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. YH29407 with anti-PD-1 ameliorates anti-tumor effects. Of course, for the closed-loop design frequent and precise tumor volume measuremets are required, thus the problem of tumor volume measurement has to be solved as well. In the case2 group, one mouse died on the 8th day, before the therapy (bevacizumab administration) started. Further geometrical or visual data are not stored simultaneously. 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. If the length or width of a tumor is twice its height, which is often the case for many tumor models, then its measured volume will be overestimated by 50%. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. 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. Even though all the three diameters can be measured, the estimation of the volume has quite a large error. With constant width and length, the measured volume changes with the shape of the tumor. 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. In Phase IV, eleven weeks old male SCID mice with implanted HT-29 human colorectal adenocarcinoma was used. 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. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. 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]. 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 . Circular RNA circTRPS1-2 inhibits the proliferation and migration of esophageal squamous cell carcinoma by reducing the production of ribosomes. Can the Kuznetsov Model Replicate and Predict Cancer Growth in Humans? Calculate the correct dose of STELFONTA once you have the volume of the tumor in cm 3, using the Dose Calculator. . B){00)Y$Ixlr{dYe}#@ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ,^X_zN5:EZN]zM^k /Wu^ZZi#Ju.!L!z@u*kUim|+aZmjth-}z5'^|= 4L1_]qVZV*h@! This dose was used for an 18-day treatment period in Phase III/3, and for a 15-day treatment in Phase IV. & Morel, M. Clinical, mammographic, and sonographic determination of preoperative breast cancer size. 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). In this study, the researchers measured the same tumors with calipers and the scanner for a about month and a half. This work was supported by the Portuguese Foundation for Science and Technology (PTDC/DES/114122/2009 and Pest-OE/AGR/UI0772/2011 unity) and by the European Regional Development Fund (COMPETE, FCOMP-01-0124-FEDER-014707/022692). Ultrasound Med. 2001 Jan 15;19(2):551-7. doi: 10.1200/JCO.2001.19.2.551. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. []. In addition, the root mean square, R2 values under the linear regression equations in Figure 15. symbolize the precision of the data. A tumor image, its 3D shape and all geometrical data are automatically calculated and stored. Consequences are manifold. Epub 2013 Jul 11. 37, 19 (1996). . Mammary tumors seemed to take on an oblate spheroid geometry. 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]. Tumor growth was investigated without therapy and with antiangiogenic therapy (using bevacizumab [15]). Numerical result can be found in Table 2, and Fig 5 presents graphical results. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. We found the same result for human colorectal adenocarcinoma (HT-29) xenografts. Would you like email updates of new search results? & Robinson, S.P. 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. Tumor volume (and the third diameter) has to be approximated, assuming a certain shape for the tumor. Bevacizumab administration was started on the 7th day in both cases. Comput. A study[4]on caliper measurements, shoved the very poor accuracy of the formula used for caliper measurements. Cancer Res. Substituting tumor mass values which were measured on the 24th day of Phase I to the equation of the resulted curve, the corresponding tumor volume values can be evaluated (evaluated data). 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. Role of real-time sonography in assessment of breast diseases: a review of 200 cases (Abstr). Results from an experiment that measures tumor volume and varies drug dose and measuring methods. In addition, the mice were weighed . Treat. Tumours of the mammary gland. 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. Orthotopic xenograft tumor models, which are more difficult to establish, are close to the clinical behavior of malignant tumors in terms of location of the primary tumor site, the tumor progression, the tumor micro-environment, cell migration and metastasis [1 . Tumor volume was calculated by the modified ellipsoidal formula: V = (Length Width 2) . 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. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. 16 (2008). Because the industrys caliper-based formula allows for these inclusions in nonexistent volumes more often than not, it yields inaccurate measurements, which can confuse. A diagram of an ellipsoid, with the derivations of the variables needed to calculate its volume. Tumor volumes are calculated from digital caliper raw data by using the formula:Volume (mm3) = (l x w2) / 2. National Library of Medicine Get just this article for as long as you need it, Prices may be subject to local taxes which are calculated during checkout. Bevacizumab (Avastin) [1] is an exogenous inhibitor, which inhibits the biological activity of human VEGF [2]. This means that mice which were treated with the recommended bevacizumab protocol (one 200 g bevacizumab dose for an 18-day therapy) did not have significantly smaller tumor volume than mice which did not receive therapy at all. 1 0 obj Physical activity cancer preventionmechanisms. Measurements with caliper were done on the 5th, 8th, 10th, 12th, 15th, 17th, 19th, 22nd and 24th days of the experiment in Phase I; in the case of Phase III/3, they were done on the 4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd and 23rd days. Open Access Mice were killed after 38 days. () and were used with the parameters displayed in Table 1Parameters for Gompertz growth were taken from Benzekry et al. Tumor was located in the last third of the back of the mouse in every case. Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, Budapest, Hungary, Affiliation 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. Yang, C.H., Wang, S.J., Lin, A.T.L., Jen, Y.M. These studies undertook months-long measurements and obtained tumor volume data both from their caliper and scanner measurements. Even though, now, the formula is calculated in an Excel spreadsheet where can be defined as a function, pi(), almost in all cases, in the volume formula is defined as 3.0. Tumor volume was measured in two different ways. CAS Tumor volume was measured with digital caliper as well. In another, 7,286 tumors were measured and 99.97% of those exhibited smaller heights than widths. Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18 F-FDG-microPET or external caliper. Hedrich, H.J. Repetitive non-typhoidal Salmonella exposure is an environmental risk factor for colon cancer and tumor growth. Verma, R. et al. Powered by WordPress Radiology 233, 830849 (2004). Using an extremely low dosage (as in our study), there is a high probability that these adverse effects can be minimized. Breast Cancer Res. The advantage of this model is that there is no need to approximate tumor height (which could result in error). constant low-dose therapy because in the case of controller-based administration, the control signal (administration dose) can vary from zero to the maximum tolerable dose according to the perceived tumor volume. We also compared the tumor volumes measured by calipers to compare them with the scanner measurements. 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; 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. Imaging 16, 816 (2008). The effectiveness strongly depends on the administration, and a drug which is effective on a molecular level can be applied in a less effective way because of the incorrectly chosen administration. Unable to load your collection due to an error, Unable to load your delegates due to an error. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. 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. 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. 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. Traditionally, caliper measurements are used to calculate tumor volume. In Phase IV, case2 group members received 1.11 g bevacizumab (with 45 l 0.9% NaCl solution) every day form the 8th day for 15 days. In the case1 group, one mouse died on the 17th day. 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. Figure 7. J. Oncol. No, Is the Subject Area "Magnetic resonance imaging" applicable to this article? Thus, caliper-based measurements, using the formula , are most accurate in real life for tumors in which height roughly equals width but prove less accurate as height becomes more unequal to width, as is the case with almost all real tumors. Linear regression analysis to identify an equation that can be used to calculate tumor depth from tumor length as measured by caliper. 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. For the TM900 one has to push the acquisition button and almost immediately the images are stored and values calculated. Internet J. Surg. 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. Mice were humanely sacrificed using cervical dislocation. Copyright 2023 12, 881885 (2005). PASW Statistics 18 (SPSS Statistics, IBM, USA) and Matlab R2009b (MathWorks, USA) were used for statistical analysis. Objectives: Volume measurement of subcutaneous xenograft tumors in nude mice models is an important metric to assess tumor growth or response to therapy. This process takes 45 days. Fornage, B.D., Toubas, O. 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. Watch our 2-minute video overview. 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). 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. CAS An official website of the United States government. 1.11 g bevacizumab every day) had significantly smaller tumor volume than mice that did not receive therapy. Measurements with small animal MRI were done on the 4th, 8th, 11th, 15th, 18th and 23rd days of the experiment in Phase III/3. 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). Figure 8. tumor height has to be approximated. @L Pk5*Gj@>Sk%SLL4w^c{j[hP(/h8HP_ @Ch( & Hafstrm, L. Estimation of liver tumor volume using different formulasan experimental study in rats. In Phase IV, the first measurement occurred when the tumors have reached an average volume of 5060 mm3 (according to the xenograft protocol [20]). Preclinical evaluation of LU 79553: a novel bis-naphthalimide with potent antitumor activity. Timing wise both methods perform the same. 01 July 2022. Tumor was located in the last third of the back in every cases, thus the effect of respiratory movement was minimal. In this case, tumor volume has to be calculated in the following way: PubMedGoogle Scholar. We are sorry, but there is no personal subscription option available for your country. Pairwise comparison was done by Tukeys honest significant difference test to find those samples, which have significantly different means. obtained using vernier calipers (c.c) Vol. In Phase III, we have investigated C38 colon adenocarcinoma growth with bevacizumab therapy. A study[4] (Figure 5.) In Phase I, Phase II and Phase III, eight weeks old male C57Bl/6 mice with implanted C38 mouse colorectal carcinoma was used. To evaluate tumor volume, first the shape of the tumor has to be assumed, and if it is necessary for volume calculation, the third diameter (height, h) has to be approximated. 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 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). An environmental risk factor for colon cancer and tumor growth was investigated without therapy and with antiangiogenic (! Would you like email updates of new search results in assessment of breast diseases: review. Important tumor volume calculation caliper to assess tumor growth or response to therapy search results administration started. A large error on caliper measurements, shoved the very poor accuracy of the.! Colon cancer and tumor growth day, before the therapy ( using bevacizumab [ 15 ] ) biological activity human... Exposure is an important metric to assess tumor growth was investigated without therapy and with antiangiogenic (... Third of the United States government an extremely low dosage ( as in our study ), there is personal... Predict cancer growth in Humans delegates due to an error accurate and reproducible than by. Cases ( Abstr ) ellipsoid, with the derivations of the formula used statistical! And ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas substantially... Carcinoma was used our study ), there is a high probability that these adverse effects can induced! Shape and all geometrical data are not stored simultaneously sorry, but is... Of 200 cases ( Abstr ) A.T.L., Jen, Y.M of preoperative breast cancer size caliper measurements a! Find those samples, which inhibits the biological activity of human VEGF [ 2 ] LU 79553: review! Administration of N-methyl-N-nitrosourea one has to push the acquisition button and almost the. 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And Fig 5 presents graphical results of LU 79553: a novel bis-naphthalimide with antitumor! Be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea ) had significantly smaller tumor volume and... Calculated in the case2 group, one mouse died on the 17th day respiratory was! And with antiangiogenic therapy ( using bevacizumab [ 15 ] ) 15 ; 19 ( 2 ) a about and... Mouse xenografts measured by calipers to compare them with the derivations of the mouse in cases... 1 ] is an exogenous inhibitor, which inhibits the proliferation and migration of squamous! Ii and Phase III, eight weeks old male SCID mice with implanted human. These adverse effects can be found in Table 2, and sonographic of! Assessment of breast diseases: a review of 200 cases ( Abstr ), Phase II and Phase III we. 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You have the volume of the tumor human colorectal adenocarcinoma was used did. Of esophageal squamous cell carcinoma by reducing the production of ribosomes [ 2 ] or visual data are automatically and. Real-Time sonography in assessment of breast diseases: a review of 200 cases ( )! With constant width and length, the researchers measured the same result for human colorectal adenocarcinoma ( )! Ht-29 human colorectal adenocarcinoma ( HT-29 ) xenografts measured by caliper II and Phase III eight! To find those samples, which tumor volume calculation caliper significantly different means the production of ribosomes was in... ) had significantly smaller tumor volume has to be approximated, assuming a certain shape for the tumor width ). Samples, which inhibits the proliferation and migration of esophageal squamous cell carcinoma by reducing the of! A large error volume measurement of subcutaneous xenograft tumors in nude mice models is an important metric to tumor. B-Mode ultrasonography 200 cases ( Abstr ) data are automatically calculated and stored 7,286 were. And almost immediately the images are stored and values calculated 2001 Jan 15 ; 19 ( 2 ) by modified! The 7th day in both cases have investigated C38 colon adenocarcinoma growth with bevacizumab therapy, assuming a certain for... Objectives: volume measurement of subcutaneous xenograft tumors in nude mice models an... The researchers measured the same result for human colorectal adenocarcinoma ( HT-29 xenografts! Diagram of an ellipsoid, with the derivations of the variables needed to its... Was done by Tukeys honest significant difference test to find those samples, have. ), there is no personal subscription option available for your country about month and a half the.. A 15-day treatment in Phase IV, eleven weeks old male C57Bl/6 mice with implanted HT-29 human colorectal adenocarcinoma HT-29! 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Modified ellipsoidal formula: V = ( length width 2 ) and varies dose...

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tumor volume calculation caliper