Clinical relevance of circulating KRAS mutated DNA in plasma from patients with advanced pancreatic cancer
We used KRAS mutations to investigate the clinical relevance of circulating tumor DNA (ctDNA) measurements in patients with advanced pancreatic cancer. Fifty-three blood samples were collected from 14 prospectively recruited patients prior to chemotherapy (gemcitabine or FOLFIRINOX) and subsequently every month during treatment. Samples were processed by density centrifugation and plasma DNA isolation. A Peptide–nucleic acid–clamp PCR was then used to detect KRAS mutations (present in >90% of pancreatic cancers) as a surrogate marker for ctDNA. (Source: Molecular Oncology)
Source: Molecular Oncology - December 16, 2015 Category: Cancer & Oncology Authors: Kjersti Tjensvoll, Morten Lapin, Tove Buhl, Satu Oltedal, Katrine Steen-Ottosen Berry, Bjørnar Gilje, Jon Arne Søreide, Millind Javle, Oddmund Nordgård, Rune Smaaland Source Type: research
Intracranial AAV-sTRAIL combined with lanatoside C prolongs survival in an orthotopic xenograft mouse model of invasive glioblastoma
Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of secreted, soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) to GBM tumors in mice and combined it with the TRAIL-sensitizing cardiac glycoside, lanatoside C (lan C). We applied this combined therapy to two different GBM models using human U87 glioma cells and primary patient-derived GBM neural spheres in culture and in orthotopic GBM xenograft models in mice. (Source: Molecular Oncology)
Source: Molecular Oncology - December 10, 2015 Category: Cancer & Oncology Authors: Matheus H.W. Crommentuijn, Casey A. Maguire, Johanna M. Niers, W. Peter Vandertop, Christian E. Badr, Thomas Würdinger, Bakhos A. Tannous Source Type: research
Editorial Board
(Source: Molecular Oncology)
Source: Molecular Oncology - December 1, 2015 Category: Cancer & Oncology Source Type: research
hnRNPA2/B1 activates cyclooxygenase-2 and promotes tumor growth in human lung cancers
Cyclooxygenase-2 (COX-2) is highly expressed in tumor cells and has been regarded as a hallmarker for cancers, but the excise regulation mechanism of COX-2 in tumorigenesis remains largely unknown. Here, we pulled down and identified a novel COX-2 regulator, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), which could specifically bind to COX-2 core promoter and regulate tumor growth in non-small-cell lung cancers (NSCLCs). Knockdown of hnRNPA2/B1 by shRNA or siRNA downregulated COX-2 expression and prostaglandin E2 (PGE2) production, and suppressed tumor cell growth in NSCLC cells in vitro and in vivo. (Source: Molecular Oncology)
Source: Molecular Oncology - November 30, 2015 Category: Cancer & Oncology Authors: Yang Xuan, Liying Ban, Jian-Jun Lu, Xiangsheng Xiao, Canhui Yi, Zhenglin Li, Wendan Yu, Mei Li, Tingting Xu, Wenjing Yang, Zhipeng Tang, Ranran Tang, Qianyi Zhang, Songshu Meng, Bilian Jin, Quentin Liu, Wenlin Huang, Wei Guo, Xiaonan Cui, Wuguo Deng Source Type: research
ΔNp63α Induces Quiescence and Downregulates the BRCA1 Pathway in Estrogen Receptor-Positive Luminal Breast Cancer Cell Line MCF7 but not in Other Breast Cancer Cell Lines
Despite apparent resection of tumors, breast cancer patients often suffer relapse due to remnant dormant tumor cells. Although quiescence of cancer stem cells is thought as one of the mechanisms regulating dormancy, the mechanism underlying quiescence is unclear. Since ΔNp63α, an isoform of p51/p63, is crucial in the maintenance of stem cells within mammary epithelium, we investigated its roles in the regulation of dormancy in normal and malignant breast cells. Inducible expression of ΔNp63α in MCF7 estrogen receptor positive (ER+) luminal breast cancer cells led to quiescence and acquisition of progenitor-like propert...
Source: Molecular Oncology - November 24, 2015 Category: Cancer & Oncology Authors: Ruhul Amin, Yuiko Morita-Fujimura, Hiroshi Tawarayama, Kentaro Semba, Natsuko Chiba, Manabu Fukumoto, Shuntaro Ikawa Source Type: research
The clinical prognostic value of molecular intrinsic tumor subtypes in older breast cancer patients: A FOCUS study analysis
It was recently proposed that the molecular breast tumor subtypes are differently distributed in the elderly breast cancer patients, and also lack prognostic value. Given the limited number of elderly patients in previous studies, the aim of this study was to determine the prognostic effect of the molecular intrinsic subtypes in a large older breast cancer population. (Source: Molecular Oncology)
Source: Molecular Oncology - November 23, 2015 Category: Cancer & Oncology Authors: Charla C. Engels, Mandy Kiderlen, Esther Bastiaannet, Antien L. Mooyaart, Ronald van Vlierberghe, Vincent T.H.B.M. Smit, Peter J.K. Kuppen, Cornelis J.H. van de Velde, G.J. Liefers Source Type: research
Genetic profiling of tumours using both circulating free DNA and circulating tumour cells isolated from the same preserved whole blood sample
Molecular information obtained from cancer patients' blood is an emerging and powerful research tool with immense potential as a companion diagnostic for patient stratification and monitoring. Blood, which can be sampled routinely, provides a means of inferring the current genetic status of patients' tumours via analysis of circulating tumour cells (CTCs) or circulating tumour DNA (ctDNA). However, accurate assessment of both CTCs and ctDNA requires all blood cells to be maintained intact until samples are processed. (Source: Molecular Oncology)
Source: Molecular Oncology - November 19, 2015 Category: Cancer & Oncology Authors: Dominic G. Rothwell, Nigel Smith, Daniel Morris, Hui Sun Leong, Yaoyong Li, Antoine Hollebecque, Mahmood Ayub, Louise Carter, Jenny Antonello, Lynsey Franklin, Crispin Miller, Fiona Blackhall, Caroline Dive, Ged Brady Source Type: research
Novel pharmacodynamic biomarkers for MYCN protein and PI3K/AKT/mTOR pathway signaling in children with neuroblastoma
There is an urgent need for improved therapies for children with high-risk neuroblastoma where survival rates remain low. MYCN amplification is the most common genomic change associated with aggressive neuroblastoma and drugs targeting PI3K/AKT/mTOR, to activate MYCN oncoprotein degradation, are entering clinical evaluation. Our aim was to develop and validate pharmacodynamic (PD) biomarkers to evaluate both proof of mechanism and proof of concept for drugs that block PI3K/AKT/mTOR pathway activity in children with neuroblastoma. (Source: Molecular Oncology)
Source: Molecular Oncology - November 19, 2015 Category: Cancer & Oncology Authors: Jennifer R. Smith, Lucas Moreno, Simon P. Heaton, Louis Chesler, Andrew D.J. Pearson, Michelle D. Garrett Source Type: research
Genetic profiling of tumors using both circulating free DNA and Circulating Tumor Cells isolated from the same preserved whole blood sample
Molecular information obtained from cancer patients' blood is an emerging and powerful research tool with immense potential as a companion diagnostic for patient stratification and monitoring. Blood, which can be sampled routinely, provides a means of inferring the current genetic status of patients' tumors via analysis of circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA). However, accurate assessment of both CTCs and ctDNA requires all blood cells to be maintained intact until samples are processed. (Source: Molecular Oncology)
Source: Molecular Oncology - November 19, 2015 Category: Cancer & Oncology Authors: Dominic G. Rothwell, Nigel Smith, Daniel Morris, Hui Sun Leong, Yaoyong Li, Antoine Hollebecque, Mahmood Ayub, Louise Carter, Jenny Antonello, Lynsey Franklin, Crispin Miller, Fiona Blackhall, Caroline Dive, Ged Brady Source Type: research
EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer
ALK gene fusion occurs in approximately 3-7% of non-small cell lung cancer (NSCLC). For patients with ALK positive NCSLC, crizotinib and ceritinib are FDA approved ALK inhibitors, however, patients inevitably acquire resistance to such therapies typically within one to two years. Interrogation of in vitro ALK-positive NSCLC cell line models of acquired resistance to first and second-generation ALK inhibitors revealed acquired epithelial-to-mesenchymal transition (EMT) mechanisms. Here we demonstrated that knockdown of upregulated mesenchymal markers in acquired resistant lines decreased the invasive and migratory capabilit...
Source: Molecular Oncology - November 19, 2015 Category: Cancer & Oncology Authors: Arjan Gower, Wei-Hsun Hsu, Shuo-Tse Hsu, Yisong Wang, Giuseppe Giaccone Source Type: research
Treg depletion in non-human primates using a novel diphtheria toxin-based anti-human CCR4 immunotoxin
In this study, we demonstrated that the anti-human CCR4 immunotoxin bound and depleted monkey CCR4+ cells in vitro. (Source: Molecular Oncology)
Source: Molecular Oncology - November 19, 2015 Category: Cancer & Oncology Authors: Zhaohui Wang, Shannon G. Pratts, Huiping Zhang, Philip J. Spencer, Ruichao Yu, Makoto Tonsho, Jigesh A. Shah, Tatsu Tanabe, Harrison R. Powell, Christene A. Huang, Joren C. Madsen, David H. Sachs, Zhirui Wang Source Type: research
Cripto: expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors
Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co-receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non-seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer. (Source: Molecular Oncology)
Source: Molecular Oncology - November 17, 2015 Category: Cancer & Oncology Authors: Cassy Spiller, Ad Gillis, Guillaume Burnet, Hans Stoop, Peter Koopman, Josephine Bowles, Leendert Looijenga Source Type: research
Intrinsic subtypes and genomic signatures of primary breast cancer and prognosis after systemic relapse
Molecular subtypes and gene expression signatures are widely used in early breast cancer but their role in metastatic disease is less explored. Two hundred-twenty patients diagnosed with primary breast cancer and subsequent relapse in Stockholm, Sweden between 1997-2006 were identified and their primary tumor was assessed for immunohistochemistry (IHC)- and PAM50-based subtypes, risk of recurrence (ROR-S) score, 21-gene and 70-gene signatures using research-based microarray expression profiles.Clinical and pathological data were retrospectively collected. (Source: Molecular Oncology)
Source: Molecular Oncology - November 17, 2015 Category: Cancer & Oncology Authors: Claudette Falato, Nicholas P. Tobin, Julie Lorent, Linda S. Lindström, Jonas Bergh, Theodoros Foukakis Source Type: research
Targeted capture massively parallel sequencing analysis of LCIS and invasive lobular cancer: repertoire of somatic genetic alterations and clonal relationships
Lobular carcinoma in situ (LCIS) has been proposed as a non-obligate precursor of invasive lobular carcinoma (ILC). Here we sought to define the repertoire of somatic genetic alterations in pure LCIS and in synchronous LCIS and ILC using targeted massively parallel sequencing. (Source: Molecular Oncology)
Source: Molecular Oncology - November 13, 2015 Category: Cancer & Oncology Authors: Rita A. Sakr, Michail Schizas, Jose Victor S. Carniello, Charlotte K.Y. Ng, Salvatore Piscuoglio, Dilip Giri, Victor P. Andrade, Marina De Brot, Raymond S. Lim, Russell Towers, Britta Weigelt, Jorge S. Reis-Filho, Tari A. King Source Type: research
vaccination: Cancer immunotherapy both personalized off-the-shelf
As cancer immunotherapy continues to benefit from novel approaches which cut immune ‘brake pedals’ (e.g. anti-PD1 and anti-CTLA4 antibodies) and push immune cell gas pedals (e.g. IL2, and IFNα) there will be increasing need to develop immune ‘steering wheels’ such as vaccines to guide the immune system specifically toward tumor associated antigens. Two primary hurdles in cancer vaccines have been: identification of universal antigens to be used in ‘off-the-shelf’ vaccines for common cancers, and 2) logistical hurdles of ex vivo production of individualized whole tumor cell vaccines. (Source: Molecular Oncology)
Source: Molecular Oncology - November 6, 2015 Category: Cancer & Oncology Authors: Linda Hammerich, Adam Binder, Joshua D. Brody Tags: Review Source Type: research
