Int. The dose depends mainly on weight. It then segments the tumor boundary (red area surrounded by the yellow boundary in Figure 12.) Using the above mentioned iterative method, the resulted equation is . Data Availability: All relevant data are within the paper. [2]no matter how accurately the length and width of the tumor are measured. Google Scholar. YH29407 with anti-PD-1 ameliorates anti-tumor effects. The variables for the volume of a tumor, as measured by a caliper, are determined by a, b, and c in Figure 1, where length L is 2a, width W is 2b, and height H is c. VT, the volume of a tumor is determined by. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. 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). For this dataset, linear curve fitting was carried out (fitted linear curve) to find the mathematical relationship between MRI-measured tumor volume and tumor mass. Isofluorane (0.95 x 2.0%) was applied for inhalational anesthesia, and intubation was performed. 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. We are sorry, but there is no personal subscription option available for your country. Automatic randomization to perform group assignments based on body weight, tumor area/volume, delta tumor volume, or any numeric value and/or user-defined formula; Frozen samples were used to create 15 m frozen cuts. No, Is the Subject Area "Renal cancer" applicable to this article? Weber, W.A. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Hoffman-Goetz, L. et al. 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. No mice died during the experiment, therefore 5 mice from the control group, and 9 mice from the case group were sacrificed on the 23rd day. P`e+"JF^ : 4:p7]k
=
Jy}! As it was discussed above, the handling of animals by calipers measurements also suffers such deformations of the animal body during the measurements. Further geometrical or visual data are not stored simultaneously. 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. 22, 921929 (2003). Caliper Measurement. 17, 905910 (2004). The aim of this article is therefore to explain of the tumor volume formula and the problems associated with the caliper measurements. 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. Levenes test showed that the sample variances are equal (p = 0.108). () and were used with the parameters displayed in Table 1Parameters for Gompertz growth were taken from Benzekry et al. Competing interests: The authors have the following interests: Coauthors PK and DG are employed by Gedeon Richter Ltd. Avastin (bevacizumab) is manufactured by Genentech, Inc., South San Francisco, California, USA; EU patent expiry in 2019 in the US and 2022 in EU. Small MRI measurements were done in the Preclinical Imaging Center of Gedeon Richter Plc. Tumor growth Tumor regression Number of Number of volume volume doublings Percentage additional halvings: Decrease in Percentage decrcase in increase Volume Area" Diameterb volume doubling number Volume Area" Diameterb Doubling of Halving of Volume 1 .o 100.0 58.7 26.0 Volume 1 .o 50.0 37.0 20.6 A typical comparison of tumor volume measurements by TumorImager-2TM with calipers. Sci Rep. 2022 Dec 26;12(1):22336. doi: 10.1038/s41598-022-25258-3. In Phase I, we have investigated tumor growth without therapy with two types of mouse tumor. On Day 14, when the tumor volume reached ~500 mm 3, the mice were . Tumor volumes measured with a Plethysmometer (VPleth) independent of caliper and scanner measurements (VC, VS) vs. VC and VS. Table 1. Description of Lesions. 39, 720 (1996). Notice that the caliper-based measurements have a larger standard deviation. An official website of the United States government. The closer the slope of a line on this graph is to 1 and the y-intercept to 0, the closer the measurements of the device it represents are to the exact values of the tumors volumes. bowel, and kidneys is when the tumor is located in . In addition, we have found that the quasi-continuous administration of bevacizumab is effective against tumor growth of C38 colon adenocarcinoma, in contrast to protocol-based treatment. 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. Homogeneity of variance was examined with Levenes test; the sample variances are equal (p = 0.052). Table 1. Med. The height and topography of the tumor is not taken into account in a caliper measurement. PubMed Central No, PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US, Corrections, Expressions of Concern, and Retractions, https://doi.org/10.1371/journal.pone.0142190, http://www.gene.com/download/pdf/avastin_prescribing.pdf, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000582/WC500029262.pdf, http://www.protocol-online.org/prot/Protocols/Xenograft-Tumor-Model-Protocol-3810.html, http://www.targeson.com/sites/default/files/content/pages/pdfs/tail_vein_protocol_2012_0.pdf. Komrek, V. Gross anatomy. In addition, the root mean square, R2 values under the linear regression equations in Figure 15. symbolize the precision of the data. []. Bethesda, MD 20894, Web Policies The second subphase (Phase III/2) was similar to Phase III/1, mice received the same dosage of bevacizumab as in Phase III/1, however sample size was higher (6 immunocompetent mice in control group, 12 immunocompetent mice in case group), and bevacizumab administration started earlier, on the 3rd day of the experiment. In Phase III/3, control group members received 200 g bevacizumab (with 455 l 0.9% NaCl solution) in one dose intraperitoneally on the 3rd day and on the 21st day. Pairwise comparison was done by Tukeys honest significant difference test to find those samples, which have significantly different means. PLoS ONE 10(11): Results of this phase can be found in [26]. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. Consequences are manifold. (3), Another relatively new but not widely used approach to estimate tumor volume is to assume hemi-ellipsoid shape [24]. For more information about PLOS Subject Areas, click Front Chem. Autopsy revealed large metastasis in the lung, this is the suspected cause of the death. Med. Catheter was placed in the tail vein for injectionaccording to the mouse tail vein injection protocol [30]to investigate drug effect. B){00)Y$Ixlr{dYe}#@ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ,^X_zN5:EZN]zM^k
/Wu^ZZi#Ju.!L!z@u*kUim|+aZmjth-}z5'^|= 4L1_]qVZV*h@! Consequently, when tumor mass data is unavailable (during the experiment), tumor volume value can be validated with MRI; in that way outlier data points (which were calculated using the two-dimensional mathematical model) can be filtered out. 20, the red dots that represent scanner-based measurements are closer to the black dotted (objective) line than the blue squares that represent caliper-based measurements. Accurately measure the tumor (in cm) using a caliper. Kobayashy, T. et al. A caliper only digitizes the length and width of the tumor. 54, 401414 (1975). Eichelerger, L.E. 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]. Clipboard, Search History, and several other advanced features are temporarily unavailable. When the tumors became palpable, measurements of tumor volume were performed (with calipers) once per week. obtained using vernier calipers (c.c) Vol. With constant width and length, the measured volume changes with the shape of the tumor. Tumor volume (and the third diameter) has to be approximated, assuming a certain shape for the tumor. {(Q~J9}=ow[5nkW"C; >tDve+7K,}g?A Notice that the red dots are generally underestimations, while the blue squares are generally overestimations; the former is because of the unmeasured part of the tumor, as discussed in Section 3.5, and the fact that tumors tend to grow under the surface of the skin rather than above it in their early stages of development, and the latter is because of the inherent overestimation in the industry-standard caliper-based formula. 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). The tumor number, from one to ten, is shown against the percent error. A direct 3d measurement tool such as the TM900 does not induce such method sensitivity but cannot exclude operator dependency of the obtained values. In Phase I, mice were sacrificed when the tumor reached a lethal size; it was on the 24th day of the experiment. Epub 2017 Mar 21. Ultrasonography as the Gold Standard for In Vivo Volumetric Determination of Chemically-induced Mammary Tumors. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time . 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. The effectiveness strongly depends on the administration, and a drug which is effective on a molecular level can be applied in a less effective way because of the incorrectly chosen administration. Since, the assumptions made to measure a 3D object with 2D measurements, the error due to the geometrical assumption are larger than the errors due to handling of the animal causing deformation of the tumor, and this aspect, in general, is ignored. Faustino-Rocha AI, Gama A, Oliveira PA, Alvarado A, Fidalgo-Gonalves L, Ferreira R, Ginja M. Faustino-Rocha AI, Silva A, Gabriel J, Teixeira-Guedes CI, Lopes C, Gil da Costa R, Gama A, Ferreira R, Oliveira PA, Ginja M. Biomed Pharmacother. Oncol. Keller M, Rohlf K, Glotzbach A, Leonhardt G, Lke S, Derksen K, Demirci , Gener D, AlWahsh M, Lambert J, Lindskog C, Schmidt M, Brenner W, Baumann M, Zent E, Zischinsky ML, Hellwig B, Madjar K, Rahnenfhrer J, Overbeck N, Reinders J, Cadenas C, Hengstler JG, Edlund K, Marchan R. J Exp Clin Cancer Res. Materials and methods: The murine CaNT subcutaneous xenograft model was used. In the concept of model-based treatment, a continuous and precise tumor volume monitoring is needed concerning which, may be possible in the near future by nanotechnology [38]. Position of the mouse was fixed to minimize the movement of the animal. In addition, the gap between tumor volume values for caliper-based control and treatment groups is smaller than that for scanner measurements; the significant p-value was over 50 times higher when using calipers (p > 0.05) than with scanners (p < 0.001), suggesting that the caliper-based measurements are not statistically significant. No, Is the Subject Area "Cancer treatment" applicable to this article? 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. . Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary, Affiliation Tumor was located in the last third of the back of the mouse in every case. BMC Med.
Fornage, B.D., Toubas, O. 1 0 obj For small tumors, the error is about 7%, while for large tumors it is 27%.[3]. Figure 8. Additionally, this technique is plagued by the inconsistent selection of tumor axes at subsequent examinations. In several recent studies ([21, 22]), tumor volume is calculated assuming ellipsoid shape: Ergonomics 37, 217229 (1994). They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. Almost 90% of the establishments that make tumor volume measurements using calipers use a modified version of the ellipsoid formula, under the incorrect assumption that a tumor is always a perfect ellipsoid. <> Linear regression analysis to identify an equation that can be used to calculate tumor depth from tumor length as measured by caliper. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. The problems with tumor volume measurements by calipers 3.1 Tumor growth: Height is not equal to the width of the tumor . Before To compare more than two samples, ANOVA test was applied. This process not only deforms the tumor mass but also creates undesirable pain on the animal. [45] have found that the combination of low-dose cyclophosphamide and ginsenoside Rg3 therapy can be more effective than the normal administration. Firstly, since the tumor is assumed to be an ellipsoid shape, and the tumors morphology often deviates significantly from this as it grows, this method will produce errors as big as 18.4%. 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