248 research outputs found
Pancreatic Cancer: Progress and Challenges in a Rapidly Moving Field
No full textAbstract
“Pancreatic Cancer: Advances in Science and Clinical Care,” a Special Conference of the American Association for Cancer Research, was held in Orlando, FL, on May 12 to 15, bringing together more than 450 basic, translational, clinical, and epidemiologic pancreatic cancer researchers as well as pancreatic cancer patients, survivors, and advocates. Pancreatic cancer remains one of the great challenges in medicine, but the accelerating pace of research and early hints of clinical successes to come were palpable throughout the meeting. Prominent meeting themes included immunology and the tumor microenvironment, heterogeneity of both the epithelial and stromal compartments, personalized medicine efforts to integrate molecular information into clinical practice, new approaches to early detection, and clinical trials using a host of novel targeted therapies. Adding to the vibrant atmosphere of the meeting, a coalition of pancreatic cancer research and support foundations participated, with several innovative initiatives announced by individual organizations. We present here a summary of meeting highlights, a series of “success factors” that will benchmark the progress of the field over the next 2 years, and three challenges to the pancreatic cancer research community as it moves toward to the goal of extending patient survival. Cancer Res; 77(5); 1060–2. ©2017 AACR.</jats:p
Phylogenetic Analyses of Texas Isolates Indicate an Evolving Subtype of the Clade B Feline Immunodeficiency Viruses
No full textRigorous phylogenetic analyses were used to compare the nucleotide sequences of feline immunodeficiency virus strains isolated from Texas and throughout the world. The envelope V3-V4 sequences and capsid gene of the Texas isolates formed a cluster between subtypes B and E. Statistical comparisons with other published sequences confirmed that the Texas group is a unique cluster, possibly a new subtype, arising from subtype B.
Feline immunodeficiency virus (FIV) was initially isolated in 1987 from a cat in California with severe immunodeficiency and has been recognized as a common worldwide feline pathogen (11, 14, 19, 20, 33). FIV-infected cats exhibit a progressive impairment of cellular immunity, leaving the animals susceptible to opportunistic infections (17, 23, 24). Similar to other lentiviruses, genetic variations may occur as a result of point mutations or recombination (1, 2). Since genetic variation and associated disease characteristics are similar between FIV and human immunodeficiency virus, FIV is a practical model for T-tropic lentiviral infection, especially for vaccine development and the design of antiviral therapies (3, 4, 11, 12, 14, 17, 21, 27, 29, 33, 34).
A number of FIV strains have been identified throughout the world, and their corresponding genomes have been partially sequenced (1, 5, 6, 10, 13, 15, 18, 19, 22, 27, 32). Studies developed on the basis of the nucleotide sequences from the envelope gene separated FIV strains into five distinct phylogenetic subtypes designated A to E (1, 2, 10, 13, 22, 27). Although geographic isolation could be a major factor in the evolution of FIV, individual subtypes are found in more than one part of the world (1, 2, 5, 13, 19, 27). For example, subtypes A and B have been isolated from cats in the United States, Europe, Japan, and Australia, and subtype C-infected cats have been identified in North America, Europe, and Taiwan. Consequently, recombinant strains have also been described (notably between subtype A and B subtypes and between B and D subtypes) (1, 2). The isolation and characterization of new FIV isolates with a broad feline representation, including high-risk feral cats, are critical for better understanding of ongoing genetic diversity
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Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA
No full text© 2015 Lanman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Abstract B39: A pilot study to establish procedures for DNA and RNA isolation from African esophageal tumor specimens
No full textAbstract
Objective: We propose to utilize tumor biospecimens from patients with esophageal squamous cell carcinoma (ESCC) to identify possible genetic, molecular, and infectious determinants of this high-incidence disease in East Africa. However, laboratory technologies in East Africa are not available to support DNA and RNA extraction and genome and transcriptome sequencing from patient specimens. In preparation for establishment of a biorepository for African ESCC specimens, we compared different fixation and preservation media for transportability over long distances and success in preserving the genetic integrity and expression profiles of ESCC.
Methods: Patients with a suspected diagnosis of ESCC at Muhimbili National Hospital in Dar es Salaam, Tanzania were identified and consented prior to endoscopic evaluations. For patients with endoscopic findings consistent with ESCC, tumor biopsies were obtained and stored using two different fixation and preservation media: PAXgene® Tissue Container (n=2) and RNAlater® (n=2). All specimens were shipped at room temperature from Dar es Salaam to San Francisco. DNA and RNA quantity was measured by nanodrop method and DNA was further confirmed by picogreen method, yielding measures of total DNA and RNA acquired (ug). DNA quality was measured as percent of total DNA degradation to between 200-1000 bp. RNA quality measure was determined by bioanalyzer output measure RNA Integrity Number (RIN).
Results: Specimens for our first 10 patients were analyzed. Average transit time of biopsy specimens in preservative at room temperature was 6.2 days (range 3.5-9.0). Tumor specimens preserved with PAXgene® yielded a mean of 7.7 ug total DNA and 8.6 ug total RNA. Tumor specimens preserved with RNAlater® yielded a mean 1.4 ug of DNA and 8.2 ug of RNA. DNA degradation products were 0% of total with PAXgene® versus 6% of total with RNAlater®. Specimens preserved with PAXgene® yielded a mean RIN of 4, while RNAlater® yielded a mean RIN of 9. DNA and RNA quality were not associated with length of time at room temperature, up to a maximum of 9 days.
Conclusion: Tissue preserved using the PAXgene® Tissue Container yielded higher DNA quantity and quality than tissue preserved in RNAlater®. RNA quantity was comparable for both mediums, but RNAlater® resulted in superior RNA quality versus PAXgene®. Both mediums allowed for flexible transport of specimens at room temperature and merit further inquiry into their potential as cost-effective methods to facilitate molecular analyses for geographically isolated diseases in Africa. Based upon our pilot data, each medium offers unique advantages. Our expanded study will continue to utilize both mediums to optimize isolation of both DNA and RNA. We will plan to present data for an enriched sample size.
Funding source: National Institutes of Health, National Cancer Institute Cancer Center Administrative Supplement to Promote Cancer Prevention and Control Research in Low and Middle Income Countries, A119617, [CA-0082629].
Citation Format: Beatrice Paul Mushi, John Greer, Charles William Cahalane, II, Msiba Selekwa, Ali Mwanga, Larry Akoko, Elia Mmbaga, Eric Collisson, Katherine Van Loon. A pilot study to establish procedures for DNA and RNA isolation from African esophageal tumor specimens [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B39.</jats:p
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A robust prognostic signature for hormone-positive node-negative breast cancer
No full textBackground: Systemic chemotherapy in the adjuvant setting can cure breast cancer in some patients that would otherwise recur with incurable, metastatic disease. However, since only a fraction of patients would have recurrence after surgery alone, the chal
What are we learning from the cancer genome?
No full textThe question “are we learning anything new?” keeps being asked when related to comprehensive gene analysis of tumours. This Review attempts to answer that question, and describes how new targets are being identified and how that knowledge is being translated into the clinic
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Ferrous Iron-Dependent Pharmacology
No full textThe recent emergence of oxidation state selective probes of cellular iron has produced a more nuanced understanding of how cells utilize this crucial nutrient to empower enzyme function, and also how labile ferrous iron contributes to iron-dependent cell death (ferroptosis) and other disease pathologies including cancer, bacterial infections, and neurodegeneration. These findings, viewed in light of the Fenton chemistry promoted by ferrous iron, suggest a new category of therapeutics exhibiting ferrous iron-dependent pharmacology. While still in its infancy, this nascent field draws inspiration from the remarkable activity and tremendous clinical impact of the antimalarial artemisinin. Here, we review recent insights into the role of labile ferrous iron in biology and disease, and describe new therapeutic approaches designed to exploit this divalent transition metal
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