The Hebrew version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Hebrew language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data, and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach\u2019s alpha, interscale correlations, and construct validity (convergent and discriminant validity). A total of 116 JIA patients (17.2% systemic, 56% oligoarticular, 20.7% RF negative poly-arthritis, and 6.1% other categories) and 98 healthy children were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Hebrew version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and in clinical research

Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer

Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we observed that depletion of STIL enhanced canonical homologous recombination repair and increased BRCA1 and RAD51 foci in response to DNA double strand breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA damaging chemotherapeutic drugs in treatment of ovarian cancer.Junta de andalucía P12-BIO-515, P. HuertasEspaña Ministerio de Economía y Competitividad SAF2013-43255-

Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer

Rabinowicz, Noa et al.Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we observed that depletion of STIL enhanced canonical homologous recombination repair and increased BRCA1 and RAD51 foci in response to DNA double strand breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA damaging chemotherapeutic drugs in treatment of ovarian cancer.This research was supported by grant OC100237 from USA Department of Defense (to S. Izraeli and A.K. Sood), by SINF (S. Izraeli and A.K. Sood), Israel Science Foundation ICORE program (S. Izraeli, A. Levy-Barda), Israel Cancer Research Foundation (N. Rabinowicz) and Israel Ministry of Science/German Cancer Research Center (S. Izraeli), Israel Ministry of Commerce “Nofar” program (SI), The Giorgio and Dora Shapiro Chair for Hematological Malignancies (SI), NIH grants (CA083639, CA098258, UH2 TR000943, and CA016672 for A.K. Sood), the RGK Foundation (A.K. Sood), the Frank McGraw Memorial Chair in Cancer Research and the American Cancer Society Research Professor Award (A.K. Sood), grants from the Regional Government of Andalucia (P12-BIO-515, P. Huertas), the Spanish Ministry of Economy and Competitivity (SAF2013-43255-P, P. Huertas) and the European Research Council (DSBRECA, P. Huertas).Peer Reviewe

Comics as an educational tool for children with juvenile idiopathic arthritis

Abstract Background This study examined whether the comic book Neta and the Medikidz Explain JIA would improve disease-related knowledge and treatment adherence among patients with juvenile idiopathic arthritis (JIA). Methods In this prospective cohort study, JIA patients answered 20 multiple-choice knowledge questions about their disease, before and after reading the comic book. Demographic, clinical, health-related quality of life and adherence data were recorded and correlated to the responses. Results We studied 61 patients with a mean age of 14 ± 3.3 (range 8–18) years, 67% female, 83% Jewish and 17% non-Jewish. Thirty-nine percent had oligoarthritis, 13% systemic, 32% polyarthritis 11% psoriatic and 5% enthesitis-related type JIA. The disease was active in 46%, 40% were treated with biologics/disease modifying anti-rheumatic drugs, and 34% were in remission on medication. Among the 53 patients who completed before and after quizzes, average score increased from 63 to 80% (P < 0.001). Non-Jewish patients initially scored lower than Jewish patients (48%), but their score increased to 79% after reading the comic book. Twenty-seven patients who also completed the quiz 1 year after the first reading retained their knowledge (79%). We did not find a statistically significant correlation between knowledge and age, sex, disease subtype, or Child Health Questionnaire quality of life scores. Adherence to medication use, physical therapy and rheumatology clinic visits were high at baseline; thus, these did not change after reading the comic. Conclusions The comic booklet Neta and the Medikidz Explain JIA is a good educational tool for increasing disease-related knowledge in children with JIA

Neuropilin-1-dependent regulation of EGF-receptor Signaling

Neuropilin-1 (NRP1) is a coreceptor for multiple extracellular ligands. NRP1 is widely expressed in cancer cells and in advanced human tumors; however, its functional relevance and signaling mechanisms are unclear. Here, we show that NRP1 expression controls viability and proliferation of different cancer cells, independent of its short intracellular tail. We found that the extracellular domain of NRP1 interacts with the EGF receptor (EGFR) and promotes its signaling cascade elicited upon EGF or TGF-\u3b1 stimulation. Upon NRP1 silencing, the ability of ligand-bound EGFR to cluster on the cell surface, internalize, and activate the downstream AKT pathway is severely impaired. EGFR is frequently activated in human tumors due to overexpression, mutation, or sustained autocrine/paracrine stimulation. Here we show that NRP1-blocking antibodies and NRP1 silencing can counteract ligand-induced EGFR activation in cancer cells. Thus our findings unveil a novel molecular mechanism by which NRP1 can control EGFR signaling and tumor growth. \ua92012 AACR