Workshop on imaging science development for cancer prevention and preemption

NIH/NCI/DCTD, Cancer Imaging Program, Bethesda, MD, USA.
Cancer biomarkers: section A of Disease markers (Impact Factor: 1.72). 02/2007; 3(1):1-33.
Source: PubMed


The concept of intraepithelial neoplasm (IEN) as a near-obligate precursor of cancers has generated opportunities to examine drug or device intervention strategies that may reverse or retard the sometimes lengthy process of carcinogenesis. Chemopreventive agents with high therapeutic indices, well-monitored for efficacy and safety, are greatly needed, as is development of less invasive or minimally disruptive visualization and assessment methods to safely screen nominally healthy but at-risk patients, often for extended periods of time and at repeated intervals. Imaging devices, alone or in combination with anticancer drugs, may also provide novel interventions to treat or prevent precancer.

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    • "As a result, there is a need to shift from the diagnosis of symptomatic pancreatic cancer to the screening of asymptomatic individuals at high risk using minimally invasive devices.6 To accomplish this, technology needs to be developed to implement preemptive and preventative procedures in order to reduce mortality rates for this type of cancer.7 Imaging through ERCP and pancreatoscopy is being examined for this purpose, as it is currently the best available means for direct visualization of the pancreatic duct.8,9 "
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    ABSTRACT: Direct visualization of pancreatic ductal tissue is critical for early diagnosis of pancreatic diseases and for guiding therapeutic interventions. A novel, ultrathin (5 Fr) scanning fiber endoscope (SFE) with tip-bending capability has been developed specifically to achieve high resolution imaging as a pancreatoscope during endoscopic retrograde cholangiopancreatography (ERCP). This device has potential to dramatically improve both diagnostic and therapeutic capabilities during ERCP by providing direct video feedback and tool guidance to clinicians. Invasiveness of the new tip-bending SFE was evaluated by a performance comparison to ERCP guide wires, which are routinely inserted into the pancreatic duct during ERCP. An in vitro test model with four force sensors embedded in a synthetic pancreas was designed to detect and compare the insertion forces for 0.89 mm and 0.53 mm diameter guide wires as well as the 1.7 mm diameter SFE. Insertions were performed through the working channel of a therapeutic duodenoscope for the two types of guide wires and using a statistically similar direct insertion method for comparison to the SFE. Analysis of the forces detected by the sensors showed the smaller diameter 0.53 mm wire produced significantly less average and maximum forces during insertion than the larger diameter 0.89 mm wire. With the use of tip-bending and optical visualization, the 1.7 mm diameter SFE produced significantly less average force during insertion than the 0.89 mm wire at every sensor, despite its larger size. It was further shown that the use of tip-bending with the SFE significantly reduced the forces at all sensors, compared to insertions when tip-bending was not used. Combining high quality video imaging with two-axis tip-bending allows a larger diameter guide wire-style device to be inserted into the pancreatic duct during ERCP with improved capacity to perform diagnostics and therapy.
    Medical Devices: Evidence and Research 11/2012; 5(1):1-12. DOI:10.2147/MDER.S27439
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    • "Cells were plated at 2×105 cells per T75 flask and treated the following day with 1 µmol/L 5-aza-2′-deoxycytidine (5-aza-dC, Sigma) [49] for 4 days during the exponential growth phase, with a change of media and drug every 24 hours. On day 5 when cells were near-confluent, they were washed with cold PBS and total RNA isolated using a Qiagen kit (Qiagen) or the mirVana miRNA kit (Ambion), according to manufacturer's instructions as described previously [50]. "
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    ABSTRACT: Cancer associated stromal fibroblasts (CAFs) undergo transcriptional and phenotypic changes that contribute to tumor progression, but the mechanisms responsible for these changes are not well understood. Aberrant DNA methylation is an important cause of transcriptional alterations in cancer cells but it is not known how important DNA methylation alterations are to CAF behavior. We used Affymetrix exon arrays to compare genes induced by the DNA methylation inhibitor 5-aza-dC in cultured pancreatic cancer associated fibroblasts, pancreatic control fibroblasts and pancreatic cancer cell lines. We found that pancreatic CAFs and control pancreatic fibroblasts were less responsive to 5-aza-dC-mediated gene reactivation than pancreatic cancer cells (mean+/-SD of genes induced ≥5-fold was 9±10 genes in 10 pancreatic CAF cultures, 17±14 genes in 3 control pancreatic fibroblast cultures, and 134±85 genes in 4 pancreatic cancer cell lines). We examined differentially expressed genes between CAFs and control fibroblasts for candidate methylated genes and identified the disintegrin and metalloprotease, ADAM12 as hypomethylated and overexpressed in pancreatic CAF lines and overexpressed in fibroblasts adjacent to primary pancreatic adenocarcinomas. Compared to pancreatic cancer cells, few genes are reactivated by DNMT1 inhibition in pancreatic CAFs suggesting these cells do not harbor many functionally important alterations in DNA methylation. CAFs may also not be very responsive to therapeutic targeting with DNA methylation inhibitors.
    PLoS ONE 09/2012; 7(9):e43456. DOI:10.1371/journal.pone.0043456 · 3.23 Impact Factor
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    ABSTRACT: Cancer surveillance is an increasing part of everyday practice in gastrointestinal Endoscopy due to the identification of high-risk groups from genetic and biomarker testing, genealogic and epidemiologic studies, and the increasing number of cancer survivors. An efficient surveillance program requires a cost-effective means for image-guided cancer detection and biopsy. A laser-based tethered-capsule endoscope with enhanced spectral imaging is introduced for unsedated surveillance of the lower esophagus. An ultrathin version of this same endoscope technology provides a 1.2-mm guidewire with imaging capability and cannula-style tools are proposed for image-guided biopsy. Advanced three-dimensional cell visualization techniques are described for increasing the sensitivity of early cancer diagnosis from hematoxylin-stained cells sampled from the pancreatic and biliary ducts.
    Gastrointestinal endoscopy clinics of North America 05/2009; 19(2):299-307. DOI:10.1016/j.giec.2009.02.002
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