Treatment of Metastatic Renal Cell Carcinoma

Purpose To review the treatment of metastatic renal cell carcinoma (RCC), including the use of new targeted therapies. Methods A search of MEDLINE (1966 to August 2008) and American Society of Clinical Oncology Meeting abstracts (2005 to May 2008) was preformed using the search terms bevacizumab, everolimus, interferon-alfa (IFN-α), interleukin-2 (IL-2), sorafenib, sunitinib, temsirolimus, and RCC. Articles most pertinent to the treatment of metastatic RCC are reviewed. Results The treatment of metastatic RCC has undergone a paradigm shift over the past 5 years from biologic response modifiers to new targeted therapies. Historically, response rates for the biological response modifiers, aldesleukin (IL-2), and IFN-α were approximately 15%. Recently, three targeted agents, sorafenib, sunitinib, and temsirolimus have been approved for the treatment of RCC. Additionally, bevacizumab has been investigated and shown to increase progression free survival in RCC. IL-2 remains the only agent to induce complete, durable remissions; however, many patients are not eligible for this therapy. Newer agents (sorafenib, sunitinib, and temsirolimus) have shown to be superior to IFN-α or placebo and bevacizumab combined with IFN-α has shown activity when compared to IFN-α alone. Unlike IL-2, the greatest benefit obtained with targeted therapies is in achieving stable disease (SD). Despite their benefit, targeted therapies have never been compared with each other in clinical trials and choosing the most appropriate agent remains challenging. To date, the optimal sequence or combination of treatments has not been defined; however, everolimus has recently demonstrated activity in patients progressing on targeted therapy. Conclusions IL-2 remains the most active regimen in inducing complete responses; however, its use is accompanied by substantial morbidity and is limited to those with a good performance status. Targeted therapies are also efficacious in the treatment of RCC, with the major benefit being induction of SD. Future research will better define the sequencing of therapies, as well as, explore the activity of novel combination regimens

Retrospective Evaluation of Venous Thromboembolism Prophylaxis in the Adult Cancer Population

Study objectives. Hospitalized cancer patients are at an increased risk for venous thromboembolism (VTE) and it is recommended they receive pharmacologic prophylaxis unless otherwise contraindicated. The majority of data supporting this recommendation comes from sub-group analyses and extrapolation of data gathered in general medical/surgical patients. This study seeks to assess the safety and efficacy of VTE prophylaxis in cancer patients admitted to our institution. Methods. Charts of patients 18—89 years of age receiving VTE prophylaxis with unfractionated heparin, low molecular weigh heparin, or fondaparinux while admitted to Karmanos Cancer Center between September and October 2007 were retrospectively reviewed. Risk factors for VTE were assessed and the efficacy/safety of the prophylactic agents was compared. Results. One-hundred and eighty consecutive patients were identified. The average number of risk factors for developing VTE was 3—4 per hospital admission in addition to an active cancer diagnosis. Three VTEs occurred in the heparin group with two patients experiencing a VTE during their admission and one experiencing a VTE within 1 month after discharge. Four (2.6%) patients receiving heparin had a major bleeding event. Minor bleeding occurred in 14.3, 11.5, and 22.2% of patients receiving heparin, enoxaparin, and fondaparinux, respectively. Conclusions. This retrospective study showed cancer patients are at increased risk for VTE, typically with 3—4 risk factors per admission. VTEs were uncommon; however, three patients receiving heparin experienced a VTE and four had a major bleeding event. Minor bleeding rates were similar among groups

Critical velocity for superfluid flow across the BEC-BCS crossover

Critical velocities have been observed in an ultracold superfluid Fermi gas throughout the BEC-BCS crossover. A pronounced peak of the critical velocity at unitarity demonstrates that superfluidity is most robust for resonant atomic interactions. Critical velocities were determined from the abrupt onset of dissipation when the velocity of a moving one dimensional optical lattice was varied. The dependence of the critical velocity on lattice depth and on the inhomogeneous density profile was studied

Sodium Bose-Einstein Condensates in an Optical Lattice

The phase transition from a superfluid to a Mott insulator has been observed in a $^{23}$Na Bose-Einstein condensate. A dye laser detuned $\approx 5$nm red of the Na $3^2$S$\to 3^2$P$_{1/2}$ transition was used to form the three dimensional optical lattice. The heating effects of the small detuning as well as the three-body decay processes constrained the timescale of the experiment. Certain lattice detunings were found to induce a large loss of atoms. These loss features were shown to be due to photoassociation of atoms to vibrational levels in the Na$_2$ $(1) ^3\Sigma_g^+$ state.Comment: Figures somewhat compromised due to size reductio

PERGA: A Paired-End Read Guided De Novo Assembler for Extending Contigs Using SVM and Look Ahead Approach

Since the read lengths of high throughput sequencing (HTS) technologies are short, de novo assembly which plays significant roles in many applications remains a great challenge. Most of the state-of-the-art approaches base on de Bruijn graph strategy and overlap-layout strategy. However, these approaches which depend on k-mers or read overlaps do not fully utilize information of paired-end and single-end reads when resolving branches. Since they treat all single-end reads with overlapped length larger than a fix threshold equally, they fail to use the more confident long overlapped reads for assembling and mix up with the relative short overlapped reads. Moreover, these approaches have not been special designed for handling tandem repeats (repeats occur adjacently in the genome) and they usually break down the contigs near the tandem repeats. We present PERGA (Paired-End Reads Guided Assembler), a novel sequence-reads-guided de novo assembly approach, which adopts greedy-like prediction strategy for assembling reads to contigs and scaffolds using paired-end reads and different read overlap size ranging from Omax to Omin to resolve the gaps and branches. By constructing a decision model using machine learning approach based on branch features, PERGA can determine the correct extension in 99.7% of cases. When the correct extension cannot be determined, PERGA will try to extend the contig by all feasible extensions and determine the correct extension by using look-ahead approach. Many difficult-resolved branches are due to tandem repeats which are close in the genome. PERGA detects such different copies of the repeats to resolve the branches to make the extension much longer and more accurate. We evaluated PERGA on both Illumina real and simulated datasets ranging from small bacterial genomes to large human chromosome, and it constructed longer and more accurate contigs and scaffolds than other state-of-the-art assemblers. PERGA can be freely downloaded at https://github.com/hitbio/PERGA.published_or_final_versio

A robust and accurate binning algorithm for metagenomic sequences with arbitrary species abundance ratio

Motivation: With the rapid development of next-generation sequencing techniques, metagenomics, also known as environmental genomics, has emerged as an exciting research area that enables us to analyze the microbial environment in which we live. An important step for metagenomic data analysis is the identification and taxonomic characterization of DNA fragments (reads or contigs) resulting from sequencing a sample of mixed species. This step is referred to as 'binning'. Binning algorithms that are based on sequence similarity and sequence composition markers rely heavily on the reference genomes of known microorganisms or phylogenetic markers. Due to the limited availability of reference genomes and the bias and low availability of markers, these algorithms may not be applicable in all cases. Unsupervised binning algorithms which can handle fragments from unknown species provide an alternative approach. However, existing unsupervised binning algorithms only work on datasets either with balanced species abundance ratios or rather different abundance ratios, but not both. Results: In this article, we present MetaCluster 3.0, an integrated binning method based on the unsupervised top-down separation and bottom-up merging strategy, which can bin metagenomic fragments of species with very balanced abundance ratios (say 1:1) to very different abundance ratios (e.g. 1:24) with consistently higher accuracy than existing methods. © The Author 2011. Published by Oxford University Press. All rights reserved.postprin

Microfluidic droplet grating for reconfigurable optical diffraction

Author name used in this publication: X. M. Zhang2009-2010 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Type I collagen from bullfrog (Rana catesbeiana) fallopian tube

Pepsin-soluble collagen (PSC) was extracted from the fallopian tube of bullfrog (Rana catesbeiana) with a yield of 16.4%, on a dry weight basis. Sodium dodecyl sulphate polyacylamide-gel electrophoresis (SDS-PAGE) showed that the PSC contained two alpha components (α1 and α2) and was classified as type I collagen. PSC was found to contain 19.5% of amino acids. PSC exhibited a maximum absorbance at 230 nm, but little absorbance near to 280 nm. The denaturation temperature for PSC was determined to be 29.6°C. These results suggest that bullfrog fallopian tube has potential as a supplement to the sources of vertebrate collagens.Key words: Bullfrog (Rana catesbeiana), pepsin-soluble collagen, type I collagen