For more information about PLOS Subject Areas, click In Phase IV, control group contained 5 mice, case1 group contained 10 mice, and case2 group contained 10 mice as well. Epub 2014 May 28. 22, 921929 (2003). In the case of Phase III/3 and Phase IV, period of time was specified according to the previous phases (Phase I and Phase III/1); mice were sacrificed on the 23rd day of the experiment. 15, 115121 (2009). Pathol. Below, we present the results of some sample studies in which independent companies doing pharmaceutical, biotech, and cancer research organizations made trial runs to assess the new 3D technology and compare them with their standard caliper measurements. Yes A 3-D illustration can be found in Fig 7. a) berry-shaped tumor; b) x-diameter of the tumor; c) y-diameter of the tumor; d) z-diameter of the tumor; e) berry-shaped tumor with ellipsoidal estimation. Exer. The tumor dimensions are L, W, and H. The volume of an ellipsoid VE, using the variables as shown in Figure 1., is. 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]. This saves money, as mice, drugs, and calipers can be costly for researchers. 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). Because tumor volume measurements used by researchers and industries are sensitive and often rely on the accuracy, the cutting-edge TumorImagerTM line of scanners is the ideal, most reliable choice for taking such sensitive measurements. & Russo, I.H. The effectiveness of bevacizumab administration was examined by statistical analysis. Data Availability: All relevant data are within the paper. 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. 2023 Jan 20;42(1):25. doi: 10.1186/s13046-022-02578-w. Zhao R, Chen P, Qu C, Liang J, Cheng Y, Sun Z, Tian H. Cell Death Discov. Materials and methods: The murine CaNT subcutaneous xenograft model was used. Tumor measurement by TumorImager-2TM. Ergonomics 37, 217229 (1994). In Phase I, we have investigated tumor growth without therapy with two types of mouse tumor. Is the Subject Area "Cancers and neoplasms" applicable to this article? Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. et al. In order to assess interobserver variation, each . Determining tumor volume is a useful and quantitative way to monitor tumor progression. Tumors should also be placed so that the tumor peak is near the center of the mask and is not highly inclined. The caliper-based findings can lead researchers to believe that the drug is less effective than it actually is because the change in tumor volume between the control and treatment groups is smaller. . 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. PLOS ONE promises fair, rigorous peer review, Fj^P;7? Fornage, B.D., Toubas, O. The most accurate volume calculations were obtained using the formula V = (W(2) 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. In Phase IV, the caliper measurement days were the 10th, 12th, 17th, 19th, 22nd and 23rd days. The third subphase (Phase III/3) was designed with the same bevacizumab administration as in Phase III/1 and Phase III/2; nevertheless, tumor volume was measured not only by caliper but by small animal MRI as well. Can the Kuznetsov Model Replicate and Predict Cancer Growth in Humans? In a study done in England, the researchers at the end of their experiment, dissected tumors and measured their weight with a precise balance, and used these weight values of the tumors to compare results of the caliper and the scanner measurements. A tumor expands in width rather than height as it grows. and calculates an interpolated surface under the tumor boundary based on the healthy surface around the tumor (navy blue line in Figure 12.). 58, 264270 (2008). (1). J. Clin. Description of Lesions. Determining tumor volume is a useful and quantitative way to monitor tumor progression. Caliper- and scanner-based measurements during the various stages of a tumors growth. After staining, fluorescence pictures were done from the slides using confocal microscope (BIO-RAD MRC-1024). The whole experiment consisted of four phases; the article focuses on the Phase III/3 and its results together with the comparison of Phase I and Phase III/3 (Fig 1). How the device is positioned over the tumor will not influence the result. ANOVA test showed significant difference between these means (p = 0.041, using 0.05 level of significance). 2001 Jan 15;19(2):551-7. doi: 10.1200/JCO.2001.19.2.551. 2013 Oct;67(8):771-6. doi: 10.1016/j.biopha.2013.06.011. Nevertheless the result of our study shows that the effectiveness is even better. FOIA The significant difference between quasi-continuous therapy (Phase III/3 case group) and tumor growth without treatment (Phase I) was proved with statistical analysis as well. Thank you for visiting nature.com. Imaging 33, 2737 (2006). Tumor was located in the last third of the back of the mouse in every case. Finding the mathematical relationship between MRI-measured tumor volume and tumor mass creates the possibility to estimate tumor volume from caliper-measured data. Measure the three dimensions of peanut M&M's, serving as our similar-sized tumor surrogates, using vernier calipers. We are sorry, but there is no personal subscription option available for your country. Analysis of Variance (ANOVA) test was used to compare more than two samples, while pairwise comparison was done by Tukeys honest significant difference (HSD) test. Table 1 shows the results for tumor volume measure- ments on seven A431 tumors, indicating next to both gold standard volumes (V w , V L ) the caliper/formula derived volume V E and the ARTIDA . 35, 18341840 (2003). The height and topography of the tumor is not taken into account in a caliper measurement. To validate our results which come from the experiments where mouse tumor vascularization was inhibited with humanized VEGF, we evaluated the results of Phase IV, where immunocompromized (SCID) mice were used with human colorectal adenocarcinoma (HT-29) xenografts. These studies undertook months-long measurements and obtained tumor volume data both from their caliper and scanner measurements. It can be carried out in vivo during the experiment due to the subcutaneous localization of the tumor. volume42,pages 217224 (2013)Cite this article. Correlation was investigated with Pearsons rank correlation test (Pearsons R) and coefficient of determination (R2). (2), Whilst studies have shown that tumors can be better estimated with ellipsoid shape than using Eq 1, calculating the volume of an ellipsoid requires the knowledge of the third parameter. Eichelerger, L.E. Yes Read the article on why you should not use calipers! 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. We have investigated the relationship between MRI-measured tumor volume and vascularization area (Phase III/3 case and control groups, 23rd (final) day of the experiment) but no significant correlation was found (same results were published in the case of Phase I [26] and Phase III/2 [23]). Pere, M., Cerar, A. Davis, P.L. Figure 5. 55, 11761180 (1995). et al. Int. obtained using vernier calipers (c.c) Vol. There are no further patents, products in development or marketed products to declare. 37, 19 (1996). To obtain Bevacizumab is a humanized monoclonal antibody, therefore the effectivity of bevacizumab therapy in mice is not trivial. 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. It was on the 10th day, since HT-29 colorectal adenocarcinoma grows slower in mice than C38 colon adenocarcinoma. Measurements with small animal MRI were done on the 4th, 8th, 11th, 15th, 18th and 23rd days of the experiment in Phase III/3. 1.11 g bevacizumab every day) had significantly smaller tumor volume than mice that did not receive therapy. Even though all the three diameters can be measured, the estimation of the volume has quite a large error. 39, 16 (1996). J. Oncol. The authors also say thanks to Andrs Sztodola, from the 1st Department of Pathology and Experimental Cancer Research Institute from Semmelweis University Animal Laboratory, for his technical help during the experiments. The C38 colorectal carcinoma line was maintained by serial subcutaneous transplantations in C57Bl/6 mice. Figure 4. It means that knowing the tumor mass, tumor volume can be estimated with suitable accuracy; hence the lack of MRI measurement can be replaced in the case of Phase I. Comparing ARTIDA-calculated tumor volumes to the volumes derived from the caliper/ellipsoid formula calculations and referenced to the gold standard volume determination method (with literature density values), as it is shown in Figure 2A. Comput. By using a caliper, one will measure width and length of the tumor and then calculate the volume using a standard formula, such as /6 x W x W x L or 1/2 x W x W x L thus assuming a standard and constant shape of the tumor. This creates the possibility of further efficient therapeutic agent use (if any) or assists the more effective direct antitumoral effect of bevacizumab. 16 (2008). Most, if not all, tumors do not fit into this category; this discrepancy results in caliper-based volume measurements including sections that do not exist in the actual tumor, or an overestimation of tumor volume measurement. However, it has to be taken into consideration that in several cases using antiangiogenic therapy, tumor shape is irregular (berry-shaped). Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, Budapest, Hungary, Affiliation []. A direct 3D volume capture instrument, such as the TM900, will make a stereographic image of the tumor and reconstruct the tumor topography and shape. Open Access Click through the PLOS taxonomy to find articles in your field. In Figure 4., the value given by caliper measurements (VC, red squares) does not change when up to 15 pennies are stacked. 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