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Breast molecular

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
Kenji Amemiya, Yosuke Hirotsu, Taichiro Goto, Hiroshi Nakagomi, Hitoshi Mochizuki, Toshio Oyama, Masao Omata
Identifying genetic alterations in tumors is critical for molecular targeting of therapy. In the clinical setting, formalin-fixed paraffin-embedded (FFPE) tissue is usually employed for genetic analysis. However, DNA extracted from FFPE tissue is often not suitable for analysis because of its low levels and poor quality. Additionally, FFPE sample preparation is time-consuming. To provide early treatment for cancer patients, a more rapid and robust method is required for precision medicine. We present a simple method for genetic analysis, called touch imprint cytology combined with massively paralleled sequencing (touch imprint cytology [TIC]-seq), to detect somatic mutations in tumors...
October 24, 2016: Cancer Medicine
Yan Guo, Jie Wu, Shilin Zhao, Fei Ye, Yinghao Su, Travis Clark, Quanhu Sheng, Brian Lehmann, Xiao-Ou Shu, Qiuyin Cai
Background. Proper rRNA depletion is crucial for the successful utilization of FFPE specimens when studying gene expression. We performed a study to evaluate two major rRNA depletion methods: Ribo-Zero and RNase H. RNAs extracted from 4 samples were treated with the two rRNA depletion methods in duplicate and sequenced (N = 16). We evaluated their reducibility, ability to detect RNA, and ability to molecularly subtype these triple negative breast cancer specimens. Results. Both rRNA depletion methods produced consistent data between the technical replicates...
2016: International Journal of Genomics
Ibiayi Dagogo-Jack, Corey M Gill, Daniel P Cahill, Sandro Santagata, Priscilla K Brastianos
Development of brain metastasis (BM) portends a dismal prognosis for patients with cancer. Melanomas and carcinomas of the lung, breast, and kidney are the most common malignancies to metastasize to the brain. Recent advances in molecular genetics have enabled the identification of actionable, clinically relevant genetic alterations within primary tumors and their corresponding metastases. Adoption of genotype-guided treatment strategies in the management of systemic malignancy has resulted in dramatic and durable responses...
October 20, 2016: Pharmacology & Therapeutics
Morgan S Schrock, Jenna R Karras, Matthew J Guggenbiller, Teresa Druck, Bahadir Batar, Kay Huebner
Expression of Fhit and Wwox protein is frequently lost or reduced in many human cancers. In this report, we provide data that further characterizes the molecular consequences of Fhit loss in the initiation of DNA double-strand breaks (DSBs), and of Wwox loss in altered repair of DSBs. We show that loss of Fhit initiates mild genome instability in early passage mouse kidney cells, confirming that DNA damage associated with Fhit-deficiency is not limited to cancer cells. We also demonstrate that the cause of Fhit-deficient DSBs: thymidine deficiency-induced replication stress, can be resolved with thymidine supplementation in early passage mouse kidney cells before extensive genome instability occurs...
September 26, 2016: Advances in Biological Regulation
Junji Itou, Sunao Tanaka, Wenzhao Li, Atsuo Iida, Atsuko Sehara-Fujisawa, Fumiaki Sato, Masakazu Toi
During metastasis, cancer cell migration is enhanced. However, the mechanisms underlying this process remain elusive. Here, we addressed this issue by functionally analyzing the transcription factor Sal-like 4 (SALL4) in basal-like breast cancer cells. Loss-of-function studies of SALL4 showed that this transcription factor is required for the spindle-shaped morphology and the enhanced migration of cancer cells. SALL4 also up-regulated integrin gene expression. The impaired cell migration observed in SALL4 knockdown cells was restored by overexpression of integrin α6 and β1...
October 20, 2016: Biochimica et Biophysica Acta
Thi Tram Chau Nguyen, Cuu Khoa Nguyen, Thi Hiep Nguyen, Ngoc Quyen Tran
In the study, four kinds of pluronics (P123, F68, F127 and F108) with varying hydrophilic-lipophilic balance (HLB) values were modified and conjugated on 4th generation of polyamidoamine dendrimer (PAMAM). The obtained results from FT-IR, (1)H NMR and GPC showed that the pluronics effectively conjugated on the dendrimer. The molecular weight of four PAMAM G4.0-Pluronics and its morphologies are in range of 200.15-377.14kDa and around 60-180nm in diameter by TEM, respectively. Loading efficiency and release of hydrophobic fluorouracil (5-FU) anticancer drug were evaluated by HPLC; Interesting that the dendrimer nanocarrier was conjugated with the highly lipophilic pluronic P123 (G4...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Barbara Wolf, Georg Goebel, Hubert Hackl, Heidi Fiegl
BACKGROUND: The transcription factor nuclear factor erythroid 2-related factor 2 (NFE2L2; previously known as NRF2) is a crucial regulator of the intracellular antioxidant response. It controls the expression of genes involved in the detoxification and elimination of reactive oxidants and electrophilic agents. The role of NFE2L2 in cancer is subject of controversial discussion, as it has been reported to have both pro-and anti-tumourigenic functions. To shed some light on this paradox, we analysed the NFE2L2 mRNA expression levels in breast cancer and its association with clinicopathological features and survival...
October 22, 2016: BMC Cancer
Mostafa M Ghorab, Mansour S Alsaid, Ghada H Al-Ansary, Ghada A Abdel-Latif, Dalal A Abou El Ella
Twenty novel chromene derivatives carrying different sulfonamide moieties (3-22) were designed and synthesized. All the newly prepared compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (T47D). Most of the synthesized compounds showed good to moderate activity (IC50 = 8.8-108.9 μM), where compound 16 (IC50 = 8.8 μM) exhibited higher activity compared to doxorubicin (IC50 = 9.8 μM). In order to determine the mechanism of the anticancer activity in T47D cells, the effect of the most potent compounds (5-8, 11-14, and 16-18) on the aromatase activity was tested...
October 13, 2016: European Journal of Medicinal Chemistry
Pat Whitworth, Peter Beitsch, Angela Mislowsky, James V Pellicane, Charles Nash, Mary Murray, Laura A Lee, Carrie L Dul, Michael Rotkis, Paul Baron, Lisette Stork-Sloots, Femke A de Snoo, Jennifer Beatty
PURPOSE: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT). OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity...
October 21, 2016: Annals of Surgical Oncology
Christina Gutierrez Bracamontes, Rebecca Lopez-Valdez, Ramadevi Subramani, Arunkumar Arumugam, Sushmita Nandy, Venkatesh Rajamanickam, Vignesh Ravichandran, Rajkumar Lakshmanaswamy
Early parity reduces the risk of breast cancer in women while nulliparity and late parity increase the risk of breast cancer. In order to translate this protection to women where early pregnancy is not feasible, much work has focused on understanding how parity confers protection against breast cancer, the molecular mechanisms by which this occurs is still not well understood. Healthy parous and nulliparous women were recruited for this study. We assessed serum protein profiles of early parous, late parous, and nulliparous women using the Phospho Explorer antibody array...
October 19, 2016: Oncotarget
Michael Chalick, Oded Jacobi, Edward Pichinuk, Christian Garbar, Armand Bensussan, Alan Meeker, Ravit Ziv, Tania Zehavi, Nechama I Smorodinsky, John Hilkens, Franz-Georg Hanisch, Daniel B Rubinstein, Daniel H Wreschner
Translation of mRNA in alternate reading frames (ARF) is a naturally occurring process heretofore underappreciated as a generator of protein diversity. The MUC1 gene encodes MUC1-TM, a signal-transducing trans-membrane protein highly expressed in human malignancies. Here we show that an AUG codon downstream to the MUC1-TM initiation codon initiates an alternate reading frame thereby generating a novel protein, MUC1-ARF. MUC1-ARF, like its MUC1-TM 'parent' protein, contains a tandem repeat (VNTR) domain. However, the amino acid sequence of the MUC1-ARF tandem repeat as well as N- and C- sequences flanking it differ entirely from those of MUC1-TM...
2016: PloS One
Katie M Parkins, Amanda M Hamilton, Ashley V Makela, Yuanxin Chen, Paula J Foster, John A Ronald
Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i...
October 21, 2016: Scientific Reports
Hui Yao, Guangchun He, Shichao Yan, Chao Chen, Liujiang Song, Thomas J Rosol, Xiyun Deng
Triple-negative breast cancer (TNBC), which accounts for 15-20% of all breast cancers, does not express estrogen receptor (ER) or progesterone receptor (PR) and lacks human epidermal growth factor receptor 2 (HER2) overexpression or amplification. These tumors have a more aggressive phenotype and a poorer prognosis due to the high propensity for metastatic progression and absence of specific targeted treatments. Patients with TNBC do not benefit from hormonal or trastuzumab-based targeted therapies because of the loss of target receptors...
September 27, 2016: Oncotarget
Piera Rizzolo, Anna Sara Navazio, Valentina Silvestri, Virginia Valentini, Veronica Zelli, Ines Zanna, Giovanna Masala, Simonetta Bianchi, Marco Scarnò, Stefania Tommasi, Domenico Palli, Laura Ottini
Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from its largely known female counterpart. We aimed at investigating whether MBC cases harbor somatic alterations of genes known as prognostic biomarkers and molecular therapeutic targets in female breast cancer.We examined 103 MBC cases, all characterized for germ-line BRCA1/2 mutations, for somatic alterations in PIK3CA, EGFR, ESR1 and CCND1 genes.Pathogenic mutations of PIK3CA were detected in 2% of MBCs...
September 27, 2016: Oncotarget
Sharon K Michelhaugh, Otto Muzik, Anthony R Guastella, Neil V Klinger, Lisa A Polin, Hancheng Cai, Yanchun Xin, Thomas J Mangner, Shaohui Zhang, Csaba Juhasz, Sandeep Mittal
: Abnormal tryptophan metabolism via the kynurenine pathway (KP) is involved in the pathophysiology of a variety of human diseases including cancers. α-[(11)C]-methyl-L-tryptophan ((11)C-AMT) positron emission tomography (PET) imaging demonstrated increased tryptophan uptake and trapping in epileptic foci and brain tumors, but the short half-life of (11)C limits its widespread clinical application. Recent in vitro studies suggested that the novel radiotracer 1-(2-[(18)F]fluoroethyl)-L-tryptophan ((18)F-FETrp) may be useful to assess tryptophan metabolism via the KP...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Rosamaria Lappano, Roberta Malaguarnera, Antonino Belfiore, Marcello Maggiolini
Certain environmental chemicals may accumulate in human serum and tissues eliciting estrogenic and/or carcinogenic effects. Therefore, there is heightened interest in determining whether environmental chemicals may increase the risk for endocrine-related tumors like breast cancer. For instance, metals as cadmium, zinc, copper, iron, nickel and aluminum have been shown to mimic estrogen action. Moreover, the exposure to these chemicals has been reported to stimulate diverse malignancies including breast cancer, which is the most common tumor in women worldwide...
October 17, 2016: Molecular and Cellular Endocrinology
Ravely Casarotti Orlandelli, Maria de Lourdes Corradi da Silva, Ana Flora Dalberto Vasconcelos, Igor Vivian de Almeida, Veronica Elisa Pimenta Vicentini, Alicia Prieto, Maria Dolores Diaz Hernandez, João Lúcio de Azevedo, João Alencar Pamphile
This study reports the characterization and antiproliferative activity of exopolysaccharides (EPS) produced by submerged cultures of the endophytes Diaporthe sp. JF766998 and Diaporthe sp. JF767007 isolated from the medicinal plant Piper hispidum Sw. Both strains secreted a crude EPS that, upon size exclusion chromatography, showed to contain a heteropolysaccharide (galactose, glucose and mannose) and a high-molecular weight glucan. Data from methylation analysis, FTIR and NMR spectroscopy ((1)H, COSY, TOCSY and HSQC-DEPT) indicated that the purified glucan consisted of a main chain of glucopyranosyl β-(1→3) linkages substituted at O-6 by glucosyl residues...
October 17, 2016: International Journal of Biological Macromolecules
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