The tumor burden is evaluated by volume calculation using caliper measurement. Several studies have investigated the effectiveness of bevacizumab therapy according to different types of cancer [3]: lung cancer [4, 5], breast cancer [68], colon cancer [9], renal cell carcinoma [10], gastric cancer [11], pancreatic cancer [12], prostate cancer [13] and melanoma [14]. Tumor was located in the last third of the back in every cases, thus the effect of respiratory movement was minimal. Generally, to make caliper measurements, the measurer first traps the tail of the mouse under her fingers, then, grabs the neck of the mouse, and aligns the mouse in her hand in a way to expose the tumor for length and width measurements. Parkin, D.M., Bray, F., Ferlay, J. In addition, the mice were weighed . Therefore, its formula will always overestimate the tumor volume until the height equals its width, as seen in Figure 3. The athymic (nude) mouse is a useful model for studying the biology and response to therapies of human tumors in vivo. Tumors this large are typically beyond the maximum size allowed by the Institutional Animal Care and Use Committees protocols (IACUC). In Phase IV, the caliper measurement days were the 10th, 12th, 17th, 19th, 22nd and 23rd days. Tumor volumes ranged from 0.5 cc to 187.9 cc, with a median of 21.8 cc. PhD from the 1st Department of Pathology and Experimental Cancer Research Institute from Semmelweis University, Budapest, for making the fluorescence pictures with confocal microscope. Radiology 254, 110118 (2010). However, it has to be taken into consideration that in several cases using antiangiogenic therapy, tumor shape is irregular (berry-shaped). Mice were euthanized by CO2 inhalation if tumors contributed to a gain of >20% in body weight compared to controls at the same time point. to calculate several estimates of tumor volume using the equations for the volume of a sphere ([4 /3]r3), Here r is average of a, b and c the volume of an e0142190. Each dot, in addition to signifying a real-life tumors width and height, also signifies through the right y-axis what percentage of a caliper-based measurement with the same width it is. How the device is positioned over the tumor will not influence the result. <> stream This is the formula most used in research and industry. Mice in Phase III/3 control and case groups, and mice in Phase IV case1 and case2 groups received bevacizumab. Measured data is the MRI-measured tumor volumetumor mass pairs on the 23rd day of Phase III/3 (case and control group). In several recent studies ([21, 22]), tumor volume is calculated assuming ellipsoid shape: The overestimation of caliper measurements is due mainly to the fact that the formula used is that of a parallelepiped, a shape unlike an ellipsoid actually represents the geometric body that is being measured. NCI CPTC Antibody Characterization Program. Results from an experiment that measures tumor volume and varies drug dose and measuring methods. Usually, 3.0 x 10 6 cells are needed per injection. Circular RNA circTRPS1-2 inhibits the proliferation and migration of esophageal squamous cell carcinoma by reducing the production of ribosomes. Mice in the control group received no treatment (5 mice); case1 group members (10 mice) received 10 mg per kg body weight bevacizumab in one dose; while case2 group members (10 mice) received 1/180 dose of control dose for 15 days. In addition, even though there is about a 20% difference between the low-dose treatment group for the scanner measurements, the caliper-based measurements do not show any effect for this dose. 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. Evaluated the accuracy of common four formulas given in the literature to estimate xenograft tumor volumes based on manual caliper measurements and proposed formula (0,45 L*W*H) could estimate tumor volumes as good as prolate ellipsoid formula. Correspondence to <> Determining tumor volume is a useful and quantitative way to monitor tumor progression. Physical activity cancer preventionmechanisms. Kim HB, Zeng CH, Kim Y, Jeong S, Kim SH, Kang JM, Park Y, Won DS, Kim JW, Ryu DS, Lim B, Park JH. Provided by the Springer Nature SharedIt content-sharing initiative, Bulletin of the National Research Centre (2022), Lab Animal (Lab Anim) Thank you for visiting nature.com. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. It can be carried out in vivo during the experiment due to the subcutaneous localization of the tumor. Secondly, the aspect of side-effects are not inconsiderable. Furthermore, caliper-based measurements cause undue stress on the animal and, by extension, the tumor, which can further distort measurements. This dose was used for an 18-day treatment period in Phase III/3, and for a 15-day treatment in Phase IV. PMID: 11208850. At this critical stage in the tumors growth, the caliper-based volume measurement will generally be larger than the tumors actual volume, since the longest axis of the parallelepiped will be partially empty. This effect is illustrated in the included video. In Phase IV, eleven weeks old male SCID mice with implanted HT-29 human colorectal adenocarcinoma was used. The size of maximum tumor volumes observed in our study fulfills the requirements of Hungarian animal experimental research protocol. One can find datasets in the last column of Table 2. In both cases, the height of the tumor will be much smaller than its length or width (Figure 2.). The figure shows the results of a mouse (C4) from control group (first row), and a mouse (E9) from case group (second row). A smaller diameter mask will help to position the tumor in the center of the scan, but it will not alter this effect. Ultrasonographic, thermographic and histologic evaluation of MNU-induced mammary tumors in female Sprague-Dawley rats. Cancer 60, 765771 (1987). Biol. Stretching of the skin around the tumor of the mouse will cause an under-estimate of the tumor volume since the tumor is pressed into the body (see Figure 13. below). a) Haematoxylin Eosin (H&E) staining was applied to investigate tumor morphology. The advantage of this model is that there is no need to approximate tumor height (which could result in error). 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. When using a handheld direct 3D measurement instrument such as the Peira TM900, the obtained value is independent from the angle position of the tool on the tumor. Carlsson, G., Gullberg, B. b) Fluorescence picture was created using CD31 antibody immunohistochemistry staining to calculate vascularization area. No, Is the Subject Area "Mathematical models" applicable to this article? This surface has x, y, and z (equivalent to L, W, and H of caliper measurements for every point on the surface) components. YH29407 with anti-PD-1 ameliorates anti-tumor effects. In that caseeven though all the three diameters can be measuredthe estimation of the volume has quite a large error. Later in a study, when a tumor grows into larger masses, the shape of the tumor can differ greatly from an ellipsoid, as shown in Figure 7. In Phase I, Phase II and Phase III, eight weeks old male C57Bl/6 mice with implanted C38 mouse colorectal carcinoma was used. Pathol. Another approach is to utilize the scan images (Figure 14.) This results in the loss of information about its real growth.. With constant width and length, the measured volume does not change with the tumor shape. In Phase III/3, control group contained 5 mice, case group contained 9 mice; all mice were implanted with C38 mouse colon adenocarcinoma. Modern Pathol. A smaller standard deviation in a set of measurements suggests a lesser possibility of error. 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. In addition, we have found that the quasi-continuous administration of bevacizumab is effective against tumor growth of C38 colon adenocarcinoma, in contrast . Yes %PDF-1.4 Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. We compared tumor volumes estimated in vivo by BLI and FLI, to those calculated by caliper measurements and found a good correlation between these two techniques (Figure 4). obtained using vernier calipers (c.c) Vol. Breast cancer measurements with magnetic resonance imaging, ultrasonography, and mammography. This creates the possibility of further efficient therapeutic agent use (if any) or assists the more effective direct antitumoral effect of bevacizumab. In order to understand inter-operator differences between operators making both caliper and scanner measurements, we conducted experiments in which multiple numbers of operators measured several tumors both with caliper and scanner. https://doi.org/10.1371/journal.pone.0142190.g005, https://doi.org/10.1371/journal.pone.0142190.t002, To find the f constant for tumor growth without therapy (Phase I), first reliable tumor volume values had to be found, since there was no MRI measurement in Phase I. Beside tumor diameters, tumor mass was measured and vascularization area was calculated in the case of the removed tumors. Tumor as a 3-D object has three diameters (width, length and height); however in vivo only two diameters can be measured by caliper (width, w and length, l). The authors declare no competing financial interests. The majority of debate over Avastin is about breast cancer because, in 2011, the US Food and Drug Administration (FDA) revoked the approval of Avastin for breast cancer treatment in the absence of decisive therapeutic benefit; however, several clinical trials suggested that Avastin can be effective in breast cancer treatment [6, 7]. Breast Cancer Res. Tumor growth was investigated without therapy and with antiangiogenic therapy (using bevacizumab [15]). calculate an average volume based on two extreme segmentations; one including most of the border, and one excluding it. 1.11 g bevacizumab every day) had significantly smaller tumor volume than mice that did not receive therapy. (Budapest, Hungary). Mice were humanely sacrificed using cervical dislocation. CAS All mice were implanted with HT-29 human colorectal adenocarcinoma. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Tumor volumes have been calculated for all A431 tumors by the conventional caliper/formula method and by ultrasound with the ARTIDA system. This paper reviews the standard technique for tumour volume assessment, calliper measurements, by conducting a statistical review of a large dataset consisting of 2,500 tumour volume measurements from 1,600 mice by multiple operators across 6 mouse strains and 20 tumour models. Additionally, we explore the impact of six different tumour . & Lin, C.A. Would you like email updates of new search results? Figure 10. To evaluate tumor volume, first the shape of the tumor has to be assumed, and if it is necessary for volume calculation, the third diameter (height, h) has to be approximated. 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]. A study[4] (Figure 5.) Enter your measurements into the Tumor Volume Calculator to determine the volume of the tumor. in The Laboratory Mouse (eds. Article These model-based protocols can be more effective than the current ones, since they provide individual treatment for the patients. Monaco performed the dose calculation of the VMAT treatment plans with the dose calculation grid of 3.0 mm by utilizing the Monte Carlo algorithm. Med. In Phase I, Phase II and Phase III, a piece of C38 colon adenocarcinoma was transplanted subcutaneously in the recipient animal on the 1st day of the experiment (approximately 2106 cells were transplanted into each mouse). & Pisani, P. Global cancer statistics, 2002. Denis, F., Paon, L. & Tranquart, F. Radiosensitivity of rat mammary tumors correlates with early vessel changes assessed by Power Doppler sonography. Epub 2013 Jul 11. Open Access Tumours of the rat. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. Traditionally their volume growth has been monitored by using a mechanical caliper. 2009, 18 (2009). Preclinical Imaging Center, Gedeon Richter Plc., Budapest, Hungary, Affiliation 47, 510 (2001). Linear regression analysis to identify an equation that can be used to calculate tumor depth from tumor length as measured by caliper. Cancer Res. Therefore, optical imaging is . 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. and transmitted securely. We have found that mice which have received therapy had tumor with irregular, and in several cases berry-shaped structure, especially when reaching large volume. produced by the TumorImager-2TM so that the animal is aligned under the mask each time similarly to the previous scan. The caliper mean-percent-error is 10.6%, nearly twice that of the scanners mean-percent-error of 4.6%. Contributed reagents/materials/analysis tools: ZS PK LK. Even though, now, the formula is calculated in an Excel spreadsheet where can be defined as a function, pi(), almost in all cases, in the volume formula is defined as 3.0. Forbes, D., Blom, H., Kostomitsopoulos, N., Moore, G. & Perretta, G. Euroguide: On the Accommodation and Care of Animals Used for Experimental and Other Scientific Purposes (Federation of European Laboratory Animal Science Associations, London, 2007). One including most of the tumor will not influence the result mask will help to position the will... 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