Samuel Singer

..Thus, this ratio may be an NMR-detectable marker of troglitazone efficacy and response to differentiation therapy for liposarcoma...

..To report preliminary results on using intensity modulated radiation therapy (IMRT) as an adjuvant treatment in primary soft tissue sarcoma (STS) of the extremity...

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..These results support the development of a clinical trial with MDM2 antagonists for liposarcoma subtypes which overexpress MDM2 and show the promise of using this expression dataset for new drug discovery in liposarcoma...

..The aim of this study was to determine the pattern of recurrence and prognostic significance of histologic subtype in a large series of patients with primary retroperitoneal liposarcoma...

..The aim of this study was to evaluate the prognostic relevance for KIT mutations in a series of GISTs in which the mutations were evaluated intensively by genomic and cDNA sequencing...

..We aimed to develop a nomogram to predict RFS after surgery in the absence of adjuvant therapy to help guide patient selection for adjuvant imatinib therapy...

..Our goal was to investigate the spectrum of pathologic response and molecular alterations in a group of GIST patients, clinically defined as having imatinib-stable/imatinib-responsive lesions, who underwent surgical resection...

..A secondary V600E BRAF mutation could represent an alternative mechanism of imatinib resistance. Kinase inhibitors targeting BRAF may be effective therapeutic options in this molecular GIST subset...

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..The purpose of this study is to determine if such concern is warranted in soft-tissue sarcoma (STS) of the extremity...

..The clinical benefit of sunitinib is genotype-dependent in regards to both primary and secondary mutations, with GIST patients harboring the KIT(AY502-3ins) exon 9 mutation being the most sensitive...

..Although the efficacy of tyrosine kinase inhibitors in metastatic GIST depends on tumor mutation status, there have been conflicting reports on the prognostic importance of KIT mutation in primary GIST...

..Our results indicate that a degree of developmental maturity can be quantitatively assigned to solid tumors, supporting the notion that transformation of a solid tumor stem cell can occur at distinct stages of maturation...

..Thus, MYC amplification may play a crucial role in the angiogenic phenotype of AS through upregulation of the miR-17-92 cluster, which subsequently downregulates THBS1, a potent endogenous inhibitor of angiogenesis...

..These results demonstrate that loss of C/EBPα is an important factor in suppressing apoptosis and maintaining the dedifferentiated state in DDLS. Restoring C/EBPα may be a useful therapeutic approach for DDLS...

..To develop a nomogram based on clinicopathologic factors to quantify the risk of local recurrence (LR) after limb-sparing surgery without adjuvant radiation (RT)...

..The patterns of failure and mechanisms of sarcoma-specific death are poorly characterized among the minority of patients with low-grade soft tissue sarcoma (STS) who succumb to disease...

..With growth inhibition at the low nanomolar range, sorafenib, by inhibiting the mitogen-activated protein kinase pathway, may prove to be a novel therapy for patients with MPNST...

..Our results indicate that targeting KIT expression and these antiapoptotic proteins with flavopiridol represents a novel means to disrupt GIST cell dependence on KIT signaling and collectively renders these cells sensitive to apoptosis...

..DSS in patients with primary RAS is significantly worse compared with sporadic STS independent of sarcoma histologic type...

..As such, we explored the potentiation of doxorubicin by flavopiridol in sarcoma, in vitro and in vivo, and conducted a phase I trial of flavopiridol with doxorubicin in patients with advanced sarcomas...

..Our results show that CD133 and CD44 are universally expressed in GIST, and may represent a lineage rather than a cancer stem cell marker...

..DSS nomograms aid in more accurate counseling of patients, identification of patients appropriate for adjuvant therapy, and stratification of patients for clinical trials and molecular analysis...

..Secondary genetic hits, such as FLT4 gene coamplification or KDR mutations, may play a role in tumor progression as well as potential therapeutic targeting...

..Pharmacologic inhibition of DNA methylation promoted apoptosis and differentiated DLPS cells in vitro and inhibited tumor growth in vivo, providing a rationale for investigating methylation inhibitors in this disease...

..This study sought to identify copy number alterations (CNA) associated with dedifferentiation of WDLS, with DDLS morphology, and with patient outcomes...

..The decrease in phosphocholine may be a potential indicator of early tumor response to the sequential treatment of irinotecan followed by flavopiridol in noninvasive and/or longitudinal studies...

..Nearly all tumors have an activating mutation in the KIT or, less often, PDGFRalpha, gene. Therapy with tyrosine kinase inhibitors benefits over 80% of patients with advanced GIST, but most patients eventually develop drug resistance...

..Our results show that ZIC1 expression is essential for liposarcomagenesis and that targeting ZIC1 or its downstream targets might lead to novel therapy for liposarcoma...

..The novel HEY1-NCOA2 fusion appears to be the defining and diagnostic gene fusion in mesenchymal chondrosarcomas...

..Treatment of metastatic GIST with imatinib mesylate results in a 2-year survival of approximately 72%. The outcome of patients with metastatic GIST not treated with tyrosine kinase inhibitors is not well defined...

..To identify the prognostic variables that predict disease-specific survival and second local recurrence-free survival in patients with recurrent retroperitoneal liposarcoma so as to guide clinical management...

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..To the authors' knowledge, few studies to date have examined the effect of chemotherapy in patients undergoing pulmonary resection for metastatic STS of the extremity...

..These data provide a basis for the activity of vascular endothelial growth factor receptor-directed therapy in the treatment of primary and radiation-induced AS...

..Treatment with IF should be considered in patients with high-risk primary extremity liposarcoma...

..We examine clinicopathologic factors associated with disease-free survival (DFS) in patients with primary and recurrent DFSP and evaluate responses to multimodality therapy...

..A large local recurrence that develops in a short interval indicates a biologically aggressive tumor with a high tumor-specific mortality. Patients who develop such recurrences are ideal subjects for systemic neoadjuvant therapy trials...

..Responses of desmoid patients to sorafenib on an expanded access program led us to review our experience...

..In this study, the authors compared rates and patterns of LR of high-grade (HG) myxofibrosarcoma with rates and patterns of HG leiomyosarcoma, which was chosen because of the similarity in incidence and general treatment approach...

..Taken together, we present a statistically robust methodology applicable to high-resolution genomic data to assess the extent and function of copy-number alterations in cancer...

..These results suggest that PPARgamma ligands may be useful in treating angiogenic diseases such as cancer by inhibiting angiogenesis...

..To identify prognostic factors related to outcome in 255 patients with synovial sarcoma and to construct a preoperative nomogram to predict the risk of disease-specific death...

..The authors sought to determine whether differences existed in patterns of outcome and morbidity between the 3 thigh compartments after limb-sparing surgery and postoperative radiation therapy (RT)...

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..Taken together, our findings suggest that miR-143 re-expression vectors or selective agents directed at miR-143 or its targets may have therapeutic value in dedifferentiated liposarcoma...

..Our results confirm LOI in several tumours expressing high levels of IGF2, which may explain the observed paraneoplastic hypoglycaemia...

..Our algorithm represents the first phylogeny-based tool to analyze the differentiation status of human tumors...

..Cancer survivors are at increased risk for second malignancies, and vigilance is thus required. The authors sought to determine whether there was an association among lymphoma, sarcoma, and the associated treatments for these diseases...

..It is controversial whether patients with NF1-associated MPNST have worse outcomes. We investigated the prognostic significance of sporadic, NF1-associated, and RT-induced MPNST...

..A recent report identified four non-syndromic, KIT/PDGFRA WT GIST harboring compound heterozygous or homozygous mutations in SDHA encoding the main subunit of the SDH complex II...

..Data regarding the patterns and the mechanisms of deregulation of the insulin growth factor (IGF) pathway in adult and paediatric gastrointestinal stromal tumours (GISTs) are limited...

..These results suggest the possibility of a newly defined subgroup of primitive round cell sarcomas characterized by CIC rearrangements, distinct from Ewing sarcoma family of tumors...

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..That acquired resistance to imatinib in GIST commonly occurs via secondary gene mutation in the KIT kinase domain has implications for strategies to delay or prevent imatinib resistance and to employ newer targeted therapies...

..Anecdotal evidence, mainly supported by isolated case reports, suggests that a subset of these patients also develop bone metastasis, especially within the spine, which was previously under-appreciated...

..Irrespective of the grade dedifferentiated liposarcoma with myxofibrosarcoma-like features should be closely monitored. Once metastases occur, they tend to follow a rapidly fatal course...

..Our study yields a detailed map of molecular alterations across diverse sarcoma subtypes and suggests potential subtype-specific targets for therapy...

..Although these data cannot be extrapolated to primary diagnosis of liposarcoma, they are important for screening and subtyping of possible recurrence...

..In the current study, the authors examined the outcomes of patients with desmoid tumors who received systemic therapy at a single institution to provide a basis for the examination of newer agents...

..Inhibition of the KIT signal-transduction pathway is a promising treatment for advanced gastrointestinal stromal tumors, which resist conventional chemotherapy...

..The susceptibility difference was measured for three different cell types: 3T3 F442A preadipocyte cells, mouse embryonic stem cells, and human red blood cells...

..Thus, FISH or RT-PCR analysis for the presence of WWTR1-CAMTA1 fusion may serve as a useful molecular diagnostic tool in challenging diagnoses...

..Margin-positive sclerosing WDLSs have a 10-year LRFS of only 17% and should undergo function-preserving re-excision when possible, or adjuvant radiotherapy...

..In recent years, intensity-modulated radiotherapy IMRT had been increasingly used. This study compared local control by IMRT versus by BRT in primary-extremity STS...

..The resonance with the broader linewidth represents creatine that is significantly motion-restricted and suggests that a creatine pool in muscle tissue is highly compartmentalized...

..A histologic-subtype specific nomogram provides accurate survival predictions. Prospective randomized clinical trials will continue to improve our care of patients with liposarcoma...

..To the authors' knowledge, there are limited data examining chemotherapy outcomes as a guide to therapeutic decisions for unresectable disease...

..Our results provide mechanistic insights regarding the cell of origin of MFH, establish what we believe is a novel tumor suppressor role for Wnt signaling, and identify a potential therapeutic differentiation strategy for sarcomas...

..Comparison of STS to normal tissues reveals a panel of upregulated genes that may be targets for future therapies...

..2 per 100,000 population per year; P < 0.01). CONCLUSIONS: Although it is an uncommon occurrence, patients who have a history of STS are at an increased risk for the development of a second primary STS...

..Tumor size however frequently plays a role in surgical approach with larger tumors tending toward laparotomy, raising concern that favorable outcomes reported for the laparoscopic approach may reflect this selection bias...

..Unlike most fat suppression techniques, this method is not compromised by the static or radiofrequency field heterogeneity and is equally efficient for all fat resonances independent of their chemical shift frequency...

..CONCLUSION: Vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma...

..CONCLUSIONS: In the current study, the MSKCC Sarcoma Nomogram was found to provide accurate survival predictions when it was applied to an external cohort of patients who were treated at UCLA...

..Finally, removal of closed suction drainage tubes should be deferred until after the brachytherapy catheters are removed to minimize complications resulting from catheter dislodgement...

..However, even in highly selected patients, the progressive and pervasive nature of the disease limits the opportunity to attain sustained relief for gastrointestinal obstructive symptoms...

..This pulse sequence methodology enables efficient water suppression for intact cells and tissue samples and eliminates signal loss from cellular metabolites...

..In patients with low-grade, completely resected sarcoma, there is a significant survival benefit with treatment in a high-volume tertiary center of excellence...

..The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST...

..Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality...

..Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs...

..To determine if ifosfamide-based chemotherapy (IF) offers a survival benefit to adult patients with primary extremity synovial sarcoma...

..The impact of arterial revascularization on long-term results, including quality of life (QOL) in women, compared with men, has not been clearly defined...