Inflammatory Related Reactions in Humans and in Canine Breast Cancers, A Spontaneous Animal Model of Disease

Inflammatory cells are emerging markers in various cancers in human trials. The relationship between the inflammatory cells response, cancer grade, and progression has been investigated experimentally in a spontaneous canine model of breast cancer and in the unselected population (18–64 years.o.) un...

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Main Authors: Domenico Tricarico, Anna Sara Convertino, Irsida Mehmeti, Girolamo Ranieri, Francesco Leonetti, Carmelo Laface, Nicola Zizzo
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.752098/full
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author Domenico Tricarico
Anna Sara Convertino
Irsida Mehmeti
Girolamo Ranieri
Francesco Leonetti
Carmelo Laface
Nicola Zizzo
author_facet Domenico Tricarico
Anna Sara Convertino
Irsida Mehmeti
Girolamo Ranieri
Francesco Leonetti
Carmelo Laface
Nicola Zizzo
author_sort Domenico Tricarico
collection DOAJ
description Inflammatory cells are emerging markers in various cancers in human trials. The relationship between the inflammatory cells response, cancer grade, and progression has been investigated experimentally in a spontaneous canine model of breast cancer and in the unselected population (18–64 years.o.) under anti-HER2 treatments that represent the most prevalent population in this cancer type. The canine data (N samples = 101) were collected retrospectively for diagnosis in our regional area and evaluated by immunohistochemistry and haemato-chemistry. The inflammatory and immune-related adverse reactions (ADR) in humans were evaluated using EudraVigilance. The “Proportional Reporting Ratio” (PRR) of the mabs was calculated for each ADR with values >2 indicative of high risk. In dogs, we found elevated immunostaining of CD68-macrophages in the lymph node of the aggressive cancer G3 and infiltrating CD20+-lymphocyte. A high density of CD20 + lymphocytes was observed in G1 and a decrease in the density was observed with the histological degree of the tumors. The animals with the sample in G1 showed reduced serum platelet and neutrophil count and elevated lymphocytes and the opposite in severely affected animals. Inflammatory reactions with edema, skin reactions, extravasation, loss of effectiveness, and platelet count decrease (PRR > 13) were found with trastuzumab emtansine in humans, in the absence of immune system reactions. Trastuzumab i.v.-s.c. showed immune system reactions, loss of effectiveness, intolerances with drug withdrawal, technological issues (PRR > 7), and neutrophil count decrease reports. These reactions were less frequently reported for pertuzumab i.v. Case reports of platelet and neutrophil count decrease were not associated with disease progression with a better outcome in humans as in canine breast cancer. Therefore, infiltrating CD68-macrophages are associated with G3, while infiltrating CD20+ and elevated serum lymphocytes in parallel with reduced platelet and neutrophil count play a favorable role in human and canine breast cancer.
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spelling doaj.art-d97bb9eb8f3a4e1992c20fa76035aefd2022-12-22T00:04:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-02-011310.3389/fphar.2022.752098752098Inflammatory Related Reactions in Humans and in Canine Breast Cancers, A Spontaneous Animal Model of DiseaseDomenico Tricarico0Anna Sara Convertino1Irsida Mehmeti2Girolamo Ranieri3Francesco Leonetti4Carmelo Laface5Nicola Zizzo6Department of Pharmacy‐Pharmaceutical Sciences, University Aldo Moro, Bari, ItalyDepartment of Pharmacy‐Pharmaceutical Sciences, University Aldo Moro, Bari, ItalyDepartment of Pharmaceutical Science, Faculty of Pharmacy, “Catholic University Our Lady of Good Counsel”, Tirana, AlbaniaInterventional and Medical Oncology Unit, Department of Pathology National Cancer Research Centre, IRCCS Istituto Tumori Giovanni Paolo II, Bari, ItalyDepartment of Pharmacy‐Pharmaceutical Sciences, University Aldo Moro, Bari, ItalyInterventional and Medical Oncology Unit, Department of Pathology National Cancer Research Centre, IRCCS Istituto Tumori Giovanni Paolo II, Bari, ItalySection of Veterinary Pathology and Comparative Oncology, Department of Veterinary Medicine, University of Bari “Aldo Moro”, Bari, ItalyInflammatory cells are emerging markers in various cancers in human trials. The relationship between the inflammatory cells response, cancer grade, and progression has been investigated experimentally in a spontaneous canine model of breast cancer and in the unselected population (18–64 years.o.) under anti-HER2 treatments that represent the most prevalent population in this cancer type. The canine data (N samples = 101) were collected retrospectively for diagnosis in our regional area and evaluated by immunohistochemistry and haemato-chemistry. The inflammatory and immune-related adverse reactions (ADR) in humans were evaluated using EudraVigilance. The “Proportional Reporting Ratio” (PRR) of the mabs was calculated for each ADR with values >2 indicative of high risk. In dogs, we found elevated immunostaining of CD68-macrophages in the lymph node of the aggressive cancer G3 and infiltrating CD20+-lymphocyte. A high density of CD20 + lymphocytes was observed in G1 and a decrease in the density was observed with the histological degree of the tumors. The animals with the sample in G1 showed reduced serum platelet and neutrophil count and elevated lymphocytes and the opposite in severely affected animals. Inflammatory reactions with edema, skin reactions, extravasation, loss of effectiveness, and platelet count decrease (PRR > 13) were found with trastuzumab emtansine in humans, in the absence of immune system reactions. Trastuzumab i.v.-s.c. showed immune system reactions, loss of effectiveness, intolerances with drug withdrawal, technological issues (PRR > 7), and neutrophil count decrease reports. These reactions were less frequently reported for pertuzumab i.v. Case reports of platelet and neutrophil count decrease were not associated with disease progression with a better outcome in humans as in canine breast cancer. Therefore, infiltrating CD68-macrophages are associated with G3, while infiltrating CD20+ and elevated serum lymphocytes in parallel with reduced platelet and neutrophil count play a favorable role in human and canine breast cancer.https://www.frontiersin.org/articles/10.3389/fphar.2022.752098/fullbreast cancerimmunoistochemistrycanine animal modelinflammationpharmacovigilance
spellingShingle Domenico Tricarico
Anna Sara Convertino
Irsida Mehmeti
Girolamo Ranieri
Francesco Leonetti
Carmelo Laface
Nicola Zizzo
Inflammatory Related Reactions in Humans and in Canine Breast Cancers, A Spontaneous Animal Model of Disease
Frontiers in Pharmacology
breast cancer
immunoistochemistry
canine animal model
inflammation
pharmacovigilance
title Inflammatory Related Reactions in Humans and in Canine Breast Cancers, A Spontaneous Animal Model of Disease
title_full Inflammatory Related Reactions in Humans and in Canine Breast Cancers, A Spontaneous Animal Model of Disease
title_fullStr Inflammatory Related Reactions in Humans and in Canine Breast Cancers, A Spontaneous Animal Model of Disease
title_full_unstemmed Inflammatory Related Reactions in Humans and in Canine Breast Cancers, A Spontaneous Animal Model of Disease
title_short Inflammatory Related Reactions in Humans and in Canine Breast Cancers, A Spontaneous Animal Model of Disease
title_sort inflammatory related reactions in humans and in canine breast cancers a spontaneous animal model of disease
topic breast cancer
immunoistochemistry
canine animal model
inflammation
pharmacovigilance
url https://www.frontiersin.org/articles/10.3389/fphar.2022.752098/full
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