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Aprepitant, a NK-1R antagonist could be employed for cytotoxic therapy induced alimentary tract mucosal inflammation
Oral Oncology xxx (2014) xxx
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the Editor Aprepitant, a NK-1R antagonist could be employed for cytotoxic therapy induced alimentary tract mucosal inflammation
at this point of time when no effective treatment has been identified in treating mucosal inflammation in cytotoxic therapy, SP/NK-1R antagonist, aprepitant could be employed to assess the role in mucosal inflammation induced by cytotoxic therapy.
We read the article by Matsumoto K et al. with great interest regarding the ‘Increased expression of 5-HT3 and NK 1 receptors in 5-fluorouracil-induced mucositis in mouse jejunum’ [1]. Chemotherapy induces the release of Substance P (SP) and its receptor NK -1R in humans, which are mediators in the emetic pathway; and hence, the NK–1R antagonist and 5-HT3 receptor antagonist are important antiemetic drugs in treating chemotherapy induced nausea and vomiting (CINV) [2]. Study of Matsumoto et al. on NK-1 receptor mRNA and the NK-1R immunoreactivities profiles in studying mucositis during 5FU treatment in mouse jejunum has shown marked achievement by showing threefold increase in NK-1R receptor. In the gastrointestinal mucosa subjected to 5 FU, NK 1 receptor immunopositive cells increase in lamina propria, and the expression of NK 1 receptor immunoreactivities increases in deep muscular plexus, indicating a role of SP/NK-1R in mucosal inflammation [1]. Hence, we would like to comment on the expression of SP/NK-1R (tachykinin peptides) in the alimentary tract mucosal inflammation in cytotoxic therapy. It is very interesting to see that the level of SP/NK-1R in alimentary tract mucosa was also altered in instances when irradiated. The level of SP/ NK-1R has showed marked variation when radiotherapy was employed in preclinical models, indicating a role in inflammation induced by ionizing radiation [3,4]. In the study, level of SP/NK1R expression in the gastrointestinal tract is directly proportional to the increasing dose of radiation dose and the immunoreactions of the SP were abundantly observed in nerve fibres in lamina propria and granulation tissue [3]. Similar findings were also observed in the study of human colon when irradiated; SP like immunoreactivity profiles in the mucosal lamina propria, muscularis mucosa, submucous plexus, smooth vessels and in myenteric plexus and the expression pattern were proportional to the radiation dose [5]. The over expression SP is not only observed in the mucosal tissue when irradiated, but in the animal models employed in studying the salivary glands, larynx, etc. [6–8]. The studies also indicate that the dose and time dependent expression pattern of SP in relation to ionizing radiation. These findings from the preclinical models indicate that, SP have a prominent role in chemotherapy and radiotherapy induced tissue reactions and indicate for more preclinical and clinical models in mucosal inflammation to assess the expression of SP. It is worth to note that over expression of SP and its receptor in CINV and pruritis has been studied effectively and treated successfully with NK-1R antagonist [9,10]. Now
References
http://dx.doi.org/10.1016/j.oraloncology.2014.04.002 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
[1] Matsumoto K, Nakajima T, Sakai H, Kato S, Sagara A, Arakawa K, et al. Increased expression of 5-HT3 and NK 1 receptors in 5-fluorouracil-induced mucositis in mouse jejunum. Dig Dis Sci 2013;58(12):3440–51. [2] Andrews PLR, Rudd JA. The role of tachykinins and the tachykinin NK1 receptor in nausea and emesis. In: Hofmann FB, editor. Handbook of experimental pharmacology. Berlin: Springer; 2004. p. 359–440. [3] Höckerfelt U, Franzén L, Forsgren S. Substance P (NK1) receptor in relation to substance P innervation in rat duodenum after irradiation. Regul Pept 2001;98(3):115–26. [4] Höckerfelt U, Franzén L, Kjörell U, Forsgren S. Parallel increase in substance P and VIP in rat duodenum in response to irradiation. Peptides 2000;21(2): 271–81. [5] Forsgren S, Höckerfelt U, Norrgård O, Henriksson R, Franzén L. Pronounced substance P innervation in irradiation-induced enteropathy–a study on human colon. Regul Pept 2000;88(1–3):1–13. [6] Aalto Y, Forsgren S, Kjörell U, Franzén L, Gustafsson H, Henriksson R. Time- and dose-related changes in the expression of substance P in salivary glands in response to fractionated irradiation. Int J Radiat Oncol Biol Phys 1995;33: 297–305. [7] Forsgren S, Franzén L, Funegård U, Gustafsson H, Henriksson R. Bilateral irradiation of head and neck induces an enhanced expression of substance P in the parasympathetic innervation of the submandibular gland. Neuroscience 1992;46(1):233–40. [8] Lidegran M, Domeij S, Dalqvist Å, Henriksson R, Franzén L, Gustafsson H, et al. Irradiation influences the expression of substance P and enkephalin in the rat larynx. Cell Tissue Res 1995;279:55–63. [9] Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapyinduced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin – the Aprepitant Protocol 052 Study Group. J Clin Oncol 2003;21(22):4112–9. [10] Santini D, Vincenzi B, Guida FM, Imperatori M, Schiavon G, Venditti O, et al. Aprepitant for management of severe pruritus related to biological cancer treatments: a pilot study. Lancet Oncol 2012;13(10):1020–4.
P.S. Satheeshkumar Minu P. Mohan Mar Baselios Dental College, Department of Oral Medicine and Radiology, Thankalam, Kothamangalam, Ernakulam, Kerala 686 691, India ⇑ Tel.: +91 9946321804 (P.S. Satheeshkumar). E-mail addresses: [email protected] (P.S. Satheeshkumar), [email protected] (M.P. Mohan) Available online xxxx
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the Editor Aprepitant, a NK-1R antagonist could be employed for cytotoxic therapy induced alimentary tract mucosal inflammation
at this point of time when no effective treatment has been identified in treating mucosal inflammation in cytotoxic therapy, SP/NK-1R antagonist, aprepitant could be employed to assess the role in mucosal inflammation induced by cytotoxic therapy.
We read the article by Matsumoto K et al. with great interest regarding the ‘Increased expression of 5-HT3 and NK 1 receptors in 5-fluorouracil-induced mucositis in mouse jejunum’ [1]. Chemotherapy induces the release of Substance P (SP) and its receptor NK -1R in humans, which are mediators in the emetic pathway; and hence, the NK–1R antagonist and 5-HT3 receptor antagonist are important antiemetic drugs in treating chemotherapy induced nausea and vomiting (CINV) [2]. Study of Matsumoto et al. on NK-1 receptor mRNA and the NK-1R immunoreactivities profiles in studying mucositis during 5FU treatment in mouse jejunum has shown marked achievement by showing threefold increase in NK-1R receptor. In the gastrointestinal mucosa subjected to 5 FU, NK 1 receptor immunopositive cells increase in lamina propria, and the expression of NK 1 receptor immunoreactivities increases in deep muscular plexus, indicating a role of SP/NK-1R in mucosal inflammation [1]. Hence, we would like to comment on the expression of SP/NK-1R (tachykinin peptides) in the alimentary tract mucosal inflammation in cytotoxic therapy. It is very interesting to see that the level of SP/NK-1R in alimentary tract mucosa was also altered in instances when irradiated. The level of SP/ NK-1R has showed marked variation when radiotherapy was employed in preclinical models, indicating a role in inflammation induced by ionizing radiation [3,4]. In the study, level of SP/NK1R expression in the gastrointestinal tract is directly proportional to the increasing dose of radiation dose and the immunoreactions of the SP were abundantly observed in nerve fibres in lamina propria and granulation tissue [3]. Similar findings were also observed in the study of human colon when irradiated; SP like immunoreactivity profiles in the mucosal lamina propria, muscularis mucosa, submucous plexus, smooth vessels and in myenteric plexus and the expression pattern were proportional to the radiation dose [5]. The over expression SP is not only observed in the mucosal tissue when irradiated, but in the animal models employed in studying the salivary glands, larynx, etc. [6–8]. The studies also indicate that the dose and time dependent expression pattern of SP in relation to ionizing radiation. These findings from the preclinical models indicate that, SP have a prominent role in chemotherapy and radiotherapy induced tissue reactions and indicate for more preclinical and clinical models in mucosal inflammation to assess the expression of SP. It is worth to note that over expression of SP and its receptor in CINV and pruritis has been studied effectively and treated successfully with NK-1R antagonist [9,10]. Now
References
http://dx.doi.org/10.1016/j.oraloncology.2014.04.002 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
[1] Matsumoto K, Nakajima T, Sakai H, Kato S, Sagara A, Arakawa K, et al. Increased expression of 5-HT3 and NK 1 receptors in 5-fluorouracil-induced mucositis in mouse jejunum. Dig Dis Sci 2013;58(12):3440–51. [2] Andrews PLR, Rudd JA. The role of tachykinins and the tachykinin NK1 receptor in nausea and emesis. In: Hofmann FB, editor. Handbook of experimental pharmacology. Berlin: Springer; 2004. p. 359–440. [3] Höckerfelt U, Franzén L, Forsgren S. Substance P (NK1) receptor in relation to substance P innervation in rat duodenum after irradiation. Regul Pept 2001;98(3):115–26. [4] Höckerfelt U, Franzén L, Kjörell U, Forsgren S. Parallel increase in substance P and VIP in rat duodenum in response to irradiation. Peptides 2000;21(2): 271–81. [5] Forsgren S, Höckerfelt U, Norrgård O, Henriksson R, Franzén L. Pronounced substance P innervation in irradiation-induced enteropathy–a study on human colon. Regul Pept 2000;88(1–3):1–13. [6] Aalto Y, Forsgren S, Kjörell U, Franzén L, Gustafsson H, Henriksson R. Time- and dose-related changes in the expression of substance P in salivary glands in response to fractionated irradiation. Int J Radiat Oncol Biol Phys 1995;33: 297–305. [7] Forsgren S, Franzén L, Funegård U, Gustafsson H, Henriksson R. Bilateral irradiation of head and neck induces an enhanced expression of substance P in the parasympathetic innervation of the submandibular gland. Neuroscience 1992;46(1):233–40. [8] Lidegran M, Domeij S, Dalqvist Å, Henriksson R, Franzén L, Gustafsson H, et al. Irradiation influences the expression of substance P and enkephalin in the rat larynx. Cell Tissue Res 1995;279:55–63. [9] Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapyinduced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin – the Aprepitant Protocol 052 Study Group. J Clin Oncol 2003;21(22):4112–9. [10] Santini D, Vincenzi B, Guida FM, Imperatori M, Schiavon G, Venditti O, et al. Aprepitant for management of severe pruritus related to biological cancer treatments: a pilot study. Lancet Oncol 2012;13(10):1020–4.
P.S. Satheeshkumar Minu P. Mohan Mar Baselios Dental College, Department of Oral Medicine and Radiology, Thankalam, Kothamangalam, Ernakulam, Kerala 686 691, India ⇑ Tel.: +91 9946321804 (P.S. Satheeshkumar). E-mail addresses: [email protected] (P.S. Satheeshkumar), [email protected] (M.P. Mohan) Available online xxxx