Genome remodelling in a basal-like breast cancer metastasis and xenograft

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour

Rockefeller New Media Foundation Proposal

Mixed Greens is a web-based artwork that uses interactivity to tell a story of the complexities of identity. It will be a mixed genre piece using documentary, fiction, sound, and text. Mixed Greens interweaves two identity stories: of my paternal grandfather and his brothers who, as Irish Jews, lived in a "gray area" between Catholics and Protestants, and later negotiated a different set of identity issues as immigrants in Boston; and that of five lesbians, who live at a contemporary edge of assimilation and difference. Mixed Greens is the third piece in what will eventually be a five-piece/fivecourse meal that I call Queer Feast: a mosaic of contemporary lesbian culture played out through its contradictions of class, ethnicity, desire, and the banality of daily existence. The five pieces/courses consist of: Cocktails & Appetizers (2001), a tale of lust and love, voyeurism and the performance of gender; Mixed Greens, a meditation on identity and assimilation; Bread and Butter, a non-linear "memoir" of the twenty-four year relationship of me and my partner; The Main Dish, a social, historical, and political narrative of lesbian culture; and As American As Apple Pie (1999), occupying the space between melodrama and sitcom, a tale of lesbian family life. This feast crosses many borders - documentary/fiction/melodrama/comedy, memoir/history/myth, ethnicity/race/class - bringing complexity to the media representation of lesbian life and culture. It also uses interactivity to explore the paradoxes of narrative itself. I will use the Rockefeller New Media Fellowship to create Mixed Greens as well as the Queer Feast web site

Preoperative Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer: Preliminary Results of a Prospective, Phase 2 Trial

Purpose: To assess the feasibility of utilizing 3-dimensional conformal accelerated partial-breast irradiation (APBI) in the preoperative setting followed by standard breast-conserving therapy. Patients and Methods: This was a prospective trial testing the feasibility of preoperative APBI followed by lumpectomy for patients with early-stage invasive ductal breast cancer. Eligible patients had T1-T2 ( 21 days after radiation therapy. Adjuvant therapy was given as per standard of care. Results: Twenty-seven patients completed treatment. With a median follow-up of 3.6 years ( range, 0.5-5 years), there have been no local or regional failures. A complete pathologic response according to hematoxylin and eosin stains was seen in 4 patients (15%). There were 4 grade 3 seromas. Patient-reported cosmetic outcome was rated as good to excellent in 79% of patients after treatment. Conclusions: Preoperative 3-dimensional conformal radiation therapy - APBI is feasible and well tolerated in select patients with early-stage breast cancer, with no reported local recurrences and good to excellent cosmetic results. The pathologic response rates associated with this nonablative APBI dose regimen are particularly encouraging and support further exploration of this paradigm. (C) 2016 Elsevier Inc. All rights reserved

Impossible subjects? In search of the maternal subject in Stories we tell (Polley 2012) and The arbor (Barnard 2010)

In 1977 Adrienne Rich wrote, ‘It is hard to write about my own mother. Whatever I do write, it is my own story I am telling’. Two years later, Michelle’s Citron’s film Daughter Rite, struggled with the same problem. It was, she later wrote, a daughter’s film, ‘incapable of imagining the mother’s story’. The difficulty of imagining and conceptualizing a specifically maternal subject is an issue that has continued to preoccupy feminist scholarship, becoming in the past ten years once more an urgent political and theoretical topic. At the same time a number of female filmmakers have returned to the issues raised by Citron’s film, using techniques which, like hers, also ask us to question the relationship between narrative, memory, and the various forms through which their claims to truth are made. Here I discuss two: Stories We Tell (Polley, 2012) and The Arbor (Barnard 2010). Both concern quests to recover the mother as subject, very different from the nurturing and devouring figure of Citron’s film. Both manipulate and question footage that claims a direct, indexical relation to ‘truth’; both construct a story which employs techniques of narrative fiction, yet operate through processes which challenge the authority of such narratives. In this article I explore the two films, to ask how far they succeed in bringing the maternal subject into view, and in so doing successfully challenge conventional notions of what a subject is and can be

Opposing Effects of Two Tissue Transglutaminase Protein Isoforms in Neuroblastoma Cell Differentiation*

We have demonstrated previously that the Myc oncoprotein blocks cancer cell differentiation by forming a novel transcriptional repressor complex with histone deacetylase and inhibiting gene transcription of tissue transglutaminase (TG2). Moreover, induction of TG2 gene transcription and transamidase activity is essential for the differentiating effects of retinoids in cancer cells. Here, we show that two structurally distinct TG2 protein isoforms, the full-length (TG2-L) and the short form (TG2-S), exert opposing effects on cell differentiation. Repression of TG2-L with small interfering RNA, which did not affect TG2-S expression, induced dramatic neuritic differentiation in neuroblastoma cells. In contrast, overexpression of TG2-S or a GTP-binding-deficient mutant of TG2-L (R580A), both of which lack the GTP-binding Arg-580 residue, induced neuroblastoma cell differentiation, which was blocked by an inhibitor of transamidase activity. Whereas N-Myc repressed and retinoid activated both TG2 isoforms, repression of TG2-L, but not simultaneous repression of TG2-L and TG2-S, enhanced neuroblastoma cell differentiation due to N-Myc small interfering RNA or retinoid. Moreover, suppression of vasoactive intestinal peptide (VIP) expression alone induced neuroblastoma cell differentiation, and VIP was up-regulated by TG2-L, but not TG2-S. Taken together, our data indicate that TG2-L and TG2-S exert opposite effects on cell differentiation due to differences in GTP binding and modulation of VIP gene transcription. Our findings highlight the potential importance of repressing the GTP binding activity of TG2-L or activating the transamidase activity of TG2-L or TG2-S for the treatment of neuroblastoma, and possibly also other Myc-induced malignancies, and for enhancing retinoid anticancer effects