FT-Raman and FTIR spectroscopy as a tools showing marker of platinum-resistant phenomena in women suffering from ovarian cancer.

Platinum-resistant phenomena in ovarian cancer is very dangerous for women suffering from this disease, because reduces the chances of complete recovery. Unfortunately, until now there are no methods to verify whether a woman with ovarian cancer is platinum-resistant. Importantly, histopathology images also were not shown differences in the ovarian cancer between platinum-resistant and platinum-sensitive tissues. Therefore, in this study, Fourier Transform InfraRed (FTIR) and FT-Raman spectroscopy techniques were used to find chemical differences between platinum-resistant and platinum-sensitive ovarian cancer tissues. Furthermore, Principal Component Analysis (PCA) and machine learning methods were performed to show if it possible to differentiate these two kind of tissues as well as to propose spectroscopy marker of platinum-resistant. Indeed, obtained results showed, that in platinum-resistant ovarian cancer tissues higher amount of phospholipids, proteins and lipids were visible, however when the ratio between intensities of peaks at 1637 cm-1 (FTIR) and at 2944 cm-1 (Raman) and every peaks in spectra was calculated, difference between groups of samples were not noticed. Moreover, structural changes visible as a shift of peaks were noticed for C-O-C, C-H bending and amide II bonds. PCA clearly showed, that PC1 can be used to differentiate platinum-resistant and platinum-sensitive ovarian cancer tissues, while two-trace two-dimensional correlation spectra (2T2D-COS) showed, that only in amide II, amide I and asymmetric CH lipids vibrations correlation between two analyzed types of tissues were noticed. Finally, machine learning algorithms showed, that values of accuracy, sensitivity and specificity were near to 100% for FTIR and around 95% for FT-Raman spectroscopy. Using decision tree peaks at 1777 cm-1, 2974 cm-1 (FTIR) and 1714 cm-1, 2817 cm-1 (FT-Raman) were proposed as spectroscopy marker of platinum-resistant.

Estrogen Receptor Signaling in Breast Cancer.

Estrogen receptor (ER) signaling is a critical regulator of cell proliferation, differentiation, and survival in breast cancer (BC) and other hormone-sensitive cancers. In this review, we explore the mechanism of ER-dependent downstream signaling in BC and the role of estrogens as growth factors necessary for cancer invasion and dissemination. The significance of the clinical implications of ER signaling in BC, including the potential of endocrine therapies that target estrogens' synthesis and ER-dependent signal transmission, such as aromatase inhibitors or selective estrogen receptor modulators, is discussed. As a consequence, the challenges associated with the resistance to these therapies resulting from acquired ER mutations and potential strategies to overcome them are the critical point for the new treatment strategies' development.

Kaiso Protein Expression Correlates with Overall Survival in TNBC Patients.

Triple-negative breast cancers (TNBCs) are histologically heterogenic invasive carcinomas of no specific type that lack distinctive histological characteristics. The prognosis for women with TNBC is poor. Regardless of the applied treatments, recurrences and deaths are observed 3-5 years after the diagnosis. Thus, new diagnostic markers and targets for personalized treatment are needed. The subject of our study-the Kaiso transcription factor has been found to correlate with the invasion and progression of breast cancer. The publicly available TCGA breast cancer cohort containing Illumina HiSeq RNAseq and clinical data was explored in the study. Additionally, Kaiso protein expression was assessed in formalin-fixed and paraffin-embedded tissue archive specimens using the tissue microarray technique. In this retrospective study, Kaiso protein expression (nuclear localization) was compared with several clinical factors in the cohort of 103 patients with TNBC with long follow-up time. In univariate and multivariate analysis, high Kaiso protein but not mRNA expression was correlated with better overall survival and disease-free survival, as well as with premenopausal age. The use of radiotherapy was correlated with better disease-free survival (DFS) and overall survival (OS). However, given the heterogeneity of TNBC and context-dependent molecular diversity of Kaiso signaling in cancer progression, these results must be taken with caution and require further studies.

The Role of Sirtuin 6 in the Deacetylation of Histone Proteins as a Factor in the Progression of Neoplastic Disease.

SIRT6 is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, predominantly located in the nucleus, that is involved in the processes of histone modification, DNA repair, cell cycle regulation, and apoptosis. Disturbances in SIRT6 expression levels have been observed in the development and progression of various types of cancer. Therefore, it is important to better understand the role of SIRT6 in biochemical pathways and assign it specific biological functions. This review aims to summarize the role of SIRT6 in carcinogenesis and tumor development. A better understanding of the factors influencing SIRT6 expression and its biological role in carcinogenesis may help to develop novel anti-cancer therapeutic strategies. Moreover, we discuss the anti-cancer effects and mechanism of action of small molecule SIRT6 modulators (both activators and inhibitors) in different types of cancer.

Imperatorin as a Promising Chemotherapeutic Agent Against Human Larynx Cancer and Rhabdomyosarcoma Cells.

Naturally occurring coumarins are bioactive compounds widely used in Asian traditional medicine. They have been shown to inhibit proliferation, induce apoptosis, and/or enhance the cytotoxicity of currently used drugs against a variety of cancer cell types. The aim of our study was to examine the antiproliferative activity of different linear furanocoumarins on human rhabdomyosarcoma, lung, and larynx cancer cell lines, and dissolve their cellular mechanism of action. The coumarins were isolated from fruits of Angelica archangelica L. or Pastinaca sativa L., and separated using high-performance counter-current chromatography (HPCCC). The identity and purity of isolated compounds were confirmed by HPLC-DAD and NMR analyses. Cell viability and toxicity assessments were performed by means of methylthiazolyldiphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. Induction of apoptosis and cell cycle progression were measured using flow cytometry analysis. qPCR method was applied to detect changes in gene expression. Linear furanocoumarins in a dose-dependent manner inhibited proliferation of cancer cells with diverse activity regarding compounds and cancer cell type specificity. Imperatorin (IMP) exhibited the most potent growth inhibitory effects against human rhabdomyosarcoma and larynx cancer cell lines owing to inhibition of the cell cycle progression connected with specific changes in gene expression, including CDKN1A. As there are no specific chemotherapy treatments dedicated to laryngeal squamous cell carcinoma and rhabdomyosarcoma, and IMP seems to be non-toxic for normal cells, our results could open a new direction in the search for effective anti-cancer agents.

Role of N-terminus in function and dynamics of sirtuin 7: an in silico study.

The sirtuin family comprises seven NAD+-dependent histone deacetylases named SIRT1 to SIRT7. The least investigated SIRT7 is currently considered as a promising therapeutic target for cardiovascular diseases, diabetes and different types of cancer. So far, its structure was not experimentally resolved, except of a fragment of its N-terminus. The aim of this study was to create in silico model of SIRT7 containing its core together with N-terminus, which is known to affect the enzyme's catalytic activity and to find pockets that could be targeted by structure-based virtual screening. Homology model of SIRT7 was prepared using X-ray structures of other sirtuins and a resolved fragment of the N-terminus of SIRT7 as templates. All atom-unbiased molecular dynamics simulations were performed. It was found that N-terminus of SIRT7 remains in spatial proximity of the catalytic core for considerable fraction of time, and therefore, it may affect its catalytic activity by helping the enzyme to hold the substrate peptide. It may also participate in holding and release of the cofactor. Preferred orientations of NAD+ and acetyl-lysine inside SIRT7 were found, with all components forming a stable complex. Molecular dynamics provided an ensemble of conformations that will be targeted with virtual screening. Reliable in silico structure of SIRT7 will be a useful tool in searching for its inhibitors, which can be potential drugs in cancer treatment.Communicated by Ramaswamy H. Sarma.

Histone Deacetylase Inhibitors and Phenotypical Transformation of Cancer Cells.

Histone deacetylase inhibitors (HDIs) are a group of potent epigenetic drugs which have been investigated for their therapeutic potential in various clinical disorders, including hematological malignancies and solid tumors. Currently, several HDIs are already in clinical use and many more are on clinical trials. HDIs have shown efficacy to inhibit initiation and progression of cancer cells. Nevertheless, both pro-invasive and anti-invasive activities of HDIs have been reported, questioning their impact in carcinogenesis. The aim of this review is to compile and discuss the most recent findings on the effect of HDIs on the epithelial-mesenchymal transition (EMT) process in human cancers. We have summarized the impact of HDIs on epithelial (E-cadherin, ß-catenin) and mesenchymal (N-cadherin, vimentin) markers, EMT activators (TWIST, SNAIL, SLUG, SMAD, ZEB), as well as morphology, migration and invasion potential of cancer cells. We further discuss the use of HDIs as monotherapy or in combination with existing or novel anti-neoplastic drugs in relation to changes in EMT.