Combination of pentoxifylline and α-galactosylceramide with radiotherapy promotes necro-apoptosis and leukocyte infiltration and reduces the mitosis rate in murine melanoma

Ruth L. Madera-Sandoval, József Tóvári, József Lövey, Ivan Ranđelović, Alejandro Jiménez-Orozco, Victor G. Hernández-Chávez, Elba Reyes-Maldonado, Armando Vega-López

Research output: Contribution to journalArticle

Abstract

Despite the success for the treatment of melanoma such as targeted molecular therapy, the use of such treatments are expensive For this reason, this study was carried out to explore the anti-cancer properties of available drugs that are able to modify the melanoma prognosis. The study was conducted in two phases: Evaluation of pharmacological effects of pentoxifylline (PTX) administered above (60 mg/kg) which is the therapeutic dose that is aimed at reducing the side-effect of radiotherapy, and of α- galactosylceramide (GalCer) administered at 100 μg/kg, as well as their combination using a murine model (BDF1 mice) of melanoma cell line (B16-F1, ATCC). For the radiotherapy phase, 9 Gy was applied in the tumor area, before (3 days), during (30 min) and after (3 days) the PTX + GalCer treatment. In both study phases, the mitosis rate, leukocyte infiltration and necro-apoptosis were assessed using histological and immunohistochemical approach and tumor volume evaluation as biomarkers. All treatments showed good prognosis results estimated as reduction of mitosis rate (PTX + GalCer after radiotherapy and GalCer), increased leukocyte infiltrate (PTX + GalCer after radiotherapy and GalCer) and necro-apoptosis augmentation (PTX + GalCer after radiotherapy and radiotherapy control). Nevertheless, a lower development of tumor volume was found in GalCer treatment. In this way, it is possible to suggest that the integrated treatment with immuno-stimulators such as GalCer, plus drug used for peripheral vascular disease (PTX) after radiotherapy is probably an alternative for controlling aggressive melanoma in murine model.

Original languageEnglish
Pages (from-to)680-689
Number of pages10
JournalActa Histochemica
Volume121
Issue number6
DOIs
StatePublished - Aug 2019

Fingerprint

Galactosylceramides
Pentoxifylline
Mitosis
Melanoma
Leukocytes
Radiotherapy
Apoptosis
Tumor Burden
Therapeutics
Molecular Targeted Therapy
Peripheral Vascular Diseases
Pharmaceutical Preparations
Neoplasms
Biomarkers
Pharmacology
Cell Line

Keywords

  • Additive effects
  • Immunotherapy
  • Melanoma second-line therapy
  • Tumor volume

Cite this

Madera-Sandoval, Ruth L. ; Tóvári, József ; Lövey, József ; Ranđelović, Ivan ; Jiménez-Orozco, Alejandro ; Hernández-Chávez, Victor G. ; Reyes-Maldonado, Elba ; Vega-López, Armando. / Combination of pentoxifylline and α-galactosylceramide with radiotherapy promotes necro-apoptosis and leukocyte infiltration and reduces the mitosis rate in murine melanoma. In: Acta Histochemica. 2019 ; Vol. 121, No. 6. pp. 680-689.
@article{b1ffde85cb6f4f5b8012446b9265b71b,
title = "Combination of pentoxifylline and α-galactosylceramide with radiotherapy promotes necro-apoptosis and leukocyte infiltration and reduces the mitosis rate in murine melanoma",
abstract = "Despite the success for the treatment of melanoma such as targeted molecular therapy, the use of such treatments are expensive For this reason, this study was carried out to explore the anti-cancer properties of available drugs that are able to modify the melanoma prognosis. The study was conducted in two phases: Evaluation of pharmacological effects of pentoxifylline (PTX) administered above (60 mg/kg) which is the therapeutic dose that is aimed at reducing the side-effect of radiotherapy, and of α- galactosylceramide (GalCer) administered at 100 μg/kg, as well as their combination using a murine model (BDF1 mice) of melanoma cell line (B16-F1, ATCC). For the radiotherapy phase, 9 Gy was applied in the tumor area, before (3 days), during (30 min) and after (3 days) the PTX + GalCer treatment. In both study phases, the mitosis rate, leukocyte infiltration and necro-apoptosis were assessed using histological and immunohistochemical approach and tumor volume evaluation as biomarkers. All treatments showed good prognosis results estimated as reduction of mitosis rate (PTX + GalCer after radiotherapy and GalCer), increased leukocyte infiltrate (PTX + GalCer after radiotherapy and GalCer) and necro-apoptosis augmentation (PTX + GalCer after radiotherapy and radiotherapy control). Nevertheless, a lower development of tumor volume was found in GalCer treatment. In this way, it is possible to suggest that the integrated treatment with immuno-stimulators such as GalCer, plus drug used for peripheral vascular disease (PTX) after radiotherapy is probably an alternative for controlling aggressive melanoma in murine model.",
keywords = "Additive effects, Immunotherapy, Melanoma second-line therapy, Tumor volume",
author = "Madera-Sandoval, {Ruth L.} and J{\'o}zsef T{\'o}v{\'a}ri and J{\'o}zsef L{\"o}vey and Ivan Ranđelović and Alejandro Jim{\'e}nez-Orozco and Hern{\'a}ndez-Ch{\'a}vez, {Victor G.} and Elba Reyes-Maldonado and Armando Vega-L{\'o}pez",
year = "2019",
month = "8",
doi = "10.1016/j.acthis.2019.06.003",
language = "Ingl{\'e}s",
volume = "121",
pages = "680--689",
journal = "Acta Histochemica",
issn = "0065-1281",
publisher = "Urban und Fischer Verlag Jena",
number = "6",

}

Combination of pentoxifylline and α-galactosylceramide with radiotherapy promotes necro-apoptosis and leukocyte infiltration and reduces the mitosis rate in murine melanoma. / Madera-Sandoval, Ruth L.; Tóvári, József; Lövey, József; Ranđelović, Ivan; Jiménez-Orozco, Alejandro; Hernández-Chávez, Victor G.; Reyes-Maldonado, Elba; Vega-López, Armando.

In: Acta Histochemica, Vol. 121, No. 6, 08.2019, p. 680-689.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Combination of pentoxifylline and α-galactosylceramide with radiotherapy promotes necro-apoptosis and leukocyte infiltration and reduces the mitosis rate in murine melanoma

AU - Madera-Sandoval, Ruth L.

AU - Tóvári, József

AU - Lövey, József

AU - Ranđelović, Ivan

AU - Jiménez-Orozco, Alejandro

AU - Hernández-Chávez, Victor G.

AU - Reyes-Maldonado, Elba

AU - Vega-López, Armando

PY - 2019/8

Y1 - 2019/8

N2 - Despite the success for the treatment of melanoma such as targeted molecular therapy, the use of such treatments are expensive For this reason, this study was carried out to explore the anti-cancer properties of available drugs that are able to modify the melanoma prognosis. The study was conducted in two phases: Evaluation of pharmacological effects of pentoxifylline (PTX) administered above (60 mg/kg) which is the therapeutic dose that is aimed at reducing the side-effect of radiotherapy, and of α- galactosylceramide (GalCer) administered at 100 μg/kg, as well as their combination using a murine model (BDF1 mice) of melanoma cell line (B16-F1, ATCC). For the radiotherapy phase, 9 Gy was applied in the tumor area, before (3 days), during (30 min) and after (3 days) the PTX + GalCer treatment. In both study phases, the mitosis rate, leukocyte infiltration and necro-apoptosis were assessed using histological and immunohistochemical approach and tumor volume evaluation as biomarkers. All treatments showed good prognosis results estimated as reduction of mitosis rate (PTX + GalCer after radiotherapy and GalCer), increased leukocyte infiltrate (PTX + GalCer after radiotherapy and GalCer) and necro-apoptosis augmentation (PTX + GalCer after radiotherapy and radiotherapy control). Nevertheless, a lower development of tumor volume was found in GalCer treatment. In this way, it is possible to suggest that the integrated treatment with immuno-stimulators such as GalCer, plus drug used for peripheral vascular disease (PTX) after radiotherapy is probably an alternative for controlling aggressive melanoma in murine model.

AB - Despite the success for the treatment of melanoma such as targeted molecular therapy, the use of such treatments are expensive For this reason, this study was carried out to explore the anti-cancer properties of available drugs that are able to modify the melanoma prognosis. The study was conducted in two phases: Evaluation of pharmacological effects of pentoxifylline (PTX) administered above (60 mg/kg) which is the therapeutic dose that is aimed at reducing the side-effect of radiotherapy, and of α- galactosylceramide (GalCer) administered at 100 μg/kg, as well as their combination using a murine model (BDF1 mice) of melanoma cell line (B16-F1, ATCC). For the radiotherapy phase, 9 Gy was applied in the tumor area, before (3 days), during (30 min) and after (3 days) the PTX + GalCer treatment. In both study phases, the mitosis rate, leukocyte infiltration and necro-apoptosis were assessed using histological and immunohistochemical approach and tumor volume evaluation as biomarkers. All treatments showed good prognosis results estimated as reduction of mitosis rate (PTX + GalCer after radiotherapy and GalCer), increased leukocyte infiltrate (PTX + GalCer after radiotherapy and GalCer) and necro-apoptosis augmentation (PTX + GalCer after radiotherapy and radiotherapy control). Nevertheless, a lower development of tumor volume was found in GalCer treatment. In this way, it is possible to suggest that the integrated treatment with immuno-stimulators such as GalCer, plus drug used for peripheral vascular disease (PTX) after radiotherapy is probably an alternative for controlling aggressive melanoma in murine model.

KW - Additive effects

KW - Immunotherapy

KW - Melanoma second-line therapy

KW - Tumor volume

UR - http://www.scopus.com/inward/record.url?scp=85067296835&partnerID=8YFLogxK

U2 - 10.1016/j.acthis.2019.06.003

DO - 10.1016/j.acthis.2019.06.003

M3 - Artículo

C2 - 31213291

AN - SCOPUS:85067296835

VL - 121

SP - 680

EP - 689

JO - Acta Histochemica

JF - Acta Histochemica

SN - 0065-1281

IS - 6

ER -