ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes

ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed to minimize false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Biochemically validated analysis in human T-cells reveals that three transcription factor oncogenes, NOTCH1, MYC, and HES1, bind one order of magnitude more promoters than previously thought. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the resolution of a more complete map of transcriptional targets reveals that MYC binds nearly all promoters bound by NOTCH1. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs

Phase 2 study of RO4929097, a gamma‐secretase inhibitor, in metastatic melanoma: SWOG 0933

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110565/1/cncr29055.pd

Updates in the management of brain metastases

The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers

Cancer cells exploit an orphan RNA to drive metastatic progression.

Here we performed a systematic search to identify breast-cancer-specific small noncoding RNAs, which we have collectively termed orphan noncoding RNAs (oncRNAs). We subsequently discovered that one of these oncRNAs, which originates from the 3' end of TERC, acts as a regulator of gene expression and is a robust promoter of breast cancer metastasis. This oncRNA, which we have named T3p, exerts its prometastatic effects by acting as an inhibitor of RISC complex activity and increasing the expression of the prometastatic genes NUPR1 and PANX2. Furthermore, we have shown that oncRNAs are present in cancer-cell-derived extracellular vesicles, raising the possibility that these circulating oncRNAs may also have a role in non-cell autonomous disease pathogenesis. Additionally, these circulating oncRNAs present a novel avenue for cancer fingerprinting using liquid biopsies

Melanoma central nervous system metastases: current approaches, challenges, and opportunities

Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here, we provide a review of the current status of the field of melanoma brain metastasis research; identify key challenges and opportunities for improving the outcomes in patients with melanoma brain metastases; and set a framework to optimize future research in this critical area

Levator anguli oris muscle based flaps for nasal reconstruction following resection of nasal skin tumours

<p>Abstract</p> <p>Background</p> <p>surgical excision remains the best tool for management of skin tumors affecting nasal skin, however many surgical techniques have been used for reconstruction of the nasal defects caused by excisional surgery. The aim of this work is the evaluation of the feasibility and outcome of levator anguli oris muscle based flaps.</p> <p>Methods</p> <p>Ninety patients of malignant nasal skin tumours were included in this study. Age was ranged from four to 78 years. For small unilateral defects affecting only one side ala nasi, levator anguli oris myocautaneous (LAOMC) flap was used in 45 patients. For unilateral compound loss of skin and mucus membrane, levator anguli oris myocautaneous mucosal (LAOMCM) flap was used in 23 patients. Very large defects; bilateral either LAOMC or LAOMCM flaps combined with forehead glabellar flaps were used to reconstruct the defect in 22 patients.</p> <p>Results</p> <p>Wound dehiscence was the commonest complication. Minor complications, in the form of haematoma and minor flap loss were managed conservatively. Partial flap loss was encountered in 6 patients with relatively larger tumours or diabetic co-morbidity, three of whom were required operative re-intervention in the form of debridement and flap refashioning, while total flap loss was not occurred at all.</p> <p>Conclusions</p> <p>Immediate nasal reconstruction for nasal skin and mucosal tumours with levator anguli oris muscle based flaps (LAOMC, LAOMCM) is feasible and spares the patient the psychic trauma due to organ loss.</p