Recent advancements in cancer immunotherapeutics

Cancer affects a wide range of organs and tissues within the body and epidemiologically is forecasted to affect almost half of the world's population. As an industry, cancer therapeutics represent a booming field. Standard treatment options, however, still heavily rely upon chemotherapeutics developed over fifty years ago. The past decade has seen a huge proliferation of different types of cancer drugs. Recently, an entirely new class of drugs has been unveiled and holds promising results of preventing further relapse incidents. Immunotherapeutics come in many varieties and currently several strategies are under intense investigation. Because these drugs harness the body's own immune system to specifically attack tumor cells, these drugs hold an advantage to current therapeutic options in that they induce notably less severe side effects, facilitating patients' abilities to maintain quality of life. In addition, these drugs potentially hold the promise to cure certain types of cancer, as the body's memory T cells will prevent relapse of the same tumor type. This review will focus on dendritic cell-based therapies, which attempt to program these antigen-presenting cell types to prime T cell responses, checkpoint blockade drugs that inhibit immunosuppression, and neoadjuvants that aim to render the surrounding tumor microenvironment more susceptible for immune attack. In addition, some documented and projected downsides to immunotherapeutics will be discussed, as well as the need to combine multiple modalities in order to create an effective and personalized treatment regimen for cancer patients

GEN MS 14 September 11th Collection Finding Aid

Description: The newspapers were acquired by the Library by subscription and gathered into this collection by the Head of Special Collections following the events of September 11th. The Collection consists of hard copies of Maine newspapers to document how the events were covered in Maine, and a remembrance ribbon, presumably produced during USM’s 2002 Remembrance events. Date Range: 2001-2002 Size of Collection: 3 ft

Perceptions of HIV/AIDS in One’s Community Predict HIV Testing

ABSTRACT: Using a subsample of respondents to the 2005 Los Angeles County health survey, we examined the relationship between perceptions of the seriousness of HIV/AIDS in one’s community and HIV testing. We constructed a propensity score-based matched sample of three groups with differing perceptions of the seriousness of HIV in their community: high perceived seriousness, low perceived seriousness, and uncertain about seriousness. We compared HIV testing behavior in the three groups before and after using propensity score matching to control for selection on observed covariates. The unadjusted comparison showed a testing rate of 30.2 % among those perceiving high seriousness, 11.4 percentage points higher than the 18.8 % testing rate among those perceiving low seriousness. After propensity score matching, the adjusted testing difference was 7.0 percentage points (p < 0.05). Those uncertain about the seriousness of HIV did not differ significantly in their testing behavior from those perceiving high seriousness

Kindlin-2 is required for myocyte elongation and is essential for myogenesis

<p>Abstract</p> <p>Background</p> <p>Integrins are required for normal muscle differentiation and disruptions in integrin signaling result in human muscle disease. The intracellular components that regulate integrin function during myogenesis are poorly understood. Unc-112 is an integrin-associated protein required for muscle development in C. elegans. To better understand the intracellular effectors of integrin signaling in muscle, we examined the mammalian homolog of Unc-112, kindlin-2.</p> <p>Results</p> <p>Kindlin-2 expression is upregulated during differentiation and highly enriched at sites of integrin localization. RNAi knockdown of kindlin-2 in C2C12 cells results in significant abnormalities during the early stages of myogenesis. Specifically, differentiating myocytes lacking kindlin-2 are unable to elongate and fail to fuse into multinucleated myotubes. These changes are correlated with decreased cell substratum adhesion and increased cell motility. They are also associated with redistribution of a known kindlin-2 binding partner, integrin linked kinase (ILK), to the membrane insoluble subcellular fraction.</p> <p>Conclusion</p> <p>In all, our study reveals kindlin-2 as a novel integrin adaptor protein important for muscle differentiation, and identifies it particularly as a critical regulator of myocyte elongation.</p

Experiences of imagery‐based treatment for anxiety in bipolar disorder: A qualitative study embedded within the image based emotion regulation feasibility randomised controlled trial

Objectives: Intrusive mental imagery is associated with anxiety in bipolar disorder (BD) and presents a novel treatment target. Imagery‐based treatments show promise in targeting anxiety and improving mood instability. This qualitative study explored experiences of receiving up to 12 sessions of a brief structured psychological intervention: Image‐Based Emotion Regulation (IBER), which targets maladaptive mental imagery in the context of BD with an aim to modify the emotional impact of these images. Design: A qualitative study embedded within the Image Based Emotion Regulation (IBER) feasibility randomised controlled trial. Methods: Semi‐structured interviews were conducted with 12 participants in the treatment arm of the trial who received IBER + treatment as usual. Data were analysed using thematic analysis. Results: Despite some initial scepticism about imagery‐focused treatment, all participants expressed broadly positive accounts of treatment experiences. High levels of engagement with imagery modification techniques, beneficial use of techniques post treatment and improvements in anxiety management and agency were described by some. Three sub‐groups were identified: those who reported a powerful transformative impact of treatment; those who embedded some new techniques into their daily lives, and those who felt they had techniques to use when needed. No participants reported overall negative experiences of the IBER treatment. Conclusions: Findings from this study highlight the value for treatment recipients of modifying the underlying meanings associated with maladaptive imagery, and the personalised skills development to manage anxiety within bipolar disorders. Findings can inform treatment refinements and further trial‐based evaluations

The IBER study: study protocol for a feasibility randomised controlled trial of Imagery Based Emotion Regulation for the treatment of anxiety in bipolar disorder.

BACKGROUND: Anxiety is highly prevalent in people diagnosed with bipolar disorder (BD), and can persist between acute episodes of mania and depression. Recent studies indicate that people with BD are prone to experiencing frequent, intrusive and emotional mental images which further fuel their levels of anxiety and mood instability. These intrusive emotional mental images represent a specific target for treatment for this disorder with the potential to reduce anxiety and improve mood stability. A new brief structured psychological intervention for BD called Imagery Based Emotion Regulation (IBER) has been developed, which translates experimental work in the area of imagery and emotion into a skills training programme to improve the regulation of intrusive and distressing emotional mental images in BD. A feasibility trial is required in order to assess whether a full randomised controlled trial is indicated in order to evaluate this approach. METHODS: The design is a two-arm feasibility randomised controlled trial (RCT), with 1:1 randomisation stratified by trial site and minimised on medication status and anxiety severity. Participants are 60 individuals diagnosed with bipolar disorder and experiencing at least a mild level of anxiety. Sites are defined by the geographical boundaries of two National Health Service (NHS) Trusts, with recruitment from NHS teams, GP surgeries and self-referral. The intervention is up to 12 sessions of Imagery Based Emotion Regulation within 16 weeks. The comparator is NHS standard care. The primary aim is to assess the feasibility of conducting a powered multi-site RCT to evaluate effectiveness. Measures of anxiety, depression, mania, mood stability and health care use will be conducted at baseline, end of treatment and at 16-week follow-up. DISCUSSION: This is the first feasibility trial of an imagery-based intervention for the treatment of anxiety in bipolar disorder. If the trial proves feasible, a large multi-site trial will be required. TRIAL REGISTRATION: ISRCTN16321795. Registered on October 16, 2018. 10.1186/ISRCTN16321795

Stop Using That: Expressing Definiteness in Korean

Definiteness is visibly expressed by definite articles in English, but some languages such as Korean lack this morphological exponent. However, speakers of such languages still mark definiteness in different ways. In this proposal, we lay out a study that examines the (re)assembly required by L1-English L2-Korean learners where the formal feature of definiteness in the L1 has to be readjusted to indirect expressions in the L2. In particular, we propose to examine how L1-English learners distinctly interpret and produce the feature [definite] that has been coded overtly (demonstrative determiners) and covertly (word order change) in Korean. The participants’ use of demonstrative and word order will be examined by using elicited production tasks and forced-choice selection tasks. We predict that the participants will perform more accurately on the demonstratives. We further hope to gain insights into how much detection, mapping, and reassembly of the linguistic feature have progressed through the experiments

Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia

Disrupted synchronized oscillatory firing of pyramidal neuronal networks in the cerebral cortex in the gamma frequency band (i.e., 30–100 Hz) mediates many of the cognitive deficits and symptoms of schizophrenia. In fact, the density of dendritic spines and the average somal area of pyramidal neurons in layer 3 of the cerebral cortex, which mediate both long-range (associational) and local (intrinsic) corticocortical connections, are decreased in subjects with this illness. To explore the molecular pathophysiology of pyramidal neuronal dysfunction, we extracted ribonucleic acid (RNA) from laser-captured pyramidal neurons from layer 3 of Brodmann’s area 42 of the superior temporal gyrus (STG) from postmortem brains from schizophrenia and normal control subjects. We then profiled the messenger RNA (mRNA) expression of these neurons, using microarray technology. We identified 1331 mRNAs that were differentially expressed in schizophrenia, including genes that belong to the transforming growth factor beta (TGF-β) and the bone morphogenetic proteins (BMPs) signaling pathways. Disturbances of these signaling mechanisms may in part contribute to the altered expression of other genes found to be differentially expressed in this study, such as those that regulate extracellular matrix (ECM), apoptosis, and cytoskeletal and synaptic plasticity. In addition, we identified 10 microRNAs (miRNAs) that were differentially expressed in schizophrenia; enrichment analysis of their predicted gene targets revealed signaling pathways and gene networks that were found by microarray to be dysregulated, raising an interesting possibility that dysfunction of pyramidal neurons in schizophrenia may in part be mediated by a concerted dysregulation of gene network functions as a result of the altered expression of a relatively small number of miRNAs. Taken together, findings of this study provide a neurobiological framework within which specific hypotheses about the molecular mechanisms of pyramidal cell dysfunction in schizophrenia can be formulated

Distinctions in gastric cancer gene expression signatures derived from laser capture microdissection versus histologic macrodissection

<p>Abstract</p> <p>Background</p> <p>Gastric cancer samples obtained by histologic macrodissection contain a relatively high stromal content that may significantly influence gene expression profiles. Differences between the gene expression signature derived from macrodissected gastric cancer samples and the signature obtained from isolated gastric cancer epithelial cells from the same biopsies using laser-capture microdissection (LCM) were evaluated for their potential experimental biases.</p> <p>Methods</p> <p>RNA was isolated from frozen tissue samples of gastric cancer biopsies from 20 patients using both histologic macrodissection and LCM techniques. RNA from LCM was subject to an additional round of T7 RNA amplification. Expression profiling was performed using Affymetrix HG-U133A arrays. Genes identified in the expression signatures from each tissue processing method were compared to the set of genes contained within chromosomal regions found to harbor copy number aberrations in the tumor samples by array CGH and to proteins previously identified as being overexpressed in gastric cancer.</p> <p>Results</p> <p>Genes shown to have increased copy number in gastric cancer were also found to be overexpressed in samples obtained by macrodissection (LS <it>P </it>value < 10^-5), but not in array data generated using microdissection. A set of 58 previously identified genes overexpressed in gastric cancer was also enriched in the gene signature identified by macrodissection (LS <it>P </it>< 10^-5), but not in the signature identified by microdissection (LS <it>P </it>= 0.013). In contrast, 66 genes previously reported to be underexpressed in gastric cancer were enriched in the gene signature identified by microdissection (LS <it>P </it>< 10^-5), but not in the signature identified by macrodissection (LS <it>P </it>= 0.89).</p> <p>Conclusions</p> <p>The tumor sampling technique biases the microarray results. LCM may be a more sensitive collection and processing method for the identification of potential tumor suppressor gene candidates in gastric cancer using expression profiling.</p