Trigeminal neuralgia treatment outcomes following Gamma Knife radiosurgery with a minimum 3-year follow-up

OBJECTIVE: Effective short-term outcomes have been well documented for trigeminal neuralgia (TN) patients treated with Gamma Knife radiosurgery (GKRS) with reported success rates of 70–90 % with median follow-up intervals of 19–75 months. Fewer series, however, have described uniform long-term follow-up data. In this study, we report our long-term institutional outcomes in patients treated with GKRS after a minimum follow-up of 36 months. METHODS: Thirty-six consecutive patients with medically intractable TN received a median radiation dose of 45 Gy applied with a single 4-mm isocenter to the affected trigeminal nerve. Follow-up data were obtained by clinical examination and telephone questionnaire. Outcome results were categorized based on the Barrow Neurological Institute (BNI) pain scale with BNI I–III considered to be good outcomes and BNI IV–V considered as treatment failure. BNI facial numbness score was used to assess treatment complications. RESULTS: The incidence of early pain relief was high (80.5 %) and relief was noted in an average of 1.6 months after treatment. At minimum follow-up of 3 years, 67 % were pain free (BNI I) and 75 % had good treatment outcome. At a mean last follow-up of 69 months, 32 % were free from any pain and 63 % were free from severe pain. Bothersome posttreatment facial numbness was reported in 11 % of the patients. A statistically significant correlation was found between age and recurrence of any pain with age >70 predicting a more favorable outcome after radiosurgery. CONCLUSION: The success rate of GKRS for treatment of medically intractable TN declines over time with 32 % reporting ideal outcome and 63 % reporting good outcome. Patients older than age 70 are good candidates for radiosurgery. This data should help in setting realistic expectations for weighing the various available treatment options

Genome co-amplification upregulates a mitotic gene network activity that predicts outcome and response to mitotic protein inhibitors in breast cancer.

BACKGROUND: High mitotic activity is associated with the genesis and progression of many cancers. Small molecule inhibitors of mitotic apparatus proteins are now being developed and evaluated clinically as anticancer agents. With clinical trials of several of these experimental compounds underway, it is important to understand the molecular mechanisms that determine high mitotic activity, identify tumor subtypes that carry molecular aberrations that confer high mitotic activity, and to develop molecular markers that distinguish which tumors will be most responsive to mitotic apparatus inhibitors. METHODS: We identified a coordinately regulated mitotic apparatus network by analyzing gene expression profiles for 53 malignant and non-malignant human breast cancer cell lines and two separate primary breast tumor datasets. We defined the mitotic network activity index (MNAI) as the sum of the transcriptional levels of the 54 coordinately regulated mitotic apparatus genes. The effect of those genes on cell growth was evaluated by small interfering RNA (siRNA). RESULTS: High MNAI was enriched in basal-like breast tumors and was associated with reduced survival duration and preferential sensitivity to inhibitors of the mitotic apparatus proteins, polo-like kinase, centromere associated protein E and aurora kinase designated GSK462364, GSK923295 and GSK1070916, respectively. Co-amplification of regions of chromosomes 8q24, 10p15-p12, 12p13, and 17q24-q25 was associated with the transcriptional upregulation of this network of 54 mitotic apparatus genes, and we identify transcription factors that localize to these regions and putatively regulate mitotic activity. Knockdown of the mitotic network by siRNA identified 22 genes that might be considered as additional therapeutic targets for this clinically relevant patient subgroup. CONCLUSIONS: We define a molecular signature which may guide therapeutic approaches for tumors with high mitotic network activity

High Chromosome Number in hematological cancer cell lines is a Negative Predictor of Response to the inhibition of Aurora B and C by GSK1070916

<p>Abstract</p> <p>Background</p> <p>Aurora kinases play critical roles in mitosis and are being evaluated as therapeutic targets in cancer. GSK1070916 is a potent, selective, ATP competitive inhibitor of Aurora kinase B and C. Translation of predictive biomarkers to the clinic can benefit patients by identifying the tumors that are more likely to respond to therapies, especially novel inhibitors such as GSK1070916.</p> <p>Methods</p> <p>59 Hematological cancer-derived cell lines were used as models for response where <it>in vitro </it>sensitivity to GSK1070916 was based on both time and degree of cell death. The response data was analyzed along with karyotype, transcriptomics and somatic mutation profiles to determine predictors of response.</p> <p>Results</p> <p>20 cell lines were sensitive and 39 were resistant to treatment with GSK1070916. High chromosome number was more prevalent in resistant cell lines (p-value = 0.0098, Fisher Exact Test). Greater resistance was also found in cell lines harboring polyploid subpopulations (p-value = 0.00014, Unpaired t-test). A review of NOTCH1 mutations in T-ALL cell lines showed an association between NOTCH1 mutation status and chromosome number (p-value = 0.0066, Fisher Exact Test).</p> <p>Conclusions</p> <p>High chromosome number associated with resistance to the inhibition of Aurora B and C suggests cells with a mechanism to bypass the high ploidy checkpoint are resistant to GSK1070916. High chromosome number, a hallmark trait of many late stage hematological malignancies, varies in prevalence among hematological malignancy subtypes. The high frequency and relative ease of measurement make high chromosome number a viable negative predictive marker for GSK1070916.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The First Generation : Women and Video, 1970-75

Hanley introduces little-seen video works produced by women making specific reference to their use of the medium, feminism, and early video technology. Wooster discusses the selected works, noting the context, features, and development of early videos and the particular issues they explore. Includes and annotated documentation of the works. Biographical notes on 21 artists. Bibl. 4 p

Making Their Mark : Women Artists Move into the Mainstream, 1970-85

Through an examination of systems of validation and economic support in art, Rosen looks at art between 1970 and 1985 and women's relation to the mainstream. Essays address women's access to professional advancement, changes that allowed women to influence the direction of art, and feminist interventions in both definitions of art and in critical practices. Documentation of the percentage of women involved in selected professional art institutions. Biographical notes. Circa 600 bibl. ref