A ribonucleotide reductase inhibitor with deoxyribonucleoside-reversible cytotoxicity
Ribonucleotide Reductase (RNR) is the sole enzyme that catalyzes the reduction of ribonucleotides into deoxyribonucleotides. Even though RNR is a recognized target for antiproliferative molecules, and the main target of the approved drug hydroxyurea, few new leads targeted to this enzyme have been developed. We have evaluated a recently identified set of RNR inhibitors with respect to inhibition of the human enzyme and cellular toxicity. One compound, NSC73735, is particularly interesting; it is specific for leukemia cells and is the first identified compound that hinders oligomerization of the mammalian large RNR subunit....
Source: Molecular Oncology - July 26, 2016 Category: Cancer & Oncology Authors: Mikael Crona, Paula Cod ó, Venkateswara Rao Jonna, Anders Hofer, Aristi P. Fernandes, Fredrik Tholander Source Type: research

Proteomic characterization of Peroxisome Proliferator-Activated Receptor- γ (PPARγ) overexpressing or silenced colorectal cancer cells unveils a novel protein network associated with an aggressive phenotype
Peroxisome proliferator-activated receptor- γ (PPARγ) is a transcription factor of the nuclear hormone receptor superfamily implicated in a wide range of processes, including tumorigenesis. Its role in colorectal cancer (CRC) is still debated; most reports support that PPARγ reduced expression is associated with poor prognosis. We employed two-dimensional differential in-gel electrophoresis (2-D DIGE) followed by liquid chromatography (LC)-tandem mass spectrometry (MS/MS) to identify differentially expressed proteins and the molecular pathways underlying PPARγ expression in CRC progression. (Source: Molecular Oncology)
Source: Molecular Oncology - July 24, 2016 Category: Cancer & Oncology Authors: Maria Rita Milone, Biagio Pucci, Tommaso Colangelo, Rita Lombardi, Federica Iannelli, Vittorio Colantuoni, Lina Sabatino, Alfredo Budillon Source Type: research

LRG1 mRNA expression in breast cancer associates with PIK3CA genotype and with aromatase inhibitor therapy outcome
This study now evaluates whether expression of mRNAs and miRs are linked to PIK3CA genotype and are independently related to AI therapy response in order to define potential expressed biomarkers for treatment outcome. (Source: Molecular Oncology)
Source: Molecular Oncology - July 21, 2016 Category: Cancer & Oncology Authors: Diana E. Ramirez-Ardila, Kirsten Ruigrok-Ritstier, Jean C. Helmijr, Maxime P. Look, Steven van Laere, Luc Dirix, Els M.J.J. Berns, Maurice P.H.M. Jansen Source Type: research

Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer
Modern technologies enable detection and characterization of circulating tumor cells (CTC) in peripheral blood samples. Thus, CTC have attracted interest as markers for therapeutic response in breast cancer. First studies have incorporated CTC analyses to guide therapeutic interventions and stratification of breast cancer patients. Aim of this study was to analyze characteristic features of CTC as biomarker for predicting resistance to HER2-targeted therapies. Therefore, CTC from metastatic breast cancer patients with HER2-negative primary tumors screened for the prospective randomized phase III trial DETECT III were explo...
Source: Molecular Oncology - July 21, 2016 Category: Cancer & Oncology Authors: Christin Gasch, Theresa Oldopp, Oliver Mauermann, Tobias  M. Gorges, Antje Andreas, Cornelia Coith, Volkmar Müller, Tanja Fehm, Wolfgang Janni, Klaus Pantel, Sabine Riethdorf Source Type: research

LRG1 mRNA expression in breast cancer associates with PIK3CA genotype and with aromatase inhibitor therapy outcome
This study now evaluates whether expression of mRNAs and miRs are linked to PIK3CA genotype and are independently related to AI therapy response in order to define potential expressed biomarkers for treatment outcome. (Source: Molecular Oncology)
Source: Molecular Oncology - July 21, 2016 Category: Cancer & Oncology Authors: Diana E. Ramirez-Ardila, Kirsten Ruigrok-Ritstier, Jean C. Helmijr, Maxime P. Look, Steven van Laere, Luc Dirix, Els M.J.J. Berns, Maurice P.H.M. Jansen Source Type: research

Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer
Modern technologies enable detection and characterization of circulating tumor cells (CTC) in peripheral blood samples. Thus, CTC have attracted interest as markers for therapeutic response in breast cancer. First studies have incorporated CTC analyses to guide therapeutic interventions and stratification of breast cancer patients. Aim of this study was to analyze characteristic features of CTC as biomarker for predicting resistance to HER2-targeted therapies. Therefore, CTC from metastatic breast cancer patients with HER2-negative primary tumors screened for the prospective randomized phase III trial DETECTIII were explor...
Source: Molecular Oncology - July 21, 2016 Category: Cancer & Oncology Authors: Christin Gasch, Theresa Oldopp, Oliver Mauermann, Tobias M. Gorges, Antje Andreas, Cornelia Coith, Volkmar M üller, Tanja Fehm, Wolfgang Janni, Klaus Pantel, Sabine Riethdorf Source Type: research

Characterization of a re-engineered, mesothelin-targeted Pseudomonas exotoxin fusion protein for lung cancer therapy
Mesothelin overexpression in lung adenocarcinomas correlates with the presence of activating KRAS mutations and poor prognosis. Hence SS1P, a mesothelin-targeted immunotoxin, could offer valuable treatment options for these patients, but its use in solid tumor therapy is hampered by high immunogenicity and non-specific toxicity. To overcome both obstacles we developed RG7787, a de-immunized cytotoxic fusion protein comprising a humanized SS1 Fab fragment and a truncated, B-cell epitope silenced, 24 kD fragment of Pseudomonas exotoxin A (PE24). (Source: Molecular Oncology)
Source: Molecular Oncology - July 12, 2016 Category: Cancer & Oncology Authors: Frieder Bauss, Martin Lechmann, Ben-Fillippo Krippendorff, Roland Staack, Frank Herting, Matthias Festag, Sabine Imhof-Jung, Friederike Hesse, Marc Pompiati, Gwendlyn Kollmorgen, Rita da Silva Mateus Seidl, Birgit Bossenmaier, Wilma Lau, Christian Schantz Source Type: research

Plasma protein profiling in a stage defined pancreatic cancer cohort – Implications for early diagnosis
In this study, a recombinant antibody microarray platform was used to analyze 213 Chinese plasma samples from PDAC patients and normal control (NC) individuals. The cohort was stratified according to disease stage, i.e. resectable disease (stage I/II), locally advanced (stage III) and metastatic disease (stage IV). Support vector machine analysis showed that all PDAC stages could be discriminated from controls and that the accuracy increased with disease progression, from stage I to IV. (Source: Molecular Oncology)
Source: Molecular Oncology - July 11, 2016 Category: Cancer & Oncology Authors: Anna Sandstr öm Gerdtsson, Christer Wingren, Helena Persson, Payam Delfani, Malin Nordström, He Ren, Xin Wen, Ulrika Ringdahl, Carl A.K. Borrebaeck, Jihui Hao Source Type: research

Plasma protein profiling in a stage defined pancreatic cancer cohort – implications for early diagnosis
In this study, a recombinant antibody microarray platform was used to analyze 213 Chinese plasma samples from PDAC patients and normal control (NC) individuals. The cohort was stratified according to disease stage, i.e. resectable disease (stage I/II), locally advanced (stage III) and metastatic disease (stage IV). Support vector machine analysis showed that all PDAC stages could be discriminated from controls and that the accuracy increased with disease progression, from stage I to IV. (Source: Molecular Oncology)
Source: Molecular Oncology - July 11, 2016 Category: Cancer & Oncology Authors: Anna Sandström Gerdtsson, Christer Wingren, Helena Persson, Payam Delfani, Malin Nordström, He Ren, Xin Wen, Ulrika Ringdahl, Carl A.K. Borrebaeck, Jihui Hao Source Type: research

Metastatic breast cancer: The Odyssey of personalization
Metastatic breast cancer is the most frequent cause of cancer death for women worldwide. In the last 15 years, a large number of new agents have entered clinical use, a result of the dramatic increase in our understanding of the molecular underpinnings of metastatic breast cancer. However, while these agents have led to better outcomes, they are also at the root cause of increasing financial pressure on healthcare systems. Moreover, decision making in an era where every year new agents are added to the therapeutic armamentarium has also become a significant challenge for medical oncologists. (Source: Molecular Oncology)
Source: Molecular Oncology - July 10, 2016 Category: Cancer & Oncology Authors: A. Sonnenblick, N. Pond é, M. Piccart Tags: Review Source Type: research

Metastatic Breast Cancer: the Odyssey of Personalization
Metastatic breast cancer is the most frequent cause of cancer death for women worldwide. In the last 15 years, a large number of new agents have entered clinical use, a result of the dramatic increase in our understanding of the molecular underpinnings of metastatic breast cancer. However, while these agents have led to better outcomes, they are also at the root cause of increasing financial pressure on healthcare systems. Moreover, decision making in an era where every year new agents are added to the therapeutic armamentarium has also become a significant challenge for medical oncologists. (Source: Molecular Oncology)
Source: Molecular Oncology - July 10, 2016 Category: Cancer & Oncology Authors: A. Sonnenblick, N. Pondé, M. Piccart Tags: Review Source Type: research

A validated microRNA profile with predictive potential in glioblastoma patients treated with bevacizumab
We investigated whether microRNA expression data from glioblastoma could be used to produce a profile that defines a bevacizumab responsive group of patients. (Source: Molecular Oncology)
Source: Molecular Oncology - June 30, 2016 Category: Cancer & Oncology Authors: Josie Hayes, Helene Thygesen, Walter Gregory, David R. Westhead, Pim J. French, Martin J. Van Den Bent, Sean E. Lawler, Susan C. Short Source Type: research