http://precedings.nature.com/subjects/cancer/ Recently posted documents in Cancer Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/3931/version/1 Synthetic "microDNAs (MIDs)"is a new class of ~ 20-25 nucleotide-long DNAs capable of repressing the activity of the target gene at the level of transcription by mechanisms that have not been clarified yet. However they are designed to target non-coding regions of the cancer causing genes, thus interfering with transcription. The inhibition might be possible through the direct binding of MIDs to cis-regulatory sites and/or to some Transcription Factors (TF) that normally activate transcription. Synthetic MIDs in some ways are similar to the newly discovered microRNAs a mechanism by which cell regulates its genetic activities at post-transcriptional level. Synthetic MIDs can provide a powerful tool to prevent massive production of mRNA by undesired gene activities. Therefore drugs are not required to interact with overwhelming number of mRNA and microRNA copies that may present unwanted side effects. In vitro studies suggest that the inhibition of the target gene starts after the first round of DNA replication, usually 24 hours after treatment depending on cell doubling time. Cell growth suppression maximizes at day 6 or 7 and the inhibition effect is sustained for weeks. We have shown that blocking of both bcl-2 and k-ras transcription by their specific microDNA Inhibitors induced apoptosis in HL60 leukemia cells and B-cell lymphomas. http://precedings.nature.com/documents/3931/version/1 Wed, 04 Nov 2009 10:28:46 UTC MicroDNAs and Transcriptional Regulation hdl:10101/npre.2009.3931.1 2009-11-04 Nature Precedings 2009-11-04T10:28:46Z Manuscript Cancer Genetics & Genomics Molecular Cell Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3930/version/1 The PSA doubling time is usually calculated from measured PSA values with an inadequate formula that tacitly assumes the absence of that process, which it is supposed to reveal. We present a modified calculational procedure which is optimized to unveil a weak second exponential process in the presence of a strong first one, using early screening data. The notion of Break Even Time (BET) indicates the stages of the processes. http://precedings.nature.com/documents/3930/version/1 Tue, 03 Nov 2009 15:41:52 UTC PSA Dynamics traditionally evaluated with an inadequate formula hdl:10101/npre.2009.3930.1 2009-11-03 Hans-Jürg Gerber Nature Precedings 2009-11-03T15:41:52Z Manuscript Cancer http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3840/version/1 We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator of the progression of normal cells through the cell cycle. To determine the role of JDP2 in vivo, we generated Jdp2 knock-out (Jdp2KO) mice by targeting exon 1 to disrupt the site of initiation of transcription. The healing of wounded skin of Jdp2KO mice proceeded more rapidly than that of control mice and more proliferating cells were found at wound margins. Fibroblasts derived from embryos of Jdp2KO mice proliferated more rapidly and formed more colonies than wild-type fibroblasts. JDP2 was recruited to the promoter of the gene for cyclin A2 (ccna2) at a previously unidentified AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin A2 mRNA. Moreover, reintroduction of JDP2 resulted in repression of transcription of ccna2 and of cell cycle progression. Thus, transcription of the gene for cyclin A2 appears to be a direct target of JDP2 in the suppression of cell proliferation. http://precedings.nature.com/documents/3840/version/1 Thu, 08 Oct 2009 20:41:55 UTC Suppression of cell cycle progression by Jun dimerization protein (JDP2) involves down-regulation of cyclin A2 hdl:10101/npre.2009.3840.1 2009-10-08 Kazunari K. Yokoyama Nature Precedings 2009-10-08T20:41:55Z Manuscript Cancer http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3815/version/1 Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled studies of interventions delivered to communities. We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation. We found limited evidence that public education campaigns reduce stage at presentation of breast cancer, malignant melanoma and retinoblastoma. http://precedings.nature.com/documents/3815/version/1 Fri, 02 Oct 2009 13:58:57 UTC Interventions to Promote Cancer Awareness and Early Presentation: Systematic Review hdl:10101/npre.2009.3815.1 2009-10-02 Nature Precedings 2009-10-02T13:58:57Z Manuscript Cancer http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3816.1 There is virtually no evidence for the effectiveness of interventions to promote early presentation in breast cancer. We tested the efficacy of an intervention to equip older women with the knowledge, skills, confidence and motivation to detect symptoms and seek help promptly, with the aim of promoting early presentation with breast cancer symptoms. We randomised 867 women aged 67 to 70 attending for their final routine appointment on the UK NHS Breast Screening Programme to receive: a scripted ten-minute interaction with a radiographer plus a booklet; a booklet alone; or usual care. The primary outcome was whether or not a woman was breast cancer aware based on knowledge of breast cancer symptoms and age-related risk; and reported breast checking. At one month, the intervention increased the proportion who were breast cancer aware compared with usual care (interaction arm: 32.8% versus 4.1%; odds ratio 24.0, 95% confidence interval 7.7 to 73.7; booklet arm: 12.7% versus 4.1%; odds ratio 4.4, 95% confidence interval 1.6 to 12.0). At one year, the effects of the interaction plus booklet, and the booklet, on breast cancer awareness were largely sustained, although the interaction plus booklet remained much more effective. Future research will evaluate whether the intervention promotes early presentation and reduces breast cancer mortality. http://dx.doi.org/10.1038/npre.2009.3816.1 Thu, 01 Oct 2009 13:54:24 UTC A randomised controlled trial of an intervention to promote early presentation of breast cancer in older women: effect on breast cancer awareness doi:10.1038/npre.2009.3816.1 2009-10-01 Nature Precedings 2009-10-01T13:54:24Z Manuscript Cancer http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3817/version/1 Objective: To assess public awareness of cancer warning signs, anticipated delay, and perceived barriers to seeking medical advice in the British population. Methods: We carried out a population-based survey using face-to-face, computer-assisted interviews to administer the Cancer Awareness Measure (CAM), a newly-developed, validated measure of cancer awareness. The sample included 2216 adults (970 male and 1246 female) recruited as part of the Office for National Statistics Opinions Survey using stratified probability sampling.Results: Awareness of cancer warning signs was low when open-ended (recall) questions were used and higher with closed (recognition) questions; but on either measure, awareness was lower in those who were male, younger, and from lower socioeconomic status (SES) groups or ethnic minorities. The most commonly endorsed barriers to help-seeking were difficulty making an appointment, worry about wasting the doctor’s time and worry about what would be found. Emotional barriers were more prominent in lower SES groups and practical barriers (e.g. too busy) more prominent in higher SES groups. Anticipated delay was lower in ethnic minority and lower SES groups. In multivariate analysis, higher symptom awareness was associated with lower anticipated delay, and more barriers with greater anticipated delay.Conclusions: A combination of public education about symptoms and empowerment to seek medical advice, as well as support at primary care level, could enhance early presentation and improve cancer outcomes. http://precedings.nature.com/documents/3817/version/1 Thu, 01 Oct 2009 10:15:56 UTC Public awareness of cancer in Britain: a population-based survey of adults hdl:10101/npre.2009.3817.1 2009-10-01 Nature Precedings 2009-10-01T10:15:56Z Manuscript Cancer http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3809.1 Plant cell cultures of Taxus provide the most reliable production methods for the anti-cancer drug paclitaxel. In order to comprehend the inherent culture heterogeneity and production variability in cell cultures, it is essential that the cellular metabolism is studied at the genomic level. Genomic stability in plant cell cultures is crucial as it affects cell growth and division, metabolite accumulation and protein synthesis. A rapid and efficient method to prepare nuclei suspensions from aggregated cell cultures of Taxus was employed. Methods were subsequently developed to simultaneously stain them for DNA and protein content using Propidium Iodide and Fluorescein Isothiocyanate respectively. Flow cytometry was used to analyze and quantify the DNA content and genome size of Taxus using known reference species as standards. Furthermore, their genomic stability was evaluated by correlating DNA content and genome size with cell size and complexity, protein content, and elicitation effects using multiparameter flow cytometry. These techniques to evaluate and correlate various culture characteristics can be very useful in designing superior bio processes for enhanced production. http://dx.doi.org/10.1038/npre.2009.3809.1 Thu, 01 Oct 2009 08:33:37 UTC Nuclear DNA and protein content evaluation in Taxus plant cell cultures using multiparameter flow cytometry doi:10.1038/npre.2009.3809.1 2009-10-01 Vishal Gaurav Nature Precedings 2009-10-01T08:33:37Z Poster Biotechnology Cancer Developmental Biology Genetics & Genomics Plant Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3771/version/1 Background: Several anti apoptotic signals have been recently identified. Aven and Survivin are broadly expressed and are conserved in mammalian species. Patients and Methods: 39 AML and 25 ALL were tested. Aven and Survivin expression were detected by RT-PCR. DNA fragmentation was carried out daily after treatment..Results: Survivin was expressed (P=0.06) more in AML (74%) than in ALL (52%). While, Aven was equally expressed in both leukemias. Patients were categorized into 3 groups based on DNA fragmentation. Absence of Aven significantly (p‹0.001) contributed to DNA fragmentation,but Survivin did not contribute as much. None of the concordant both positive Survivin and Aven were in group III (the good 5 day fragmentation, (P< 0.001). Survivin was statistically related to CD7 expression (P<0.001) in AML only. There was a significant dissociation between Aven and Survivin in AML (p=0.03) and near significant dissociation in ALL (p=0.07). Conclusion: Aven seems to be more important as an inhibitor of apoptosis than survivin in acute leukemia. The presence of both confers a survival disadvantage and a significantly worse DNA fragmentation pattern suggesting a synergistic inhibition of apoptosis. The highly significant relation between CD7 and survivin expression might suggest their involvement in a common signal transduction pathway. http://precedings.nature.com/documents/3771/version/1 Wed, 23 Sep 2009 15:40:49 UTC Aven and Survivin Expression in Egyptian Acute Leukemia and Their Relation to Apoptosis hdl:10101/npre.2009.3771.1 2009-09-23 Magda Assem Nature Precedings 2009-09-23T15:40:49Z Manuscript Cancer http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3741/version/1 This study was designed to investigate the influence of TSER and MTHFR polymorphisms on the clinical outcomes of patients with colorectal cancer receiving 5-FU-based chemotherapy. Genomic DNA was isolated from 103 frozen or paraffin-embedded tissues of colorectal cancer patients. The genotypes of two common polymorphisms were determined by PCR-RFLP. Patient prognoses were compared with genotype groups and analyzed according to tumor location. Polymorphisms of TSER and MTHFR 677C>T were not significantly associated with clinicopathological factors. There were no differences in prognosis between genotypes or functional groups when the TSER and MTHFR groups were considered separately. However, analysis of combined genotypes of the TSER and the MTHFR 677C>T polymorphisms were associated with the survival rate of colorectal cancer patients who received 5-FU-based chemotherapy (p=0.028). Prognosis of colorectal cancer patients was significantly different between proximal colon and distal colon cancers (p=0.002). However, prognosis did not receive any effect of the combined genotype when analyzed according to tumor location, such as proximal and distal colon cancer. The combined TSER and MTHFR 677C>T genotypes can be prognostic factors in colorectal cancer, where gene-gene interactions between the genotypes may occur. http://precedings.nature.com/documents/3741/version/1 Fri, 11 Sep 2009 09:41:44 UTC Polymorphisms of TSER and MTHFR are associated with prognosis of fluoropyrimidine-based therapy in colorectal cancer patients hdl:10101/npre.2009.3741.1 2009-09-11 Nam Keun Kim Nature Precedings 2009-09-11T09:41:44Z Manuscript Cancer Genetics & Genomics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3682/version/1 The Hedgehog (Hh) pathway contributes to prostate cancer growth and progression. The presence of robust Shh expression in both normal prostate and localized cancer challenged us to explain the unique growth promoting effect in cancer. We show here that paracrine Hh signaling exerts a non-cell autonomous effect on xenograft tumor growth and that Hh pathway activation in myofibroblasts alone is sufficient to stimulate tumor growth. Nine genes regulated by Hh in the mesenchyme of the developing prostate were found to be regulated in the stroma of Hh over-expressing xenograft tumors. Correlation analysis of gene expression in matched specimens of benign and malignant human prostate tissue revealed a partial 5 gene fingerprint of Hh-regulated expression in stroma of all cancers and the complete 9 gene fingerprint in the subset of tumors exhibiting a reactive stroma. No expression fingerprint was observed in benign tissues. We conclude that changes in the prostate stroma due to association with cancer result in an altered transcriptional response to Hh that mimics the growth promoting actions of the fetal mesenchyme. Patients with an abundance of myofibroblasts in biopsy tissue may comprise a sub-group that will exhibit a particularly good response to anti-Hedgehog therapy. http://precedings.nature.com/documents/3682/version/1 Wed, 26 Aug 2009 20:02:40 UTC The Sonic Hedgehog Pathway Stimulates Prostate Tumor Growth by Paracrine Signaling and Recaptures Embryonic Gene Expression in Tumor Myofibroblasts hdl:10101/npre.2009.3682.1 2009-08-26 Aubie Shaw Nature Precedings 2009-08-26T20:02:40Z Manuscript Cancer Developmental Biology http://creativecommons.org/licenses/by/3.0/