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Cancer breast

Daniel Panchik, Sarah Masco, Patrice Zinnikas, Brooke Hillriegel, Tori Lauder, Erica Suttmann, Vernon Chinchilli, Maureen McBeth, William Hermann
BACKGROUND:  Breast cancer-related lymphedema (BCRL) affects many areas of daily living. Individuals with lymphedema may experience chronic and progressive swelling, recurrent skin infections, and decreased self-image and quality of life. For many years, it was considered best practice for this population to avoid exercise; however, in recent years, research has begun to challenge this belief. This systematic review and meta-analyses examined the recent literature on the effects of exercise for patients with, or at risk for, BCRL to inform best practice...
June 23, 2018: Journal of Reconstructive Microsurgery
Louise M Stewart, Katrina Spilsbury, Susan Jordan, Colin Stewart, C D'Arcy J Holman, Aime Powell, Joanne Reekie, Paul Cohen
BACKGROUND: Ovarian carcinoma is not a single disease, but rather a collection of subtypes with differing molecular properties and risk profiles. The most common of these, and the subject of this work, is high-grade serous ovarian carcinoma (HGSC). METHODS: In this population-based study we identified a cohort of 441,382 women resident in Western Australia who had ever been admitted to hospital in the State. Of these, 454 were diagnosed with HGSC. We used Cox regression to derive hazard ratios (HRs) comparing the risk of disease in women who had each of a range of medical diagnoses and surgical procedures with women who did not...
June 20, 2018: Cancer Epidemiology
Michael P Shea, Kathleen A O'Leary, Kyle A Wegner, Chad M Vezina, Linda A Schuler
Metastatic estrogen receptor alpha positive (ERα+) cancers account for most breast cancer mortality. Cancer stem cells (CSCs) and dense/stiff extracellular matrices are implicated in aggression and therapy resistance. We examined this interplay and response to mTOR inhibition using ERα+ adenocarcinomas from NRL-PRL females in combination with Col1a1tmJae/+ (mCol1a1) mice, which accumulate collagen-I around growing tumors. Orthotopic transplantation of tumor cells to mCol1a1 but not wildtype hosts resulted in striking desmoplasia...
June 20, 2018: Cancer Letters
Kazem Zibara, Asad Zeidan, Khalil Mallah, Nouhad Kassem, Ali Awwad, Frédéric Mazurier, Bassam Badran, Nabil El-Zein
PACAP has opposing roles ranging from activation to inhibition of tumor growth and PACAP agonists/antagonists could be used in tumor therapy. In this study, the effect of PACAP stimulation on signaling pathways was investigated in MCF-7 human adenocarcinoma breast cancer cells. Results showed that MCF-7 cells express VPAC1 and VPAC2, but not PAC1, receptors. In addition, PACAP increased the phosphorylation levels of STAT1, Src and Raf within seconds, confirming their involvement in early stages of PACAP signaling whereas maximal phosphorylation of AKT, ERK and p38 was reached 10 to 20 min later...
June 20, 2018: Cellular Signalling
Manli Liu, Yan Qi, Lili Zhao, Dongdong Chen, Yang Zhou, Hongrun Zhou, Yanmin Lv, Lu Zhang, Shan Jin, Shugang Li, Hong Zou, Wei Jia, Cuicui Wang, Jinfang Jiang, Weihua Liang, Lijuan Pang, Feng Li
Synovial sarcoma (SS) is a highly aggressive malignant soft tissue sarcoma with typical characteristics of both epithelial and mesenchymal differentiation. Matrix metalloproteinase-14 (MMP-14) is reported to play an important role in some of these tumors. It induces epithelial-to-mesenchymal transition (EMT) in some carcinomas, such as breast and prostate cancers. However, the role of MMP-14 in the pathogenesis of SS remains unclear. Therefore, we investigated the role of MMP-14 and EMT/mesenchymal-to-epithelial transition (MET) in SS...
June 20, 2018: Human Pathology
Kirsten L Moek, Rudolf S N Fehrmann, Bert van der Vegt, Elisabeth G E de Vries, Derk Jan A de Groot
Glypican 3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is overexpressed in ∼70% to 80% of hepatocellular carcinomas (HCCs), but uncommonly expressed in healthy tissues. This raised interest in GPC3 as drug target, and several GPC3-targeting drugs are in clinical development. We therefore predicted GPC3 protein overexpression across tumors and validated these predictions. Functional genomic mRNA profiling was applied to expression profiles of 18,055 patient-derived tumor samples to predict GPC3 overexpression at the protein level in 60 tumor types and subtypes using healthy tissues as reference...
June 20, 2018: American Journal of Pathology
Jacek Koszuk, Tomasz Bartosik, Jakub Wojciechowski, Wojciech Wolf, Anna Janecka, Joanna Drogosz, Angelika Długosz, Urszula Krajewska, Marek Mirowski, Tomasz Janecki
An efficient synthetic strategy to 3-methylidene-2,3-dihydroquinolin-4(1H)-ones variously substituted in position 2 has been developed. The title compounds were synthesized in the reaction sequence involving reaction of diethyl methylphosphonate with methyl 2-(tosylamino)benzoate, condensation of thus formed diethyl 2-(2-N-tosylphenyl)2-oxoethylphosphonate with various aldehydes followed by successful application of the obtained 3-diethoxyphosphoryl-1,2-dihydroquinolin-4-ols as Horner-Wadsworth-Emmons reagents for the olefination of formaldehyde...
June 23, 2018: Chemistry & Biodiversity
Peter G F Watson, Hamed Bekerat, Pavlos Papaconstadopoulos, Stephen Davis, Jan Seuntjens
PURPOSE: Intraoperative radiotherapy using The INTRABEAM System (Carl Zeiss Meditec AG, Jena, Germany), a miniature low-energy X-ray source, has proven to be an effective modality in the treatment of breast cancer. However, some uncertainties remain in its dosimetry. In this work, we investigated the INTRABEAM system dosimetry by performing ionization chamber and radiochromic film measurements of absorbed dose in a water phantom. METHODS: Ionization chamber measurements were performed with a PTW 34013 parallel-plate soft X-ray chamber at source to detector distances of 5 mm to 30 mm in a water phantom...
June 23, 2018: Medical Physics
Annie Xiao, Jennie Crosby, Martha Malin, Hyejoo Kang, Maxine Washington, Yasmin Hasan, Steven J Chmura, Hania A Al-Hallaq
PURPOSE: We calculated setup margins for whole breast radiotherapy during voluntary deep-inspiration breath-hold (vDIBH) using real-time surface imaging (SI). METHODS AND MATERIALS: Patients (n = 58) with a 27-to-31 split between right- and left-sided cancers were analyzed. Treatment beams were gated using AlignRT by registering the whole breast region-of-interest to the surface generated from the simulation CT scan. AlignRT recorded (three-dimensional) 3D displacements and the beam-on-state every 0...
June 22, 2018: Journal of Applied Clinical Medical Physics
Chwanrow Karim Baban, Liam Devane, James Geraghty
Developed countries face significant population ageing in the near future. Within 20 years, the average age will approach 50 years and the largest population cohort will be those over 65 years. The incidence of breast cancer increases with age, with a risk in women of 0.44% by the age of 30, 3.82% by the age of 70 and 10% by the age of 80. Breast cancer is responsible for one out of every three cancer-related deaths. Elderly patients have higher mortality rates and most breast cancer-related deaths are observed in women over 65...
June 23, 2018: Irish Journal of Medical Science
Silvia Gramolelli, Jianpin Cheng, Ines Martinez-Corral, Markus Vähä-Koskela, Endrit Elbasani, Elisa Kaivanto, Ville Rantanen, Krista Tuohinto, Sampsa Hautaniemi, Mark Bower, Caj Haglund, Kari Alitalo, Taija Mäkinen, Tatiana V Petrova, Kaisa Lehti, Päivi M Ojala
The transcription factor PROX1 is essential for development and cell fate specification. Its function in cancer is context-dependent since PROX1 has been shown to play both oncogenic and tumour suppressive roles. Here, we show that PROX1 suppresses the transcription of MMP14, a metalloprotease involved in angiogenesis and cancer invasion, by binding and suppressing the activity of MMP14 promoter. Prox1 deletion in murine dermal lymphatic vessels in vivo and in human LECs increased MMP14 expression. In a hepatocellular carcinoma cell line expressing high endogenous levels of PROX1, its silencing increased both MMP14 expression and MMP14-dependent invasion in 3D...
June 22, 2018: Scientific Reports
Puja Khanna, Joan Shuying Lee, Amornpun Sereemaspun, Haeryun Lee, Gyeong Hun Baeg
Dysregulated JAK/STAT signaling has been implicated in breast cancer metastasis, which is associated with high relapse risks. However, mechanisms underlying JAK/STAT signaling-mediated breast tumorigenesis are poorly understood. Here, we showed that GRAMD1B expression is upregulated on IL-6 but downregulated upon treatment with the JAK2 inhibitor AG490 in the breast cancer MDA-MB-231 cells. Notably, Gramd1b knockdown caused morphological changes of the cells, characterized by the formation of membrane ruffling and protrusions, implicating its role in cell migration...
June 22, 2018: Scientific Reports
Jeongmin Lee, Sung Hun Kim, Bong Joo Kang
The purpose of this study was to investigate imaging parameters predicting pathologic complete response (pCR) in pretreatment dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) in breast cancer patients who were treated with neoadjuvant chemotherapy (NAC). A total of 74 patients who received NAC followed by surgery were retrospectively reviewed. All patients underwent breast MRI before NAC. Perfusion parameters including Ktrans, Kep and Ve of tumor were measured three-dimensionally. These perfusion parameters of background parenchyma of contralateral breasts were analyzed two-dimensionally...
June 22, 2018: Scientific Reports
Rui Han, Shanzhi Gu, Yujiao Zhang, Anqi Luo, Xin Jing, Lin Zhao, Xinhan Zhao, Lingxiao Zhang
The chemokine (C-C motif) ligand 2 (CCL2) with its cognate receptor chemokine (C-C motif) receptor 2 (CCR2) plays important roles in tumor invasion and metastasis. However, the mechanisms and mediators for autocrine CCL2 and CCL2-CCR2 axis remain elusive in breast cancer. Here we examined the levels of CCL2 in 4 breast cancer cell lines along with 57 human breast cancer specimens and found them significantly increased with presence of 17β-estradiol (E2) in estrogen receptor (ER)-positive breast cancer cells, while anti-estrogen treatment weakened this enhancement...
June 22, 2018: Scientific Reports
Li Xu, Ryan Gordon, Rebecca Farmer, Abhinandan Pattanayak, Andrew Binkowski, Xiaoke Huang, Michael Avram, Sankar Krishna, Eric Voll, Janet Pavese, Juan Chavez, James Bruce, Andrew Mazar, Antoinette Nibbs, Wayne Anderson, Lin Li, Borko Jovanovic, Sean Pruell, Matias Valsecchi, Giulio Francia, Rick Betori, Karl Scheidt, Raymond Bergan
Increased cancer cell motility constitutes a root cause of end organ destruction and mortality, but its complex regulation represents a barrier to precision targeting. We use the unique characteristics of small molecules to probe and selectively modulate cell motility. By coupling efficient chemical synthesis routes to multiple upfront in parallel phenotypic screens, we identify that KBU2046 inhibits cell motility and cell invasion in vitro. Across three different murine models of human prostate and breast cancer, KBU2046 inhibits metastasis, decreases bone destruction, and prolongs survival at nanomolar blood concentrations after oral administration...
June 22, 2018: Nature Communications
Richard Tancredi, Jenny Furlanetto, Sibylle Loibl
There is growing interest in the endocrine treatment (ET) of premenopausal women with hormone receptor positive (HR+) metastatic breast cancer (MBC). This review summarizes available data on endocrine therapy for this patient subset and aims to define the most appropriate treatment approach. The combination of luteinizing hormone-releasing hormone (LHRH) agonists plus tamoxifen seems effective and safe and is considered as being superior to either approach alone; still, single-agent therapy remains an acceptable treatment option...
June 22, 2018: Oncologist
Marie Lange, Natacha Heutte, Sabine Noal, Olivier Rigal, Jean-Emmanuel Kurtz, Christelle Lévy, Djelila Allouache, Chantal Rieux, Johan Lefel, Bénédicte Clarisse, Alexandra Leconte, Corinne Veyret, Philippe Barthélémy, Nadine Longato, Laure Tron, Hélène Castel, Francis Eustache, Bénédicte Giffard, Florence Joly
BACKGROUND: Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. PATIENTS AND METHODS: Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched)...
June 22, 2018: Oncologist
Gautam Sethi, Muthu K Shanmugam, Frank Arfuso, Alan Prem Kumar
Evolving strategies to counter cancer initiation and progression rely on the identification of novel therapeutic targets that exploit the aberrant genetic changes driving oncogenesis. Several chromatin associated enzymes have been shown to influence post-translational modification on DNA, histones, and non-histone proteins. Any deregulation of this core group of enzymes often leads to cancer development. Ubiquitylation of histone H2B in mammalian cells was identified over three decades ago. An exciting really interesting new gene (RING) family of E3 ubiquitin ligases, known as RNF20 and RNF40, monoubiquitinates histone H2A at K119 or H2B at K120 and is known to function in transcription elongation, DNA double strand break repair processes, maintenance of chromatin differentiation, and exerting tumor suppressor activity...
June 22, 2018: Bioscience Reports
Andrea C Chaikovsky, Julien Sage
Inhibitors of the cyclin-dependent kinases 4 and 6 (CDK4/6) were originally designed to block proliferation and cell cycle progression of cancer cells in which the activity of these kinases is dysregulated. CDK4/6 inhibitors have already been FDA-approved for the treatment of estrogen receptor (ER)-positive breast cancer and are being tested in numerous other cancer types. However, several recent studies have identified novel effects of CDK4/6 inhibitors on tumor growth, most notably an indirect effect resulting from the activation of immune surveillance...
June 22, 2018: Molecular Cancer Research: MCR
Aparna Shinde, Sarah Libring, Aktan Alpsoy, Ammara Abdullah, James A Schaber, Luis Solorio, Michael K Wendt
Both epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are linked to metastasis via their ability to increase invasiveness and enhance tumor-initiating capacity. Growth factors, cytokines and chemotherapies present in the tumor microenvironment (TME) are capable of inducing EMT, but the role of the extracellular matrix (ECM) in this process remains poorly understood. Here, a novel tessellated three-dimensional (3D) polymer scaffolding is used to produce a fibrillar fibronectin matrix that induces a EMT-like event that includes phosphorylation of STAT3 and requires expression of β1 integrin...
June 22, 2018: Molecular Cancer Research: MCR
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