gene copy number status...
October 24, 2016: Annals of Surgery
Malgorzata Banys-Paluchowski, Eike Burandt, Joanna Banys, Stefan Geist, Guido Sauter, Natalia Krawczyk, Peter Paluchowski
Breast cancer (BC) in men represents between 0.5% and 1% of all BC diagnosed each year. We report a case of advanced BC in a 62-year-old male treated at our interdisciplinary Breast Cancer Center. The patient presented with a newly diagnosed large, symptomatic mass in his left breast. Clinical examination showed a not movable mass of 16 cm diameter, deforming the whole breast; the overlying skin was livid and hypervascularized. Enlarged lymph nodes were palpable in the axillary pit. He had no concomitant diseases at time of presentation...
October 10, 2016: World Journal of Clinical Oncology
Sasha E Stanton, Mary L Disis
Tumor infiltrating lymphocytes (TIL) play an essential role in mediating response to chemotherapy and improving clinical outcomes in all subtypes of breast cancer. Triple negative breast cancers (TN) are most likely to have tumors with >50 % lymphocytic infiltrate, termed lymphocyte predominant breast cancer, and derive the greatest survival benefit from each 10 % increase in TIL. The majority of HER2(+) breast cancers have similar level of immune infiltrate as TN breast cancer yet the presence of TILs has not shown the same survival benefit...
2016: Journal for Immunotherapy of Cancer
Tomoki Tamura, Taizo Hirata, Masahiro Tabata, Shiro Hinotsu, Akinobu Hamada, Takayuki Motoki, Takayuki Iwamoto, Taeko Mizoo, Tomohiro Nogami, Tadahiko Shien, Naruto Taira, Junji Matsuoka, Hiroyoshi Doihara
Docetaxel is a standard treatment for patients with advanced or recurrent breast cancer. The recommended dose is 60 to 100 mg/m2. Previous study have shown that the tumor response rates of patients who received docetaxel monotherapy at doses of 60, 75, and 100 mg/m2 were 22.1% , 23.3% , and 36.0% , respectively, and there was a significant relationship between the dose and response. In Europe and the United States, docetaxel is approved at a dose of 100 mg/m2, and Japanese guidelines also recommend a dose of 100 mg/m2...
October 2016: Acta Medica Okayama
Sinead Toomey, Stephen F Madden, Simon J Furney, Yue Fan, Mark McCormack, Carragh Stapleton, Mattia Cremona, Gianpiero L Cavalleri, Malgorzata Milewska, Naomi Elster, Aoife Carr, Joanna Fay, Elaine W Kay, Susan Kennedy, John Crown, William M Gallagher, Bryan T Hennessy, Alex J Eustace
BACKGROUND: Trastuzumab treatment for women with HER2-positive breast cancer (BC) resulted in the significant improvement of both relapse free survival (RFS) and overall survival (OS). However, many women who are classified as HER2-positive do not respond. Many studies have focused on the role of somatic mutations rather than germline polymorphisms in trastuzumab resistance. RESULTS: We completed an Agena MassArray screen of 10 ERBB-family single nucleotide polymorphisms (SNPs) in 194 adjuvant trastuzumab treated HER2-positive BC patients...
October 20, 2016: Oncotarget
Sara Westrøm, Tina B Bønsdorff, Nasir Abbas, Øyvind S Bruland, Thora J Jonasdottir, Gunhild M Mælandsmo, Roy H Larsen
BACKGROUND: Osteosarcoma is a rare form of cancer but with a substantial need for new active drugs. There is a particular need for targeted therapies to combat metastatic disease. One possible approach is to use an antibody drug conjugate or an antibody radionuclide conjugate to target the osteosarcoma metastases and circulating tumor cells. Herein we have evaluated a radiolabeled monoclonal antibody targeting CD146 both in vitro and in vivo. METHODS AND RESULTS: A murine monoclonal anti-CD146 IgG1 isotype antibody, named OI-3, was developed along with recombinant chimeric versions with human IgG1 or human IgG3 Fc sequences...
2016: PloS One
Dai Horiuchi, Roman Camarda, Alicia Y Zhou, Christina Yau, Olga Momcilovic, Sanjeev Balakrishnan, Alexandra N Corella, Henok Eyob, Kai Kessenbrock, Devon A Lawson, Lindsey A Marsh, Brittany N Anderton, Julia Rohrberg, Ratika Kunder, Alexey V Bazarov, Paul Yaswen, Michael T McManus, Hope S Rugo, Zena Werb, Andrei Goga
Triple-negative breast cancer (TNBC), in which cells lack expression of the estrogen receptor (ER), the progesterone receptor (PR) and the ERBB2 (also known as HER2) receptor, is the breast cancer subtype with the poorest outcome. No targeted therapy is available against this subtype of cancer owing to a lack of validated molecular targets. We previously reported that signaling involving MYC-an essential, pleiotropic transcription factor that regulates the expression of hundreds of genes-is disproportionally higher in triple-negative (TN) tumors than in receptor-positive (RP) tumors...
October 24, 2016: Nature Medicine
Paola Caria, Silvia Cantara, Daniela Virginia Frau, Furio Pacini, Roberta Vanni, Tinuccia Dettori
Extensive research is dedicated to understanding if sporadic and familial papillary thyroid carcinoma are distinct biological entities. We have previously demonstrated that familial papillary thyroid cancer (fPTC) cells exhibit short relative telomere length (RTL) in both blood and tissues and that these features may be associated with chromosome instability. Here, we investigated the frequency of HER2 (Human Epidermal Growth Factor Receptor 2) amplification, and other recently reported genetic alterations in sporadic PTC (sPTC) and fPTC, and assessed correlations with RTL and BRAF mutational status...
October 21, 2016: International Journal of Molecular Sciences
Zehra Kaya, Mustafa Akkiprik, Sevgi Karabulut, Irem Peker, Gokce Gullu Amuran, Tolga Ozmen, Bahadır M Gulluoglu, Handan Kaya, Ayse Ozer
BACKGROUND: Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. METHODS: Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues...
October 24, 2016: Journal of Clinical Laboratory Analysis
A Chiche, M Moumen, M Romagnoli, V Petit, H Lasla, P Jézéquel, P de la Grange, J Jonkers, M-A Deugnier, M A Glukhova, M M Faraldo
Triple-negative breast cancer is a heterogeneous disease characterized by the expression of basal cell markers, no estrogen or progesterone receptor expression and a lack of HER2 overexpression. Triple-negative tumors often display activated Wnt/β-catenin signaling and most have impaired p53 function. We studied the interplay between p53 loss and Wnt/β-catenin signaling in stem cell function and tumorigenesis, by deleting p53 from the mammary epithelium of K5ΔNβcat mice displaying a constitutive activation of Wnt/β-catenin signaling in basal cells...
October 24, 2016: Oncogene
Carlynn Willmore-Payne, Kristy Damjanovich-Colmenares, Alexandra V Pasi, Theresa L Werner, H Evin Gulbahce, Erinn Downs-Kelly, Katherine B Geiersbach
OBJECTIVES: Guidelines suggest that secondary reflex testing may be useful for resolving HER2 status in breast cancers with equivocal results by both immunohistochemistry (IHC) and in situ hybridization (ISH). We compared two reflex ISH assays and a polymerase chain reaction (PCR) assay for this application. METHODS: Twenty-nine breast cancers with equivocal IHC and ISH results were retested two ways: (1) ISH using differentially labeled probes targeting ERBB2 (HER2, 17q12) and either RAI1 (17p11...
October 22, 2016: American Journal of Clinical Pathology
Lin Shan, Xing Zhou, Xinhua Liu, Yue Wang, Dongxue Su, Yongqiang Hou, Na Yu, Chao Yang, Beibei Liu, Jie Gao, Yang Duan, Jianguo Yang, Wanjin Li, Jing Liang, Luyang Sun, Kexin Chen, Chenghao Xuan, Lei Shi, Yan Wang, Yongfeng Shang
Although clinically associated with severe developmental defects, the biological function of FOXK2 remains poorly explored. Here we report that FOXK2 interacts with transcription corepressor complexes NCoR/SMRT, SIN3A, NuRD, and REST/CoREST to repress a cohort of genes including HIF1β and EZH2 and to regulate several signaling pathways including the hypoxic response. We show that FOXK2 inhibits the proliferation and invasion of breast cancer cells and suppresses the growth and metastasis of breast cancer. Interestingly, FOXK2 is transactivated by ERα and transrepressed via reciprocal successive feedback by HIF1β/EZH2...
October 14, 2016: Cancer Cell
Helen Keeman, Gavin C Harris
No abstract text is available yet for this article.
February 2016: Pathology
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