Educational and social late effects of childhood cancer and related clinical, personal, and familial characteristics

Abstract

The protein human CC chemokine ligand 2 (CCL2, also known as monocyte chemoattractant protein 1 or MCP‐1) has been synthesized using a combination of solid phase peptide synthesis (SPPS) and native chemical ligation (NCL). The thioester‐peptide segment was synthesized using the sulfonamide safety‐catch linker and 9‐fluorenylmethoxycarbonyl (Fmoc) SPPS, and pseudoproline dipeptides were used to facilitate the synthesis of both CCL2 fragments. After assembly of the full‐length peptide chain by NCL, a glutathione redox buffer was used to fold and oxidize the CCL2 protein. Synthetic human CCL2 binds to and activates the CCR2 receptor on THP‐1 cells, as expected. CCL2 was crystallized and the structure was determined by X‐ray diffraction at 1.9‐Å resolution. The structure of the synthetic protein is very similar to that of a previously reported structure of recombinant human CCL2, although the crystal form is different. The functional CCL2 dimer for the crystal structure reported here is formed around a crystallographic twofold axis. The dimer interface involves residues Val9‐Thr10‐Cys11, which form an intersubunit antiparallel β‐sheet. Comparison of the CCL2 dimers in different crystal forms indicates a significant flexibility of the quaternary structure. To our knowledge, this is one of the first crystal structures of a protein prepared using the sulfonamide safety‐catch linker and NCL. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 350–359, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

Educational outcomes among survivors of childhood cancer in British Columbia, Canada

“…Leukemia survivors had poorer results for numeracy and reading tests than for writing. Unlike the results reported by Barrera et al, 13 neuroblastoma survivors in our study were not more likely to have academic problems; however, in agreement with Mitby et al, 15 they did use special education services more often. Unfortunately, in our study there, were insufficient numbers of survivors in diagnostic subgroups or with multiple Original Article .118…”

“…Other studies that have assessed different populations with fewer outcome measures have reported an excess risk of poor educational achievement among survivors of CNS tumors and leukemia. 9,13,15 The reciprocal pattern of enrollment of survivors in English and Communications 12 and the reduced enrollment of survivors in Math 12, coupled with the lack of difference in Grade 12 examination results between survivors and the student sample, suggest that there may be self-selection for ability in these subjects. In particular, the findings for Math 12 most likely reflect difficulties in mathematic skills; mathematic deficits and poor arithmetic achievement have been reported previously among childhood cancer survivors.…”

“…[3][4][5] Educational difficulties among survivors have been reported by survivors, parents, and teachers. [6][7][8] Survivors attain lower levels of education, [9][10][11][12] have increased use of special education services, [13][14][15][16] and have a greater likelihood of grade repetition. 13,17 There is considerable evidence of adverse neurocognitive late effects, [18][19][20][21] including lower intelligence quotient scores, 22,23 that may inhibit educational performance.…”

“…Younger age at diagnosis and/or treatment 7,14,[24][25][26] ; cranial or craniospinal radiotherapy (CRT) and/or intrathecal methotrexate (IT MTX) 15,24,25,[27][28][29] ; higher therapeutic doses of CRT or IT MTX 17,24 ; and diagnoses of central nervous system (CNS) tumors, leukemia (particularly acute lymphoblastic leukemia [ALL]), Hodgkin lymphoma, or neuroblastoma 13,15,30 as well as being female, [30][31][32][33] of lower socioeconomic status (SES), 20 and having a longer time since diagnosis 24 have been reported to be associated with an increased risk of poorer educational outcomes. Previous studies have not always assessed the potential confounding effects of missed school, 34 SES, 35 and physical health or physical impairments.…”

“…36 Some studies have included inappropriate comparison groups, or no comparison group, 23,37 or small sample sizes. 38 Studies of educational effects commonly have used self-reported or proxy-reported data, 13,30 which are subject to reporting bias. 34 To our knowledge, only 2 studies, 4,5 both population-based, have investigated educational achievement using standardized achievement tests.…”