Prostate transglutaminase (TGase-4) antagonizes the anti-tumour action of MDA-7/IL-24 in prostate cancer

Background Transglutamiase-4 (TGase-4), also known as prostate transglutaminase, belongs to the TGase family and is uniquely expressed in the prostate gland. The functions of this interesting protein are not clearly defined. In the present study, we have investigated an unexpected link between TGase-4 and the melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24), a cytokine known to regulate the growth and apoptosis of certain cancer and immune cells. Methods Frozen sections of normal and malignant human prostate tissues and human prostate cancer (PCa) cell lines PC-3 and CA-HPV-10, cell lines expressing low and high levels of TGase-4, and recombinant MDA-7/IL-24 (rhMDA-7/IL-24) were used. Expression construct for human TGase-4 was generated using a mammalian expression vector with full length human TGase-4 isolated from normal human prostate tissues. PC-3 cells were transfected with expression construct or control plasmid. Stably transfected cells for control transfection and TGase-4 over expression were created. Similarly, expression of TGase-4 in CA-HPV-10 cells were knocked down by way of ribozyme transgenes. Single and double immunofluorescence microscopy was used for localization and co-localization of TGase-4 and MDA-7/IL-24 in PCa tissues and cells with antibodies to TGase-4; MDA-7/IL-24; IL-20alpha; IL-20beta and IL-22R. Cell-matrix adhesion, attachment and migration were by electric cell substrate impedance sensing and growth by in vitro cell growth assay. A panel of small molecule inhibitors, including Akt, was used to determine signal pathways involving TGase-4 and MDA-7/IL-24. Results We initially noted that MDA-7 resulted in inhibition of cell adhesion, growth and migration of human PCa PC-3 cells which did not express TGase-4. However, after the cells over-expressed TGase-4 by way of transfection, the TGase-4 expressing cells lost their adhesion, growth and migratory inhibitory response to MDA-7. On the other hand, CA-HPV-10 cells, a cell type naturally expressing high levels of TGase-4, had a contrasting response to MDA-7 when compared with PC-3 cells. Inhibitor to Akt reversed the inhibitory effect of MDA-7, only in PC-3 control cells, but not the TGase-4 expressing PC-3 cells. In human prostate tissues, TGase-4 was found to have a good degree of co-localization with one of the MDA-7 receptor complexes, IL-20Ra. Conclusion The presence of TGase-4 has a biological impact on a prostate cancer cell's response to MDA-7. TGase-4, via mechanism(s) yet to be identified, blocked the action of MDA-7 in prostate cancer cells. This has an important implication when considering the use of MDA-7 as a potential anticancer cytokine in prostate cancer therapies

The impact of paratracheal lymph node metastasis in squamous cell carcinoma of the hypopharynx

The aim of this study was to analyze the prevalence and prognostic importance of paratracheal lymph nodes in squamous cell carcinoma of the hypopharynx. A retrospective review of 64 previously untreated patients with squamous cell carcinoma (SCC) of the hypopharynx that underwent surgery was performed. Ipsilateral paratracheal lymph node metastases occurred in 22% (14 out of 64) and the mean number of paratracheal lymph nodes dissected per side was 2.3 (range 1–6). Contralateral paratracheal lymph node metastases were present in 2% (1 out of 42). Sixty-seven percent with postcricoid SCC and 22% with pyriform sinus SCC developed clinical node-positive ipsilateral paratracheal lymph node metastases, whereas 11% with posterior pharyngeal wall SCC developed paratracheal metastases. There was a significant correlation between paratracheal lymph node metastasis and cervical metastasis (p = 0.005), and the primary tumor site (postcricoid, 57.1%; pyriform sinus, 20.0%; posterior pharyngeal wall, 8.3%) (p = 0.039). Patients with no evidence of paratracheal lymph node metastasis may have a survival benefit (5-year disease-specific survival rate, 60 vs. 29%). However, this result did not reach statistical significance (p = 0.071). The patients with SCC of the postcricoid and/or pyriform sinus were at risk for ipsilateral paratracheal lymph node metastasis; furthermore, patients with paratracheal node metastasis had a high frequency of cervical metastasis and a poorer prognosis. Therefore, routine ipsilateral paratracheal node dissection is recommended during the surgical treatment of patients with SCC of the postcricoid and/or pyriform sinus with clinical node metastases

Effect of Grain Size and Shape on Undrained Behaviour of Sands

The stress–strain and stress path characteristics of sands are influenced by their grain size, shape, and packing. Morphological characteristics and size of particles play important role on the undrained shear strength of sands. Often, effects of these parameters are complex and cannot be easily distinguished. This study advances the knowledge of the role of particle size and shape on the undrained shear strength of sands. To eliminate the consequence of morphological characteristics, two sands with different particle sizes but similar angularity, and another sand with different roundness were selected for the study. These morphological characteristics for all three sands were determined from the analysis of scanning electron microscope images. F131 sand with higher median grain size and lower shape factors (rᵣ and rₛ) had highest undrained peak shear strength and phase transformation value. Undrained strength (qₚₜ) and effective principal stress (P′ₚₜ) in phase transformation point had direct relationship with grain median grain size (D₅₀) and inversely effect of shape factor (rᵣ and rₛ). F131 and F161 sands represented highest peak and ultimate steady-state strengths, respectively. Flow potential appeared to be directly proportional with (rᵣ and rₛ) and inversely with D₅₀. The peak index decreased with increasing shape factors (rᵣ and rₛ)

Allah n'est pas obligé d'Ahmadou Kourouma: Une gymnastiquie langagière

Avec seulement quatre romans publiés en vingt-quatre ans, Ahmadou Kourouma s'est imposé comme l'un des écrivains les plus importants du conti- nent africain. Dans ses romans: Les soleils des Indépendances (1976), Monné, outrages et défis (1990), En attendant le vote des bêtes sauvages (1999) et Allah n'est pas obligé (2000), l'écrivain ivoirien dénonce les souffrances de l' Afrique noire. Il les dénonce avec les yeux des Africains et les décrit dans une langue calquée sur la leur. En effet, son style étonne, choque, séduit. Kourouma ne s'est pas contenté de «penser la langue»comme tout autre écrivain francophone; son oeuvre ne témoigne pas seulement d'une sorte d'hétérogénéité langagière comme c'est le cas en général chez les écrivains qui vivent le conflit des langues et des cultures; il est allé plus loin. Sa grande innovation comme dit si bien l'un des chercheurs, «réside dans le fait de proposer une oeuvre dont le protagoniste est à tout considérer le style-oui, le style malinké transposé en français

Climate social science—Any future for ‘blue sky research’ in management studies?

Summary The environmental humanities call for post-disciplinary approaches to meet the vexing problem of climate change. However, scholars have not scrutinised how management and organisation studies (MOS) could contribute to such an endeavour. This research note explores common surfaces of contact between the natural and social sciences, with the goal of unravelling the legitimate positions to speak from about climate change. The findings suggest that scholars in MOS are exposed to ecological reasoning, which undergirds underdog heroism, disciplinary confusion and a debasement of political subjectivity. As a counter strategy, I suggest that we affirm a ‘blue-sky research’ approach that would support alternative research paths and a more traditional will to know—to advance ‘climate social science’

Switchable Gene Expression in Escherichia coli Using a Miniaturized Photobioreactor

We present a light-switchable gene expression system for both inducible and switchable control of gene expression at a single cell level in Escherichia coli using a previously constructed light-sensing system. The lambda cl repressor gene with an LVA degradation tag was expressed under the control of the ompC promoter on the chromosome. The green fluorescent protein (GFP) gene fused to a lambda repressor-repressible promoter was used as a reporter. This light-switchable system allows rapid and reversible induction or repression of expression of the target gene at any desired time. This system also ensures homogenous expression across the entire cell population. We also report the design of a miniaturized photobioreactor to be used in combination with the light-switchable gene expression system. The miniaturized photobioreactor helps to reduce unintended induction of the light receptor due to environmental disturbances and allows precise control over the duration of induction. This system would be a good tool for switchable, homogenous, strong, and highly regulatable expression of target genes over a wide range of induction times. Hence, it could be applied to study gene function, optimize metabolic pathways, and control biological systems both spatially and temporally.open0