The Use of PET-CT in the Assessment of Patients with Colorectal Carcinoma

Colorectal cancer is the third most commonly diagnosed cancer, accounting for 53,219 deaths in 2007 and an estimated 146,970 new cases in the USA during 2009. The combination of FDG PET and CT has proven to be of great benefit for the assessment of colorectal cancer. This is most evident in the detection of occult metastases, particularly intra- or extrahepatic sites of disease, that would preclude a curative procedure or in the detection of local recurrence. FDG PET is generally not used for the diagnosis of colorectal cancer although there are circumstances where PET-CT may make the initial diagnosis, particularly with its more widespread use. In addition, precancerous adenomatous polyps can also be detected incidentally on whole-body images performed for other indications; sensitivity increases with increasing polyp size. False-negative FDG PET findings have been reported with mucinous adenocarcinoma, and false-positive findings have been reported due to inflammatory conditions such as diverticulitis, colitis, and postoperative scarring. Therefore, detailed evaluation of the CT component of a PET/CT exam, including assessment of the entire colon, is essential

LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation

The actin and microtubule cytoskeletons are critically important for cancer cell proliferation, and drugs that target microtubules are widely-used cancer therapies. However, their utility is compromised by toxicities due to dose and exposure. To overcome these issues, we characterized how inhibition of the actin and microtubule cytoskeleton regulatory LIM kinases could be used in drug combinations to increase efficacy. A previously-described LIMK inhibitor (LIMKi) induced dose-dependent microtubule alterations that resulted in significant mitotic defects, and increased the cytotoxic potency of microtubule polymerization inhibitors. By combining LIMKi with 366 compounds from the GSK Published Kinase Inhibitor Set, effective combinations were identified with kinase inhibitors including EGFR, p38 and Raf. These findings encouraged a drug discovery effort that led to development of CRT0105446 and CRT0105950, which potently block LIMK1 and LIMK2 activity in vitro, and inhibit cofilin phosphorylation and increase αTubulin acetylation in cells. CRT0105446 and CRT0105950 were screened against 656 cancer cell lines, and rhabdomyosarcoma, neuroblastoma and kidney cancer cells were identified as significantly sensitive to both LIMK inhibitors. These large-scale screens have identified effective LIMK inhibitor drug combinations and sensitive cancer types. In addition, the LIMK inhibitory compounds CRT0105446 and CRT0105950 will enable further development of LIMK-targeted cancer therapy

Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately mimic the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report a mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 (≤20%) immunotherapy as human HNSCCs. Remarkably, we find that >70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform to accelerate the development of immunotherapeutic options for HNSCC

Increasing the Yield of Irish Brown Crab (Cancer pagurus) during Processing without Adversely Affecting Shelf-Life

During the processing of Irish Brown Crab (Cancer pagurus), protein and moisture are released and losses up to 10% (by weight) are common. The objective of this study was to investigate the use of clean label ingredients to reduce this loss, without adversely affecting shelf-life or promoting the growth of spoilage bacteria. Following preliminary studies, 5% (w/v) sodium caseinate (SC) and (5%, w/v) potato starch (PS), with and without (0.5%, w/v) ascorbic acid (AA) were selected. Ninety crabs (30 per treatment) were soaked and boiled in water (control 1), AA (control 2), SC, PS, SC plus AA, or PS plus AA and analyzed for cook loss as well as pH, aw, water holding capacity (WHC), and microbial shelf-life (total viable count (TVC), total Enterobacteriaceae count (TEC), and spoilage bacteria) during 28 days storage at 4 ◦ C. On average, 11.1% of the control 1 weight was lost during processing. This was reduced to 8.0% when treated with AA (control 2) and to 3.5%, 4.7%, 5.8%, and 2.3% with SC, PS, SC plus AA, and PS plus AA, respectively. None of these treatments negatively impacted on shelf-life and similar growth curves were observed for TVC, TEC, Pseudomonas spp., Clostridium spp., lactic acid bacteria (LAB), and hydrogen disulphide producing bacteria, regardless of treatment. It was therefore concluded that, subject to sensory evaluation and validation under commercial conditions, these natural ingredients could be used to substantially increase the yield and hence commercial value of crab meat, without adversely affecting shelf-life.Department of Agriculture, Food and the Marin

Metered Cryospray™: a novel uniform, controlled, and consistent in vivo application of liquid nitrogen cryogenic spray

Typically, wood-based composite materials have been developed through empirical studies. In these products, the constituent wood elements have broad spectrums regarding species, size, and anatomical orientation relative to their own dimensions. To define special strength and stiffness properties during a long-term study, two types of corrugated wood composite panels were developed for possible structural utilization. The constitutional elements of the newly developed products included Appalachian hardwood veneer residues (side clippings) and/or rejected low quality, sliced veneer sheets. The proposed primary usage of these veneer-based panels is in applications where the edgewise loading may cause buckling (e.g., web elements of I-joists, shear-wall and composite beam core materials). This paper describes the development of flat and corrugated panels, including furnish preparations and laboratory-scale manufacturing processes as well as the determination of key mechanical properties. According to the results in parallel to grain direction bending, tension and compression strengths exceeded other structural panels’ similar characteristics, while the rigidities were comparable. Based on the research findings, sliced veneer clipping waste can be transformed into structural panels or used as reinforcement elements in beams and sandwich-type products

Rapid identification of human muscle disease with fibre optic Raman spectroscopy

The diagnosis of muscle disorders (“myopathies”) can be challenging and new biomarkers of disease are required to enhance clinical practice and research. Despite advances in areas such as imaging and genomic medicine, muscle biopsy remains an important but time-consuming investigation. Raman spectroscopy is a vibrational spectroscopy application that could provide a rapid analysis of muscle tissue, as it requires no sample preparation and is simple to perform. Here, we investigated the feasibility of using a miniaturised, portable fibre optic Raman system for the rapid identification of muscle disease. Samples were assessed from 27 patients with a final clinico-pathological diagnosis of a myopathy and 17 patients in whom investigations and clinical follow-up excluded myopathy. Multivariate classification techniques achieved accuracies ranging between 71–77%. To explore the potential of Raman spectroscopy to identify different myopathies, patients were subdivided into mitochondrial and non-mitochondrial myopathy groups. Classification accuracies were between 74–89%. Observed spectral changes were related to changes in protein structure. These data indicate fibre optic Raman spectroscopy is a promising technique for the rapid identification of muscle disease that could provide real time diagnostic information. The application of fibre optic Raman technology raises the prospect of in vivo bedside testing for muscle diseases which would significantly streamline the diagnostic pathway of these disorders

A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

The twentieth century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and waterborne illnesses are frequent, multidrug-resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the twenty-first century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program, we think that the time is at hand to redefine the pathogen-host research paradigm

Visualising biological data: a semantic approach to tool and database integration

<p>Abstract</p> <p>Motivation</p> <p>In the biological sciences, the need to analyse vast amounts of information has become commonplace. Such large-scale analyses often involve drawing together data from a variety of different databases, held remotely on the internet or locally on in-house servers. Supporting these tasks are <it>ad hoc </it>collections of data-manipulation tools, scripting languages and visualisation software, which are often combined in arcane ways to create cumbersome systems that have been customised for a particular purpose, and are consequently not readily adaptable to other uses. For many day-to-day bioinformatics tasks, the sizes of current databases, and the scale of the analyses necessary, now demand increasing levels of automation; nevertheless, the unique experience and intuition of human researchers is still required to interpret the end results in any meaningful biological way. Putting humans in the loop requires tools to support real-time interaction with these vast and complex data-sets. Numerous tools do exist for this purpose, but many do not have optimal interfaces, most are effectively isolated from other tools and databases owing to incompatible data formats, and many have limited real-time performance when applied to realistically large data-sets: much of the user's cognitive capacity is therefore focused on controlling the software and manipulating esoteric file formats rather than on performing the research.</p> <p>Methods</p> <p>To confront these issues, harnessing expertise in human-computer interaction (HCI), high-performance rendering and distributed systems, and guided by bioinformaticians and end-user biologists, we are building reusable software components that, together, create a toolkit that is both architecturally sound from a computing point of view, and addresses both user and developer requirements. Key to the system's usability is its direct exploitation of semantics, which, crucially, gives individual components knowledge of their own functionality and allows them to interoperate seamlessly, removing many of the existing barriers and bottlenecks from standard bioinformatics tasks.</p> <p>Results</p> <p>The toolkit, named Utopia, is freely available from <url>http://utopia.cs.man.ac.uk/</url>.</p