Inflammation and tissue repair markers distinguish the nodular sclerosis and mixed cellularity subtypes of classical Hodgkin's lymphoma

Background: Classical Hodgkin's lymphoma (cHL), although a malignant disease, has many features in common with an inflammatory condition. The aim of this study was to establish the molecular characteristics of the two most common cHL subtypes, nodular sclerosis (NS) and mixed cellularity (MC), based on molecular profiling and immunohistochemistry, with special reference to the inflammatory microenvironment. Methods: We analysed 44 gene expression profiles of cHL whole tumour tissues, 25 cases of NS and 19 cases of MC, using Affymetrix chip technology and immunohistochemistry. Results: In the NS subtype, 152 genes showed a significantly higher expression, including genes involved in extracellular matrix (ECM) remodelling and ECM deposition similar to wound healing. Among these were SPARC, CTSK and COLI. Immunohistochemistry revealed that the NS-related genes were mainly expressed by macrophages and fibroblasts. Fifty-three genes had a higher expression in the MC subtype, including several inflammation-related genes, such as C1Qα, C1Qβ and CXCL9. In MC tissues, the C1Q subunits were mainly expressed by infiltrating macrophages. Conclusions and interpretations: We suggest that the identified subtype-specific genes could reflect different phases of wound healing. Our study underlines the potential function of infiltrating macrophages in shaping the cHL tumour microenvironment

Exploring the cultural dimensions of environmental victimization

It has become increasingly clear in recent years that our understanding of ‘victimisation’ is informed by a whole range of societal and political factors which extend well beyond whatever particular form of words appears in any given directive, code or legislative instrument concerning crime, crime victims or criminal justice systems. In this paper, I will seek for the first time to apply recent developments in our understanding of so-called 'cultural victimology' to the issue of environmental harm and its impact on human and non-human animals. McCGarry and Waklate (2015) characterise cultural victimology as broadly comprising of two key aspects. These are the wider sharing and reflection of individual and collective victimisation experiences on the one hand and, on the other, the mapping of those experiences through the criminal justice process. In this discussion I will examine how environmental victimisation is viewed by and presented to society at large and will argue that such representations often fail, as a form of testimony, to adequately convey the traumas involved. Nor is this achieved through the application of present models of criminal, civil or administrative justice regimes in many jurisdictions. This lack of cultural acknowledgement of the harms vested on environmental victims, it is argued, afford us a clearer understand of the continued reticence amongst lawmakers, politicians and legal practitioners to adequately address the impacts of such victimisation through effective justice or regulatory mechanisms. This is unfortunate given that the often collective nature of environmental victimisation makes this particularly suited to a more cultural analysis and understanding. It is argued that various forms of environmental mediation processes might hold the key to this cultural reticence to accept environmental harm as a 'real' and pressing problem as compared to other criminal and civil justice concerns

Criminal redress in cases of environmental victimisation: a defence

In recent years growing concern has been voiced in the environmental justice literature regarding the ability of criminal justice mechanisms to adequately address environmental harms, especially when such harms are perpetrated by large corporations. Commentators argue that criminal justice processes are often ill-suited to the particular features of environmental cases, where the chain of causation between wrongful actions/omissions and environmentally harmful consequence can be very complex and extend over the course of many years. As an alternative, many such commentators now favour the adoption of more administrative resolutions when corporate bodies breach their environmental obligations (which may or may not amount to ‘crimes’). Others favour the use of civil sanction regimes, which is now the preferred approach of the UK Environment Agency. In this paper I will argue that the debate on how best to respond to environmental harm has so far neglected to factor in the perspective of the victims of those harms and, in particular, their need for redress. I will argue that by incorporating such a perspective, as opposed to focusing largely on questions of efficiency and cost-effectiveness, the criminal justice route still has much to recommended it, especially in relation to the provision of meaningful redress and/or compensation to the victims of environmental harm. Consequently, this paper will provide a victimological defence of the criminal justice process, and of criminal penalties, in their application to cases of environmental harms

Immunosenescence and lymphomagenesis

One of the most important determinants of aging-related changes is a complex biological process emerged recently and called \u201cimmunosenescence\u201d. Immunosenescence refers to the inability of an aging immune system to produce an appropriate and effective response to challenge. This immune dysregulation may manifest as increased susceptibility to infection, cancer, autoimmune disease, and vaccine failure. At present, the relationship between immunosenescence and lymphoma in elderly patients is not defined in a satisfactory way. This review presents a brief overview of the interplay between aging, cancer and lymphoma, and the key topic of immunosenescence is addressed in the context of two main lymphoma groups, namely Non Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL). Epstein Barr Virus (EBV) plays a central role in the onset of neoplastic lymphoproliferation associated with immunological changes in aging, although the pathophysiology varies vastly among different disease entities. The interaction between immune dysfunction, immunosenescence and Epstein Barr Virus (EBV) infection appears to differ between NHL and HL, as well as between NHL subtypes

Environmental harm and environmental victims: scoping out a ‘green victimology'

In this paper I intend to discuss the adaptability of victimological study to the question of ‘environmental victimisation’. The impact on those affected by environment crime, or other environmentally damaging activities, is one that has received scarce attention in the mainstream victimological literature (see Williams, 1996). The role or position of such victims in criminal justice and/or other processes has likewise rarely been topic of academic debate. I have recently expanded upon various aspects of this subject and surrounding issues at greater length (Hall, 2013) but for the purposes of this article I wish to expand specifically on what a so-called ‘green victimology’ might look like, together with some of the particular questions and challenges it will face

Deep Learning-Enabled MS/MS Spectrum Prediction Facilitates Automated Identification Of Novel Psychoactive Substances.

The market for illicit drugs has been reshaped by the emergence of more than 1100 new psychoactive substances (NPS) over the past decade, posing a major challenge to the forensic and toxicological laboratories tasked with detecting and identifying them. Tandem mass spectrometry (MS/MS) is the primary method used to screen for NPS within seized materials or biological samples. The most contemporary workflows necessitate labor-intensive and expensive MS/MS reference standards, which may not be available for recently emerged NPS on the illicit market. Here, we present NPS-MS, a deep learning method capable of accurately predicting the MS/MS spectra of known and hypothesized NPS from their chemical structures alone. NPS-MS is trained by transfer learning from a generic MS/MS prediction model on a large data set of MS/MS spectra. We show that this approach enables a more accurate identification of NPS from experimentally acquired MS/MS spectra than any existing method. We demonstrate the application of NPS-MS to identify a novel derivative of phencyclidine (PCP) within an unknown powder seized in Denmark without the use of any reference standards. We anticipate that NPS-MS will allow forensic laboratories to identify more rapidly both known and newly emerging NPS. NPS-MS is available as a web server at https://nps-ms.ca/, which provides MS/MS spectra prediction capabilities for given NPS compounds. Additionally, it offers MS/MS spectra identification against a vast database comprising approximately 8.7 million predicted NPS compounds from DarkNPS and 24.5 million predicted ESI-QToF-MS/MS spectra for these compounds

Differential expression of a new isoform of DLG2 in renal oncocytoma

BACKGROUND: Renal oncocytoma, a benign tumour of the kidney, may pose a differential diagnostic problem due to overlapping phenotype with chromophobe renal cell carcinoma or other types of renal cell tumours. Therefore, identification of molecular markers would be of great value for molecular diagnostics of this tumour type. METHODS: In the current study we applied various techniques, including Affymetrix microarray hybridization and semiquantitative RT-PCR, to identify genes expressed differentially in renal oncocytomas. Subsequently, we used RACE and Northern blot hybridization to characterize the potential candidates for molecular diagnosis. RESULTS: We have identified new isoform of DLG2 gene, which contains 3'-end exons of the known DLG2 gene along with the hypothetical gene FLJ37266. The new isoform is specifically upregulated in renal oncocytoma, whereas the known DLG2 gene is downregulated in this type of kidney tumour. CONCLUSION: The new isoform of DLG2 is the promising candidate gene for molecular differential diagnostics of renal oncocytoma

Chromophobe renal cell cancer - review of the literature and potential methods of treating metastatic disease

Chromophobe renal cell carcinoma (ChRCC) is a subtype of renal cell carcinoma (RCC). ChRCC is diagnosed mainly in 6th decade of life. An incidence of ChRCC is similar in both men and woman. Eighty six percent of ChRCCs cases are diagnosed in stage 1 or 2. Prognosis of ChRCC is better than in other types of RCC. Five- and 10-year disease free survival (DFS) for ChRCC was 83.9% and 77.9%, respectively. Expression of immunohistological markers: cytokeratins (CK), vimentin, epithelial membrane antigen (EMA), CD10 could be potentially helpful in diagnosis of different subtypes of RCC. From all conventional RCC, CD 117 was detected (overexpression) in membrane of cells ChRCC

Small Interfering RNA against Transcription Factor STAT6 Leads to Increased Cholesterol Synthesis in Lung Cancer Cell Lines

STAT6 transcription factor has become a potential molecule for therapeutic intervention because it regulates broad range of cellular processes in a large variety of cell types. Although some target genes and interacting partners of STAT6 have been identified, its exact mechanism of action needs to be elucidated. In this study, we sought to further characterize the molecular interactions, networks, and functions of STAT6 by profiling the mRNA expression of STAT6 silenced human lung cells (NCI-H460) using microarrays. Our analysis revealed 273 differentially expressed genes after STAT6 silencing. Analysis of the gene expression data with Ingenuity Pathway Analysis (IPA) software revealed Gene expression, Cell death, Lipid metabolism as the functions associated with highest rated network. Cholesterol biosynthesis was among the most enriched pathways in IPA as well as in PANTHER analysis. These results have been validated by real-time PCR and cholesterol assay using scrambled siRNA as a negative control. Similar findings were also observed with human type II pulmonary alveolar epithelial cells, A549. In the present study we have, for the first time, shown the inverse relationship of STAT6 with the cholesterol biosynthesis in lung cancer cells. The present findings are potentially significant to advance the understanding and design of therapeutics for the pathological conditions where both STAT6 and cholesterol biosynthesis are implicated viz. asthma, atherosclerosis etc