Patterns of progression in malignant glioma following anti-VEGF therapy: perceptions and evidence

Antiangiogenic treatment has recently become an integral part of modern cancer therapy targeting the vasculature of numerous aggressive malignancies including glioblastoma. There is preclinical evidence that antiangiogenic therapies promote glioma cell invasiveness. In clinical series, upon progression on antiangiogenic therapy with the vascular endothelial growth factor-directed antibody bevacizumab (BEV), glioblastoma has been reported to display a more infiltrative pattern of recurrence. This distant spread at recurrence or progression and a gliomatosis cerebri-like growth pattern is best detectable on fluid-attenuated inversion recovery MRI. The frequency of up to 20% to 30% of such a pattern in BEV-treated patients is higher than expected to occur without BEV. Older reports and common clinical knowledge estimate the frequency of diffuse or distant spread in recurrent glioblastoma at 10%. This observation stimulated two streams of research. One is to overcome this often insidious adverse effect of antiangiogenic treatment, to optimize antiangiogenic therapies and to face this major challenge, integrating antiangiogenic with anti-invasive mechanisms into one combined treatment concept. The second is questioning a specific property of antiangiogenic therapy to induce diffuse or distant spread. Here, alternative hypotheses of increased awareness and better imaging as well as invasiveness being part of the natural course of the disease have been tested. Without doubt, migration and invasiveness are major obstacles to successful glioma therapy, notably local therapies, both in the natural course of the disease and in the concept of "evasive resistance." However, clinical analyses of case series, matched pairs analyses, and follow-up on the BRAIN trial (A Study to Evaluate Bevacizumab Alone or in Combination with Irinotecan for Treatment of Glioblastoma Multiforme), which led to accelerated approval of BEV for recurrent glioblastoma in the United States, have not supported a specific propensity of BEV to induce diffuse growth or distant spread at recurrence

Secondary uses and the governance of de-identified data: Lessons from the human genome diversity panel

<p>Abstract</p> <p>Background</p> <p>Recent changes to regulatory guidance in the US and Europe have complicated oversight of secondary research by rendering most uses of de-identified data exempt from human subjects oversight. To identify the implications of such guidelines for harms to participants and communities, this paper explores the secondary uses of one de-identified DNA sample collection with limited oversight: the Human Genome Diversity Project (HGDP)-Centre d'Etude du Polymorphisme Humain, Fondation Jean Dausset (CEPH) Human Genome Diversity Panel.</p> <p>Methods</p> <p>Using a combination of keyword and cited reference search, we identified English-language scientific articles published between 2002 and 2009 that reported analysis of HGDP Diversity Panel samples and/or data. We then reviewed each article to identify the specific research use to which the samples and/or data was applied. Secondary uses were categorized according to the type and kind of research supported by the collection.</p> <p>Results</p> <p>A wide variety of secondary uses were identified from 148 peer-reviewed articles. While the vast majority of these uses were consistent with the original intent of the collection, a minority of published reports described research whose primary findings could be regarded as controversial, objectionable, or potentially stigmatizing in their interpretation.</p> <p>Conclusions</p> <p>We conclude that potential risks to participants and communities cannot be wholly eliminated by anonymization of individual data and suggest that explicit review of proposed secondary uses, by a Data Access Committee or similar internal oversight body with suitable stakeholder representation, should be a required component of the trustworthy governance of any repository of data or specimens.</p

DNA and cultures of remembrance: anthropological genetics, biohistories and biosocialities

The article engages current human population genetic research or anthropological genetics with an emphasis on its popular forms. A general discussion of the production of biohistories on the basis of DNA analyses is elaborated by focusing on what I call the Genographic network: the Genographic Project and the associated genetic ancestry companies as well as book and film productions. In order to gain an understanding of the specificity of what is also referred to as genetic history, the development of notions such as a genetic heritage, the gene as historical document, and the DNA as archive of history are briefly treated, before approaching the recent commercializations and medializations of group-specific and personalized genetic history and identity. It is here that the challenge of joining history and DNA becomes most evident: on the one hand, the genetic knowledge is presented as particularly authentic and accurate on the basis of its epistemic objects and quantitative and technological approaches. On the other hand, in order for biohistorical identities and socialities to form, the knowledge needs to be rendered in a narrative, esthetically appealing way. This also points to differences vis-à-vis medical genomics in that neither anthropological genetics, nor the biosocialities it facilitates, are oriented towards hope for future health solutions. In offering supposedly purely anthropological knowledge about who we are and where we come from, anthropological genetics is part of backward-looking socialities. It is part of cultures of remembrance