MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Molecular Oncology' source. Wed, 08 Feb 2012 08:41:50 +0100 http://www.medworm.com/index.php?rid=5638225&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001517%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638225 Sun, 29 Jan 2012 13:24:35 +0100 5638225 http://www.medworm.com/index.php?rid=5638227&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001451%2Fabstract%3Frss%3Dyes Abstract: Epidermal growth factor receptor (EGFR) is a validated target in different human malignancies. EGFR tyrosine kinase inhibitors (TKIs) are known to contribute considerably to the extension of progression-free survival in EGFR-mutant non-small cell lung cancer and monoclonal antibodies (mAbs) targeting EGFR have also improved the efficacy outcomes in KRAS wild-type colorectal cancer. Nevertheless, a significant percentage of lung and colorectal cancer patients do not respond to anti-EGFR agents and secondary resistance after initial benefit is a challenging reality faced by clinicians. Extensive preclinical work on the potential mechanisms of resistance to EGFR inhibitors in different disease settings has guided the development of second-generation irreversible EGFR TKIs, more eff... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638227 Wed, 14 Dec 2011 05:00:00 +0100 5638227 http://www.medworm.com/index.php?rid=5638226&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001414%2Fabstract%3Frss%3Dyes Abstract: Since the early clinical studies of cancer immunotherapy, the question arose as to whether it was possible to combine it with standard cancer treatments, mostly chemotherapy. The answer, now, is past history. The combined use of immunotherapy and chemotherapy is not only possible but, in certain cases, can be advantageous, depending on the drug, the dose and the combination modalities. In order to find the best synergisms between the two treatments and to turn weak immunotherapeutic interventions into potent anticancer instruments, it is mandatory to understand the complex mechanisms responsible for the positive interactions between chemotherapy and immunotherapy. In this article, we review the current knowledge on mechanisms involved in the immunostimulating activity of chemothe... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638226 Fri, 09 Dec 2011 05:00:00 +0100 5638226 http://www.medworm.com/index.php?rid=5638229&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911100144X%2Fabstract%3Frss%3Dyes Abstract: The uPA/uPAR system is known to play a critical role in angiogenesis of glioblastoma. Previously, we have shown that shRNA against uPA and uPAR attenuates angiogenesis by blocking nuclear translocation of angiogenin, inhibition of angiopoietin/Tie2 signaling, and regulating several other pro-angiogenic, angiostatic and anti-angiogenic molecules. Further analysis revealed that GM-CSF, a pleiotropic cytokine, was significantly inhibited in U87MG and 4910 co-cultures with endothelial cells transfected with shRNA against uPA and uPAR. The role of the uPA/uPAR system in this process is not completely understood. Analysis of tumor conditioned medium of U87MG, 4910 and HMECs transfected with shRNA against uPA or uPAR alone or in combination (pU2) revealed inhibition of GM-CSF-enhanced s... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638229 Thu, 08 Dec 2011 05:00:00 +0100 5638229 http://www.medworm.com/index.php?rid=5638234&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001426%2Fabstract%3Frss%3Dyes Abstract: The clinical benefit of anthracyclines has been connected to HER2 status, TOP2A status and centromere 17 copy numbers (CEN-17). Data from a clinical trial randomizing patients to anthracyclines was used to assess whether the number of CEN-17 in breast cancers may predict incremental responsiveness to anthracyclines besides what is obtained when used relatively to TOP2A and HER2. As cut sections of paraffin-embedded tissue are prone to truncation of nuclei, strict definition of ploidy levels is lacking. We therefore used normal breast tissue to assist define ploidy levels in cut sections. Fluorescence in situ hybridization (FISH) with centromere 17 (CEN-17) and TOP2A was performed on 120 normal breast specimens. The diploid CEN-17 copy number was reduced from the expected two sign... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638234 Mon, 05 Dec 2011 05:00:00 +0100 5638234 http://www.medworm.com/index.php?rid=5638228&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001438%2Fabstract%3Frss%3Dyes Abstract: The technological advances of the last twenty years together with the dramatic increase in computational power have injected new life into systems-level thinking in Medicine. This review emphasizes the close relationship of Systems Pathology to Systems Biology and delineates the differences between Systems Pathology and Clinical Systems Pathology. It also suggests an algorithm to support the application of systems-level thinking to clinical research, proposes applying systems-level thinking to the health care systems and forecasts an acceleration of preventive medicine as a result of the coupling of personal genomics with systems pathology.Highlights: ► This review defines Systems Pathology. ► Relates it to Systems Biology. ► Defines Clinical System Biology. ► Discusses d... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638228 Mon, 05 Dec 2011 05:00:00 +0100 5638228 http://www.medworm.com/index.php?rid=5638230&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001402%2Fabstract%3Frss%3Dyes In conclusion, aberrant methylation in CRABP-II reduces the expression of CRABP-II that in turn confers RA resistance in medulloblastoma cells. Determination of CRABP-II expression or methylation status may enable a personalized RA therapy in patients with medulloblastomas and other types of cancers.Highlights: ► CRABP-II is silenced in RA-resistant medulloblastoma/MB cells due to promoter methylation. ► Restoration of CRABP-II expression overcomes RA-resistant property of MB cells. ► Inhibition of CRABP-II expression reduces RA sensitivity of MB cells. ► CRABP-II expression patterns are highly variable in medulloblastoma tissues. ► Evaluation of CRABP-II expression would be of values in personalized RA therapy for MB patients. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638230 Fri, 02 Dec 2011 05:00:00 +0100 5638230 http://www.medworm.com/index.php?rid=5638231&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001372%2Fabstract%3Frss%3Dyes This study demonstrated that elevated reactive oxygen species (ROS) levels derived from both mitochondria and NADPH oxidase were required for VEGF expression in NSCLC cells. Atorvastatin administration could significantly inhibit VEGF expression both in vitro and in vivo via inhibition of ROS production. Atorvastatin inhibited ROS generation partly through suppression of Rac1/NADPH oxidase activity. Specifically, atorvastatin could upregulate the activity of glutathione peroxidase (GPx) and catalase, which are responsible for elimination of hydrogen peroxide (H2O2) in the mitochondria and peroxisomes, respectively. Thus, inhibition of ROS production by concomitant suppression of Rac1/NADPH oxidase activity and upregulation of the activity of GPx and catalase contributes critically to ato... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638231 Wed, 30 Nov 2011 05:00:00 +0100 5638231 http://www.medworm.com/index.php?rid=5638232&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001360%2Fabstract%3Frss%3Dyes In this study, we first confirmed that the down-regulation of MTUS1/ATIP was a frequent event in oral tongue squamous cell carcinoma (OTSCC) and the premalignant lesion (leukoplakia). We further demonstrated that the down-regulation of MTUS1/ATIP was correlated with poor differentiation and enhanced proliferation (Ki67 proliferation index). Statistical analysis suggests that the down-regulation of MTUS1/ATIP was associated with reduced overall survival. Isoform specific quantitative RT-PCR assays revealed that ATIP1, ATIP3a and ATIP3b were the major isoforms of the MTUS1 gene products in oral tongue epithelial cells. Significant down-regulations were observed for all 3 ATIP isoforms in OTSCC as compared to matching normal tissues. In vitro functional study showed that the restoration of A... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638232 Mon, 28 Nov 2011 05:00:00 +0100 5638232 http://www.medworm.com/index.php?rid=5440428&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001268%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5440428 Fri, 25 Nov 2011 01:57:34 +0100 5440428 http://www.medworm.com/index.php?rid=5638233&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001359%2Fabstract%3Frss%3Dyes In this study, we analyzed the expression pattern of all subtypes of AQPs, and found that 8 out of 13 AQPs expressed in melanoma cells. To understand the role of aberrant expression of AQP in this disease, we over-expressed AQP3 and AQP9 in human melanoma WM266.4 cells and found that both AQPs significantly increased the chemoresistance of WM266.4 cells to arsenite. Functional studies showed that AQP3 and AQP9 can inhibit cell apoptosis induced by arsenite through down-regulating p53 and up-regulating Bcl-2 and XIAP. Our data suggest the implication of APQ in melanoma progression and that the over-expression of AQP3 and AQP9 contributes to the chemoresistance of melanoma to arsenite.Highlights: ► We identify the expression pattern of all subtypes of AQP in melanoma cells. ► Over-expres... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638233 Mon, 21 Nov 2011 05:00:00 +0100 5638233 http://www.medworm.com/index.php?rid=5440429&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001207%2Fabstract%3Frss%3Dyes Abstract: Cancer represents a complex group of heterogeneous diseases. While many cancers share fundamental biological processes (hallmarks of cancer) necessary for their development and progression, cancers also distinguish themselves by their dependence on distinct oncogenic pathways. Over the last decade, targeted therapies have been introduced to the clinic with variable success. In truth, single targeted therapies may be successful in only a subset of malignancies but insufficient to address malignancies that often rely on multiple pathways, thus evading single targeted agents. Investigators have recently identified potentially functional components of the human genome that were previously thought to have no biological function. This discovery has added to the already established comp... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5440429 Mon, 07 Nov 2011 05:00:00 +0100 5440429 http://www.medworm.com/index.php?rid=5440430&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001220%2Fabstract%3Frss%3Dyes Abstract: Chemotherapy represents a mainstay and powerful adjuvant therapy in the treatment of cancer. The field has evolved from drugs possessing all-encompassing cell-killing effects to those with highly targeted, specific mechanisms of action; a direct byproduct of enhanced understanding of tumorigenic processes. However, advances regarding development of agents that target key molecules and dysregulated pathways have had only modest impacts on patient survival. Several biological barriers preclude adequate delivery of drugs to tumors, and remain a formidable challenge to overcome in chemotherapy. Currently, the field of nanomedicine is enabling the delivery of chemotherapeutics, including repositioned drugs and siRNAs, by giving rise to carriers that provide for protection from degrada... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5440430 Mon, 31 Oct 2011 04:00:00 +0100 5440430 http://www.medworm.com/index.php?rid=5638235&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001190%2Fabstract%3Frss%3Dyes Abstract: DNA ploidy analysis is useful for prognostication in cancer patients, but the genomic details underlying ploidy changes are not fully understood. To improve this understanding, we compared DNA ploidy status with karyotypic and comparative genomic hybridization data on 51 endometrial adenocarcinomas. Out of 34 DNA diploid tumors evaluated by CGH, 16 (47%) showed imbalances, though only two had more than four copy number changes. Ten (29%) had aberrations involving chromosome 1, seven (21%) involving chromosome 10, while one tumor had a chromosome 8 aberration. Four of the seven DNA tetraploid tumors (57%) had imbalances detected by CGH with two (29%) having more than four. Six out of eight DNA aneuploid tumors showed imbalances by CGH, with five (63%) having more than four. The ab... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5638235 Fri, 28 Oct 2011 04:00:00 +0100 5638235 http://www.medworm.com/index.php?rid=5440432&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001219%2Fabstract%3Frss%3Dyes Abstract: Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase and scaffold protein localized to focal adhesions, is uniquely positioned at the convergence point of integrin and receptor tyrosine kinase signal transduction pathways. FAK is overexpressed in many tumor cells, hence various inhibitors targeting its activity have been tested for anti-tumor activity. However, the direct effects of these pharmacologic agents on the endothelial cells of the vasculature have not been examined. Using primary human umbilical vein endothelial cells (HUVEC), we characterized the effects of two FAK inhibitors, PF-573,228 and FAK Inhibitor 14 on essential processes for angiogenesis, such as migration, proliferation, viability and endothelial cell tube formation. We observed that treatment with eit... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5440432 Wed, 26 Oct 2011 04:00:00 +0100 5440432 http://www.medworm.com/index.php?rid=5440435&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001189%2Fabstract%3Frss%3Dyes Abstract: Gene therapy has become an important strategy for treatment of malignancies, but problems remains concerning the low gene transferring efficiency, poor transgene expression and limited targeting specific tumors, which have greatly hampered the clinical application of tumor gene therapy. Gallbladder cancer is characterized by rapid progress, poor prognosis, and aberrantly high expression of Survivin. In the present study, we used a human tumor-specific Survivin promoter-regulated oncolytic adenovirus vector carrying P53 gene, whose anti-cancer effect has been widely confirmed, to construct a wide spectrum, specific, safe, effective gene-viral therapy system, AdSurp-P53. Examining expression of enhanced green fluorecent protein (EGFP), E1A and the target gene P53 in the oncolytic a... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5440435 Mon, 24 Oct 2011 04:00:00 +0100 5440435 http://www.medworm.com/index.php?rid=5260293&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001050%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5260293 Thu, 29 Sep 2011 01:00:58 +0100 5260293 http://www.medworm.com/index.php?rid=5440431&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911100113X%2Fabstract%3Frss%3Dyes Abstract: Risk assessment of future breast cancer risk through exposure to sex steroids currently relies on clinical scorings such as mammographic density. Knowledge about the gene expression patterns in existing breast cancer tumors may be used to identify risk factors in the breast tissue of women still free of cancer. The differential effects of estradiol, estradiol together with gestagens, or tibolone on breast cancer-related gene expression in normal breast tissue samples taken from postmenopausal women may be used to identify gene expression profiles associated with a higher breast cancer risk. Breast tissue samples were taken from 33 healthy postmenopausal women both before and after a six month treatment with either 2mg micronized estradiol [E2], 2mg micronized estradiol and 1mg no... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5440431 Mon, 26 Sep 2011 04:00:00 +0100 5440431 http://www.medworm.com/index.php?rid=5260294&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111001013%2Fabstract%3Frss%3Dyes Researchers in Europe can start planning for a push toward applied science and collaboration with industrial enterprises and small businesses alike as the European Commission looks ahead in hammering out its next long-term research framework programme, a grant and funding enterprise worth perhaps €80 billion leading through the end of the decade. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5260294 Fri, 09 Sep 2011 04:00:00 +0100 5260294 http://www.medworm.com/index.php?rid=5440437&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000962%2Fabstract%3Frss%3Dyes Abstract: Time to freezing tumor tissue for RNA expression analysis will always vary to some extent. To evaluate the effect of ischemia time, tumor tissue from ten breast cancer patients was collected and aliquots of tissue were snap frozen at different time points after surgery (0, 0.5, 1, 3 and 6 h). Using miRNA and mRNA expression microarrays and statistical analysis, 56 miRNAs and 1788 mRNAs were found to be significantly altered with ischemia time up to six hours. Several of the 56 miRNAs have been reported to play a role in cancer, such as hsa-miR-663 and hsa-miR-125a-3p. Known stress response genes such as GADD45B, JUND and FOSB were among the mRNAs most significantly affected by time to freezing. A novel statistical method for identification of consistently correlated miRNA–mRNA... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5440437 Wed, 07 Sep 2011 04:00:00 +0100 5440437 http://www.medworm.com/index.php?rid=5440436&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000950%2Fabstract%3Frss%3Dyes This study showed that fusion involving the MLL gene can be generated through various chromosomal rearrangements such as translocations, insertions and deletions, some being complex or cryptic. A systematic approach should be used in all cases of acute leukemia starting with FISH analyses using a commercially available MLL split signal probe. Then, the analysis has to be completed, if necessary, by further molecular cytogenetic and genomic PCR methods.Highlights: ► The MLL gene fuses with a great number of partner genes in acute leukemia. ► Molecular cytogenetic and genomic PCR methods allow identification of novel genes. ► Complex chromosomal rearrangements involving the MLL gene are frequent events. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5440436 Thu, 01 Sep 2011 04:00:00 +0100 5440436 http://www.medworm.com/index.php?rid=5440433&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000822%2Fabstract%3Frss%3Dyes Abstract: The transcription factor SOX11 is a novel diagnostic marker for mantle cell lymphoma (MCL), distinguishing this aggressive tumor from potential simulators. Recent data also show that the level of SOX11 correlates to in vitro growth properties in MCL, as well as the clinical progression. We have previously shown that MCL-associated pathways, such as Rb-E2F, are dysregulated leading to decreased proliferation upon overexpression of SOX11, emphasizing the impact of SOX11 on MCL-specific gene expression and growth control. However, it remains to be determined which growth regulatory pathways that are induced upon SOX11 knock-down, leading to an increased cellular growth. Consequently, we established a model cell line with constitutive down-regulation of SOX11. The highly proliferati... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5440433 Thu, 25 Aug 2011 04:00:00 +0100 5440433 http://www.medworm.com/index.php?rid=5440434&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000834%2Fabstract%3Frss%3Dyes Conclusions: Our results show a potential role of NFIB as a novel target in ER negative breast cancers.Highlights: ► We hypothesized that NFIB protein expression can be a novel target in breast cancer. ► We examine the NFIB expression in breast cancer cell lines and tissues. ► NFIB expression was associated with breast cancer subtypes. ► Silencing NFIB in HCC1954 cells resulted in decreased proliferation. ► NFIB can be a novel target for ER negative breast cancer. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5440434 Tue, 16 Aug 2011 04:00:00 +0100 5440434 http://www.medworm.com/index.php?rid=5260295&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000810%2Fabstract%3Frss%3Dyes This study provides evidence that elevated mitochondrial metabolism decreases cancer progression. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5260295 Fri, 12 Aug 2011 04:00:00 +0100 5260295 http://www.medworm.com/index.php?rid=5260296&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000780%2Fabstract%3Frss%3Dyes Abstract: ABCB6 is a mitochondrial transporter that regulates porphyrin biosynthesis. ABCB6 expression is upregulated in hepatocellular carcinoma (HCC) but the significance of this upregulation to HCC is not known. In the present study, we investigated: 1) ABCB6 expression in 18 resected human hepatocellular carcinoma (HCC) tissues and 3 human hepatoma cell lines; 2) pattern of ABCB6 expression during liver disease progression; and 3) functional significance of ABCB6 expression to HCC using the hepatoma cell line Huh7. ABCB6 expression was determined by real-time quantitative reverse transcription-polymerase chain reaction and western blotting. ABCB6 expression was upregulated in all the HCC specimens and the three-hepatoma cell lines. Increased ABCB6 expression correlated with liver disea... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5260296 Mon, 08 Aug 2011 04:00:00 +0100 5260296 http://www.medworm.com/index.php?rid=5175552&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000809%2Fabstract%3Frss%3Dyes Abstract: Aneuploidy, often preceded by tetraploidy, is one of the hallmarks of solid tumors. Indeed, both aneuploidy and tetraploidy are oncogenic occurrences that are sufficient to drive neoplastic transformation and cancer progression. True to form, the tumor suppressor p53 obstructs propagation of these dangerous chromosomal events by either instigating irreversible cell cycle arrest or apoptosis. The tumor suppressor Lats2, along with other tumor inhibitory proteins such as BRCA1/2 and BubR1, are central to p53-dependent elimination of tetraploid cells. Not surprisingly, these proteins are frequently inactivated or downregulated in tumors, synergizing with p53 inactivation to establish an atmosphere of “tolerance” for a non-diploid state.Highlights: ► Aneuploidy is a tumorigenic... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5175552 Sun, 07 Aug 2011 23:00:00 +0100 5175552 http://www.medworm.com/index.php?rid=5175550&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000792%2Fabstract%3Frss%3Dyes Over the last decade there have been many breakthroughs in our understanding of the biology and molecular pathogenesis of cancer, however, the sad truth is that cancer remains one of the top killers of mankind. In fact, due to the overall ageing of the world’s population and ongoing changes of lifestyle in the populations of large developing countries such as China, the global incidence of cancer is expected to increase, rather than decrease, in the near future (). This unfortunate scenario provides a strong motivation to translate the advances achieved by basic research into efforts aiming at improving the clinical management of cancer patients. Such translational efforts encompass improvements in early diagnosis, providing new function-based sub-classification schemes for various types... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5175550 Sun, 07 Aug 2011 23:00:00 +0100 5175550 http://www.medworm.com/index.php?rid=5260297&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000779%2Fabstract%3Frss%3Dyes Abstract: Cathepsin B and urokinase plasminogen activator receptor (uPAR) are overexpressed in gliomas. Deregulation of the G1 phase cell cycle machinery is a common feature of cancers. p27Kip1 (p27) is one of the major cyclin-CDK regulators in the G1 phase. uPAR and cathepsin B downregulation was recently shown to induce p27 expression through PI3K/Akt/FOXO3a signaling. Since uPAR and cathepsin B knockdown also decreased phosphorylation of ERK, we hypothesized that ERK also has a role to play in p27 induction. As induction of p27 is due to an increase in gene transcription, we investigated the roles of c-Myc and E2F1 transcription factors which have been shown to potently affect p27 promoter activity. In the present study, shRNA against cathepsin B and uPAR as well as specific inhibitors,... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5260297 Fri, 05 Aug 2011 04:00:00 +0100 5260297 http://www.medworm.com/index.php?rid=5260298&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000767%2Fabstract%3Frss%3Dyes Abstract: In attempt to discover novel aberrantly hypermethylated genes with putative tumor suppressor function in epithelial ovarian cancer (EOC), we applied expression profiling following pharmacologic inhibition of DNA methylation in EOC cell lines. Among the genes identified, one of particular interest wаs DOK1, or downstream of tyrosine kinase 1, previously recognized as a candidate tumor suppressor gene (TSG) for leukemia and other human malignancies. Using bisulfite sequencing, we determined that a 5′-non-coding DNA region (located at nt −1158 to −850, upstream of the DOK1 translation start codon) was extensively hypermethylated in primary serous EOC tumors compared with normal ovarian specimens; however, this hypermethylation was not associated with DOK1 suppression. On the ... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5260298 Thu, 04 Aug 2011 04:00:00 +0100 5260298 http://www.medworm.com/index.php?rid=5175558&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000743%2Fabstract%3Frss%3Dyes Abstract: Poly (ADP-ribose) polymerase (PARP) inhibitors effectively kill tumours defective in the BRCA1 or BRCA2 genes through the concept of synthetic lethality. It is suggested that PARP inhibitors cause an increase in DNA single-strand breaks (SSBs), which are converted during replication to irreparable toxic DNA double-strand breaks (DSBs) in BRCA1/2 defective cells. There are a number of recent reports challenging this model. Here, alternative models that are not mutually exclusive are presented to explain the synthetic lethality between BRCA1/2 and PARP inhibitors. One such model proposes that PARP inhibition causes PARP-1 to be trapped onto DNA repair intermediates, especially during base excision repair. This may in turn cause obstruction to replication forks, which require BRCA-d... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5175558 Sun, 31 Jul 2011 23:00:00 +0100 5175558 http://www.medworm.com/index.php?rid=5175549&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000871%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5175549 Sun, 31 Jul 2011 23:00:00 +0100 5175549 http://www.medworm.com/index.php?rid=5175556&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000755%2Fabstract%3Frss%3Dyes Abstract: Trying to kill cancer cells by generating DNA damage is by no means a new idea. Radiotherapy and genotoxic drugs are routinely used in cancer therapy. More recent developments also explored the potential of targeting the DNA damage response (DDR) in order to increase the toxicity of radio- and chemo- therapy. Chk1 inhibitors have pioneered studies in this regard. Interestingly, early studies noted that Chk1 inhibitors were particularly toxic for p53-deficient cells. The model proposed for this observation was that this effect was due to the simultaneous abrogation of the G2 (Chk1) and G1 (p53) checkpoints. We here challenge this view, and propose a model where the toxicity of Chk1 inhibitors is rather due to the fact that these compounds generate high loads of replicative stress ... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5175556 Wed, 27 Jul 2011 23:00:00 +0100 5175556 http://www.medworm.com/index.php?rid=5260301&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000718%2Fabstract%3Frss%3Dyes Abstract: JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS-2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non-neoplastic tissues) using real-time polymerase chain reaction. JS-2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS-2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression l... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5260301 Wed, 20 Jul 2011 04:00:00 +0100 5260301 http://www.medworm.com/index.php?rid=5260299&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000731%2Fabstract%3Frss%3Dyes Abstract: To understand the importance of frequent deletions at chromosome 11q24.1-24.2 region in breast carcinoma, alterations (deletion/methylation) of the candidate genes LOH11CR2A, ROBO3, ROBO4, HEPACAM, PIG8 and CHEK1 located in this region were analyzed in 106 breast carcinoma samples. Among these genes, LOH11CR2A showed highest frequency of deletion (56%), followed by PIG8 (35%), CHEK1 (31%) and ROBO3/ROBO4/HEPACAM loci (28%). Comparable frequency of promoter methylation (26–35%) was observed for LOH11CR2A, CHEK1 and PIG8. Overall alterations (deletion/methylation) of these genes were in the following order: LOH11CR2A (60%) > PIG8 (46%) > CHEK1 (41%) and showed significant association with each other. Breast carcinoma samples that were estrogen/progesterone receptor negative s... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5260299 Mon, 18 Jul 2011 04:00:00 +0100 5260299 http://www.medworm.com/index.php?rid=5175554&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911100072X%2Fabstract%3Frss%3Dyes Abstract: The cellular response to DNA damage is vital for maintaining genomic stability and preventing undue cell death or cancer formation. The DNA damage response (DDR), most robustly mobilized by double-strand breaks (DSBs), rapidly activates an extensive signaling network that affects numerous cellular systems, leading to cell survival or programmed cell death. A major component of the DDR is the widespread modulation of gene expression. We analyzed together six datasets that probed transcriptional responses to ionizing radiation (IR) – our novel experimental data and 5 published datasets – to elucidate the scope of this response and identify its gene targets. According to the mRNA expression profiles we recorded from 5 cancerous and non-cancerous human cell lines after exposure t... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5175554 Sun, 17 Jul 2011 23:00:00 +0100 5175554 http://www.medworm.com/index.php?rid=5175555&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911100069X%2Fabstract%3Frss%3Dyes Abstract: The integrity of the human genome is constantly threatened by genotoxic agents that cause DNA damage. Inefficient or inaccurate repair of DNA lesions triggers genome instability and can lead to cancer development or even cell death. Cells counteract the adverse effects of DNA lesions by activating the DNA damage response (DDR), which entails a coordinated series of events that regulates cell cycle progression and repair of DNA lesions. Efficient DNA repair in living cells is complicated by the packaging of genomic DNA into a condensed, often inaccessible structure called chromatin. Cells utilize post-translational histone modifications and ATP-dependent chromatin remodeling to modulate chromatin structure and increase the accessibility of the repair machinery to lesions embedded... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5175555 Sun, 10 Jul 2011 23:00:00 +0100 5175555 http://www.medworm.com/index.php?rid=5260300&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000706%2Fabstract%3Frss%3Dyes Abstract: Pin1 specifically recognizes and catalyzes the cis-trans isomerization of phosphorylated-Ser/Thr-Pro bonds, which modulate the stability, localization, and function of numerous Pin1 targets involved in tumor progression. However, the role of Pin1 in cancer remains enigmatic as the gene is located on chromosome 19p13.2, which is a region subject to loss of heterozygosity in several tumors. Since Pin1 protein is frequently under-expressed in kidney cancer, we have explored its role in human clear cell renal cell carcinoma (ccRCC). Here we show evidence for PIN1 gene deletion and mRNA under-expression as a mechanism of Pin1 reduction in ccRCC tumors. We demonstrate that restoration of Pin1 in cell lines found to be deficient in Pin1 protein expression can attenuate the growth of c... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5260300 Thu, 07 Jul 2011 04:00:00 +0100 5260300 http://www.medworm.com/index.php?rid=4877459&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000561%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877459 Mon, 30 May 2011 14:57:24 +0100 4877459 http://www.medworm.com/index.php?rid=5175557&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000500%2Fabstract%3Frss%3Dyes Abstract: There is increasing evidence that glioblastoma possess ‘stem-like’ cells, low concentrations of which can initiate a tumour. It has been proposed that these cells are radioresistant, and that this property contributes to the poor treatment outcomes of these tumours. In this paper we propose that radioresistance is not simply an intrinsic characteristic of glioma stem cells but a result of interactions between these cells and microenvironmental factors, i.e. the ‘microenvironment – stem cell unit’. The critical role of the microenvironment, along with glioma stem cells, is supported directly or indirectly by the following observations: glioma stem cells have been shown to reside preferentially in specific niches, the characteristics of which are known to influence cellul... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5175557 Sun, 29 May 2011 23:00:00 +0100 5175557 http://www.medworm.com/index.php?rid=5175551&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000512%2Fabstract%3Frss%3Dyes Abstract: Human cancers are characterized by the presence of genomic instability. Recently, two studies have catalogued the presence of a specific class of genomic aberrations, large deletions and insertions, in a few thousand human cancers and reported that most of the prevalent recurrent focal deletions targeted common fragile sites and large genes. In various experimental systems, deletions in common fragile sites and large genes have been linked to the presence of DNA replication stress. Thus, taken together, these results suggest the presence of DNA replication stress in human cancers, consistent with the recently proposed oncogene-induced DNA damage model for cancer development.Highlights: ► High throughput studies characterizing genomic instability in human cancers were reviewed. ... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5175551 Sun, 29 May 2011 23:00:00 +0100 5175551 http://www.medworm.com/index.php?rid=5175553&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000524%2Fabstract%3Frss%3Dyes Abstract: Centrosome abnormalities occur commonly in cancer, and contribute to chromosomal instability and tumorigenesis. New evidence on a phylogenetically conserved mechanism termed ‘centrosomal clustering’ provides exciting insights into how cells with supernumerary centrosomes adapt to avoid lethal multipolar divisions. Here, we highlight the emerging molecular basis of centrosome clustering, and its impact on asymmetric divisions of stem cells, chromosomal (in)stability and malignant transformation. Finally, pharmacological inhibition of centrosome clustering promises to selectively target tumor cells.Highlights: ► Centrosome abnormalities occur commonly in cancer. ► Centrosome clustering enables cells with extra centrosomes to divide successfully. ► We discuss the molecular... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=5175553 Thu, 26 May 2011 23:00:00 +0100 5175553 http://www.medworm.com/index.php?rid=4877462&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000494%2Fabstract%3Frss%3Dyes In the corner of her lab deep in a brightly-colored postindustrial campus on the south side of Amsterdam, Connie Jimenez can measure the strides being made in her field of proteomics: it sits there in the form of a new mass spectrometer. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877462 Wed, 04 May 2011 23:00:00 +0100 4877462 http://www.medworm.com/index.php?rid=4877461&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911100041X%2Fabstract%3Frss%3Dyes Personalised medicine, which involves finding the driving mutations of individual patient’s tumours and then matching them up to targeted therapies, is widely heralded as the future of oncology. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877461 Sun, 01 May 2011 23:00:00 +0100 4877461 http://www.medworm.com/index.php?rid=4877463&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000408%2Fabstract%3Frss%3Dyes Abstract: Despite huge efforts in development of drugs targeting oncogenic signalling, the number of such drugs entering clinical practice to date remains limited. Rational use of biomarkers for drug candidate selection and early monitoring of response to therapy may accelerate this process. Magnetic resonance spectroscopy (MRS) can be used to assess metabolic effects of drug treatment both in vivo and in vitro, and technological advances are continuously increasing the utility of this non-invasive method. In this review, we summarise the use of MRS for monitoring the effect of targeted anticancer drugs, and discuss the potential role of MRS in the context of personalised cancer treatment.Highlights: ► Cancer cell metabolism is frequently changed after treatment with targeted drugs. �... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877463 Thu, 28 Apr 2011 23:00:00 +0100 4877463 http://www.medworm.com/index.php?rid=4877464&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000391%2Fabstract%3Frss%3Dyes Abstract: Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abolished the antitumoural effect. In addit... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877464 Wed, 13 Apr 2011 23:00:00 +0100 4877464 http://www.medworm.com/index.php?rid=4771800&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000378%2Fabstract%3Frss%3Dyes Since the report in 2008 of a near complete response to imatinib in a patient with metastatic melanoma harboring KIT mutation, hope that some disseminated melanomas might also be cured by targeted treatments rose among the community (). After several years of failures and frustration, the treatment of metastatic cutaneous melanoma is eventually advancing. Ipilimumab, a human monoclonal antibody that binds to CTLA-4, has opened the way in demonstrating for the first time ever an improved overall survival in patients with stage IV melanoma (), and the targeted anti-BRAF therapy with PLX4032 given in patients with stage IV Braf mutated melanoma has showed extremely encouraging and durable responses in a phase 2 trial (). However, resistance to BRAF inhibitors is a significant clinical challen... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771800 Tue, 12 Apr 2011 23:00:00 +0100 4771800 http://www.medworm.com/index.php?rid=4877460&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911100038X%2Fabstract%3Frss%3Dyes An overview of Personal Profiles can be found at http://www.moloncol.org. Hedvig Hricak (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877460 Sun, 10 Apr 2011 23:00:00 +0100 4877460 http://www.medworm.com/index.php?rid=4877465&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000317%2Fabstract%3Frss%3Dyes In this study we investigate PIAS3 expression in both non-small cell lung cancer (NSCLC) cell lines and human resected NSCLC specimens. ► Expression of PIAS3 is variable in lung cancer cells lines with 2 of 3 squamous cell carcinoma (SCC) cell lines having no or little PIAS3 protein expression. Similarly, the majority of human SCCs of the lung lack PIAS3 expression by immunohistochemistry. ► High PIAS3 expression generally correlates with decreased phosphorylated STAT3 in both SCC cell lines and human specimens. ► No mutations in PIAS3 gene or significant CpG island methylation was seen in NSCLC cell lines. ► Exposure of cells to an agent blocking proteosomal degradation results in a significant increase in PIAS3. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877465 Wed, 06 Apr 2011 23:00:00 +0100 4877465 http://www.medworm.com/index.php?rid=4771799&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000354%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771799 Thu, 31 Mar 2011 23:00:00 +0100 4771799 http://www.medworm.com/index.php?rid=4771805&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000287%2Fabstract%3Frss%3Dyes Abstract: The FoxP3 (forkhead box P3) gene is an X-linked gene that is submitted to inactivation. It is an essential transcription factor in CD4+CD25+FoxP3 regulatory T cells, which are therapeutic targets in disseminated cutaneous melanoma. Moreover, FoxP3 is an important tumor suppressor gene in carcinomas and has putative cancer suppressor gene function in cutaneous melanoma as well. Therefore understanding the structure and function of the FoxP3 gene is crucial to gaining insight into the biology of melanoma to better develop immunotherapeutics and future therapeutic strategies. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771805 Wed, 30 Mar 2011 23:00:00 +0100 4771805 http://www.medworm.com/index.php?rid=4877466&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000305%2Fabstract%3Frss%3Dyes Abstract: Differentiation-inducing therapy has been proposed to be a novel potential approach to treat malignant gliomas. Glial fibrillary acidic protein (GFAP) is a well-known specific astrocyte biomarker and acts as a tumor suppressor gene (TSG) in glioma pathogenesis. Previously we reported that a traditional biotoxin cholera toxin could induce malignant glioma cell differentiation characterized by morphologic changes and dramatic GFAP expression. However, the molecular mechanisms underlying GFAP induction are still largely unknown. Here we demonstrate that an oncogenic pathway interleukin-6/janus kinase-2/signal transducer and activator of transcription 3 (IL-6/JAK2/STAT3) cascade mediates the cholera toxin-induced GFAP expression. Cholera toxin dramatically stimulated GFAP expression ... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877466 Sun, 27 Mar 2011 23:00:00 +0100 4877466 http://www.medworm.com/index.php?rid=4771802&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000299%2Fabstract%3Frss%3Dyes Abstract: In the initial period after melanoma was recognised as a disease entity in the early 1800’s, it was subclassified on the basis of its presumed origin (from a precursor naevus, from a melanocytic precursor lesion acquired during adult life or in previously blemish-fee skin). In 1967 the eminent American pathologist, Dr Wallace Clark, proposed a histogenetic classification for melanoma in which the disease was subdivided predominantly on the basis of histopathological features of the intra-epidermal component of the tumour adjacent to any dermal invasive component. The subtypes were superficial spreading melanoma (SSM), lentigo maligna melanoma (LMM) and nodular melanoma (NM). Whilst additional entities, including acral lentiginous melanoma, mucosal melanoma, desmoplastic melanom... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771802 Sun, 27 Mar 2011 23:00:00 +0100 4771802 http://www.medworm.com/index.php?rid=4877468&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000263%2Fabstract%3Frss%3Dyes Abstract: The focus of the current investigational study was to examine whether circulating nucleic acids (i.e., DNA and microRNAs) have the potential to become suitable blood-based markers for diagnosis and progression of lung cancer. The concentrations of cell-free DNA and four circulating microRNAs (miR10b, miR34a, miR141 and miR155) as well as the caspase activity were measured in serum of 35 lung cancer patients (19 non-small-cell lung cancer, 8 small cell lung cancer patients and 8 patients with indefinite cancer type), 7 patients with benign lung tumors and 28 healthy individuals by PicoGreen, TaqMan MicroRNA, and Caspase-Glo®3/7 assay, respectively. The data were correlated with the established risk factors for lung cancer progression. The concentrations of cell-free DNA (p = 0.... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877468 Mon, 07 Mar 2011 00:00:00 +0100 4877468 http://www.medworm.com/index.php?rid=4877467&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000275%2Fabstract%3Frss%3Dyes In this study we determined the complete miRNome of mycosis fungoides (MF), the most common type of cutaneous T cell lymphoma. The miRNA profile of skin biopsies from 19 patients with tumor stage MF and 12 patients with benign inflammatory dermatoses (eczema and lichen planus) were compared by microarray analysis. We identified 49 miRNAs that are differentially expressed in tumor stage MF compared to benign inflammatory dermatoses using ANOVA analysis (P  (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877467 Mon, 07 Mar 2011 00:00:00 +0100 4877467 http://www.medworm.com/index.php?rid=4771806&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000251%2Fabstract%3Frss%3Dyes Abstract: Cancer testis antigens (CTA) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches, and prompted the development of several clinical trials of CTA-based vaccine therapy. Driven by this practical clinical interest, a more detailed characterization of CTA biology has been recently undertaken. So far, at least 70 families of CTA, globally accounting for about 140 members, have been identified. Most of these CTA are expressed during spermatogenesis, but their function is still largely unknown. Epigene... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771806 Mon, 21 Feb 2011 00:00:00 +0100 4771806 http://www.medworm.com/index.php?rid=4771801&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000214%2Fabstract%3Frss%3Dyes Abstract: Activating mutations in BRAF, a constituent of the map kinase pathway, were first discovered as being most prevalent in melanoma in 2002. Only recently have potent and selective, orally available inhibitors of BRAF emerged for clinical testing and demonstrated clear evidence of tumor regression in the majority of patients whose tumors harbor a BRAF mutation. While these early observations suggest that the BRAF targeted therapy will become part of the standard treatment paradigm for patients with advanced melanoma, it is also clear that a majority of these responses are incomplete and temporary. Therefore, the focus of the melanoma field has shifted to understanding the limits of the first generation of selective BRAF inhibitors with regard to safety and efficacy, the context of s... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771801 Fri, 18 Feb 2011 00:00:00 +0100 4771801 http://www.medworm.com/index.php?rid=4771809&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000238%2Fabstract%3Frss%3Dyes Abstract: Vitamin D is a fat-soluble steroid hormone, which is essential to health and for which epidemiological studies suggest a role in autoimmune disease, infections, cardiovascular disease and cancer. It is ingested in foods such as oily fish and supplements, so that average levels vary between countries, but most individuals worldwide make most of their vitamin D as a result of the effects of sun exposure on the skin. Many studies in different populations around the world have in recent years shown that sub-optimal levels of vitamin D ( (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771809 Mon, 14 Feb 2011 00:00:00 +0100 4771809 http://www.medworm.com/index.php?rid=4771808&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000184%2Fabstract%3Frss%3Dyes Abstract: A typical array experiment yields at least tens of thousands of measurements on often not more than a hundred patients, a situation often denoted as the curse of dimensionality. With a focus on prognostic multi-biomarker scores derived from microarrays, we highlight the multidimensionality of the problem and the issues in the multidimensionality of the data. We go over several statistical challenges raised by this curse occurring in each step of microarray analysis on patient data, from the hypothesis and the experimental design to the analysis methods, interpretation of results and clinical utility. Different analytical tools and solutions to answer these challenges are provided and discussed. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771808 Fri, 11 Feb 2011 00:00:00 +0100 4771808 http://www.medworm.com/index.php?rid=4771807&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000202%2Fabstract%3Frss%3Dyes Abstract: Outcome in melanoma patients with advanced disease is poor and systemic treatment seems to benefit only a subset of patients. Predictive markers identifying these patients are currently not available. Early studies showed an association of immune-related side effects such as vitiligo and autoimmune thyroiditis with response to IL-2 or IFNα treatment. However, conflicting data have been reported as well, mentioning the effect of a higher rate of immune-related toxicities during prolonged administration of the drug in responders. The review discusses the prognostic significance of autoimmunity during various forms of immunotherapy and stresses the importance of correcting for guarantee-time bias. In addition, other immune-related factors which have been associated with melanoma pr... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771807 Fri, 11 Feb 2011 00:00:00 +0100 4771807 http://www.medworm.com/index.php?rid=4771804&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000226%2Fabstract%3Frss%3Dyes Abstract: Melanoma prognosis is based on specific pathological features at the primary lesion. In metastatic patients, the extent of lymph node involvement is also an important prognosis indicator. Many progression markers both in tissues and serum, including circulating tumor cells, have been studied and new molecular markers are awaited from high-throughput screenings to discriminate between clinical stages and predict disease progression.The present review focuses on human tyrosinase related protein 1 also known as gp75 glycoprotein (Tyrp1/gp75), a melanosomal protein involved in the pigmentary machinery of the melanocyte and often used as differentiation marker, with a special emphasis on its emerging roles in the malignant melanocyte and melanoma progression. (Source: Molecular Oncolo... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771804 Fri, 11 Feb 2011 00:00:00 +0100 4771804 http://www.medworm.com/index.php?rid=4771803&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000196%2Fabstract%3Frss%3Dyes Abstract: Angiogenesis is a pivotal process for growth, invasion and spread of the majority of solid tumors including melanoma. Anti-angiogenic agents have not been systematically tested in patients with advanced melanoma. Clinical efficacy of angiogenesis inhibitors targeting endothelial cells has not been as affirmative as initially hoped and improved clinical outcomes have been observed in combination with chemotherapy or additional drugs for many types of human cancer. However, angiogenesis is not only dependent on endothelial cell invasion and proliferation, it also requires pericyte coverage of vascular sprouts for stabilization and maturation of vascular walls. Recent data suggest that pericytes might be able to confer resistance to anti-vascular endothelial growth factor (VEGF) the... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4771803 Fri, 11 Feb 2011 00:00:00 +0100 4771803 http://www.medworm.com/index.php?rid=4877470&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911100024X%2Fabstract%3Frss%3Dyes On page 276, right column, Figure 5c should read Figure 6c in line 8 and 10 from the bottom. Due to an unfortunate error a wrong profile was displayed in the upper panel of Figure 6b. The text in the lower panel of Figure 6c should read chr11p instead of chr10p. The corrected figure and legend are given below. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877470 Thu, 10 Feb 2011 00:00:00 +0100 4877470 http://www.medworm.com/index.php?rid=4877469&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000159%2Fabstract%3Frss%3Dyes Abstract: Interest continues to build around the early application of patient selection markers to prospectively identify patients likely to show clinical benefit from cancer therapies. Hypothesis generation and clinical strategies often begin at the preclinical stage where responder and nonresponder tumor cell lines are first identified and characterized. In the present study, we investigate the drivers of in vivo resistance to the γ-secretase inhibitor RO4929097. Beginning at the tissue culture level, we identified apparent IL6 and IL8 expression differences that characterized tumor cell line response to RO4929097. We validated this molecular signature at the preclinical efficacy level identifying additional xenograft models resistant to the in vivo effects of RO4929097. Our data sugges... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4877469 Mon, 31 Jan 2011 00:00:00 +0100 4877469 http://www.medworm.com/index.php?rid=4406600&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789111000056%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406600 Fri, 28 Jan 2011 14:31:11 +0100 4406600 http://www.medworm.com/index.php?rid=4406602&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001298%2Fabstract%3Frss%3Dyes An overview of Personal Profiles can be found at http://www.moloncol.org. Ruedi Aebersold (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406602 Thu, 06 Jan 2011 00:00:00 +0100 4406602 http://www.medworm.com/index.php?rid=4406601&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001304%2Fabstract%3Frss%3Dyes Molecular Oncology is now entering into its fifth year of existence. Gone are the early days where the journal struggled to establish itself while finding the best possible way to implement the vision underlying its foundation. Molecular Oncology aims to provide the scientific community with a platform where scientists can show-case personal opinions as well as outreaching their original research to other scientists. The journal intends to serve readers not only by publishing state-of-the-art research, but also by providing a coherent body of reviews, often combined into thematic issues, planned to broadly and comprehensively address timely topics. We offer this topical content at no charge, either to authors or readers. Molecular Oncology also aims at influencing the political agenda in t... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406601 Mon, 27 Dec 2010 00:00:00 +0100 4406601 http://www.medworm.com/index.php?rid=4406608&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001262%2Fabstract%3Frss%3Dyes Abstract: The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes– Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by performing genome-wide scans of CpG methylation in breast cancer samples with known expression-based subtypes. Unsupervised hierarchical clustering using a set of most varying loci clustered the tumors into a Luminal A majority (82%) cluster, Basal-like/ErbB2+ majority (86%) cluster and a non-specific cluster with samples that were also inconclusive in their expression-based subtype correlations. Contributing methylation loci were both gene associated loci (30%) and non-g... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406608 Fri, 10 Dec 2010 00:00:00 +0100 4406608 http://www.medworm.com/index.php?rid=4406605&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001250%2Fabstract%3Frss%3Dyes Abstract: In recent years, our knowledge on estrogen receptors (ER) has been modified profoundly with the identification and the deciphering of the role of its protein effectors, as well as with the deeper insight of its molecular structure/function dynamics, characteristics associated with its nucleo-cytoplasmic-membrane shuttling properties. Also, significant progress has been made concerning its turn-over and associated final proteasomal degradation processes. These advances could lead in the near future to the design and the synthesis of novel receptor-interacting drugs. Recently, a number of receptor-related peptides acting as specific ER ligands have been identified and extensively studied with respect to their estrogenic/antiestrogenic activities. Among them, ERα17p, a synthetic a... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406605 Mon, 06 Dec 2010 00:00:00 +0100 4406605 http://www.medworm.com/index.php?rid=4406607&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001286%2Fabstract%3Frss%3Dyes Abstract: Breast cancer is a heterogeneous disease that can be divided in subtypes based on histology, gene expression profiles as well as differences in genomic aberrations. Distinct global DNA methylation profiles have been reported in normal breast epithelial cells as well as in breast tumors. However, the influence of the tumor methylome on the previously described subgroups of breast cancer is not fully understood. Here we report the DNA methylation profiles of 80 breast tumors using a panel of 807 cancer related genes interrogating 1505 CpG sites. We identified three major clusters based on the methylation profiles; one consisting of mainly tumors of myoepithelial origin and two other clusters with tumors of predominantly luminal epithelial origin. The clusters were different with re... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406607 Fri, 03 Dec 2010 00:00:00 +0100 4406607 http://www.medworm.com/index.php?rid=4406603&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001274%2Fabstract%3Frss%3Dyes Abstract: Breast cancer is a heterogeneous disease in terms of histology, therapeutic response, dissemination patterns to distant sites, and patient outcomes. Global gene expression analyses using high-throughput technologies have helped to explain much of this heterogeneity and provided important new classifications of cancer patients. In the last decade, genomic studies have established five breast cancer intrinsic subtypes (Luminal A, Luminal B, HER2-enriched, Claudin-low, Basal-like) and a Normal Breast-like group. In this review, we dissect the most recent data on this genomic classification of breast cancer with a special focus on the Claudin-low subtype, which appears enriched for mesenchymal and stem cell features. In addition, we discuss how the combination of standard clinical-pa... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406603 Wed, 01 Dec 2010 00:00:00 +0100 4406603 http://www.medworm.com/index.php?rid=4168471&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001171%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4168471 Tue, 16 Nov 2010 04:49:07 +0100 4168471 http://www.medworm.com/index.php?rid=4168463&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001110%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4168463 Tue, 16 Nov 2010 04:49:05 +0100 4168463 http://www.medworm.com/index.php?rid=4406604&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001079%2Fabstract%3Frss%3Dyes We report that MAPK activation by RET2A leads to a transient induction of N-Myc mRNA and protein levels, and that N-Myc induction is required to maintain low p18 and p27 levels. Induced N-Myc levels correlate with increased binding of N-Myc to an initiator consensus binding site in the p18 promoter, and this binding is essential for RET2A-mediated transcriptional regulation of p18. Finally, loss of N-Myc induction prevents RET2A-mediated hyperproliferation. Our results demonstrate for the first time that N-Myc is a downstream target of RET2A signaling, and propose that induction of N-Myc by RET2A is a key step leading to lower p18 levels during MEN2A tumorigenesis. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406604 Mon, 15 Nov 2010 00:00:00 +0100 4406604 http://www.medworm.com/index.php?rid=4406610&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001055%2Fabstract%3Frss%3Dyes We examined the composition of the Chromosomal Passenger Complex (CPC) at various mitotic phases and after chemical treatments using is-PLA with antibodies against the core CPC subunits Aurora B, INCENP, Survivin and Borealin. Our results support the notion that the core CPC functions as a single structural unit at centromeres in early mitosis and at central spindle after the onset of anaphase. Treatment of cells with the Aurora B inhibitor ZM447439 diminished the is-PLA signals at centromeres suggesting that Aurora B activity contributes to structural maintenance and/or proper subcellular localization of the core CPC. Is-PLA-based analysis of interaction between INCENP and Polo-like kinase 1 (Plk1) proposes that the kinase co-travels with CPC during late mitosis. The data illustrates both... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406610 Mon, 25 Oct 2010 00:00:00 +0100 4406610 http://www.medworm.com/index.php?rid=4406609&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001067%2Fabstract%3Frss%3Dyes Abstract: Background: Although imatinib mesylate has revolutionized the management of patients with gastrointestinal stromal tumor (GIST), resistance and progression almost inevitably develop with long-term monotherapy. To enhance imatinib-induced cytotoxicity and overcome imatinib-resistance in GIST cells, we examined the antitumor effects of the pro-apoptotic Bcl-2/Bcl-xL inhibitor ABT-737, alone and in combination with imatinib.Methods: We treated imatinib-sensitive, GIST-T1 and GIST882, and imatinib-resistant cells with ABT-737 alone and with imatinib. We determined the anti-proliferative and apoptotic effects by cell viability assay, flow cytometric apoptosis and cell cycle analysis, immunoblotting, and nuclear morphology. Synergism was determined by isobologram analysis.Results: The ... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406609 Mon, 25 Oct 2010 00:00:00 +0100 4406609 http://www.medworm.com/index.php?rid=4168465&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001018%2Fabstract%3Frss%3Dyes Abstract: Individualizing cancer therapy for molecular targeted inhibitors requires a new class of molecular profiling technology that can map the functional state of the cancer cell signal pathways containing the drug targets. Reverse phase protein microarrays (RPMA) are a technology platform designed for quantitative, multiplexed analysis of specific phosphorylated, cleaved, or total (phosphorylated and non-phosphorylated) forms of cellular proteins from a limited amount of sample. This class of microarray can be used to interrogate tissue samples, cells, serum, or body fluids. RPMA were previously a research tool; now this technology has graduated to use in research clinical trials with clinical grade sensitivity and precision. In this review we describe the application of RPMA for mult... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4168465 Thu, 21 Oct 2010 00:00:00 +0100 4168465 http://www.medworm.com/index.php?rid=4168464&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001043%2Fabstract%3Frss%3Dyes Cancer represents one of the major global health concerns affecting the human race today. It affects developing as well as developed nations, and the situation is set to deteriorate worldwide as the global burden of cancer is expected to increase with the continuing growth and ageing of the world's population (). To date, there have been substantial advances in basic cancer research which have led to a better understanding of the biological processes underlying disease pathogenesis, a development that has been prompted by the explosive growth in the number of novel high-throughput technologies available for the analysis of genes and their products. We no longer examine the behavior of one single gene or protein but rather scrutinize changes – mRNA, miRNA, polymorphisms, and whatnot - at... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4168464 Thu, 21 Oct 2010 00:00:00 +0100 4168464 http://www.medworm.com/index.php?rid=4168470&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001031%2Fabstract%3Frss%3Dyes Abstract: Our limited understanding of the biological impact of the whole spectrum of early breast lesions together with a lack of accurate molecular-based risk criteria for the diagnosis and assignment of prognostic significance to biopsy findings presents an important problem in the clinical management of patients harboring precancerous breast lesions. As a result, there is a need to identify biomarkers that can better determine the outcome of early breast lesions by identifying subpopulations of cells in breast premalignant disease that are at high-risk of progression to invasive disease. A first step towards achieving this goal will be to define the molecular phenotypes of the various cell types and precursors – generated by the stem cell hierarchy – that are present in normal and ... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4168470 Mon, 18 Oct 2010 00:00:00 +0100 4168470 http://www.medworm.com/index.php?rid=4168469&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110001006%2Fabstract%3Frss%3Dyes Abstract: MALDI Imaging Mass Spectrometry is a molecular analytical technology capable of simultaneously measuring multiple analytes directly from intact tissue sections. Histological features within the sample can be correlated with molecular species without the need for target-specific reagents such as antibodies. Several studies have demonstrated the strength of the technology for uncovering new markers that correlate with disease severity as well as prognosis and therapeutic response. This review describes technological aspects of imaging mass spectrometry together with applications in cancer research. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4168469 Mon, 04 Oct 2010 00:00:00 +0100 4168469 http://www.medworm.com/index.php?rid=4168466&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911000102X%2Fabstract%3Frss%3Dyes Abstract: Reversible protein phosphorylation serves as a basis for regulating a number of cellular processes. Aberrant activation of kinase signaling pathways is commonly associated with several cancers. Recent developments in phosphoprotein/phosphopeptide enrichment strategies and quantitative mass spectrometry have resulted in robust pipelines for high-throughput characterization of phosphorylation in a global fashion. Today, it is possible to profile site-specific phosphorylation events on thousands of proteins in a single experiment. The potential of this approach is already being realized to characterize signaling pathways that govern oncogenesis. In addition, chemical proteomic strategies have been used to unravel targets of kinase inhibitors, which are otherwise difficult to charact... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4168466 Mon, 04 Oct 2010 00:00:00 +0100 4168466 http://www.medworm.com/index.php?rid=4168467&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000979%2Fabstract%3Frss%3Dyes Abstract: Emerging proteomic tools and mass spectrometry play pivotal roles in protein identification, quantification and characterization, even in complex biological samples. The cancer secretome, namely the whole collection of proteins secreted by cancer cells through various secretory pathways, has only recently been shown to have significant potential for diverse applications in oncoproteomics. For example, secreted proteins might represent putative tumor biomarkers or therapeutic targets for various types of cancer. Consequently, many proteomic strategies for secretome analysis have been extensively deployed over the last few years. These efforts generated a large amount of information awaiting deeper mining, better understanding and careful interpretation. Distinct sub-fields, such a... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4168467 Fri, 17 Sep 2010 00:00:00 +0100 4168467 http://www.medworm.com/index.php?rid=3966474&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000876%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3966474 Wed, 15 Sep 2010 05:22:11 +0100 3966474 http://www.medworm.com/index.php?rid=4168468&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000967%2Fabstract%3Frss%3Dyes Abstract: Nanotechnology has enabled a renaissance in the diagnosis of cancers. This is due, in part to the ability to develop agents bearing multiple functionalities, including those utilized for targeting, imaging, and therapy, allowing for the tailoring of the properties of the nanomaterials. Whereas many nanomaterials exhibit localization to diseased tissues via intrinsic targeting, the addition of targeting ligands, such as antibodies, peptides, aptamers, and small molecules, facilitates far more sensitive cancer detection. As such, this review focuses upon some of the most poignant examples of the utility of affinity ligand targeted nanoagents in the detection of cancer. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4168468 Thu, 09 Sep 2010 00:00:00 +0100 4168468 http://www.medworm.com/index.php?rid=4406606&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000839%2Fabstract%3Frss%3Dyes Abstract: Many tissue kallikrein (KLK) genes and proteins are candidate diagnostic, prognostic and predictive biomarkers for ovarian cancer (OCa). We previously demonstrated that the KLK locus (19q13.3/4) is subject to copy-number gains and structural rearrangements in a pilot study of cell lines and ovarian cancer primary tissues, shown to overexpress KLK gene family members. To determine the overall frequency of genomic instability and copy-number changes, a retrospective study was conducted using formalin-fixed paraffin embedded (FFPE) tissues. Eighty-one chemotherapy naïve serous OCas were examined using 3-colour fluorescence in situ hybridization (FISH) to identify structural and numerical changes on 19q, including the KLK locus; in addition to immunohistochemistry (IHC) for KLK6... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=4406606 Wed, 18 Aug 2010 00:00:00 +0100 4406606 http://www.medworm.com/index.php?rid=3966480&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000827%2Fabstract%3Frss%3Dyes Abstract: Brain tumors, which are typically very heterogeneous at the cellular level, appear to have a stem cell foundation. Recently, investigations from multiple groups have found that human as well as experimental mouse brain tumors contain subpopulations of cells that functionally behave as tumor stem cells, driving tumor growth and generating tumor cell progeny that form the tumor bulk, but which then lose tumorigenic ability. In human glioblastomas, these tumor stem cells express neural precursor markers and are capable of differentiating into tumor cells that express more mature neural lineage markers. In addition, modeling brain tumors in mice suggests that neural precursor cells more readily give rise to full blown tumors, narrowing potential cells of origin to those rarer brain c... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3966480 Sun, 15 Aug 2010 23:00:00 +0100 3966480 http://www.medworm.com/index.php?rid=3824716&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000669%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3824716 Sat, 31 Jul 2010 23:00:00 +0100 3824716 http://www.medworm.com/index.php?rid=3966475&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000621%2Fabstract%3Frss%3Dyes Since the declaration of war on cancer some four decades ago, there has been an exponential growth in our understanding of the genetic and cellular mechanisms that contribute to cancer. As a consequence, a number of revolutionary drugs such as imatinib and trastuzumab have emerged, representing the first wave in a new era of targeted therapy. However, the range of new weapons with a proven track record in targeting cancer is surprisingly limited, highlighting the need for new approaches to improve cancer treatment and outcomes. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3966475 Tue, 27 Jul 2010 23:00:00 +0100 3966475 http://www.medworm.com/index.php?rid=3966477&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911000061X%2Fabstract%3Frss%3Dyes Abstract: Tissue stem cells have been linked to cancers of epithelial origin including the prostate. There are three relevant issues concerning stem cells and cancer that rely solely on functional studies: 1. Are there tissue-regenerating stem cells in the adult organ? 2. Can tissue-regenerating cells serve as targets for transformation? 3. Do primary tumors contain tumor-propagating (cancer stem) cells? We will review the recent literature with respect to these critical issues to provide a direct link between primitive cells and prostate cancer. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3966477 Thu, 22 Jul 2010 23:00:00 +0100 3966477 http://www.medworm.com/index.php?rid=3824723&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000591%2Fabstract%3Frss%3Dyes Abstract: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT-PCR was used for validation. All DCIS and invasive samples could be classified into the “intrinsic” molecular subtypes defined for invasive breast cancer. H... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3824723 Sun, 04 Jul 2010 23:00:00 +0100 3824723 http://www.medworm.com/index.php?rid=3824717&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000608%2Fabstract%3Frss%3Dyes An overview of Personal Profiles can be found at http://www.moloncol.org. Carlo M. Croce (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3824717 Sun, 04 Jul 2010 23:00:00 +0100 3824717 http://www.medworm.com/index.php?rid=3966483&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000542%2Fabstract%3Frss%3Dyes Abstract: Melanoma, like most cancers, is a disease that wreaks havoc mostly through its propensity to spread and establish secondary tumors at sites that are anatomically distant from the primary tumor. The consideration of models of cancer progression is therefore important to understand the essence of this disease. Previous work has suggested that melanoma may propagate according to a cancer stem cell (CSC) model in which rare tumorigenic and bulk non-tumorigenic cells are organized into stable hierarchies within tumors. However, recent studies using assays that are more permissive for revealing tumorigenic potential indicate that it will not be possible to cure patients by focusing research and therapy on rare populations of cells within melanoma tumors. Studies of the nature of tumori... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3966483 Thu, 01 Jul 2010 23:00:00 +0100 3966483 http://www.medworm.com/index.php?rid=3966479&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000517%2Fabstract%3Frss%3Dyes Abstract: The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self-renewing cell populations that constitute the bulk of the tumor. Although, the CSC hypothesis does not directly address the cell of origin of cancer, it is postulated that tissue-resident stem or progenitor cells are the most common targets of transformation. Clinically, CSCs are predicted to mediate tumor recurrence after chemo- and radiation-therapy due to the relative inability of these modalities to effectively target CSCs. If this is the case, then CSC must be efficiently targeted to achieve a true cure. Similarities between normal and malignant stem cells, at the levels of cell-surface proteins, molecular pathway... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3966479 Wed, 23 Jun 2010 23:00:00 +0100 3966479 http://www.medworm.com/index.php?rid=3824722&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000505%2Fabstract%3Frss%3Dyes Abstract: Elevated cyclooxygenase-2 (COX-2) expression is observed in a variety of premalignant neoplastic tissues, suggesting COX-2 expression might serve as a potential indicator of subsequent tumor development. However, it has not been possible to compare the relationship between Cox-2 gene expression in premalignant lesions and their subsequent fate, because conventional studies require tissue destruction for analysis of gene expression. To monitor COX-2 expression non-invasively during tumor development, we created a Cox-2 luciferase knock-in mouse, Cox-2luc, in which the firefly luciferase coding region replaces the Cox-2 coding region. Luciferase activity was non-invasively, quantitatively and repeatedly monitored in Cox-2luc/+ mice subjected to DMBA/TPA multistage skin tumor induct... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3824722 Tue, 22 Jun 2010 23:00:00 +0100 3824722 http://www.medworm.com/index.php?rid=3824719&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000499%2Fabstract%3Frss%3Dyes Abstract: The role of acquired chromosomal rearrangements in oncogenesis (cytogenomics) and tumor progression is now well established. These alterations are multiple and diverse and the products of these rearranged genes play an essential role in the transformation and growth of cancer cells. The validity of this assumption is demonstrated by the development of specific inhibitors or antibodies that eliminate tumoral cells by targeting some of these changes. Imatinib, an inhibitor of the tyrosine kinase ABL, the prototype of these targeting drugs, is yielding complete remissions in most CML patients. Knowledge of chromosomal abnormalities is becoming an essential contribution to the diagnosis and prognosis of cancers but also for monitoring minimal residual disease or relapse. The concept ... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3824719 Sun, 20 Jun 2010 23:00:00 +0100 3824719 http://www.medworm.com/index.php?rid=3966481&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000487%2Fabstract%3Frss%3Dyes Abstract: Solid tumours are the most common cancers and represent a major therapeutic challenge. The cancer stem cell hypothesis is an attractive model to explain the functional heterogeneity commonly observed in solid tumours. It proposes a hierarchical organization of tumours, in which a subpopulation of stem cell-like cells sustains tumour growth, metastasis, and resistance to therapy. We will present the most recent advances in the cancer stem cell field, with particular emphasis on pancreatic cancer as one of the deadliest human tumours, and highlight open questions and caveats to be addressed in future studies. There is increasing evidence that solid tumours including pancreatic cancer are hierarchically organized and sustained by a distinct subpopulation of cancer stem cells. Howeve... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3966481 Tue, 15 Jun 2010 23:00:00 +0100 3966481 http://www.medworm.com/index.php?rid=3966482&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000475%2Fabstract%3Frss%3Dyes Abstract: Transient or long-term quiescence, the latter referred to as dormancy are fundamental features of at least some adult stem cells. The status of dormancy is likely a critical mechanism for the observed resistance of normal HSCs and leukemic stem cells (LSCs) to anti-proliferative chemotherapy. Recent studies have revealed cytokines such as Interferon-alpha (IFNα) and G-CSF as well as arsenic trioxide (As2O3) to be efficient agents for promoting cycling of dormant HSCs and LSCs. Most interestingly, such cell cycle activated stem cells become exquisitely sensitive to killing by different chemotherapeutic agents, suggesting that dormant LSCs in patients may be targeted by a sequential two-step protocol involving an initial activation by IFNα, G-CSF or As2O3, followed by targeted ch... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3966482 Sun, 13 Jun 2010 23:00:00 +0100 3966482 http://www.medworm.com/index.php?rid=3966478&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000359%2Fabstract%3Frss%3Dyes Abstract: Lung cancer is a devastating disease and a major therapeutic burden with poor survival rates. The discovery of rare cells with stem cell-like properties in solid tumours is emerging as an important area of cancer research and may help explain the resistance of these tumours to current therapeutics. Despite rapid developments in cancer stem cell research in other solid tumours, progress in the lung has been hampered by an incomplete understanding of the epithelial stem cell hierarchy, the heterogeneity of disease and the lack of a suitable in vivo transplantation model to assess stem cell behaviour. In this review we critically discuss what is currently known about the role of normal stem cells and cancer-initiating cells in lung tumour development, and briefly discuss strategies ... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3966478 Sun, 13 Jun 2010 23:00:00 +0100 3966478 http://www.medworm.com/index.php?rid=3966476&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000347%2Fabstract%3Frss%3Dyes Abstract: Cancer in the 21st century has become the number one cause of death in developed countries. Although much progress has been made in improving patient survival, tumour relapse is one of the important causes of cancer treatment failure. An early observation in the study of cancer was the heterogeneity of tumours. Traditionally, this was explained by a combination of genomic instability of tumours and micro environmental factors leading to diverse phenotypical characteristics. It was assumed that cells in a tumour have an equal capacity to propagate the cancer. This model is currently known as the stochastic model. Recently, the Cancer stem cell model has been proposed to explain the heterogeneity of a tumour and its progression. According to this model, the heterogeneity of tumours... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3966476 Sun, 13 Jun 2010 23:00:00 +0100 3966476 http://www.medworm.com/index.php?rid=3703908&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000396%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703908 Mon, 31 May 2010 23:00:00 +0100 3703908 http://www.medworm.com/index.php?rid=3703910&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000335%2Fabstract%3Frss%3Dyes Abstract: Genetic and lifestyle/environmental factors are implicated in the aetiology of breast cancer. This review summarizes the current state of knowledge on rare high penetrance mutations, as well as moderate and low-penetrance genetic variants implicated in breast cancer aetiology. We summarize recent discoveries from large collaborative efforts to combine data from candidate gene studies, and to conduct genome-wide association studies (GWAS), primarily in breast cancers in the general population. These findings are compared with results from collaborative efforts aiming to identify genetic modifiers in BRCA1 and BRCA2 carriers. Breast cancer is a heterogeneous disease, and tumours from BRCA1 and BRCA2 carriers display distinct pathological characteristics when compared with tumours u... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703910 Sun, 30 May 2010 23:00:00 +0100 3703910 http://www.medworm.com/index.php?rid=3703916&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000323%2Fabstract%3Frss%3Dyes Abstract: Defining the pathways through which tumors progress is critical to our understanding and treatment of cancer. We do not routinely sample patients at multiple time points during the progression of their disease, and thus our research is limited to inferring progression a posteriori from the examination of a single tumor sample. Despite this limitation, inferring progression is possible because the tumor genome contains a natural history of the mutations that occur during the formation of the tumor mass. There are two approaches to reconstructing a lineage of progression: (1) inter-tumor comparisons, and (2) intra-tumor comparisons. The inter-tumor approach consists of taking single samples from large collections of tumors and comparing the complexity of the genomes to identify ear... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703916 Wed, 12 May 2010 23:00:00 +0100 3703916 http://www.medworm.com/index.php?rid=3703914&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000244%2Fabstract%3Frss%3Dyes Abstract: Epigenetic changes can be defined as stable molecular alterations of a cellular phenotype such as the gene expression profile of a cell that are heritable during somatic cell divisions (and sometimes germ line transmissions) but do not involve changes of the DNA sequence itself. Epigenetic phenomena are mediated by several molecular mechanisms comprising histone modifications, polycomb/trithorax protein complexes, small non-coding or antisense RNAs and DNA methylation. These different modifications are closely interconnected. Epigenetic regulation is critical in normal growth and development and closely conditions the transcriptional potential of genes. Epigenetic mechanisms convey genomic adaption to an environment thereby ultimately contributing towards given phenotype. In this... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703914 Sun, 09 May 2010 23:00:00 +0100 3703914 http://www.medworm.com/index.php?rid=3703913&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000311%2Fabstract%3Frss%3Dyes Abstract: Micro-RNAs (miRs) are a recently described class of genes, encoding small non-coding RNA molecules, which primarily act by down-regulating the translation of target mRNAs. miRs are involved in a range of normal physiological processes, notably differentiation and cell type determination. It has become apparent that they are also key factors in cancer, playing both oncogenic and tumour-suppressing roles. We discuss here what is known of miR biology in the normal breast, and of their emerging roles in breast cancer. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703913 Sun, 09 May 2010 23:00:00 +0100 3703913 http://www.medworm.com/index.php?rid=3824721&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911000030X%2Fabstract%3Frss%3Dyes Abstract: The KIT mutation D816V is associated with autonomous growth of mast cells (MC) and is detectable in most patients with systemic mastocytosis (SM), including cases with associated hematologic non-MC-lineage disease (AHNMD). Recently, KIT D816V was reported to be expressed in patients with acute myeloid leukemia (AML). However, it was not clarified whether these patients have co-existing occult SM. We investigated neoplastic cells in 101 patients with AML for expression of KIT D816V. In 7/101 patients (6.9%), KIT D816V was detectable. After a thorough histologic, molecular, and biochemical analysis, all 7 cases were found to have an associated SM, leading to the final diagnosis SM-AML. Microdissected tryptase+ MC displayed KIT D816V in all patients tested, whereas CD34+ blasts exhi... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3824721 Sun, 02 May 2010 23:00:00 +0100 3824721 http://www.medworm.com/index.php?rid=3703917&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478911000027X%2Fabstract%3Frss%3Dyes Abstract: Chemoresistance remains the main reason for therapeutic failure in breast cancer as well as most other solid tumours. While gene expression profiles related to prognosis have been developed, so far use of such signatures as well as single markers has been of limited value predicting drug resistance. Novel technologies, in particular with regard to high through-put sequencing holds great promises for future identification of the key “driver” mechanisms guiding chemosensitivity versus resistance in breast cancer as well as other malignant conditions. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703917 Sun, 02 May 2010 23:00:00 +0100 3703917 http://www.medworm.com/index.php?rid=3703912&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000281%2Fabstract%3Frss%3Dyes Abstract: Triple-negative breast cancers (TNBC), characterized by absence of estrogen receptor (ER), progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), are typically associated with poor prognosis, due to aggressive tumor phenotype(s), only partial response to chemotherapy and present lack of clinically established targeted therapies. Advances in the design of individualized strategies for treatment of TNBC patients require further elucidation, by combined ‘omics’ approaches, of the molecular mechanisms underlying TNBC phenotypic heterogeneity, and the still poorly understood association of TNBC with BRCA1 mutations. An overview is here presented on TNBC profiling in terms of expression signatures, within the functional genomic bre... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703912 Sun, 02 May 2010 23:00:00 +0100 3703912 http://www.medworm.com/index.php?rid=3703909&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000293%2Fabstract%3Frss%3Dyes Breast cancer (BC), like all cancers is considered to be a genetic disease in the sense that both germline and somatic mutations may be the cause of tumour initiation and development. Our molecular understanding of the role of cancer associated genes and gene products has evolved over the past 20 years. Some gene mutations are linked to inherited cancer syndromes, while other genetic alterations have been found to be associated with certain morphological stages. Furthermore, the type and location of mutations in certain genes have been associated with response to therapy and poor disease outcome. Although part of the genetic «makeup» of patients with elevated cancer risk has been identified, as well as part of the genetic «makeup» of primary breast carcinomas, several issues remain unr... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703909 Sun, 02 May 2010 23:00:00 +0100 3703909 http://www.medworm.com/index.php?rid=3703911&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000268%2Fabstract%3Frss%3Dyes Abstract: Breast cancer is a heterogeneous disease, comprising multiple entities associated with distinctive histological and biological features, clinical presentations and behaviours and responses to therapy. Microarray-based technologies have unravelled the molecular underpinning of several characteristics of breast cancer, including metastatic propensity and histological grade, and have led to the identification of prognostic and predictive gene expression signatures. Furthermore, a molecular taxonomy of breast cancer based on transcriptomic analysis has been proposed. However, microarray studies have primarily focused on invasive ductal carcinomas of no special type. Owing to the relative rarity of special types of breast cancer, information about the biology and clinical behaviour of... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703911 Sun, 25 Apr 2010 23:00:00 +0100 3703911 http://www.medworm.com/index.php?rid=3703915&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000232%2Fabstract%3Frss%3Dyes Abstract: Breast cancer is a heterogeneous disease, appreciable by molecular markers, gene-expression profiles, and most recently, patterns of genomic alteration. In particular, genomic profiling has revealed three distinct patterns of DNA copy-number alteration: a “simple” type with few gains or losses of whole chromosome arms, an “amplifier” type with focal high-level DNA amplifications, and a “complex” type marked by numerous low-amplitude changes and copy-number transitions. The three patterns are associated with distinct gene-expression subtypes, and preferentially target different loci in the genome (implicating distinct cancer genes). Moreover, the different patterns of alteration imply distinct underlying mechanisms of genomic instability. The amplifier pattern may aris... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703915 Mon, 19 Apr 2010 23:00:00 +0100 3703915 http://www.medworm.com/index.php?rid=3703918&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000220%2Fabstract%3Frss%3Dyes As much training as a physician has in the complexities and nuances of a disease like cancer, nothing can prepare them for the labyrinthine rules and twisted economics that occur at the hazy crossroads where pharmaceutical manufacturers and insurance companies meet. Nowhere is this more true than in America, which is the world's most important single market for drugs, as well as it's most expensive. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3703918 Wed, 24 Mar 2010 00:00:00 +0100 3703918 http://www.medworm.com/index.php?rid=3824720&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000207%2Fabstract%3Frss%3Dyes Abstract: Activated Cdc42-associated Kinase, ACK1, is a non-receptor tyrosine kinase with numerous interacting partners, including Cdc42 and EGFR. Gene amplification and overexpression of ACK1 were found in many cancer types such as those of the lung and prostate. Previously, we identified both somatic- and germ line missense mutations in the ACK1 coding sequence, by surveying 261 cancer cell lines and 15 control tissues. Here, we verified and characterized the non-synonymous mutation, ACK-S985 N, located in the ubiquitin association domain of the protein.Both overexpression and silencing experiments in MCF7 and A498 cells, respectively, demonstrated a role of the ACK1 S985 N mutation in enhancing cell proliferation, migration and anchorage-independent growth as well as the epithelial–me... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3824720 Mon, 22 Mar 2010 00:00:00 +0100 3824720 http://www.medworm.com/index.php?rid=3824718&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000219%2Fabstract%3Frss%3Dyes Abstract: We document an EGFR mutation in a patient with papillary renal cell cancer with a history of multiple therapies, including interferon-alfa, interleukin-2, 5-fluorouracil, and interferon-alfa together with 13-cis-retinoic acid, to which floxuridine was later added, and thalidomide maintenance therapy for six years. We provide a succinct review of the PubMed-derived literature on EGFR mutations in diverse tumors, which indicates that a subset of patients with various tumor types may harbor EGFR mutations. A 32-year old woman with sporadic, metastatic papillary renal cancer was found to harbor an EGFR kinase domain mutation in addition to the MET kinase mutation typically found in this disease. Since lung cancer patients with EGFR mutations often respond well to EGFR inhibitor thera... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3824718 Thu, 18 Mar 2010 00:00:00 +0100 3824718 http://www.medworm.com/index.php?rid=3367038&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000116%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3367038 Tue, 16 Mar 2010 13:51:56 +0100 3367038 http://www.medworm.com/index.php?rid=3367039&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000074%2Fabstract%3Frss%3Dyes In stage IV malignant melanoma four innovative new classes of treatment: immunotherapy, targeted treatments, anti angiogenesis agents and chemo ablation are transforming the landscape. The article reviews the progress reported at recent European meetings, and looks to a future where knowledge of the complete genome sequence of individual melanoma tumours may allow patients to be offered tailored treatments. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3367039 Fri, 19 Feb 2010 00:00:00 +0100 3367039 http://www.medworm.com/index.php?rid=3367043&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000050%2Fabstract%3Frss%3Dyes Abstract: Membrane-initiated androgen actions have now been acknowledged, even though a specific binding site has not been biochemically characterized yet. Recent data indicate that testosterone–BSA, a non-permeable testosterone analog, can exert specific actions in breast cancer cell lines, including proper transcriptional effects, independent of the intracellular androgen sites. In the present work we explore the effects of testosterone–BSA in two specifically modified pathways, revealed by early trascriptome analysis, namely the non-genotropic androgen signaling and the HIF1α pathway. We provide evidence that p38 MAPK and PI3K/Akt/NFκB and/or Rho/Actin pathways are directly involved in testosterone-induced apoptosis, while the JNK/c-JUN pathway is involved in membrane site-initiat... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3367043 Thu, 11 Feb 2010 00:00:00 +0100 3367043 http://www.medworm.com/index.php?rid=3367041&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000062%2Fabstract%3Frss%3Dyes In this study, we used 18F-FDG microPET and micro computerized tomography (microCT) to investigate glucose uptake in the DMBA/TPA chemically-induced multistage mouse skin carcinogenesis model. 18F-FDG uptake is significantly higher in all papillomas than in surrounding skin. Elevated 18F-FDG uptake is observed when tumors can be identified morphologically, but not before. Although 18F-FDG uptake is high in all fully invasive, malignant skin squamous cell carcinomas, uptake in papillomas and microinvasive malignant squamous cell carcinomas is variable and does not exhibit any correlation with tumor stage. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3367041 Thu, 11 Feb 2010 00:00:00 +0100 3367041 http://www.medworm.com/index.php?rid=3367046&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000049%2Fabstract%3Frss%3Dyes An unfortunate error occurred in the columns pT category and pN category of Supplemental Table 1. The corrected table can be found, in the online version, at doi:10.1016/j.molonc.2010.01.003. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3367046 Fri, 22 Jan 2010 00:00:00 +0100 3367046 http://www.medworm.com/index.php?rid=3367044&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000037%2Fabstract%3Frss%3Dyes We examined the production and secretion of VEGF(165) in various primary cancer cells derived from malignant effusions, and the role of exogenous VEGF165 as a mediator of effusion formation. VEGF165 was constantly secreted by all cultured tumor cells in an mTOR-dependent manner, as it was inhibited by the mTOR inhibitor rapamycin. Secreted VEGF165 showed functional activity by inducing endothelial leakiness and tumor cell-transendothelial migration in vitro, effects which could be reverted by the anti-VEGF antibody bevacizumab.Thus, mTOR inhibitors as well as bevacizumab should be considered as potential agents in cancer patients suffering from malignant effusions. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3367044 Fri, 15 Jan 2010 00:00:00 +0100 3367044 http://www.medworm.com/index.php?rid=3367042&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789110000025%2Fabstract%3Frss%3Dyes Abstract: The Prep1 homeodomain transcription factor is essential for embryonic development. 25% of hypomorphic Prep1i/i embryos, expressing the gene at 2% of the normal levels, survive pregnancy and live a normal-length life. Later in life, however, these mice develop spontaneous pre-tumoral lesions or solid tumors (lymphomas and carcinomas). In addition, transplantation of E14.5 fetal liver (FL) Prep1i/i cells into lethally irradiated mice induces lymphomas. In agreement with the above data, haploinsufficiency of a different Prep1-deficient (null) allele accelerates EμMyc lymphoma growth. Therefore Prep1 has a tumor suppressor function in mice.Immunohistochemistry on tissue micrroarrays (TMA) generated from three distinct human cohorts comprising a total of some 1000 human tumors reveal... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3367042 Wed, 13 Jan 2010 00:00:00 +0100 3367042 http://www.medworm.com/index.php?rid=3130578&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001446%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3130578 Thu, 31 Dec 2009 13:47:32 +0100 3130578 http://www.medworm.com/index.php?rid=3367040&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001550%2Fabstract%3Frss%3Dyes Abstract: Glycosylation is the stepwise procedure of covalent attachment of oligosaccharide chains to proteins or lipids, and alterations in this process have been associated with malignant transformation. Simultaneous analysis of the expression of all glycan-related genes clearly gives the advantage of enabling a comprehensive view of the genetic background of the glycobiological changes in cancer cells. Studies focusing on the expression of the whole glycome have now become possible, which prompted us to review the present knowledge on glycosylation in relation to breast cancer diagnosis and progression, in the light of available expression data from tumors and breast tissue of healthy individuals. We used various data resources to select a set of 419 functionally relevant genes involved... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3367040 Mon, 21 Dec 2009 00:00:00 +0100 3367040 http://www.medworm.com/index.php?rid=3130585&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001409%2Fabstract%3Frss%3Dyes Abstract: Breast cancer is by far the most common diagnosed form of cancer and the leading cause of cancer death in women today. Clinically useful biomarkers for early detection of breast cancer could lead to a significant reduction in mortality. Here we describe a detailed analysis using gel-based proteomics in combination with mass spectrometry and immunohistochemistry (IHC) of the tumour interstitial fluids (TIF) and normal interstitial fluids (NIF) collected from 69 prospective breast cancer patients. The goal of this study was to identify abundant cancer up-regulated proteins that are externalised by cells in the tumour microenvironment of most if not all these lesions. To this end, we applied a phased biomarker discovery research strategy to the analysis of these samples rather than ... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3130585 Fri, 04 Dec 2009 00:00:00 +0100 3130585 http://www.medworm.com/index.php?rid=3130584&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001392%2Fabstract%3Frss%3Dyes Abstract: Patients with locally advanced rectal cancer often receive preoperative radio-chemotherapy (RCT). The mechanisms of tumour response to radiotherapy are not understood. The aim of this study was to identify the effects of RCT on gene expression in rectal tumour and normal rectal tissue. For that purpose tissue samples from 21 patients with resectable adenocarcinomas were collected for use in whole genome-microarray based gene expression analysis. A factorial experimental design allowed us to determine the effect of RCT on tumour tissue alone by removing the effect of radiation on normal tissue. This resulted in 1327 differentially expressed genes in tumour tissue with p (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3130584 Fri, 27 Nov 2009 00:00:00 +0100 3130584 http://www.medworm.com/index.php?rid=3367045&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001380%2Fabstract%3Frss%3Dyes Abstract: Copy number changes in TOP2A have frequently been linked to ERBB2 (HER2) amplified breast cancers. To study this relationship, copy number changes of ERBB2 and TOP2A were investigated by fluorescence in situ hybridization (FISH) in two cell lines; one characterized by having amplification of both genes and the other by having amplification of ERBB2 and deletion of TOP2A. The characteristics are compared to findings on paired ERBB2 and TOP2A data from 649 patients with invasive breast cancer from a previously published biomarker study. The physical localization of FISH signals in metaphase spreads from cell lines showed that simultaneous amplification is not a simple co-amplification of a whole amplicon containing both genes. Most gene signals are translocated to abnormal marker c... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3367045 Thu, 26 Nov 2009 00:00:00 +0100 3367045 http://www.medworm.com/index.php?rid=2960399&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001252%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960399 Thu, 05 Nov 2009 13:48:49 +0100 2960399 http://www.medworm.com/index.php?rid=2960384&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001173%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960384 Thu, 05 Nov 2009 13:48:47 +0100 2960384 http://www.medworm.com/index.php?rid=3130582&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001318%2Fabstract%3Frss%3Dyes Abstract: This review analyzes the state of the art of targeted therapies for several tumors, starting from the paradigmatic example of Imatinib treatment in chronic myelogenous leukemia (CML). We discuss how rare tumors can be models for various mechanisms of receptor tyrosine kinase (RTK) activation, and provide the opportunity to develop new therapies also for more common cancer types. We discuss the activation of the downstream RTK effectors as further targets for therapies in colorectal cancer. Finally, we highlight how a novel multidimensional approach which adds an in silico dimension to the in vitro and in vivo approach, can predict clinical results. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3130582 Thu, 05 Nov 2009 00:00:00 +0100 3130582 http://www.medworm.com/index.php?rid=3130579&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001306%2Fabstract%3Frss%3Dyes Introducing the Presidential session, Julio E. Celis, chairman of the Policy Committee of ECCO and scientific director of the Institute of Cancer Biology at the Danish Cancer Society in Copenhagen, said that the main objective of the session was to provide a unified approach to cancer research in Europe. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3130579 Mon, 02 Nov 2009 00:00:00 +0100 3130579 http://www.medworm.com/index.php?rid=3130580&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001136%2Fabstract%3Frss%3Dyes The United States began its “war on cancer” with the National Cancer Act of 1971, which authorized the creation of a new kind of facility that would combine research, clinical work, community outreach, prevention strategies, and population studies. Today, there are 41 institutions across the country which have been designated Comprehensive Cancer Centers by the National Cancer Institute (NCI). (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3130580 Mon, 26 Oct 2009 00:00:00 +0100 3130580 http://www.medworm.com/index.php?rid=3130583&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001124%2Fabstract%3Frss%3Dyes Abstract: Cytotoxicity of the topoisomerase II (topoII) poison etoposide has been ascribed to the persistent covalent trapping of topoII in DNA cleavage complexes that become lethal as cells replicate their DNA. However, short term etoposide treatment also leads to subsequent cell death, suggesting that the lesions that lead to cytotoxicity arise rapidly and prior to the onset DNA replication. In the present study 1h treatment with 25μM etoposide was highly toxic and initiated a double-stranded DNA damage response as reflected by the recruitment of ATM, MDC1 and DNA-PKcs to γH2AX foci. While most DNA breaks were rapidly repaired upon withdrawal of the etoposide treatment, the repair machinery remained engaged in foci for at least 24h following withdrawal. TopoII siRNA ablation showed the... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3130583 Fri, 16 Oct 2009 00:00:00 +0100 3130583 http://www.medworm.com/index.php?rid=3130581&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001112%2Fabstract%3Frss%3Dyes We present a benchmark tool for scientific research organizations where, contrary to existing models, the group leader is placed in a central position within the organization. We used it in a pilot benchmark study involving six research institutions. Our study shows that data collection and data comparison based on this new tool can be achieved. It proved possible to compare relative performance and organizational characteristics and to generate suggestions for improvement for most participants. However, strict definitions of the parameters used for the benchmark and a thorough insight into the organization of each of the benchmark partners is required to produce comparable data and draw firm conclusions. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=3130581 Mon, 05 Oct 2009 00:00:00 +0100 3130581 http://www.medworm.com/index.php?rid=2960392&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001100%2Fabstract%3Frss%3Dyes Abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Active immunotherapies and molecules targeting tyrosine kinase receptors both offer new avenues for the treatment of NSCLC. Furthermore, their combinations or their administration along with standard treatments enlarges the potential for clinical benefit. Moreover, the discovery of biomarkers predicting the response to these new therapies should allow a better selection of patients susceptible to optimally benefit from these treatments. In this paper, we review the most promising active immunotherapies, antibodies and small molecules in the context of NSCLC management, focusing on compounds in phase III clinical development. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960392 Tue, 22 Sep 2009 00:00:00 +0100 2960392 http://www.medworm.com/index.php?rid=2960388&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001094%2Fabstract%3Frss%3Dyes Abstract: A paradigm shift in research culture is needed in order to set up the large ambitious trials needed to make personalised medicine a reality. Emma Wilkinson talks to the experts about the hurdles they face and what needs to change. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960388 Fri, 28 Aug 2009 00:00:00 +0100 2960388 http://www.medworm.com/index.php?rid=2960385&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001033%2Fabstract%3Frss%3Dyes An overview of Personal Profiles can be found at http://www.moloncol.org. Anton Berns Director of Research, The Netherlands Cancer Institute. Professor of Experimental Genetics of Inherited Diseases, University of Amsterdam. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960385 Fri, 07 Aug 2009 00:00:00 +0100 2960385 http://www.medworm.com/index.php?rid=2960397&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109001021%2Fabstract%3Frss%3Dyes Abstract: The number of relevant and well-characterized cell lines and xenograft models for studying human breast cancer are few, and may represent a limitation for this field of research. With the aim of developing new breast cancer model systems for in vivo studies of hormone dependent and independent tumor growth, progression and invasion, and for in vivo experimental therapy studies, we collected primary mammary tumor specimens from patients, and implanted them in immunodeficient mice. Primary tumor tissue from 29 patients with breast cancer was implanted subcutaneously with matrigel in SCID mice, in the presence of continuous release of estradiol. The tumors were transferred into new animals when reaching a diameter of 15mm and engrafted tumors were harvested for morphological and mol... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960397 Thu, 06 Aug 2009 00:00:00 +0100 2960397 http://www.medworm.com/index.php?rid=2960396&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478910900101X%2Fabstract%3Frss%3Dyes This study, therefore, for the first time documents permissiveness of lymphoma cells to oncolytic herpes viruses and introduces ELK as a suitable factor for predicting tumor susceptibility to these novel anticancer agents. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960396 Wed, 05 Aug 2009 00:00:00 +0100 2960396 http://www.medworm.com/index.php?rid=2960395&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000878%2Fabstract%3Frss%3Dyes Abstract: Transforming growth-interacting factor (TGIF) is a homeobox transcriptional repressor that has been implicated in holoprosencephaly and various types of cancer. TGIF is expressed in hematopoietic stem cells and modulates TGF-β and retinoic acid (RA) signaling, both of which play an important role in hematopoiesis. We recently reported that TGIF's levels correlate inversely with survival in patients with acute myelogenous leukemia. Here we present the first direct evidence of a role for TGIF in myelopoiesis. We used short hairpin RNA interference to define the effects of TGIF knockdown on proliferation and differentiation of myeloid leukemia-derived cell lines. Decreased TGIF expression resulted in reduced proliferation and differentiation and lower expression of CEBPβ, CEBPε, ... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960395 Wed, 05 Aug 2009 00:00:00 +0100 2960395 http://www.medworm.com/index.php?rid=2664740&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000969%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2664740 Fri, 31 Jul 2009 23:00:00 +0100 2664740 http://www.medworm.com/index.php?rid=2664731&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS157478910900091X%2Fabstract%3Frss%3Dyes (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2664731 Fri, 31 Jul 2009 23:00:00 +0100 2664731 http://www.medworm.com/index.php?rid=2960394&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000866%2Fabstract%3Frss%3Dyes Abstract: c-Src non-receptor tyrosine kinase is an important component of the platelet-derived growth factor (PDGF) receptor signaling pathway. c-Src has been shown to mediate the mitogenic response to PDGF in fibroblasts. However, the exact components of PDGF receptor signaling pathway mediated by c-Src remain unclear. Here, we used stable isotope labeling with amino acids in cell culture (SILAC) coupled with mass spectrometry to identify Src-family kinase substrates involved in PDGF signaling. Using SILAC, we were able to detect changes in tyrosine phosphorylation patterns of 43 potential c-Src kinase substrates in PDGF receptor signaling. This included 23 known c-Src kinase substrates, of which 16 proteins have known roles in PDGF signaling while the remaining 7 proteins have not previo... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960394 Fri, 17 Jul 2009 00:00:00 +0100 2960394 http://www.medworm.com/index.php?rid=2960387&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000854%2Fabstract%3Frss%3Dyes The pursuit of excellence has been a dominant theme in the career of Fotis Kafatos, a distinguished malaria researcher, who is now taking his high standards forward in providing support for the very brightest young scientists in Europe, as part of his presidency of The European Research Council. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960387 Mon, 13 Jul 2009 00:00:00 +0100 2960387 http://www.medworm.com/index.php?rid=2960389&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000842%2Fabstract%3Frss%3Dyes In order to make progress in cancer research in the coming years, it's important first to understand the greatest hurdles standing in the way of federal funding for cancer research. From a patient's perspective, the media, for one thing, does a very poor job of educating and serving the public about cancer issues. The media tends to cover cancer when it strikes a celebrity. The problem is that the coverage is all human interest, and sometimes assumes the character of a death watch. I heard a cable news anchor, who lost a sister-in-law to breast cancer, explains how her producers almost never wanted to do stories related to cancer unless a celebrity was involved. Thus, TV, radio, newspapers, and blogs all fail to focus on substantive issues in cancer research including the lack of funding f... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2960389 Mon, 06 Jul 2009 00:00:00 +0100 2960389 http://www.medworm.com/index.php?rid=2664734&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000829%2Fabstract%3Frss%3Dyes Abstract: Signal transduction along the Ras/MAPK pathway has been generally thought to take place at the plasma membrane. It is now evident that the plasma membrane is not the only platform capable of Ras/MAPK signal induction. Fusion of Ras with green fluorescent protein and the development of genetically encoded fluorescent probes for Ras activation have revealed signaling events on a variety of intracellular membranes including endosomes, the Golgi apparatus and the endoplasmic reticulum. Thus, the Ras/MAPK pathway is spatially compartmentalized within cells and this may afford greater complexity of signal output. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2664734 Wed, 01 Jul 2009 23:00:00 +0100 2664734 http://www.medworm.com/index.php?rid=2664732&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000830%2Fabstract%3Frss%3Dyes Any encyclopedia definition of “Endocytosis” will include statements such as “eukaryotic cells use endocytosis to internalize plasma membrane, surface receptors and their bound ligands, nutrients, bacterial toxins, immunoglobulins, viruses, and various extracellular soluble molecules” (). In other words, the canonical view of endocytosis has, for a long time, been that of a process designed to bring nutrients and/or other types of molecules inside the cell and, at the same time, to regulate the composition of the plasma membrane. Of course, endocytosis does all of this, and more… much more. The approaches that are being used to define molecular and biological details of all these “mores” constitute the leitmotif that unites the contributions included in this thematic issue of... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2664732 Wed, 01 Jul 2009 23:00:00 +0100 2664732 http://www.medworm.com/index.php?rid=2664735&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000805%2Fabstract%3Frss%3Dyes Abstract: Although endocytosis has traditionally been understood as a signal attenuation mechanism, an emerging view considers endocytosis as an integral part of signal propagation and processing. On the short time scale, trafficking of endocytic vesicles contributes to signal propagation from the surface to distant targets, with bi-directional communication between signalling and trafficking. Mathematical modelling helps combine the mechanistic, molecular knowledge with rigorous analysis of the complex output dynamics of endocytosis in time and space. Simulations reveal novel roles for endocytosis, including the control of cell polarity, enhancing the spatial signal propagation, and controlling the signal magnitudes, kinetics, and synchronization with stimulus dynamics. (Source: Molecular... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2664735 Sun, 28 Jun 2009 23:00:00 +0100 2664735 http://www.medworm.com/index.php?rid=2664736&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000817%2Fabstract%3Frss%3Dyes Abstract: Accumulating evidence argues that many proteins governing membrane sorting during endocytosis participate also in nuclear signaling and transcriptional regulation, mostly by modulating the activity of various nuclear factors. Some adaptors and accessory proteins acting in clathrin-mediated internalization, as well as endosomal sorting proteins can undergo nuclear translocation and affect gene expression directly, while for others the effects may be more indirect. Although it is often unclear to what extent the endocytic and nuclear functions are interrelated, several of such proteins are implicated in the regulation of cell proliferation and tumorigenesis, arguing that their dual-function nature may be of physiological importance. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2664736 Sun, 21 Jun 2009 23:00:00 +0100 2664736 http://www.medworm.com/index.php?rid=2664733&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000787%2Fabstract%3Frss%3Dyes Abstract: Endocytosis and recycling are essential components of the wiring enabling cells to perceive extracellular signals and transduce them in a temporally and spatially controlled fashion, directly influencing not only the duration and intensity of the signaling output, but also their correct location. Here, we will discuss key experimental evidence that support how different internalization routes, the generation of diverse endomembrane platforms, and cycles of internalization and recycling ensure polarized compartmentalization of signals, regulating a number of physiological and pathologically-relevant processes in which the resolution of spatial information is vital for their execution. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2664733 Thu, 18 Jun 2009 23:00:00 +0100 2664733 http://www.medworm.com/index.php?rid=2664739&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000799%2Fabstract%3Frss%3Dyes Abstract: Autophagy, a well-described cellular mechanism for lysosomal degradation of cytoplasmic content, has emerged as a tumour suppression pathway. Recent evidence indicates that the tumour suppressor function of autophagy is mediated by scavenging of damaged oxidative organelles, thereby preventing accumulation of toxic oxygen radicals that would cause genome instability. Paradoxically, however, in some cases autophagy can also promote the survival of cancer cells once tumours have developed. This is attributed to the ability of autophagy to promote cell survival under conditions of poor nutrient supply, as often faced by solid tumours and metastasising cancer cells. In addition, autophagy is frequently upregulated in tumours as a response to therapy and may protect tumours against th... Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2664739 Wed, 17 Jun 2009 23:00:00 +0100 2664739 http://www.medworm.com/index.php?rid=2664738&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000763%2Fabstract%3Frss%3Dyes Abstract: Endocytosis is an important regulator of cell–cell signaling and endocytic trafficking has been increasingly implicated in control of tumor suppression. Recent insights from Drosophila indicate that impairment of multiple trafficking steps which lead to receptor degradation can cause tumor formation in epithelial organs. These tumors are characterized by sustained activation of a number of mitogenic signaling pathways, and by subversion of epithelial polarity and the apoptotic response. Cooperation between such alterations, as well as tumor–host interactions, is also observed. The recapitulation of several hallmarks of human cancers in fly tumors provides a framework to understand the role of defective endocytosis in cancer. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2664738 Wed, 17 Jun 2009 23:00:00 +0100 2664738 http://www.medworm.com/index.php?rid=2664737&cid=s_38555_6_f&fid=38555&url=http%3A%2F%2Fwww.moloncol.org%2Farticle%2FPIIS1574789109000775%2Fabstract%3Frss%3Dyes Abstract: Carcinogenesis can be initiated in adult stem cells, suggesting that tumours arise as a consequence of stem-cell dysfunction. In the fruitfly, cancer arises in stem cells that fail to undergo asymmetric cell division. In flies and mammals, a specific regulation of the endocytic trafficking machinery allows stem cells to self-renew and generate the differentiating cells required to form and maintain mature organs. We review recent findings suggesting that an understanding of the relationship between endocytosis, asymmetric cell division, stem cells and cancer will be crucial to unravel the cell biological basis of tumourigenesis. (Source: Molecular Oncology) Molecular Oncology journals http://www.medworm.com/rss/comments.php?id=2664737 Wed, 17 Jun 2009 23:00:00 +0100 2664737