MeSH As it was discussed above, the handling of animals by calipers measurements also suffers such deformations of the animal body during the measurements. The caliper, unlike the scanner, does not consider that the height of the stack changes while the length and width remain the same. Lee, J., Koh, D. & Ong, C.N. Faustino-Rocha, A., Oliveira, P., Pinho-Oliveira, J. et al. Table 1. The manipulation of the handheld tool is at least as easy as holding a measurement caliper. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. Exer. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. The results of the three investigated cases using C38 mouse colon adenocarcinoma (Phase I, Phase III/3 control group, and Phase III/3 case group) were compared using tumor volume values from MRI measurements (Phase III/3 control and case groups, 23rd day) and evaluated data (Phase I MRI tumor volume calculated from linear curve fit, 24th day). (9). https://doi.org/10.1371/journal.pone.0142190.t003. 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. 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. 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. (1). The 1st Department of Pathology and Experimental Cancer Research of the Semmelweis University (Budapest, Hungary) and the Physiological Controls Group of the Obuda University (Budapest, Hungary) began collaborating on antiangiogenic therapy research in 2012including the current experimental investigations. Yang, C.H., Wang, S.J., Lin, A.T.L., Jen, Y.M. official website and that any information you provide is encrypted Mice were monitored daily by personnel experienced in recognizing signs of morbidity (illness, injury, or abnormal behavior) also in weekends and holidays. 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]. Tumors this large are typically beyond the maximum size allowed by the Institutional Animal Care and Use Committees protocols (IACUC). 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; The post hoc test resulted in the following. Numerical result can be found in Table 2, and Fig 5 presents graphical results. An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. The system includes database, data management and processing software and can be complemented with a weight . From the abovementioned methods, the consequence is that the promising new direction in tumor volume evaluation is the dimension reduction, namely to find a statistical constant which can replace the need of measuring the tumor height. In Phase III/3, case group members received one-tenth dose of control dose intraperitoneally spread over 18 days. Typical side-effects and adverse events are arterial and venous thromboembolic events, bleeding, hypertension, febrile neutropenia, infections, proteinuria, mucositis, and hand-foot syndrome. sharing sensitive information, make sure youre on a federal 2001 Jan 15;19(2):551-7. doi: 10.1200/JCO.2001.19.2.551. First of all, our hypothesis according to the importance of administration is proved. Ergonomics 37, 217229 (1994). Therefore, its formula will always overestimate the tumor volume until the height equals its width, as seen in Figure 3. The widely accepted method for calculating the volume of subcutaneous tumors is to measure the length and width of the tumor with a caliper, and, while assuming that the tumor is the shape of an ellipsoid and that the height of the tumor is equal to its width, use the formula for the volume of an ellipsoid. & Pisani, P. Global cancer statistics, 2002. Russo J, Russo IH, Rogers AE, van Zwieten MJ, Gusterson B. Toxicol Pathol. 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]. 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. An official website of the United States government. %PDF-1.4 Different operators have different ways of holding the animal and tumor while performing the measurement. Determining tumor volume is a useful and quantitative way to monitor tumor progression. Res. Modulation of mammary tumor vascularization by mast cells: Ultrasonographic and histopathological approaches. Tumor growth can take place under such conditions; however delivery of chemotherapeutic drugs is obstructed. In Phase IV, case1 group members received 200 g bevacizumab (with 200 l 0.9% NaCl solution) in one dose intraperitoneally on the 8th day. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. (4). Position of the mouse was fixed to minimize the movement of the animal. CAS <> stream & Hafstrm, L. Estimation of liver tumor volume using different formulasan experimental study in rats. One common measure of efficacy is the T/C ratio, the ratio of tumor volume in control versus treated mice at a specified Imaging 33, 2737 (2006). Fornage, B.D., Toubas, O. where f is a constant which belongs to a certain tumor type. 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. The cause of death was tumor toxicity; however, none of the clinical criteria for euthanasia could be observed at these animals. 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. In Figure 15., the linear regression equation for the best-fit line for VPleth values on the y-axis along with VC and VS values would be approximately y x, or y 1.00x + 0.00. It means that a mouse of the case group received 1.11 g bevacizumab (with 45 l 0.9% NaCl solution) every day from the 3rd day for 20 days. Better results can be obtained by proper handling of the mice. Preclinical evaluation of LU 79553: a novel bis-naphthalimide with potent antitumor activity. J. Oncol. Correspondence to Tumor diameters are measured with digital calipers, and the tumor volume in mm 3 is calculated by the formula: Volume = (width) 2 x length/2; Reference Jacob et al, Gene Ther Mol Biol . Finally, measurements made with the TumorImager scanner showed a significant difference 10 days earlier between the treatment and control group as opposed to caliper-based measurements. Caliper measurements, rather than measuring the actual volume of a tumor, measure the volume of a parallelepiped that surrounds it. Lab Animal P`e+"JF^ : 4:p7]k = Jy}! Combining Mechanisms of Growth Arrest in Solid Tumours: A Mathematical Investigation, Dramatic increase in volume versus length of invasive ductal carcinoma mimicking intramammary lymph node in a small nodular lesion, Alteration in Inflammasome Cytokine Profile and Functional Plasticity of Macrophage Phenotype in Arsenic(0) Nanoparticle Treated Murine Fibrosarcoma, Tumoral CD105 promotes immunosuppression, metastasis, and angiogenesis in renal cell carcinoma, Cancel On the other hand, values given by a scanner (VS, red triangles) more closely follow the true volume of the pennies (VT, blue diamonds). Would you like email updates of new search results? [45] have found that the combination of low-dose cyclophosphamide and ginsenoside Rg3 therapy can be more effective than the normal administration. A tumor tends to be flat early into its growth, and later as time advances, the treatment groups tumors may shrink especially in height if the compound of interest is effective. In this phase, three groups were created. Tumor volumes have been calculated for all A431 tumors by the conventional caliper/formula method and by ultrasound with the ARTIDA system. Sci Rep. 2022 Dec 26;12(1):22336. doi: 10.1038/s41598-022-25258-3. In order to assess interobserver variation, each . Google Scholar. 1 0 obj The means of the samples are mpIV_control = 0.65, mpIV_case1 = 0.70, mpIV_case2 = 0.46. Clarys, J.P. & Marfell-Jones, M.J. Soft tissue segmentation of the body and fractionation of the upper and lower limbs. Westerlind, K.C. Tumor volumes measured with a Plethysmometer (VPleth) independent of caliper and scanner measurements (VC, VS) vs. VC and VS. Table 1. ISSN 1548-4475 (online) In this case, tumor volume has to be calculated in the following way: Tumor Volume Measurement The closer the shape of the tumor is to a perfect ellipsoid, as in the region of the graph in which H closely W, the more closely caliper measurements mirror real-life measurements. J Clin Oncol. Since 2 tumors were unidentifiable on the PET scan only 18 tumors were available for . Since the real geometric object assumed to represent the tumor is a parallelepiped (rather than an ellipsoid), the flat bottom surface of it will leave a larger section of the tumor below than the interpolated surface following the body contour of the animal as seen in Figure 10, below. In each case the reference value is the MRI-measured tumor volume. Yes One can find datasets in Table 3. The defined shape of an actual tumor (red) and the shape measured by a caliper (blue box). Measurements with small animal MRI were done on the 4th, 8th, 11th, 15th, 18th and 23rd days of the experiment in Phase III/3. Examination of tumor growth belongs not only to the basic medical research, but to the biomedical engineering field as well. 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. These images were applied to calculate vascularization area by using ImageJ (NIH, USA) [33] software (Fig 4). The volume calculation algorithm relies on the surface interpolated based on the surrounding healthy tissue. (Fig 2). Please enable it to take advantage of the complete set of features! 2022 Dec 20;3(12):100852. doi: 10.1016/j.xcrm.2022.100852. 17, 905910 (2004). Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. In order to assess the accuracy of tumor measurements by the scanner, we measured the volume of many tumors with a caliper (VC) and with the scanner (VS) first, then after terminating the animals we dissected tumors right around the edges and measured their volumes by dipping them in an accurate volume (VPleth) measuring device called Plethysmometer[8]. 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. 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. Mrio Ginja. Berg, W.A. 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. A smaller standard deviation in a set of measurements suggests a lesser possibility of error. In order to assess interobserver variation, each . In this study, researchers used paclitaxel, a well-known anti-cancer drug since its reaction to cancerous tumors is traceable to assess the results of the scanner measurements. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. https://doi.org/10.1038/laban.254. 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. 2015 Feb;43(2):145-70. doi: 10.1177/0192623314532036. NCI CPTC Antibody Characterization Program. Breast cancer measurements with magnetic resonance imaging, ultrasonography, and mammography. Homogeneity of variance was examined with Levenes test; the sample variances are equal (p = 0.052). Tumors should also be placed so that the tumor peak is near the center of the mask and is not highly inclined. b) Fluorescence picture was created using CD31 antibody immunohistochemistry staining to calculate vascularization area. Usually, 3.0 x 10 6 cells are needed per injection. Google Scholar. Calipers are invasive; they create undue stress on the animal through the awkward handling of the mouse by one hand during the measuring process. In Phase III/3, control group contained 5 mice, case group contained 9 mice; all mice were implanted with C38 mouse colon adenocarcinoma. 19, 6170 (1989). The dose depends mainly on weight. & Bullock, G.) 253257 (Elsevier Academic, Boston, 2004). 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. Enable it to take advantage of the complete set of features operators have different ways of holding the and. Toxicol Pathol the upper and lower limbs but to the basic medical research, but to the importance administration... Tumor peak is near the center of the complete set of features in a model... 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