A novel technique to assess chromatin texture using pixel optical densitometry in oral squamous cell carcinoma

Background: The early detection of neoplasia is the prime aim of a diagnostician. Altered chromatin distribution is the earliest microscopic change observed in malignant transformation making it a valuable morphometric parameter. This study was aimed to assess and correlate the progressive changes in chromatin texture from normal to varying grades of premalignancies to malignancy of the oral cavity. Methods: Thirty‐four archival tissue specimens categorized as normal buccal mucosa (5), low‐grade epithelial dysplasia (11), high‐grade epithelial dysplasia (7), and squamous cell carcinoma (11) were stained with Feulgen reaction. Pixel optical densitometry histograms were obtained from analysis of an average of 300 cells/case using ImageJ software. Nine histogram curve characteristics (including area under the curve, area integer percentage, center, centroid) were then analyzed statistically for differences between the four groups. Results: Area integer percentage (P = 0.002), center (P = 0.038), and centroid (P = 0.021) were statistically significant within the four groups The parameters showed a dip in their value from normal to low‐grade dysplasia but showed a steady increase in high‐grade dysplasia and carcinoma. Conclusion: The optical density characteristics had the ability to differentiate the progression of neoplastic changes by extracting information of the chromatin distribution not quantifiable by routine microscopy. The early clumping of chromatin in the periphery in low‐grade dysplasia followed by progressively increasing chromatin aggregates in high‐grade dysplasia and carcinoma correlated well with the shift observed in the histogram center and centroid. The novel pixel optical densitometry technique efficiently predicted malignant transformation. Microsc. Res. Tech. 75:1119–1123, 2012. © 2012 Wiley Periodicals, Inc.     

A potential impact of A Disintegrin and Metalloproteinase DomainLike Protein Decysin-1 (ADAMDEC1) on clear cell renal cell carcinoma propagation

Clear cell renal cell carcinoma (KIRC) is the most common and aggressive malignancy subtype of renal neoplasmthat arises from proximal convoluted tubules. It is characterized by poor clinical outcomes and high mortality of patients dueto the lack of specific biomarkers for varying stages of the disease and no effective treatment. Proteases are associated withthe development of several malignant tumors in humans by their ability to degrade extracellular matrices, facilitatingmetastasis. Herein, differentially expressed genes in KIRC cases compared to healthy kidneys were screened out from theGene Expression Profiling Interactive Analysis (GEPIA) database. This data was applied to determine the most elevatedprotease in KIRC and as a result, A Disintegrin and Metalloproteinase Domain-Like Protein Decysin-1 (ADAMDEC1)was selected. This expression pattern was exclusive for KIRC and not observed for papillary and chromophobe renal cellcarcinomas, in which ADAMDEC1 was at the same level in tumors and non-cancer specimens. Furthermore, theADAMDEC1 significant increase was detected in the fourteen other human malignancies compared to healthy samples,which suggested its strong involvement in cancer development. Next, GEPIA and Pathology Atlas correlatedADAMDEC1 high expression with more advanced tumor grade and shorter survival of KIRC patients. Xena FunctionalGenomics Explorer presented that ADAMDEC1 could be hypermethylated in some tumor cases and one somaticmutation in the gene sequence was detected. Finally, a Search Tool for the Retrieval of Interacting Genes/Proteins;STRING base was utilized to predict the interactions of ADAMDEC1 with other molecules and construct the signalingnetwork. In summary, ADAMDEC1 showed the tremendous potential to be the predictive marker for the KIRC and itsdevelopment. Therefore, this review with data analysis can be a good base for further in vitro and in vivo research thatexperimentally can confirm the ADAMDEC1 as prognostic biomarkers and therapeutic target of KIRC.     

IR780 loaded hollow MnO₂ nanoparticles for dual-mode imaging and enhanced photodynamic therapy of oral squamous cell carcinoma

Photodynamic therapy (PDT) has emerged as a novel therapeutic modality for cancer treatment, but its therapeutic efficacy is severely limited by the hypoxic tumor microenvironment (TME). Here we designed an innovative multifunctional nano-platform which consists of a hollow MnO₂ shell and internal photosensitizer IR780. It is not only used for multimodal imaging of oral squamous cell carcinoma (OSCC), but also for adjustment hypoxic TME to enhance cancer treatment. Hollow MnO₂ can promote decomposition of tumor endogenous H₂O₂ to relieve tumor hypoxia, thereby enhancing the effect of photodynamic therapy. Photosensitizer IR780 generates singlet oxygen under laser irradiation to kill tumor cells, playing photodynamic effect, can also act as the contrast agents for photoacoustic and fluorescence multiple imaging, providing potential imaging capability for cancer therapeutic guidance and monitoring. Our research results in this article show that HMnO₂-IR780 nanocomposite exhibits good biocompatibility and nontoxicity, strong PA/FL imaging contrast, excellent oxygen production capacity and outstanding photodynamic therapy effect. This finding provides a new idea for multimodal imaging-guided nanotherapy for OSCC.     

Differential mRNA expression in peripheral blood is associated with oral squamous cell carcinoma: Recent advances and future challenges

Oral squamous cell carcinoma (OSCC) is a malignant tumor triggered by the accumulation of multiple gene mutations in oral epithelial cells. Different OSCC-related biomarkers have been reported in circulation in the peripheral blood that support the occurrence and development of OSCC. Recent advances in high-throughput and highly sensitive detection methods have overcome the limitation of the low concentration of most peripheral blood biomarkers. Hence, blood biomarker detection has become an efficient screening tool for the early diagnosis of OSCC. The growing data available in public cancer and gene databases have provided new foundations for OSCC research. In particular, the identification of OSCC biomarkers using bioinformatic tools has shed new light on the underlying mechanisms as well as on the genetic landscape of OSCC. More recently, mRNA targeting therapies have emerged as valuable anticancer treatment strategies, as they allow for the regulation of the expression of certain functional proteins to reverse genetic abnormalities or induce tissue repair. Thus, mRNA-targeting therapies can be used to regulate the expression of antigens, antibodies, or cellular receptors by immune cells. Particularly, anti-cancer cellular immunotherapy carrying specific mRNAs has attracted significant attention in OSCC treatment. Here, we review the present knowledge on the role of peripheral blood mRNAs in the diagnosis, treatment, development, and prognosis of OSCC. Moreover, we address future research prospects of mRNAs in the peripheral blood in OSCC and the opportunities and challenges that may arise in future clinical therapeutic applications.     

A novel prognostic gene signature,nomogram and immune landscape based on tanshinone IIA drug targets for hepatocellular carcinoma: Comprehensive bioinformatics analysis and <i>in vitro</i> experiments

Background: Tanshinone IIA, one of the main ingredients of Danshen, is used to treat hepatocellular carcinoma (HCC). However, potential targets of the molecule in the therapy of HCC are unknown. Methods: In this study, we collected the tanshinone IIA targets from public databases for investigation. We screened differentially expressed genes (DEGs) across HCC and normal tissues using mRNA expression profiles from The Cancer Genome Atlas (TCGA). Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression models were used to identify and construct the prognostic gene signature. Results: Finally, we discovered common genes across tanshinone IIA targets and HCC DEGs. We reported Fatty acid binding protein-6 (FABP6), Polo-like Kinase 1 (PLK1), deoxythymidylate kinase (DTYMK), Uridine Cytidine Kinase 2 (UCK2), Enhancer of Zeste Homolog 2 (EZH2), and Cytochrome P450 2C9 (CYP2C9) as components of a gene signature. The six-gene signature’s prognostic ability was evaluated using the Kaplan-Meier curve, time-dependent receiver operating characteristic (ROC), multivariate Cox regression analysis, and the nomogram. The mRNA level and protein expression of UCK2 were experimentally validated after treatment with different concentrations of tanshinone IIA in HEPG2 cells. CIBERSORTx, TIMER2.0, and GEPIA2 tools were employed to explore the relationship between the prognostic signature and immune cell infiltration. Conclusion: We established a six-gene signature as a reliable model with significant therapeutic possibility for prognosis and overall survival estimation in HCC patients, which might also benefit medical decision-making for appropriate treatment.