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https://www.readbyqxmd.com/read/29352646/synthesis-and-biological-evaluation-of-anti-cancer-agents-that-selectively-inhibit-her2-over-expressed-breast-cancer-cell-growth-via-down-regulation-of-her2-protein
#1
Anran Zhao, Qiaoyun Zheng, Cody M Orahoske, Nethrie D Idippily, Morgan M Ashcraft, Aicha Quamine, Bin Su
Compound JCC76 selectively inhibited the proliferation of human epidermal growth factor 2 (Her2) over-expressed breast cancer cells. In the current study, a ligand based structural optimization was performed to generate new analogs, and we identified derivatives 16 and 17 that showed improved activity and selectivity against Her2 positive breast cancer cells. A structure activity relationship (SAR) was summarized. Compounds 16 and 17 were also examined by western blot assay to check their effect on Her2 protein...
January 12, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29352645/diversity-oriented-synthesis-of-chromene-xanthene-hybrids-as-anti-breast-cancer-agents
#2
M Srinivas Lavanya Kumar, Jyotsana Singh, Sudipta Kumar Manna, Saroj Maji, Rituraj Konwar, Gautam Panda
A diverse library of chromene-xanthene hybrids were synthesized through intramolecular Friedel-Crafts reaction of the arenoxy carbinols. Examples include first incorporation of amino acid tyrosine into xanthene skeletons with polar functionalities. A careful structural evaluation revealed that tyrosine crafted chromene-xanthene hybrids exhibited good activities against breast cancer cell lines MCF-7, MDA-MB-231. The lead compound 16 displays significant cell cycle arrest at G1 phase and induces apoptosis in MDA-MB-231 cells...
January 6, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29352629/an-in-silico-comparative-dosimetric-study-of-postmastectomy-locoregional-irradiation-using-intensity-modulated-vs-3-dimensional-conventional-radiotherapy
#3
Pooja Khullar, Charu Garg, Sujit Nath Sinha, Inderjit Kaur, Niloy Ranjan Datta
An in silico dosimetric evaluation of intensity-modulated radiation therapy (IMRT) vs 3-dimensional conventional radiation therapy (3D-CRT) treatment plans in postmastectomy radiation therapy (PMRT) to the chest wall and regional lymphatics was conducted. Twenty-five consecutive patients with breast cancer referred for locoregional PMRT, stages T2-4 with N1-3, were planned to receive 50 Gy in 25 fractions with IMRT. Additionally, a 3D-CRT plan was generated using identical contours for the clinical target volumes (CTV), planning target volumes (PTV), and organs at risk (OAR)...
January 15, 2018: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
https://www.readbyqxmd.com/read/29352595/axillary-tumour-burden-in-women-with-one-abnormal-node-on-ultrasound-compared-to-women-with-multiple-abnormal-nodes
#4
S Puri, N Sharma, R G Newcombe, M Kaushik, M Al-Attar, S Pascaline, M Hajaj, M G Wallis, B Elsberger, A Goyal
AIM: To determine if the number of abnormal nodes seen on preoperative axillary ultrasound (AUS) is a predictor of the number of positive nodes at histology for women with needle-biopsy-proven positive nodes. MATERIALS AND METHODS: This prospective multicentre cohort study included consecutive patients with early breast cancer who had needle-biopsy-proven positive nodes on AUS and underwent axillary lymph node dissection (ALND) between October 2015 and July 2016...
January 15, 2018: Clinical Radiology
https://www.readbyqxmd.com/read/29352572/phase-i-combination-study-of-the-parp-inhibitor-veliparib-plus-carboplatin-and-gemcitabine-in-patients-with-advanced-ovarian-cancer-and-other-solid-malignancies
#5
Heidi J Gray, Katherine Bell-McGuinn, Gini F Fleming, Mihaela Cristea, Hao Xiong, Danielle Sullivan, Yan Luo, Mark D McKee, Wijith Munasinghe, Lainie P Martin
OBJECTIVE: Determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of veliparib combined with carboplatin and gemcitabine in patients with advanced ovarian cancer and other nonhematologic malignancies. METHODS: In this phase I study, patients with metastatic or unresectable solid tumors and ≤2 prior chemotherapy regimens received veliparib combined with carboplatin area under the curve (AUC) 4 on day 1 and gemcitabine 800mg/m2 on days 1 and 8 of a 21-day cycle for maximum 10cycles, followed by optional veliparib maintenance therapy...
January 15, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29352569/patient-navigation-reduces-time-to-care-for-patients-with-breast-symptoms-and-abnormal-screening-mammograms
#6
Elaine McKevitt, Carol Dingee, Rebecca Warburton, Jin-Si Pao, Carl J Brown, Christine Wilson, Urve Kuusk
INTRODUCTION: Concern has been raised about delays for patients presenting with breast symptoms in Canada. Our objective was to determine if our Rapid Access Breast Clinic (RABC) improved care for patients presenting with breast symptoms compared to the traditional system (TS). METHODS: A retrospective chart review tabulated demographic, surgical, pathology and radiologic information. Wait times to care were determined for patients presenting with symptomatic and screen detected breast problems...
January 5, 2018: American Journal of Surgery
https://www.readbyqxmd.com/read/29352566/in-hospital-cerebrovascular-outcomes-of-patients-with-atrial-fibrillation-and-cancer-from-the-national-inpatient-sample-database
#7
Ayman Elbadawi, Islam Y Elgendy, Le Dung Ha, Basarat Baig, Marwan Saad, Hussain Adly, Gbolahan O Ogunbayo, Odunayo Olorunfemi, Matthew S Mckillop, Scott A Maffett
Limited data are available regarding the impact of cancer on cerebrovascular accidents in patients with atrial fibrillation (AF). We queried the Nationwide Inpatient Survey Database to identify patients who have diagnostic code for AF. We performed a 1:1 propensity matching based on the CHA2DS2VASc score and other risk factors between patients with AF who had lung, breast, colon, and esophageal cancer, and those who did not (control). The final cohort included a total of 31,604 patients. The primary outcome of in-hospital cerebrovascular accidents (CVA) was lower in the cancer group than in the control group (4% vs 7%, p < 0...
December 20, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/29352368/endocrine-therapy-and-related-issues-in-hormone-receptor-positive-early-breast-cancer-a-roundtable-discussion-by-the-breast-cancer-therapy-expert-group-bcteg
#8
REVIEW
Jame Abraham, Humberto Caldera, Robert Coleman, Anthony Elias, Matthew P Goetz, Muaiad Kittaneh, Elyse Lower, Reshma Mahtani, E Terry Mamounas, Mark Pegram, Hope Rugo, Lee Schwartzberg, Tiffany Traina, Chuck Vogel
PURPOSE: Management of breast cancer is a rapidly evolving field, and, although evidence-based guidelines are available for clinicians to provide direction on critical issues in patient care, clinicians often left to address these issues in the context of community practice situations with their patients. These include the patient's comorbid conditions, actual versus perceived benefit of treatments, patient's compliance as well as financial/reimbursement issues, and long-term tolerability of therapy...
January 19, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29352246/u-box-ubiquitin-ligase-ppil2-suppresses-breast-cancer-invasion-and-metastasis-by-altering-cell-morphology-and-promoting-snai1-ubiquitination-and-degradation
#9
Zhaojun Jia, Miao Wang, Shujing Li, Xiahui Li, Xiao-Yan Bai, Zhaowei Xu, Yangyang Yang, Bowen Li, Yanan Li, Huijian Wu
Metastasis is the leading cause of breast cancer fatalities. To develop new therapeutic strategies, the mechanisms underlying breast cancer invasion and metastasis need to be further investigated. Peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the cyclophilin family. Proteins within this family are the major cytosolic binding proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has been reported to potentially be involved in cell migration, its role in breast cancer is still unclear...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352243/nucleolin-and-erbb2-inhibition-reduces-tumorigenicity-of-erbb2-positive-breast-cancer
#10
Eya Wolfson, Shira Solomon, Eran Schmukler, Yona Goldshmit, Ronit Pinkas-Kramarski
ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell's growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives cellular transformation and cancer development. Recently, we have shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein nucleolin, an interaction which enhances cell transformation in vitro, and increases mortality risk and disease progression rate in human breast cancer patients...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352235/systems-modeling-accurately-predicts-responses-to-genotoxic-agents-and-their-synergism-with-bcl-2-inhibitors-in-triple-negative-breast-cancer-cells
#11
Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen H M Prehn
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#12
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352214/handheld-magnetic-probe-with-permanent-magnet-and-hall-sensor-for-identifying-sentinel-lymph-nodes-in-breast-cancer-patients
#13
Masaki Sekino, Akihiro Kuwahata, Tetsu Ookubo, Mikio Shiozawa, Kaichi Ohashi, Miki Kaneko, Itsuro Saito, Yusuke Inoue, Hiroyuki Ohsaki, Hiroyuki Takei, Moriaki Kusakabe
The newly developed radioisotope-free technique based on magnetic nanoparticle detection using a magnetic probe is a promising method for sentinel lymph node biopsy. In this study, a novel handheld magnetic probe with a permanent magnet and magnetic sensor is developed to detect the sentinel lymph nodes in breast cancer patients. An outstanding feature of the probe is the precise positioning of the sensor at the magnetic null point of the magnet, leading to highly sensitive measurements unaffected by the strong ambient magnetic fields of the magnet...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352164/determinants-of-breast-size-in-asian-women
#14
Li Yan Lim, Peh Joo Ho, Jenny Liu, Wen Yee Chay, Min-Han Tan, Mikael Hartman, Jingmei Li
Breast size as a risk factor of breast cancer has been studied extensively with inconclusive results. Here we examined the associations between breast size and breast cancer risk factors in 24,353 Asian women aged 50 to 64 years old enrolled in a nationwide mammography screening project conducted between October 1994 and February 1997. Information on demographic and reproductive factors was obtained via a questionnaire. Breast size was ascertained as bust line measured at study recruitment and total breast area measured from a mammogram...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352052/estrogen-receptor-positive-breast-cancer-exploiting-signaling-pathways-implicated-in-endocrine-resistance
#15
REVIEW
Adam M Brufsky, Maura N Dickler
Advancements in molecular profiling and endocrine therapy (ET) have led to more focused clinical attention on precision medicine. These advances have expanded our understanding of breast cancer (BC) pathogenesis and hold promising implications for the future of therapy. The estrogen receptor-α is a predominant endocrine regulatory protein in the breast and in estrogen-induced BC. Successful targeting of proteins and genes within estrogen receptor (ER) nuclear and nonnuclear pathways remains a clinical goal...
January 19, 2018: Oncologist
https://www.readbyqxmd.com/read/29351960/the-impact-of-diabetes-on-breast-cancer-treatments-and-outcomes-a-population-based-study
#16
Iliana C Lega, Peter C Austin, Hadas D Fischer, Kinwah Fung, Monika K Krzyzanowska, Eitan Amir, Lorraine L Lipscombe
OBJECTIVE: Women with breast cancer and diabetes face worse outcomes than those with breast cancer without diabetes; however, the contribution of comorbidity to these disparities remains unclear. We evaluated the impact of diabetes on receipt of cancer treatments as well as mortality while accounting for other comorbidities. RESEARCH DESIGN AND METHODS: Ontario administrative databases were used to compare the rate of receipt of breast cancer treatments between women with and without diabetes...
January 19, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29351904/er%C3%AE-mediated-nuclear-sequestration-of-rsk2-is-required-for-er-breast-cancer-tumorigenesis
#17
Katarzyna A Ludwik, Oliver Gene McDonald, David R Brenin, Deborah A Lannigan
Although ribosomal protein S6 kinase A3 (RSK) activation status positively correlates with patient responses to anti-estrogen hormonal therapies, the mechanistic basis for these observations is unknown. Using multiple in vitro and in vivo models of ER+ breast cancer, we report that ERα sequesters active RSK2 into the nucleus to promote neoplastic transformation and facilitate metastatic tumor growth. RSK2 physically interacted with ERα through its N-terminus to activate a pro-neoplastic transcriptional network critical to the ER+ lineage in the mammary gland, thereby providing a gene signature that effectively stratified patient tumors according to ERα status...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29351903/integrative-genomic-analysis-predicts-causative-cis-regulatory-mechanisms-of-the-breast-cancer-associated-genetic-variant-rs4415084
#18
Yi Zhang, Mohith Manjunath, Shilu Zhang, Deborah Chasman, Sushmita Roy, Jun S Song
Previous genome-wide association studies (GWAS) have identified several common genetic variants that may significantly modulate cancer susceptibility. However, the precise molecular mechanisms behind these associations remain largely unknown; it is often not clear whether discovered variants are themselves functional or merely genetically linked to other functional variants. Here we provide an integrated method for identifying functional regulatory variants associated with cancer and their target genes by combining analyses of expression quantitative trait loci (eQTL), a modified version of allele-specific expression (ASE) that systematically utilizes haplotype information, transcription factor (TF) binding preference, and epigenetic information...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29351902/targeting-the-sphk1-s1p-s1pr1-axis-that-links-obesity-chronic-inflammation-and-breast-cancer-metastasis
#19
Masayuki Nagahashi, Akimitsu Yamada, Eriko Katsuta, Tomoyoshi Aoyagi, Wei-Ching Huang, Krista P Terracina, Nitai C Hait, Jeremy C Allegood, Junko Tsuchida, Kizuki Yuza, Masato Nakajima, Manabu Abe, Kenji Sakimura, Sheldon Milstien, Toshifumi Wakai, Sarah Spiegel, Kazuaki Takabe
Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) which mediates cancer pathogenesis. A high fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29351901/xiap-regulation-by-mnk-links-mapk-and-nf%C3%AE%C2%BAb-signaling-to-determine-an-aggressive-breast-cancer-phenotype
#20
Myron K Evans, Michael C Brown, Joseph Geradts, Xuhui Bao, Timothy J Robinson, Mohit Kumar Jolly, Peter Vermeulen, Gregory M Palmer, Matthias Gromeier, Herbert Levine, Michael A Morse, Steven Van Laere, Gayathri R Devi
Hyperactivation of the NFκB pathway is a distinct feature of inflammatory breast cancer (IBC), a highly proliferative and lethal disease. Gene expression studies in IBC patient tissue have linked epidermal growth factor receptor (EGFR/HER2)-mediated MAPK signaling to NFκB hyperactivity, but the mechanism(s) by which this occurs remain unclear. Here, we report that the X-linked inhibitor of apoptosis protein (XIAP) plays a central role in linking these two pathways. XIAP overexpression correlated with poor prognoses in breast cancer patients and was frequently observed in untreated IBC patient primary tumors...
January 19, 2018: Cancer Research
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