Vanina Araceli Medina

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide, with a mortality rate almost equal to its incidence, highlighting the urgent need for novel biomarkers and therapeutic targets. This pilot study aims to investigate the potential value of histamine H ₃ receptor (H ₃ R) as a prognostic biomarker for this lethal disease. We analyzed the H ₃ R expression in PDAC using the RNA sequencing data set from The Cancer Genome Atlas (Pan-Cancer Atlas). In addition, H ₃ R protein levels were evaluated by immunohistochemistry in 27 PDAC samples and compared with adjacent preneoplastic pancreatic tissue of the same patient, and with 10 non-related healthy pancreatic tissues. This preliminary study shows that the H ₃ R is barely expressed in healthy tissue. Interestingly, H ₃ R was detected in 96% of PDAC samples, and its expression in tumoral tissue was significantly higher when compared with its expression in preneoplastic tissue, and it was associated with a better prognosis in terms of overall survival. Present findings suggest that H ₃ R may serve as a potential prognostic biomarker in PDAC. Future research aimed at elucidating the role of H ₃ R in PDAC biology and its prognostic value in larger patient cohorts is warranted:

Achieving better clinical outcomes in cancer research requires a deeper understanding of tumoral biology and the application of this knowledge within a clinic setting. The aim of this review is to briefly summarize the current knowledge on H₃R molecular pharmacology, the clinical use of H₃R antagonists, and the most recent findings reporting H₃R role in cancer biology. We will discuss in detail the current landscape and clinical perspectives of the modulation of this H₃R on cancer progression and treatment. We propose H₃R as a promising molecular target for cancer drug repurposing and development.

Pharmacoscintigraphy has emerged as an essential tool in the research and development of nanomedicines, particularly in the field of nanotheranostics. By enabling the real-time, non-invasive tracking of their biodistribution, pharmacokinetics, and therapeutic efficacy, these imaging techniques provide invaluable insights that drive the optimization of nanomedicine formulations. The integration of gamma scintigraphy, SPECT, and PET imaging has significantly enhanced our understanding of nanocarrier behavior, supporting their clinical translation by ensuring precise targeting, minimizing off-target effects, and improving therapeutic outcomes. Future advancements in hybrid imaging modalities, novel radionuclide tracers, and personalized imaging-guided therapies will further expand the impact of pharmacoscintigraphy in nanomedicine. Additionally, the increasing recognition of imaging-based validation in regulatory approval processes underscores the growing importance of these techniques in drug development. As nanotheranostics continues to evolve, radionuclide imaging will remain a pivotal component in their preclinical and clinical evaluation, facilitating safer and more effective precision medicine approaches.

Pharmascintigraphy has emerged as an essential tool in the research and development of nanomedicines, particularly in the field of nanotheranostics. By enabling real-time, non-invasive tracking of their biodistribution, pharmacokinetics, and therapeutic efficacy, these imaging techniques provide invaluable insights that drive the optimization of na-nomedicine formulations. The integration of gamma scintigraphy, SPECT, and PET im-aging has significantly enhanced our understanding of nanocarrier behavior, supporting their clinical translation by ensuring precise targeting, minimizing off-target effects, and improving therapeutic outcomes. Future advancements in hybrid imaging modalities, novel radionuclide tracers, and personalized imaging-guided therapies will further ex-pand the impact of pharmacoscintigraphy in nanomedicine. Additionally, the increasing recognition of imaging-based validation in regulatory approval processes underscores the growing importance of these techniques in drug development. As nanotheranostics con-tinue to evolve, radionuclide imaging will remain a pivotal component in their preclinical and clinical evaluation, facilitating safer and more effective precision medicine ap-proaches.

Editorial: Women in anti-inflammatory and immunomodulating agents: 2022

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Currently, paclitaxel (PTX) represents the first-line therapy for TNBC; however it presents a hydrophobic behavior and produces severe adverse effects. The aim of this work is to improve the therapeutic index of PTX through the design and characterization of novel nanomicellar polymeric formulations composed of a biocompatible copolymer Soluplus^® (S), surface-decorated with glucose (GS), and co-loaded either with histamine (HA, 5 mg/mL) and/or PTX (4 mg/mL). Their micellar size, evaluated by dynamic light scattering, showed a hydrodynamic diameter between 70 and 90 nm for loaded nanoformulations with a unimodal size distribution. Cytotoxicity and apoptosis assays were performed to assess their efficacy in vitro in human MDA-MB-231 and murine 4T1 TNBC cells rendering optimal antitumor efficacy in both cell lines for the nanoformulations with both drugs. In a model of TNBC developed in BALB/c mice with 4T1 cells, we found that all loaded micellar systems reduced tumor volume and that both HA and HA-PTX-loaded SG micelles reduced tumor weight and neovascularization compared with the empty micelles. We conclude that HA-PTX co-loaded micelles in addition to HA-loaded formulations present promising potential as nano-drug delivery systems for cancer chemotherapy.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. There are neither universally accepted prognostic markers nor molecular targets related to TNBC. The histamine H4 receptor (H4R) has been characterized in TNBC experimental models, demonstrating its critical role in tumor development and progression. In this study, H4R expression was compared in breast cancer subtypes and correlated with clinical features using The Cancer Genome Atlas data (Pan-Cancer Atlas). The H4R status was further evaluated by immunohistochemistry in 30 TNBC human samples in relation to clinicopathological parameters. Results indicate that H4R was downregulated in basal-like/TNBC compared with luminal A and normal breast-like tumors. The higher expression of H4R was associated with improved progression-free and overall survival outcomes in basal-like/TNBC. H4R immunoreactivity was detected in about 70% of tumors, and its expression was positively correlated with the levels in the histologically normal peritumoral tissue. High H4R expression in peritumoral tissue correlated with reduced number of lymph node involvement and unifocal TNBC, while it was associated with increased patient survival. In conclusion, the H4R might represent a potential prognostic biomarker in TNBC. Further studies in large cohorts are needed to better understand the significance of H4R in breast cancer biology:

The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of the role of histamine in numerous physiological and pathological conditions, including tumor development and progression. The lymph nodes of patients with malignant lymphomas have shown to contain high levels of histamine, however, less is known regarding the expression and function of the H4R in T-cell lymphoma (TCL). In this work we demonstrate the expression of H4R isoforms (mRNA and protein) in three human aggressive TCL (OCI-Ly12, Karpas 299, and HuT78). Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability in a dose-dependent manner (p < 0.05). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands. Importantly, we screened a drug repurposing library of 433 FDA-approved compounds (1 μM) in combination with histamine (10 μM) in Hut78 cells. Histamine produced a favorable antitumor effect with 18 of these compounds, including the histone deacetylase inhibitor panobinostat. Apoptosis, proliferation, and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that the H4R is expressed in TCL, and it is involved in histamine-mediated responses.