Furthermore, caliper-based measurements cause undue stress on the animal and, by extension, the tumor, which can further distort measurements. 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). First is to find an appropriate mathematical model for tumor volume evaluation from caliper-measured data. 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). The volume above the red area is not occupied by the tumor, as seen in Figure 8. Comparing ARTIDA-calculated tumor volumes to the volumes derived from the caliper/ellipsoid formula calculations and referenced to the gold standard volume determination method (with literature density values), as it is shown in Figure 2A. Faustino-Rocha AI, Gama A, Oliveira PA, Alvarado A, Fidalgo-Gonalves L, Ferreira R, Ginja M. Faustino-Rocha AI, Silva A, Gabriel J, Teixeira-Guedes CI, Lopes C, Gil da Costa R, Gama A, Ferreira R, Oliveira PA, Ginja M. Biomed Pharmacother. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. The closer the slope of a line on this graph is to 1 and the y-intercept to 0, the closer the measurements of the device it represents are to the exact values of the tumors volumes. mum tumor volume of 0.6 mL was reached. Biol. Calipers are invasive; they create undue stress on the animal through the awkward handling of the mouse by one hand during the measuring process. That is independent from the use of a direct optical 3D measurement tool or a caliper. 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. To obtain Experimentally induced mammary tumors in rats. This effect is illustrated in the included video. We found out that due to this unmeasured part, the dissected tumor volumes were about 6% larger than the scan results. Sci. Department of Veterinary Sciences, University of Trs-os-Montes and Alto Douro, Vila Real, Portugal, Ana Faustino-Rocha, Jacinta Pinho-Oliveira, Catarina Teixeira-Guedes& Ruben Soares-Maia, Department of Veterinary Sciences, Animal and Veterinary Research Centre, University of Trs-os-Montes and Alto Douro, Vila Real, Portugal, Paula A. Oliveira, Bruno Colao, Maria Joo Pires& Jorge Colao, Laboratory for Process, Environmental and Energy Engineering, Faculty of Engineering, University of Porto, Porto, Portugal, Faculty of Veterinary Medicine of Lusophone University of Humanities and Technologies, Lisboa, Portugal, Department of Chemistry, Organic Chemistry of Natural Products and Agrifood, Mass Spectrometry Center, University of Aveiro, Aveiro, Portugal, Department of Veterinary Sciences, Centre for Research and Technology of Agro-Environment and Biological Sciences, University of Trs-os-Montes and Alto Douro, Vila Real, Portugal, You can also search for this author in Tumor volumes measured with a Plethysmometer (VPleth) independent of caliper and scanner measurements (VC, VS) vs. VC and VS. Table 1. Davis, P.L. <> stream 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. The site is secure. Pathol. For the TM900 one has to push the acquisition button and almost immediately the images are stored and values calculated. Oncol. 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. One of them died on the 18th day, and another one on the 23rd day. This creates the possibility of further efficient therapeutic agent use (if any) or assists the more effective direct antitumoral effect of bevacizumab. Cancer Inst. Circular RNA circTRPS1-2 inhibits the proliferation and migration of esophageal squamous cell carcinoma by reducing the production of ribosomes. Autopsy revealed only minimal local tumor; however death was not caused by tumor. 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. 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. No animals were sacrificed before the experimental endpoint. In Phase IV, control group contained 5 mice, case1 group contained 10 mice, and case2 group contained 10 mice as well. This formula was the starting point of our examination to find an appropriate mathematical model. Figure 14. Figure 8. Lifetime dose-response relationships for mammary tumor induction by a single administration of N-methyl-N-nitrosourea. Normality was investigated with one-sample Kolmogorov-Smirnov test; each sample has normal distribution (ppI = 0.883, ppIII/3_case = 0.716, ppIII/3_control = 0.869). Caliper- and scanner-based measurements during the various stages of a tumors growth. The athymic (nude) mouse is a useful model for studying the biology and response to therapies of human tumors in vivo. 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. The most accurate volume calculations were obtained using the formula V = (W2 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. Tumor morphology was investigated using standard Haematoxylin Eosin staining on the samples stored in formalin. On the bottom left graph in Fig. Fornage, B.D., Toubas, O. We are sorry, but there is no personal subscription option available for your country. 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 . 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. 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. Res. Examination of tumor growth belongs not only to the basic medical research, but to the biomedical engineering field as well. Similarly, we may have the possibility to a) measure the tumor volume using nanotechnology, b) create a pump for drug administration and c) design control algorithms for specific tumor types. In this study, the researchers measured the same tumors with calipers and the scanner for a about month and a half. The figure shows the results of a mouse (C4) from control group (first row), and a mouse (E9) from case group (second row). 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. The cause of death was tumor toxicity; however, none of the clinical criteria for euthanasia could be observed at these animals. ISSN 1548-4475 (online) In this way, the targeted therapy can be used in a much more individualized form. . 55, 11761180 (1995). This is the formula most used in research and industry. 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. Med. 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. Med. 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. 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. Clipboard, Search History, and several other advanced features are temporarily unavailable. FOIA 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. 2022 Dec 5;10:998013. doi: 10.3389/fchem.2022.998013. https://doi.org/10.1371/journal.pone.0142190.g006. %PDF-1.4 A smaller standard deviation in a set of measurements suggests a lesser possibility of error. (4). In Phase I, mice were sacrificed when the tumor reached a lethal size; it was on the 24th day of the experiment. Careers. The specific roles of these authors are articulated in the author contributions section. Tumor 6, located at the middle right, is the only tumor shown whose shape is closest to an ellipsoid, albeit still an imperfect one. CAS Results of this phase can be found in [26]. For the sake of convenience, establishments will simplify and H. They, for historical reasons (when this formula was stated being used, all the calculations were done in ones head), incorrectly assume that is equal to 3.0 and that the height of a tumor (H) is equal to its width (W). Our hypothesis is that the effectiveness of a lower dosage with a quasi-continuous therapy can be comparable with the protocol therapy. Tumor Volume Formula for Caliper Measurements, 3. 54, 401414 (1975). 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 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). 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. Cancer 83, 621628 (1998). Would you like email updates of new search results? This estimation has the same disadvantage as ellipsoid estimation, i.e. Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors: relationship to histologic assessment of hypoxia and fibrosis. Comp. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. Bookshelf Objectives: Volume measurement of subcutaneous xenograft tumors in nude mice models is an important metric to assess tumor growth or response to therapy. The first column shows the tumor values which were calculated using the two-dimensional mathematical model; the second column represents the protocol-based tumor volumes. Tumor Volume Measurement A direct 3D volume capture instrument, such as the TM900, will make a stereographic image of the tumor and reconstruct the tumor topography and shape. In the case of Phase III/3 and Phase IV, period of time was specified according to the previous phases (Phase I and Phase III/1); mice were sacrificed on the 23rd day of the experiment. Result of Phase III/2 was that the effectiveness of the small amount of quasi-continuous dosage is comparable with the effectiveness of one large dose [23], however this result is only based on caliper-measured data. Internet J. Surg. In Phase II, the toxicology investigation of the applied angiogenic inhibitor (bevacizumab) was performed; there was no tumor implantation into mice in this phase. 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. Weber, W.A. The true volume (VT) of a stack of pennies as measured by caliper (VC) and scanner (VS). 2009, 18 (2009). The data reveals that the mean volume of PTV is 60.8 53.9 cc where these targets exhibit no significant difference between each modality. Radiology 157, 54 (1985). https://doi.org/10.1371/journal.pone.0142190.g008. A direct 3d measurement tool such as the TM900 does not induce such method sensitivity but cannot exclude operator dependency of the obtained values. 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 <> J. Ultrasound Med. 55, 74108 (2005). At some point, the scanner measurements showed a p-value between the treatment group in question and the control, 0.05, which generally experiments stops for a 95% confidence level measurements. When the tumors became palpable, measurements of tumor volume were performed (with calipers) once per week. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in contracts here. In Figure 4., the value given by caliper measurements (VC, red squares) does not change when up to 15 pennies are stacked. Tumor volume measurement cannot happen right after tumor implantation. bowel, and kidneys is when the tumor is located in . Mice were humanely sacrificed using cervical dislocation. Biol. Traditionally their volume growth has been monitored by using a mechanical caliper. Komrek, V. Gross anatomy. Mice were killed after 38 days. Different operators have different ways of holding the animal and tumor while performing the measurement. 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. Lifetime dose-response relationships for mammary tumor induction by a single administration of N-methyl-N-nitrosourea samples stored in formalin proliferation and of. 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