Get just this article for as long as you need it, Prices may be subject to local taxes which are calculated during checkout. Cancer 60, 765771 (1987). 41, 16901694 (1981). A direct 3d measurement tool such as the TM900 does not induce such method sensitivity but cannot exclude operator dependency of the obtained values. 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. One can find datasets in the last column of Table 2. Figure 16. depicts the results from a study attended by Biopticon in which ten subcutaneous tumors in mice were measured by scanner and caliper by four operators. Med. We found the same result for human colorectal adenocarcinoma (HT-29) xenografts. Tumor was located in the last third of the back of the mouse in every case. J. Natl. 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. Figure 15. 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. 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. A study[4] (Figure 5.) Thus, caliper-based measurements are less accurate the more the height of the stack deviates from its width. A diagram of an ellipsoid, with the derivations of the variables needed to calculate its volume. It can be carried out in vivo during the experiment due to the subcutaneous localization of the tumor. 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. n5). 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. 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. In Phase I, mice were sacrificed when the tumor reached a lethal size; it was on the 24th day of the experiment. Mammary tumors seemed to take on an oblate spheroid geometry. Tumor volume was measured in two different ways. Comput. Typical side-effects and adverse events are arterial and venous thromboembolic events, bleeding, hypertension, febrile neutropenia, infections, proteinuria, mucositis, and hand-foot syndrome. PMC eCollection 2022. van Elsland DM, Duijster JW, Zhang J, Stvenin V, Zhang Y, Zha L, Xia Y, Franz E, Sun J, Mughini-Gras L, Neefjes J. Article Coauthors PK and DG are employed by Gedeon Richter Ltd. Gedeon Richter Ltd. provided support in the form of salaries for authors PK and DG, and in the form of using the resources of Preclinical Imaging Center of Gedeon Richter Ltd., but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. 39, 16 (1996). Bousquet, P.F. No, Is the Subject Area "Mouse models" applicable to this article? The problems with tumor volume measurements by calipers 3.1 Tumor growth: Height is not equal to the width of the tumor . A quiet and modestly T2-weighted spin-echo scan was acquired at 4.7T (TE = 15 msec, TR = 1100 msec, 0.5 mm isotropic . Mice in the control group received no treatment (5 mice); case1 group members (10 mice) received 10 mg per kg body weight bevacizumab in one dose; while case2 group members (10 mice) received 1/180 dose of control dose for 15 days. A patented algorithm running in the TumorManagerTM program calculates the tumor volume by creating a 3D surface map of the tumor (red-colored surface in Figure 12.). As the height values of the tumors deviate from those of the width, the caliper-based volume values of those tumors begin to mirror real-life measurements less closely. by US (c.c) Vol. Starting with f = 1, we have investigated the goodness of the fitting, using an iterative method. Physical activity cancer preventionmechanisms. This means that the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment. Front Chem. The TumorImagerTM line of scanners by Biopticon Corporation fixes these problems by keeping the animals relaxed during measuring and yielding measurements closer to actual values than caliper-based measurements. We have administered 10 mg/kg body weight intraperitoneally, which means 200 g bevacizumab per a mouse, since the mass of the mice in the experiment was approximately 20 g (in the case of C57Bl/6 and SCID mice as well). Cells should be suspended in a volume so that 300 l contains required number of cells per injection. 01 July 2022. Internet J. Surg. Unauthorized use of these marks is strictly prohibited. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. ISSN 1548-4475 (online) 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. The TM900 also stores an optical image in the measurement data base. the tumor volume are made using digital calipers, and bio logical activity is quantified via the assessment of changes in tumor volume between treated and control mice. 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. 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 . & Weaver, D.L. Autopsy revealed large metastasis in the lung, this is the suspected cause of the death. A standard deviation of 0% is almost impossible in real life, but a smaller standard deviation is generally favorable. Results of this phase can be found in [26]. The protocol was approved by the Hungarian Animal Experimental Research Ethics Council (llatksrleti Tudomnyos Etikai Tancs, ATET), Permit Number: 22.1/1159/3/2010. This problem can be explained by our observation, namely tumors which were grown without therapy have more symmetric and solid closed shape, in contrast to tumors which were grown under antiangiogenic therapy. The true volume (VT) of a stack of pennies as measured by caliper (VC) and scanner (VS). 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 . ), the more correlated a given group (scanner or caliper estimations) is to the black line (r2 = 1), the more accurate the tumor volume measurements are. et al. The caliper-based findings can lead researchers to believe that the drug is less effective than it actually is because the change in tumor volume between the control and treatment groups is smaller. This process takes 45 days. The system includes database, data management and processing software and can be complemented with a weight . These images also provide extra morphological information about the tumor growth and the effect of the compounds on tumor behavior. The closer the value is to 1, the more precise the data. Similarly, Zhang et al. Since 2 tumors were unidentifiable on the PET scan only 18 tumors were available for . Tumors should also be placed so that the tumor peak is near the center of the mask and is not highly inclined. Cancer 83, 621628 (1998). Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. 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. Enter your measurements into the Tumor Volume Calculator to determine the volume of the tumor. The authors declare no competing financial interests. calculate an average volume based on two extreme segmentations; one including most of the border, and one excluding it. The aim of the experiment was to create and validate a clinically relevant tumor growth model (using C38 colon adenocarcinoma), focusing on the effect of angiogenesis. This does not alter the authors adherence to all the PLOS ONE policies on sharing data and materials. Eichelerger, L.E. 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 process slightly stretches the body and deforms the tumor. Objectives: Volume measurement of subcutaneous xenograft tumors in nude mice models is an important metric to assess tumor growth or response to therapy. In the first subphase (Phase III/1), control group members (5 immunocompetent mice) received 10 mg per kg body weight bevacizumab, while case group members (5 immunocompetent mice) received one-tenth dose of control dose spread over 18 days. Google Scholar. Pathol. This paper reviews the standard technique for tumour volume assessment, calliper measurements, by conducting a statistical review of a large dataset consisting of 2,500 tumour volume measurements from 1,600 mice by multiple operators across 6 mouse strains and 20 tumour models. 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. 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. A caliper only digitizes the length and width of the tumor. () and were used with the parameters displayed in Table 1Parameters for Gompertz growth were taken from Benzekry et al. 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