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BackgroundClavicular hook plates are effective fixation devices for distal clavicle fractures and severe acromioclavicular joint dislocations. However, increasing number of studies has revealed that subacromial portion of the hook may induce acromial bony erosion, shoulder impingement, or even rotator cuff damage. By sonographic evaluation, we thus intended to determine whether the presence of hook plate may induce subacromial shoulder impingement and its relationship relative to surrounding subacromial structures.MethodsWe prospectively followed 40 patients with either distal clavicle fracture or acromioclavicular joint dislocation that had surgery using the Arbeitsgemeinschaft für Osteosynthesefragen (AO) clavicular hook plate. All patients were evaluated by monthly clinical and radiographic examinations. Static and dynamic musculoskeletal sonography examinations were performed at final follow-up before implant removal. Clinical results for pain, shoulder function, and range of motion were evaluated using Constant-Murley and Disability of Arm, Shoulder, and Hand (DASH) scores.ResultsClinically, 15 out of 40 patients (37.5%) presented with subacromial impingement syndrome and their functional scores were poorer than the non-impinged patients. Among them, six patients were noted to have rotator cuff lesion. Acromial erosion caused by hook pressure developed in 20 patients (50%).ConclusionsWe demonstrated by musculoskeletal sonography that clavicular hook plate caused subacromial shoulder impingement and rotator cuff lesion. The data also suggest an association between hardware-induced impingement and poorer functional scores. To our knowledge, the only solution is removal of the implant after bony consolidation/ligamentous healing has taken place. Thus, we advocate the removal of the implant as soon as bony union and/or ligamentous healing is achieved.

Glycosylation is the most complex post-translational modification of proteins. Altered glycans on the tumor- and host-cell surface and in the tumor microenvironment have been identified to mediate critical events in cancer pathogenesis and progression. Tumor-associated glycan changes comprise increased branching of N-glycans, higher density of O-glycans, generation of truncated versions of normal counterparts, and generation of unusual forms of terminal structures arising from sialylation and fucosylation. The functional role of tumor-associated glycans (Tn, sTn, T, and sLea/x) is dependent on the interaction with lectins. Lectins are expressed on the surface of immune cells and endothelial cells or exist as extracellular matrix proteins and soluble adhesion molecules. Expression of tumor-associated glycans is involved in the dysregulation of glycogenes, which mainly comprise glycosyltransferases and glycosidases. Furthermore, genetic and epigenetic mechanisms on many glycogenes are associated with malignant transformation. With better understanding of all aspects of cancer-cell glycomics, many tumor-associated glycans have been utilized for diagnostic, prognostic, and therapeutic purposes. Glycan-based therapeutics has been applied to cancers from breast, lung, gastrointestinal system, melanomas, and lymphomas but rarely to neuroblastomas (NBs). The success of anti-disialoganglioside (GD2, a glycolipid antigen) antibodies sheds light on glycan-based therapies for NB and also suggests the possibility of protein glycosylation-based therapies for NB. This review summarizes our understanding of cancer glycobiology with a focus of how protein glycosylation and associated glycosyltransferases affect cellular behaviors and treatment outcome of various cancers, especially NB. Finally, we highlight potential applications of glycosylation in drug and cancer vaccine development for NB.

The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P ¼ 0.0004) over this period, 69.3±1.9% in 1997-2001 to 77.4±1.7% in 2002-2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997-2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy 450 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy 450, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.

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Nitric oxide (NO) can regulate osteoblast activities. This study was aimed to evaluate the protective effects of pretreatment with sodium nitroprusside (SNP) as a source of NO on hydrogen peroxide-induced osteoblast insults and its possible mechanisms. Exposure of human osteosarcoma MG63 cells to hydrogen peroxide significantly increased cellular oxidative stress, but decreased ALP activity and cell viability, inducing cell apoptosis. Pretreatment with 0.3 mM SNP significantly lowered hydrogen peroxide-induced cell insults. Treatment of human MG63 cells with hydrogen peroxide inhibited Bcl-2 mRNA and protein production, but pretreatment with 0.3 mM SNP significantly ameliorated such inhibition. Sequentially, hydrogen peroxide decreased the mitochondrial membrane potential, but increased the levels of cytochrome c and caspase-3 activity. Pretreatment with 0.3 mM SNP significantly lowered such alterations. Exposure to hydrogen peroxide decreased Runx2 mRNA and protein syntheses. However, pretreatment with 0.3 mM SNP significantly lowered the suppressive effects. Runx2 knockdown using RNA interference inhibited Bcl-2 mRNA production in human MG63 cells. Protection of pretreatment with 0.3 mM SNP against hydrogen peroxide-induced alterations in ALP activity, caspase-3 activity, apoptotic cells, and cell viability were also alleviated after administration of Runx2 small interference RNA. Thus, this study shows that pretreatment with 0.3 mM SNP can protect human MG63 cells from hydrogen peroxide-induced apoptotic insults possibly via Runx2-involved regulation of bcl-2 gene expression.

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Aberrant expression of the simple mucin-type carbohydrate antigens such as T, Tn, sialyl-T and sialyl-Tn is associated with poor prognosis in several cancers. b1,3-N-acetylglucosaminyltransferase-3 (B3GNT3), a member of the b3GlcNAcT family, is responsible for forming extended core 1 (T antigen) oligosaccharides. The role of B3GNT3, which is expressed in various tissues including human fetal brain, in regulating neuroblastoma (NB) formation and cell behaviors remains unclear. Here, we showed that increased B3GNT3 expression evaluated using immunohistochemistry in NB tumor tissues correlated well with the histological grade of differentiation as well as a favorable Shimada's subset of pathology. Univariate and multivariate analyses revealed that positive B3GNT3 expression in tumor tissues predicted a favorable prognosis in NB patients independent of other prognostic markers. B3GNT3 overexpression suppresses T antigen formation and malignant phenotypes including migration and invasion of SK-N-SH cells, whereas B3GNT3 knockdown enhances these phenotypes of SK-N-SH cells. Moreover, B3GNT3 expression decreased phosphorylation of focal adhesion kinase (FAK), Src, paxillin, Akt and ERK1 ⁄ 2. We conclude that B3GNT3 predicts a favorable cancer behavior of NB and suppresses malignant phenotypes by modulating mucin-type O-glycosylation and signaling in NB cells. (Cancer Sci 2013; 104: 1600-1608 N euroblastoma (NB) is the most common extracranial solid tumor in childhood, accounting for 8-10% of all pediatric malignancies. This tumor arises from primordial neuroepithelial cells of the neural crest.(1,2) The behavior of NB is markedly heterogeneous, ranging from spontaneous differentiation or regression into ganglioneuroblastoma (GNB) or ganglioneuroma with a favorable prognosis to highly undifferentiated tumors with a rapid progression and very poor outcomes.(3) Metastasis, a NB staging factor, is found in 50-60% of all NB cases, and advanced NB typically metastasize to distant lymph nodes, bone marrow, bone, liver or other organs. Although the overall prognosis for NB patients has improved remarkably with recent advances in therapies, the long-term survival of patients with high-risk NB remains poor despite intensive multimodal therapy.(1,2) Thus, finding new prognostic factors is required to further understand NB pathogenesis and to tailor therapies for improving treatment outcomes of patients with unfavorable NB.Glycosylation is one of the most important processes in posttranslational modification of proteins. It is commonly found that oligosaccharide structures of glycoproteins are changed during malignant transformations.(4) Because the sugar chains of glycoproteins are essential for maintaining ordered intercellular interactions among differentiated cells in multicellular organisms, alterations in the sugar chains constitute the molecular basis of abnormal intercellular behaviors in tumor cells, such as invasion into the surrounding tissues and metastasis. (5) There are two major types of protein glycosylation in mam...