All surgery and sacrifice were performed under sodium pentobarbital anaesthesia (Nembutal, 70 mg/kg). In Figure 4., the value given by caliper measurements (VC, red squares) does not change when up to 15 pennies are stacked. by water displace ment (c.c) Vol. Pere, M., Cerar, A. Position of the mouse was fixed to minimize the movement of the animal. 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. Treat. Yes Analyzed the data: JS ZS PK DG DAD LK. The means of the samples are mpIV_control = 0.65, mpIV_case1 = 0.70, mpIV_case2 = 0.46. Figure 17. When using calipers there is dependency in the measured data of the positioning by the operator of the tool on the xenograft. For the most precise result, tumor mass values, which were measured at the end of the experiment, were compared in the statistical analysis. 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. Consequences are manifold. Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. In Phase IV, control group members received no bevacizumab. 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). 58, 264270 (2008). et al. This creates the possibility of further efficient therapeutic agent use (if any) or assists the more effective direct antitumoral effect of bevacizumab. Role of real-time sonography in assessment of breast diseases: a review of 200 cases (Abstr). How the device is positioned over the tumor will not influence the result. Of course, for the closed-loop design frequent and precise tumor volume measuremets are required, thus the problem of tumor volume measurement has to be solved as well. In several recent studies ([21, 22]), tumor volume is calculated assuming ellipsoid shape: Bevacizumab (Avastin) [1] is an exogenous inhibitor, which inhibits the biological activity of human VEGF [2]. 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. N-nitrosomethylurea as mammary gland carcinogen in rats. Isofluorane (0.95 x 2.0%) was applied for inhalational anesthesia, and intubation was performed. Normality was investigated with one-sample Kolmogorov-Smirnov test, and homogeneity of variance (homoscedasticity) was examined with Levenes test. Provided by the Springer Nature SharedIt content-sharing initiative, Bulletin of the National Research Centre (2022), Lab Animal (Lab Anim) Enter your measurements into the Tumor Volume Calculator to determine the volume of the tumor. Tumor Volume Formula for Caliper Measurements, 3. A tumor expands in width rather than height as it grows. No, Is the Subject Area "Cancer treatment" applicable to this article? 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. Mice were killed after 38 days. Front Chem. As it was discussed above, the handling of animals by calipers measurements also suffers such deformations of the animal body during the measurements. 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). No, Is the Subject Area "Renal cancer" applicable to this article? PLOS ONE promises fair, rigorous peer review, Med. The authors declare no competing financial interests. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. 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. Figure 3. Sci Rep. 2022 Dec 26;12(1):22336. doi: 10.1038/s41598-022-25258-3. In vivo measurements of tumor metabolism and growth after administration of enzastaurin using small animal FDG positron emission tomography. Med. This can happen if the mouse is pressed into the mask or if the body is stretched when held. Tumor segmentation by TumorImager-2TM. Tumor growth inhibition rate (%); can be calculated using the following formula: = (Vc 1 -Vt 1 )/ (Vc 0 -Vt 0) X 100. where, Vc 1 is the mean tumor volume in the control group at the time of tumor . Tumor 6, located at the middle right, is the only tumor shown whose shape is closest to an ellipsoid, albeit still an imperfect one. If this surface intersects above the bottom of the tumor, then the volume estimation of the tumor will be smaller than the true value as can be seen from Figure 9. (1). Typical side-effects and adverse events are arterial and venous thromboembolic events, bleeding, hypertension, febrile neutropenia, infections, proteinuria, mucositis, and hand-foot syndrome. When tumor cells become able to produce proangiogenic factors (the process is called as angiogenic switch), it will result in abnormal and inefficient vascular network (with high vascular permeability and poor perfusion) due to the hurried process of vessel formation. Thank you for visiting nature.com. For small tumors, the error is about 7%, while for large tumors it is 27%.[3]. Calipers are invasive; they create undue stress on the animal through the awkward handling of the mouse by one hand during the measuring process. Figure 15. Notice that the caliper-based measurements have a larger standard deviation. Funding: This work was supported by Hungarian Scientific Research Fund (OTKA), http://www.otka.hu/en, No: K-112993 (Jnos) and Bolyai Research Scholarship of the Hungarian Academy of Sciences, http://mta.hu/cikkek/?node_id=26057, No: 425_12. 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 this phase, control group members received no treatment; case1 group members received one 200 g bevacizumab dose; while case2 group members received 1.11 g bevacizumab daily for 15 days (the total dose of case2 group members is the one-twelfth dose of case1 group members). Eichelerger, L.E. J. Ultrasound Med. Med. Treat. The cells are forced to grow laterally because of the surface tension of the skin above, and the flesh below, which therefore expand the width of the tumor length and widthwise rather than along its height. . Yes Clarke, R. Animal models of breast cancer: their diversity and role in biomedical research. Cancer Inst. When the tumors became palpable, measurements of tumor volume were performed (with calipers) once per week. Mice were monitored daily by personnel experienced in recognizing signs of morbidity (illness, injury, or abnormal behavior) also in weekends and holidays. Lifetime dose-response relationships for mammary tumor induction by a single administration of N-methyl-N-nitrosourea. Kim HB, Zeng CH, Kim Y, Jeong S, Kim SH, Kang JM, Park Y, Won DS, Kim JW, Ryu DS, Lim B, Park JH. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. 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. Make sure you get accurate measurements for length, width and height. Frozen samples were used to create 15 m frozen cuts. Parkin, D.M., Bray, F., Ferlay, J. Starting with f = 1, we have investigated the goodness of the fitting, using an iterative method. This means that continuous, low dose antiangiogenic factor (VEGF) administration is needed. In Phase IV, approximately 2.9106 cells were injected subcutaneously into each SCID mouse. Average of tumor volumes for every measurement days of the experiment can be seen in Fig 8. Breathing was monitored with piezoelectric transducer; temperature of the body was measured by rectal thermometer. Cancer Res. Examining the relationship between MRI-measured tumor volume and tumor mass values, we have found a very strong linear correlation (R = 0.998, R2 = 0.996, p < 0.0001). @L Pk5*Gj@>Sk%SLL4w^c{j[hP(/h8HP_ @Ch( [45] have found that the combination of low-dose cyclophosphamide and ginsenoside Rg3 therapy can be more effective than the normal administration. An official website of the United States government. Tumor volume determined by microCT, 18 F-FDG-PET and external caliper Tumor volume measured by microCT, PET and caliper all correlated (P < 0.001) with reference volume (figure 1).MicroCT versus reference volume (n = 20) had the best fit of line y = 1.01 0.04x - 6.1 6.3 (R 2 = 0.97; p < 0.001). Tracking tumor growth with real tumor scan pictures. The closer the value is to 1, the more precise the data. & Russo, I.H. Open Access CAS Using a caliper, growth of the tumor in height is not measured as only width and length changes will . This is the formula most used in research and industry. Tumor volume was measured with digital caliper. In each case the reference value is the MRI-measured tumor volume. 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]. Yes Even though all the three diameters can be measured, the estimation of the volume has quite a large error. Figure 13. 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. 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. Radiology 233, 830849 (2004). Powered by WordPress
Hoffman-Goetz, L. et al.
41, 16901694 (1981). 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. PubMed Determining tumor volume is a useful and quantitative way to monitor tumor progression. 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]. PASW Statistics 18 (SPSS Statistics, IBM, USA) and Matlab R2009b (MathWorks, USA) were used for statistical analysis. Evaluation of prostate volume by transabdominal ultrasonography with modified ellipsoid formula at different stages of benign prostatic hyperplasia. Results of this phase can be found in [26]. Eur. mum tumor volume of 0.6 mL was reached. Figure 14. For both one has to have the ease of hand and get used to manipulation of the instrument. 19, 6170 (1989). A structured light-based system for scanning subcutaneous tumors in laboratory animals. Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth. a) Haematoxylin Eosin (H&E) staining was applied to investigate tumor morphology. Med. Disclaimer. Using an extremely low dosage (as in our study), there is a high probability that these adverse effects can be minimized. When the tumors became palpable, measurements of tumor volume were performed under sodium anaesthesia. Probability that these adverse effects can be seen in Fig 8 a review of 200 cases ( Abstr.! The mask or if the mouse was fixed to minimize the movement of the positioning by the operator the! The estimation of the positioning by the operator of the volume has quite a large.. M frozen cuts days of the volume has quite a large error = 0.65, mpIV_case1 0.70. 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