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No, Is the Subject Area "Magnetic resonance imaging" applicable to this article? The authors declare no competing financial interests. Pathol. The dose depends mainly on weight. A smaller diameter mask will help to position the tumor in the center of the scan, but it will not alter this effect. Thirty-two tumors (46%) were nonspherical, as defined above; of these, 19 tumors were nonspherical in the x-y plane, 10 tumors were nonspherical in the y-z plane, and 24 tumors were nonspherical in the x-z plane. Numerical result can be found in Table 2, and Fig 5 presents graphical results. Cell Rep Med. Med. The https:// ensures that you are connecting to the We have administered 10 mg/kg body weight intraperitoneally, which means 200 g bevacizumab per a mouse, since the mass of the mice in the experiment was approximately 20 g (in the case of C57Bl/6 and SCID mice as well). Lifetime dose-response relationships for mammary tumor induction by a single administration of N-methyl-N-nitrosourea. Predicting tumor volume in radical prostatectomy specimens from patients with prostate cancer. Effects of tamoxifen and melatonin on mammary gland cancer induced by N-methyl-N-nitrosourea and by 7,12-dimethylbenz(a)anthracene, respectively, in female Sprague-Dawley rats. Our hypothesis is that the effectiveness of a lower dosage with a quasi-continuous therapy can be comparable with the protocol therapy. 55, 74108 (2005). The cause of death was tumor toxicity; however, none of the clinical criteria for euthanasia could be observed at these animals. & Weaver, D.L. In longitudinal studies, sequential measurements of tumor volume with a non-invasive method are essential. Lab Animal It can be carried out in vivo during the experiment due to the subcutaneous localization of the tumor. M}{Gt{zj|&cXx[k?CZ ~AjTxMr0 '~ix$mj/)9?$ t-o6MkVXs's}^E6-^_Yrv#w&r7w@WsQs]#G g$Cn. For more information about PLOS Subject Areas, click Figure 5. Cancer 83, 621628 (1998). Figure 16. depicts the results from a study attended by Biopticon in which ten subcutaneous tumors in mice were measured by scanner and caliper by four operators. Tracking tumor growth with real tumor scan pictures. produced by the TumorImager-2TM so that the animal is aligned under the mask each time similarly to the previous scan. We compared the volumes, areas . In order to estimate tumor volume by external caliper, the greatest longitudinal diameter (length) and the greatest transverse diameter (width) were determined while mice were scruffed and conscious. Accurately measure the tumor (in cm) using a caliper. Kim DK, Synn CB, Yang SM, Kang S, Baek S, Oh SW, Lee GJ, Kang HW, Lee YS, Park JS, Kim JH, Byeon Y, Kim YS, Lee DJ, Kim HW, Park JD, Lee SS, Lee JY, Lee JB, Kim CG, Hong MH, Lim SM, Kim HR, Pyo KH, Cho BC. To overcome all of these difficulties (continuity of the administration and side-effects), model identification should be determined and then a control algorithm (controller) can be designed for the created mathematical model. Breast Cancer Res. In addition, studies using CT scans concluded that CT yielded tumor volume values 11 to 12% less (an underestimate) than those which were measured by calipers, and that CT-based measurements yielded more accurate and consistent values than caliper-based measurements[6, 7]. Article A graph depicting tumor volume in mm3, as measured by a caliper compared to its actual volume, vs. days. Yes Finally, measurements made with the TumorImager scanner showed a significant difference 10 days earlier between the treatment and control group as opposed to caliper-based measurements. Figure 16. This is a preview of subscription content, access via your institution. The most recent ESMO (European Society for Medical Oncology) consensus guidelines suggest that treatment discontinuation or maintenance are feasible options after 46 months of full-dose first-line therapy to treat colon and rectal adenocarcinoma [37]. 16 (2008). This work was supported by the Portuguese Foundation for Science and Technology (PTDC/DES/114122/2009 and Pest-OE/AGR/UI0772/2011 unity) and by the European Regional Development Fund (COMPETE, FCOMP-01-0124-FEDER-014707/022692). This means that continuous, low dose antiangiogenic factor (VEGF) administration is needed. After fixing in methanol, rat anti-mouse CD31 antibody (1:50, 550274 BD PHARMINGEN) was applied as primer antibody, and FITC conjugated anti-rat CD31 antibody (1:100, Jackson Immunoresearch, 712-095-150) was applied on the slides as secondary antibody. Significance of rat mammary tumors for human risk assessment. Caliper Measurement. Combining Mechanisms of Growth Arrest in Solid Tumours: A Mathematical Investigation, Dramatic increase in volume versus length of invasive ductal carcinoma mimicking intramammary lymph node in a small nodular lesion, Alteration in Inflammasome Cytokine Profile and Functional Plasticity of Macrophage Phenotype in Arsenic(0) Nanoparticle Treated Murine Fibrosarcoma, Tumoral CD105 promotes immunosuppression, metastasis, and angiogenesis in renal cell carcinoma, Cancel Cancer Inst. CAS () and were used with the parameters displayed in Table 1Parameters for Gompertz growth were taken from Benzekry et al. In addition, the root mean square, R2 values under the linear regression equations in Figure 15. symbolize the precision of the data. (Budapest, Hungary). The explanation of the effectiveness of low dose VEGF therapy is the following ([3944]). Clin. This approach presents an alternative to calipers which, although cheap, fast, and easy to use, introduce many biases for tumor volume estimation. Case1 group members received one 200 g bevacizumab dose on the 8th day, case2 group members received 1.11 g bevacizumab from the 8th day every day for 15 days. Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, Budapest, Hungary, Affiliation Please enable it to take advantage of the complete set of features! Accuracy of Optical Imaging for Measuring Tumor Burden In Vivo . Since 2004, the target therapy of bevacizumab (Avastin) is widely used to treat colorectal [9], kidney [10], cervical [34], ovarian [35], non-small cell lung cancers [5], melanoma [14] and certain brain tumors (e.g. In both cases, the height of the tumor will be much smaller than its length or width (Figure 2.). However, if the treatment is lengthy, the problem of side-effects also has to be considered. Tumor segmentation by TumorImager-2TM. Yes For various tumors in mice, only one can be approximated in volume by an ellipsoid. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). 39, 16 (1996). The effectiveness of bevacizumab administration was examined by statistical analysis. J. Oncol. All mice were implanted with HT-29 human colorectal adenocarcinoma. In Phase IV, eleven weeks old male SCID mice with implanted HT-29 human colorectal adenocarcinoma was used. Treat. Lee, J., Koh, D. & Ong, C.N. Fj^P;7? Mice were humanely sacrificed using cervical dislocation. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. recurrent glioblastoma (rGBM) [36]) as a first or second line treatment, usually in combination with chemo- or immunotherapy. Bevacizumab administration was started on the 7th day in both cases. This effect is illustrated in the included video. Thank you for visiting nature.com. Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18 F-FDG-microPET or external caliper. As it was discussed above, the handling of animals by calipers measurements also suffers such deformations of the animal body during the measurements. Tumor volume was measured in two different ways. The study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. One can see from Table 2 that the goodness of the fit is different in the case of Phase I (tumor growth without therapy) and in the case of Phase III/3 (tumor growth with antiangiogenic therapy). This means that mice which were treated with the recommended bevacizumab protocol (one 200 g bevacizumab dose for an 18-day therapy) did not have significantly smaller tumor volume than mice which did not receive therapy at all. The true volume (VT) of a stack of pennies as measured by caliper (VC) and scanner (VS). In the first subphase (Phase III/1), control group members (5 immunocompetent mice) received 10 mg per kg body weight bevacizumab, while case group members (5 immunocompetent mice) received one-tenth dose of control dose spread over 18 days. 58, 264270 (2008). by Mammog raphy (c.c) . Tumor volume was measured with digital caliper as well. In caliper measurements, two values, for length and width, must be recorded for one tumor in each animal; this means that for every 100 animals studied, at least 200 measurements must be made and recorded. 2001 Jan 15;19(2):551-7. doi: 10.1200/JCO.2001.19.2.551. The closer the shape of the tumor is to a perfect ellipsoid, as in the region of the graph in which H closely W, the more closely caliper measurements mirror real-life measurements. We have found that there is significant difference between the means of the samples (p = 0.002, using 0.05 level of significance). 2023 Jan 12;9(1):5. doi: 10.1038/s41420-023-01300-9. In order to estimate tumor volume by external caliper, the greatest longitudinal diameter (length) and the greatest transverse diameter (width) were determined while mice were scruffed and conscious. The technique of using calipers to measure the volume of a tumor has problems associated with both the instrument itself and the methods used in calculating volume[1]. Secondly, the aspect of side-effects are not inconsiderable. This helps to calculate accurate tumor volume from caliper measured data which will be useful for further animal experiments and as a consequence no small MRI measurements will be needed. sharing sensitive information, make sure youre on a federal Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. They then used different formulas to calculate tumor volume from these tumor measurements and compared the calculated tumor volumes with the real tumor volume to identify the formulas that gave the most accurate volume calculations. Res. Contrast agents improve the visibility, but it is an extra strain to the organism, which can be lethal to animals which are in the final stage of cancer. Med. While the scanner only overestimates by about 2%, the caliper overestimates by 32%, as shown by the slope of the line being 1.32. Hence, the first step has to be the vasculature normalization with the reconstruction of the balance of pro- and antiangiogenic factors. Measurements of tumors, in the context of research and industry, are expected to be accurate; it is unacceptable that this inaccurate formula has stood so long as the industry standard. Yes The effectiveness of the quasi-continuous (daily) 1/180 dosage (1.11 g relative to 200 g) using C38 mouse colon adenocarcinoma was more effective than one large dose. {(Q~J9}=ow[5nkW"C; >tDve+7K,}g?A Google Scholar. VC refers to tumor volume values calculated through the formula VT = 0.5 L W2, and VCH refers to those through the formula VT = 0.5 L W H. VS refers to measurements taken by the scanner, and % Inc. refers to the percent increase between VS and VCH. That is independent from the use of a direct optical 3D measurement tool or a caliper. Mammary tumors seemed to take on an oblate spheroid geometry. Ultrasonographic, thermographic and histologic evaluation of MNU-induced mammary tumors in female Sprague-Dawley rats. Monitoring tumor volume through a direct 3D measurement will include changes in all three directions, height, width and length thus resulting in more accurate realistic data. The most accurate volume calculations were obtained using the formula V = (W2 L)/2 for caliper measurements and the formula V = (4/3) (L/2) (L/2) (D/2) for ultrasonography measurements, where V is tumor volume, W is tumor width, L is tumor length and D is tumor depth. First way is the caliper measurement; in that case tumor diameters (width, length) are measured with digital caliper. Radiology 254, 110118 (2010). PLOS ONE promises fair, rigorous peer review, On Day 14, when the tumor volume reached ~500 mm 3, the mice were . These images also provide extra morphological information about the tumor growth and the effect of the compounds on tumor behavior. Federal government websites often end in .gov or .mil. In Figure 4., the value given by caliper measurements (VC, red squares) does not change when up to 15 pennies are stacked. In order to assess interobserver variation, each . Homogeneity of variance was examined with Levenes test; the sample variances are equal (p = 0.052). The precision of the clinical criteria for euthanasia could be observed at these.. The height of the balance of pro- and antiangiogenic factors R2 values under the regression! Not inconsiderable, none of the effectiveness of a lower dosage with a non-invasive method are essential >,... Non-Invasive method are essential handling of animals by calipers measurements also suffers such deformations of the tumor will much! 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