Prinsip dan Aplikasi Hewan Model dalam Penelitian Kanker
Kata Kunci:
Prinsip, Aplikasi Hewan Model, Penelitian KankerSinopsis
Pengembangan terapi antikanker yang efektif dan aman merupakan salah satu tantangan terbesar dalam dunia medis modern. Kemajuan fundamental dalam bidang ini sangat bergantung pada penggunaan model praklinis yang mampu mereplikasi kompleksitas biologi tumor manusia secara akurat. Buku ajar ini disusun untuk mengisi celah penting dalam literatur ilmiah berbahasa Indonesia, dengan menyajikan panduan komprehensif mengenai penggunaan hewan model non-rekayasa genetika (Non-GMO) dalam penelitian onkologi. Fokus utama buku ini adalah pada model-model yang diinduksi secara kimiawi atau melalui transplantasi, yang sering kali menawarkan keunggulan dalam meniru heterogenitas dan progresi sporadis kanker pada manusia. Urgensi pemahaman mendalam terhadap model-model ini semakin meningkat seiring dengan kesadaran akan pentingnya validitas eksternal dan relevansi klinis dari sebuah penelitian. Tujuan penulisan buku ini adalah untuk membekali para mahasiswa, peneliti, dan akademisi dengan pengetahuan teoretis dan praktis yang kokoh, mulai dari filosofi pemilihan model, standardisasi prosedur, hingga analisis hasil yang valid dan etis.
Bab
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PRAKATA
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KATA PENGANTAR
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DAFTAR ISI
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Bab 1 FILOSOFI DAN JUSTIFIKASI PENGGUNAAN HEWAN MODEL
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Bab 2 STANDAR LINGKUNGAN DAN NUTRISI UNTUK HEWAN MODEL KANKER
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Bab 3 UJI TOKSISITAS BAHAN ALAM UNTUK RISET ANTIKANKER
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Bab 4 RUTE PEMBERIAN KANDIDAT OBAT ANTIKANKER
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Bab 5 MONITORING TUMOR
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Bab 6 PROSEDUR NEKROPSI DAN PENGAMBILAN SAMPEL BIOLOGIS
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Bab 7 MODEL KANKER PAYUDARA
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Bab 8 MODEL KANKER KOLOREKTAL
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Bab 9 MODEL KANKER KULIT
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Bab 10 MODEL KANKER PROSTAT
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Bab 11 MODEL KANKER DARAH DAN KELENJAR GETAH BENING (LEUKEMIA & LYMPHOMA)
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Bab 12 ANALISIS EFEK ANTIKANKER PADA HEWAN MODEL KANKER
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Bab 13 PEMBACAAN SEDIAAN IMUNOHISTOKIMIA MENGGUNAKAN SOFTWARE
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Bab 14 ETIKA PENELITIAN DAN PENYUSUNAN DOKUMEN KAJI ETIK (ETHICAL CLEARANCE)
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REFERENSI
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GLOSARIUM
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PROFIL PENULIS
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Referensi
Abou, D. S., et al. (2015). In vivo imaging of cancer models: a multifaceted approach. Trends in Cancer, 1(1), 52-67. https://doi.org/10.1016/j.trecan.2015.08.005
Acevedo-Arozena, A., et al. (2008). A comprehensive assessment of the ENU-induced mouse mutant repertoire. Science, 321(5887), 394-400.
Aeffner, F., et al. (2019). Introduction to digital image analysis in whole-slide imaging: a white paper from the Digital Pathology Association. Journal of Pathology Informatics, 10, 9. https://doi.org/10.4103/jpi.jpi_82_18
Affara, N. I., et al. (2021). Models of Cutaneous Squamous Cell Carcinoma. Frontiers in Oncology, 11, 702742. https://doi.org/10.3389/fonc.2021.702742
Alizadeh, A. A., et al. (2015). Toward understanding and exploiting tumor heterogeneity. Nature Medicine, 21(8), 846–853. https://doi.org/10.1038/nm.3915
Arriaga-Canon, C., et al. (2020). The role of diet and lifestyle in prostate cancer: insight from DNA methylation and animal models. Nutrients, 12(9), 2697. https://doi.org/10.3390/ nu12092697
Aslantürk, Ö. S. (2018). In Vitro Cytotoxicity and Cell Viability Assays: Principles, Advantages, and Disadvantages. In Genotoxicity and Mutagenicity. IntechOpen. https://doi.org/10.5772/ intechopen.71927
Ballesta, A., Innominato, P. F., Dallmann, R., Rand, D. A., & Lévi, F. A. (2017). Systems Chronotherapeutics. Pharmacological Reviews, 69(2), 161–199. https://doi.org/10.1124/pr.116.013441
Bankhead, P., et al. (2017). QuPath: Open source software for digital pathology image analysis. Scientific Reports, 7(1), 16878. https://doi.org/10.1038/s41598-017-17204-5
Barrow, P. C. (2017). Developmental and reproductive toxicology. In Haschek and Rousseaux's Handbook of Toxicologic Pathology (3rd ed., Vol. 1, pp. 587-633). Academic Press. https://doi.org/10.1016/B978-0-12-801533-1.00021-X
Baumans, V. (2011). Environmental enrichment for laboratory rodents and rabbits: requirements of rodents, rabbits, and research. ILAR Journal, 46(2), 162-170. https://doi.org/10. 1093/ilar.46.2.162
Boopathy, L., Arumugam, S., Ponnusamy, K., Kumar, S., Gopal, T., Durai, S., Ravikumar, S., & Arumugam, M. (2025). Animal Models: A Tool for Colon Cancer Research. Cell Biochemistry and Function, 43. https://doi.org/10.1002/cbf.70087
Bosland, M. C. (2019). Animal models for the study of prostate carcinogenesis. Journal of Cellular Physiology, 234(5), 5529-5540. https://doi.org/10.1002/jcp.27406
Botham, P. A. (2004). Acute toxicity testing in animals. Toxicology in Vitro, 18(2), 225-230. https://doi.org/10.1016/j.tiv.2003.10.001
Cao, L., Liu, X., Lin, E. J., Wang, C., Choi, E. Y., Riban, V., ... & During, M. J. (2010). Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition. Cell, 142(1), 52-64. https://doi.org/10.1016/j. cell.2010.05.029
Carbone, L. (2021). Pain management standards in the eighth edition of the Guide for the Care and Use of Laboratory Animals. Journal of the American Association for Laboratory Animal Science, 51(3), 322-328.
Cardiff, R. D., et al. (2017). The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting. Oncogene, 36(16), 2247-2263. https://doi.org/10.1038/onc.2016.364
Carpenter, A. E., et al. (2006). CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biology, 7(10), R100. https://doi.org/10.1186/gb-2006-7-10-r100
Chapin, R. E., et al. (2004). The role of the alternative animal screening assays in the US National Toxicology Program. Farmaco, 59(9), 701-704. https://doi.org/10.1016/j.farmac. 2004.07.005
Cora, M. C. (2022). The Importance of Rodent Models in Carcinogenicity Testing. Toxicologic Pathology, 50(2), 269–279. https://doi.org/10.1177/01926233211068969
Cross, S. E., et al. (2018). Topical drug delivery in preclinical models of skin cancer. Journal of Controlled Release, 279, 14-25. https://doi.org/10.1016/j.jconrel.2018.04.004
El-Kenawi, A. E., & El-Remessy, A. B. (2013). Angiogenesis inhibitors in cancer therapy: mechanistic perspective on classification and treatment rationales. British Journal of Pharmacology, 170(4), 712-729. https://doi.org/10.1111/bph.12344
Evans, G. O. (2008). Animal Clinical Chemistry: A Primer for Toxicologists. CRC press.
Filipski, E., King, V. M., Li, X., Granda, T. G., Mormont, M. C., Liu, X., ... & Lévi, F. (2009). Host circadian clock as a control point in tumor progression. Journal of the National Cancer Institute, 95(22), 1731-1736. https://doi.org/10.1093/jnci/djg113
Force, T., et al. (2007). Cardiotoxicity of cancer chemotherapy: a scientific and clinical overview. Circulation, 115(5), e123-e127. https://doi.org/10.1161/CIRCULATIONAHA.106.671343
Fridman, W. H., et al. (2012). The immune contexture in human tumours: impact on clinical outcome. Nature Reviews Cancer, 12(4), 298–306. https://doi.org/10.1038/nrc3245
Gaba, R. C., et al. (2011). Animal models of transarterial chemoembolization for hepatocellular carcinoma. Journal of Vascular and Interventional Radiology, 22(11), 1593-1600. https://doi.org/10.1016/j.jvir.2011.08.016
Ganguly, S. S., Li, X., & Miranti, C. K. (2021). The host microenvironment influences prostate cancer invasion, systemic spread, bone colonization, and metastasis. Frontiers in Oncology, 11, 718302. https://doi.org/10.3389/fonc. 2021.718302
Gao, X., Sanderson, S. M., Dai, Z., Reid, M. A., Cooper, D. E., Lu, M., ... & Locasale, J. W. (2019). Dietary methionine influences therapy in mouse cancer models and alters human metabolism. Nature, 572(7769), 397-401. https://doi.org/10. 1038/s41586-019-1437-1
Gaskill, B. N., et al. (2020). The impact of the cage environment on the welfare and utility of laboratory mice. Animal Welfare, 29(3), 227-243. https://doi.org/10.7120/09627286.29.3.227
Gnanasekaran, S., et al. (2021). The impact of diet on animal models of cancer. Cancers, 13(11), 2636. https://doi.org/10.3390/ cancers13112636
Graffi, I., et al. (1968). Virus of the hamster papova-lymphoma. Journal of the National Cancer Institute, 40(5), 867-878.
Grankvist, R., et al. (2019). Pharmacokinetic and pharmacodynamic considerations in the use of osmotic pumps in preclinical studies. Journal of Pharmacological and Toxicological Methods, 97, 1-6. https://doi.org/10.1016/j.vascn.2019.03.001
Groeneveld, S., et al. (2021). Best practices for tissue sample handling for molecular analysis in preclinical research. Journal of Pharmacological and Toxicological Methods, 111, 107095. https://doi.org/10.1016/j.vascn.2021.107095
Gu, F. X., et al. (2012). Local and systemic delivery of cancer therapeutics. Advanced Drug Delivery Reviews, 64(12), 1293-1306. https://doi.org/10.1016/j.addr.2012.06.007
Haines, D. C., et al. (2001). Pathology of aging B6;129 mice. Toxicologic Pathology, 29(6), 653-661. https://doi.org/10.1 080/019262301753385988
Hardy, B., et al. (2017). Genetic toxicology: The evolution of the science and the regulatory landscape. Toxicology Research and Application, 1, 2397847317735398. https://doi.org/10.1177/ 2397847317735398
Harvell, D. M., et al. (2019). The N-methyl-N-nitrosourea (MNU) rat model of hormone-responsive breast cancer. Journal of Visualized Experiments, (145), e59155. https://doi.org/ 10.3791/59155
Hayashi, M., et al. (2016). The micronucleus test: a guide to its use in genetic toxicology. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 811, 27-80. https://doi.org/ 10.1016/j.mrgentox.2016.05.006
Haynes, B. F., et al. (2010). Cardio-oncology: Clinical and translational research using the rabbit model of HTLV-1 infection. Journal of Translational Medicine, 8, 1-12.
Hedrick, M. (2017). Routes of administration in preclinical studies. In A Comprehensive Guide to Toxicology in Preclinical Drug Development (pp. 231-252). Academic Press.
Heiman, M. L., & Greenway, F. L. (2016). A healthy formulation for weight loss and maintenance: the role of purified ingredients. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 310(11), R1131-R1137. https://doi.org/ 10.1152/ajpregu.00085.2016
Hiddinga, B. I., et al. (2019). Preclinical evaluation of drug combinations for cancer therapy. Trends in Pharmacological Sciences, 40(12), 929-940. https://doi.org/10.1016/j.tips.2019. 10.002
Holliday, D. L., & Grunda, J. M. (2010). The 4T1 murine mammary carcinoma model. In Tumor Models in Cancer Research (pp. 265-276). Humana Press. https://doi.org/10.1007/978-1-60761-941-3_13
Hor, S. Y., et al. (2022). A review of the preclinical toxicity evaluation of herbal medicines. Frontiers in Pharmacology, 13, 901551. https://doi.org/10.3389/fphar.2022.901551
Hsu, C. Y., et al. (2019). A practical guide for the administration of substances to laboratory animals. Journal of Visualized Experiments, (149), e59223. https://doi.org/10.3791/59223
ICH. (2000). S5(R2) Guideline on detection of toxicity to reproduction for medicinal products & toxicity to male fertility. International Council for Harmonisation.
ICH. (2005). S6(R1) Preclinical safety evaluation of biotechnology-derived pharmaceuticals. International Council for Harmonisation.
ICH. (2011). S2(R1) Guidance on genotoxicity testing and data interpretation for pharmaceuticals intended for human use. International Council for Harmonisation.
Ittmann, M., et al. (2013). Animal models of human prostate cancer: the consensus report of the New York meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee. Cancer Research, 73(9), 2718-2736. https://doi.org/10.1158/0008-5472.CAN-12-4213
Jackson, S. J., et al. (2017). The influence of the host on the outcome of chemotherapy in preclinical cancer models. Cancer Research, 77(12), 3128-3135. https://doi.org/10.1158/0008-5472.CAN-16-3343
Jensen, M. M., et al. (2018). The validity and reproducibility of caliper-based tumour volume measurements in preclinical cancer studies. PLoS One, 13(9), e0203561. https://doi.org/10.1371/ journal.pone.0203561
Jiang, W., et al. (2017). Local drug delivery in cancer chemotherapy. Expert Opinion on Drug Delivery, 14(1), 61-75. https://doi.org/10.1080/17425247.2016.1218413
Johnstone, C. N., et al. (2015). E0771, a syngeneic mouse mammary cancer model for assessing cancer metabolism and drug response in vivo. Disease Models & Mechanisms, 8(10), 1339-1347. https://doi.org/10.1242/dmm.020473
Kawabata, T. T., & Germolec, D. R. (2018). Immunotoxicology. In Casarett & Doull’s Toxicology: The Basic Science of Poisons (9th ed.). McGraw-Hill.
Kier, L. D. (2010). Veterinary Necropsy Procedures. CRC Press.
Kim, I. S. (2018). Immune-competent mouse models for triple-negative breast cancer. BMB Reports, 51(3), 118–125. https://doi.org/10.5483/BMBRep.2018.51.3.029
Kling, R. R. (2023). Carcinogen-induced mouse models of breast cancer. Methods in Molecular Biology, 2643, 23-34. https://doi.org/10.1007/978-1-0716-2949-3_2
Kokolus, K. M., et al. (2013). Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature. Proceedings of the National Academy of Sciences, 110(50), 20176-20181. https://doi.org/10.1073/pnas.1304291110
Langford, D. J., Bailey, A. L., Chanda, M. L., Clarke, S. E., Drummond, T. E., Echols, S., ... & Mogil, J. S. (2010). Coding of facial expression of pain in the laboratory mouse. Nature Methods, 7(6), 447-449. https://doi.org/10.1038/nmeth.1455
Le, C. P., Nowell, C. J., Kim-Fuchs, C., & Sloan, E. K. (2016). Chronic stress in mice drives blood vessel formation. Nature Communications, 7(1), 1-12. https://doi.org/10.1038/ ncomms10634
Li, J. J., & Li, S. A. (1984). Estrogen-induced tumorigenesis in the Syrian hamster: roles of metabolism and hormonal effects. Archives of Toxicology. Supplement, 7, 113–127. https://doi.org/10.1007/978-3-642-69919-0_12
Li, Z., Zheng, W., Wang, H., Cheng, Y., Fang, Y., Wu, F., Sun, G., Sun, G., Lv, C., & Hui, B. (2021). Application of Animal Models in Cancer Research: Recent Progress and Future Prospects. Cancer Management and Research, 13, 2455–2475. https://doi.org/10.2147/cmar.s302565
Liu, K., et al. (2024). Animal models of skin cancer: A comprehensive review. Journal of Dermatological Science, 113(2), 65-74. https://doi.org/10.1016/j.jdermsci.2023.12.004
Logan, R. W., et al. (2022). The impact of circadian disruption on the tumour microenvironment. Nature Reviews Cancer, 22(2), 75-90. https://doi.org/10.1038/s41568-021-00424-6
Lope, V., et al. (2022). The role of obesity in the relationship between diet and breast cancer. Nutrients, 14(3), 666. https://doi.org/10.3390/nu14030666
Lukas, G., et al. (2009). Intraperitoneal administration of drugs: a review of the literature. Journal of Applied Toxicology, 29(1), 1-13. https://doi.org/10.1002/jat.1384
Mahmoud, N. S., et al. (2022). Selectivity of anticancer agents. European Journal of Medicinal Chemistry, 239, 114510. https://doi.org/10.1016/j.ejmech.2022.114510
Malone, K. E., et al. (2012). Epidemiology of leukemia. In Schottenfeld and Fraumeni Cancer Epidemiology and Prevention. Oxford University Press.
Mandarano, M., et al. (2022). Omega-3 fatty acids and the immune system in cancer. Seminars in Cancer Biology, 85, 203-219. https://doi.org/10.1016/j.semcancer.2022.04.004
Mann, P. C., et al. (2012). Best practices for the conduct of the nonclinical portion of toxicology studies. Toxicologic Pathology, 40(5), 727–739. https://doi.org/10.1177/ 0192623312443836
Marabelle, A., et al. (2017). Intratumoral immunotherapy: a new frontier in cancer treatment. Annals of Oncology, 28(suppl_12), xii33-xii43. https://doi.org/10.1093/annonc/ mdx643
Medina, D. (2005). The prevention of breast cancer by dietary factors. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 591(1-2), 160-170. https://doi.org/10.1016/j. mrfmmm.2005.03.026
Meurens, F., Summerfield, A., Nauwynck, H., Saif, L., & Gerdts, V. (2012). The pig: a model for human infectious diseases. Trends in microbiology, 20(1), 50–57. https://doi.org/10.1016/j. tim.2011.11.002
Meyerholz, D. K., & Beck, A. P. (2018). Principles and approaches for reproducible scoring of tissue stains in research. Laboratory Investigation, 98(7), 844-855. https://doi.org/10.1038/s41374-018-0057-0
Mina, L. A., et al. (2015). Tumor-infiltrating lymphocytes in triple-negative breast cancer. Breast Cancer, 22(2), 113-119. https://doi.org/10.1007/s12282-014-0557-y
Møller, P. (2018). The comet assay: a versatile tool for assessing DNA damage and repair. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 812, 1-2. https://doi.org/10.1016/j.mrfmmm.2018.06.002
Mori, M., et al. (2019). Intra-articular drug delivery systems for the treatment of osteoarthritis. Advanced Drug Delivery Reviews, 146, 221-240. https://doi.org/10.1016/j.addr.2019.09.001
Morse, H. C., 3rd, et al. (2012). Bethesda proposals for classification of lymphoid neoplasms in mice. Blood, 120(19), 3869-3886.
Mortelmans, K., & Zeiger, E. (2000). The Ames Salmonella/microsome mutagenicity assay. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 455(1-2), 29-60. https://doi.org/10.1016/s0027-5107(00)00064-6
Moser, V. C. (2011). Functional assays for neurotoxicity testing. Toxicologic Pathology, 39(1), 36-45. https://doi.org/10.1177/ 0192623310389333
Müller-Newen, G., et al. (2017). Ethylnitrosourea-induced leukemia in mice: A model for human AML. Blood Cancer Journal, 7, e555.
Nascimento-Gonçalves, E., Mendes, B., Silva-Reis, R., Faustino-Rocha, A., Gama, A., & Oliveira, P. (2021). Animal Models of Colorectal Cancer: From Spontaneous to Genetically Engineered Models and Their Applications. Veterinary Sciences, 8(4), 59. https://doi.org/10.3390/vetsci8040059
National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. (2011). Guide for the Care and Use of Laboratory Animals. 8th edition. National Academies Press (US). https://www.ncbi.nlm.nih. gov/books/NBK54050/
Neto, Í., Rocha, J., Gaspar, M., & Reis, C. (2023). Experimental Murine Models for Colorectal Cancer Research. Cancers, 15(9), 2570. https://doi.org/10.3390/cancers15092570
Nigro, E., et al. (2020). Ultraviolet Radiation and the Skin: An In-Depth Review of the Skh-1 Mouse Model. Cancers, 12(12), 3823. https://doi.org/10.3390/cancers12123823
Nowak-Sliwinska, P., et al. (2023). Consensus guidelines for the use and interpretation of angiogenesis assays. Angiogenesis, 26, 369–428. https://doi.org/10.1007/s10456-022-09855-4
OECD. (2002). Test No. 423: Acute Oral Toxicity - Acute Toxic Class Method. OECD Publishing, Paris. https://doi.org/10.1787/ 9789264070943-en
Pamphile, R., et al. (2022). The importance of in vitro toxicology in drug discovery. Expert Opinion on Drug Discovery, 17(7), 735-746. https://doi.org/10.1080/17460441.2022.2078693
Pantanowitz, L., et al. (2022). Twenty years of digital pathology: An overview of the road travelled, what is on the horizon, and the emergence of cyberpathology. Journal of Pathology Informatics, 13, 100159. https://doi.org/10.1016/j. jpi.2022.100159
Parasuraman, S., et al. (2010). Blood collection in small laboratory animals. Journal of Pharmacology & Pharmacotherapeutics, 1(2), 87–93. https://doi.org/10.4103/0976-500X.72350
Patel, J., et al. (2022). Hamster models of melanoma: History, biology, and current applications. Pigment Cell & Melanoma Research, 35(1), 28-39. https://doi.org/10.1111/pcmr.13010
Paz, C. A., et al. (2012). Intrathecal therapy for leptomeningeal metastases: a review. Journal of Neuro-Oncology, 106(2), 205-213. https://doi.org/10.1007/s11060-011-0661-8
Pellizzon, M. A., & Ricci, M. R. (2020). The common challenges of diet-induced preclinical models of metabolic diseases. Animal Models and Experimental Medicine, 3(3), 205-217. https://doi.org/10.1002/ame2.12122
Plaa, G. L., & Hewitt, W. R. (Eds.). (1989). Toxicology of the liver. Raven Press.
Powell, M. D., et al. (2013). Large animal models for leukemia research. Current Protocols in Pharmacology, 60(1), 1-15.
Prokop, S., et al. (2019). CNS drug delivery: a focus on the blood-brain barrier. Expert Review of Neurotherapeutics, 19(11), 1083-1094. https://doi.org/10.1080/14737175.2019.1656514
Rai, S. N., et al. (2021). Animal models of prostate cancer: from discovery to clinical trials. American Journal of Translational Research, 13(8), 8689-8714.
Ramaiah, S. K. (2011). A toxicologist guide to the diagnostic interpretation of hepatic clinical pathology data in rodents. Toxicologic Pathology, 39(2), 383-394. https://doi.org/10. 1177/0192623310395535
Rauth, S., et al. (2017). Preclinical imaging in cancer research. Expert Opinion on Drug Discovery, 12(4), 385-397. https://doi.org/10.1080/17460441.2017.1294833
Richmond, J. (2020). The 3Rs: A Past, Present, and Future of Animal Experimentation. Animal Technology and Welfare, 19(1), 1-14.
Richmond, J. Y., & McKinney, R. W. (Eds.). (2014). Biosafety in microbiological and biomedical laboratories. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institutes of Health.
Rieger, A. M., Nelson, K. L., Konowalchuk, J. D., & Barreda, D. R. (2011). Modified annexin V/propidium iodide apoptosis assay for accurate assessment of cell death. Journal of visualized experiments: JoVE, (50), 2597. https://doi.org/10.3791/2597
Routy, B., Le Chatelier, E., Derosa, L., et al. (2018). Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science, 359(6371), 91–97. https://doi.org/ 10.1126/science.aan3706
Ruehl-Fehlert, C., et al. (2003). A harmonized nomenclature for proliferative and non-proliferative lesions of the rat and mouse haematolymphoid system. Toxicologic Pathology, 31(Suppl), 75–90. https://doi.org/10.1080/01926230390174952
Ruggieri, A., Liberto, M. C., & Fiume, G. (2021). The 3Rs in Oncology: An Update on the Role of In Vivo Models. Cancers, 13(16), 4169. https://doi.org/10.3390/cancers13164169
Ruifrok, A. C., & Johnston, D. A. (2001). Quantification of histochemical staining by color deconvolution. Analytical and Quantitative Cytology and Histology, 23(4), 291-299.
Russo, J., & Russo, I. H. (1996). Experimentally induced mammary tumors in rats. Breast Cancer Research and Treatment, 39(1), 7–20. https://doi.org/10.1007/BF01806093
Saban, R., et al. (2014). A murine model of bladder cancer: technical aspects of the procedure. Journal of Visualized Experiments, (87), e51433. https://doi.org/10.3791/51433
Schacht, M. A., et al. (2020). The porcine prostate: a clinically relevant model for the evaluation of focal ablation technologies. Urology, 141, 186.e1-186.e7. https://doi.org/10.1016/j. urology.2020.03.036
Schraverus, H., Larondelle, Y., & Page, M. (2022). Beyond the Lab: What We Can Learn about Cancer from Wild and Domestic Animals. Cancers, 14(24), 6177. https://doi.org/10.3390/cancers14246177
Sellers, R. S., et al. (2022). Use of Animal Models in Translational Research. Veterinary Pathology, 59(1), 8-24. https://doi.org/10.1177/03009858211042738
Sewduth, R., & Georgelou, K. (2024). Relevance of Carcinogen-Induced Preclinical Cancer Models. Journal of Xenobiotics, 14(1), 96–109. https://doi.org/10.3390/jox14010006
Shamseddine, A. A., et al. (2021). N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis: a model for ER-positive breast cancer. Cancers, 13(16), 4153. https://doi.org/10.3390/cancers13164153
Sivandzade, F., et al. (2019). The role of mitochondria in neurodegenerative diseases. Journal of cellular physiology, 234(8), 12693-12702. https://doi.org/10.1002/jcp.28185
Slater, N. A., et al. (2021). The two-stage model of skin carcinogenesis: A critical review. Experimental Dermatology, 30(8), 1045-1055. https://doi.org/10.1111/exd.14362
Slaoui, M., & Fiette, L. (2011). Histopathology procedures: from tissue sampling to histopathological evaluation. In Drug Safety Evaluation (pp. 69-82). Humana Press. https://doi.org/10. 1007/978-1-60761-849-2_4
Slaoui, M., et al. (2018). Histopathology of the rat immune system. In Toxicologic Pathology.
Sonabend, A. M., et al. (2020). Local drug delivery for the treatment of glioblastoma. Nature Reviews Clinical Oncology, 17(9), 557-575. https://doi.org/10.1038/s41571-020-0381-0
Southam, D. S., et al. (2016). Intranasal administration of drugs to the lungs of mice. Journal of Visualized Experiments, (111), e54112. https://doi.org/10.3791/54112
Stokes, W. S. (2000). Humane endpoints in animal experimentation for biomedical research and testing. ILAR Journal, 41(2), 59-60. https://doi.org/10.1093/ilar.41.2.59
Stritt, M., et al. (2020). Orbit Image Analysis: An open-source whole slide image analysis tool. PLoS Computational Biology, 16(2), e1007313. https://doi.org/10.1371/journal.pcbi.1007313
Sutton, T. T., et al. (2022). A review of preclinical toxicology study designs for new drug development. Journal of Pharmacological and Toxicological Methods, 116, 107198. https://doi.org/10.1016/j.vascn.2022.107198
Talbert, E. E., & Guttridge, D. C. (2016). The role of IKK in cancer-associated cachexia. Molecular and Cellular Endocrinology, 438, 23-31. https://doi.org/10.1016/j.mce.2016.08.019
Tan, J. L., et al. (2021). Topical and transdermal drug delivery for the treatment of skin cancers. Advanced Drug Delivery Reviews, 173, 219-242. https://doi.org/10.1016/j.addr.2021.03.016
Theodoulidis, V. I., et al. (2021). The abscopal effect in cancer immunotherapy. Clinical Oncology, 33(3), 187-197. https://doi.org/10.1016/j.clon.2020.12.012
Turner, P. V., et al. (2011). Administration of substances to laboratory animals: the why, the how, and the when. Journal of the American Association for Laboratory Animal Science, 50(5), 576-591.
Vaidya, V. S., Waikar, S. S., & Ferguson, M. A. (2008). Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clinical Toxicology, 46(8), 701-714. https://doi.org/10.1080/15563650802243884
Varghese, F., et al. (2014). Immunohistochemistry methods for formalin-fixed paraffin-embedded tissue sections. Methods in Molecular Biology, 1180, 47-74. https://doi.org/10.1007/978-1-4939-1062-5_5
Vesely, M. D., Kershaw, M. H., Schreiber, R. D., & Smyth, M. J. (2011). Natural innate and adaptive immunity to cancer. Annual Review of Immunology, 29, 235–271. https://doi.org/10.1146/ annurev-immunol-031210-101324
Vlachogiannis, G., et al. (2021). Patient-derived xenografts and allografts in cancer research. Trends in Cancer, 7(9), 802-817. https://doi.org/10.1016/j.trecan.2021.03.003
Voelkl, B., et al. (2020). Reproducibility of preclinical animal research improves with standardisation of the study design. Nature Reviews Neuroscience, 21(11), 633-634. https://doi.org/10. 1038/s41583-020-0356-9
Wang, T., Chen, Z., Zhang, Y., Liu, M., Sui, H., & Tang, Q. (2025). Recent advances in the development and application of colorectal cancer mouse models. Frontiers in Pharmacology, 16. https://doi.org/10.3389/fphar.2025.1553637
Wang, Y., et al. (2023). Species differences in skin carcinogenesis: A comparative analysis of mouse and rat models. Toxicologic Pathology, 51(4), 189-201. https://doi.org/10.1177/01926233 231178901
Wang, Y., Zhang, L., Feng, W., Liu, W., Xue, X., & Feng, S. (2025). Research advancements and evaluation of multifactor‐induced murine models for gastric cancer. Animal Models and Experimental Medicine, 8, 1923-1934. https://doi.org/10.1002/ ame2.70043
Whittaker, A. L., et al. (2021). The role of refinement in improving animal welfare and scientific outcomes in research. Animals, 11(11), 3045. https://doi.org/10.3390/ani11113045
Wlodkowic, D., et al. (2011). Apoptosis and beyond: assessing cell death with mitochondrial membrane potential probes. Methods, 54(2), 209-214. https://doi.org/10.1016/j.ymeth. 2011.02.002
Wong, G., et al. (2023). The Skh-1 hairless mouse model: A review of its use in photobiology and photocarcinogenesis. Photochemistry and Photobiology, 99(3), 567-580. https://doi.org/10.1111/php.13789
Workman, P., et al. (2010). Guidelines for the welfare and use of animals in cancer research. British Journal of Cancer, 102(11), 1555-1577. https://doi.org/10.1038/sj.bjc.6605642
Xue, Y., Shi, W., Lun, B., Kan, M., Jia, M., Wu, Y., & Yang, L. (2025). Preclinical research models for endometrial cancer: development and selection of animal models. Frontiers in Oncology, 15. https://doi.org/10.3389/fonc.2025.1512616
Zhang, L., et al. (2025). Mechanisms and applications of N-Methyl-N’-nitro-N-nitrosoguanidine in animal tumor models: current situation and challenges. Frontiers in Oncology, 15. https://doi.org/10.3389/fonc.2025.1681270
Zhang, X., Xu, Y., Cao, J., Li, T., Wang, J., Tao, J., Zhang, L., & Li, Z. (2025). Mechanisms and applications of N-Methyl-N’-nitro-N-nitrosoguanidine in animal tumor models: current situation and challenges. Frontiers in Oncology, 15. https://doi.org/10.3389/fonc.2025.1681270
Zhou, J., Liu, C., Amornphimoltham, P., Cheong, S., Gutkind, J., Chen, Q., & Wang, Z. (2024). Mouse Models for Head and Neck Squamous Cell Carcinoma. Journal of Dental Research, 103(6), 585–595. https://doi.org/10.1177/00220345241240997
Zhou, Y., Xia, J., Xu, S., She, T., Zhang, Y., Sun, Y., Wen, M., Jiang, T., Xiong, Y., & Lei, J. (2023). Experimental mouse models for translational human cancer research. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1095388
Zwicker, A., et al. (2023). Porcine skin as a model for human wound healing and scarring. Burns & Trauma, 11, tkad003. https://doi.org/10.1093/burnst/tkad003
