Aspirin and antiplatelet treatments in cancer.

Platelets have been hypothesized to promote certain neoplastic malignancies; however, antiplatelet drugs are still not part of routine pharmacological cancer prevention and treatment protocols. Paracrine interactions between platelets and cancer cells have been implicated in potentiating the dissemination, survival within the circulation, and extravasation of cancer cells at distant sites of metastasis. Signals from platelets have also been suggested to confer epigenetic alterations, including upregulating oncoproteins in circulating tumor cells, and secretion of potent growth factors may play roles in promoting mitogenesis, angiogenesis, and metastatic outgrowth. Thrombocytosis remains a marker of poor prognosis in patients with solid tumors. Experimental data suggest that lowering of platelet count may reduce tumor growth and metastasis. On the basis of the mechanisms by which platelets could contribute to cancer growth and metastasis, it is conceivable that drugs reducing platelet count or platelet activation might attenuate cancer progression and improve outcomes. We will review select pharmacological approaches that inhibit platelets and may affect cancer development and propagation. We begin by presenting an overview of clinical cancer prevention and outcome studies with low-dose aspirin. We then review current nonclinical development of drugs targeted to platelet binding, activation, and count as potential mitigating agents in cancer.

Hemocompatibility of polyzwitterion-modified titanium dioxide nanotubes.

Titanium dioxide nanotubes (TNTs) have attracted increasing interest as implantable materials due to their many desirable properties. However, their blood compatibility remains an issue. In this paper, TNTs of different diameters were modified with two types of zwitterionic polymers, poly(sulfobetaine methacrylate) (pSBMA) and poly(carboxybetaine methacrylate) (pCBMA), which were grafted onto the TNTs using ARGET-ATRP (activators regenerated by electron transfer atom transfer radical polymerization) method. Both pSBMA and pCBMA brushes coatings were found to greatly reduce adsorption of bovine serum albumin (BSA) and fibrinogen (Fib) onto the TNTs, showing excellent protein resistance. Moreover, the effects of the surface topography on the amount of protein adsorption were largely suppressed by the polyzwitterion coatings. The conformation of the protein adsorbed to the substrates was analyzed at the molecular level by Fourier-transform infrared reflection spectroscopy (FT-IR), which revealed that the BSA adsorbed on the polyzwitterion-modified TNTs adopted significantly different secondary structures from that on the virgin TNTs, whereas the conformation of the adsorbed Fib remained basically the same. The polyzwitterion-modified TNTs were found to be non-hemolytic, and platelet adhesion and activation was significantly reduced, showing excellent blood compatibility.

Blood and fibroblast responses to thermoset BisGMA-TEGDMA/glass fiber-reinforced composite implants in vitro.

OBJECTIVES: This in vitro study was designed to evaluate both blood and human gingival fibroblast responses on fiber-reinforced composite (FRC) aimed to be used as oral implant abutment material. MATERIAL AND METHODS: Two different types of substrates were investigated: (a) Plain polymer (BisGMA 50%-TEGDMA 50%) and (b) FRC. The average surface roughness (Ra) was measured using spinning-disk confocal microscope. The phase composition was identified using X-ray diffraction analyzer. The degree of monomer conversion (DC%) was determined using FTIR spectrometry. The blood response, including the blood-clotting ability and platelet adhesion morphology, was evaluated. Fibroblast cell responses were studied in cell culture environment using routine test conditions. RESULTS: The Ra of the substrates investigated was less than 0.1 µm with no signs of surface crystallization. The DC% was 89.1 ± 0.5%. The FRC substrates had a shorter clotting time and higher platelets activation state than plain polymer substrates. The FRC substrates showed higher (P < 0.01-0.001) amount of adhered cells than plain polymer substrates at all time points investigated. The strength of attachment was evaluated using serial trypsinization, the number of cells detached from FRC substrates was 59 ± 5%, whereas those detached from the plane polymer substrates was 70 ± 5%, indicating a stronger (P < 0.01) cell attachment on the FRC surfaces. Fibroblasts grew more efficiently on FRC than on plain polymer substrates, showing significantly higher (P < 0.01) cell metabolic activities throughout the experiment. CONCLUSIONS: The presence of E-glass fibers enhances blood and fibroblast responses on composite surfaces in vitro.

Massive Spontaneous Suprachoroidal Hemorrhage in a Patient With Type 1 Chronic Myeloid Leukemia and Lymphoplasmacytic Lymphoma: Case Report and Review of the Literature.

Purpose: This work reports a rare case of spontaneous suprachoroidal hemorrhage (SSCH) and summarizes the literature on its treatment options and outcomes. Methods: A case report and comprehensive literature review are presented on the medical and surgical management of SSCH on PubMed from 1998 to 2021. Results: The literature search revealed 58 studies, 33 of which included 52 eyes of 47 patients. Surgical treatment typically consisted of choroidal drainage with posterior sclerotomies combined with pars plana vitrectomy and silicone oil placement. Medical therapy involved intraocular pressure control with laser peripheral iridotomy and topical, oral, and intravenous medication. Conclusions: In cases of SSCH, conservative management and a prompt workup should be initiated to identify the cause before proceeding with surgery. If the initial workup does not reveal a cause, medical and surgical treatments are both viable and the decision is at the discretion of the treating physician.

UHMWPE/HA biocomposite compatibilized by organophilic montmorillonite: An evaluation of the mechanical-tribological properties and its hemocompatibility and performance in simulated blood fluid.

The low interaction between ultra high molecular weight polyethylene (UHMWPE) and hydroxyapatite (HA) has been one of the problems that results in a composite material with low mechanical and tribological performance due to the formation of agglomerates and microstructural defects. These properties affect the quality of the material when used for total joint implants and other applications in hard tissue engineering. This study investigated the effect of the addition of organophilic bentonite (BO) into the interface HA and UHMWPE. The composite was prepared by wet milling in a planetary mill and then by compression molding. The composites samples were characterized by XRD, FTIR, SEM and DSC. The tensile and tribological mechanical properties were also evaluated. Furthermore, in vitro degradation using simulated blood fluid (SBF) and hemocompatibility was performed. The results suggest that the addition of 10 wt% of organophilic bentonite improved the interface between the UHMWPE and HA by exfoliation/intercalation, presenting the best results of modulus of elasticity, tensile strength, coefficient of friction and rate of wear. The composite UHMWPE/HA/BO-10 wt% presented low water absorption and induced the growth of apatite crystals on its surface. Additionally, its hemocompatibility index is within normal limits and induced a low adhesion and agglomeration of platelets in contact with human blood, evidencing that the UHMWPE/HA/BO-10 wt% composite is promising for application in bone tissue engineering.

A single-cell analysis platform for electrochemiluminescent detection of platelets adhesion to endothelial cells based on Au@DL-ZnCQDs nanoprobes.

A novel single-cell analysis platform (SCA) was developed for the investigation of platelets adhesion to single human umbilical vein endothelial cell (HUVEC) via using the adhesion molecule (E-selectin) on the damaged HUVEC as the marker site, and integrating electrochemiluminescence (ECL) with the ultrasensitive Au@DL-ZnCQDs nanoprobes. The Au@DL-ZnCQDs nanocomposite, a kind of double layer zinc-coadsorbed carbon quantum dot (ZnCQDs) core-shell nanoprobe, was firstly constructed by using gold nanoparticles (AuNPs) as the core to load with ZnCQDs and then the citrate-modified silver nanoparticles (AgNPs) as the bridge to link AuNPs-ZnCQDs with ZnCQDs to form the core-shell with double layer ZnCQDs (DL-ZnCQDs) nanoprobe, revealed a 10-fold signal amplification. The H2O2-induced oxidative damage HUVECs were utilized as the cellular model on which anti-E-selectin functionalized nanoprobes specially recognized E-selectin, the SCA showed that the ECL signals decreased with platelets adhesion to single HUVEC. The proposed SCA could effectively and dynamically monitor the adhesion between single HUVEC and platelets in the absence and presence of collagen activation, moreover, be able to quantitatively detect the number of platelets adhesion to single HUVEC, and show a good analytical performance with linear range from 1 to 15 platelets. In contrast, the HUVEC was down-regulated the expression of adhesion molecules by treating with quercetin inhibitor, and the SCA also exhibited the feasibility for analysis of platelets adhesion to single HUVEC. Therefore, the single-cell analysis platform provided a novel and promising protocol for analysis of the single intercellular adhesion, and it will be beneficial to elucidate the pathogenesis of cardiovascular diseases.

The influence of surface chemistry on adsorbed fibrinogen conformation, orientation, fiber formation and platelet adhesion.

Thrombosis is a clear risk when any foreign material is in contact with the bloodstream. Here we propose an immunohistological stain-based model for non-enzymatic clot formation that enables a facile screen for the thrombogenicity of blood-contacting materials. We exposed polymers with different surface chemistries to protease-free human fibrinogen. We observed that on hydrophilic surfaces, fibrinogen is adsorbed via αC regions, while the γ400-411 platelet-binding dodecapeptide on the D region becomes exposed, and fibrinogen fibers do not form. In contrast, fibrinogen is adsorbed on hydrophobic surfaces via the relatively hydrophobic D and E regions, exposing the αC regions while rendering the γ400-411 inaccessible. Fibrinogen adsorbed on hydrophobic surfaces is thus able to recruit other fibrinogen molecules through αC regions and polymerize into large fibrinogen fibers, similar to those formed in vivo in the presence of thrombin. Moreover, the γ400-411 is available only on the large fibers not elsewhere throughout the hydrophobic surface after fibrinogen fiber formation. When these surfaces were exposed to gel-sieved platelets or platelet rich plasma, a uniform monolayer of platelets, which appeared to be activated, was observed on the hydrophilic surfaces. In contrast, large agglomerates of platelets were clustered on fibers on the hydrophobic surfaces, resembling small nucleating thrombi. Endothelial cells were also able to adhere to the monomeric coating of fibrinogen on hydrophobic surfaces. These observations reveal that the extent and type of fibrinogen adsorption, as well as the propensity of adsorbed fibrinogen to bind platelets, may be modulated by careful selection of surface chemistry. STATEMENTS OF SIGNIFICANCE: Thrombosis is a well-known side effect of the introduction of foreign materials into the bloodstream, as might exist in medical devices including but not limited to stents, valves, and intravascular catheters. Despite many reported studies, the body's response to foreign materials in contact with the blood remains poorly understood. Current preventive methods consist of drug eluting coatings on the devices or the systemic administration of standard anticoagulants. Here we present a potential mechanism by which surface chemistry can affects fibrinogen conformation and thus affects platelet adhesion and consequently thrombus formation. Our findings suggest a possible coating which enables endothelial cell adhesion while preventing platelet adhesion.