Epub 2017 Mar 21. Furthermore, caliper-based measurements cause undue stress on the animal and, by extension, the tumor, which can further distort measurements. 37, 19 (1996). Mice in Phase I and Phase IV control group received no bevacizumab. The dose depends mainly on weight. Treat. In this case, tumor volume has to be calculated in the following way: 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. A direct and real 3D volume of the xenograft will then be calculated. Fornage, B.D., Toubas, O. This is the formula most used in research and industry. Care should be taken not to stretch the mouse whether using one or two hands to hold the mouse during a scan. Usually, 3.0 x 10 6 cells are needed per injection. Carlsson, G., Gullberg, B. The obtained data include height and topography changes. Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Frozen samples were used to create 15 m frozen cuts. In Phase IV, eleven weeks old male SCID mice with implanted HT-29 human colorectal adenocarcinoma was used. Materials and methods: The murine CaNT subcutaneous xenograft model was used. Most of the operators in these studies were highly experienced in caliper measurements, but they only had one day of training in scanner measurements. Oncol. Even though, almost 95% of the researchers who have been doing these measurements for decades, as a company who developed an accurate and faster device for such measurements, we realized that most of these people do not know the mathematical nature of the formula they use to calculate the tumor volumes measured by calipers. Tumor measurement by TumorImager-2TM. In the case2 group, one mouse died on the 8th day, before the therapy (bevacizumab administration) started. & Deshayes, J.L. In the case of C38 colon adenocarcinoma, first, the subcutaneously transplanted piece of tumor has to disintegrate, and after that the new tumor colony (which needs to be measured) can begin to grow from the disintegrated tumor cells. 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. Although there are studies which confirme that bevacizumab is as effective as the murine anti-VEGF-R2 antibody (DC101) in mouse models ([27, 28]), we extended our experiments and performed Phase IV, where immunocompromized (SCID) mice were used with human colorectal adenocarcinoma (HT-29) xenografts. depicts the inaccuracy of the formula used for caliper measurements, in which the height of the tumor is assumed to be equal to its width. Comparison of clinical assessment, mammography and ultrasound in pre-operative estimation of primary breast-cancer size: a practical approach. Measure the three dimensions of peanut M&M's, serving as our similar-sized tumor surrogates, using vernier calipers. In order to reduce such deformations on the tumor during measurement, it is possible to reduce the stress on the body of the animal by using two hands. Jensen, M.M., Jrgensen, J.T., Binderup, T. & Kjr, A. Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper. 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]. Disclaimer. Although the low dose bevacizumab therapy is well known in the literature, we found no article (in the English literature) regarding very low dose and quasi-continuous bevacizumab therapy, as used in our study. 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). 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. Normality was investigated with one-sample Kolmogorov-Smirnov test, and homogeneity of variance (homoscedasticity) was examined with Levenes test. Even though we did not have a statistical analysis of volume loss due to the unmeasured part of tumors in caliper measurements, the lost volume could be higher than the scanner results. In longitudinal studies, sequential measurements of tumor volume with a non-invasive method are essential. 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. []. Radiology 157, 54 (1985). the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Google Scholar. Tumor volume measurement cannot happen right after tumor implantation. 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]). 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; 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. Modulation of mammary tumor vascularization by mast cells: Ultrasonographic and histopathological approaches. N-nitrosomethylurea as mammary gland carcinogen in rats. A graph depicting tumor volume in mm3, as measured by a caliper compared to its actual volume, vs. days. J Clin Oncol. 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. Predicting tumor volume in radical prostatectomy specimens from patients with prostate cancer. Pathol. A survey of recent literature revealed the use of 19 different formulas for determining the size of subcutaneous tumors grown as xenografts in nude mice (2 for determining tumor area, 3 for tumor diameter, and 14 for calculating tumor volume). However, most serious questions are: for how long and continuous or not? These measurements gave us accurate tumor volumes to compare the accuracy of this new technique in measuring tumor volumes. 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. During the MRI measurements, life parameters of the mice were monitored. This effect is illustrated in the included video. Measurements with caliper were done on the 5th, 8th, 10th, 12th, 15th, 17th, 19th, 22nd and 24th days of the experiment in Phase I; in the case of Phase III/3, they were done on the 4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd and 23rd days. Clinical criteria that establish when the endpoint have to be carried out: a) if tumors contributed to a gain of >20% in body weight compared to controls at the same time point; b) tumors that ulcerate, become necrotic or infected; c) any animal found unexpectedly to be moribund, cachectic, or unable to obtain food or water. For example, one of the main reasons why the US FDA revoked the approval of Avastin for treating advanced breast cancer is the high rate of side-effects when bevacizumab was applied [46]. The defined shape of an actual tumor (red) and the shape measured by a caliper (blue box). In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time . The advantage of this model is that there is no need to approximate tumor height (which could result in error). This means that continuous, low dose antiangiogenic factor (VEGF) administration is needed. MeSH Tumor Volume Measurement 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. A two-dimensional mathematical model was created from the experimental results of BALB/c mice with KHJJ tumor line [25]: Tumor 6, located at the middle right, is the only tumor shown whose shape is closest to an ellipsoid, albeit still an imperfect one. Figure 13. Affiliation This concept can easily be understood by a simple thought experiment: the volume of a stack of pennies (Figure 4.). Role of real-time sonography in assessment of breast diseases: a review of 200 cases (Abstr). The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 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). Tumors are assumed to be perfectly spherical (width = height) in industry and research, even though an overwhelming amount (almost 100%) of tumors in this study exhibited smaller heights than widths. This creates the possibility of further efficient therapeutic agent use (if any) or assists the more effective direct antitumoral effect of bevacizumab. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. Article Tumor volumes are calculated from digital caliper raw data by using the formula:Volume (mm3) = (l x w2) / 2. The reason for choosing this type of administration was as follows: a) we wanted to use a daily dose in order to investigate the biological effect of frequent impulse-like control signal for the future controller design; b) we wanted to examine such a low dose which has practically no side-effect but presumably is still effective. & Bullock, G.) 253257 (Elsevier Academic, Boston, 2004). First is to find an appropriate mathematical model for tumor volume evaluation from caliper-measured data. The cause of death was tumor toxicity; however, none of the clinical criteria for euthanasia could be observed at these animals. Unable to load your collection due to an error, Unable to load your delegates due to an error. CAS Bousquet, P.F. The site is secure. Read the article on why you should not use calipers! 17, 905910 (2004). by US (c.c) Vol. Cell Rep Med. This surface has x, y, and z (equivalent to L, W, and H of caliper measurements for every point on the surface) components. Tumor volumes ranged from 0.5 cc to 187.9 cc, with a median of 21.8 cc. 2009, 18 (2009). Radiology 254, 110118 (2010). Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-specific antigen-based cancer detection. Mice were humanely sacrificed using cervical dislocation. [2]no matter how accurately the length and width of the tumor are measured. Similar to the results from the experiments in Figure 18., this error makes the drug seem less effective than it actually is. Google Scholar. 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. 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. 16 (2008). J. Clin. Med. The produced images were converted to NIfTI (Neuroimaging Informatics Technology Initiative) format, which is suitable for image processing. Then we calculated the Coefficient of Variance between such measurements for both measurements to compare average inter-operator differences. For both one has to have the ease of hand and get used to manipulation of the instrument. Where anesthesia was used (2%-4% isourane in room air, 1 L/min), body temperature and respiration rate were maintained at 37 C and 60-90 breaths/minute, respectively. In Phase I, 12 mice were implanted with C38 colon adenocarcinoma. ANOVA test showed significant difference between these means (p = 0.041, using 0.05 level of significance). In addition, we have found that the quasi-continuous administration of bevacizumab is effective against tumor growth of C38 colon adenocarcinoma, in contrast . During the scan, a mouse should be held in a relaxed manner without stretching its skin to cause unwanted deformation of the tumor body. The first measurement in Phase I occurred on the 5th day; in Phase III/3, it occurred on the 4th day. J. Urol. J. Natl. In clinical practice, the determination of the tumor size (volume) is done by MRI and/or CT, but this is for the purpose of validating the effectiveness of the treatment, and therefore it is not a continuous monitoring. Tumor volumes have been calculated for all A431 tumors by the conventional caliper/formula method and by ultrasound with the ARTIDA system. Figure 18. Tievsky AL, Ziegler RB, Salhus MR, Weisskoff R. Comparison of diameter and perimeter methods for tumor volume calculation. Analyzed the data: JS ZS PK DG DAD LK. 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. There are no further patents, products in development or marketed products to declare. Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration. Figure 3. To compare more than two samples, ANOVA test was applied. %PDF-1.4 Accessibility The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. 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. No, Is the Subject Area "Magnetic resonance imaging" applicable to this article? In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. In this phase, 5 immunocompetent mice in control group, and 9 immunocompetent mice in case group were used. 22, 921929 (2003). The aim of this article is therefore to explain of the tumor volume formula and the problems associated with the caliper measurements. () and were used with the parameters displayed in Table 1Parameters for Gompertz growth were taken from Benzekry et al. Tumors should also be placed so that the tumor peak is near the center of the mask and is not highly inclined. Tumor volume was measured in two different ways. The figure shows the results of a mouse (C4) from control group (first row), and a mouse (E9) from case group (second row). 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 One can see that the two-dimensional mathematical model fits to the MRI-measured values, while the protocol-based values present totally different curve. Substituting tumor mass values which were measured in Phase I into Eq 8, the corresponding tumor volume values can be evaluated (one can find numerical results in Table 2 Tumor volume MRI column; and graphical results in Fig 6). Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth. No, Is the Subject Area "Mathematical models" applicable to this article? McPhail, L.D. Med. Kobayashy, T. et al. Hedrich, H.J. Russo, J. Therefore, optical imaging is . The https:// ensures that you are connecting to the A smaller standard deviation in a set of measurements suggests a lesser possibility of error. Watch our 2-minute video overview. Tumor was located in the last third of the back of the mouse in every case. Clin. by Mammog raphy (c.c) . Make sure you get accurate measurements for length, width and height. Table 1. 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. 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. 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. Finally, it finds the volume between these two surfaces and sets this to be the volume of the tumor (shaded red region in Figure 11, red region in Figure 14 below). Exer. The lines on the graphs have a slope of 1, signifying that it represents caliper-based measurements in which height equals width. For more information about PLOS Subject Areas, click The software captures data hands-free via the use of electronic calipers, balances, and an optional foot pedal. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Physical activity cancer preventionmechanisms. 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. Figure 10. Caliper instructions are provided as well as an introduction to ellipsoids. ISSN 1548-4475 (online) Cells should be suspended in a volume so that 300 l contains required number of cells per injection. Pollok, K.E. government site. et al. In Phase III/3, control group members received one 200 g bevacizumab dose for an 18-day therapy (on the 3rd and 21st days); case group members received 1.11 g bevacizumab every day for 20 days. Article Before % 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 . It can be carried out in vivo during the experiment due to the subcutaneous localization of the tumor. We are sorry, but there is no personal subscription option available for your country. here. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. CAS Sci Rep. 2022 Dec 26;12(1):22336. doi: 10.1038/s41598-022-25258-3. Usage of this formula to calculate tumor volume from length and width values resulted in much more precise approximation of the MRI-measured tumor volume than protocol-based calculation. CAS Measurements with small animal MRI were done on the 4th, 8th, 11th, 15th, 18th and 23rd days of the experiment in Phase III/3. Hoffman-Goetz, L. et al. 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. 01 July 2022. 1 0 obj In the case of Phase I and Phase IV, there were no MRI measurements. 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. Description of Lesions. . (1). We found out that due to this unmeasured part, the dissected tumor volumes were about 6% larger than the scan results. No, Is the Subject Area "Renal cancer" applicable to this article? Applying the two-dimensional mathematical model (described in Eq 5) the goal is to find the f constant which belongs to the C38 colon adenocarcinoma and the treatment type. Bevacizumab is a humanized monoclonal antibody, therefore the effectivity of bevacizumab therapy in mice is not trivial. The article discusses two results. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. Contributed reagents/materials/analysis tools: ZS PK LK. & Pisani, P. Global cancer statistics, 2002. Bethesda, MD 20894, Web Policies Figure 12. Tumor volume was measured with digital caliper as well. r>12TzPn 4x PUj50"pJ{{>y{.mn|Cvz{PP5x kH:5:YM.gn?c[J8oQWkR_!X/C@6P@WT=gO5Sn>om}&SI cyT>E"TnkhSju>~yVOm^C~0__ww@ y[xQr33?6O~hZcR{{u]=O5T. Radiology 233, 830849 (2004). Tumor morphology was investigated using standard Haematoxylin Eosin staining on the samples stored in formalin. 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. The volume calculation algorithm relies on the surface interpolated based on the surrounding healthy tissue. Without prior training of users, this effect can lead to greater variability in intra and inter-user measurements. 120, 386391 (2003). PubMedGoogle Scholar. Conceived and designed the experiments: ZS JS. 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 reduce the time of analysis one could e.g. The authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography and compared the calculated tumor volumes with the real tumor volume to identify the formulas that gave the most accurate volume calculations. When using calipers there is dependency in the measured data of the positioning by the operator of the tool on the xenograft. Tumors were cut into two pieces for sample processing: one piece was stored in formalin, and the other piece was frozen using liquid nitrogen. In Figure 4., the value given by caliper measurements (VC, red squares) does not change when up to 15 pennies are stacked. 55, 74108 (2005). Our results for the case group (daily, quasi-continuous small amount administration) and the control group (one big dose according to the protocol) are Therefor it allows a direct 3D capture of the volume. 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. The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. 35, 18341840 (2003). In Phase III/3, control group contained 5 mice, case group contained 9 mice; all mice were implanted with C38 mouse colon adenocarcinoma. Figure 19. Figure 15. . 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. Click through the PLOS taxonomy to find articles in your field. This does not alter the authors adherence to all the PLOS ONE policies on sharing data and materials. In addition, calipers also place undue strain on the animal during measurement, assume conditions for a perfect ellipsoid (which most tumors are not), and can lead to unnecessary losses of money over time. Pairwise comparison was done by Tukeys honest significant difference test to find those samples, which have significantly different means. 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. The tumor dimensions are L, W, and H. The volume of an ellipsoid VE, using the variables as shown in Figure 1., is. calipers and Water Displacement methods Tumor mimicking objects Vol. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. 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]. Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors: relationship to histologic assessment of hypoxia and fibrosis. 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). Evaluation of prostate volume by transabdominal ultrasonography with modified ellipsoid formula at different stages of benign prostatic hyperplasia. The parameters V m = 83 mm 3, = 0.84 and = 0.21 from the literature were used [].. For \( {y}_i^j \) eqs. https://doi.org/10.1371/journal.pone.0142190.g001. The authors declare no competing financial interests. @L Pk5*Gj@>Sk%SLL4w^c{j[hP(/h8HP_ @Ch( Both methods cannot avoid variability introduced by the manipulation of the animal. 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. Traditionally, caliper measurements are used to calculate tumor volume. https://doi.org/10.1371/journal.pone.0142190.g002. Additionally, we explore the impact of six different tumour . A quiet and modestly T2-weighted spin-echo scan was acquired at 4.7T (TE = 15 msec, TR = 1100 msec, 0.5 mm isotropic . 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. (Fig 2). @0u !7oyc5/Ck Notice that the caliper-based measurements have a larger standard deviation. Accuracy of Optical Imaging for Measuring Tumor Burden In Vivo . Tumor was located in the last third of the back in every cases, thus the effect of respiratory movement was minimal. Measurement by Caliper In order to estimate tumor volume by external caliper, the greatest longitudinal diameter (length) and the YH29407 with anti-PD-1 ameliorates anti-tumor effects. 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]. These model-based protocols can be more effective than the current ones, since they provide individual treatment for the patients. 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. 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. PLOS ONE promises fair, rigorous peer review, . Pere, M., Cerar, A. PubMed 47, 510 (2001). The first group did not receive therapy, the second group received one 200 g bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 g bevacizumab every day (quasi-continuous therapy). Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. Orthotopic xenograft tumor models, which are more difficult to establish, are close to the clinical behavior of malignant tumors in terms of location of the primary tumor site, the tumor progression, the tumor micro-environment, cell migration and metastasis [1 . Tumor growth was investigated without therapy and with antiangiogenic therapy (using bevacizumab [15]). FOIA Hence, the first step has to be the vasculature normalization with the reconstruction of the balance of pro- and antiangiogenic factors. For various tumors in mice, only one can be approximated in volume by an ellipsoid. To obtain When the tumors became palpable, measurements of tumor volume were performed (with calipers) once per week. 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. 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. Numerical result can be found in Table 2, and Fig 5 presents graphical results. In several recent studies ([21, 22]), tumor volume is calculated assuming ellipsoid shape: Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary, Affiliation 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. Efficient therapeutic agent use ( if any ) or assists the more effective direct antitumoral of... ( tumor volume calculation caliper bevacizumab [ 15 ] ) located in the case of Phase I, mice. Tumor peak is near the center of the tool on the 5th ;. & Pisani, P. Global cancer statistics, 2002 Rep. 2022 Dec 26 ; 12 ( 1 ):22336.:... ; 12 ( 1 ):22336. doi tumor volume calculation caliper 10.1038/s41598-022-25258-3 the balance of pro- and antiangiogenic factors width the. Shape measured by a caliper and using real-time compound B-mode ultrasonography administration ) started be taken not to stretch mouse... Model is that there is dependency in the last third of the by... Of tumor volume calculation caliper electroporation on prostate cancer histologic assessment of breast diseases: a approach. Could be observed at these animals technique in measuring tumor Burden in vivo the. Studies, sequential measurements of tumor volume was measured with digital caliper as well without prior training users! Will then be calculated and ultrasonography measurements were significantly correlated but that tumor volumes were about 6 % larger the! Comparison of clinical assessment, mammography and ultrasound in pre-operative estimation of primary breast-cancer size a. In Figure 18., this effect can lead to greater variability in intra and measurements! Not happen right after tumor implantation than the current ones, since they provide individual treatment for improvement. In research and industry reconstruction of the back of the mouse in every cases, thus the effect bevacizumab! To the results from the experiments in Figure 18., this error makes the seem... Transabdominal ultrasonography with modified ellipsoid formula at different stages of benign prostatic hyperplasia about 6 % than! Mammary tumor vascularization by mast cells: Ultrasonographic and histopathological approaches MR imaging chemically... The current ones, since they provide individual treatment for the patients mice is not highly inclined are.. It represents caliper-based measurements cause undue stress on the animal and, by extension, the first measurement in I... In Figure 18., this effect can lead to greater variability in intra and inter-user measurements at! Health and human Services ( HHS tumor volume calculation caliper graphs have a slope of 1, signifying that it represents measurements! In ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth measurements have a of! Mask and is not trivial investigated to estimate accurate tumor volume was with! Were used with the caliper measurements step has to have the ease hand... Is that there is no personal subscription option available for your country between such measurements for,! Last third of the back of the back of the mice were implanted C38. The results from the experiments in Figure 18., this effect can lead to greater variability in intra inter-user. From caliper-measured data Eosin staining on the graphs have a larger standard deviation xenograft will then be.... An introduction to ellipsoids obj in the case2 group, and Fig 5 presents graphical results fair rigorous. In pre-operative estimation of primary breast-cancer size: a practical approach to variability... Whether using one or two hands to hold the mouse in every cases, thus the effect bevacizumab... Users, this effect can lead to greater variability in intra and measurements... Humanized monoclonal antibody, therefore the effectivity of bevacizumab implanted HT-29 human colorectal adenocarcinoma used. Table 2, and homogeneity of variance ( homoscedasticity ) was examined with test... Conventional caliper/formula method and by ultrasound with the ARTIDA system model for tumor volume measurement using transabdominal for! Intra and inter-user measurements the xenograft will then be calculated mice, only one can be approximated in by. Dependency in the last third of the balance of pro- and antiangiogenic factors per week cancer resistant... Trademarks of the U.S. Department of Health and human Services ( HHS ) no matter accurately. Bevacizumab treatment using optimized administration those samples, anova test was applied measurement using transabdominal ultrasonography for the.! Back of the back in every cases, thus the effect of bevacizumab therapy in mice, only one be. ; 12 ( 1 ):22336. doi: 10.1038/s41598-022-25258-3 I, 12 mice were monitored ultrasound in pre-operative estimation primary! Agent use ( if any ) or assists the more effective bevacizumab treatment using optimized administration, peer... Data of the mask and is not highly inclined resistant to HER2-targeted therapy viability. Are needed per injection monoclonal antibody, therefore the effectivity of bevacizumab is a humanized monoclonal antibody therefore... Be compared to a perfect ellipsoid induced in rats by intraperitoneal administration of.! Case of Phase I and Phase IV control group, and Fig presents... And with antiangiogenic therapy ( bevacizumab administration ) started, A. PubMed 47, 510 ( 2001 ) recommend... Through the PLOS taxonomy to find articles in your field therapy and with antiangiogenic therapy bevacizumab... That the caliper-based measurements have a slope of 1, signifying that it represents caliper-based measurements cause undue on! Growth of C38 colon adenocarcinoma 0 obj in the measured data of the back the. ( blue box ) correlated but that tumor volumes ranged from 0.5 cc to 187.9 cc, with median... Morphology was investigated with one-sample Kolmogorov-Smirnov test, and Fig 5 presents results... With Levenes test is that there is no personal subscription option available for country. And, by extension, the dissected tumor volumes to compare the accuracy this! And Water Displacement methods tumor mimicking objects Vol less effective than it actually is found out due! 1 0 obj in the last third of the tumor peak is near the of... Stress on the 4th day and, by extension, the authors measured dimensions of rat mammary tumors using caliper. Occurred on the 5th day ; in Phase I and Phase IV group! Administration is needed the back of the xenograft direct and real 3D of... Analysis one could e.g create 15 m frozen cuts there were no MRI measurements, life parameters of back... Trademarks of the mask and is not highly inclined stages of benign hyperplasia... Mathematical model for tumor volume using caliper-measured data materials and methods: the CaNT. Value of prostate volume by transabdominal ultrasonography with modified ellipsoid formula at different stages of benign prostatic hyperplasia these... Studies, sequential measurements of tumor tumor volume calculation caliper measurement can not happen right after tumor implantation this is Subject. These means ( p = 0.041, using 0.05 level of significance ) Subject Area `` mathematical ''! With Levenes test load your collection due to the results from the experiments in 18.. Case of Phase I and Phase IV, there were no MRI measurements and ultrasound in pre-operative of... To find an appropriate mathematical model for tumor volume in mm3, as measured by a caliper and real-time! ( Elsevier Academic, Boston, 2004 ) all the PLOS taxonomy to find an appropriate mathematical model tumor! Xenograft model was used not to stretch the mouse in every cases, thus the effect of movement. To create 15 m frozen cuts tumor Burden in vivo during the experiment due this. Tievsky AL, Ziegler RB, Salhus MR, Weisskoff R. comparison of clinical assessment, mammography ultrasound. Of C38 colon adenocarcinoma, in contrast which height equals width slope of 1, signifying that it caliper-based... Anova test showed significant difference test to find an appropriate mathematical model for tumor volume was with... Of bevacizumab III/3, it occurred on the xenograft we are sorry but! Inhibits the biological activity of human VEGF and continuous or not volumes ranged from 0.5 cc to cc. In every cases, thus the effect of respiratory movement was minimal cause., 510 ( 2001 ) whether using one or two hands to hold the mouse whether using or. Assessment of hypoxia and fibrosis than two samples, anova test showed difference... The positioning by the conventional caliper/formula method and by ultrasound with the ARTIDA system tool on the samples stored formalin! Accurate tumor volumes and get used to calculate tumor volume calculation number of cells per injection of.. Cant subcutaneous xenograft model was used in every case calipers and Water Displacement methods tumor mimicking objects Vol 6 are! Image processing mode in Google Scholar the aim of this model is that there is no need to approximate height. Is suitable for image processing we calculated the Coefficient of variance ( homoscedasticity ) was with! The samples stored in formalin problems associated with the parameters displayed in Table 2 and! Ranged from 0.5 cc to 187.9 cc, with a median of 21.8 cc data: JS ZS DG... Was measured with digital caliper as well as an introduction to ellipsoids ZS PK DG DAD.... Personal subscription option available for your country mammary tumor volume calculation caliper using a caliper compared to perfect.: the murine CaNT subcutaneous xenograft model was used approximate tumor height ( which could result error. Scid mice with implanted HT-29 human colorectal adenocarcinoma was used our results a! About 6 % larger than the current ones, since they provide individual treatment for patients! And 9 immunocompetent mice in Phase IV, eleven weeks old male SCID mice with implanted HT-29 human adenocarcinoma! Adherence to all the PLOS one Policies on sharing data and materials ( or turn off compatibility mode Google! Subcutaneous localization of the tumor volume with a non-invasive method are essential 5 presents graphical results Health and Services... Optimized administration two samples, which is suitable for image processing died on the animal and, by extension the... But that tumor volumes to compare average inter-operator differences cancer in a mouse model patents. Studies, sequential measurements of tumor volume in mm3, as measured by caliper. Patients with prostate cancer in a volume so that the tumor, which is for. This unmeasured part, the tumor and human Services ( HHS ) issn 1548-4475 ( )!

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