Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue malignant tumor. Treatment of RMS usually includes primary tumor resection along with systemic chemotherapy. Two-dimensional (2D) cell culture systems and animal models have been extensively used for investigating the potential efficacy of new RMS treatments. However, RMS cells behave differently in 2D culture than in vivo, which has recently inspired the adoption of three-dimensional (3D) culture environments. In the current paper, we will describe the detailed methodology we have developed for fabricating a 3D engineered model to study alveolar RMS (ARMS) in vitro. This model consists of a thermally cross-linked collagen disk laden with RMS cells that mimics the structural and bio-chemical aspects of the tumor extracellular matrix (ECM). This process is highly reproducible and produces a 3D engineered model that can be used to analyze the cytotoxicity and autophagy induction of drugs on ARMS cells. The most improtant bullet points are as following: We fabricated 3D model of ARMS. The current ARMS 3D model can be used for screening of chemotherapy drugs. We developed methods to detect apoptosis and autophagy in ARMS 3D model to detect the mechansims of chemotherapy agents.

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via changes to carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian cells that digests damaged organelles and misfolded proteins via lysosomal degradation is closely associated with metabolism in mammalian cells acting as a meter of cellular ATP levels. In this review, we discuss the changes in glycolytic and lipid biosynthetic pathways in mammalian cells and their impact on carcinogenesis via the autophagy pathway. Also, we discuss the impact of these metabolic pathways on autophagy in lung cancer.

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via changes to carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian cells that digests damaged organelles and misfolded proteins via lysosomal degradation, is closely associated with metabolism in mammalian cells, acting as a meter of cellular ATP levels. In this review, we discuss the changes in glycolytic and lipid biosynthetic pathways in mammalian cells and their impact on carcinogenesis via the autophagy pathway. In addition, we discuss the impact of these metabolic pathways on autophagy in lung cancer.

Background: Curcumin is a natural polyphenol and lead compound of the rhizomes of curcuma longa that it has been widely used for pharmacological activities. Objective: In this study, series of novel derivatives of curcumin, which this group was linked to a 2-amino-4-phenylpyran-3-carbonitrile system, have been synthesized and tested for their antitumor activities in-vitro against a panel of three human cancer cell lines (MCF-7, A2780, and U-87MG). Method: The in-vitro cytotoxic activity of the synthesized compounds was tested on three cancer cell lines (MCF-7, A2780, and U87MG) using MTT colorimetric assay. Meanwhile, the ability of the active compounds to induce apoptosis in cancer cells was investigated by examination of caspase-3 and caspase-9 and mitochondrial membrane potential assay. Results: Under relatively mild conditions in ethanol, the reaction of a series of substrates afforded the corresponding derivatives of curcumin mostly in good yields (13 analogues, 48-94% yields). Bioassay results indicated that compounds L6 (para-Bromo), L9 (paraNitro) and L12 (meta-Methoxy) were the most active members in this study demonstrating potent activities against A2780 cancer cells and experimental results of fluorescent staining and flow cytometry analysis revealed that L6 and L9 could induce apoptosis in A2780 cells with apoptosis ratios of about 40% and 46%, respectively at 24 h of treatment at 15.35 µM and 23µM in A2780 cells. On the other hand, they could increase the caspase-3 activity slightly (10%), while had no significant impact on the activities of caspase-9. Conclusion: Those two derivatives could be considered as useful templates for future development to obtain more potent antitumor agents.

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Synthesisand enzyme-based evaluation of analogues L-tyrosine thiol carboxylic acid inhibitor of metallo-βlactamase ABSTRACT The emergence of drug-resistant pathogenic bacteria is occurring due to the global overuse and misuse of b-lactam antibiotics. Infections caused by some bacteria which secrete metallo-b-lactamases (enzymes that inactivate b-lactam antibiotics) are increasingly prevalent and have become a major worldwide threat to human health. These bacteria are resistant to b-lactam antibiotics and MBL-inhibitor/b-lactam antibiotic combination therapy can be a strategy to overcome this problem. So far, no clinically available inhibitors of metallo-b-lactamases (MBLs) have been reported. In this study, L-benzyl tyrosine thiol carboxylic acid analogues (2a-2k) were synthesized after the study of computational simulation by adding of methyl, chloro, bromo and nitro groups to the benzyl ring for investigation of SAR analysis. Although the synthesized molecules 2a-k shows the potent inhibitory effects against metallo-b-lactamase (IMP-1) with the range of K ic values of 1.04-4.77 mM, they are not as potent as the candidate inhibitor.GRAPHICAL ABSTRACT ARTICLE HISTORY