Tumours of the rat. These images also provide extra morphological information about the tumor growth and the effect of the compounds on tumor behavior. Data Availability: All relevant data are within the paper. Yes Open Access 60, 21012103 (2000). & Pisani, P. Global cancer statistics, 2002. Pathol. 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 We found out that due to this unmeasured part, the dissected tumor volumes were about 6% larger than the scan results. 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. Figure 18. shows the results of an experiment in which mice were given different doses of a drug and their tumors were measured both with a caliper or TumorImager scanner. Description of Lesions. One can see that the two-dimensional mathematical model fits to the MRI-measured values, while the protocol-based values present totally different curve. Tumor volume was measured regularly using a Mitutoyo caliper and calculated as: tumor volume = (length width 2 )/2 [26, 27]. The athymic (nude) mouse is a useful model for studying the biology and response to therapies of human tumors in vivo. BMC Med. 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. 2. Sport. PASW Statistics 18 (SPSS Statistics, IBM, USA) and Matlab R2009b (MathWorks, USA) were used for statistical analysis. The tumor burden is evaluated by volume calculation using caliper measurement. Frozen samples were used to create 15 m frozen cuts. PhD from the 1st Department of Pathology and Experimental Cancer Research Institute from Semmelweis University, Budapest, for making the fluorescence pictures with confocal microscope. No, Is the Subject Area "Mouse models" applicable to this article? Also, at beginning of the tumor growth when the tumor is invisible or when a tumor shrinks due to the effectiveness of the drug, in order to measure the volume of such an invisible tumor, it is a general practice to palpate the tumor area to reveal some mass to measure. Several studies have investigated the effectiveness of bevacizumab therapy according to different types of cancer [3]: lung cancer [4, 5], breast cancer [68], colon cancer [9], renal cell carcinoma [10], gastric cancer [11], pancreatic cancer [12], prostate cancer [13] and melanoma [14]. This effect is illustrated in the included video. Yes A two-dimensional mathematical model was created from the experimental results of BALB/c mice with KHJJ tumor line [25]: 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). 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]. () and were used with the parameters displayed in Table 1Parameters for Gompertz growth were taken from Benzekry et al. % In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. et al. (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. 35, 18341840 (2003). 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]. Examination of tumor growth belongs not only to the basic medical research, but to the biomedical engineering field as well. a) Haematoxylin Eosin (H&E) staining was applied to investigate tumor morphology. In Phase IV, the caliper measurement days were the 10th, 12th, 17th, 19th, 22nd and 23rd days. 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 . @L Pk5*Gj@>Sk%SLL4w^c{j[hP(/h8HP_ @Ch( 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 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. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. Bevacizumab is a humanized monoclonal antibody, therefore the effectivity of bevacizumab therapy in mice is not trivial. 58, 264270 (2008). Kubatka, P. et al. 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 . This estimation has the same disadvantage as ellipsoid estimation, i.e. Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. 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). 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. The dose depends mainly on weight. Hence, the first step has to be the vasculature normalization with the reconstruction of the balance of pro- and antiangiogenic factors. Radiology 233, 830849 (2004). & https://doi.org/10.1371/journal.pone.0142190.g001. As is the case with caliper measurements, if the tumor appears visibly flattened and is hard to see by eye then the mouse should be repositioned. et al. endobj by Mammog raphy (c.c) . This concept can easily be understood by a simple thought experiment: the volume of a stack of pennies (Figure 4.). Using the above mentioned iterative method, the resulted equation is Better results can be obtained by proper handling of the mice. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. 3.4. . If one measures the volume of a penny using calipers and uses the widely accepted formula, repeating the measurement each time another penny is added to the stack, the stack will yield the same volume each time, regardless of how many pennies are stacked. Mice were humanely sacrificed using cervical dislocation. A direct 3d measurement tool such as the TM900 does not induce such method sensitivity but cannot exclude operator dependency of the obtained values. A graph depicting tumor volume in mm3, as measured by a caliper compared to its actual volume, vs. days. The effectiveness of bevacizumab administration was examined by statistical analysis. (Budapest, Hungary). 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. 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. Front Chem. Even though all the three diameters can be measured, the estimation of the volume has quite a large error. 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. For both one has to have the ease of hand and get used to manipulation of the instrument. Kim DK, Synn CB, Yang SM, Kang S, Baek S, Oh SW, Lee GJ, Kang HW, Lee YS, Park JS, Kim JH, Byeon Y, Kim YS, Lee DJ, Kim HW, Park JD, Lee SS, Lee JY, Lee JB, Kim CG, Hong MH, Lim SM, Kim HR, Pyo KH, Cho BC. {(Q~J9}=ow[5nkW"C; >tDve+7K,}g?A A typical comparison of tumor volume measurements by TumorImager-2TM with calipers. Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Hoffman-Goetz, L. et al. n5). Scientific Reports The closer the value is to 1, the more precise the data. The manipulation of the handheld tool is at least as easy as holding a measurement caliper. Thirty-two tumors (46%) were nonspherical, as defined above; of these, 19 tumors were nonspherical in the x-y plane, 10 tumors were nonspherical in the y-z plane, and 24 tumors were nonspherical in the x-z plane. The TM900 also stores an optical image in the measurement data base. Citation: Spi J, Kovcs L, Drexler DA, Kocsis P, Gajri D, Spi Z (2015) Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy. The effectiveness of the quasi-continuous (daily) 1/180 dosage (1.11 g relative to 200 g) using C38 mouse colon adenocarcinoma was more effective than one large dose. Breast Cancer Res. Med. VC refers to tumor volume values calculated through the formula VT = 0.5 L W2, and VCH refers to those through the formula VT = 0.5 L W H. VS refers to measurements taken by the scanner, and % Inc. refers to the percent increase between VS and VCH. (6) (7). Lee, J., Koh, D. & Ong, C.N. During the scan, a mouse should be held in a relaxed manner without stretching its skin to cause unwanted deformation of the tumor body. Sci Rep. 2022 Dec 26;12(1):22336. doi: 10.1038/s41598-022-25258-3. 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. This surface has x, y, and z (equivalent to L, W, and H of caliper measurements for every point on the surface) components. Article (4). Contrast agents improve the visibility, but it is an extra strain to the organism, which can be lethal to animals which are in the final stage of cancer. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. After fixing in methanol, rat anti-mouse CD31 antibody (1:50, 550274 BD PHARMINGEN) was applied as primer antibody, and FITC conjugated anti-rat CD31 antibody (1:100, Jackson Immunoresearch, 712-095-150) was applied on the slides as secondary antibody. (8) Mrio Ginja. Figure 17. NCI CPTC Antibody Characterization Program. The .gov means its official. Tumours of the mammary gland. Isofluorane (0.95 x 2.0%) was applied for inhalational anesthesia, and intubation was performed. Mice in Phase III/3 control and case groups, and mice in Phase IV case1 and case2 groups received bevacizumab. B){00)Y$Ixlr{dYe}#@ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ,^X_zN5:EZN]zM^k /Wu^ZZi#Ju.!L!z@u*kUim|+aZmjth-}z5'^|= 4L1_]qVZV*h@! and JavaScript. Later in a study, when a tumor grows into larger masses, the shape of the tumor can differ greatly from an ellipsoid, as shown in Figure 7. 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 . Position of the mouse was fixed to minimize the movement of the animal. bowel, and kidneys is when the tumor is located in . A direct and real 3D volume of the xenograft will then be calculated. Unable to load your collection due to an error, Unable to load your delegates due to an error. & trukelj, B. N-methylnitrosourea induced breast cancer in rat, the histopathology of the resulting tumours and its drawbacks as a model. Figure 13. Considering the possibility of precise tumor volume determination and the effective quasi-continuous drug administration, it opens a new treatment choice based on closed-loop control. However, it has to be taken into consideration that in several cases using antiangiogenic therapy, tumor shape is irregular (berry-shaped). Caliper instructions are provided as well as an introduction to ellipsoids. : All relevant data are within the paper nude ) mouse is a model... 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