Mẫu hạch lympho của nhóm IR và IR+MEL

Một phần của tài liệu (LUẬN văn THẠC sĩ) đánh giá khả năng bảo vệ mô lành của chuột mang khối u khi điều trị bằng xạ trị thông qua các chỉ tiêu huyết học, hóa sinh và mô học (Trang 53 - 65)

Mẫu hạch lympho của nhóm IR ở độ phóng đại 1X (15A) và 4X (15B) Mẫu hạch lympho của nhóm IR+MEL ở độ phóng đại 1X (15C) và 4X (15D)

Từ các mẫu tiêu bản mô hạch lympho, có thể thấy rằng nhóm NIL khơng gây u, khơng điều trị thì cấu trúc hạch rõ ràng với các nang lympho lớn, xoang nang giãn rộng chứa đại thực bào. Nhóm NC thể hiện sự phát triển tại chỗ của khối u, có di căn vào tổ chức mô, do không được điều trị bằng xạ trị. Khi dùng tia xạ, đối với nhóm IR và IR+MEL, ngăn tế bào ung thư phát triển, những tổn

thương cũng khơng cịn, và khơng có di căn hạch. Tuy nhiên, khi điều trị với melanin trước khi xạ trị thì tác dụng cũng chưa được rõ ràng ưu việt hơn.

KẾT LUẬN VÀ KIẾN NGHỊ

Từ các kết quả thu được, chúng tôi rút ra một số kết luận sau:

 Xạ trị bằng tia X có tác dụng tiêu diệt tế bào ung thư, thu nhỏ kích thước khối u đáng kể. Bên cạnh đó, chiếu xạ tia X gây ra nhiều tác dụng phụ không mong muốn, bao gồm: giảm khả năng sinh trưởng, phát triển của chuột; giảm số lượng hay tỉ lệ vài thành phần quan trọng trong máu (bạch cầu, tiểu cầu, tỉ lệ tế bào lympho).

 Melanin có khả năng làm giảm tác dụng phụ của tia X trong quá trình xạ trị. Cụ thể, điều trị bằng phương pháp hợp kết hợp xạ trị và bổ sung melanin với vai trò như chất bảo vệ (nhóm IR+MEL) làm tăng số lượng tiểu cầu (22,4 %), số lượng bạch cầu (55,6 %), tỷ lệ bạch cầu lympho (8,8 %) hơn so với điều trị khối u chỉ bằng xạ trị (nhóm IR).

 Ngoài ra, từ các kết quả mô học cũng thể hiện được rằng khi bổ sung melanin trước khi xạ trị có khả năng làm giảm sự xơ hóa mơ lách cũng như sung huyết mô hạch lympho, tổ chức nhanh phục hồi hơn so với liệu pháp xạ trị thơng thường.

Để có thể phát triển nghiên cứu và ứng dụng trong thực tiễn, chúng tơi có một số kiến nghị như sau:

 Phân tích sự thay đổi của các loại tế bào miễn dịch trong quá trình xạ trị.  Cần nghiên cứu thêm phương pháp sử dụng melanin nhằm làm tăng hiệu

quả điều trị hay giảm thiểu tác dụng phụ của xạ trị.

 Mở rộng nghiên cứu hơn về các gen khác, mô khác hay đối tượng nghiên cứu khác.

TÀI LIỆU THAM KHẢO

Tiếng Việt:

1. Trịnh Bình (2015), Mơ – Phơi, phần mơ học, Nhà xuất bản Y học, Hà Nội, tr.

128-137.

Tiếng Anh:

2. Albertus B. Mostert, Benjamin J. Powell, Francis L. Pratt, et al. (2012). “Role of semiconductivity and ion transport in the electrical conduction of melanin”, Proc Natl Acad Sci USA, 109(23): 8943-8947.

3. AL-Mufarrej SI, Hassib AM, Hussein MF, “Effect of melanin extract from black cumin seeds (Nigella sativa L.) on Humoral Antibody Response to Sheep Red Blood cells in Albino Rats”, J. Appl. Anim. Res, 2006; 29:337-341.

4. Baraldi PG, Bovero A, Fruttarolo F, Preti D, Tabrizi MA, Pavani MG, Romagnoli R (2004), “DNA minor groove binders as potential antitumor and antimicrobial agents”, Med Res Rev, 24(4):475–528.

5. Brash DE, Rudolph JA, Simon JA, et al. (1991), “A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma”, Proc Natl Acad Sci USA, 88:10124-10128.

6. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018), “Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries”,Ca Cancer J Clin 2018;68:394–424.

7. Brenner M, Hearing VJ. (2008), “The Protective Role of Melanin Against UV Damage in Human Skin”, Photochem Photobiol. 84(3): 539–549.

8. Brittenden, J., Heys, S. D., Ross, J., & Eremin (1996), “Natural killer cells and cancer”, Cancer 77 (7), pp. 1226–1243.

9. C. Andreadisa, K.V., T. Sidirasc, I.T., K.A., and Mouratidoua D. (2003), “5- Fluorouracil and cisplatin in the treatment of advanced oral cancer”, Oral Oncology, 39 (4), pp. 380-385.

10. Chai LY, Netea MG, Sugui J, Vonk AG, van de Sande WW, Warris A, Kwon- Chung KJ, Kullberg BJ (2009), “Aspergillus fumigatus conidial melanin modulates host cytokine response”, Immunobiol.15: 915-920.

11. Chidambaram M, Krishnasamy K (2014), “Drug-drug/drug-excipient compatibility studies on curcumin using non-thermal methods”, Adv Pharm Bull, 4(3):309–312.

12. Chu M, Hai W, Zhang Z, Wo F, Wu Q, et al. (2016), “Melanin nanoparticles derived from a homology of medicine and food for sentinel lymph node mapping and photothermal in vivo cancer therapy”, Biomaterials. 91:182-199. 13. Citrin D, C.A., Hyodo F, Baum Bj, Krishna Mc, Mitchell Jb (2010),

“Radioprotectors and mitigators of radiation-induced normal tissue injury”,

Oncologist, 15 (4), pp. 360–371.

14. Conklin KA. (2004), “Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness”, Integr Cancer Ther, 3(4):294–300.

15. Coppé Jp, D.P., Krtolica a, Campisi J (2010), “The senescence-associated secretory phenotype: the dark side of tumor suppression”, Annu Rev Pathol, 5,

pp. 99–118.

16. Daly MJ, Gaidamakova EK, Matrosova VY, Kiang JG, Fukumoto R, Lee DY, Wehr NB, Viteri GA, Berlett BS, Levine RL (2010), “Small-molecule antioxidant proteome-shields in Deinococcus radiodurans”, PLoS One,

5(9):e12570.

17. Dominguez-Gadea L, Cerezo L (2011), “Decontamination of radioisotopes”,

18. Eva Maria (2009), “Studies of Proteins that Regulate Melanin Synthesis”,

Toronto.

19. Ewald Ja, D.J., Wilding G, Jarrard Df (2010), “Therapy-induced senescence in cancer”, J Natl Cancer Inst, 102 (20), pp. 1536-1546.

20. Fedorocko P, Mackova O (1996), “Radioprotective effects of combination broncho-vaxom, a macrophage activator, and indomethacin, an inhibitor of prostaglandin production: relationship to myelopoiesis”, Eur J Haematol, 56(1– 2):54–61.

21. Felix CC, Hyde JS, Sarna T, Sealy RC (1978), “Interactions of melanin with metal ions. Electron spin resonance evidence for chelate complexes of metal ions with free radicals”, J. Am. Chem. Soc, 100: 3922-3926.

22. Garcia Borron J. C., A. Malek Z. and C. C. Jimenez (2014), “MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation”, Pigment cell & melanoma research, 27, pp. 699-720.

23. Ghoneum M, Badr El-Din NK, Abdel Fattah SM, Tolentino L (2013), “Arabinoxylan rice bran (MGN-3/Biobran) provides protection against whole- body γ-irradiation in mice via restoration of hematopoietic tissues”, J Radiat Res, 54(3):419–429.

24. Gilchrest BA, Eller MS, Geller AC, Yaar M. (1999), “The pathogenesis of melanoma induced by ultraviolet radiation”, N Engl J Med. 340:1341-1348. 25. Glasauer A, C.N. (2014), “Targeting antioxidants for cancer therapy”, Biochem

Pharmacol, 92 (1), pp. 90–101.

26. Gloster HM, Jr, Neal K. (2006), “Skin cancer in skin of color”, J Am Acad Dermatol, 55:761-744.

27. Goyal PK, Gehlot P (2009), “Radioprotective effects of Aloe vera leaf extract on Swiss albino mice against whole-body gamma irradiation”, J Environ Pathol Toxicol Oncol, 28(1):53–61.

28. Grabowski M, Banecki B, Kadzinski L, Jakobkiewicz-Banecka J, Kazmierkiewicz R, Gabig-Ciminska M, Wegrzyn G, Wegrzyn A, Banecka- Majkutewicz Z (2015), “Genistein inhibits activities of methylenetetrahydrofolate reductase and lactate dehydrogenase, enzymes which use NADH as a substrate”, Biochem Biophys Res Commun, 465(3):363– 367.

29. Gurova K (2009), “New hopes from old drugs: revisiting DNA-binding small molecules as anticancer agents”, Future Oncol, 5(10):1685–1704.

30. Ha Hc, T.A., Nelkin Bd, Casero Ra Jr (2000), “Reactive oxygen species are critical for the growth and differentiation of medullary thyroid carcinoma cells”, Clin Cancer Res, 6 (9), pp. 3783–3787.

31. Halder RM, Bridgeman-Shah S. (1995), “Skin cancer in African Americans”,

Cancer. 75:667-673.

32. Herodin FF, Bourin P, Mayol JF, Lataillade JJ, Drouet M (2003), “Short- injection of antiapoptotic cytokine combinations soon after lethal γ -irradiation promotes survival”, Blood, 101:2609–2616.

33. Hoogduijn MJ, Cemeli E, Anderso D., Wood JM, Thody A (2004), “Melanin protects against H2O2- induced DNA strand breaks through its ability to bind Ca2+”, Exp Cell Res, 294: 60-67.

34. Hung YC, Huang GS, Sava VM, Makan S, Hong MY (2008), “Camellia sinensis tea melanin suppresses transformation of the aryl hydrocarbon receptor and prevents against dioxin-induced toxicity in mice”, Int. J Food Sci Technol,

43, 261-269.

35. Hutchison S, Rae C, Tesson M. et al. (2014), “Evaluation of Melanin-Targeted Radiotherapy in Combination with Radiosensitizing Drugs for the Treatment of Melanoma”, Cancer and Oncology Research, 2(4): 58-67.

36. Jagetia GC (2007), “Radioprotective Potential of plants and herbs against the effects of ionizing radiation”, J Clin Biochem Nutr, 40(2):74–81.

37. Jindal A, Agrawal A, Goyal PK (2010), “Influence of Rosemarinus officinalis extract on radiation-induced intestinal injury in mice”, J Environ Pathol Toxicol Oncol, 29(3):169–179.

38. Ka, C. (2004), “Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness”, Integr Cancer Ther, 3 (4), pp. 294–300.

39. Kaidbey KH, Agin PP, Sayre RM, Kligman AM (1979), “Photoprotection by melanin - a comparison of black and Caucasian skin”, J Am Acad Dermatol,

1:249–260.

40. Karlsson O, Lindquist NG (2013), “Melanin affinity and its possible role in neurodegeneration”, J Neural Transm, 120(12):1623-30.

41. Karlsson O Lindquist NG (2016), “Melanin and neuromelanin binding of drugs and chemicals: toxicological implications”, Arch Toxicol, Aug, 90(8):1883-91. 42. Keall, P. (2017), “Explainer: what is cancer radiotherapy and why do we need

proton beam therapy?”.

43. Kollias N, Sayre RM, Zeise L, Chedekel MR (1991), “Photoprotection by melanin”, J Photochem Photobiol B, 9:135-160.

44. Kumar A, Selvan TG, Tripathi AM, Choudhary S, Khan S, Adhikari JS, Chaudhury NK (2015), “Sesamol attenuates genotoxicity in bone marrow cells of whole-body gamma-irradiated mice”, Mutagenesis, 30(5):651–661.

45. Kumar CG, Mongolla P, Pombala S, Kamle A, Joseph J (2011), “Physicochemical characterization and antioxidant activity of melanin from a novel strain of Aspergillus bridgeri”, ICTF-Lett Appl Microbiol, 53:350-358. 46. Kunwar, A., Adhikary, B., Jayakumar, S., Barik, A., Chattopadhyay, S.,

Raghukumar, S., & Priyadarsini, K. I. (2012), Melanin, a promising

radioprotector: Mechanisms of actions in a mice model. Toxicol. Appl. Pharm.,

47. Kvam E, Tyrrell RM (1997), “Induction of oxidative DNA base damage in human skin cells by UV and near visible radiation”, Carcinogenesis, 18:2379-

2384.

48. Larsson BS (1993), Interaction Between Chemicals and Melanin Pigment. Cell

Research, 6:127–133.

49. Lord B, Hendry JH (1995), “Radiation toxicology: bone marrow and leukemia”, Radiation toxicology: bone marrow and leukemia, Lord JH (ed) Taylor & Francis, London, pp 1–21.

50. Manning JT, Bundred PE, Henzi P (2003), “Melanin and HIV in sub-Saharan Africa”, J Theor Biol, 223(1):131-133.

51. Mishra K, A.G (2017), “Appraisal of biochemical classes of radioprotectors: evidence, current status and guidelines for future development”, Biotech, 7 (5), pp. 292.

52. Mohagheghpour N, Waleh N, Garger SJ, Dousman L, Grill LK, Tusé D (2000), “Synthetic melanin suppresses production of pro-inflammatory cytokines”, Cell

Immunol, 199:25-36.

53. Montefiori DC, Zhou JY (1991), “Selective antiviral activity of synthetic soluble Ltyrosine and L-dopa melanins against human immunodeficiency virus in vitro”, Antiviral Res, 15(1):11-25.

54. Müller M, Elsässer HP (2013), “Alterations in the secretory pattern of dermal dendritic cells following melanin uptake”, Cell Tissue Res, 352: 599-610. 55. Nair CK, Parida DK, Nomura T (2001), “Radioprotectors in radiotherapy”, J

Radiat Res, 42(1):21–37.

56. Nguyen Thi Le Na, S.D.L., Nguyen Le Minh Tri, Nguyen Thi Bich, Loan H.a.S., Nguyen Linh Toan, Ha Phuong Thu, Hoang Thi My Nhung, Nguyen , and Lai Thanh N.T.V.A., Nguyen Dinh Thang (2019), “Nanomelanin

potentially protects the spleen from radiotherapy-associated damage and enhances immunoactivity in tumor-bearing mice”, Materials, 12 (10).

57. Öberg F, Haseeb A, Ahnfelt M, Pontén F, Westermark B, El-Obeid A (2009), “Herbal melanin activates TLR4/NF-kappaB signaling pathway”,

Phytomedicine, 16:477-84.

58. Pasco D, Pugh ND, Khan I, Moraes R (2005), “Immunostimulatory agents in botanicals”, US patent, 20050002962.

59. Pico Jl, A.-G.A., Naccache P (1998), “Mucositis: its occurrence, consequences and treatment in the oncology setting”, Oncologist, 3 (6), pp. 446-451.

60. Pugh ND, Balachandran P, Lata H, Dayan FE, Joshi V, Bedir E, Makino T, Moraes R, Khan I, Pasco DS (2005), “Melanin: dietary mucosal immune modulator from Echinacea and Other botanical supplements”, Int Immunopharmacol, 5:637-647.

61. Pugh ND, Tamta H, Balachandran P, Wu X, Howell J, Dayan FE, Pasco DS (2008), “The majority of in vitro macrophage activation exhibited by extracts of some immune enhancing botanicals is due to bacterial lipoproteins and lipopolysaccharides”, Int Immunopharmacol, 8:1023-1032.

62. Rastogi S, Pandey MM, Rawat AK (2015), “Traditional herbs: a remedy for cardiovascular disorders”, Phytomedicine.

63. Revskaya E, Jongco AM, Sellers RS, et al (2009), “Radioimmunotherapy of Experimental Human Metastatic Melanoma with Melanin-Binding Antibodies and in Combination with Dacarbazine”, Clin Cancer Res, 15(7):2373-2379. 64. Riley PA (1997), “Molecules in focus: Melanin”, The International Journal of

Biochemistry & Cell Biology, 29:1235-1239.

65. Samarth RM, Goyal PK, Kumar A (2004), “Protection of swiss albino mice against whole-body gamma irradiation by Mentha piperita (Linn.)”, Phytother Res, 18(7):546–550.

66. Sander CS, Chang H, Hamm F, Elsner P, Thiele JJ (2004), “Role of oxidative stress and the antioxidant network in cutaneous carcinogenesis”, Int J Dermatol, 43:326-335.

67. Satoh K, Onodera T, Omoso K, Takeda-Yano K, Katayama T, Oono Y, Narumi I (2016), “Draft genome sequence of the radioresistant bacterium Deinococcus grandis, isolated from freshwater fish in Japan”, Genome Announc.

68. Sauer H, W.M., Hescheler J (2001), “Reactive oxygen species as intracellular messengers during cell growth and differentiation”, Cell Physiol Biochem, 11

(4), pp. 173-186.

69. Sava V, Galkin B, Hong MY, Yang PC, Huang GS (2001), “A novel melanin- like pigment derived from black tea leaves with immuno-stimulating activity”,

Food Research International,b, 34:337–343.

70. Schweitzer AD, Revskaya E, Chu P, et al. (2010), “Melanin-covered nanoparticles for protection of bone marrow during radiation therapy of cancer”, Int J Radiat Oncol BiolPhys, 78(5): 1494–1502.

71. Shcherb VV, Babitskaya VG, Kurchenko VPN, Ikonnikova, NV, Kukulyanskaya TA (2000), “Antioxidant properties of fungal melanin pigments”, Appled biochemistry and microbiology, 36: 491-495.

72. Sidibe S, Saal F, Rhodes-Feuillette A, et al. (1996), “Effects of serotonin and melanin on in vitro HIV-1 infection”, J Biol Regul Homeost Agents, 10(1):19-

24.

73. Simon JD, Peles D, Wakamatsu K, Ito S, “Current challenges in understanding melanogenesis: bridging chemistry, biological control, morphology and function”, Pigment Cell Melanoma Res, 22; 563–579.

74. Singh Vk, H.-J.M (2016), “γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status”, Int J Mol Sci, 17 (5), pp. 663.

75. Szabo G, Gerald AB, Pathak MA, Fitzpatrick TB (1969), “Racial differences in the fate of melanosomes in human epidermis”, Nature, 222:1081-1082.

76. Tornaletti S, Pfeifer GP (1996), “UV damage and repair mechanisms in mammalian cells”, Bioessays, 18:221-228.

77. Travis LB, Hodgson D, Allan JM, Van Leeuwen FE (2008), “Second Cancers”, In DeVita VT Jr., Lawrence TS, Rosenberg SA, editors, Cancer: Principles and Practice of Oncology, 8th ed, Philadelphia: Lippincott Williams and

Wilkins.

78. Turner PR, Deoy WA (1996), “The mutagenic properties of DNA minor- groove binding ligands”, Mutat Res, 355(1–2):141–169.

79. Valerie K, Y.A., Hagan Mp, Et Al (2007), “Radiation-induced cell signaling: inside- out and outside-in”, Mol Cancer Ther, 3 (6), pp. 789-801.

80. Watt F. M. and Jensen K. B. (2009), “Epidermal stem cell diversity and quiescence”, EMBO molecular medicine, 1, pp. 260-267.

81. Weiss JF, Landauer MR (2003), “Protection against ionizing radiation by antioxidant nutrients and phytochemicals”, Toxicology, 189(1–2):1–20.

82. Wilms, H., P. Rosenstiel, J. Sievers, G. Deuschl, L. Zecca, and R. Lucius (2003), “Activation of microglia by human neuromelanin is NF-κB dependent and involves p38 mitogen activated protein kinase: Implications for Parkinson’s disease FASEB J 17:500–502", J Photochem Photobiol B Biol,

63:41–51.

83. Wu Y, Shan L, Yang S, Ma A (2008), “Identification and antioxidant activity of melanin isolated from Hypoxylon archeri, a companion fungus of Tremella fuciformi”, Journal of Basic microbiology, 48: 217–221.

84. Yamamori T, Y.H., Yamazumi M, Et Al (2012), “Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and

mitochondrial content under control of the cell cycle checkpoint”, Free Radic Biol Med, 53 (2), pp. 260-270.

85. Yoshino F, Y.A., Nakajima a, Wada-Takahashi S, Takahashi Ss, Lee Mc (2013), “Alteration of the redox state with reactive oxygen species for 5- fluorouracil-induced oral mucositis in hamsters”, PloS One, 8 (12), pp. e82834. 86. Yoshino F, Y.A., Nakajima a, Wada-Takahashi S, Takahashi Ss, Lee Mc (2013), “Alteration of the redox state with reactive oxygen species for 5- fluorouracil-induced oral mucositis in hamsters”, PloS One, 8 (12), pp. e82834. 87. Ziegler A, Leffell DJ, Kunala S, et al. (1993), “Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers”, Proc Natl Acad Sci U

S A. 90:4216-4220.

88. http://gco.iarc.fr/

89. http://www.cancer.gov/about-cancer/treatment/ 90. https://www.nccs.com.sg/

Một phần của tài liệu (LUẬN văn THẠC sĩ) đánh giá khả năng bảo vệ mô lành của chuột mang khối u khi điều trị bằng xạ trị thông qua các chỉ tiêu huyết học, hóa sinh và mô học (Trang 53 - 65)

Tải bản đầy đủ (PDF)

(65 trang)