An integrative transcriptome analysis reveals potential predictive, prognostic biomarkers and therapeutic targets in colorectal cancer.

BACKGROUND: A deep understanding of potential molecular biomarkers and therapeutic targets related to the progression of colorectal cancer (CRC) from early stages to metastasis remain mostly undone. Moreover, the regulation and crosstalk among different cancer-driving molecules including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs) in the transition from stage I to stage IV remain to be clarified, which is the aim of this study. METHODS: We carried out two separate differential expression analyses for two different sets of samples (stage-specific samples and tumor/normal samples). Then, by the means of robust dataset analysis we identified distinct lists of differently expressed genes (DEGs) for Robust Rank Aggregation (RRA) and weighted gene co-expression network analysis (WGCNA). Then, comprehensive computational systems biology analyses including mRNA-miRNA-lncRNA regulatory network, survival analysis and machine learning algorithms were also employed to achieve the aim of this study. Finally, we used clinical samples to carry out validation of a potential and novel target in CRC. RESULTS: We have identified the most significant stage-specific DEGs by combining distinct results from RRA and WGCNA. After finding stage-specific DEGs, a total number of 37 DEGs were identified to be conserved across all stages of CRC (conserved DEGs). We also found DE-miRNAs and DE-lncRNAs highly associated to these conserved DEGs. Our systems biology approach led to the identification of several potential therapeutic targets, predictive and prognostic biomarkers, of which lncRNA LINC00974 shown as an important and novel biomarker. CONCLUSIONS: Findings of the present study provide new insight into CRC pathogenesis across all stages, and suggests future assessment of the functional role of lncRNA LINC00974 in the development of CRC.

Eco-friendly synthesis of carbon nanotubes and their cancer theranostic applications.

Carbon nanotubes (CNTs) with attractive physicochemical characteristics such as high surface area, mechanical strength, functionality, and electrical/thermal conductivity have been widely studied in different fields of science. However, the preparation of these nanostructures on a large scale is either expensive or sometimes ecologically unfriendly. In this context, plenty of studies have been conducted to discover innovative methods to fabricate CNTs in an eco-friendly and inexpensive manner. CNTs have been synthesized using various natural hydrocarbon precursors, including plant extracts (e.g., tea-tree extract), essential oils (e.g., eucalyptus and sunflower oil), biodiesel, milk, honey, and eggs, among others. Additionally, agricultural bio-wastes have been widely studied for synthesizing CNTs. Researchers should embrace the usage of natural and renewable precursors as well as greener methods to produce various types of CNTs in large quantities with the advantages of cost-effectiveness and environmentally benign features. In addition, multifunctionalized CNTs with improved biocompatibility and targeting features are promising candidates for cancer theranostic applications owing to their attractive optical, chemical, thermal, and electrical properties. This perspective discusses the recent developments in eco-friendly synthesis of CNTs using green chemistry-based techniques, natural renewable resources, and sustainable catalysts, with emphasis on important challenges and future perspectives and highlighting techniques for the functionalization or modification of CNTs. Significant and promising cancer theranostic applications as well as their biocompatibility and cytotoxicity issues are also discussed.

Anti-HER2 VHH Targeted Fluorescent Liposome as Bimodal Nanoparticle for Drug Delivery and Optical Imaging.

OBJECTIVES: The aim of this study was to formulate fluorescent-labeled targeted immunoliposome to visualize the delivery and distribution of drugs in real-time. METHODS: In this study, fluorescent-labeled liposomes were decorated with anti-HER2 VHH or Herceptin to improve the monitoring of intracellular drug delivery and tumor cell tracking with minimal side effects. The conjugation efficiency of antibodies was analyzed by SDS-PAGE silver staining. In addition, the physicochemical characterization of liposomes was performed using DLS and TEM. Finally, confocal microscopy visualized nanoparticles in the target cells. RESULTS: Quantitative and qualitative methods characterized the intracellular uptake of 110±10 nm particles with near 70% conjugation efficiency. In addition, live-cell trafficking during hours of incubation was monitored by wide-field microscopy imaging. The results show that the fluorescent- labeled nanoparticles can specifically bind to HER2-positive breast cancer with minimal off-target delivery. CONCLUSION: These nanoparticles can have several applications in personalized medicine, especially drug delivery and real-time visualization of cancer therapy. Moreover, this method also can be applied in the targeted delivery of contrast agents in imaging and thermotherapy.

Effect of dietary caraway essential oils on expression of ß-catenin during 1,2-dimethylhydrazine-induced colonic carcinogenesis.

We have recently reported that the inhibition of colonic premalignant lesions induced by 1,2-dimethylhydrazine (DMH) is mediated by the interference of caraway oil components in the activities of the main hepatic xenobiotic metabolizing enzymes. The present study was carried out to examine the effect of dietary caraway oils on the progression of cancer, with emphasis on ß-catenin expression in the colon during DMH-induced colonic carcinogenesis. For this purpose, colon cancer was induced by DMH in rats (20 mg/kg body weight for 5 weeks) and groups of animals were given dietary caraway essential oils at two levels (0.01 and 0.1%) for 16 weeks. After 16 weeks and at the end of the experimental period the colon tissue biopsies were processed for histopathological examination and the expression of ß-catenin at mRNA and protein levels was estimated by polymerase chain reaction and enzyme-linked immunosorbent assay. The formation of premalignant lesions based on aberrant crypt foci (ACF) in DMH-treated rats was greatly inhibited (72-87%) in rats given dietary essential oils when compared to respective controls. There was a correlation between the number of colonic ACF formation and the expression levels of ß-catenin measured at protein and mRNA levels. These results indicate that the Wnt/ß-catenin signaling pathway is activated during colon cancer promotion and that the expression of colonic ß-catenin is altered in long-term caraway oil feeding, leading to suppression of DMH-induced premalignant lesions in rat colon.