Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice

Marten, Katharina; Bremer, Christoph; Khazaie, Khashayarsha; Sameni, Mansoureh; Sloane, Bonnie F.; Tung, Ching–Hsuan; Weissleder, Ralph

doi:10.1053/gast.2002.30990

Cited by 202 publications

(137 citation statements)

References 36 publications

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…The protease overexpression that is seen at the tumor site is qualitatively similar to that seen via ex vivo imaging of small bowel adenomas in Apc Min1/2 mice. 13 Interestingly, fluorescence is seen in the bowel adjacent to the protruding tumor. Subsequent dissection and histologic analysis revealed that, similar to Figure 3d, the tumor had infiltrated below the adjacent mucosal surface and had spread in the submucosa superficial to the muscularis externa, with some invasion of this layer as well.…”

Section: Resultsmentioning

confidence: 99%

A novel mouse model for segmental orthotopic colon cancer

Alencar¹,

King²,

Funovics³

et al. 2005

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Spontaneous colon tumor mouse strains offer numerous advantages in modeling disease. However, the wide temporal window in which lesions form and the stochastic nature of lesion location require larger cohorts for assessment of disease modulation. Reliable, reproducible and inexpensive mouse models of early-stage and invasive cancer would add to existing transgenic models. We show a new method for the creation of orthotopic murine tumors centered in the mucosal and submucosal layers anywhere in the colon, allowing creation of lesions of known age, location and extent. The system overcomes the disadvantages of heterotopic implantation and allows evaluation of lesions distally in the colon as well as proximally, thereby providing an additional method to study the effects of regionality. Invasion, host vascularization and application to disparate cell lines are demonstrated. Noninvasive imaging with magnetic resonance and colonoscopy, allowed in part by the tumor location, show potential applications of this approach. ' 2005 Wiley-Liss, Inc.Key words: colon cancer; mouse model; colonoscopy; magnetic resonance imaging A number of spontaneous colorectal tumor mouse strains have been developed that model human cancer syndromes, such as HNPCC, 1 and familial adenomatous polyposis. 2-5 These mouse models, which allow monitoring of the phenotypic effects of known genetic alterations, have proved invaluable in understanding disease course and evaluating novel therapies. 6 The typically slower growth rates in the resulting spontaneous tumors compared to implanted cell lines more closely emulate the rates of human tumor growth. However, many of the most-used mouse models form adenomas primarily in the small bowel, with relatively few lesions in the descending and sigmoid colon. Noninvasive serial imaging of small bowel lesions to evaluate anatomic size changes is quite challenging in humans and markedly more difficult in mice. Additionally, few transgenic models of invasive colorectal cancer exist; 7 the commonly used Apc Min1/2 mice typically develop adenomas but not invasive adenocarcinomas.A disadvantage for the use of these models to evaluate therapeutics is that the broad temporal variability in lesion formation and the difficulty in nondestructive serial evaluation require very large cohorts of animals to be examined over extended periods of time to realize efficacy of treatment, with mortality often used as an end point. Alternatively, heterotopic s.c. implantation of tumor cell lines suffers from incongruent host stroma, which has been shown to change tumorigenicity 8 and cell cycle regulation 9 for implanted tumors compared to implantation in the native tissue bed. Additionally, direct injection of tumor cells into murine colonic mucosa or submucosa is technically difficult and has not been reported. We hypothesized that orthotopic implantation could be achieved with focal enzymatic disruption of the colonic mucosal layer only and placement of tumor cells intraluminally. The resulting tumors ''arise'' from the muco...

show abstract

Section: Resultsmentioning

confidence: 99%

A novel mouse model for segmental orthotopic colon cancer

Alencar¹,

King²,

Funovics³

et al. 2005

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…For a review of intravital microscopy see several excellent recent review articles [18,20,21]. Macroscopic fluorescence reflectance imaging (FRI) is a useful technique when probing superficial structures (<5 mm deep), for example during endoscopy [22,23], dermatological imaging [3], intraoperative imaging [24], probing tissue autofluorescence [25,26] or small animal imaging [27]. Fluorescence molecular tomography is the newest imaging technology that has recently been shown to localize and quantify fluorescent probes threedimensionally in deep tissues at high sensitivities [28,29] (Fig.…”

Section: A Imaging In the Near-infraredmentioning

confidence: 99%

Shedding light onto live molecular targets

Weissleder

Ntziachristos

2003

Nat Med

Self Cite

1,781

1,319

View full text Add to dashboard Cite

Abstract-Optical sensing of specific molecular targets and pathways deep inside living mice has become possible as a result of a number of advances. These include design of biocompatible near-infrared fluorochromes, development of targeted and activatable 'smart' imaging probes, engineered photoproteins and advances in photon migration theory and reconstruction. Together, these advances will provide new tools making it possible to understand more fully the functioning of protein networks, diagnose disease earlier and speed along drug discovery.

show abstract

“…51 In 2002, Cy5.5-PGC-Cathepsin B imaging was used to discriminate adenomatous polyps in APC-mice from normal mucosa. 53 This study provided opportunities for selective removal of polyps, thereby reducing the transformation of polyps to colorectal cancer. 53 More recent probes using this concept are the ProSense 680 and 750 dyes (Visen medical).…”

Section: Probes That Are Activated By Tumor-associated Proteasesmentioning

confidence: 98%

“…Three probes have been designed so far by one research group and they are all activated by protease Cathepsin B. [51][52][53][54][55][56] This protease is known to be up-regulated in areas of inflammation, necrosis, angiogenesis and focal invasion. 57 Being optically silent when injected, the probes have a low background signal which results in higher signal-to-background ratios when compared to nonspecific probes.…”

Section: Probes That Are Activated By Tumor-associated Proteasesmentioning

confidence: 99%

The use of fluorescent dyes and probes in surgical oncology

Velde

Veerman

Subramaniam

et al. 2010

European Journal of Surgical Oncology (EJSO)

133

View full text Add to dashboard Cite

Aims and background: Improved visualization of surgical targets inside of the patient helps to improve radical resection of the tumor while sparing healthy surrounding tissue. In order to achieve an image, optical contrast must be generated by properties intrinsic to the tissue, or require the attachment of special visualization labels to the tumor. In this overview the current status of the clinical use of fluorescent dyes and probes are reviewed. Methods:In this review, all experimental and clinical studies concerning fluorescent imaging were included. In addition, in the search for the optimal fluorescent imaging modality, all characteristics of a fluorescent dye were described. Findings and Conclusions:Although the technique of imaging through fluorescence sounds promising and several animal models show efficacy, official approval of these agents for further clinical evaluation, is eagerly awaited.

show abstract

Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice

Cited by 202 publications

References 36 publications

A novel mouse model for segmental orthotopic colon cancer

A novel mouse model for segmental orthotopic colon cancer

Shedding light onto live molecular targets

The use of fluorescent dyes and probes in surgical oncology

Contact Info

Product

Resources

About