MMPs-responsive silk spheres for controlled drug release within tumor microenvironment.

Silk is a biocompatible and biodegradable material that enables the formation of various morphological forms, including nanospheres. The functionalization of bioengineered silk makes it possible to produce particles with specific properties. In addition to tumor cells, the tumor microenvironment (TME) includes stromal, immune, endothelial cells, signaling molecules, and the extracellular matrix (ECM).

Endotoxin reduction from biotech silk material inhibits the production of anti-silk antibodies in mice.

Eliminating endotoxins is a common problem in the development of biotechnologically produced pharmaceuticals or biomaterials. Residual endotoxins in the final sample may hamper the properties of the product or induce severe adverse effects. Developing an effective downstream purification protocol that ensures a lack of minimal endotoxin content in the final product can be a challenging task.

In vivo study of the immune response to bioengineered spider silk spheres.

Bioengineered MS1 silk is derived from major ampullate spidroin 1 (MaSp1) from the spider Nephila clavipes. The MS1 silk was functionalized with the H2.1 peptide to target Her2-overexpressing cancer cells.

Systemic and Local Silk-Based Drug Delivery Systems for Cancer Therapy.

For years, surgery, radiotherapy, and chemotherapy have been the gold standards to treat cancer, although continuing research has sought a more effective approach. While advances can be seen in the development of anticancer drugs, the tools that can improve their delivery remain a challenge. As anticancer drugs can affect the entire body, the control of their distribution is desirable to prevent systemic toxicity.

MS1-type bioengineered spider silk nanoparticles do not exhibit toxicity in an mouse model.

Due to factors such as silk sequence, purification, degradation, morphology and functionalization, each silk variant should be individually tested for potential toxicity.   toxicological evaluation of the previously characterized bioengineered H2.1MS1 spider silk particles that can deliver chemotherapeutics to human epidermal growth factor receptor 2-positive breast cancer.

Functionalized silk spheres selectively and effectively deliver a cytotoxic drug to targeted cancer cells in vivo.

Background: Chemotherapy is often a first-line therapeutic approach for the treatment of a wide variety of cancers. Targeted drug delivery systems (DDSs) can potentially resolve the problem of chemotherapeutic drug off-targeting effects. Herein, we examined in vivo models to determine the efficacy of Her2-targeting silk spheres (H2.

Silk Particles as Carriers of Therapeutic Molecules for Cancer Treatment.

Although progress is observed in cancer treatment, this disease continues to be the second leading cause of death worldwide. The current understanding of cancer indicates that treating cancer should not be limited to killing cancer cells alone, but that the target is the complex tumor microenvironment (TME). The application of nanoparticle-based drug delivery systems (DDS) can not only target cancer cells and TME, but also simultaneously resolve the severe side effects of various cancer treatment approaches, leading to more effective, precise, and less invasive therapy.

Drug affinity and targeted delivery: double functionalization of silk spheres for controlled doxorubicin delivery into Her2-positive cancer cells.

Background: The optimal drug delivery system should be biocompatible, biodegradable, and allow the sustained release of the drug only after it reaches the target cells. Silk, as a natural polymer, is a great candidate for building drug carriers. Genetically engineered silks offer the possibility of functionalization.

Silk Materials Functionalized via Genetic Engineering for Biomedical Applications.

The great mechanical properties, biocompatibility and biodegradability of silk-based materials make them applicable to the biomedical field. Genetic engineering enables the construction of synthetic equivalents of natural silks. Knowledge about the relationship between the structure and function of silk proteins enables the design of bioengineered silks that can serve as the foundation of new biomaterials.

Brain perfusion evaluated by perfusion-weighted magnetic resonance imaging before and after stenting internal carotid artery stenosis in asymptomatic and symptomatic patients.

Purpose: To evaluate the brain perfusion with MRI perfusion weighted imaging (PWI) before and after ICA stenting in asymptomatic and symptomatic patients.

Materials And Methods: PWI was performed 3-21 days before and 3 days after ICA stenting in 31 asymptomatic patients with ICA >70% stenosis - Group I, and in 14 symptomatic patients with ICA >50% stenosis - Group II. PWI was evaluated qualitatively and quantitatively in 5 cerebral territories with: mean transit time (MTT), cerebral blood volume (CBV) and cerebral blood flow (CBF).

[Current status of drug-eluting stents and drug-eluting balloons in patients with stable coronary artery disease--an expert consensus document of the Association for Percutaneous Cardiovascular Interventions and Polish Cardiac Society].

Despite a dramatic reduction in restenosis and target vessel revascularisation rates by drug eluting stents (DES), conflicting concerns have been raised over the risk for late DES thrombosis when compared to bare metal stents. Certainly, the heterogeneity of DES results from the introduction of a great variety of new DES types with diverse efficacy and safety parameters. Furthermore, we observe a steady increase in DES availability without parallel and robust data from randomised clinical trials.

Association of non-specific inflammatory activation with early mortality in patients with ST-elevation acute coronary syndrome treated with primary angioplasty.

Background: The association of inflammatory markers with mortality in ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) remains controversial, so in the present study the relationships of high-sensitivity C-reactive protein (hs-CRP), total white blood cell (WBC) count, neutrophil (N) and lymphocyte (L) counts and the N/L ratio with occurrence of in-hospital mortality were assessed in patients with STEMI treated with primary PCI.

Methods And Results: Inflammatory parameters were assessed on admission in 1,078 consecutive, unselected patients with STEMI admitted for primary PCI. In-hospital death occurred in 6.

Differences in presentation and management of stable angina from East to West in Europe: a comparison between Poland and the UK.

Aims: Variations in the resources, stability and priorities of health care systems conceivably affect their capacity to implement health care reform and ensure an evidence based approach to health care. Such variation may partially account for differences in cardiovascular mortality rates between former communist states in Central Europe and Western European countries, but specific data on this subject is sparse. The aim of this study was to compare the presentation of stable angina to cardiology services in Poland vs.

Comparison of prognostic value of epicardial blood flow and early ST-segment resolution after primary coronary angioplasty. ANIN--Myocardial Infarction Registry.

Background: TIMI scale is commonly used for angiographic assessment of reperfusion effectiveness and early risk stratification in patients treated with primary angioplasty for ST-elevation myocardial infarction (STEMI). Since ST-resolution analysis allows a noninvasive insight into the reperfusion status at the myocardial tissue level, it may be a better predictor of outcome after primary angioplasty.

Aim: To compare the prognostic value of the reperfusion effectiveness evaluation based on either the epicardial blood flow assessment according to the TIMI scale, or ST-segment resolution analysis in patients treated with primary coronary angioplasty for STEMI.

Comparison of different methods of ST segment resolution analysis for prediction of 1-year mortality after primary angioplasty for acute myocardial infarction.

Background: Resolution of ST segment elevation corresponds with myocardial tissue reperfusion and correlates with clinical outcome after ST elevation myocardial infarction. Simpler method evaluating the extent of maximal deviation persisting in a single ECG lead was an even stronger mortality predictor. Our aim was to evaluate and compare prognostic accuracy of different methods of ST segment elevation resolution analysis after primary percutaneous coronary intervention (PCI) in a real-life setting.

Cardiac amyloidosis diagnosed by endomyocardial biopsy. Clinical, histopathological, immunohistochemical and ultrastructural studies.

Background: The heart is often involved by primary (AL) and familial transthyretin-related (ATTR) amyloidosis. Endomyocardial biopsy is a valuable diagnostic method, useful in detection and recognition of the type of amyloid.

Aim: The aim of the study was to determine the type of amyloid deposits found in endomyocardial biopsies, using histochemical, immunohistochemical and ultrastructural methods.

Angiographic restenosis following intravascular beta-brachytherapy does not correlate with delivered dose: a study with dose volume histograms. Recurrence of in-stent restenosis after brachytherapy.

Introduction: Vascular brachytherapy reduces recurrence after treatment of in-stent restenosis. However, there are still failures. The aims of the study were to investigate the relationship between two distinct dose prescriptions and the calculated dose delivered versus binary angiographic restenosis.

Acute myocardial infarction complicated by cardiogenic shock. In-hospital and mid-term results of invasive treatment in the National Institute of Cardiology, Warsaw-Anin.

Background: Mortality in acute myocardial infarction (MI) complicated by cardiogenic shock approaches 90%, regardless of the type of pharmacological treatment.

Aim: To assess in-hospital and mid-term results of invasive treatment of patients with acute MI with ST segment elevation (STEMI) complicated by cardiogenic shock.

Methods: From a prospective registry of all patients admitted to our institution for urgent coronary angiography due to acute coronary syndrome between February 2001 and June 2002, patients with STEMI, symptom duration up to 12 hours and cardiogenic shock diagnosed on admission were identified.

Familial dilated cardiomyopathy: evidence for clinical and immunogenetic heterogeneity.

Background: There is increasing awareness of the familial nature of dilated cardiomyopathy (DCM). Mutations in the genes coding for cytoskeletal and sarcomere proteins have been identified. Phenotyping of familial DCM (FDCM) may help to improve genetic diagnosis.