Pollok, K.E. & Lin, C.A. Westerlind, K.C. Tumor volume measurement cannot happen right after tumor implantation. (Inbred C57Bl/6 mice from our institute were used throughout the studies.) Yes Autopsy revealed large metastasis in the lung, this is the suspected cause of the death. 01 July 2022. Open Access 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. 37, 19 (1996). Tumor volume was calculated by the modified ellipsoidal formula: V = (Length Width 2) . <> Therefore, optical imaging is . government site. In the case of Phase I, no similar problem occurs; the two-dimensional mathematical model can handle great values as well (e.g. and transmitted securely. et al. . 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. This concept can easily be understood by a simple thought experiment: the volume of a stack of pennies (Figure 4.). Lifetime dose-response relationships for mammary tumor induction by a single administration of N-methyl-N-nitrosourea. 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. 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. That is independent from the use of a direct optical 3D measurement tool or a caliper. 3.4. Figure 19. () and were used with the parameters displayed in Table 1Parameters for Gompertz growth were taken from Benzekry et al. Mice in Phase I and Phase IV control group received no bevacizumab. & Hafstrm, L. Estimation of liver tumor volume using different formulasan experimental study in rats. 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. 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. In Phase I, Phase II and Phase III, eight weeks old male C57Bl/6 mice with implanted C38 mouse colorectal carcinoma was used. Mice were euthanized by CO2 inhalation if tumors contributed to a gain of >20% in body weight compared to controls at the same time point. 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. Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-specific antigen-based cancer detection. In Phase IV, approximately 2.9106 cells were injected subcutaneously into each SCID mouse. Usually, 3.0 x 10 6 cells are needed per injection. Copyright 2023 It then segments the tumor boundary (red area surrounded by the yellow boundary in Figure 12.) https://doi.org/10.1371/journal.pone.0142190.g006. No, Is the Subject Area "Mouse models" applicable to this article? The second result which is discussed in the article is comparison of the effectiveness of bevacizumab administration in the case of protocol-based and quasi-continuous therapies. et al. 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 Discover a faster, simpler path to publishing in a high-quality journal. In Phase III/3, case group members received one-tenth dose of control dose intraperitoneally spread over 18 days. 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 Measurement Unmeasured part of the tumor for caliper, Figure 11. Treat. 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. Objectives: Volume measurement of subcutaneous xenograft tumors in nude mice models is an important metric to assess tumor growth or response to therapy. In Phase IV, the caliper measurement days were the 10th, 12th, 17th, 19th, 22nd and 23rd days. In order to assess interobserver variation, each . 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. 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. In the experiment 9.4 Tesla field strength Varian small-animal MRI was used. In that caseeven though all the three diameters can be measuredthe estimation of the volume has quite a large error. Generally, to make caliper measurements, the measurer first traps the tail of the mouse under her fingers, then, grabs the neck of the mouse, and aligns the mouse in her hand in a way to expose the tumor for length and width measurements. All surgery and sacrifice were performed under sodium pentobarbital anaesthesia (Nembutal, 70 mg/kg). Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration. Cancer Res. Bousquet, P.F. 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). https://doi.org/10.1371/journal.pone.0142190.g004. Correlation was investigated with Pearsons rank correlation test (Pearsons R) and coefficient of determination (R2). (8) Ultrasonography as the Gold Standard for In Vivo Volumetric Determination of Chemically-induced Mammary Tumors. Possible mechanisms mediating an association between physical activity and breast cancer. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. Further geometrical or visual data are not stored simultaneously. The site is secure. Tumors should also be placed so that the tumor peak is near the center of the mask and is not highly inclined. Figure 1. All surgery and sacrifice were performed under sodium pentobarbital anaesthesia (Nembutal, 70 mg/kg), and all efforts were made to minimize suffering. Average of tumor volumes for every measurement days of the experiment can be seen in Fig 8. This effect is illustrated in the included video. to calculate several estimates of tumor volume using the equations for the volume of a sphere ([4 /3]r3), Here r is average of a, b and c the volume of an official website and that any information you provide is encrypted The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Bizberg Themes, By Memorial Sloan Kettering Cancer Center. by US (c.c) Vol. 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. In Phase IV, the first measurement occurred when the tumors have reached an average volume of 5060 mm3 (according to the xenograft protocol [20]). Circular RNA circTRPS1-2 inhibits the proliferation and migration of esophageal squamous cell carcinoma by reducing the production of ribosomes. Examination of tumor growth belongs not only to the basic medical research, but to the biomedical engineering field as well. Stretching of the skin around the tumor of the mouse will cause an under-estimate of the tumor volume since the tumor is pressed into the body (see Figure 13. below). Pursuant to one-sample Kolmogorov-Smirnov test, each sample has normal distribution (ppIV_control = 0.981, ppIV_case1 = 0.998, ppIV_case2 = 0.854). 41, 16901694 (1981). Hence, the first step has to be the vasculature normalization with the reconstruction of the balance of pro- and antiangiogenic factors. Even though all the three diameters can be measured, the estimation of the volume has quite a large error. Using the mathematical model, different dosage algorithms can be designed for antiangiogenic cancer therapy [1619]. Exer. recurrent glioblastoma (rGBM) [36]) as a first or second line treatment, usually in combination with chemo- or immunotherapy. PMC . No mice died during the experiment, therefore 5 mice from the control group, and 9 mice from the case group were sacrificed on the 23rd day. Bevacizumab administration was started on the 7th day in both cases. Most, if not all, tumors do not fit into this category; this discrepancy results in caliper-based volume measurements including sections that do not exist in the actual tumor, or an overestimation of tumor volume measurement. Figure 15. 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). Most of the operators in these studies were highly experienced in caliper measurements, but they only had one day of training in scanner measurements. As it was discussed above, the handling of animals by calipers measurements also suffers such deformations of the animal body during the measurements. . Yes In Phase I, tumor growth was investigated without antiangiogenic therapy for 24 days (mice were sacrificed when the tumor reached a lethal size). Influence of breast cancer histology on the relationship between ultrasound and pathology tumor size measurements. Gullino, P.M., Pettigrew, H.M. & Grantham, F.H. 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. Eichelerger, L.E. You are using a browser version with limited support for CSS. For ultrasonography measurements, we calculated tumor volume . Bethesda, MD 20894, Web Policies 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. 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