Compression Therapy in Dermatology. / Terapia compresiva en Dermatología.

The benefit of lower limb compression therapy is not limited to chronic venous insufficiency or/and lymphoedema. Thanks to its anti-edema and anti-inflammatory effects, compression therapy is considered a beneficial adjuvant therapy to treat atypical wounds, inflammatory dermatoses, cellulitis, and traumatic wounds in the absence of contraindications. Strict contraindications are limited to severe peripheral arterial disease and decompensated heart failure. The variability of commercially available compression materials and systems, such as short-stretch bandages, multi-component systems, zinc oxide bandages, medical adaptive compression systems, ulcer compression stockings or medical compression stockings, facilitates the adaptation of compression therapy to the individual needs of each patient. Compared to venous leg ulcers, low pressures of 20mmHg are often sufficient to treat dermatological disorders, with higher patient tolerance and compliance.

Exposure of Calophyllum antillanum seeds to liquid nitrogen delays seedling emergence and decreases leaf anthraquinones.

BACKGROUND: Trees within the Calophyllum genus are multi-use trees that produce valuable wood, phytochemicals with a range of biological activities, and seed oil as a source of biodiesel. As a consequence of climate change, there is a need to develop strategies to preserve valuable plant genetic resources. Cryopreservation represents the most suitable option for the long-term storage of germplasm with minimal space and maintenance requirements. OBJECTIVE: To determine appropriate methods to cryopreserve seeds of Calophyllum antillanum and maintain secondary compound production. MATERIALS AND METHODS: Seeds at a moisture content of 6% were used to evaluate two treatments: seeds immersed in liquid nitrogen and control seeds. Biosynthetic pathway efficiency was assessed post-cryo by determining anthraquinone contents in roots, stems and leaves following 30 and 75 d of seedling growth. RESULTS: The results indicated that exposure to liquid nitrogen delayed germination and seedling emergence for a period of up to 45 d after seed sowing. By 60 d of cultivation, no significant differences in plant growth were observed for cryostored and control seeds. The levels of anthraquinones, which were also measured in seeds and seedlings, were lower in plants regenerated from cryostored seeds following 30 d of growth, but there were no differences in roots and stems by 75 d of growth. Furthermore, the difference in leaf anthraquinone levels for cryopreserved and control seeds at 75 d was much smaller than at 30 d. CONCLUSION: The low initial anthraquinone levels in emerging seedlings correlated with the initial slow growth of cryopreserved seeds.

The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trial.

Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients.

Validation of a short-form of the Freiburg Life Quality Assessment for lymphoedema (FLQA-LS) instrument.

BACKGROUND: Chronic lymphoedema (CLE) is a burdensome disease of multiple causes leading to significant reductions in health-related quality of life (HRQoL). A specific method to assess HRQoL is the Freiburg Life Quality Assessment for lymphoedema (FLQA-L), which consists of 92 items. OBJECTIVES: To develop and validate a short form of the FLQA-L with improved psychometric properties and feasibility. METHODS: The FLQA-L validation data were reanalysed by patients and experts. The application of factor analysis enabled the exclusion of lower-load items. An optimized short version of the questionnaire (FLQA-LS) with 33 items was generated and tested in a validation study on patients with different forms of CLE. RESULTS: In total, 348 patients with CLE of the upper or lower extremities were included (mean age 57.3 years, range 24-89; 90.8% female), and data from 301 patients could be analysed. Overall, 42.8% of the patients had secondary lymphoedema, 23.6% had primary lymphoedema, 9.5% had lipoedema and 24.1% had lipolymphoedema. The lower extremities were mostly affected (64.4% of the patients presented with leg involvement and 17.5% with both arm and leg impairment). The FLQA-LS showed good internal consistency, with high Cronbach's alpha in the subscales and in the global scale ranging between 0.79 and 0.94. Regarding convergent validity, a good correlation was found with the general HRQoL questionnaire EQ-5D (r = 0.72, P < 0.001). CONCLUSIONS: FLQA-LS is an improved version of the FLQA-L questionnaire for chronic lymphoedema. It demonstrated validity and feasibility and can be easily used in clinical practice and research studies.

Clinical efficacy of desensitizing mouthwashes for the control of dentin hypersensitivity and root sensitivity: a systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to evaluate the scientific evidence on the efficacy of desensitizing mouthwashes for the treatment of dentin hypersensitivity (DH) and root sensitivity (RS). MATERIAL AND METHODS: A thorough search in MEDLINE, PubMed and Cochrane Plus Library was conducted up to February 2015. Randomized clinical trials, parallel, double-blinded and placebo-controlled, with a follow-up of at least 6 weeks, reporting changes on response to tactile stimuli, thermal/evaporative stimuli or patients' subjective assessment of the pain experienced during their daily life after the home use of desensitizing mouthwashes were considered for inclusion. RESULTS: The screening of titles and abstracts resulted in seven publications meeting the eligibility criteria. The desensitizing agents evaluated were potassium nitrate (n = 5), aluminium lactate (n = 1) and sodium fluoride (n = 1). A meta-analysis for each of the hypersensitivity stimuli was performed. Results demonstrated statistically significant reduction in sensitivity scores favouring test group when DH was assessed by means of patients' self-reported pain experience (SMD at 8 weeks = 0.77; 95% CI [0.23; 1.31]; P = 0.005). No significant effects were detected in response to tactile or thermal/evaporative stimuli. Meta-regression analysis demonstrated a tendency towards an increased effect favouring test group for the patients' subjective perception, whereas tactile and thermal/evaporative stimuli showed a slight tendency towards a reduction in the efficacy of the test mouthwash. CONCLUSIONS: There exists a tendency towards a decrease in DH or RS scores with time in both treatment groups, with significant differences in favour of test group when sensitivity is evaluated in terms of patients' self-reported sensitivity symptoms.

Evaluation of new chlorhexidine- and cetylpyridinium chloride-based mouthrinse formulations adjunctive to scaling and root planing: pilot study.

OBJECTIVE: To compare the effect of two newly formulated chlorhexidine (CHX) and cetylpyridinium chloride (CPC) mouthrinses after scaling and root planing (SRP) in terms of clinical, microbiological, patient-based variables and adverse events, with a positive control with the same active components, already marketed and tested. METHODS: A pilot, randomized clinical trial, double-blind, parallel design with 1-month follow-up was conducted. Chronic periodontitis patients requiring non-surgical periodontal therapy were enrolled and randomly assigned to: (i) SRP and test-1 (new reformulation: 0.12% CHX and 0.05% CPC); (ii) SRP and test-2 (new formulation: 0.03% CHX and 0.05% CPC); or (iii) SRP and positive control (commercial product: 0.12% CHX and 0.05% CPC). All variables were evaluated at baseline and 1 month after SRP. Quantitative variables were compared by means of anova or Kruskal-Wallis test and qualitative variables by chi-square or McNemar tests. RESULTS: Thirty patients (10 per group) were included. After 1 month, there were significant differences among groups in plaque levels (P = 0.016) as test-1 showed less sites with plaque than test-2 (31.15% [standard error-SE 2.21%] versus 49.39% [SE 4.60%), respectively). No significant differences were found for global patient perception of the product or in adverse effects. Test groups showed better results in levels and proportions (P = 0.022) of Capnocytophaga spp. CONCLUSIONS: Within the limitations of this pilot study, it can be concluded that the newly formulated 0.12% CHX and 0.05% CPC mouthrinse showed larger plaque level reductions, without showing more adverse effects, when compared to the other two mouthrinses, after SRP.

Babesia divergens apical membrane antigen-1 (BdAMA-1): A poorly polymorphic protein that induces a weak and late immune response.

Babesiosis is an important veterinary and zoonotic tick borne disease caused by the hemoprotozoan Babesia spp. which infects red blood cell of its vertebrate host. In order to control the infection, vaccination that targets molecules involved in the invasion process of red blood cells could provide a good alternative to chemotherapy. Among these molecules, Apical Membrane Antigen-1 (AMA-1) has been described as an excellent vaccine candidate in Plasmodium spp. In this paper, we have investigated AMA-1 of Babesia divergens (BdAMA-1) as vaccine candidate by evaluating its polymorphism and by studying the humoral response against BdAMA-1 of sheep experimentally infected with B. divergens. Polymorphism of BdAMA-1 was investigated by sequencing the corresponding gene of 9 B. divergens isolates from different geographical areas in France. Two Bdama-1 haplotypes (A and B) could be defined based on 2 non-synonymous point mutations. In silico prediction of linear epitopes revealed that the antigenicity of the 2 haplotypes is very similar. Antibody production against the extracellular domain of BdAMA-1 is weak and late, between 1 and 5 months after the inoculation of parasites. Both IgG1 and IgG2 are components of the anti-BdAMA-1 response. These results indicate that while BdAMA-1 may not be an immuno-dominant antigen, it could induce a mixed type 1 and type 2 immune response. In light of these results, the potential of BdAMA-1 as vaccine candidate is discussed.

Platelet-rich plasma: applications in dermatology.

In recent years, the use of platelet-rich plasma has increased notably in a range of diseases and settings. Uses of these products now go beyond skin rejuvenation therapy in patients with facial ageing. Good outcomes for other dermatological indications such as skin ulcers and, more recently, alopecia have been reported in case series and controlled studies. However, these indications are not currently included in the labeling given that stronger scientific evidence is required to support their real benefits. With the increased use of these products, dermatologists need to become familiar with the underlying biological principles and able to critically assess the quality and outcomes of the studies of these products in different skin diseases.

A test of the nature of cosmic acceleration using galaxy redshift distortions.

Observations of distant supernovae indicate that the Universe is now in a phase of accelerated expansion the physical cause of which is a mystery. Formally, this requires the inclusion of a term acting as a negative pressure in the equations of cosmic expansion, accounting for about 75 per cent of the total energy density in the Universe. The simplest option for this 'dark energy' corresponds to a 'cosmological constant', perhaps related to the quantum vacuum energy. Physically viable alternatives invoke either the presence of a scalar field with an evolving equation of state, or extensions of general relativity involving higher-order curvature terms or extra dimensions. Although they produce similar expansion rates, different models predict measurable differences in the growth rate of large-scale structure with cosmic time. A fingerprint of this growth is provided by coherent galaxy motions, which introduce a radial anisotropy in the clustering pattern reconstructed by galaxy redshift surveys. Here we report a measurement of this effect at a redshift of 0.8. Using a new survey of more than 10,000 faint galaxies, we measure the anisotropy parameter beta = 0.70 +/- 0.26, which corresponds to a growth rate of structure at that time of f = 0.91 +/- 0.36. This is consistent with the standard cosmological-constant model with low matter density and flat geometry, although the error bars are still too large to distinguish among alternative origins for the accelerated expansion. The correct origin could be determined with a further factor-of-ten increase in the sampled volume at similar redshift.

Environmental management of Aznalcóllar mine and its influence in the hydrogeochemical of the pit lake.

Since its 1995 closure and the subsequent 1998 accident, the Aznalcóllar mine pit has been used as a disposal site for diverse metal-rich materials, such as the polluted soils removed during the cleaning of areas along the Guadiamar River, waste rock, pyrite sludge, and ashes deriving from pyrite roasting. At present, the mining pit is partly flooded and contains a highly acidic (pH 2.7) pit lake with approximately 6 Mm3 of metal and sulphate-rich water. Recent detailed research performed in the area has proven that the reaction of the lake water with both the dumping mining wastes and the inflow of acid mine waters are strongly modifying the water quality of the pit lake. A major change was identified in the water quality that resulted from the dumping of 1.4 Mm3 of pyritic wastes during 2005 and 2006. The oxidative dissolution of this mineral has resulted in: (1) a total consumption of dissolved oxygen, (2) a notable increase of electric conductivity (from 8.6 to 12 mS/cm) and (3) a strong acidification (pH from 4.2 to 2.7) and an important heating that was observed as a result of the exothermic character of pyrite oxidation. Despite the total lack of oxidizing agents-such as 02 and Fe(III) (Fe[III] < 5% total Fe)-in the pit lake, pyrite is being oxidized with a continuous increase of the SO(4)2- and Fe concentrations.

New vascular structure in broiler breast: breast-vessel.

Chickens intensively selected for accelerating growth rate and enhanced muscle mass has resulted in the occurrence of breast alterations with a negative consumers perception. Together with the already known breast abnormalities (White Striping, Wooden Breast and Spaghetti Meat) a new one has been described by the consumers as a "long and thin worm". For this reason, the aim of this work was to macroscopically and microscopically describe this structure in broiler breast. To this end, 2 different experiments were performed. In the first one, 4 broiler breasts from a supermarket were analysed. Thereafter, a second experiment was carried out on an experimental farm simulating field management conditions in order to confirm the results of the first experiment. To this end, 120 chickens were reared in an experimental farm up to 42 d. Breast samples were collected and analysed macroscopically and microscopically to assess the abnormality on the broiler breast. In both experiments, the results of the analysis showed the finding of tubular structures located on the surface of pectoralis major muscle compatible with arteries. So far, currently, this occurrence has not been described in the literature and we propose calling this new broiler breast feature as breast-vessel.

Validation of the Spanish Wound-QoL Questionnaire. / Validación de la versión española del cuestionario Wound-QoL.

BACKGROUND AND AIMS: The Wound-QoL is a validated and feasible questionnaire for measuring disease-specific health-related quality of life in chronic wounds, originally developed for use in German. The objective of this study was to translate the Wound-QoL for use in clinical care and in clinical trials in Spain and to validate this version. MATERIALS AND METHODS: Two independent fourth- and back translations of the Wound-QoL from the original German version were conducted, followed by an expert consensus of the resulting versions. After refinement, the final tool was piloted in N=10 patients and then used in the validation study. RESULTS: A total of 115 patients were recruited. Mean age was 69.5 (SD 14.5) years, 60.0% were female. The Spanish version of Wound-QoL showed high internal consistency (Cronbach's alpha>0.8 in all scales). Factor analysis resulted in the same scales as the original version. There were satisfactory distribution characteristics of the global score and the subscales. Construct validity and convergent validity with other outcomes (generic QoL, healing rate) were satisfactory. The vast majority of patients considered the Wound-QoL a simple and feasible tool. Mean time needed for completing the questionnaire was 5minutes. Overall, 99.1% of the participants found it easy to understand the questions and 94.7% stated that the questionnaire suits the personal situation. CONCLUSIONS: The Spanish version of the Wound-QoL shows good validity in clinical practice. It can be recommended for use in clinical routine and trials.

Combined therapeutic effect of a monoclonal anti-idiotype tumor vaccine against NeuGc-containing gangliosides with chemotherapy in a breast carcinoma model.

Anti-idiotypic monoclonal antibodies (mAb) have been evaluated for actively induced immunotherapy with encouraging results. However, rational combination of cancer vaccines with chemotherapy may improve the therapeutic efficacy of these two approaches used separately. The main objective of this study was to evaluate the antitumor effect of the co-administration of 1E10 (Racotumomab), a monoclonal anti-idiotype tumor vaccine against an IgM mAb, named P3 that reacts specifically with NeuGc-containing gangliosides and low-dose Cyclophosphamide in a mammary carcinoma model. F3II tumor-bearing mice were immunized subcutaneously with 100 microg of 1E10 mAb in Alum or with 150 mg/m(2) of Cyclophosphamide intravenously 7 days after the tumor inoculation. While a limited antitumor effect was induced by a single 1E10 mAb immunization; its co-administration with low-dose Cyclophosphamide reduced significantly the F3II mammary carcinoma growth. That response was comparable with the co-administration of the standard high-dose chemotherapy for breast cancer based on 60 mg/m(2) of Doxorubicin and 600 mg/m(2) of Cyclophosphamide, without toxicity signs. Combinatorial chemo-immunotherapy promoted the CD8(+) lymphocytes tumor infiltration and enhanced tumor apoptosis. Furthermore, 1E10 mAb immunization potentiated the antiangiogenic effect of low-dose Cyclophosphamide. Additionally, splenic myeloid cells Gr1(+)/CD11b(+) associated with a suppressor phenotype were significantly reduced in F3II tumor-bearing mice immunized with 1E10 mAb alone or in combination with low-dose Cyclophosphamide. This data may provide a rational for chemo-immunotherapy combinations with potential medical implications in breast cancer.

CD6 synergistic co-stimulation promoting proinflammatory response is modulated without interfering with the activated leucocyte cell adhesion molecule interaction.

The CD6 membrane-proximal scavenger receptor cysteine-rich domain (SRCR3) includes the activated leucocyte cell adhesion molecule (ALCAM) binding site. CD6-ALCAM mediates a low-affinity interaction and their long-term engagement contributes to the immunological synapse. Their ligation may play a dual function, facilitating stable adhesion between the antigen-presenting cells and T cells during the early activation phase and later in the proliferative phase of the immune response. This study explored the strength of the CD6 co-stimulatory effect and whether CD6 co-stimulation with its natural ligand ALCAM also contributes to the lymphocyte effector differentiation. It was found that CD6-ALCAM interaction in vitro induced a synergistic co-stimulation of normal human peripheral blood mononuclear cells, defined by Bliss analysis. CD6 co-stimulation enhanced the CD3 proliferative efficacy by 23-34%. Moreover, a fivefold increment in the CD25 molecules number with a distinct gene transcription profile associated with cell activation, differentiation, survival and adhesion molecules was observed over CD3 single activation. Additionally, CD6 co-stimulation in excess interleukin (IL)-2 promotes a preferentially proinflammatory response. Besides, a CD6 membrane-distal domain (SRCR1)-specific non-depleting monoclonal antibody (mAb) inhibited the induced proliferation in the presence of ALCAM, reducing interferon-γ, IL-6 and tumour necrosis factor-α production. These results suggest that CD6 co-stimulation enhances the intrinsic activity of the CD3 activation pathway and contributes to the T helper type 1 subset commitment, enhancing the IL-2 sensitivity of recent activated human lymphocytes. It supports the role of CD6 as a susceptibility gene for pathological autoimmunity leading to tissue inflammation, and its relevance for targeted therapy.

Theory and Practice of Compression Therapy for Treating and Preventing Venous Ulcers. / Principios teórico-prácticos de la terapia compresiva para el tratamiento y prevención de la úlcera venosa.

Compression therapy is the basis for treating the cause of venous ulcers and preventing recurrence. Various systems are currently available for applying compression and adapting them to patients' needs can improve adherence to treatment. Understanding the principles that underlie compression therapy is essential for success. Although this paper focuses mainly on venous ulcers, compression has also proven beneficial for other conditions, such as lymphedema and wounds resulting from injury or inflammation.

Could polypropylene mesh impair male reproductive organs? Experimental study with different methods of implantation.

PURPOSE: To evaluate the vas deferens and testicles of rats submitted to bilateral inguinotomy and polypropylene (PP) mesh placement. METHOD: Sixty Wistar rats were randomized into three groups: Control (inguinotomy only), mesh placement over the vas deferens (Mesh-DD) or under the spermatic funiculus (Mesh-SF). The following analyses were performed: vas deferens morphometry (lumen area and wall thickness), quantification of collagen fibers, spermatogenesis, apoptosis (cleaved caspase-3 and TUNEL) and cellular proliferation (Ki67). Quantitative gene expression (qPCR) for apoptosis and inflammatory cytokines were evaluated by RT-PCR. RESULTS: In the apoptosis pathway, Mesh-DD showed one upregulated gene (Il10) and three downregulated genes (Fadd, Tnfrsf1b and Xiap). In Mesh-SF, 17 genes were downregulated. In the inflammation pathway (Mesh-DD), one gene was upregulated (Il1r1), and one gene was downregulated (Ccl12). In Mesh-SF, three genes were upregulated (Il1r1, Tnfsf13b and Csf1), and two were downregulated (Ccl12 and Csf2). PP mesh placement preserved spermatogenesis and did not alter the vas deferens or the testicle. In the ductus deferens, there was reduced luminal area (30 days), increased wall thickness (90 days), and increased type III collagen and cell proliferation (30 and 90 days) (p < 0.05). In the testicle, cell proliferation was greater in the Mesh-DD (p < 0.05). CONCLUSIONS: PP mesh, whether or not in direct contact with spermatic funicular structures, induces changes that were not sufficient to cause damage to the evaluated organs.

[Trends in the incidence of venous thromboembolism in Galicia over a ten year period]. / Evolución de la incidencia de la enfermedad tromboembólica venosa en Galicia durante diez años (2006-2015).

OBJECTIVE: To analyse the trend of serious thromboembolic episodes in Galicia from 2006 to 2015. METHODS: A retrospective observational study was performed using the public network of the Galician Health Service over the 10 year period (2006-2015). It included patients with a primary diagnosis in their discharge report of pulmonary thromboembolism (PTE), stroke, or deep vein thrombosis (DVT). DATA SOURCE: Servizo de admisión e documentación clínica, Subdirección de Información e Servizos Tecnolóxicos e Instituto Galego de Estatística. Measurement variables: the number of new cases of thromboembolism occurred in one year, cumulative incidence (number of new cases/ 100,000 persons years), mortality during hospital admission, and annual percentage change (APC). RESULTS: A total of 50,611 hospital admissions due to a venous thromboembolic event were identified. The highest incidence was found for stroke in men aged 80 years or older, with 940.84 new cases per 100,000 population per year. All thromboembolic events were more common in men, with the exception of PTE in young and older women. A continued increased was identified in all the thromboembolic events with an APC of 2.20%. The temporal evolution of the cumulative incidence for PTE was split into two segments, with an annual increase of 10.65% from 2006 to 2011, and a smaller increase since 2011. The cumulative incidence trend showed an APC for stroke of 1.56%. CONCLUSION: This study reveals an increase in the evolutionary trend of hospital admissions for PTE and stroke during the period 2006-2015 in Galicia.

Association of autologous punch grafting, TLC-NOSF dressing and multitype compression therapy to rapidly achieve wound closure in hard-to-heal venous leg ulcers.

OBJECTIVE: To document the efficacy of a combined therapeutic strategy in achieving rapid wound healing in patients with long-standing ulcers. MATERIALS AND METHODS: Outpatients with hard-to-heal venous leg ulcers were included in an interventional, prospective, single-arm, mono-centre study and treated with autologous punch grafting, TLC-NOSF dressing and multi-type compression therapy. The primary outcome was the percentage of healed wounds by week 12. Secondary outcomes included time-to-reach wound closure, wound area reduction, treatment acceptability and safety. RESULTS: From November 2018 to October 2019, 42 patients with 51 ulcers were included (23 males, 70.6±40.8 years old, with multiple comorbidities). Despite poor wound healing prognosis at baseline (47% of recurrent ulcers, with a mean duration of 15 months and a mean area of 12.6cm2), wound healing was achieved in 47 ulcers (92%) after a mean period of treatment of 25±13 days. A relative wound area reduction>75% was also reached in three additional ulcers by the last evaluation visit. No adverse event related to the procedure was reported throughout the study period. The associated treatment were very well tolerated and accepted by the patients. CONCLUSIONS: The evaluated procedure induced fast re-epithelisation of the treated ulcers. Based on our experience, this simple and successful reparative strategy may be considered as an interesting option in the treatment of venous leg ulcers of poor prognosis.

Radiosensitisation of U87MG brain tumours by anti-epidermal growth factor receptor monoclonal antibodies.

As epidermal growth factor receptor (EGFR) has been reported to be a radiation response modulator, HER inhibitors are regarded to act as potential radiosensitisers. Our study examined the role of nimotuzumab and cetuximab both, the two monoclonal antibodies (mAbs) to EGFR, as radiosensitisers in a murine glioma model in vivo. Co-administration of both the antibodies with radiation increased the radiosensitivity of U87MG, resulting in a significant delay of subcutaneous (s.c.) tumour growth. Furthermore, the addition of antibodies to the radiation decreased brain tumour sizes and is inhibited by 40-80% the increased tumour cell invasion provoked by radiotherapy, although promoted tumour cell apoptosis. Whereas nimotuzumab led to a reduction in the size of tumour blood vessels and proliferating cells in s.c. tumours, cetuximab had no significant antiangiogenic nor antiproliferative activity. In contrast, cetuximab induced a more marked inhibition of EGFR downstream signalling compared with nimotuzumab. Moreover, both antibodies reduced the total number of radioresistant CD133+ cancer stem cells (CSCs). These results were encouraging, and showed the superiority of combined treatment of mAbs to EGFR and radiation over each single therapy against glioblastoma multiforme (GBM), confirming the role of these drugs as radiosensitisers in human GBM. In addition, we first showed the ability of mAb specifics against EGFR to target radioresistant glioma CSC, supporting the potential use in patients.