Pigmented melanoma cell migration study on murine syngeneic B16F10 melanoma cells or tissue transplantation models

Melanoma is a lethal form of skin cancer with poor prognosis, especially due to the early metastatic feature. Recent studies have shown that the melanin pigment influences the nanomechanical properties and, therefore, the metastatic behavior of the melanoma cells. We aimed to study the growth of subcutaneously transplanted syngeneic melanoma tissue in female C57BL/6 mice harvested from a mouse with a four-week B16F10 melanoma. Also, we studied the effect of the melanin pigment loading on the peritumoral migratory abilities of melanoma cells. Even when the syngeneic transplant was different (cultured cells vs. tumor tissue), the morphological features and the tumor growth were similar in both groups of mice. Heavily pigmented melanoma cells had low migration abilities. Angiogenesis, the depigmentation phenomenon, and the cell shape changes were related to pigmented melanoma cell migration along the matrix collagen fibers of peritumoral structures: the abluminal face of the vessels (angiotropism), the endomysium, and the nerves (neurotropism). The replacement of the histopathological growth pattern, the absence of angiogenesis, and rapidly tumor-bearing emboli were correlated with amelanotic and low pigmented melanoma cells. This study demonstrated that syngeneic melanoma tissue transplantation was a viable technique, and that the melanin pigment loading level can affect the melanoma cell migration profile

Pigmented melanoma cell migration study on murine syngeneic B16F10 melanoma cells or tissue transplantation models

Melanoma is a lethal form of skin cancer with poor prognosis, especially due to the early metastatic feature. Recent studies have shown that the melanin pigment influences the nanomechanical properties and, therefore, the metastatic behavior of the melanoma cells. We aimed to study the growth of subcutaneously transplanted syngeneic melanoma tissue in female C57BL/6 mice harvested from a mouse with a four-week B16F10 melanoma. Also, we studied the effect of the melanin pigment loading on the peritumoral migratory abilities of melanoma cells. Even when the syngeneic transplant was different (cultured cells vs. tumor tissue), the morphological features and the tumor growth were similar in both groups of mice. Heavily pigmented melanoma cells had low migration abilities. Angiogenesis, the depigmentation phenomenon, and the cell shape changes were related to pigmented melanoma cell migration along the matrix collagen fibers of peritumoral structures: the abluminal face of the vessels (angiotropism), the endomysium, and the nerves (neurotropism). The replacement of the histopathological growth pattern, the absence of angiogenesis, and rapidly tumor-bearing emboli were correlated with amelanotic and low pigmented melanoma cells. This study demonstrated that syngeneic melanoma tissue transplantation was a viable technique, and that the melanin pigment loading level can affect the melanoma cell migration profile

Innate Immune Response as a New Challenge in Periodontal Inflammation

Gingivitis and periodontitis are induced by numerous pathogenic microbiota hosted in the subgingival biofilm that first trigger the innate immune response. Innate immune response is part of a homeostatic system which is the first line defence and defines the host inherited resistance to infection. Both genetic and environmental factors are involved in variable individual susceptibility to inflammation of periodontal tissues. That is why, although more than 600 bacterial species have been detected in the periodontal plaque, the type of bacteria incriminated in the development of the inflammation is still unclear. Moreover, in the last decade gene polymorphisms have been largely recognised as important conditions associated with increased susceptibility to periodontal diseases. Manipulating the immune response by the development of drugs that inhibit adverse host reactions and promote beneficial effects might be of therapeutic or prophylactic importance. This work intends to assess the importance of Toll-like receptors as main effectors of the innate immune response in the triggering, maintenance and progression of periodontal inflammation, as well as of the involvement of synthetic molecules targeting TLR signalling pathways in treating periodontal diseases

Administration Routes as Modulators of the Intrahepatic Distribution and Anti-Anemic Activity of Salicylic Acid/Fe3O4 Nanoparticles

The liver is a key organ in the pharmacokinetics of iron oxide nanoparticles (IONPs). This paper examined how the intravenous (IV) or intragastric (IG) route of administration influenced the intrahepatic distribution or therapeutic effects of IONPs. Wistar rats, some with bleeding-induced anemia, and iron oxide nanoparticles functionalized with salicylic acid (SaIONPs), with an average hydrodynamic diameter of 73 nm, compatible with rat sinusoid fenestrations, were used in this study. Light microscopy and multispectral camera analysis of Prussian blue labeled SaIONPs allowed mapping of intrahepatic nanoparticle deposits and revealed intrahepatic distribution patterns specific to each route of administration: loading of Kupffer cells and periportal hepatocytes when the IV route was used and predominant loading of hepatocytes when the IG route was used. Reducing the time to return to baseline values for hemoglobin (HGB) in rats with bleeding-induced anemia with IV or IG therapy has proven the therapeutic potential of SaIONPs in such anemias. The long-term follow-up showed that IV therapy resulted in higher HGB values. Proper use of the administration routes may modulate intrahepatic distribution and therapeutic effects of nanoparticles. These results may be beneficial in theragnosis of liver disease

Phenotypic Switching of B16F10 Melanoma Cells as a Stress Adaptation Response to Fe3O4/Salicylic Acid Nanoparticle Therapy

Melanoma is a melanocyte-derived skin cancer that has a high heterogeneity due to its phenotypic plasticity, a trait that may explain its ability to survive in the case of physical or molecular aggression and to develop resistance to therapy. Therefore, the therapy modulation of phenotypic switching in combination with other treatment modalities could become a common approach in any future therapeutic strategy. In this paper, we used the syngeneic model of B16F10 melanoma implanted in C57BL/6 mice to evaluate the phenotypic changes in melanoma induced by therapy with iron oxide nanoparticles functionalized with salicylic acid (SaIONs). The results of this study showed that the oral administration of the SaIONs aqueous dispersion was followed by phenotypic switching to highly pigmented cells in B16F10 melanoma through a cytotoxicity-induced cell selection mechanism. The hyperpigmentation of melanoma cells by the intra- or extracellular accumulation of melanic pigment deposits was another consequence of the SaIONs therapy. Additional studies are needed to assess the reversibility of SaIONs-induced phenotypic switching and the impact of tumor hyperpigmentation on B16F10 melanoma’s progression and metastasis abilities

Iron Oxide/Salicylic Acid Nanoparticles as Potential Therapy for B16F10 Melanoma Transplanted on the Chick Chorioallantoic Membrane

Unfavorable prognoses and low survival rates are specific features of metastatic melanoma that justify the concern for the development of new therapeutic strategies. Lately, nanotechnology has become an attractive field of study due to recent advances in nanomedicine. Using a chick chorioallantoic membrane (CAM) implanted with xenografts harvested from C57BL/6 mice with B16F10 melanoma cells, we studied the effects of iron oxide nanoparticles functionalized with salicylic acid (SaMNPs) as a form of therapy on the local development of xenotransplants and CAM vessels. The SaMNPs induced an anti-angiogenic effect on the CAM vessels, which accumulated preferentially in the melanoma cells and induced apoptosis and extensive xenograft necrosis. As a result, this slowed the increase in the xenograft volume and reduced the melanoma cells’ ability to metastasize locally and distally. Further, we demonstrate the use of the chick CAM model as a tool for testing the action of newly synthesized nanocomposites on melanoma xenotransplants. The SaMNPs had a therapeutic effect on B16F10 melanoma due to the synergistic action of the two components of its structure: the coating of the salicylic acid with antiangiogenic and chemotherapeutic action and the core of iron oxides with cytotoxic action