High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas.

Primitive round cell sarcomas of childhood and young adults have been problematic to diagnose and classify. Our goal was to investigate the pathologic and molecular characteristics of small blue round cell tumors (SBRCT) that remained unclassified after exhaustive immunohistochemistry and molecular screening to exclude known sarcoma-related translocations. As rare examples of EWSR1-negative SBRCT have been shown to carry rearrangements for FUS and CIC genes, we undertook a systematic screening for these two genes.

Patterns of care, prognosis, and survival in patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib.

Background: Data regarding the management and outcome of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to 1st-line imatinib and 2nd-line sunitinib are limited.

Methods: Medical records of 223 imatinib-resistant and sunitinib-resistant GIST who were treated in 11 major referral centers were reviewed.

Results: The three most frequent drugs used in the 3rd-line setting were: nilotinib n = 67 (29.

Pigmentary changes in a patient treated with imatinib.

Imatinib mesylate (STI 571; Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) is an orally available tyrosine kinase inhibitor that targets a constitutively activated BCR-ABL tyrosine kinase with additional inhibitory effects on platelet derived growth factor (PDGF) receptors alpha and beta, and KIT. It has revolutionized the treatment of adult and pediatric patients with Philadelphia chromosome positive chronic myelogenous leukemia (CML) and is also FDA-approved for KIT-positive advanced gastrointestinal tumor (GIST) and dermatofibrosarcoma protuberans. A wide spectrum of dermatologic toxicities has been associated with this agent, among which a maculopapular rash is the most common event.

Comparison of doxorubicin and weekly paclitaxel efficacy in metastatic angiosarcomas.

Background: Data regarding the role of anthracyclines and taxanes as first-line treatments of metastatic angiosarcoma are limited.

Methods: Records of 117 metastatic angiosarcoma patients who were treated with either doxorubicin or weekly paclitaxel were reviewed.

Results: Seventy-five patients (64%) were treated with weekly paclitaxel and 42 (36%) with single-agent doxorubicin.

Advanced well-differentiated/dedifferentiated liposarcomas: role of chemotherapy and survival.

Background: Data regarding the role of systemic therapy in patients with advanced well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS) are limited.

Methods: From 2000 to 2010, 208 patients with advanced WDLPS/DDLPS received chemotherapy in 11 participating institutions. Clinical and pathological data were collected by reviewing medical records.

R1507, a monoclonal antibody to the insulin-like growth factor 1 receptor, in patients with recurrent or refractory Ewing sarcoma family of tumors: results of a phase II Sarcoma Alliance for Research through Collaboration study.

Purpose: The type 1 insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the pathogenesis of the Ewing sarcoma family of tumors (ESFT). We conducted a multicenter phase II study of the fully human IGF-1R monoclonal antibody R1507 in patients with recurrent or refractory ESFT.

Patients And Methods: Patients ≥ 2 years of age with refractory or recurrent ESFT received R1507 at doses of 9 mg/kg intravenously one a week or 27 mg/kg intravenously every three weeks.

A nonrandom association of gastrointestinal stromal tumor (GIST) and desmoid tumor (deep fibromatosis): case series of 28 patients.

Background: Gastrointestinal stromal tumors (GISTs) and desmoid tumors (DTs) are two rare mesenchymal tumor. Anecdotal reports of individuals with both diseases led us to make the hypothesis that the association is a nonrandom event as the probability would be extremely low to observe such cases if they were independent events.

Patients And Methods: We evaluated the existence of patients with GIST and DT in a large multicenter cohort at 10 institutions in the United States, Australia and Europe.

Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis.

Background: ALK gene rearrangement defines a new molecular subtype of non-small-cell lung cancer (NSCLC). In a recent phase 1 clinical trial, the ALK tyrosine-kinase inhibitor (TKI) crizotinib showed marked antitumour activity in patients with advanced, ALK-positive NSCLC. To assess whether crizotinib affects overall survival in these patients, we did a retrospective study comparing survival outcomes in crizotinib-treated patients in the trial and crizotinib-naive controls screened during the same time period.

Efficacy of imatinib mesylate for the treatment of locally advanced and/or metastatic tenosynovial giant cell tumor/pigmented villonodular synovitis.

Background: Pigmented villonodular synovitis (PVNS) (also known as diffuse-type giant cell tumor) and tenosynovial giant cell tumors (TGCT) are rare, usually benign neoplasms that affect the synovium and tendon sheaths in young adults. These tumors are driven by the overexpression of colony stimulating factor-1 (CSF1). CSF1 is expressed by a minority of tumor cells, which, in turn attract non-neoplastic inflammatory cells that express CSF1 receptor (CSF1R) through a paracrine effect.

Advances in sarcoma genomics and new therapeutic targets.

Increasingly, human mesenchymal malignancies are being classified by the abnormalities that drive their pathogenesis. Although many of these aberrations are highly prevalent within particular sarcoma subtypes, few are currently targeted therapeutically. Indeed, most subtypes of sarcoma are still treated with traditional therapeutic modalities, and in many cases sarcomas are resistant to adjuvant therapies.

Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification.

Crizotinib is a dual MET and ALK inhibitor. Currently, clinical development of crizotinib is focused primarily on ALK rearranged non-small cell lung cancer (NSCLC). Here we report an NSCLC patient with de novo MET amplification but no ALK rearrangement who achieved a rapid and durable response to crizotinib indicating is also a bona fide MET inhibitor.

A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites.

The classification of epithelioid vascular tumors remains challenging, as there is considerable morphological overlap between tumor subtypes, across the spectrum from benign to malignant categories. A t(1;3)(p36.3;q25) translocation was reported in two cases of epithelioid hemangioendothelioma (EHE), however, no follow-up studies have been performed to identify the gene fusion or to assess its prevalence in a larger cohort of patients.

A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials.

Purpose: To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors.

Methods: This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and April 2008. Trabectedin was administered intravenously as 1 of 3 schedules: 24-hour infusion every 3 weeks (q3wk 24-h; n = 570/2,818 cycles), 3-hour infusion every 3 weeks (q3wk 3-h; n = 258/1,003 cycles), and 3-hour infusion for three consecutive weeks every 4 weeks (qwk 3-h; n = 304/1,198 cycles).

Activity of Sorafenib against desmoid tumor/deep fibromatosis.

Background: Desmoid tumors (deep fibromatoses) are clonal connective tissue malignancies that do not metastasize, but have a significant risk of local recurrence, and are associated with morbidity and occasionally mortality. Responses of desmoid patients to sorafenib on an expanded access program led us to review our experience.

Methods: After Institutional Review Board (IRB) approval, we reviewed data for 26 patients with desmoid tumors treated with sorafenib.

Using multidimensional projection techniques for reaching a high distinguishing ability in biosensing.

Recent advances in the control of molecular engineering architectures have allowed unprecedented ability of molecular recognition in biosensing, with a promising impact for clinical diagnosis and environment control. The availability of large amounts of data from electrical, optical, or electrochemical measurements requires, however, sophisticated data treatment in order to optimize sensing performance. In this study, we show how an information visualization system based on projections, referred to as Projection Explorer (PEx), can be used to achieve high performance for biosensors made with nanostructured films containing immobilized antigens.

Predictive impact of DNA repair functionality on clinical outcome of advanced sarcoma patients treated with trabectedin: a retrospective multicentric study.

Aim: Trabectedin sensitivity is increased in cells with functional nucleotide excision DNA repair, whereas efficient homologous recombination repair leads to resistance. On this basis, a retrospective study of mRNA expression of BRCA1 (breast cancer susceptibility 1 gene), XPG (Xeroderma pigmentosum group G gene) and ERCC1 (excision-repair cross complementing group 1 gene) in tumour samples from sarcoma patients treated with trabectedin was conducted, to correlate DNA repair profiles with patient outcome.

Materials And Methods: Quantification of expression in paraffin embedded tumour samples from 245 patients with advanced sarcomas was performed by qRT-PCR (quantitative real-time polymerase chain reaction).

Information visualization techniques for sensing and biosensing.

The development of new methods and concepts to visualize massive amounts of data holds the promise to revolutionize the way scientific results are analyzed, especially when tasks such as classification and clustering are involved, as in the case of sensing and biosensing. In this paper we employ a suite of software tools, referred to as PEx-Sensors, through which projection techniques are used to analyze electrical impedance spectroscopy data in electronic tongues and related sensors. The possibility of treating high dimension datasets with PEx-Sensors is advantageous because the whole impedance vs.

Benign mesenchymal stromal cells in human sarcomas.

Purpose: Recent evidence suggests that at least some sarcomas arise through aberrant differentiation of mesenchymal stromal cells (MSCs), but MSCs have never been isolated directly from human sarcoma specimens.

Experimental Design: We examined human sarcoma cell lines and primary adherent cultures derived from human sarcoma surgical samples for features of MSCs. We further characterized primary cultures as either benign or malignant by the presence of tumor-defining genetic lesions and tumor formation in immunocompromised mice.

Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor.

Small molecule kinase inhibitors have irrevocably altered cancer treatment. March 2010 marks the 10th anniversary of using imatinib in gastrointestinal stromal tumors (GIST), a cardinal example of the utility of such targeted therapy in a solid tumor. Before imatinib, metastatic GIST was frustrating to treat due to its resistance to standard cytotoxic chemotherapy.

Biosensors for efficient diagnosis of leishmaniasis: innovations in bioanalytics for a neglected disease.

The need for reliable, fast diagnostics is closely linked to the need for safe, effective treatment of the so-called "neglected" diseases. The list of diseases with no field-adapted diagnostic tools includes leishmaniasis, shigella, typhoid, and bacterial meningitis. Leishmaniasis, in particular, is a parasitic disease caused by Leishmania spp.

Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumor (IMT) is a distinctive mesenchymal neoplasm characterized by a spindle-cell proliferation with an inflammatory infiltrate. Approximately half of IMTs carry rearrangements of the anaplastic lymphoma kinase (ALK) locus on chromosome 2p23, causing aberrant ALK expression. We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation.

Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.

Background: Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non-small-cell lung cancers, representing 2 to 7% of such tumors. We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase.

Methods: After screening tumor samples from approximately 1500 patients with non-small-cell lung cancer for the presence of ALK rearrangements, we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial.