Predictors of Survival for Patients with Non-small Cell Lung Cancer and Synchronous Brain Metastases with FDG-PET/CT Staging

Purpose: The clinical course of patients diagnosed with non-small cell lung cancer (NSCLC) with brain metastases (BM) at presentation is variable. Here we seek to identify predictors of survival in patients staged with FDG-PET/CT. American Association of Physicists in Medicine (AAPM) 52nd Annual Meeting July 18-22, Philadelphia, P

Decrease of Morbidity and Cost of Care with Prophylactic Cranial Irradiation for Non-small Cell Lung Cancer

Purpose: While several studies analyze the incidence of brain metastases in patients with non-small cell lung cancer (NSCLC) treated with prophylactic cranial irradiation (PCI), there is little data available on how this treatment can affect medical cost and morbidity. Our goal was to analyze those issues patients encounter secondary to brain metastases, often in the final months of their lives, and to support the hypothesis of economic benefit and cost effectiveness resulting from the use of PCI in this population. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Combination of Vorinostat with Whole-brain Radiotherapy in the Treatment of Brain Metastases

Background: A third of patients with solid malignancies develop brain metastases. Expected overall survival is 4-7 months depending on age, performance status, and extracranial disease. Standard treatment is controversial; however, the majority of patients receive wholebrain radiation therapy at some point. Vorinostat (suberoylanilide hydroxamic acid, SAHA), an FDA-approved HDAC inhibitor, has been demonstrated to radiosensitize tumor cells in vitro, as assessed by both radiation-induced DNA damage and clonogenic cell survival (Munshi et al. Molecular Cancer Therapeutics 5, 1967-1974, 2006). We have shown that vorinostat downregulates key genes involved in double-strand DNA repair (Rad50, Rad51, XRCC2, XRCC3, XRCC6), as assessed by quantitative PCR. This suggests that the drug’s mechanism of radiosensitization is epigenetic coordinated inhibition of the DNA repair process. We hypothesize that the combination of vorinostat with whole-brain radiation therapy will be both safe and efficacious. American Society of Clinical Oncology (ASCO) 46th Annual Meeting June 4-8, Chicago, IL

Dosimetric Evaluation of Tumor Tracking in 4D Radiotherapy

Purpose: In some patients the tumors in lung, pancreas, liver, breast, and other organs move significantly during cardiac and breathing cycles. In this study we have investigated the dosimetric benefits of real-time tumor tracking for patients who were diagnosed with lung cancer. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Reirradiation for Recurrent Meningioma

Purpose/Objective(s): Management options for meningioma include observation, surgical resection, and radiation therapy (RT). In cases of progressive or recurrent disease after RT, similar options exist. The control rate following a second course of RT is unknown. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

RNF17 blocks promiscuous activity of PIWI proteins in mouse testes

PIWI proteins and their associated piRNAs protect germ cells from the activity of mobile genetic elements. Two classes of piRNAs-primary and secondary-are defined by their mechanisms of biogenesis. Primary piRNAs are processed directly from transcripts of piRNA cluster loci, whereas secondary piRNAs are generated in an adaptive amplification loop, termed the ping-pong cycle. In mammals, piRNA populations are dynamic, shifting as male germ cells develop. Embryonic piRNAs consist of both primary and secondary species and are mainly directed toward transposons. In meiotic cells, the piRNA population is transposon-poor and largely restricted to primary piRNAs derived from pachytene piRNA clusters. The transition from the embryonic to the adult piRNA pathway is not well understood. Here we show that RNF17 shapes adult meiotic piRNA content by suppressing the production of secondary piRNAs. In the absence of RNF17, ping-pong occurs inappropriately in meiotic cells. Ping-pong initiates piRNA responses against not only transposons but also protein-coding genes and long noncoding RNAs, including genes essential for germ cell development. Thus, the sterility of Rnf17 mutants may be a manifestation of a small RNA-based autoimmune reaction

An atlas of chromatoid body components

The genome of male germ cells is actively transcribed during spermatogenesis to produce phase-specific protein-coding mRNAs and a considerable amount of different noncoding RNAs. Ribonucleoprotein (RNP) granule-mediated RNA regulation provides a powerful means to secure the quality and correct expression of the requisite transcripts. Haploid spermatids are characterized by a unique, unusually large cytoplasmic granule, the chromatoid body (CB), which emerges during the switch between the meiotic and post-meiotic phases of spermatogenesis. To better understand the role of the CB in male germ cell differentiation, we isolated CBs from mouse testes and revealed its full RNA and protein composition. We showed that the CB is mainly composed of RNA-binding proteins and other proteins involved RNA regulation. The CB was loaded with RNA, including pachytene piRNAs, a diverse set of mRNAs, and a number of uncharacterized long noncoding transcripts. The CB was demonstrated to accumulate nascent RNA during all the steps of round spermatid differentiation. Our results revealed the CB as a large germ cell-specific RNP platform that is involved in the control of the highly complex transcriptome of haploid male germ cells