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The antimicrobial peptide pardaxin exerts potent anti-tumor activity against canine perianal gland adenoma.

Pan CY, Lin CN, Chiou MT, Yu CY, Chen JY, Chien CH - Oncotarget (2015)

Bottom Line: Local injection of pardaxin resulted in a significant reduction of perianal gland adenoma growth between 28 and 38 days post-treatment.Surgical resection of canine histiocytomas revealed large areas of ulceration, suggesting that pardaxin acts like a lytic peptide.Pardaxin treatment was not associated with significant variations in blood biochemical parameters or secretion of immune-related proteins.

View Article: PubMed Central - PubMed

Affiliation: Department and Graduate Institute of Aquaculture, National Kaohsiung Marine University, Nanzih Dist., Kaohsiung, Taiwan.

ABSTRACT
Pardaxin is an antimicrobial peptide of 33 amino acids, originally isolated from marine fish. We previously demonstrated that pardaxin has anti-tumor activity against murine fibrosarcoma, both in vitro and in vivo. In this study, we examined the anti-tumor activity, toxicity profile, and maximally-tolerated dose of pardaxin treatment in dogs with different types of refractory tumor. Local injection of pardaxin resulted in a significant reduction of perianal gland adenoma growth between 28 and 38 days post-treatment. Surgical resection of canine histiocytomas revealed large areas of ulceration, suggesting that pardaxin acts like a lytic peptide. Pardaxin treatment was not associated with significant variations in blood biochemical parameters or secretion of immune-related proteins. Our findings indicate that pardaxin has strong therapeutic potential for treating perianal gland adenomas in dogs. These data justify the veterinary application of pardaxin, and also provide invaluable information for veterinary medicine and future human clinical trials.

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Morphological changes in the perianal gland adenoma of dog #6 during treatment with pardaxin for 28 days(a) (A) Lesions were ulcerated and protruding, due to the masses (arrow) in the 12 o'clock direction from the anus at day 0 (before pardaxin treatment). (B) The 17th day after pardaxin treatment. The perianal gland adenoma exhibits cyanosis and appears black. (C) The 26th day after pardaxin treatment. The perianal gland adenoma had burst open, leaving a hollow aperture. (D) The 33rd day after pardaxin treatment. The wound had begun to heal. (E) The 37th and (F) 121st day after pardaxin treatment. Pardaxin treatment was stopped on the 29th day. (b) Morphological changes in the perianal gland adenoma of dog #13 during treatment with pardaxin for 28 days. (A) Prior to treatment on day 0. (B) The 7th, (C) 14th, (D) 21st, (E) 24th, and (F) 28th day of pardaxin treatment. (c) Morphological changes in the perianal gland adenoma to the upper left of the anus of dog #14 during treatment with pardaxin for 38 days. (A) Prior to treatment on day 0. (B) The 3rd, (C) 11th, (D) 17th, (E) 38th, and (F) 47th day of pardaxin treatment. The green arrow indicates the location of the perianal gland adenoma. (d) Morphological changes in the perianal gland adenoma to the upper right of the anus of dog #14 during treatment with pardaxin for 31 days. (A) Prior to treatment on day 0. (B) The 7th, (C) 17th, (D) 21st, (E) 38th, and (F) 43rd day of pardaxin treatment. The green arrow indicates the location of the perianal gland adenoma.
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Figure 3: Morphological changes in the perianal gland adenoma of dog #6 during treatment with pardaxin for 28 days(a) (A) Lesions were ulcerated and protruding, due to the masses (arrow) in the 12 o'clock direction from the anus at day 0 (before pardaxin treatment). (B) The 17th day after pardaxin treatment. The perianal gland adenoma exhibits cyanosis and appears black. (C) The 26th day after pardaxin treatment. The perianal gland adenoma had burst open, leaving a hollow aperture. (D) The 33rd day after pardaxin treatment. The wound had begun to heal. (E) The 37th and (F) 121st day after pardaxin treatment. Pardaxin treatment was stopped on the 29th day. (b) Morphological changes in the perianal gland adenoma of dog #13 during treatment with pardaxin for 28 days. (A) Prior to treatment on day 0. (B) The 7th, (C) 14th, (D) 21st, (E) 24th, and (F) 28th day of pardaxin treatment. (c) Morphological changes in the perianal gland adenoma to the upper left of the anus of dog #14 during treatment with pardaxin for 38 days. (A) Prior to treatment on day 0. (B) The 3rd, (C) 11th, (D) 17th, (E) 38th, and (F) 47th day of pardaxin treatment. The green arrow indicates the location of the perianal gland adenoma. (d) Morphological changes in the perianal gland adenoma to the upper right of the anus of dog #14 during treatment with pardaxin for 31 days. (A) Prior to treatment on day 0. (B) The 7th, (C) 17th, (D) 21st, (E) 38th, and (F) 43rd day of pardaxin treatment. The green arrow indicates the location of the perianal gland adenoma.

Mentions: Dog patient #6, an 8-year-old, intact, mixed breed male, was observed to bear an intradermal nodule around the anus (3.960 cm2) prior to pardaxin treatment. After 28 days of pardaxin treatment, the perianal gland adenoma had disappeared (Fig 2). On physical examination, the lesion of the perianal area was found to be ulcerated (Fig. 3a). The perianal gland adenoma was surrounded by fibrous capsules and stroma. The dog received a single daily intratumoral injection of 10 mg/ml pardaxin (2 ml/day; pardaxin was dissolved in PBS). At day 19, a significant reduction in perianal gland adenoma volume was observed, and the adenoma mass ultimately burst (Fig. 3a (C, D)). The last day of pardaxin treatment was day 28. The wound remained under observation, and was found to have healed completely by the 121st day (Fig. 3a). Thus, pardaxin treatment resulted in complete regression of tumor tissue of perianal gland adenoma. However, treatment with pardaxin induced rapid adenoma cell lysis, which manifested as a visible necrotic adenoma at 28 days after the first intratumoral injection.


The antimicrobial peptide pardaxin exerts potent anti-tumor activity against canine perianal gland adenoma.

Pan CY, Lin CN, Chiou MT, Yu CY, Chen JY, Chien CH - Oncotarget (2015)

Morphological changes in the perianal gland adenoma of dog #6 during treatment with pardaxin for 28 days(a) (A) Lesions were ulcerated and protruding, due to the masses (arrow) in the 12 o'clock direction from the anus at day 0 (before pardaxin treatment). (B) The 17th day after pardaxin treatment. The perianal gland adenoma exhibits cyanosis and appears black. (C) The 26th day after pardaxin treatment. The perianal gland adenoma had burst open, leaving a hollow aperture. (D) The 33rd day after pardaxin treatment. The wound had begun to heal. (E) The 37th and (F) 121st day after pardaxin treatment. Pardaxin treatment was stopped on the 29th day. (b) Morphological changes in the perianal gland adenoma of dog #13 during treatment with pardaxin for 28 days. (A) Prior to treatment on day 0. (B) The 7th, (C) 14th, (D) 21st, (E) 24th, and (F) 28th day of pardaxin treatment. (c) Morphological changes in the perianal gland adenoma to the upper left of the anus of dog #14 during treatment with pardaxin for 38 days. (A) Prior to treatment on day 0. (B) The 3rd, (C) 11th, (D) 17th, (E) 38th, and (F) 47th day of pardaxin treatment. The green arrow indicates the location of the perianal gland adenoma. (d) Morphological changes in the perianal gland adenoma to the upper right of the anus of dog #14 during treatment with pardaxin for 31 days. (A) Prior to treatment on day 0. (B) The 7th, (C) 17th, (D) 21st, (E) 38th, and (F) 43rd day of pardaxin treatment. The green arrow indicates the location of the perianal gland adenoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 3: Morphological changes in the perianal gland adenoma of dog #6 during treatment with pardaxin for 28 days(a) (A) Lesions were ulcerated and protruding, due to the masses (arrow) in the 12 o'clock direction from the anus at day 0 (before pardaxin treatment). (B) The 17th day after pardaxin treatment. The perianal gland adenoma exhibits cyanosis and appears black. (C) The 26th day after pardaxin treatment. The perianal gland adenoma had burst open, leaving a hollow aperture. (D) The 33rd day after pardaxin treatment. The wound had begun to heal. (E) The 37th and (F) 121st day after pardaxin treatment. Pardaxin treatment was stopped on the 29th day. (b) Morphological changes in the perianal gland adenoma of dog #13 during treatment with pardaxin for 28 days. (A) Prior to treatment on day 0. (B) The 7th, (C) 14th, (D) 21st, (E) 24th, and (F) 28th day of pardaxin treatment. (c) Morphological changes in the perianal gland adenoma to the upper left of the anus of dog #14 during treatment with pardaxin for 38 days. (A) Prior to treatment on day 0. (B) The 3rd, (C) 11th, (D) 17th, (E) 38th, and (F) 47th day of pardaxin treatment. The green arrow indicates the location of the perianal gland adenoma. (d) Morphological changes in the perianal gland adenoma to the upper right of the anus of dog #14 during treatment with pardaxin for 31 days. (A) Prior to treatment on day 0. (B) The 7th, (C) 17th, (D) 21st, (E) 38th, and (F) 43rd day of pardaxin treatment. The green arrow indicates the location of the perianal gland adenoma.
Mentions: Dog patient #6, an 8-year-old, intact, mixed breed male, was observed to bear an intradermal nodule around the anus (3.960 cm2) prior to pardaxin treatment. After 28 days of pardaxin treatment, the perianal gland adenoma had disappeared (Fig 2). On physical examination, the lesion of the perianal area was found to be ulcerated (Fig. 3a). The perianal gland adenoma was surrounded by fibrous capsules and stroma. The dog received a single daily intratumoral injection of 10 mg/ml pardaxin (2 ml/day; pardaxin was dissolved in PBS). At day 19, a significant reduction in perianal gland adenoma volume was observed, and the adenoma mass ultimately burst (Fig. 3a (C, D)). The last day of pardaxin treatment was day 28. The wound remained under observation, and was found to have healed completely by the 121st day (Fig. 3a). Thus, pardaxin treatment resulted in complete regression of tumor tissue of perianal gland adenoma. However, treatment with pardaxin induced rapid adenoma cell lysis, which manifested as a visible necrotic adenoma at 28 days after the first intratumoral injection.

Bottom Line: Local injection of pardaxin resulted in a significant reduction of perianal gland adenoma growth between 28 and 38 days post-treatment.Surgical resection of canine histiocytomas revealed large areas of ulceration, suggesting that pardaxin acts like a lytic peptide.Pardaxin treatment was not associated with significant variations in blood biochemical parameters or secretion of immune-related proteins.

View Article: PubMed Central - PubMed

Affiliation: Department and Graduate Institute of Aquaculture, National Kaohsiung Marine University, Nanzih Dist., Kaohsiung, Taiwan.

ABSTRACT
Pardaxin is an antimicrobial peptide of 33 amino acids, originally isolated from marine fish. We previously demonstrated that pardaxin has anti-tumor activity against murine fibrosarcoma, both in vitro and in vivo. In this study, we examined the anti-tumor activity, toxicity profile, and maximally-tolerated dose of pardaxin treatment in dogs with different types of refractory tumor. Local injection of pardaxin resulted in a significant reduction of perianal gland adenoma growth between 28 and 38 days post-treatment. Surgical resection of canine histiocytomas revealed large areas of ulceration, suggesting that pardaxin acts like a lytic peptide. Pardaxin treatment was not associated with significant variations in blood biochemical parameters or secretion of immune-related proteins. Our findings indicate that pardaxin has strong therapeutic potential for treating perianal gland adenomas in dogs. These data justify the veterinary application of pardaxin, and also provide invaluable information for veterinary medicine and future human clinical trials.

Show MeSH
Related in: MedlinePlus