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Abstract: Metastasis of primary tumors to distant sites and their inherent or acquired resistance to currently available therapies pose major clinical challenge to the successful treatment of cancer. The identification of tumor-coded genes and how they contribute to the progression of cancer is required to improve patient outcomes. Recently, cells that have undergone the epithelial–mesenchymal transition (EMT), which share characteristics with cancer stem cells (CSC) have been implicated to play a role in drug resistance and metastasis of several types of cancer. In this review, we discuss the relationship among transglutaminase 2 (TG2), the EMT, and CSCs in inflammation and cancer. TG2 is a structurally and functionally complex protein implicated in such diverse processes as tissue fibrosis, wound healing, apoptosis, neurodegenerative disorders, celiac disease, atherosclerosis and cancer. Depending on the cellular context, TG2 can either promote or inhibit cell death. Increased expression of TG2 in several types of cancer cells has been associated with increased cell invasiveness, cell survival and decreased survival of patients with cancer. Down-regulation of TG2 by small interfering RNA (siRNA) or its inhibition by small molecule inhibitors has been shown to significantly enhances the therapeutic efficacy of anticancer drugs and inhibit metastatic spread. In addition, TG2-regulated pathways are involved in promoting or protecting normal and tumor cells from death-induced signaling. We discuss the contribution of TG2-regulated pathways to the development of drug resistance and progression to metastatic disease and the therapeutic potential of TG2 for treating advanced-stage cancer. [ABSTRACT FROM AUTHOR]

Abstract: Drug resistance and metastasis are major impediments for the successful treatment of cancer. A common feature among drug resistant and metastatic tumor cells is that they exhibit profound resistance to apoptosis. This property enables cancer cells not only to grow and survive in stressful environments (metastasis) but also to display resistance against many anticancer agents. Therefore, perturbation of the intrinsic apoptotic pathways of cancer cells will affect their ability to respond to chemotherapy and to metastasize and survive in distant sites. Recent studies have demonstrated that cancer cells and cancer cell lines selected for resistance against chemotherapeutic drugs or isolated from metastatic sites, express elevated levels of the multifunctional protein, tissue transglutaminase (TG2). TG2 is the most diverse and ubiquitous member of the transglutaminase family of proteins that is implicated to play a role in apoptosis, wound healing, cell migration, cell attachment, cell growth, angiogenesis, and matrix assembly. TG2 can associate with certain β members of the integrin family of proteins (β1, β3, β4, and β5) and promote stable interaction between cells and the extracellular matrix (ECM), resulting in increased cell survival, cell migration, and invasion. Additionally, TG2 forms a ternary complex with IκB/p65:p50 and results in constitutive activation of the nuclear transcription factor-κB (NF-κB). Moreover, TG2 expression in cancer cells leads to constitutive activation of the focal adhesion kinase (FAK) and its downstream PI3K/Akt survival pathway. Importantly, the inhibition of endogenous TG2 by small interfering RNA (siRNA) resulted in the reversal of drug resistance and the invasive phenotype. Conversely, ectopic expression of TG2 promoted cell survival, cell motility and invasive functions of cancer cells. This review discusses the current thinking and implications of increased TG2 expression in development of drug resistance and metastasis by cancer cells. [Copyright &y& Elsevier]

Abstract: All-trans retinoic acid (RA) treatment of patients with acute promyelocytic leukemia (APL) induces complete remission in more than 90% of the cases. Although RA therapy is well tolerated, about 25% of APL patients develop a potentially fatal condition called retinoic acid syndrome (RAS). Molecular mechanisms underlying the development of RAS pathogenesis, especially those that result in the damage of endothelial cells remain elusive. In the present study, we found that RA treatment induces the expression of interferon-γ (IFN-γ) and interleukin-1β (IL-1β) in peripheral blast cells from APL patients. IFN-γ and IL-1β also exerted synergistic effect in driving human umbilical cord endothelial cells (HUVECs) and human lung microvascular endothelial cells (HLMVECs) into apoptosis. RA also upregulated the expression of CD38, an ectoenzyme responsible for the generation of the calcium messenger cyclic ADP-ribose. Importantly, RA-induced CD38 expression promoted strong attachment of leukemia cells to endothelial cells, and incubation of endothelial cells with either high concentration (100ng/ml) of IFN-γ alone or low concentration of IL-1β and IFN-γ (10ng/ml, each) induced strong apoptotic responses as revealed by caspase-8 activation and DNA fragmentation. Our results suggest that these RA-induced events could contribute to the development of RAS pathogenesis in patients with APL. [Copyright &y& Elsevier]

• The study suggested a sustainable biomass-derived sintering process. • An acceptable 10% substitution by raw biomass and 30% by wood charcoal. • An optimal replacement of 30% coke by sawdust and charcoal combined. • A negative response for 100% coke substitution by biomass. • Monitoring of the sintering indices for coke and biomass-based sintering process. This study investigates the sintering behavior of iron ore and its modification regarding the conventional and alternative fuel delivery systems. The modification aims to find an established alternative source of fuel for sintering which would be greener and cleaner. In the process, it will additionally facilitate the development of sustainable technology for cleaner production. The novel strategy mentioned here depends on biomass for heating and reduction purposes. Even though biomass is yet to be validated as a fuel source, there have been widespread research activities across the globe on its usage and efficacy as an alternate fuel source. Previously, several experiments failed in developing the desired quality of sinter by complete substitution with biomass. In the present study, sintering was carried out with variable proportions of biomass and coke to seek out the optimum quantity of biomass that could effectively replace coke. It succeeded in replacing coke by 10% of sawdust, 30% of wood charcoal, and 30% by a combination of sawdust and charcoal. The temperature-time profile indicated the potential of charcoal to generate the maximum temperature in the shortest interval. An opposite response was recorded in the case of sawdust. Coke was found to generate a relatively lower temperature in a relatively long period as compared to charcoal. Sinter reducibility and strength properties were also examined during the present study to determine the technical feasibility of the suggested method. [ABSTRACT FROM AUTHOR]

Iron ore sintering is an energy-intensive process that converts iron ore fines into an agglomerated porous mass. Sintering plays a prominent pre-processing role in blast furnace smelting operations because of its unsuitability with finer ores. In recent years, the conventional sintering method using coke/coal is being gradually discarded due to environmental degradation. As a result, there is a need for extensive research on sustainable technologies and cleaner fuel sources with lesser carbon footprints. The recent trend is towards the use of biomass. Although biomass is carbon neutral and environmentally friendly energy source, its energy value is comparatively low and inferior. Nevertheless, biomass is emerging to be a viable alternative. In the present study, life cycle assessment has been carried out between the conventional and eco-friendly method of sintering to reveal comparative economic and environmental aspects. The assessment witnessed a 10% reduction in the production cost which is offered with biomass incorporation. Moreover, biomass addition ensured a reduction in emissive indices by 6% for COx, 15.25% for NOx and 20.79% for SOx. Although these reported values are only for the 30% biomass replacement and are subject to enhance with higher biomass proportions. Image 1 • Evolution of biomass-derived metallurgical sintering process. • Assessment of the conventional process for emission generation study. • LCA of the modified process comparative to the coal-based conventional process. • Carbon footprint reduction and production cost reduction. • Comparison of the footprint and the cost-effectiveness for both the processes. [ABSTRACT FROM AUTHOR]

Abstract: Many studies have supported a role for inflammation in prostate tumour growth. However, the contribution of inflammation to the development of castration-resistant prostate cancer remains largely unknown. Based on observations that aberrant expression of the proinflammatory protein tissue transglutaminase (TG2) is associated with development of drug resistance and metastatic phenotype in multiple cancer types, we determined TG2 expression in prostate cancer cells. Herein we report that human prostate cancer cell lines with low expression of androgen receptor (AR) had high basal levels of TG2 expression. Also, overexpression of TG2 negatively regulated AR mRNA and protein expression and attenuated androgen sensitivity of prostate cancer cells. TG2 expression in prostate cancer cells was associated with increased invasion and resistance to chemotherapy. Mechanistically, TG2 activated nuclear factor (NF)-κB and induced epithelial–mesenchymal transition. TG2/NF-κB-mediated decrease in AR expression resulted from transcriptional repression involving cis-interaction of NF-κB in a complex with TG2 with the 5′-untranslated region of AR. Negative regulation of AR could be partially abrogated by repression of TG2 or NF-κB (p65/RelA) by gene-specific small interfering RNA. These results suggested that a novel pathway links androgen dependence with TG2-regulated inflammatory signalling and hence may make TG2 a novel therapeutic target for the prevention and treatment of castration-resistant prostate cancer. [Copyright &y& Elsevier]