Abstract

Literature Review

Radiation-induced salivary gland damage/dysfunction in head and neck cancer: Nano-bioengineering strategies and artificial intelligence for prevention, therapy and reparation

Ziyad S Haidar*

Published: 20 December, 2022 | Volume 6 - Issue 3 | Pages: 027-044

Saliva is produced by and secreted from salivary glands. It is an extra-cellular fluid, 98% water, plus electrolytes, mucus, white blood cells, epithelial cells, enzymes, and anti-microbial agents. Saliva serves a critical role in the maintenance of oral, dental, and general health and well-being. Hence, alteration(s) in the amount/quantity and/or quality of secreted saliva may induce the development of several oro-dental variations, thereby the negatively-impacting overall quality of life. Diverse factors may affect the process of saliva production and quantity/quality of secretion, including medications, systemic or local pathologies and/or reversible/irreversible damage. Herein, chemo- and/or radio-therapy, particularly, in cases of head and neck cancer, for example, are well-documented to induce serious damage and dysfunction to the radio-sensitive salivary gland tissue, resulting in hypo-salivation, xerostomia (dry mouth) as well as numerous other adverse Intra-/extra-oral, medical and quality-of-life issues. Indeed, radio-therapy inevitably causes damage to the normal head and neck tissues including nerve structures (brain stem, spinal cord, and brachial plexus), mucous membranes, and swallowing muscles. Current commercially-available remedies as well as therapeutic interventions provide only temporary symptom relief, hence, do not address irreversible glandular damage. Further, despite salivary gland-sparing techniques and modified dosing strategies, long-term hypo-function remains a significant problem. Although a single governing mechanism of radiation-induced salivary gland tissue damage and dysfunction has not been yet elucidated, the potential for synergy in radio-protection (mainly, and possibly -reparation) via a combinatorial approach of mechanistically distinct strategies, has been suggested and explored over the years. This is, undoubtfully, in parallel to the ongoing efforts in improving the precision, safety, delivery, and efficacy of clinical radiotherapy protocols/outcomes, and in designing, developing, evaluating and optimizing (for translation) new artificial intelligence, technological and bio-pharmaceutical alternatives, topics covered in this review.

Read Full Article HTML DOI: 10.29328/journal.jro.1001044 Cite this Article Read Full Article PDF

Keywords:

Artificial intelligence; Bioengineering; Biomimicry; Chemo-radio therapy; Irradiation; Radioprotection; Salivary gland; Xerostomia; Head and neck cancer; Oro-dental health

References

  1. Cancer Fact Sheet World Health Organization. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed Oct 23, 2020.
  2. International Agency for Research on Cancer IARC. 2019, GLOBOCAN 2018, Cancer Incidence and Mortality Worldwide. Lyon: International Agency for Research on Cancer. http://gco.iarc.fr/today/fact-sheets-cancers. Accessed Aug 25, 2020.
  3. Yan K, Agrawal N, Gooi Z. Head and Neck Masses. Med Clin North Am. 2018 Nov;102(6):1013-1025. doi: 10.1016/j.mcna.2018.06.012. Epub 2018 Sep 20. PMID: 30342605.
  4. Cognetti DM, Weber RS, Lai SY. Head and neck cancer: an evolving treatment paradigm. Cancer. 2008 Oct 1;113(7 Suppl):1911-32. doi: 10.1002/cncr.23654. PMID: 18798532; PMCID: PMC2751600.
  5. Jaffray DA, Gospodarowicz MK. Radiation Therapy for Cancer. 2015. ISBN 9781464803499.
  6. Shetty AV, Wong DJ. Systemic Treatment for Squamous Cell Carcinoma of the Head and Neck. Otolaryngol Clin North Am. 2017 Aug;50(4):775-782. doi: 10.1016/j.otc.2017.03.013. PMID: 28755705.
  7. Barazzuol L, Coppes RP, van Luijk P. Prevention and treatment of radiotherapy-induced side effects. Mol Oncol. 2020 Jul;14(7):1538-1554. doi: 10.1002/1878-0261.12750. Epub 2020 Jun 24. PMID: 32521079; PMCID: PMC7332214.
  8. Gil Z, Fliss DM. Contemporary management of head and neck cancers. Isr Med Assoc J. 2009 May;11(5):296-300. PMID: 19637508.
  9. Deloch L, Derer A, Hartmann J, Frey B, Fietkau R, Gaipl US. Modern Radiotherapy Concepts and the Impact of Radiation on Immune Activation. Front Oncol. 2016 Jun 20;6:141. doi: 10.3389/fonc.2016.00141. PMID: 27379203; PMCID: PMC4913083.
  10. Baskar R, Dai J, Wenlong N, Yeo R, Yeoh KW. Biological response of cancer cells to radiation treatment. Front Mol Biosci. 2014 Nov 17;1:24. doi: 10.3389/fmolb.2014.00024. PMID: 25988165; PMCID: PMC4429645.
  11. Manukian G, Bar-Ad V, Lu B, Argiris A, Johnson JM. Combining Radiation and Immune Checkpoint Blockade in the Treatment of Head and Neck Squamous Cell Carcinoma. Front Oncol. 2019 Mar 6;9:122. doi: 10.3389/fonc.2019.00122. PMID: 30895168; PMCID: PMC6414812.
  12. Jensen SB, Vissink A, Limesand KH, Reyland ME. Salivary Gland Hypofunction and Xerostomia in Head and Neck Radiation Patients. J Natl Cancer Inst Monogr. 2019 Aug 1;2019(53):lgz016. doi: 10.1093/jncimonographs/lgz016. PMID: 31425600.
  13. Wu VWC, Leung KY. A Review on the Assessment of Radiation Induced Salivary Gland Damage After Radiotherapy. Front Oncol. 2019 Oct 17;9:1090. doi: 10.3389/fonc.2019.01090. PMID: 31750235; PMCID: PMC6843028.
  14. Miranda-Rius J, Brunet-Llobet L, Lahor-Soler E, Farré M. Salivary Secretory Disorders, Inducing Drugs, and Clinical Management. Int J Med Sci. 2015 Sep 22;12(10):811-24. doi: 10.7150/ijms.12912. PMID: 26516310; PMCID: PMC4615242.
  15. Ghannam MG, Singh P, Anatomy H , Salivary Glands N. StatPearls 2019 Available from https://www.ncbi.nlm.nih.gov/books/NBK538325/. Accessed Jan 29, 2020.
  16. Punj A. Secretions of Human Salivary Gland. Secretions of Human Salivary Gland, Salivary Glands - New Approaches in Diagnostics and Treatment, Işıl Adadan Güvenç, IntechOpen. 2018. doi: 10.5772/intechopen.75538. Available from: https://www.intechopen.com/books/salivary-glands-new-approaches-in-diagnostics-and-treatment/secretions-of-human-salivary-gland.
  17. Benn AM, Thomson WM. Saliva: an overview. N Z Dent J. 2014 Sep;110(3):92-6. PMID: 25265747.
  18. Tiwari M. Science behind human saliva. J Nat Sci Biol Med. 2011 Jan;2(1):53-8. doi: 10.4103/0976-9668.82322. PMID: 22470235; PMCID: PMC3312700.
  19. Proctor GB. The physiology of salivary secretion. Periodontol 2000. 2016 Feb;70(1):11-25. doi: 10.1111/prd.12116. PMID: 26662479.
  20. Qin R, Steel A, Fazel N. Oral mucosa biology and salivary biomarkers. Clin Dermatol. 2017 Sep-Oct;35(5):477-483. doi: 10.1016/j.clindermatol.2017.06.005. Epub 2017 Jun 27. PMID: 28916029.
  21. Farnaud SJ, Kosti O, Getting SJ, Renshaw D. Saliva: physiology and diagnostic potential in health and disease. ScientificWorldJournal. 2010 Mar 16;10:434-56. doi: 10.1100/tsw.2010.38. PMID: 20305986; PMCID: PMC5763701.
  22. Fábián TK, Beck A, Fejérdy P, Hermann P, Fábián G. Molecular mechanisms of taste recognition: considerations about the role of saliva. Int J Mol Sci. 2015 Mar 13;16(3):5945-74. doi: 10.3390/ijms16035945. PMID: 25782158; PMCID: PMC4394514.
  23. von Bültzingslöwen I, Sollecito TP, Fox PC, Daniels T, Jonsson R, Lockhart PB, Wray D, Brennan MT, Carrozzo M, Gandera B, Fujibayashi T, Navazesh M, Rhodus NL, Schiødt M. Salivary dysfunction associated with systemic diseases: systematic review and clinical management recommendations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Mar;103 Suppl:S57.e1-15. doi: 10.1016/j.tripleo.2006.11.010. PMID: 17379156.
  24. Dashtipour K, Bhidayasiri R, Chen JJ, Jabbari B, Lew M, Torres-Russotto D. RimabotulinumtoxinB in sialorrhea: systematic review of clinical trials. J Clin Mov Disord. 2017 Jun 6;4:9. doi: 10.1186/s40734-017-0055-1. PMID: 28593050; PMCID: PMC5460542.
  25. Jost WH, Friedman A, Michel O, Oehlwein C, Slawek J, Bogucki A, Ochudlo S, Banach M, Pagan F, Flatau-Baqué B, Dorsch U, Csikós J, Blitzer A. Long-term incobotulinumtoxinA treatment for chronic sialorrhea: Efficacy and safety over 64 weeks. Parkinsonism Relat Disord. 2020 Jan;70:23-30. doi: 10.1016/j.parkreldis.2019.11.024. Epub 2019 Nov 26. PMID: 31794936.
  26. Frydrych AM. Dry mouth: Xerostomia and salivary gland hypofunction. Aust Fam Physician. 2016 Jul;45(7):488-92. PMID: 27610431.
  27. Azuma N, Katada Y, Kitano S, Sekiguchi M, Kitano M, Nishioka A, Hashimoto N, Matsui K, Iwasaki T, Sano H. Correlation between salivary epidermal growth factor levels and refractory intraoral manifestations in patients with Sjögren's syndrome. Mod Rheumatol. 2014 Jul;24(4):626-32. doi: 10.3109/14397595.2013.850766. Epub 2013 Nov 5. PMID: 24252043.
  28. Millsop JW, Wang EA, Fazel N. Etiology, evaluation, and management of xerostomia. Clin Dermatol. 2017 Sep-Oct;35(5):468-476. doi: 10.1016/j.clindermatol.2017.06.010. Epub 2017 Jun 27. PMID: 28916028.
  29. Tan ECK, Lexomboon D, Sandborgh-Englund G, Haasum Y, Johnell K. Medications That Cause Dry Mouth As an Adverse Effect in Older People: A Systematic Review and Metaanalysis. J Am Geriatr Soc. 2018 Jan;66(1):76-84. doi: 10.1111/jgs.15151. Epub 2017 Oct 26. PMID: 29071719.
  30. Vissink A, Mitchell JB, Baum BJ, Limesand KH, Jensen SB, Fox PC, Elting LS, Langendijk JA, Coppes RP, Reyland ME. Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: successes and barriers. Int J Radiat Oncol Biol Phys. 2010 Nov 15;78(4):983-91. doi: 10.1016/j.ijrobp.2010.06.052. PMID: 20970030; PMCID: PMC2964345.
  31. Schaue D, Kachikwu EL, McBride WH. Cytokines in radiobiological responses: a review. Radiat Res. 2012 Dec;178(6):505-23. doi: 10.1667/RR3031.1. Epub 2012 Oct 29. PMID: 23106210; PMCID: PMC3723384.
  32. Williams JP, McBride WH. After the bomb drops: a new look at radiation-induced multiple organ dysfunction syndrome (MODS). Int J Radiat Biol. 2011 Aug;87(8):851-68. doi: 10.3109/09553002.2011.560996. Epub 2011 Mar 21. PMID: 21417595; PMCID: PMC3314299.
  33. Mohammadi N, Seyyednejhad F, Alizadeh Oskoee P, Savadi Oskoee S, Mofidi N. Evaluation of Radiation-induced Xerostomia in Patients with Nasopharyngeal Carcinomas. J Dent Res Dent Clin Dent Prospects. 2007 Summer;1(2):65-70. doi: 10.5681/joddd.2007.011. Epub 2007 Sep 10. PMID: 23277836; PMCID: PMC3525927.
  34. Strojan P, Hutcheson KA, Eisbruch A, Beitler JJ, Langendijk JA, Lee AWM, Corry J, Mendenhall WM, Smee R, Rinaldo A, Ferlito A. Treatment of late sequelae after radiotherapy for head and neck cancer. Cancer Treat Rev. 2017 Sep;59:79-92. doi: 10.1016/j.ctrv.2017.07.003. Epub 2017 Jul 18. PMID: 28759822; PMCID: PMC5902026.
  35. Franzén L, Funegård U, Ericson T, Henriksson R. Parotid gland function during and following radiotherapy of malignancies in the head and neck. A consecutive study of salivary flow and patient discomfort. Eur J Cancer. 1992;28(2-3):457-62. doi: 10.1016/s0959-8049(05)80076-0. PMID: 1591063.
  36. Siddiqui F, Movsas B. Management of Radiation Toxicity in Head and Neck Cancers. Semin Radiat Oncol. 2017 Oct;27(4):340-349. doi: 10.1016/j.semradonc.2017.04.008. PMID: 28865517.
  37. Berk LB, Shivnani AT, Small W Jr. Pathophysiology and management of radiation-induced xerostomia. J Support Oncol. 2005 May-Jun;3(3):191-200. PMID: 15915820.
  38. Hammerlid E, Silander E, Hörnestam L, Sullivan M. Health-related quality of life three years after diagnosis of head and neck cancer--a longitudinal study. Head Neck. 2001 Feb;23(2):113-25. doi: 10.1002/1097-0347(200102)23:2<113::aid-hed1006>3.0.co;2-w. PMID: 11303628.
  39. Hall SC, Hassis ME, Williams KE, Albertolle ME, Prakobphol A, Dykstra AB, Laurance M, Ona K, Niles RK, Prasad N, Gormley M, Shiboski C, Criswell LA, Witkowska HE, Fisher SJ. Alterations in the Salivary Proteome and N-Glycome of Sjögren's Syndrome Patients. J Proteome Res. 2017 Apr 7;16(4):1693-1705. doi: 10.1021/acs.jproteome.6b01051. Epub 2017 Mar 24. PMID: 28282148; PMCID: PMC9668345.
  40. Jehmlich N, Stegmaier P, Golatowski C, Salazar MG, Rischke C, Henke M, Völker U. Differences in the whole saliva baseline proteome profile associated with development of oral mucositis in head and neck cancer patients undergoing radiotherapy. J Proteomics. 2015 Jul 1;125:98-103. doi: 10.1016/j.jprot.2015.04.030. Epub 2015 May 19. PMID: 25997676.
  41. Thomson WM. Dry mouth and older people. Aust Dent J. 2015 Mar;60 Suppl 1:54-63. doi: 10.1111/adj.12284. PMID: 25762042.
  42. Cereda E, Cappello S, Colombo S, Klersy C, Imarisio I, Turri A, Caraccia M, Borioli V, Monaco T, Benazzo M, Pedrazzoli P, Corbella F, Caccialanza R. Nutritional counseling with or without systematic use of oral nutritional supplements in head and neck cancer patients undergoing radiotherapy. Radiother Oncol. 2018 Jan;126(1):81-88. doi: 10.1016/j.radonc.2017.10.015. Epub 2017 Oct 27. PMID: 29111172.
  43. Li Y, Taylor JM, Ten Haken RK, Eisbruch A. The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy. Int J Radiat Oncol Biol Phys. 2007 Mar 1;67(3):660-9. doi: 10.1016/j.ijrobp.2006.09.021. Epub 2006 Dec 4. PMID: 17141973; PMCID: PMC2001308.
  44. Jiang N, Zhao Y, Jansson H, Chen X, Mårtensson J. Experiences of xerostomia after radiotherapy in patients with head and neck cancer: A qualitative study. J Clin Nurs. 2018 Jan;27(1-2):e100-e108. doi: 10.1111/jocn.13879. Epub 2017 Jul 5. PMID: 28514511.
  45. Wang W, Xiong W, Wan J, Sun X, Xu H, Yang X. The decrease of PAMAM dendrimer-induced cytotoxicity by PEGylation via attenuation of oxidative stress. Nanotechnology. 2009 Mar 11;20(10):105103. doi: 10.1088/0957-4484/20/10/105103. Epub 2009 Feb 16. PMID: 19417510.
  46. Nadig SD, Ashwathappa DT, Manjunath M, Krishna S, Annaji AG, Shivaprakash PK. A relationship between salivary flow rates and Candida counts in patients with xerostomia. J Oral Maxillofac Pathol. 2017 May-Aug;21(2):316. doi: 10.4103/jomfp.JOMFP_231_16. PMID: 28932047; PMCID: PMC5596688.
  47. Kagami H, Wang S, Hai B. Restoring the function of salivary glands. Oral Dis. 2008 Jan;14(1):15-24. doi: 10.1111/j.1601-0825.2006.01339.x. PMID: 18173444.
  48. Villa A, Abati S. Risk factors and symptoms associated with xerostomia: a cross-sectional study. Aust Dent J. 2011 Sep;56(3):290-5. doi: 10.1111/j.1834-7819.2011.01347.x. PMID: 21884145.
  49. Bressan V, Bagnasco A, Aleo G, Catania G, Zanini MP, Timmins F, Sasso L. The life experience of nutrition impact symptoms during treatment for head and neck cancer patients: a systematic review and meta-synthesis. Support Care Cancer. 2017 May;25(5):1699-1712. doi: 10.1007/s00520-017-3618-7. Epub 2017 Feb 15. PMID: 28204992.
  50. Grundmann O, Mitchell GC, Limesand KH. Sensitivity of salivary glands to radiation: from animal models to therapies. J Dent Res. 2009 Oct;88(10):894-903. doi: 10.1177/0022034509343143. PMID: 19783796; PMCID: PMC2882712.
  51. de Castro G Jr, Guindalini RS. Supportive care in head and neck oncology. Curr Opin Oncol. 2010 May;22(3):221-5. doi: 10.1097/CCO.0b013e32833818ff. PMID: 20186057.
  52. Gu J, Zhu S, Li X, Wu H, Li Y, Hua F. Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and meta-analysis based on randomized controlled trials. PLoS One. 2014 May 2;9(5):e95968. doi: 10.1371/journal.pone.0095968. PMID: 24788761; PMCID: PMC4008569.
  53. Riley P, Glenny AM, Hua F, Worthington HV. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Cochrane Database Syst Rev. 2017 Jul 31;7(7):CD012744. doi: 10.1002/14651858.CD012744. PMID: 28759701; PMCID: PMC6483146.
  54. Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, Wasserman TH, Cohen GI, Emami B, Gradishar WJ, Mitchell RB, Thigpen JT, Trotti A 3rd, von Hoff D, Schuchter LM. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009 Jan 1;27(1):127-45. doi: 10.1200/JCO.2008.17.2627. Epub 2008 Nov 17. PMID: 19018081.
  55. Vissink A, Jansma J, Spijkervet FK, Burlage FR, Coppes RP. Oral sequelae of head and neck radiotherapy. Crit Rev Oral Biol Med. 2003;14(3):199-212. doi: 10.1177/154411130301400305. PMID: 12799323.
  56. Braam PM, Terhaard CH, Roesink JM, Raaijmakers CP. Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy. Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):975-80. doi: 10.1016/j.ijrobp.2006.06.045. Epub 2006 Sep 11. PMID: 16965864.
  57. Teng F, Fan W, Luo Y, Ju Z, Gong H, Ge R, Tong F, Zhang X, Ma L. Reducing Xerostomia by Comprehensive Protection of Salivary Glands in Intensity-Modulated Radiation Therapy with Helical Tomotherapy Technique for Head-and-Neck Cancer Patients: A Prospective Observational Study. Biomed Res Int. 2019 Jul 14;2019:2401743. doi: 10.1155/2019/2401743. PMID: 31380414; PMCID: PMC6662416.
  58. Marzouki HZ, Elkhalidy Y, Jha N, Scrimger R, Debenham BJ, Harris JR, O'Connell DA, Seikaly H. Modification of the submandibular gland transfer procedure. Laryngoscope. 2016 Nov;126(11):2492-2496. doi: 10.1002/lary.26029. Epub 2016 May 12. PMID: 27171786.
  59. Rao AD, Coquia S, De Jong R, Gourin C, Page B, Latronico D, Dah S, Su L, Clarke S, Schultz J, Rosati LM, Fakhry C, Wong J, DeWeese TL, Quon H, Ding K, Kiess A. Effects of biodegradable hydrogel spacer injection on contralateral submandibular gland sparing in radiotherapy for head and neck cancers. Radiother Oncol. 2018 Jan;126(1):96-99. doi: 10.1016/j.radonc.2017.09.017. Epub 2017 Oct 3. PMID: 28985953.
  60. Ho J, Firmalino MV, Anbarani AG, Takesh T, Epstein J, Wilder-Smith P. Effects of A Novel Disc Formulation on Dry Mouth Symptoms and Enamel Remineralization in Patients With Hyposalivation: An In Vivo Study. Dentistry (Sunnyvale). 2017 Feb;7(2):411. doi: 10.4172/2161-1122.1000411. Epub 2017 Feb 13. PMID: 28713645; PMCID: PMC5505684.
  61. Ogawa M, Oshima M, Imamura A, Sekine Y, Ishida K, Yamashita K, Nakajima K, Hirayama M, Tachikawa T, Tsuji T. Functional salivary gland regeneration by transplantation of a bioengineered organ germ. Nat Commun. 2013;4:2498. doi: 10.1038/ncomms3498. PMID: 24084982; PMCID: PMC3806330.
  62. Zhang NN, Huang GL, Han QB, Hu X, Yi J, Yao L, He Y. Functional regeneration of irradiated salivary glands with human amniotic epithelial cells transplantation. Int J Clin Exp Pathol. 2013 Sep 15;6(10):2039-47. PMID: 24133581; PMCID: PMC3796225.
  63. Okazaki Y, Kagami H, Hattori T, Hishida S, Shigetomi T, Ueda M. Acceleration of rat salivary gland tissue repair by basic fibroblast growth factor. Arch Oral Biol. 2000 Oct;45(10):911-9. doi: 10.1016/s0003-9969(00)00035-2. PMID: 10973565.
  64. Michalopoulou F, Petraki C, Philippou A, Analitis A, Msaouel P, Koutsilieris M. Expression of IGF-IEc Isoform in Renal Cell Carcinoma Tissues. Anticancer Res. 2020 Nov;40(11):6213-6219. doi: 10.21873/anticanres.14641. PMID: 33109558.
  65. Tran D, Bergholz J, Zhang H, He H, Wang Y, Zhang Y, Li Q, Kirkland JL, Xiao ZX. Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence. Aging Cell. 2014 Aug;13(4):669-78. doi: 10.1111/acel.12219. Epub 2014 Apr 30. PMID: 25070626; PMCID: PMC4118446.
  66. Xiao N, Lin Y, Cao H, Sirjani D, Giaccia AJ, Koong AC, Kong CS, Diehn M, Le QT. Neurotrophic factor GDNF promotes survival of salivary stem cells. J Clin Invest. 2014 Aug;124(8):3364-77. doi: 10.1172/JCI74096. Epub 2014 Jul 18. PMID: 25036711; PMCID: PMC4109543.
  67. Swick A, Kimple RJ. Wetting the whistle: neurotropic factor improves salivary function. J Clin Invest. 2014 Aug;124(8):3282-4. doi: 10.1172/JCI77194. Epub 2014 Jul 18. PMID: 25036702; PMCID: PMC4109536.
  68. Kojima T, Kanemaru S, Hirano S, Tateya I, Suehiro A, Kitani Y, Kishimoto Y, Ohno S, Nakamura T, Ito J. The protective efficacy of basic fibroblast growth factor in radiation-induced salivary gland dysfunction in mice. Laryngoscope. 2011 Sep;121(9):1870-5. doi: 10.1002/lary.21873. Epub 2011 Aug 16. PMID: 22024837.
  69. Thula TT, Schultz G, Tran-Son-Tay R, Batich C. Effects of EGF and bFGF on irradiated parotid glands. Ann Biomed Eng. 2005 May;33(5):685-95. doi: 10.1007/s10956-005-1853-z. PMID: 15981868.
  70. Borges L, Rex KL, Chen JN, Wei P, Kaufman S, Scully S, Pretorius JK, Farrell CL. A protective role for keratinocyte growth factor in a murine model of chemotherapy and radiotherapy-induced mucositis. Int J Radiat Oncol Biol Phys. 2006 Sep 1;66(1):254-62. doi: 10.1016/j.ijrobp.2006.05.025. PMID: 16904525.
  71. Lombaert IM, Brunsting JF, Wierenga PK, Kampinga HH, de Haan G, Coppes RP. Keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem/progenitor pool. Stem Cells. 2008 Oct;26(10):2595-601. doi: 10.1634/stemcells.2007-1034. Epub 2008 Jul 31. PMID: 18669914.
  72. Choi JS, Shin HS, An HY, Kim YM, Lim JY. Radioprotective effects of Keratinocyte Growth Factor-1 against irradiation-induced salivary gland hypofunction. Oncotarget. 2017 Feb 21;8(8):13496-13508. doi: 10.18632/oncotarget.14583. PMID: 28086221; PMCID: PMC5355115.
  73. Meyer S, Chibly AM, Burd R, Limesand KH. Insulin-Like Growth Factor-1-Mediated DNA Repair in Irradiated Salivary Glands Is Sirtuin-1 Dependent. J Dent Res. 2017 Feb;96(2):225-232. doi: 10.1177/0022034516677529. Epub 2016 Nov 16. PMID: 28106504; PMCID: PMC5331616.
  74. Grundmann O, Fillinger JL, Victory KR, Burd R, Limesand KH. Restoration of radiation therapy-induced salivary gland dysfunction in mice by post therapy IGF-1 administration. BMC Cancer. 2010 Aug 10;10:417. doi: 10.1186/1471-2407-10-417. PMID: 20698985; PMCID: PMC3087323.
  75. Baum BJ, Zheng C, Cotrim AP, Goldsmith CM, Atkinson JC, Brahim JS, Chiorini JA, Voutetakis A, Leakan RA, Van Waes C, Mitchell JB, Delporte C, Wang S, Kaminsky SM, Illei GG. Transfer of the AQP1 cDNA for the correction of radiation-induced salivary hypofunction. Biochim Biophys Acta. 2006 Aug;1758(8):1071-7. doi: 10.1016/j.bbamem.2005.11.006. Epub 2005 Dec 5. PMID: 16368071.
  76. Redman RS. On approaches to the functional restoration of salivary glands damaged by radiation therapy for head and neck cancer, with a review of related aspects of salivary gland morphology and development. Biotech Histochem. 2008 Jun;83(3-4):103-30. doi: 10.1080/10520290802374683. PMID: 18828044; PMCID: PMC2740375.
  77. Cotrim AP, Sowers A, Mitchell JB, Baum BJ. Prevention of irradiation-induced salivary hypofunction by microvessel protection in mouse salivary glands. Mol Ther. 2007 Dec;15(12):2101-6. doi: 10.1038/sj.mt.6300296. Epub 2007 Aug 28. PMID: 17726456.
  78. Guo L, Gao R, Xu J, Jin L, Cotrim AP, Yan X, Zheng C, Goldsmith CM, Shan Z, Hai B, Zhou J, Zhang C, Baum BJ, Wang S. AdLTR2EF1α-FGF2-mediated prevention of fractionated irradiation-induced salivary hypofunction in swine. Gene Ther. 2014 Oct;21(10):866-73. doi: 10.1038/gt.2014.63. Epub 2014 Jul 17. PMID: 25030610.
  79. Wang JF, Liu C, Zhang Q, Huang GH. Research progress in the radioprotective effect of the canonical Wnt pathway. Cancer Biol Med. 2013 Jun;10(2):61-71. doi: 10.7497/j.issn.2095-3941.2013.02.001. PMID: 23882420; PMCID: PMC3719192.
  80. Vidya Priyadarsini R, Senthil Murugan R, Nagini S. Aberrant activation of Wnt/β-catenin signaling pathway contributes to the sequential progression of DMBA-induced HBP carcinomas. Oral Oncol. 2012 Jan;48(1):33-9. doi: 10.1016/j.oraloncology.2011.08.008. Epub 2011 Sep 15. PMID: 21924667.
  81. Huang J, Qu Q, Guo Y, Xiang Y, Feng D. Tankyrases/β-catenin Signaling Pathway as an Anti-proliferation and Anti-metastatic Target in Hepatocarcinoma Cell Lines. J Cancer. 2020 Jan 1;11(2):432-440. doi: 10.7150/jca.30976. PMID: 31897238; PMCID: PMC6930431.
  82. Orme MH, Giannini AL, Vivanco MD, Kypta RM. Glycogen synthase kinase-3 and Axin function in a beta-catenin-independent pathway that regulates neurite outgrowth in neuroblastoma cells. Mol Cell Neurosci. 2003 Nov;24(3):673-86. doi: 10.1016/s1044-7431(03)00229-x. PMID: 14664817.
  83. Garan A, Akyüz S, Oztürk LK, Yarat A. Salivary parameters and caries indices in children with black tooth stains. J Clin Pediatr Dent. 2012 Spring;36(3):285-8. doi: 10.17796/jcpd.36.3.21466m672t723713. PMID: 22838232.
  84. Nusse R, Clevers H. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell. 2017 Jun 1;169(6):985-999. doi: 10.1016/j.cell.2017.05.016. PMID: 28575679.
  85. Huang H, He X. Wnt/beta-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol. 2008 Apr;20(2):119-25. doi: 10.1016/j.ceb.2008.01.009. Epub 2008 Mar 12. PMID: 18339531; PMCID: PMC2390924.
  86. Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005 Jan-Mar;9(1):59-71. doi: 10.1111/j.1582-4934.2005.tb00337.x. PMID: 15784165; PMCID: PMC6741304.
  87. Doble BW, Woodgett JR. GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci. 2003 Apr 1;116(Pt 7):1175-86. doi: 10.1242/jcs.00384. PMID: 12615961; PMCID: PMC3006448.
  88. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995 Dec 21-28;378(6559):785-9. doi: 10.1038/378785a0. PMID: 8524413.
  89. Krasilnikov MA. Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation. Biochemistry (Mosc). 2000 Jan;65(1):59-67. PMID: 10702641.
  90. Huang L, Fu L. Mechanisms of resistance to EGFR tyrosine kinase inhibitors. Acta Pharm Sin B. 2015 Sep;5(5):390-401. doi: 10.1016/j.apsb.2015.07.001. Epub 2015 Jul 26. PMID: 26579470; PMCID: PMC4629442.
  91. Torres MA, Eldar-Finkelman H, Krebs EG, Moon RT. Regulation of ribosomal S6 protein kinase-p90(rsk), glycogen synthase kinase 3, and beta-catenin in early Xenopus development. Mol Cell Biol. 1999 Feb;19(2):1427-37. doi: 10.1128/MCB.19.2.1427. PMID: 9891076; PMCID: PMC116071.
  92. Dailey L, Ambrosetti D, Mansukhani A, Basilico C. Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev. 2005 Apr;16(2):233-47. doi: 10.1016/j.cytogfr.2005.01.007. Epub 2005 Mar 5. PMID: 15863038.
  93. Alcaraz E, Vilardell J, Borgo C, Sarró E, Plana M, Marin O, Pinna LA, Bayascas JR, Meseguer A, Salvi M, Itarte E, Ruzzene M. Effects of CK2β subunit down-regulation on Akt signalling in HK-2 renal cells. PLoS One. 2020 Jan 7;15(1):e0227340. doi: 10.1371/journal.pone.0227340. PMID: 31910234; PMCID: PMC6946142.
  94. Kennedy SG, Wagner AJ, Conzen SD, Jordán J, Bellacosa A, Tsichlis PN, Hay N. The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev. 1997 Mar 15;11(6):701-13. doi: 10.1101/gad.11.6.701. PMID: 9087425.
  95. Hakim SG, Ribbat J, Berndt A, Richter P, Kosmehl H, Benedek GA, Jacobsen HC, Trenkle T, Sieg P, Rades D. Expression of Wnt-1, TGF-β and related cell-cell adhesion components following radiotherapy in salivary glands of patients with manifested radiogenic xerostomia. Radiother Oncol. 2011 Oct;101(1):93-9. doi: 10.1016/j.radonc.2011.07.032. Epub 2011 Aug 30. PMID: 21885141.
  96. Hai B, Yang Z, Shangguan L, Zhao Y, Boyer A, Liu F. Concurrent transient activation of Wnt/β-catenin pathway prevents radiation damage to salivary glands. Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):e109-16. doi: 10.1016/j.ijrobp.2011.11.062. Epub 2012 Feb 16. PMID: 22342093; PMCID: PMC3340568.
  97. Haidar ZS. Bio-Inspired/-Functional Colloidal Core-Shell Polymeric-Based NanoSystems: Technology Promise in Tissue Engineering, Bioimaging and NanoMedicine. Polymers . 2010; 2: 323-352. https://doi.org/10.3390/polym2030323.
  98. Riley P, Glenny AM, Hua F, Worthington HV. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Cochrane Database Syst Rev. 2017 Jul 31;7(7):CD012744. doi: 10.1002/14651858.CD012744. PMID: 28759701; PMCID: PMC6483146.
  99. Ocampo J, Vásquez B, Sandoval C, Navarrete J, Haidar ZS, Olate, S. Características Morfocuantitativas de la Glándula Submandibular de Ratón (Mus musculus)/ Morphocuantitative Characteristics of the Mouse (Mus musculus) Submandibular Gland. International Journal of Morphology. 2020; 38: 570-577. https://dx.doi.org/10.4067/S0717-95022020000300570.
  100. Ocampo J, Olate S, Haidar ZS, Vásquez B, Hiposialia y .Xerostomía Post Irradiación: Terapias Innovadoras en el Campo Biomolecular/Hyposialia and Xerostomy Post Irradiation: Innovative Therapies in the Biomolecular Field. International Journal of Morphology 2019; 37: 1564-1571. https://dx.doi.org/10.4067/S0717-95022019000401564.
  101. Arany S, Xu Q, Hernady E, Benoit DS, Dewhurst W, Ovitt S, C. E. Pro-apoptotic gene knockdown mediated by nanocomplexed siRNA reduces radiation damage in primary salivary gland cultures. J. Cell. Biochem. 2012; 113, 1955–65, doi:10.1002/jcb.24064.
  102. Yoon YJ, Shin HS, Lim JY. A hepatocyte growth factor/MET-induced antiapoptotic pathway protects against radiation-induced salivary gland dysfunction. Radiother Oncol. 2019 Sep;138:9-16. doi: 10.1016/j.radonc.2019.05.012. Epub 2019 May 25. PMID: 31136962.
  103. Tai G, Zhang H, Du J, Chen G, Huang J, Yu J, Cai J, Liu F. TIGAR overexpression diminishes radiosensitivity of parotid gland fibroblast cells and inhibits IR-induced cell autophagy. Int J Clin Exp Pathol. 2015 May 1;8(5):4823-9. PMID: 26191173; PMCID: PMC4503045.
  104. Wie SM, Wellberg E, Karam SD, Reyland ME. Tyrosine Kinase Inhibitors Protect the Salivary Gland from Radiation Damage by Inhibiting Activation of Protein Kinase C-δ. Mol Cancer Ther. 2017 Sep;16(9):1989-1998. doi: 10.1158/1535-7163.MCT-17-0267. Epub 2017 Jun 21. PMID: 28637715; PMCID: PMC5587414.
  105. Choi JS, An HY, Shin HS, Kim YM, Lim JY. Enhanced tissue remodelling efficacy of adipose-derived mesenchymal stem cells using injectable matrices in radiation-damaged salivary gland model. J Tissue Eng Regen Med. 2018 Feb;12(2):e695-e706. doi: 10.1002/term.2352. Epub 2017 May 7. PMID: 27860388.
  106. Zeidan YH, Xiao N, Cao H, Kong C, Le QT, Sirjani D. Botulinum Toxin Confers Radioprotection in Murine Salivary Glands. Int J Radiat Oncol Biol Phys. 2016 Apr 1;94(5):1190-7. doi: 10.1016/j.ijrobp.2015.12.371. Epub 2015 Dec 29. PMID: 26907915; PMCID: PMC4839970.
  107. An HY, Shin HS, Choi JS, Kim HJ, Lim JY, Kim YM. Adipose Mesenchymal Stem Cell Secretome Modulated in Hypoxia for Remodeling of Radiation-Induced Salivary Gland Damage. PLoS One. 2015 Nov 3;10(11):e0141862. doi: 10.1371/journal.pone.0141862. PMID: 26529411; PMCID: PMC4631328.
  108. Xu L, Yang X, Cai J, Ma J, Cheng H, Zhao K, Yang L, Cao Y, Qin Q, Zhang C, Zhang Q, Sun X. Resveratrol attenuates radiation-induced salivary gland dysfunction in mice. Laryngoscope. 2013 Nov;123(11):E23-9. doi: 10.1002/lary.24276. Epub 2013 Jul 12. PMID: 23794219.
  109. Okumura H, Nasu M, Yosue T. Effects of amifostine administration prior to irradiation to the submandibular gland in mice: autoradiographic study using 3H-leucine. Okajimas Folia Anat Jpn. 2009 Feb;85(4):151-60. doi: 10.2535/ofaj.85.151. PMID: 19408584.
  110. Cotrim AP, Sowers A, Mitchell JB, Baum BJ. Prevention of irradiation-induced salivary hypofunction by microvessel protection in mouse salivary glands. Mol Ther. 2007 Dec;15(12):2101-6. doi: 10.1038/sj.mt.6300296. Epub 2007 Aug 28. PMID: 17726456.
  111. Cotrim AP, Hyodo F, Matsumoto K, Sowers AL, Cook JA, Baum BJ, Krishna MC, Mitchell JB. Differential radiation protection of salivary glands versus tumor by Tempol with accompanying tissue assessment of Tempol by magnetic resonance imaging. Clin Cancer Res. 2007 Aug 15;13(16):4928-33. doi: 10.1158/1078-0432.CCR-07-0662. PMID: 17699873.
  112. Cotrim AP, Sowers AL, Lodde BM, Vitolo JM, Kingman A, Russo A, Mitchell JB, Baum BJ. Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model. Clin Cancer Res. 2005 Oct 15;11(20):7564-8. doi: 10.1158/1078-0432.CCR-05-0958. PMID: 16243832.
  113. Aonuma M, Nasu M, Iwata H, Yosue T. Radioprotection of the murine submandibular gland by isoproterenol: autoradiography study with 3H-leucine. Odontology. 2004 Sep;92(1):14-21. doi: 10.1007/s10266-004-0032-7. PMID: 15490300.
  114. Vitolo JM, Cotrim AP, Sowers AL, Russo A, Wellner RB, Pillemer SR, Mitchell JB, Baum BJ. The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model. Clin Cancer Res. 2004 Mar 1;10(5):1807-12. doi: 10.1158/1078-0432.ccr-03-0194. PMID: 15014035.
  115. Rasey JS, Krohn KA, Menard TW, Spence AM. Comparative biodistribution and radioprotection studies with three radioprotective drugs in mouse tumors. Int J Radiat Oncol Biol Phys. 1986 Aug;12(8):1487-90. doi: 10.1016/0360-3016(86)90200-2. PMID: 3019965.
  116. Rasey JS, Nelson NJ, Mahler P, Anderson K, Krohn KA, Menard T. Radioprotection of normal tissues against gamma rays and cyclotron neutrons with WR-2721: LD50 studies and 35S-WR-2721 biodistribution. Radiat Res. 1984 Mar;97(3):598-607. PMID: 6328565.
  117. Varghese JJ, Schmale IL, Mickelsen D, Hansen ME, Newlands SD, Benoit DSW, Korshunov VA, Ovitt CE. Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection. J Dent Res. 2018 Oct;97(11):1252-1259. doi: 10.1177/0022034518767408. Epub 2018 Apr 10. Erratum in: J Dent Res. 2018 Aug;97(9):1070. PMID: 29634396; PMCID: PMC6151913.
  118. Shin HS, Lee S, Kim YM, Lim JY. Hypoxia-Activated Adipose Mesenchymal Stem Cells Prevents Irradiation-Induced Salivary Hypofunction by Enhanced Paracrine Effect Through Fibroblast Growth Factor 10. Stem Cells. 2018 Jul;36(7):1020-1032. doi: 10.1002/stem.2818. Epub 2018 Apr 10. PMID: 29569790.
  119. Toshkov IA, Gleiberman AS, Mett VL, Hutson AD, Singh AK, Gudkov AV, Burdelya LG. Mitigation of Radiation-Induced Epithelial Damage by the TLR5 Agonist Entolimod in a Mouse Model of Fractionated Head and Neck Irradiation. Radiat Res. 2017 May;187(5):570-580. doi: 10.1667/RR14514.1. Epub 2017 Mar 21. PMID: 28323577; PMCID: PMC5541767.
  120. Xu L, Yang X, Chen J, Ge X, Qin Q, Zhu H, Zhang C, Sun X. Simvastatin attenuates radiation-induced salivary gland dysfunction in mice. Drug Des Devel Ther. 2016 Jul 13;10:2271-8. doi: 10.2147/DDDT.S105809. PMID: 27471375; PMCID: PMC4948692.
  121. Crescenti EJ, Medina VA, Croci M, Sambuco LA, Prestifilippo JP, Elverdin JC, Bergoc RM, Rivera ES. Radioprotection of sensitive rat tissues by oligoelements Se, Zn, Mn plus Lachesis muta venom. J Radiat Res. 2011;52(5):557-67. doi: 10.1269/jrr.11031. PMID: 21952314.
  122. Coppes RP, Vissink A, Zeilstra LJ, Konings AW. Muscarinic receptor stimulation increases tolerance of rat salivary gland function to radiation damage. Int J Radiat Biol. 1997 Nov;72(5):615-25. doi: 10.1080/095530097143112. PMID: 9374441.
  123. Coppes RP, Zeilstra LJ, Vissink A, Konings AW. Sialogogue-related radioprotection of salivary gland function: the degranulation concept revisited. Radiat Res. 1997 Sep;148(3):240-7. PMID: 9291355.
  124. Menard TW, Izutsu KT, Ensign WY, Keller PJ, Morton TH, Truelove EL. Radioprotection by WR-2721 of gamma-irradiated rat parotid gland: effect on gland weight and secretion at 8-10 days post irradiation. Int J Radiat Oncol Biol Phys. 1984 Sep;10(9):1555-9. doi: 10.1016/0360-3016(84)90502-9. PMID: 6090361.
  125. Sodicoff M, Conger AD. Radioprotection of the rat parotid gland by cAMP. Radiat Res. 1983 Oct;96(1):90-4. PMID: 6312484.
  126. Sodicoff M, Conger AD. Radioprotection of the rat parotid gland by WR-2721 and isoproterenol and its modification by propranolol. Radiat Res. 1983 Apr;94(1):97-104. PMID: 6304806.
  127. Pratt NE, Sodicoff M, Liss J, Davis M, Sinesi M. Radioprotection of the rat parotid gland by WR-2721: morphology at 60 days post-irradiation. Int J Radiat Oncol Biol Phys. 1980 Apr;6(4):431-5. doi: 10.1016/0360-3016(80)90056-5. PMID: 6248498.
  128. Sodicoff M, Conger AD, Pratt NE, Trepper P. Radioprotection by WR-2721 against long-term chronic damage to the rat parotid gland. Radiat Res. 1978 Oct;76(1):172-9. PMID: 216048.
  129. Abedi SM, Yarmand F, Motallebnejad M, Seyedmajidi M, Moslemi D, Bijani A, Hosseinimehr SJ. Radioprotective Effect of Thymol Against Salivary Glands Dysfunction Induced by Ionizing Radiation in Rats. Iran J Pharm Res. 2016 Fall;15(4):861-866. PMID: 28243283; PMCID: PMC5316265.
  130. Palaniyandi S, Odaka Y, Green W, Abreo F, Caldito G, De Benedetti A, Sunavala-Dossabhoy G. Adenoviral delivery of Tousled kinase for the protection of salivary glands against ionizing radiation damage. Gene Ther. 2011 Mar;18(3):275-82. doi: 10.1038/gt.2010.142. Epub 2010 Nov 4. PMID: 21048794.
  131. Timiri Shanmugam PS, Dayton RD, Palaniyandi S, Abreo F, Caldito G, Klein RL, Sunavala-Dossabhoy G. Recombinant AAV9-TLK1B administration ameliorates fractionated radiation-induced xerostomia. Hum Gene Ther. 2013 Jun;24(6):604-12. doi: 10.1089/hum.2012.235. PMID: 23614651; PMCID: PMC3689188.
  132. Hakim SG, Benedek GA, Su YX, Jacobsen HC, Klinger M, Dendorfer A, Hemmelmann C, Meller B, Nadrowitz R, Rades D, Sieg P. Radioprotective effect of lidocaine on function and ultrastructure of salivary glands receiving fractionated radiation. Int J Radiat Oncol Biol Phys. 2012 Mar 15;82(4):e623-30. doi: 10.1016/j.ijrobp.2011.09.017. Epub 2012 Jan 13. PMID: 22245203.
  133. Hakim SG, Kosmehl H, Lauer I, Nadrowitz R, Wedel T, Sieg P. A comparative study on the protection profile of lidocaine, amifostine, and pilocarpin on the parotid gland during radiotherapy. Cancer Res. 2005 Nov 15;65(22):10486-93. doi: 10.1158/0008-5472.CAN-05-0023. PMID: 16288041.
  134. Lotz S, Caselitz J, Tschakert H, Rehpenning W, Seifert G. Radioprotection of minipig salivary glands by orciprenaline-carbachol. An ultrastructural and semiquantitative light microscopic study. Virchows Arch A Pathol Anat Histopathol. 1990;417(2):119-28. doi: 10.1007/BF02190529. PMID: 2114690.
  135. Guo L, Gao R, Xu J, Jin L, Cotrim AP, Yan X, Zheng C, Goldsmith CM, Shan Z, Hai B, Zhou J, Zhang C, Baum BJ, Wang S. AdLTR2EF1α-FGF2-mediated prevention of fractionated irradiation-induced salivary hypofunction in swine. Gene Ther. 2014 Oct;21(10):866-73. doi: 10.1038/gt.2014.63. Epub 2014 Jul 17. PMID: 25030610.
  136. McDonald S, Meyerowitz C, Smudzin T, Rubin P. Preliminary results of a pilot study using WR-2721 before fractionated irradiation of the head and neck to reduce salivary gland dysfunction. Int J Radiat Oncol Biol Phys. 1994 Jul 1;29(4):747-54. doi: 10.1016/0360-3016(94)90562-2. PMID: 8040020.
  137. Baum RP, Langbein T, Singh A, Shahinfar M, Schuchardt C, Volk GF, Kulkarni H. Injection of Botulinum Toxin for Preventing Salivary Gland Toxicity after PSMA Radioligand Therapy: an Empirical Proof of a Promising Concept. Nucl Med Mol Imaging. 2018 Feb;52(1):80-81. doi: 10.1007/s13139-017-0508-3. Epub 2018 Jan 11. PMID: 29391917; PMCID: PMC5777965.
  138. Vacha P, Fehlauer F, Mahlmann B, Marx M, Hinke A, Sommer K, Richter E, Feyerabend T. Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection? Strahlenther Onkol. 2003 Jun;179(6):385-9. doi: 10.1007/s00066-003-1016-1. PMID: 12789464.
  139. Scrimger RA, Seikaly H, Vos LJ, Harris J, O'Connell D, Ghosh S, Debenham B, Jha N. Combination of submandibular salivary gland transfer and intensity-modulated radiotherapy to reduce dryness of mouth (xerostomia) in patients with head and neck cancer. Head Neck. 2018 Nov;40(11):2353-2361. doi: 10.1002/hed.25339. Epub 2018 Sep 3. PMID: 30175876.
  140. Teng F, Fan W, Luo Y, Ju Z, Gong H, Ge R, Tong F, Zhang X, Ma L. Reducing Xerostomia by Comprehensive Protection of Salivary Glands in Intensity-Modulated Radiation Therapy with Helical Tomotherapy Technique for Head-and-Neck Cancer Patients: A Prospective Observational Study. Biomed Res Int. 2019 Jul 14;2019:2401743. doi: 10.1155/2019/2401743. PMID: 31380414; PMCID: PMC6662416.
  141. Saito E, Watari I, Mizumachi-Kubono M, Hsu-Hayashi S, Ono T. Occlusional Modifications Reversibly Alter Aquaporin 5 Expression and Localization in Rat Salivary Glands. Front Physiol. 2020 Jun 10;11:528. doi: 10.3389/fphys.2020.00528. PMID: 32587522; PMCID: PMC7298139.
  142. Liu X, Gong B, de Souza LB, Ong HL, Subedi KP, Cheng KT, Swaim W, Zheng C, Mori Y, Ambudkar IS. Radiation inhibits salivary gland function by promoting STIM1 cleavage by caspase-3 and loss of SOCE through a TRPM2-dependent pathway. Sci Signal. 2017 Jun 6;10(482):eaal4064. doi: 10.1126/scisignal.aal4064. PMID: 28588080; PMCID: PMC5798857.
  143. Wang TS, Coppens I, Saorin A, Brady NR, Hamacher-Brady A. Endolysosomal Targeting of Mitochondria Is Integral to BAX-Mediated Mitochondrial Permeabilization during Apoptosis Signaling. Dev Cell. 2020 Jun 22;53(6):627-645.e7. doi: 10.1016/j.devcel.2020.05.014. Epub 2020 Jun 5. PMID: 32504557; PMCID: PMC7433306.
  144. Marmary Y, Adar R, Gaska S, Wygoda A, Maly A, Cohen J, Eliashar R, Mizrachi L, Orfaig-Geva C, Baum BJ, Rose-John S, Galun E, Axelrod JH. Radiation-Induced Loss of Salivary Gland Function Is Driven by Cellular Senescence and Prevented by IL6 Modulation. Cancer Res. 2016 Mar 1;76(5):1170-80. doi: 10.1158/0008-5472.CAN-15-1671. Epub 2016 Jan 12. Erratum in: Cancer Res. 2016 May 1;76(9):2846. PMID: 26759233.
  145. Adwan TS, Ohm AM, Jones DNM, Humphries MJ, Reyland ME. Regulated binding of importin-α to protein kinase Cδ in response to apoptotic signals facilitates nuclear import. J Biol Chem. 2011 Oct 14;286(41):35716-35724. doi: 10.1074/jbc.M111.255950. Epub 2011 Aug 24. PMID: 21865164; PMCID: PMC3195609.
  146. van Dijk LV, Fuller CD. Artificial Intelligence and Radiomics in Head and Neck Cancer Care: Opportunities, Mechanics, and Challenges. Am Soc Clin Oncol Educ Book. 2021 Mar;41:1-11. doi: 10.1200/EDBK_320951. PMID: 33929877; PMCID: PMC8218312.
  147. Maleki F, Le WT, Sananmuang T, Kadoury S, Forghani R. Machine Learning Applications for Head and Neck Imaging. Neuroimaging Clin N Am. 2020 Nov;30(4):517-529. doi: 10.1016/j.nic.2020.08.003. PMID: 33039001.
  148. Chinnery T, Arifin A, Tay KY, Leung A, Nichols AC, Palma DA, Mattonen SA, Lang P. Utilizing Artificial Intelligence for Head and Neck Cancer Outcomes Prediction From Imaging. Can Assoc Radiol J. 2021 Feb;72(1):73-85. doi: 10.1177/0846537120942134. Epub 2020 Jul 31. PMID: 32735452.
  149. Mahmood H, Shaban M, Rajpoot N, Khurram SA. Artificial Intelligence-based methods in head and neck cancer diagnosis: an overview. Br J Cancer. 2021 Jun;124(12):1934-1940. doi: 10.1038/s41416-021-01386-x. Epub 2021 Apr 19. PMID: 33875821; PMCID: PMC8184820.
  150. Abdel Razek AAK, Khaled R, Helmy E, Naglah A, AbdelKhalek A, El-Baz A. Artificial Intelligence and Deep Learning of Head and Neck Cancer. Magn Reson Imaging Clin N Am. 2022 Feb;30(1):81-94. doi: 10.1016/j.mric.2021.06.016. PMID: 34802583.

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