Current status of gene therapy for breast cancer: progress and challenges

Breast cancer is characterized by a series of genetic mutations and is therefore ideally placed for gene therapy intervention. The aim of gene therapy is to deliver a nucleic acid-based drug to either correct or destroy the cells harboring the genetic aberration. More recently, cancer gene therapy has evolved to also encompass delivery of RNA interference technologies, as well as cancer DNA vaccines. However, the bottleneck in creating such nucleic acid pharmaceuticals lies in the delivery. Deliverability of DNA is limited as it is prone to circulating nucleases; therefore, numerous strategies have been employed to aid with biological transport. This review will discuss some of the viral and nonviral approaches to breast cancer gene therapy, and present the findings of clinical trials of these therapies in breast cancer patients. Also detailed are some of the most recent developments in nonviral approaches to targeting in breast cancer gene therapy, including transcriptional control, and the development of recombinant, multifunctional bio-inspired systems. Lastly, DNA vaccines for breast cancer are documented, with comment on requirements for successful pharmaceutical product development

Spectra associated to symmetric monoidal bicategories

We show how to construct a Gamma-bicategory from a symmetric monoidal bicategory, and use that to show that the classifying space is an infinite loop space upon group completion. We also show a way to relate this construction to the classic Gamma-category construction for a bipermutative category. As an example, we use this machinery to construct a delooping of the K-theory of a bimonoidal category as defined by Baas-Dundas-Rognes.Comment: 27 pages; originally submitted as: "An Infinite Loop Space Structure for K-theory of Bimonoidal Categories", this version has essentially the same content, but the organization is differen

Multifunctional Delivery Systems for Cancer Gene Therapy

This chapter examines key concepts with respect to cancer gene therapy and the current issues with respect to non-viral delivery. The biological and molecular barriers that need to be overcome before effective non-viral delivery systems can be appropriately designed for oncology applications are highlighted and ways to overcome these are discussed. Strategies developed to evade the immune response are also described and targeted gene delivery is examined with the most effective strategies highlighted. Finally, this chapter proposes a new way forward based on a growing body of evidence that supports a multifunctional delivery approach involving the creation of vectors, with a unique molecular architecture designed using a bottom-up approach

Delivery of nucleic acids for cancer gene therapy: overcoming extra- and intra-cellular barriers

The therapeutic potential of cancer gene therapy has been limited by the difficulty of delivering genetic material to target sites. Various biological and molecular barriers exist which need to be overcome before effective nonviral delivery systems can be applied successfully in oncology. Herein, various barriers are described and strategies to circumvent such obstacles are discussed, considering both the extracellular and intracellular setting. Development of multifunctional delivery systems holds much promise for the progression of gene delivery, and a growing body of evidence supports this approach involving rational design of vectors, with a unique molecular architecture. In addition, the potential application of composite gene delivery platforms is highlighted which may provide an alternative delivery strategy to traditional systemic administration. </jats:p

The Prognostic Significance of Combining VEGFA, FLT1 and KDR mRNA Expressions in Brain Tumors

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The significance of combining VEGFA, FLT1, and KDR expressions in colon cancer patient prognosis and predicting response to bevacizumab

Targeting angiogenesis through inhibition of the vascular endothelial growth factor (VEGF) pathway has been successful in the treatment of late stage colorectal cancer. However, not all patients benefit from inhibition of VEGF. Ras status is a powerful biomarker for response to anti-epidermal growth factor receptor therapy; however, an appropriate biomarker for response to anti-VEGF therapy is yet to be identified. VEGF and its receptors, FLT1 and KDR, play a crucial role in colon cancer progression; individually, these factors have been shown to be prognostic in colon cancer; however, expression of none of these factors alone was predictive of tumor response to anti-VEGF therapy. In the present study, we analyzed the expression levels of VEGFA, FLT1, and KDR in two independent colon cancer datasets and found that high expression levels of all three factors afforded a very poor prognosis. The observation was further confirmed in another independent colon cancer dataset, wherein high levels of expression of this three-gene signature was predictive of poor prognosis in patients with proficient mismatch repair a wild-type KRas status, or mutant p53 status. Most importantly, this signature also predicted tumor response to bevacizumab, an antibody targeting VEGFA, in a cohort of bevacizumab-treated patients. Since bevacizumab has been proven to be an important drug in the treatment of advanced stage colon cancer, our results suggest that the three-gene signature approach is valuable in terms of its prognostic value, and that it should be further evaluated in a prospective clinical trial to investigate its predictive value to anti-VEGF treatment

On the embeddability of certain infinitely divisible probability measures on Lie groups

We describe certain sufficient conditions for an infinitely divisible probability measure on a class of connected Lie groups to be embeddable in a continuous one-parameter convolution semigroup of probability measures. (Theorem 1.3). This enables us in particular to conclude the embeddability of all infinitely divisible probability measures on certain Lie groups, including the so called Walnut group (Corollary 1.5). The embeddability is concluded also under certain other conditions (Corollary 1.4 and Theorem 1.6).Comment: 24 page

Tannaka-Krein duality for Hopf algebroids

We develop the Tannaka-Krein duality for monoidal functors with target in the categories of bimodules over a ring. The \coend of such a functor turns out to be a Hopf algebroid over this ring. Using the result of a previous paper we characterize a small abelian, locally finite rigid monoidal category as the category of rigid comodules over a transitive Hopf algebroid.Comment: 25 pages, final version, to appear in Israel Journal of Mathematic