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https://www.readbyqxmd.com/read/29044863/identification-of-somatic-genetic-alterations-in-ovarian-clear-cell-carcinoma-with-next-generation-sequencing
#1
Yusuke Shibuya, Hideki Tokunaga, Sakae Saito, Kazurou Shimokawa, Fumiki Katsuoka, Li Bin, Kaname Kojima, Masao Nagasaki, Masayuki Yamamoto, Nobuo Yaegashi, Jun Yasuda
Ovarian clear cell carcinoma (OCCC) is the most refractory subtype of ovarian cancer and more prevalent in Japanese than Caucasians (25% and 5% of all ovarian cancer, respectively). The aim of this study is to discover the genomic alterations that may cause OCCC and effective molecular targets for chemotherapy. Paired genomic DNAs of 48 OCCC tissues and corresponding non-cancerous tissues were extracted from formalin-fixed, paraffin embedded specimens collected between 2007 and 2015 at Tohoku University Hospital...
October 16, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29044505/diagnostic-pathology-of-early-systemic-cancer-erbb2-gene-amplification-in-single-disseminated-cancer-cells-determines-patient-survival-in-operable-esophageal-cancer
#2
Martin Hoffmann, Sophie Pasch, Thomas Schamberger, Matthias Maneck, Birte Möhlendick, Sarah Schumacher, Gero Brockhoff, Wolfram Trudo Knoefel, Jakob Izbicki, Bernhard Polzer, Nikolas H Stoecklein, Christoph A Klein
Early metastatic dissemination and evolution of disseminated cancer cells (DCCs) outside the primary tumor is one reason for the failure of adjuvant therapies because it generates molecular geno- and phenotypes different from primary tumors which still underlie therapy decisions. Since ERBB2 amplification in esophageal DCCs but not in primary tumor cells predict outcome, we aimed to establish an assay with diagnostic reliability for single DCCs or circulating tumor cells (CTCs). For this we evaluated copy number alterations of more than 600 single DCCs from multiple cancer types to define reference regions suitable for quantification of target regions, such as ERBB2...
October 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29037469/management-of-patients-with-adenocarcinoma-or-squamous-cancer-of-the-esophagus
#3
David H Ilson, Richard Hillegersberg
Esophageal cancer is characterized by the early and frequent metastasis. Surgery is the primary treatment for early-stage disease, whereas patients with patients with locally advanced disease receive peri-operative chemotherapy or chemoradiotherapy. Squamous cancers can be treated with primary chemoradiotherapy without surgery, depending on their response to therapy and patient tolerance for subsequent surgery. Chemotherapy with a fluorinated pyrimidine and a platinum agent, followed by later treatment with taxanes and irinotecan, provides some benefit...
October 13, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29030491/autophagy-is-activated-in-the-ovarian-tissue-of-polycystic-ovary-syndrome
#4
Da Li, Yue You, Fang-Fang Bi, Tie-Ning Zhang, Jiao Jiao, Tian-Ren Wang, Yi-Ming Zhou, Zi-Qi Shen, Xiu-Xia Wang, Qing Yang
The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic disorders is increasingly being recognized, but few studies have investigated the role of autophagy in PCOS. Here, transmission electron microscopy demonstrated that autophagy was enhanced in the ovarian tissue from both humans and rats with PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed increases in the autophagy marker protein light chain 3B (LC3B), whereas levels of the autophagy substrate SQSTM1/p62 were decreased...
October 13, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29029499/generation-and-characterization-of-erbb2-car-engineered-cytokine-induced-killer-cells-for-the-treatment-of-high-risk-soft-tissue-sarcoma-in-children
#5
Michael Merker, Verena Pfirrmann, Sarah Oelsner, Simone Fulda, Thomas Klingebiel, Winfried S Wels, Peter Bader, Eva Rettinger
Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2(nd)-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3(+) T cell phenotype showed up to 85% cell surface expression of the respective CAR...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29025596/rank-and-egfr-in-invasive-breast-carcinoma
#6
Anastasios D Papanastasiou, Chaido Sirinian, Eva Plakoula, Vassiliki Zolota, Ioannis K Zarkadis, Haralabos P Kalofonos
Breast cancer is the most common malignancy, affecting one in eight women in North America and Europe. The human epidermal growth factor receptor (EGFR) protein comprises a major determinant of normal development but also cancer. RANK receptor (Receptor Activator of Nuclear factor-κB) is a tumor necrosis superfamily member and a binding partner for RANKL, which was recently implicated in breast cancer initiation, progression and metastasis. Here we provide preliminary evidence of a possible interplay between RANK and EGFR signaling in breast cancer...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29024937/protein-biomarkers-predictive-for-response-to-anti-egfr-treatment-in-ras-wild-type-metastatic-colorectal-carcinoma
#7
Astrid Lièvre, Bérèngere Ouine, Jim Canet, Aurélie Cartier, Yael Amar, Wulfran Cacheux, Odette Mariani, Rosine Guimbaud, Janick Selves, Thierry Lecomte, Serge Guyetant, Ivan Bieche, Frédérique Berger, Leanne de Koning
BACKGROUND: Metastatic colorectal cancer (mCRC) patients with mutant KRAS or NRAS are ineligible for anti-epidermal growth factor receptor (anti-EGFR) therapy, as RAS mutations activate downstream pathways independently of EGFR and induce primary resistance. However, even among RAS wild-type (WT) patients, only a fraction responds to anti-EGFR therapy, suggesting that other mechanisms of resistance exist. We hypothesise that different (epi)genetic alterations can lead to primary anti-EGFR resistance and that the crucial end point is the activation of protein signalling pathways...
October 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29024812/inhibition-of-pyruvate-carboxylase-by-1%C3%AE-25-dihydroxyvitamin-d-promotes-oxidative-stress-in-early-breast-cancer-progression
#8
Tomasz Wilmanski, Xuanzhu Zhou, Wei Zheng, Aparna Shinde, Shawn S Donkin, Michael Wendt, John R Burgess, Dorothy Teegarden
Maintaining reductive-oxidative (redox) balance is an essential feature in breast cancer cell survival, with cellular metabolism playing an integral role in maintaining redox balance through its supply of reduced NADPH. In the present studies, the effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on redox balance was investigated in early stages of breast cancer. Treatment with 1,25(OH)2D promoted oxidative stress in MCF10A-ras and MCF10A-ErbB2 breast epithelial cells, as measured by the decreased ratios of NADPH/NADP+ and reduced to oxidized glutathione (GSH/GSSG)...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29023096/graphene-liquid-enclosure-for-single-molecule-analysis-of-membrane-proteins-in-whole-cells-using-electron-microscopy
#9
Indra N Dahmke, Andreas Verch, Justus Hermannsdörfer, Diana B Peckys, Robert S Weatherup, Stephan Hofmann, Niels de Jonge
Membrane proteins govern many important functions in cells via dynamic oligomerization into active complexes. However, analytical methods to study their distribution and functional state in relation to the cellular structure are currently limited. Here, we introduce a technique for studying single-membrane proteins within their native context of the intact plasma membrane. SKBR3 breast cancer cells were grown on silicon microchips with thin silicon nitride windows. The cells were fixed, and the epidermal growth factor receptor ErbB2 was specifically labeled with quantum dot (QD) nanoparticles...
October 16, 2017: ACS Nano
https://www.readbyqxmd.com/read/28982707/post-injury-induction-of-activated-erbb2-selectively-hyperactivates-denervated-schwann-cells-and-promotes-robust-dorsal-root-axon-regeneration
#10
Seung Baek Han, Hyukmin Kim, Hyunkyoung Lee, Matthew Grove, George M Smith, Young-Jin Son
Following nerve injury, denervated Schwann cells (SCs) convert to repair SCs, which enable regeneration of peripheral axons. However, the repair capacity of SCs and the regenerative capacity of peripheral axons are limited. In the present studies we examined a potential therapeutic strategy to enhance the repair capacity of SCs, and tested its efficacy in enhancing regeneration of dorsal root (DR) axons, whose regenerative capacity is particularly weak. We used male and female mice of a doxycycline-inducible transgenic line to induce expression of constitutively active ErbB2 (caErbB2) selectively in SCs after DR crush or transection...
October 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28978093/molecular-characterization-of-circulating-colorectal-tumor-cells-defines-genetic-signatures-for-individualized-cancer-care
#11
Say Li Kong, Xingliang Liu, Nur-Afidah Mohamed Suhaimi, Kenneth Jia Hao Koh, Min Hu, Daniel Yoke San Lee, Igor Cima, Wai Min Phyo, Esther Xing Wei Lee, Joyce A Tai, Yu Miin Foong, Jess Honganh Vo, Poh Koon Koh, Tong Zhang, Jackie Y Ying, Bing Lim, Min-Han Tan, Axel M Hillmer
Studies on circulating tumor cells (CTCs) have largely focused on platform development and CTC enumeration rather than on the genomic characterization of CTCs. To address this, we performed targeted sequencing of CTCs of colorectal cancer patients and compared the mutations with the matched primary tumors. We collected preoperative blood and matched primary tumor samples from 48 colorectal cancer patients. CTCs were isolated using a label-free microfiltration device on a silicon microsieve. Upon whole genome amplification, we performed amplicon-based targeted sequencing on a panel of 39 druggable and frequently mutated genes on both CTCs and fresh-frozen tumor samples...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978063/predictive-value-of-molecular-subtyping-in-nmibc-by-rt-qpcr-of-erbb2-esr1-pgr-and-mki67-from-formalin-fixed-tur-biopsies
#12
Johannes Breyer, Ralph Markus Wirtz, Wolfgang Otto, Mark Laible, Kornelia Schlombs, Philipp Erben, Maximilian Christian Kriegmair, Robert Stoehr, Sebastian Eidt, Stefan Denzinger, Maximilian Burger, Arndt Hartmann
Expression of ESR1, PGR, HER2 and Ki67 is important for risk stratification and therapy in breast cancer. Hormone receptor expression can also be found in MIBC, reflecting luminal and basal subtypes of breast cancer. Thus the purpose was to investigate on the mRNA expression of the aforementioned markers and their prognostic value in pT1 bladder cancer. Retrospective analysis of clinical data and Formalin-Fixed Paraffin-Embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder was performed...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974323/synthesis-and-photophysical-properties-of-a-fluorescent-cyanoquinoline-probe-for-profiling-erbb2-kinase-inhibitor-response
#13
Heajin Lee, Ralf Landgraf, James N Wilson
A fluorescent probe targeting the ERBB2 receptor tyrosine was designed, synthesized and evaluated as reporter of ERBB2 dynamics in overexpressing BT474, i.e. Her2(+), cells. Two cyanoquinazoline (CQ) probes modeled after type-I (CQ1) or active state and type-II (CQ2) or inactive state inhibitors were designed and synthesized with extended π systems that impart binding-induced, turn-on fluorescence. Solution spectroscopy revealed that CQ1 exhibited attractive photophysical properties and displayed turn-on emission in the presence of purified, soluble ERBB2 kinase domain, while CQ2 was found to be non-emissive, likely due to quenching via a photoinduced electron transfer mechanism...
September 23, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28974261/the-150-most-important-questions-in-cancer-research-and-clinical-oncology-series-questions-57-66-edited-by-chinese-journal-of-cancer
#14
EDITORIAL
(no author information available yet)
Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 10 more questions are presented as followed. Question 57. What are the major stresses that drive the formation, progression, and metastasis of a cancer? Question 58. What is the mechanism responsible for altering an acidic intracellular pH and a basic extracellular pH in normal tissue cells to a basic intracellular pH and an acidic extracellular pH in cancer cells, a fundamental and yet largely ignored phenomenon? Question 59...
October 3, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28961851/comprehensive-genomic-profiles-of-metastatic-and-relapsed-salivary-gland-carcinomas-are-associated-with-tumor-type-and-reveal-new-routes-to-targeted-therapies
#15
J S Ross, L M Gay, K Wang, J-A Vergilio, J Suh, S Ramkissoon, H Somerset, J M Johnson, J Russell, S Ali, A B Schrock, D Fabrizio, G Frampton, V Miller, P J Stephens, J A Elvin, D W Bowles
Background: Relapsed/metastatic salivary gland carcinomas (SGCs) have a wide diversity of histologic subtypes associated with variable clinical aggressiveness and response to local and systemic therapies. We queried whether comprehensive genomic profiling could define the tumor subtypes and uncover clinically relevant genomic alterations, revealing new routes to targeted therapies for patients with relapsed and metastatic disease. Patients and methods: From a series of 85 686 clinical cases, DNA was extracted from 40 µm of formalin-fixed paraffin embedded (FFPE) sections for 623 consecutive SGC...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28947975/phenformin-inhibits-growth-and-epithelial-mesenchymal-transition-of-erbb2-overexpressing-breast-cancer-cells-through-targeting-the-igf1r-pathway
#16
Zhiying Guo, Ming Zhao, Erin W Howard, Qingxia Zhao, Amanda B Parris, Zhikun Ma, Xiaohe Yang
Reports suggest that metformin, a popular anti-diabetes drug, prevents breast cancer through various systemic effects, including insulin-like growth factor receptor (IGFR) regulation. Although the anti-cancer properties of metformin have been well-studied, reports on a more bioavailable/potent biguanide, phenformin, remain sparse. Phenformin exerts similar functional activity to metformin and has been reported to impede mammary carcinogenesis in rats. Since the effects of phenformin on specific breast cancer subtypes have not been fully explored, we used ErbB2-overexpressing breast cancer cell and animal models to test the anti-cancer potential of phenformin...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28947957/cooperative-but-distinct-early-co-signaling-events-originate-from-erbb2-and-erbb1-receptors-upon-trastuzumab-treatment-in-breast-cancer-cells
#17
Paola Bagnato, Alessia Castagnino, Katia Cortese, Maria Bono, Silvia Grasso, Grazia Bellese, Tiziana Daniele, Richard Lundmark, Paola Defilippi, Patrizio Castagnola, Carlo Tacchetti
ERBB2 receptor belongs to the ERBB tyrosine kinase receptor family. At variance to the other family members, ERBB2 is a constitutively active orphan receptor. Upon ligand binding and activation, ERBB receptors form homo- or hetero-dimers with the other family members, including ERBB2, promoting an intracellular signaling cascade. ERBB2 is the preferred dimerization partner and ERBB2 heterodimers signaling is stronger and longer acting compared to heterodimers between other ERBB members. The specific contribution of ERBB2 in heterodimer signaling is still undefined...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28945887/hybrid-capture-based-genomic-profiling-of-circulating-tumor-dna-from-patients-with-estrogen-receptor-positive-metastatic-breast-cancer
#18
J H Chung, D Pavlick, R Hartmaier, A B Schrock, L Young, B Forcier, P Ye, M K Levin, H Burris, L M Gay, A D Hoffman, P J Stephens, G M Frampton, D M Lipson, D M Nguyen, S Ganesan, B H Park, L T Vahdat, B Leyland-Jones, T I Mughal, L Pusztai, J O'Shaughnessy, V A Miller, J S Ross, S M Ali
Background: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative...
August 31, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28945843/next-generation-sequencing-ngs-of-cell-free-circulating-tumor-dna-and-tumor-tissue-in-patients-with-advanced-urothelial-cancer-a-pilot-assessment-of-concordance
#19
P C Barata, V S Koshkin, P Funchain, D Sohal, A Pritchard, S Klek, T Adamowicz, D Gopalakrishnan, J Garcia, B Rini, P Grivas
Background: Advances in cancer genome sequencing have led to the development of various next-generation sequencing (NGS) platforms. There is paucity of data regarding concordance of different NGS tests carried out in the same patient. Methods: Here, we report a pilot analysis of 22 patients with metastatic urinary tract cancer and available NGS data from paired tumor tissue [FoundationOne (F1)] and cell-free circulating tumor DNA (ctDNA) [Guardant360 (G360)]. Results: The median time between the diagnosis of stage IV disease and the first genomic test was 23...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28944885/exploring-the-key-genes-and-pathways-of-osteosarcoma-with-pulmonary-metastasis-using-a-gene-expression-microarray
#20
Zhongju Shi, Hengxing Zhou, Bin Pan, Lu Lu, Zhijian Wei, Linlin Shi, Xue Yao, Yi Kang, Shiqing Feng
Osteosarcoma is a common and highly malignant tumour in children and teenagers that is characterized by drug resistance and high metastatic potential. Patients often develop pulmonary metastasis and have a low survival rate. However, the mechanistic basis for pulmonary metastasis remains unclear. To identify key gene and pathways associated with pulmonary metastasis of osteosarcoma, the authors downloaded the gene expression dataset GSE85537 and obtained the differentially expressed genes (DEGs) by analyzing high‑throughput gene expression in primary tumours and lung metastases...
September 21, 2017: Molecular Medicine Reports
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