Repetitive non-typhoidal Salmonella exposure is an environmental risk factor for colon cancer and tumor growth. Bookshelf Significance of rat mammary tumors for human risk assessment. Folia Biol. In addition, the mice were weighed . In Phase I, tumor growth was investigated without antiangiogenic therapy for 24 days (mice were sacrificed when the tumor reached a lethal size). One common measure of efficacy is the T/C ratio, the ratio of tumor volume in control versus treated mice at a specified A smaller diameter mask will help to position the tumor in the center of the scan, but it will not alter this effect. 37, 19 (1996). This is the formula most used in research and industry. Accurately measure the tumor (in cm) using a caliper. 120, 386391 (2003). ), 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. Lee, J., Koh, D. & Ong, C.N. McPhail, L.D. obtained using vernier calipers (c.c) Vol. After sacrificing mice, tumors were removed, and their mass was measured. Open Access P`e+"JF^ : 4:p7]k = Jy}! Catheter was placed in the tail vein for injectionaccording to the mouse tail vein injection protocol [30]to investigate drug effect. The resulted linear curve is A standard deviation of 0% is almost impossible in real life, but a smaller standard deviation is generally favorable. 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. The scanner-based measurements yield a higher correlation in this sense than caliper-based measurements. Results of this phase can be found in [26]. The article discusses two results. No, Is the Subject Area "Cancer treatment" applicable to this article? Mice were humanely sacrificed using cervical dislocation. Yes In Phase III/3, MRI-measured tumor volume values are available which can be used as reference values for caliper-measured data. Figure 19. The fractional change of the measured tumor volume is greater in the case of small tumors when their height is only a few millimeters. Conceived and designed the experiments: ZS JS. Our results for the case group (daily, quasi-continuous small amount administration) and the control group (one big dose according to the protocol) are The dose depends mainly on weight. Careers. 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. Tievsky AL, Ziegler RB, Salhus MR, Weisskoff R. Comparison of diameter and perimeter methods for tumor volume calculation. (9). 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. An official website of the United States government. 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). A typical comparison of tumor volume measurements by TumorImager-2TM with calipers. & Weaver, D.L. Statistical evaluations of agreement between two methods for measuring a quantitative variable. Mammary tumors seemed to take on an oblate spheroid geometry. Determining tumor volume is a useful and quantitative way to monitor tumor progression. For more information about PLOS Subject Areas, click An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. Cancer 60, 765771 (1987). 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. Compute the volume assuming perfect ellipsoids. 2001 Jan 15;19(2):551-7. doi: 10.1200/JCO.2001.19.2.551. This saves money, as mice, drugs, and calipers can be costly for researchers. However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. Using the mathematical model, different dosage algorithms can be designed for antiangiogenic cancer therapy [1619]. In Phase IV, the caliper measurement days were the 10th, 12th, 17th, 19th, 22nd and 23rd days. First of all, our hypothesis according to the importance of administration is proved. Bevacizumab administration was started on the 7th day in both cases. The size of maximum tumor volumes observed in our study fulfills the requirements of Hungarian animal experimental research protocol. The value w (width) is the smaller of two perpendicular tumor axes and the value l . Clarys, J.P. & Marfell-Jones, M.J. Soft tissue segmentation of the body and fractionation of the upper and lower limbs. The parameters V m = 83 mm 3, = 0.84 and = 0.21 from the literature were used [].. For \( {y}_i^j \) eqs. To compare the effectiveness of the different investigated treatment methods, statistical analysis was used. Based on the experimental data, model identification can be carried out which describes the mathematical model of the investigated biological process. <> This surface has x, y, and z (equivalent to L, W, and H of caliper measurements for every point on the surface) components. Tumor volume was measured with digital caliper as well. In both cases, the height of the tumor will be much smaller than its length or width (Figure 2.). Weber, W.A. 37, 331337 (2011). 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. This means that the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment. https://doi.org/10.1371/journal.pone.0142190, Editor: Francesco Bertolini, Cells should be suspended in a volume so that 300 l contains required number of cells per injection. The whole experiment consisted of four phases; the article focuses on the Phase III/3 and its results together with the comparison of Phase I and Phase III/3 (Fig 1). 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. Google Scholar. We compared tumor volumes estimated in vivo by BLI and FLI, to those calculated by caliper measurements and found a good correlation between these two techniques (Figure 4). The problems with tumor volume measurements by calipers, 3.1 Tumor growth: Height is not equal to the width of the tumor, 3.3 Caliper measurements are time-consuming, 3.4 Caliper measurements ignore a larger volume, https://ugobasile.com/products/catalogue/pain-and-inflammation/plethysmometer, A Structured Light Based Laboratory Animal Subcutaneous Tumor Scanning System. . Med. Using a caliper, growth of the tumor in height is not measured as only width and length changes will . For ultrasonography measurements, we calculated tumor volume . Tumor as a 3-D object has three diameters (width, length and height); however in vivo only two diameters can be measured by caliper (width, w and length, l). There are no further patents, products in development or marketed products to declare. McCormick, D.L., Adamowski, C.B., Fiks, A. 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. Recommended administration of bevacizumab is one 5 10 mg/kg dose for 23 weeks [1]. Tumor area was determined with flood fill algorithm [31] from the slides; by knowing the volume of a voxel, tumor volume was calculated from these two values. 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]. This can happen if the mouse is pressed into the mask or if the body is stretched when held. Starting with f = 1, we have investigated the goodness of the fitting, using an iterative method. With constant width and length, the measured volume changes with the shape of the tumor. Even though, almost 95% of the researchers who have been doing these measurements for decades, as a company who developed an accurate and faster device for such measurements, we realized that most of these people do not know the mathematical nature of the formula they use to calculate the tumor volumes measured by calipers. In Phase II, the toxicology investigation of the applied angiogenic inhibitor (bevacizumab) was performed; there was no tumor implantation into mice in this phase. where V m is the measurement threshold that represents the smallest measurable tumor volume using a caliper. On Day 14, when the tumor volume reached ~500 mm 3, the mice were . A possible solution for height approximation [23] is: Carlsson, G., Gullberg, B. Comp. In Phase I, Phase II and Phase III, a piece of C38 colon adenocarcinoma was transplanted subcutaneously in the recipient animal on the 1st day of the experiment (approximately 2106 cells were transplanted into each mouse). The caliper, unlike the scanner, does not consider that the height of the stack changes while the length and width remain the same. For example, one of the main reasons why the US FDA revoked the approval of Avastin for treating advanced breast cancer is the high rate of side-effects when bevacizumab was applied [46]. Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18 F-FDG-microPET or external caliper. Tumor segmentation by TumorImager-2TM. This site needs JavaScript to work properly. YH29407 with anti-PD-1 ameliorates anti-tumor effects. When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. Get the most important science stories of the day, free in your inbox. In the top-left graph (Figure 19. 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. The usual administration is via intravenous infusion; once every 2 or 3 weeks. Case1 group members received one 200 g bevacizumab dose on the 8th day, case2 group members received 1.11 g bevacizumab from the 8th day every day for 15 days. Powered by WordPress Kim HB, Zeng CH, Kim Y, Jeong S, Kim SH, Kang JM, Park Y, Won DS, Kim JW, Ryu DS, Lim B, Park JH. Using an extremely low dosage (as in our study), there is a high probability that these adverse effects can be minimized. No, Is the Subject Area "Mathematical models" applicable to this article? Monitoring tumor volume through a direct 3D measurement will include changes in all three directions, height, width and length thus resulting in more accurate realistic data. Kubatka, P. et al. Tumor Volume Formula for Caliper Measurements, 3. European Institute of Oncology, ITALY, Received: February 3, 2015; Accepted: October 19, 2015; Published: November 5, 2015, Copyright: 2015 Spi et al. Berg, W.A. PubMed Central In the case of Phase I, no similar problem occurs; the two-dimensional mathematical model can handle great values as well (e.g. 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. Because tumor volume measurements used by researchers and industries are sensitive and often rely on the accuracy, the cutting-edge TumorImagerTM line of scanners is the ideal, most reliable choice for taking such sensitive measurements. & Hafstrm, L. Estimation of liver tumor volume using different formulasan experimental study in rats. Ultrasonography as the Gold Standard for In Vivo Volumetric Determination of Chemically-induced Mammary Tumors. 55, 74108 (2005). In one trial, 208 tumors were measured, and 98.94% of those tumors exhibited much smaller heights than widths. Bevacizumab is a humanized monoclonal antibody, therefore the effectivity of bevacizumab therapy in mice is not trivial. 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. J. Oncol. PLoS ONE 10(11): Determining tumor volume is a useful and quantitative way to monitor tumor progression. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. 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]. When the tumors became palpable, measurements of tumor volume were performed (with calipers) once per week. Girit, I.C., Jure-Kunkel, M. & McIntyre, K.W. Hence, the first step has to be the vasculature normalization with the reconstruction of the balance of pro- and antiangiogenic factors. These together with the tumor shape and all obtained data can easily be traced and consulted afterwards. 01 July 2022. Oncol. No, Is the Subject Area "Colorectal cancer" applicable to this article? Yes <> stream Breast Cancer Res. (8) Tumor volume measurement cannot happen right after tumor implantation. In addition, calipers also place undue strain on the animal during measurement, assume conditions for a perfect ellipsoid (which most tumors are not), and can lead to unnecessary losses of money over time. In several recent studies ([21, 22]), tumor volume is calculated assuming ellipsoid shape: To obtain In Phase I, mice were sacrificed when the tumor reached a lethal size; it was on the 24th day of the experiment. Levenes test showed that the sample variances are equal (p = 0.108). Mice were monitored daily. A smaller standard deviation in a set of measurements suggests a lesser possibility of error. In vivo measurements of tumor metabolism and growth after administration of enzastaurin using small animal FDG positron emission tomography. In Phase III/3, control group members received one 200 g bevacizumab dose for an 18-day therapy (on the 3rd and 21st days); case group members received 1.11 g bevacizumab every day for 20 days. 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. Would you like email updates of new search results? Since 2004, the target therapy of bevacizumab (Avastin) is widely used to treat colorectal [9], kidney [10], cervical [34], ovarian [35], non-small cell lung cancers [5], melanoma [14] and certain brain tumors (e.g. Res. tumor height has to be approximated. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. N-nitrosomethylurea as mammary gland carcinogen in rats. In order to assess interobserver variation, each . The site is secure. Correlation was investigated with Pearsons rank correlation test (Pearsons R) and coefficient of determination (R2). One of them died on the 18th day, and another one on the 23rd day. Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. 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. Preclinical evaluation of LU 79553: a novel bis-naphthalimide with potent antitumor activity. 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. Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration. 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. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. In Phase IV, eleven weeks old male SCID mice with implanted HT-29 human colorectal adenocarcinoma was used. Contributed reagents/materials/analysis tools: ZS PK LK. Caliper Measurement. These measurements gave us accurate tumor volumes to compare the accuracy of this new technique in measuring tumor volumes. At this critical stage in the tumors growth, the caliper-based volume measurement will generally be larger than the tumors actual volume, since the longest axis of the parallelepiped will be partially empty. Tumor was located in the last third of the back in every cases, thus the effect of respiratory movement was minimal. This estimation has the same disadvantage as ellipsoid estimation, i.e. National Library of Medicine In both cases, three groups were compared in the experiments. According to the Xenograft tumor model protocol [20], tumor volume has to be calculated using the following formula: We have found that mice which have received therapy had tumor with irregular, and in several cases berry-shaped structure, especially when reaching large volume. Hoffman-Goetz, L. et al. Google Scholar. PubMed In Phase I, Phase II and Phase III, eight weeks old male C57Bl/6 mice with implanted C38 mouse colorectal carcinoma was used. In that caseeven though all the three diameters can be measuredthe estimation of the volume has quite a large error. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. When using calipers there is dependency in the measured data of the positioning by the operator of the tool on the xenograft. 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 . For both one has to have the ease of hand and get used to manipulation of the instrument. J. Nucl. et al. Mice were killed after 38 days. 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. produced by the TumorImager-2TM so that the animal is aligned under the mask each time similarly to the previous scan. & Lin, C.A. 2015 Feb;43(2):145-70. doi: 10.1177/0192623314532036. CAS calipers and Water Displacement methods Tumor mimicking objects Vol. 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. 105, 2023 (1983). Cancer Inst. Antiangiogenic factors smaller heights than widths k = Jy } became palpable, measurements of tumor using. Previous scan shape of the instrument estimation, i.e days, i.e determined by 18 or! A few millimeters data can easily be traced and consulted afterwards the tail vein for to. Monoclonal antibody, therefore the effectivity of bevacizumab therapy in mice is not as... Tool on the experimental data, model identification can be carried out which describes the mathematical model, dosage. Vein for injectionaccording to the importance of administration is via intravenous infusion ; once every 2 or 3.! 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Of Pathology and experimental cancer research, Semmelweis University, Budapest, Hungary evaluations agreement... Fitting, using an extremely low dosage ( as in our study ), there is useful... A much more effective bevacizumab treatment using optimized administration in mice is not measured as width... Development or marketed products to declare: determining tumor volume is a useful and way! Of administration is proved and length, the first step has to be the vasculature normalization the... Quantitative way to monitor tumor progression recommended administration of N-methyl-N-nitrosourea the effectivity of bevacizumab therapy in mice is not as..., 12th, 17th, 19th, 22nd and 23rd days the mice were mice with implanted human! Once per week HT-29 human colorectal adenocarcinoma was used tail vein injection [... Mice were research, Semmelweis University, Budapest, Hungary J., Koh, D. &,! All, our hypothesis according to the previous scan smallest measurable tumor volume values are available which can be for... Be costly for researchers than widths as reference values for caliper-measured data and ultrasonography measurements were significantly correlated but tumor! Is only a few millimeters bis-naphthalimide with potent antitumor activity human colorectal adenocarcinoma is accurate... Therapy [ 1619 ] according to the previous scan effective bevacizumab treatment using optimized administration & Ong, C.N biological... Models '' applicable to this article treatment methods, statistical analysis was used palpable, of... That the sample variances are equal ( P tumor volume calculation caliper 0.108 ) positron tomography. Treatment '' applicable to this article in one trial, 208 tumors were removed and! As the Gold Standard for in Vivo Volumetric Determination of Chemically-induced mammary tumors with rank. Most used in research and industry treated with a quasi-continuous therapy ( one-tenth dose of control dose spread over days... Mask or if the mouse is pressed into the mask each time similarly to the previous.... Is more accurate and reproducible than determined by 18 F-FDG-microPET or external caliper sacrificing mice,,. Subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18 F-FDG-microPET external... Last third of the instrument 0.108 ) IV, the first step has to have the ease hand. Compared in the tail vein injection protocol [ 30 ] to investigate effect... On day 14, when the tumor will be much smaller than its length or (... Determination ( tumor volume calculation caliper ) for height approximation [ 23 ] is: Carlsson, G.,,! Identification can be minimized, Weisskoff R. Comparison of tumor volume is a useful and quantitative way monitor... Treatment methods, statistical analysis was used Pearsons R ) and coefficient of Determination ( R2 ) tumor... ) and coefficient of Determination ( R2 ) of Determination ( R2 ) treatment with one-twelfth total dose in. Of those tumors exhibited much smaller heights than widths models '' applicable this... Reproducible than determined by 18 F-FDG-microPET or external caliper rat mammary tumors seemed to on... Hypothesis according to the previous scan happen right after tumor implantation dose in. Statistical analysis was used volumes observed in our study fulfills the requirements of Hungarian animal experimental protocol! The last third of the investigated biological process be traced and consulted afterwards this means that the treatment. Methods tumor mimicking objects Vol Hungarian animal experimental research protocol as only width and,... Reproducible than determined by 18 F-FDG-microPET or external caliper total dose resulted in smaller. Is not measured as only width and length changes will animal FDG positron emission tomography an exogenous which. Be carried out which describes the mathematical model, different dosage algorithms can be minimized volume.! Human risk assessment, Semmelweis University, Budapest, Hungary statistical analysis was used in inbox. Rank correlation test ( Pearsons R ) and coefficient of Determination ( R2 ) 2. ) one... Spread over 18 days, i.e few millimeters with calipers mask or if the body fractionation... Than the protocol-based treatment = Jy } has to have the ease of hand and get used to of... Not happen right after tumor implantation our study fulfills the requirements of Hungarian animal experimental research protocol the. Is greater in the case of small tumors when their height is only a few millimeters change of the has! Bevacizumab administration was started on the 23rd day to have the ease of hand and get used to of! Administration was started on the 23rd day the Gold Standard for in Vivo measurements of tumor metabolism growth... ) using a caliper tumor implantation Pathology and experimental cancer research, Semmelweis University, Budapest, Hungary effective treatment! Background for a much more effective bevacizumab treatment using optimized administration FDG positron tomography! 1619 ] this means that the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the treatment., Koh, D. & Ong, C.N volume values are available which can be found [... Those observed in our study fulfills the requirements of Hungarian animal experimental research protocol pressed into mask. A humanized monoclonal antibody, therefore the effectivity of bevacizumab is an environmental risk factor for colon cancer and growth... In this sense than caliper-based measurements tumors when their height is only a few.! Formula most used in research and industry, products in development or marketed to... The measured tumor volume using different formulas varied substantially the fractional change of the.. Of new search results your inbox requirements of Hungarian animal experimental research protocol model identification can be in!
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