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Molecular biology and breast cancer

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https://www.readbyqxmd.com/read/28222068/inhibition-of-cdk5-induces-cell-death-of-tumor-initiating-cells
#1
Melanie M Mandl, Siwei Zhang, Melanie Ulrich, Elisa Schmoeckel, Doris Mayr, Angelika M Vollmar, Johanna Liebl
BACKGROUND: Tumour-initiating cells (TICs) account for chemoresistance, tumour recurrence and metastasis, and therefore represent a major problem in tumour therapy. However, strategies to address TICs are limited. Recent studies indicate Cdk5 as a promising target for anti-cancer therapy and Cdk5 has recently been associated with epithelial-mesenchymal transition (EMT). However, a role of Cdk5 in TICs has not been described yet. METHODS: Expression of Cdk5 in human cancer tissue was analysed by staining of a human tissue microarray (TMA)...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28219246/dna-generated-electric-current-biosensor
#2
Lanshuang Hu, Shengqiang Hu, Linyan Guo, Congcong Shen, Minghui Yang, Avraham Rasooly
In addition to its primary function as a genetic material, deoxyribonucleic acid (DNA) is also a potential biologic energy source for molecular electronics. For the first time, we demonstrate that DNA can generate a redox electric current. As an example of this new functionality, DNA generated redox current was used for electrochemical detection of human epidermal growth factor receptor 2 (HER2), a clinically important breast cancer biomarker. To induce redox current, the phosphate of the single stranded DNA aptamer backbone was reacted with molybdate to form redox molybdophosphate precipitate and generate an electrochemical current of ∼16...
February 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28214331/pomc-maintains-tumor-initiating-properties-of-tumor-tissue-derived-long-term-cultured-breast-cancer-stem-cells
#3
Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P Zhou, Mien-Chie Hung, Xiaoming Xie
The identification and understanding of the molecular network of cancer stem cells (CSCs) have had a profound impact on our view of carcinogenesis and treatment strategy. Unfortunately, a major problem is that serial passages of CSCs from clinical solid tumor specimens currently are not available in any lab, and thus, reported data are difficult to confirm and intensively interrogated. Here, we have generated two tumor tissue-derived breast CSC (BCSC) lines that showed prolonged maintenance over 20 serial passages in vitro, while retaining their tumor-initiating biological properties...
February 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28213333/hmba-is-a-putative-hsp70-activator-stimulating-hexim1-expression-that-is-down-regulated-by-estrogen
#4
Rati Lama, Chunfang Gan, Nethrie Idippily, Viharika Bobba, David Danielpour, Monica Montano, Bin Su
Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is identified as a novel inhibitor of estrogen stimulated breast cell growth, and it suppresses estrogen receptor-α transcriptional activity. HEXIM1 protein level has been found to be downregulated by estrogens. Recently, HEXIM1 has been found to inhibit androgen receptor transcriptional activity as well. Researchers have used Hexamethylene bis-acetamide (HMBA) for decades to stimulate HEXIM1 expression, which also inhibit estrogen stimulated breast cancer cell gene activation and androgen stimulated prostate cancer gene activation...
February 14, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28210624/rna-sequencing-analysis-reveals-interactions-between-breast-cancer-or-melanoma-cells-and-the-tissue-microenvironment-during-brain-metastasis
#5
Ryo Sato, Teppei Nakano, Mari Hosonaga, Oltea Sampetrean, Ritsuko Harigai, Takashi Sasaki, Ikuko Koya, Hideyuki Okano, Jun Kudoh, Hideyuki Saya, Yoshimi Arima
Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non-small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28210563/neoadjuvant-therapy-for-treatment-of-breast-cancer-the-way-forward-or-simply-a-convenient-option-for-patients
#6
COMMENT
Abhishek Chatterjee, John K Erban
The complexity of managing early stage breast cancer is well known. Optimal treatment is increasingly multidisciplinary and in the modern era informed by sophisticated molecular tools to help select and guide therapy. Major phase III trials have determined that the order of systemic therapy relative to surgery does not influence important endpoints such as event free survival and overall survival (OS), but questions remain as to how best to utilize these most essential services. For example, there is still uncertainty regarding the ideal timing, intensity, and duration of proposed therapy...
February 2017: Gland Surgery
https://www.readbyqxmd.com/read/28208703/androgen-receptor-signaling-in-salivary-gland-cancer
#7
REVIEW
Martin G Dalin, Philip A Watson, Alan L Ho, Luc G T Morris
Salivary gland cancers comprise a small subset of human malignancies, and are classified into multiple subtypes that exhibit diverse histology, molecular biology and clinical presentation. Local disease is potentially curable with surgery, which may be combined with adjuvant radiotherapy. However, metastatic or unresectable tumors rarely respond to chemotherapy and carry a poorer prognosis. Recent molecular studies have shown evidence of androgen receptor signaling in several types of salivary gland cancer, mainly salivary duct carcinoma...
February 8, 2017: Cancers
https://www.readbyqxmd.com/read/28199325/breast-cancer-subtype-of-french-women-is-not-influenced-by-socioeconomic-status-a-population-based-study
#8
Aviane Auguste, Marion Cortet, Tienhan Sandrine Dabakuyo-Yonli, Ludivine Launay, Laurent Arnould, Isabelle Desmoulins, Patrick Roignot, Ariane Darut-Jouve, Marie-Laure Poillot, Aurélie Bertaut, Patrick Arveux
CONTEXT: The molecular subtype of breast tumours plays a major role in cancer prognosis and treatment options. Triple negative tumours (TN) carry the worst prognosis and affects most frequently women of low socioeconomic status (SES). Studies have shown that non-biologic factors, such as the socioeconomic status could have an influence on tumour biology. To this date no study has been done investigating this association in French women. The objective is to study the association between the SES and the molecular tumour subtype of breast cancer patients in the French county of Côte d'Or...
2017: PloS One
https://www.readbyqxmd.com/read/28197838/the-growing-role-of-cdk4-6-inhibitors-in-treating-hormone-receptor-positive-advanced-breast-cancer
#9
REVIEW
Ami N Shah, Massimo Cristofanilli
Single-agent endocrine therapy has been the standard therapeutic choice for the management of hormone receptor (HR)-positive, Her2-negative advanced breast cancer (ABC) for decades. However, the rapidly accumulating data regarding the biological role and safety of CDK4/6 inhibitors and the first-in-class approval of palbociclib have made these novel agents an essential component of treatment for HR-positive ABC. In the frontline setting, palbociclib in combination with endocrine therapy showed an improvement in progression-free survival (PFS) by 10 months to nearly 25 months when compared with endocrine therapy alone and a clinical benefit rate (CBR = stable disease >24 weeks + partial response + complete response) of 85%...
January 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28195406/synthesis-biological-evaluations-and-molecular-docking-studies-on-dna-binding-interaction-of-platinum-ii-rollover-complexes-containing-phosphorus-donor-ligands
#10
Masood Fereidoonnezhad, Maryam Niazi, Mahnaz Shahmohammadi Beni, Shima Mohammadi, Zeinab Faghih, Zahra Faghih, Hamid R Shahsavari
A series of cyclometalated rollover complexes [PtMe(κ²N,C-bipyO-H)(L)], 2a-2c, bipyO-H = cyclometalated 2,2'-bipyridine N-oxide, L = PCy₃ (2a), PPh₂py (2-(diphenylphosphino)pyridine, 2b), P(OPh)₃ (2c), was synthesized by reacting of complex [PtMe(κ²N,C-bipyO-H)(SMe₂)], 1, with various monodentate phosphine and phosphite ligands. These complexes were characterized by means of NMR spectroscopy and the structures of 2a confirmed by single-crystal X-ray diffraction. 1 was treated with bis(diphenylphosphino)methane (dppm) in a 1 : 1 ratio to give corresponding complex [PtMe(κ²N,C-bipyO-H)(η¹P-dppm)], 3b, in which dppm ligand acts as a monodentate pendant ligand...
February 14, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28194627/fragment-based-in-silico-modeling-of-multi-target-inhibitors-against-breast-cancer-related-proteins
#11
Alejandro Speck-Planche, M Natália D S Cordeiro
Breast cancer is the most frequent cancer reported in women, being responsible for hundreds of thousands of deaths. Chemotherapy has proven to be effective against this malignant neoplasm depending on different biological factors such as the histopathology, grade, and stage, among others. However, breast cancer cells have become resistant to current chemotherapeutic regimens, urging the discovery of new anti-breast cancer drugs. Computational approaches have the potential to offer promising alternatives to accelerate the search for potent and versatile anti-breast cancer agents...
February 13, 2017: Molecular Diversity
https://www.readbyqxmd.com/read/28191587/cytotoxic-responses-of-carnosic-acid-and-doxorubicin-on-breast-cancer-cells-in-butterfly-shaped-microchips-in-comparison-to-2d-and-3d-culture
#12
Ece Yildiz-Ozturk, Sultan Gulce-Iz, Muge Anil, Ozlem Yesil-Celiktas
Two dimensional (2D) cell culture systems lack the ability to mimic in vivo conditions resulting in limitations for preclinical cell-based drug and toxicity screening assays and modelling tumor biology. Alternatively, 3D cell culture systems mimic the specificity of native tissue with better physiological integrity. In this regard, microfluidic chips have gained wide applicability for in vitro 3D cancer cell studies. The aim of this research was to develop a 3D biomimetic model comprising culture of breast cancer cells in butterfly-shaped microchip to determine the cytotoxicity of carnosic acid and doxorubicin on both estrogen dependent (MCF-7) and independent (MDA-MB231) breast cancer cells along with healthy mammary epithelial cells (MCF-10A) in 2D, 3D Matrigel™ and butterfly-shaped microchip environment...
February 13, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28186846/in-vitro-mouse-and-human-serum-stability-of-a-heterobivalent-dual-target-probe-that-has-strong-affinity-to-gastrin-releasing-peptide-and-neuropeptide-y1-receptors-on-tumor-cells
#13
Arijit Ghosh, Natarajan Raju, Michael Tweedle, Krishan Kumar
Receptor-targeting radiolabeled molecular probes with high affinity and specificity are useful in studying and monitoring biological processes and responses. Dual- or multiple-targeting probes, using radiolabeled metal chelates conjugated to peptides, have potential advantages over single-targeting probes as they can recognize multiple targets leading to better sensitivity for imaging and radiotherapy when target heterogeneity is present. Two natural hormone peptide receptors, gastrin-releasing peptide (GRP) and Y1, are specifically interesting as their expression is upregulated in most breast and prostate cancers...
February 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28177203/biology-and-insights-into-the-role-of-cohesin-protease-separase-in-human-malignancies
#14
Nenggang Zhang, Debananda Pati
Separase, an enzyme that resolves sister chromatid cohesion during the metaphase-to-anaphase transition, plays a pivotal role in chromosomal segregation and cell division. Separase protein, encoded by the extra spindle pole bodies like 1 (ESPL1) gene, is overexpressed in numerous human cancers including breast, bone, brain, and prostate. Separase is oncogenic, and its overexpression is sufficient to induce mammary tumours in mice. Either acute or chronic overexpression of separase in mouse mammary glands leads to aneuploidy and tumorigenesis, and inhibition of separase enzymatic activity decreases the growth of human breast tumour xenografts in mice...
February 8, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28169235/prediction-of-heterogeneity-in-breast-cancer-immunophenotype-at-ductal-carcinoma-in-situ-stage
#15
Manish Rohilla, Amanjit Bal, Gurpreet Singh, Kusum Joshi
INTRODUCTION: Ductal carcinoma in situ (DCIS) is considered a heterogeneous lesion at the molecular level. However, there is a paucity of literature about the existence of molecular subtypes in DCIS which can predict their biological behavior at the preinvasive stage. MATERIALS AND METHODS: Precise prevalence of molecular subtypes of pure DCIS and DCIS component of infiltrating duct carcinoma (IDC) was evaluated using immunohistochemistry and correlated with known prognostic factors...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28162208/-the-genetic-basis-and-clinical-application-of-heterogeneity-of-breast-cancer
#16
T Li
Breast cancer is comprised of a group of heterogeneous diseases that differ significantly in their clinic-pathologic characteristics and molecular profiles. For many years, this disease has been classified according to the integral clinicopathological factors, to provide a dictates for institution of therapeutic approach. Over the past decades, several waves of technology have advanced the characterization of mutations in cancer genomes, especially the emerge and application of high-through next-generation sequencing technique...
February 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/28156095/optimized-translocator-protein-ligand-for-optical-molecular-imaging-and-screening
#17
Jun Li, Jarrod A Smith, Eric S Dawson, Allie Fu, Michael L Nickels, Michael L Schulte, H Charles Manning
Translocator protein (TSPO) is a validated target for molecular imaging of a variety of human diseases and disorders. Given its involvement in cholesterol metabolism, TSPO expression is commonly elevated in solid tumors, including glioma, colorectal cancer, and breast cancer. TSPO ligands capable of detection by optical imaging are useful molecular tracers for a variety of purposes that range from quantitative biology to drug discovery. Leveraging our prior optimization of the pyrazolopyrimidine TSPO ligand scaffold for cancer imaging, we report herein a new generation of TSPO tracers with superior binding affinity and suitability for optical imaging and screening...
February 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28152060/expression-quantitative-trait-loci-qtl-in-tumor-adjacent-normal-breast-tissue-and-breast-tumor-tissue
#18
Alejandro Quiroz-Zárate, Benjamin J Harshfield, Rong Hu, Nick Knoblauch, Andrew H Beck, Susan E Hankinson, Vincent Carey, Rulla M Tamimi, David J Hunter, John Quackenbush, Aditi Hazra
We investigate 71 single nucleotide polymorphisms (SNPs) identified in meta-analytic studies of genome-wide association studies (GWAS) of breast cancer, the majority of which are located in intergenic or intronic regions. To explore regulatory impacts of these variants we conducted expression quantitative loci (eQTL) analyses on tissue samples from 376 invasive postmenopausal breast cancer cases in the Nurses' Health Study (NHS) diagnosed from 1990-2004. Expression analysis was conducted on all formalin-fixed paraffin-embedded (FFPE) tissue samples (and on 264 adjacent normal samples) using the Affymetrix Human Transcriptome Array...
2017: PloS One
https://www.readbyqxmd.com/read/28148541/silencing-the-roadblocks-to-effective-tnbc-treatments-by-sirna-nanoparticles
#19
Jenny G Parvani, Mark W Jackson
Over the past decade, RNA interference (RNAi) has been ubiquitously utilized to study biological function in vitro, however limitations were associated with its utility in vivo. More recently, small interfering RNA (siRNA) nanoparticles with improved biocompatibility have gained prevalence as a potential therapeutic option for the treatment of various diseases. The adaptability of siRNA nanoparticles enables the delivery of virtually any siRNA, which is especially advantageous for therapeutic applications in heterogeneous diseases that lack unifying molecular features, such as triple negative breast cancer (TNBC)...
February 1, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28145887/organ-specific-isogenic-metastatic-breast-cancer-cell-lines-exhibit-distinct-raman-spectral-signatures-and-metabolomes
#20
Paul T Winnard, Chi Zhang, Farhad Vesuna, Jeon Woong Kang, Jonah Garry, Ramachandra Rao Dasari, Ishan Barman, Venu Raman
Molecular characterization of organ-specific metastatic lesions, which distinguish them from the primary tumor, will provide a better understanding of tissue specific adaptations that regulate metastatic progression. Using an orthotopic xenograft model, we have isolated isogenic metastatic human breast cancer cell lines directly from organ explants that are phenotypically distinct from the primary tumor cell line. Label-free Raman spectroscopy was used and informative spectral bands were ascertained as differentiators of organ-specific metastases as opposed to the presence of a single universal marker...
January 27, 2017: Oncotarget
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