Histamine: a potential cytoprotective agent to improve cancer therapy?

Chemotherapy along with radiotherapy is a major treatment of medical oncology. Despite their therapeutic effects achieving local tumor control and in many cases controlling metastasis, both approaches can produce serious adverse effects to normal tissues either immediately or during the long term after treatment. Thus, their related toxicity frequently outweigh clinical benefits and worsen patient's quality of life.Regardless of the high incidence of cancer therapy-associated adverse reactions (e.g., hepato, hemato and cardio toxicities) and their significant impact on morbidity, mortality and health economics; as far as we know, there are no standard, clinically approved, effective agents that could improve the therapeutic index of chemo and radiotherapy, controlling these devastating side effects in patients undergoing anti-tumoral treatments.1, 2 Therefore, the development of pharmacological approaches to effectively prevent conventional cancer therapy-induced toxicity is of utmost importance.Fil: Martinel Lamas, Diego José. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Nicoud, Melisa Beatriz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Cremaschi, Graciela Alicia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin

Thyroid status modulates T lymphoma growth via cell cycle regulatory proteins and angiogenesis

We have shown in vitro that thyroid hormones (THs) regulate the balance between proliferation and apoptosis of T lymphoma cells. The effects of THs on tumor development have been studied, but the results are still controversial. Herein, we show the modulatory action of thyroid status on the in vivo growth of T lymphoma cells. For this purpose, euthyroid, hypothyroid, and hyperthyroid mice received inoculations of EL4 cells to allow the development of solid tumors. Tumors in the hyperthyroid animals exhibited a higher growth rate, as evidenced by the early appearance of palpable solid tumors and the increased tumor volume. These results are consistent with the rate of cell division determined by staining tumor cells with carboxyfluorescein succinimidyl ester. Additionally, hyperthyroid mice exhibited reduced survival. Hypothyroid mice did not differ significantly from the euthyroid controls with respect to these parameters. Additionally, only tumors from hyperthyroid animals had increased expression levels of proliferating cell nuclear antigen and active caspase 3. Differential expression of cell cycle regulatory proteins was also observed. The levels of cyclins D1 and D3 were augmented in the tumors of the hyperthyroid animals, whereas the cell cycle inhibitors p16/INK4A (CDKN2A) and p27/Kip1 (CDKN1B) and the tumor suppressor p53 (TRP53) were increased in hypothyroid mice. Intratumoral and peritumoral vasculogenesis was increased only in hyperthyroid mice. Therefore, we propose that the thyroid status modulates the in vivo growth of EL4 T lymphoma through the regulation of cyclin, cyclin-dependent kinase inhibitor, and tumor suppressor gene expression, as well as the stimulation of angiogenesis.Fil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina ; ArgentinaFil: Valli, Eduardo. Pontificia Universidad Católica Argentina ; ArgentinaFil: Cayrol, Maria Florencia. Pontificia Universidad Católica Argentina ; ArgentinaFil: Paulazo, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Díaz Flaqué, María Celeste. Pontificia Universidad Católica Argentina ; ArgentinaFil: Klecha, Alicia Juana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Colombo, L.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cremaschi, Graciela Alicia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Pontificia Universidad Católica Argentina ; ArgentinaFil: Barreiro Arcos, María Laura. Pontificia Universidad Católica Argentina ; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin

Study of the antitumour effects and the modulation of immune response by histamine in breast cancer

Background: The aim of this work was to improve the knowledge of the role of histamine in breast cancer by assessing the therapeutic efficacy of histamine and histamine H4 receptor (H4R) ligands in a triple-negative breast cancer (TNBC) model developed in immunocompetent hosts. By using publicly available genomic data, we further investigated whether histidine decarboxylase (HDC) could be a potential biomarker. Methods: Tumours of 4T1 TNBC cells were orthotopically established in BALB/c mice. Treatments employed (mg kg−1): histamine (1 and 5), JNJ28610244 (H4R agonist, 1 and 5) and JNJ7777120 (H4R antagonist, 10). Results: Increased HDC gene expression is associated with better relapse-free and overall survival in breast cancer patients. Histamine treatment (5 mg kg−1) of 4T1 tumour-bearing mice reduced tumour growth and increased apoptosis. Although no immunomodulatory effects were observed in wild-type mice, significant correlations between tumour weight and cytotoxic lymphocyte infiltration were detected in H4R knockout mice. H4R agonist or antagonist differentially modulated tumour growth and immunity in 4T1 tumour-bearing mice. Conclusions: Histamine plays a complex role and stands out as a promising drug for TNBC treatment, which deserves to be tested in clinical settings. HDC expression level is associated with clinicopathological characteristics, suggesting a prognostic value in breast cancer.Fil: Nicoud, Melisa Beatriz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Massari, Noelia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Táquez Delgado, Mónica Alejandra. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Formoso, Karina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Herrero Ducloux, María Verónica. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Martinel Lamas, Diego José. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Cremaschi, Graciela Alicia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin

Histamine H4 receptor: insights into a potential therapeutic target in breast cancer

Breast cancer is the second most common cancer worldwide, and the leading cause of cancer death in women. Several studies underlined the critical role of histamine in breast cancer development and progression. This review addresses the latest evidence regarding the involvement of histamine and histamine receptors in breast cancer, focusing particularly in the histamine H4 receptor (H4R). Histamine concentration in breast cancer tissues was found to be higher than that in normal tissues of healthy controls by means of an increase in the activity of histidine decarboxylase (HDC), the enzyme involved in histamine production. The expression of H4R in different experimental models and human biopsies, the associated biological responses, as well as the in vivo treatment of experimental tumors with H4R ligands is reviewed. Evidence demonstrates that the H4R exhibits a key role in histamine-mediated biological processes such as cell proliferation, senescence and apoptosis in breast cancer. The polymorphisms of the H4R and HDC genes and their association with breast cancer risk and malignancy reinforce the critical (patho)physiological role of H4R in breast cancer. In addition, H4R agonists display anti-tumor effects in vivo in a triple negative breast cancer model. The findings support the exploitation of the H4R as a molecular target for breast cancer drug development.Fil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisotopos; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Rivera, Elena Susana. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisotopos; ArgentinaFil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisotopos; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin

Hepato and Cardiotoxicity of Chemotherapeutic Treatment Evaluated by Means of Small Animal Imaging

Background: Chemotherapy is one of the most common approaches for cancer treatment. Particularly Doxorubicin has been proven to be effective in the treatment of many soft and solid tumors for locally advanced and metastatic cancer. It is not easy to clinically evaluate the chemotoxic or chemoprotective effect of some drugs, even more when there is a subclinical toxicity. Objective: To determine the usefulness of the hepatobiliary, colloid and cardiac scintigraphies, employing 99mTc-disida, 99mTc-phytate and 99mTc-sestamibi respectively, in the evaluation of the hepato and cardiotoxicity of two chemotherapeutic treatments assessed in rats. Method: Two groups were submitted to doxorubicin (DOX) treatment and one was co-administered with histamine (DOX+HIS). Static 99mTc-phytate and 99mTc-sestamibi scintigraphies as well as a dynamic 99mTc-disida study were performed in a small field of view gamma camera at: 0 weeks (control), 1 week and 2 weeks of treatment. Imagenological parameters were calculated: Liver/Bone Marrow ratio (L/BM), Heart/Background ratio (H/B) and time to the maximum (Tmax) for 99mTc-phytate, 99mTc-sestamibi and 99mTc-disida extraction, respectively. Results: Control (L/BM= 98±3; H/B=2.3±0.4; Tmax=8±3), DOX (L/BM: 85±3, 80±3; H/B, 3.5±0.5, 3.3±0.5 and Tmax 6±1, 4±1) for 1 and 2 weeks respectively and DOX+HIS (L/BM: 99±0.3, 98±1; H/B 2.9±0.5, 2.9±0.5 and Tmax, 8±2, 9±2) for 1 and 2 weeks, respectively. Histological analysis showed cardio and hepatotoxicity induced by doxorubicin. Conclusion: Imagenological parameters showed differences among treated and control groups and between both chemotherapy treatments. Thus, these radiopharmaceutical functional approaches were able to reflect heart and liver toxicity produced by doxorubicin.Fil: Tesan, Fiorella Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Portillo, Mariano Gastón. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Martinel Lamas, Diego José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Medina, Vanina Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Salgueiro, María Jimena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Zubillaga, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Differential mechanisms of action are involved in chlorpyrifos effects in estrogen-dependent or -independent breast cancer cells exposed to low or high concentrations of the pesticide

It has reported that many environmental compounds may display estrogenic actions and these findings led to researchers to associate breast cancer risk with the use of some pesticides. The aim of this work was to investigate the effect of chlorpyrifos (CPF) on cell proliferation and the ERα-dependence of this action employing MCF-7 and MDA-MB-231 breast cancer cell lines. We have also analyzed CPF action on the cell cycle distribution and the cyclins that are implicated in G1-S and intra-S checkpoints. Finally, the action on cell death and ROS production were studied. We demonstrated the ability of CPF 0.05 μM to induce cell proliferation through ERα in hormone-dependent breast cancer cells. In contrast, CPF 50 μM induces intra-S arrest modifying checkpoints proteins, through a mechanism that may involve changes in redox balance in MCF-7. In MDA-MB-231, we have found that CPF 50 μM produces an arrest in G2/M phase which could be related to the capacity of the pesticide for binding to tubulin sites altering microtubules polymerization. Altogether, our results provide new evidences on the action of the pesticide CPF as an environmental breast cancer risk factor due to the effects that causes on the mechanisms that modulate breast cell proliferation.Fil: Ventura, Clara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Núñez, Mariel Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Miret, Noelia Victoria. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Venturino, Andres. Universidad Nacional del Comahue; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rivera, Elena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Role of H4 receptor in histamine-mediated responses in human melanoma

We have previously reported that histamine at micromolar concentrations reduces the proliferation of melanoma cell lines. It is also known that melanoma cells express histamine H1, H2 and H3 receptors. The aim of this work was to investigate the presence of histamine H4 receptor (H4R) in human melanoma cells and its associated biological processes. In order to better understand the importance of histamine in tumor development, we explored the expression of H4R in human melanoma tissue biopsies. The expression of H4R in WM35 and M1/15 cells was analyzed by RT-PCR, Western blot and immunocytochemistry. To characterize the biological responses we evaluated cell proliferation by clonogenic assay and BrdU incorporation. In addition, cell senescence and differentiation were determined by β-galactosidase enzyme assay and dopa oxidase activity, respectively. The expression levels of H4R were determined by immunohistochemistry in 19 samples of human malignant lesions. Results indicate that melanoma cells express H4R at the mRNA and protein level. By using histamine agonists, antagonists and H4 siRNA we showed that the inhibitory effect of histamine on proliferation was in part mediated through the stimulation of the H4R. The decrease in proliferation was associated with an induction of cell senescence and an increase in melanogenesis that is a differentiation marker of these cells. Furthermore, H4R was expressed in 42% of human melanoma biopses. To our knowledge this is the first report that describes the presence of the H4R in melanoma cells and tissue suggesting a potential therapeutic application of H4R ligands.Fil: Massari, Noelia Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Cricco, Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Croci, Máximo. Instituto de Inmunooncología; ArgentinaFil: Sambuco, Lorena Andrea. Instituto de Inmunooncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Bergoc, Rosa Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Rivera, Elena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Antitumoral ans inmunomodulatory role for histamine in breast cancer

It is well known that histamine is a key regulator of inmune cell functions and it also modulates cancer cell proliferation. The aim of this work was to investigate the effect of histamine and its H4 receptor (H4R) agonist (JNJ28610244) on tumour growth and in the inmune tumour microenvironment as a whole, in a triple negative breast cancer (TNBC) syngeneic model developed in inmunocompetent mice. Tumours of tne TNBC cell line 4T1 were established in Balb/c mice. Treatments employed: histamine (1 or 5mg/kg) and JNJ28610244 (1 or 5mg kg). Results show that histamine treatment (5mg/kg) reduces tumour growth more effectively that JNJ28610244. Histamine but the agonist increases tumour apoptosis and it reduces the number of intratumoural vessels. Histamine also reduces immunosuppression throught the modulation of the tumour microenvironment, as it increasesthe tumour secretion of IFN gamma and reduces the number of T regulatory (Treg) lymphocytes in lymph nodes and spleen. A lower concretation (1mg/kg) of JNJ28610244 reduces tumour size while no inmunomodulatory effects are observed in the immune cell subsets studied. In contrast, a higher concentration (5mg/kg) is not able to decrease tumour growth probably because of the immunosuppressive effect produced in the tumour microenvironment, showing increased levels of interleukin (IL)-10 and decreased levels of IFNy in tumours and increased infiltrating Treg cells in tumour draining lymph nodes. These results highlight the critical interplay between tumour cells and host immune response that determine the clinical therapeutic outcomes and suggest that histamine is a key pleiotropic mediator with therapeutic benefits in TNBC.Fil: Nicoud, Melisa Beatriz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Massari, Noelia Andrea. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Táquez Delgado, Mónica Alejandra. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Formoso, Karina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Herrero Ducloux, María Verónica. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Martinel Lamas, Diego José. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaLXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVI Reunión Anual de la Sociedad Argentina de Inmunología; Reunión Anual de la Sociedad Argentina de FisiologíaMar del PlataArgentinaSociedad Argentina de Investigacion ClinicaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaSociedad Argentina de VirologíaSociedad Argentina de Nanomedicina

Pharmacological targeting of histamine H4 receptor in periodontal disease

Objective: The objective of this study was to investigate whether histamine H4 receptor (H4R) antagonists could prevent experimental periodontitis (EP)-induced histological, functional and inflammatory alterations in submandibular gland (SMG), periodontal bone and gingiva. Methods: Bilateral EP was induced for 2 weeks in anaesthetized male rats. The effect of systemic and local administration of H4R antagonists (JNJ7777120, JNJ10191584) on histopathology and functionality of SMG, bone loss and gingival inflammation was evaluated. Results: The subcutaneous administration of JNJ7777120 prevented periodontitis-induced SMG histological injury, reducing vacuolization and apoptosis and additionally reversed the increased prostaglandin E2 (PGE2) levels in SMG while it partially reversed the methacholine-induced salivation reduction produced by periodontitis. JNJ7777120 attenuated bone loss and the increased PGE2 levels and inflammatory infiltration in gingival tissue of rats with periodontitis. Finally, local administration of JNJ7777120 and JNJ10191584 was also beneficial for improving periodontal parameters. Conclusions: H4 receptor antagonists are able to ameliorate periodontitis-induced injury on SMG, gingival tissue and bone structure, suggesting that pharmacological targeting of H4R could be an attractive strategy to improve periodontal health.Fil: Prestifilippo, J. P.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Fernández Solari, José Javier. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinel Lamas, Diego José. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rios, Carlos Ezequiel. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mohn, Claudia Ester. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perazzo, Juan C.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rivera, E. S.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Elverdin, J. C.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin

Therapeutic potential of histamine H4 receptor agonists in triple-negative human breast cancer experimental model

The presence of the histamine H₄ receptor (H₄R) was previously reported in benign and malignant lesions and cell lines derived from the human mammary gland. The aim of this work was to evaluate the effects of H₄R ligands on the survival, tumour growth rate and metastatic capacity of breast cancer in an experimental model.Fil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Croci, Máximo. Instituto de Inmunooncología; ArgentinaFil: Carabajal, Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; ArgentinaFil: Crescenti, Ernesto J. V.. Instituto de Inmunooncología; ArgentinaFil: Sambuco, Lorena Andrea. Instituto de Inmunooncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Massari, Noelia Andrea. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Bergoc, Rosa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; ArgentinaFil: Rivera, Elena Susana. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; ArgentinaFil: Medina, Vanina Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentin