Fibrin-binding, peptide amphiphile micelles for targeting glioblastoma.

Glioblastoma-targeted drug delivery systems facilitate efficient delivery of chemotherapeutic agents to malignant gliomas, while minimizing systemic toxicity and side effects. Taking advantage of the fibrin deposition that is characteristic of tumors, we constructed spherical, Cy7-labeled, targeting micelles to glioblastoma through the addition of the fibrin-binding pentapeptide, cysteine-arginine-glutamic acid-lysine-alanine, or CREKA. Conjugation of the CREKA peptide to Cy7-micelles increased the average particle size and zeta potential.

No effects of anodal transcranial direct stimulation on language abilities in early rehabilitation of post-stroke aphasic patients.

Background And Purpose: Recent research suggests that an increased level of stroke-affected left hemisphere cortical (especially frontal) excitability is associated with better language improvement in aphasic patients. Anodal transcranial direct current stimulation (A-tDCS), increasing cortical activity, may facilitate perilesional left hemisphere recruitment to subserve language processing and enhance effects of behavioural therapy. The aim of the study (randomized, double-blind, sham-controlled) was to evaluate the effectiveness of repeated A-tDCS over Broca area as a strategy to enhance aphasia recovery during early post-stroke rehabilitation.

Inhibition of MMP14 potentiates the therapeutic effect of temozolomide and radiation in gliomas.

Metalloproteinases are membrane-bound proteins that play a role in the cellular responses to antiglioma therapy. Previously, it has been shown that treatment of glioma cells with temozolomide (TMZ) and radiation (XRT) induces the expression of metalloproteinase 14 (MMP14). To investigate the role of MMP14 in gliomagenesis, we used several chemical inhibitors which affect MMP14 expression.

Multifunctional nanoparticles for brain tumor imaging and therapy.

Brain tumors are a diverse group of neoplasms that often carry a poor prognosis for patients. Despite tremendous efforts to develop diagnostic tools and therapeutic avenues, the treatment of brain tumors remains a formidable challenge in the field of neuro-oncology. Physiological barriers including the blood-brain barrier result in insufficient accumulation of therapeutic agents at the site of a tumor, preventing adequate destruction of malignant cells.

Anodal transcranial direct current stimulation in early rehabilitation of patients with post-stroke non-fluent aphasia: a randomized, double-blind, sham-controlled pilot study.

Purpose: Recent research in patients with chronic aphasia shows an association between excitatory anodal transcranial direct current stimulation (A-tDCS) of the stroke-affected left hemisphere coupled with speech and language therapy (SLT) and better language performance. The present study aimed to investigate this association during the early post-stroke rehabilitation period, when adaptive changes are most possible on neurophysiological and behavioral levels.

Methods: We randomized 24 patients with non-fluent aphasia to receive 15 consecutive sessions (5 days/week for 3 weeks) of A-tDCS (1 mA, 10 min; n = 14) or sham tDCS (S-tDCS: 1 mA, 25 sec; n = 10) over Broca's area followed by 45-min SLT.

Magnetic resonance imaging tracking of ferumoxytol-labeled human neural stem cells: studies leading to clinical use.

Numerous stem cell-based therapies are currently under clinical investigation, including the use of neural stem cells (NSCs) as delivery vehicles to target therapeutic agents to invasive brain tumors. The ability to monitor the time course, migration, and distribution of stem cells following transplantation into patients would provide critical information for optimizing treatment regimens. No effective cell-tracking methodology has yet garnered clinical acceptance.

Intranasal delivery of mesenchymal stem cells significantly extends survival of irradiated mice with experimental brain tumors.

Treatment options of glioblastoma multiforme are limited due to the blood-brain barrier (BBB). In this study, we investigated the utility of intranasal (IN) delivery as a means of transporting stem cell-based antiglioma therapeutics. We hypothesized that mesenchymal stem cells (MSCs) delivered via nasal application could impart therapeutic efficacy when expressing TNF-related apoptosis-inducing ligand (TRAIL) in a model of human glioma.

The timing of neural stem cell-based virotherapy is critical for optimal therapeutic efficacy when applied with radiation and chemotherapy for the treatment of glioblastoma.

Glioblastoma multiforme (GBM) remains fatal despite intensive surgical, radiotherapeutic, and chemotherapeutic interventions. Neural stem cells (NSCs) have been used as cellular vehicles for the transportation of oncolytic virus (OV) to therapeutically resistant and infiltrative tumor burdens throughout the brain. The HB1.

N-acetylcysteine amide augments the therapeutic effect of neural stem cell-based antiglioma oncolytic virotherapy.

Current research has evaluated the intrinsic tumor-tropic properties of stem cell carriers for targeted anticancer therapy. Our laboratory has been extensively studying in the preclinical setting, the role of neural stem cells (NSCs) as delivery vehicles of CRAd-S-pk7, a gliomatropic oncolytic adenovirus (OV). However, the mediated toxicity of therapeutic payloads, such as oncolytic adenoviruses, toward cell carriers has significantly limited this targeted delivery approach.

Nanoparticle-programmed self-destructive neural stem cells for glioblastoma targeting and therapy.

A 3-step glioblastoma-tropic delivery and therapy method using nanoparticle programmed self-destructive neural stem cells (NSCs) is demonstrated in vivo: 1) FDA-approved NSCs for clinical trials are loaded with pH-sensitive MSN-Dox; 2) the nanoparticle conjugates provide a delayed drug-releasing mechanism and allow for NSC migration towards a distant tumor site; 3) NSCs eventually undergo cell death and release impregnated MSN-Dox, which subsequently induces toxicity towards surrounding glioma cells.

Transcranial magnetic stimulation combined with speech and language training in early aphasia rehabilitation: a randomized double-blind controlled pilot study.

Background: Functional neuroimaging studies with poststroke aphasia patients have shown increased activation of the unaffected hemisphere, which hypothetically reflects a maladaptive strategy of brain reorganization.

Objective: We investigated whether repetitive transcranial magnetic stimulation (rTMS) inhibiting the right-hemisphere homologue of Broca's area improves language restitution if combined with speech/language therapy.

Methods: Forty aphasic patients during the subacute phase of ischemic stroke were randomized to a 3-week aphasia rehabilitation protocol in combination with real or sham rTMS.

A preclinical evaluation of neural stem cell-based cell carrier for targeted antiglioma oncolytic virotherapy.

Background: Oncolytic adenoviral virotherapy (OV) is a highly promising approach for the treatment of glioblastoma multiforme (GBM). In practice, however, the approach is limited by poor viral distribution and spread throughout the tumor mass.

Methods: To enhance viral delivery, replication, and spread, we used a US Food and Drug Administration-approved neural stem cell line (NSC), HB1.

Effects of repeated anodal tDCS coupled with cognitive training for patients with severe traumatic brain injury: a pilot randomized controlled trial.

Objective: To determine whether cumulative anodal transcranial direct current stimulation (A-tDCS) of the left dorsolateral prefrontal cortex (DLPFC) could enhance rehabilitation of memory and attention in patients with traumatic brain injury (TBI).

Setting: Inpatient and outpatient neurorehabilitation unit.

Participants: Twenty-three adult patients, 4- to 92- months post severe TBI.

Targeting Tregs in Malignant Brain Cancer: Overcoming IDO.

One of the hallmark features of glioblastoma multiforme (GBM), the most common adult primary brain tumor with a very dismal prognosis, is the accumulation of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). Regulatory T cells (Tregs) segregate into two primary categories: thymus-derived natural Tregs (nTregs) that develop from the interaction between immature T cells and thymic epithelial stromal cells, and inducible Tregs (iTregs) that arise from the conversion of CD4(+)FoxP3(-) T cells into FoxP3 expressing cells. Normally, these Treg subsets complement one another's actions by maintaining tolerance of self-antigens, thereby suppressing autoimmunity, while also enabling effective immune responses toward non-self-antigens, thus promoting infectious protection.

Gliadel for brain metastasis.

With therapies for systemic malignancy improving, life expectancy for cancer patients is becoming increasingly dependent on control of brain metastatic disease. Despite improvements in surgical and radiotherapy modalities for control of brain metastasis, the prognosis for patients with brain metastases is poor. The development of controlled release polymers has lead to novel new therapies for malignant brain tumors consisting of direct surgical delivery of chemotherapy agents to the tumor bed and sustained chemotherapy release over a prolonged period of time.

Design of a synthetic simulator for pediatric lumbar spine pathologies.

Object: Simulation has become an important tool in neurosurgical education as part of the complex process of improving residents' technical expertise while preserving patient safety. Although different simulators have already been designed for a variety of neurosurgical procedures, spine simulators are still in their infancy and, at present, there is no available simulator for lumbar spine pathologies in pediatric neurosurgery. In this paper the authors describe the peculiarities and challenges involved in developing a synthetic simulator for pediatric lumbar spine pathologies, including tethered spinal cord syndrome and open neural tube defects.

Association between BDNF-196 G>A and BDNF-270 C>T polymorphisms, BDNF concentration, and rTMS-supported long-term rehabilitation outcome after ischemic stroke.

Background: The efficacy of rehabilitation in ischemic stroke patients likely varies because of brain plasticity. One of the main neurotrophins in the central nervous system is brain-derived neurotrophic factor (BDNF).

Objectives: This study aimed to determine allelic and genotypic distribution of BDNF-196 G>A and -270 C>T polymorphisms, and to assess the impact of repetitive transcranial magnetic stimulation (rTMS) on serum BDNF concentrations measured before rehabilitation, after the first 6 h of rehabilitation, and after 3 weeks of rehabilitation.

Understanding glioma stem cells: rationale, clinical relevance and therapeutic strategies.

Glioblastoma multiforme is one of the most aggressive brain tumors in adults. Despite the use of the best available multimodal therapeutic approaches, the prognosis remains dismal. The identification of glioma stem cells (GSCs) has offered new hope to affected patients, since it could explain, in part, the highly heterogeneous nature of this tumor and its chemo- and radio-resistance.

Drug-loaded nanoparticle systems and adult stem cells: a potential marriage for the treatment of malignant glioma?

Despite all recent advances in malignant glioma research, only modest progress has been achieved in improving patient prognosis and quality of life. Such a clinical scenario underscores the importance of investing in new therapeutic approaches that, when combined with conventional therapies, are able to effectively eradicate glioma infiltration and target distant tumor foci. Nanoparticle-loaded delivery systems have recently arisen as an exciting alternative to improve targeted anti-glioma drug delivery.

Oncolytic virotherapy for malignant glioma: translating laboratory insights into clinical practice.

Glioblastoma multiforme, one of the most common and aggressive brain tumors in adults, is highly resistant to currently available therapies and often recurs. Due to its poor prognosis and difficult management, there is an urgent need for the development and translation of new anti-glioma therapeutic approaches into the clinic. In this context, oncolytic virotherapy arises as an exciting treatment option for glioma patients.

Lyme disease: review.

Lyme disease is a multi-organ animal-borne disease, caused by spirochetes of Borrelia burgdorferi (Bb), which typically affect the skin, nervous system, musculoskeletal system and heart. A history of confirmed exposure to tick bites, typical signs and symptoms of Lyme borreliosis and positive tests for anti-Bb antibodies, are the basis of a diagnosis. A two-step diagnosis is necessary: the first step is based on a high sensitivity ELISA test with positive results confirmed by a more specific Western blot assay.

WNT10B/β-catenin signalling induces HMGA2 and proliferation in metastatic triple-negative breast cancer.

Wnt/β-catenin signalling has been suggested to be active in basal-like breast cancer. However, in highly aggressive metastatic triple-negative breast cancers (TNBC) the role of β-catenin and the underlying mechanism(s) for the aggressiveness of TNBC remain unknown. We illustrate that WNT10B induces transcriptionally active β-catenin in human TNBC and predicts survival-outcome of patients with both TNBC and basal-like tumours.

Eosinophilic reaction in nasal cytology in patients sensitive to perennial and seasonal allergens.

Nasal exfoliative cytology is a complementary tool in diagnostics of allergic (AR) and non-allergic (NAR) rhinitis. The aim of the study was to determine the usefulness of the nasal cytology in patients sensitive to common inhalant allergens with positive SPT(+) and negative SPT(-) (Skin Prick Tests) depending on the symptoms of intermittent and persistent rhinitis. The study was performed in a group of 285 patients treated in the Department of Allergology University Hospital in Krakow, suspected on AR in 2008-2010.

[Life-threatening drug reactions in children].

Adverse drug reactions in children are serious public health problem. The overall incidence of ADRs is estimated at about 9.5% in hospitalized children and about 1.

[The risk of malaria during travel, observations in the department of infectious diseases in Cracow from 1996 to 2010].

Unlabelled: Actually in Poland malaria is not present as an endemic disease, but is one of the most common "imported" diseases. In its mild form it is an awkward illness with recurring fever, whereas the more severe form, which is caused by Plasmodium falciparum can be life-threatening.

Aim Of The Study: Epidemiological and clinical analysis on malaria-infected patients hospitalized in the Department of Infectious Diseases in Cracow from 1996 to 2010.