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Heterogeneity breast metastasis

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
Erik R Nelson, Shenduo Li, Margaret Kennedy, Sturgis Payne, Kelly Kilibarda, Jeffrey Groth, Michelle Bowie, Edgardo Parilla-Castellar, Gustaaf de Ridder, Paul Kelly Marcom, Matthew Lyes, Bercedis L Peterson, Michael Cook, Salvatore V Pizzo, Donald P McDonnell, Robin E Bachelder
BACKGROUND: Although most triple-negative breast cancer (TNBC) patients initially respond to chemotherapy, residual tumor cells frequently persist and drive recurrent tumor growth. Previous studies from our laboratory and others' indicate that TNBC is heterogeneous, being composed of chemo-sensitive and chemo-resistant tumor cell subpopulations. In the current work, we studied the invasive behaviors of chemo-resistant TNBC, and sought to identify markers of invasion in chemo-residual TNBC...
October 18, 2016: Oncotarget
Iben Kümler, Eva Balslev, Ann S Knop, Nils Brünner, Tobias W Klausen, Sofie S Jespersen, Signe L Nielsen, Dorte L Nielsen
Tumor heterogeneity has been shown for several cancers including breast cancer (BC). Despite the fact that expression of tumor markers may change throughout the metastatic process, rebiopsies at the time of recurrence are still not performed routinely at all institutions. The aims of the study were to evaluate changes in biomarker profiles during the metastatic process and to investigate whether previous anthracycline or endocrine therapy given in the adjuvant setting could affect the biomarker profile in metastatic lesions...
October 7, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Jack R Staunton, Wilfred Vieira, King Leung Fung, Ross Lake, Alexus Devine, Kandice Tanner
One of the hallmarks of the malignant transformation of epithelial tissue is the modulation of stromal components of the microenvironment. In particular, aberrant extracellular matrix (ECM) remodeling and stiffening enhances tumor growth and survival and promotes metastasis. Type I collagen is one of the major ECM components. It serves as a scaffold protein in the stroma contributing to the tissue's mechanical properties, imparting tensile strength and rigidity to tissues such as those of the skin, tendons, and lungs...
September 2016: Cellular and Molecular Bioengineering
E Vandendriessche, G Van De Putte, R Van Den Broecke, Etm De Jonge
AIM: Intra and inter tumour heterogeneity is a known feature in cancer because tumour cells undergo changes at genetic and epigenetic level as they spread from their primary tumour site. Adjuvant treatment protocols in breast cancer are currently based on the biological characteristics of the primary tumour, which in most cases has been removed surgically. Considering tumour heterogeneity in metastases we examined the present status of knowledge regarding measurable differences in tumour profiling between the primary breast tumour and its synchronous axillary lymph node metastases (ALNM) and if so whether adjuvant therapy directed towards the tumour characteristics of the ALNM instead of those of the primary tumour is more effective...
December 28, 2015: Facts, Views & Vision in ObGyn
Cristina L Cotarelo, Arno Schad, Charles James Kirkpatrick, Jonathan P Sleeman, Erik Springer, Marcus Schmidt, Sonja Thaler
Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by arresting cells at risk of malignant transformation. Nevertheless, numerous findings suggest that senescent cells may conversely promote tumor progression through the development of the senescence-associated secretome they produce. It is likely that the composition and the physiological consequences mediated by the senescence secretome are dependent on the oncogenes that trigger the senescence program. Breast cancer represents a heterogenous disease that can be divided into breast cancer subtypes due to different subsets of genetic and epigenetic abnormalities...
October 4, 2016: Oncotarget
A E Witt, C-W Lee, T I Lee, D J Azzam, B Wang, C Caslini, F Petrocca, J Grosso, M Jones, E B Cohick, A B Gropper, C Wahlestedt, A L Richardson, R Shiekhattar, R A Young, T A Ince
Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology...
October 3, 2016: Oncogene
Saroj Niraula, Alberto Ocana
BACKGROUND: Breast cancer is heterogeneous at different levels: biologic subtypes, intratumoral areas, and sites of metastases. Randomized controlled trials (RCTs) classify metastatic sites as visceral or non-visceral, but this has little influence in treatment decisions, particularly in the absence of clinical urgency. Indeed, it is unclear if response to treatments differs among sites of metastases. PATIENTS AND METHODS: RCTs investigating 3 different anticancer strategies in metastatic breast cancer were identified: (1) new hormonal therapy, (2) new targeted therapies in hormone receptor positive tumours (everolimus or palbociclib), and (3) new anti-HER2 therapies...
September 20, 2016: Cancer Treatment Reviews
Haruka Nakada, Hiroshi Nakagomi, Yosuke Hirotsu, Kenji Amemiya, Hitoshi Mochizuki, Masayuki Inoue, Toshio Oyama, Masao Omata
Tumor heterogeneity has been suggested based on clinical and pathological findings. Several clinical findings can be explained by tumor evolution during progression and metastasis. We herein report a case of metastatic breast cancer indicated tumor heterogeneity by clinical findings and a genomic analysis. A 64-year-old woman with advanced breast cancer was treated with primary chemotherapy, to which primary tumor responded. After a 6 month treatment pause, lung, liver, and skin metastases developed and her serum tumor markers were elevated...
September 29, 2016: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Wang Jinling, Sun Sijing, Zhang Jie, Wang Guinian
BACKGROUND: There is an urgent need for novel noninvasive prognostic molecular tumor marker for monitoring the recurrence of breast cancer. MicroRNA-21 (miR-21) play a crucial role in the progression and aggressiveness of breast cancer, but its prognostic significance for patients with breast cancer remains inconclusive. The aim of this meta-analysis is to summarize the role of circulating miR-21 as a molecular marker in patients with breast cancer. MATERIAL AND METHODS: Eligible studies were searched from the PubMed, EMBASE and Web of Science databases...
August 16, 2016: Artificial Cells, Nanomedicine, and Biotechnology
Bajin Wei, Minya Yao, Chunyang Xing, Wei Wang, Jia Yao, Yun Hong, Yu Liu, Peifen Fu
Breast cancer (BC) is the most common female malignancy within the spectrum of human cancer. One promising way to reduce the mortality and morbidity of BC is to explore novel diagnostic markers for early diagnosis and prognostication. The neutrophil lymphocyte ratio (NLR) is a good reflection of inflammation, which plays an important role in tumor progression and metastasis. However, the association between NLR and BC prognosis remains unclear. The aim of this meta-analysis is to explore the prognostic value of NLR in BC...
2016: OncoTargets and Therapy
Prasad R Dandawate, Dharmalingam Subramaniam, Roy A Jensen, Shrikant Anant
Breast cancer is the most common form of cancer diagnosed in women worldwide and the second leading cause of cancer-related deaths in the USA. Despite the development of newer diagnostic methods, selective as well as targeted chemotherapies and their combinations, surgery, hormonal therapy, radiotherapy, breast cancer recurrence, metastasis and drug resistance are still the major problems for breast cancer. Emerging evidence suggest the existence of cancer stem cells (CSCs), a population of cells with the capacity to self-renew, differentiate and be capable of initiating and sustaining tumor growth...
October 2016: Seminars in Cancer Biology
Fang Yang, Jing Xu, Lin Tang, Xiaoxiang Guan
Breast cancers have been increasingly recognized as malignancies displaying frequent inter- and intra-tumor heterogeneity. This heterogeneity is represented by diverse subtypes and complexity within tumors, and impinges on response to therapy, metastasis, and prognosis. Cancer stem cells (CSCs), a subpopulation of cancer cells endowed with self-renewal and differentiation capacity, have been suggested to contribute to tumor heterogeneity. The CSC concept posits a hierarchical organization of tumors, at the apex of which are stem cells that drive tumor initiation, progression, and recurrence...
August 16, 2016: Cellular and Molecular Life Sciences: CMLS
Jing Xu, Lei Huang, Jun Li
BACKGROUND & AIMS: DNA ploidy, a DNA flow cytometry parameter, reflects tumor cell cycle. In breast cancer (BC), ploidy status characterizes genotypic stability and potential metastatic capacity. It is suggested that aneuploidy is an independent prognosticator for BC patients and could aid for individualized medicine. There are extensive studies concerning the prognostic significance of DNA aneuploidy, however, its clinical utility remains controversial. Herein we conducted a meta-analysis to determine the correlation between DNA ploidy status and BC characteristics and survival...
August 9, 2016: Oncotarget
Y Xu, L Qin, T Sun, H Wu, T He, Z Yang, Q Mo, L Liao, J Xu
The heterogeneous breast cancers can be classified into different subtypes according to their histopathological characteristics and molecular signatures. Foxa1 expression is linked with luminal breast cancer (LBC) with good prognosis, whereas Twist1 expression is associated with basal-like breast cancer (BLBC) with poor prognosis owing to its role in promoting epithelial-to-mesenchymal transition (EMT), invasiveness and metastasis. However, the regulatory and functional relationships between Twist1 and Foxa1 in breast cancer progression are unknown...
August 15, 2016: Oncogene
Ming Yin, Heath B Mackley, Joseph J Drabick, Harold A Harvey
Primary breast sarcoma (PBS) is a rare and heterogeneous group of malignancies with limited publications. We obtained data from the Surveillance, Epidemiology, and End Results Program and performed analysis to determine clinicopathological characteristics of PBS and estimate their associations with overall survival (OS) and cancer-specific survival (CSS). Median age of PBS was 55-59 years and median OS was 108 months. Age, overlap or entire breast involvement, tumor histology, and tumor spread were associated with poor survival outcomes...
2016: Scientific Reports
Yu-Heng Cheng, Yu-Chih Chen, Riley Brien, Euisik Yoon
Recent research suggests that cancer stem-like cells (CSCs) are the key subpopulation for tumor relapse and metastasis. Due to cancer plasticity in surface antigen and enzymatic activity markers, functional tumorsphere assays are promising alternatives for CSC identification. To reliably quantify rare CSCs (1-5%), thousands of single-cell suspension cultures are required. While microfluidics is a powerful tool in handling single cells, previous works provide limited throughput and lack automatic data analysis capability required for high-throughput studies...
October 7, 2016: Lab on a Chip
Weiqiang Chen, Steven G Allen, Ajaya Kumar Reka, Weiyi Qian, Shuo Han, Jianing Zhao, Liwei Bao, Venkateshwar G Keshamouni, Sofia D Merajver, Jianping Fu
BACKGROUND: Circulating tumor cells (CTCs) have shown prognostic relevance in many cancer types. However, the majority of current CTC capture methods rely on positive selection techniques that require a priori knowledge about the surface protein expression of disseminated CTCs, which are known to be a dynamic population. METHODS: We developed a microfluidic CTC capture chip that incorporated a nanoroughened glass substrate for capturing CTCs from blood samples. Our CTC capture chip utilized the differential adhesion preference of cancer cells to nanoroughened etched glass surfaces as compared to normal blood cells and thus did not depend on the physical size or surface protein expression of CTCs...
2016: BMC Cancer
John P Harrelson, Michael W Lee
The changes in breast cancer cells that contribute to tumor evolution, heterogeneity, metastasis and ultimately drug resistance are shaped by numerous genetic changes including alterations in cellular metabolism. These include intermediary metabolic pathways such as glycolysis, the citric acid cycle oxidative phosphorylation, amino acid synthesis and lipid metabolism. However, cancer cells also exhibit key alterations in other metabolic pathways involved in drug metabolism such as cytochrome P450 enzymes, sulfotransferase and steroid sulfatases that are involved in the synthesis of estrogens and themselves serve as drug targets...
August 3, 2016: Pharmacology & Therapeutics
Kimberly M Stroka, Bin Sheng Wong, Marey Shriver, Jude M Phillip, Denis Wirtz, Aikaterini Kontrogianni-Konstantopoulos, Konstantinos Konstantopoulos
Obscurins are a family of RhoGEF-containing proteins with tumor and metastasis suppressing roles in breast epithelium. Downregulation of giant obscurins in normal breast epithelial cells leads to reduced levels of active RhoA and of its downstream effectors. Herein, we elucidate how depletion of giant obscurins affects the response of breast epithelial cells to changes in the mechanical properties of the microenvironment. We find that knockdown of obscurins increases cell morphodynamics, migration speed, and diffusivity on polyacrylamide gels of ≥ 1 kPa, presumably by decreasing focal adhesion area and density as well as cell traction forces...
August 1, 2016: Oncotarget
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