Purpose: Neuropeptide Y (NPY) is a pleiotropic peptide, which is involved in many biological mechanisms important in regulation of cell growth and survival. The aim of this study was a comprehensive analysis of the NPY system in prostate pathology. Methods: The study was based on immunohistochemical analysis of NPY and its receptors, Y1R, Y2R and Y5R, in tissue samples from benign prostate (BP), primary prostate cancer (PCa) and PCa bone metastases. Tissue microarray (TMA) technique was employed, with analysis of multiple cores from each specimen. Intensity of the immunoreactivity and expression index (EI), as well as distribution of the immunostaining in neoplastic cells and stromal elements were evaluated. Perineural invasion (PNI) and extraprostatic extension (EPE) were areas of special interests. Moreover, a transwell migration assay on the LNCaP PCa cell line was used to assess the chemotactic properties of NPY. Results: Morphological analysis revealed homogeneous membrane and cytoplasmic pattern of NPY staining in cancer cells and its membrane localization with apical accentuation in BP glands. All elements of the NPY system were upregulated in pre-invasive prostate intraepithelial neoplasia, PCa and metastases. EI and staining intensity of NPY receptors were significantly higher in PCa then in BP with correlation between Y2R and Y5R. The strength of expression of the NPY system was further increased in the PNI and EPE areas. In bone metastases, Y1R and Y5R presented high expression scores. Conclusion: The results of our study suggest that the NPY system is involved in PCa, starting from early stages of its development to disseminated states of the disease, and participates in the invasion of PCa into the auto and paracrine matter.

Intratumor heterogeneity implies heterogeneous protein function, facilitating tumor adaptation which results in therapeutic failure. We hypothesized that tumor heterogeneity at protein level may influence the course of the disease. As a single biopsy might not represent the full biologic complexity of the tumor, we have analyzed immunohistochemically four different cores obtained from each primary tumor within the cohort of 364 patients with endometrial cancer (EC). The following proteins were examined: estrogen receptor 1 (ESR1), progesterone receptor, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, receptor tyrosine-protein kinase erbB-3, v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4, phosphatidylinositol-4,5-bisphosphate 3-kinase, phosphorylated v-akt murine thymoma viral oncogene homolog 1, v-myc avian myelocytomatosis viral oncogene homolog, DNA topoisomerase II alpha 170 kDa (TOP2A), cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein p53, RAD21 homolog, S. pombe, and runt-related transcription factor 1. Particularly strong correlation was found between TOP2A and CDKN2A heterogeneity and higher stage of the disease (P = .0002 and P = .0003, respectively). Most correlations with clinicopathologic data were observed for ESR1 heterogeneity that correlated with non-endometrioid carcinomas (P=.02), higher stage (P=.005), grade (P=.01), and the presence of metastases (P = .01). Thirty-nine (11.0%) patients were classified as "globally heterogeneous". Cumulative tumor heterogeneity strongly correlated with the presence of metastases, higher stage, and higher grade of the disease (all P b .05). It also carried negative prognostic value (P=.0008). We show that the degree of heterogeneity in EC might serve as a clinically valid molecular marker.

Background: Endometrial cancer (EC) is a hormone-related disease, showing highly diverse features of ER/PR/HER2 status-based molecular subtypes. Long noncoding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) has recently emerged as a key molecule in many cancers, triggering epithelial-mesenchymal transition (EMT)–mediated cancer stem cell (CSC) formation, but little is known about its significance in EC. Thus, we aimed to investigate the clinical significance of HOTAIR itself in different molecular subtypes of EC and possible links between HOTAIR, EMT and CSC-related markers. Methods: The study group included 156 consecutive, stage I-IV EC patients treated between 2000 and 2010. ER, PR and HER2 protein expression were examined by immunohistochemistry (IHC) on tissue microarrays. RT-qPCR was used to analyze the expression levels of HOTAIR, EMT-related genes – SNAIL and SLUG – and the CSCs marker CD133. Results: Molecular subtypes, defined as ER/PR+HER2+, ER/PR+HER2-, ER-PR-HER2+ and ER-PR-HER2-, occurred in 40.2%, 52.3%, 4.7% and 1.9% of cases, respectively. The expression of HOTAIR did not differ between the subtypes, but high HOTAIR expression correlated with shorter overall survival (p = 0.04) in the entire group. The expression levels of HOTAIR, SNAIL, SLUG and CD133 were similar in defined EC molecular subtypes. Conclusions: Our data do not confirm the role of HOTAIR in EMT-mediated CSC formation in EC. Neither does the diversity of EC molecular subtypes influence these processes. But HOTAIR expression could serve as an independent prognostic factor in EC. The clinical importance of the above discoveries requires further studies.

Graphene and graphene-based materials have attracted growing interest for potential applications in medicine because of their good biocompatibility, cargo capability and possible surface functionalizations. In parallel, prototypic graphene-based devices have been developed to diagnose, imaging and track tumor growth in cancer patients. There is a growing number of reports on the use of graphene and its functionalized derivatives in the design of innovative drugs delivery systems, photothermal and photodynamic cancer therapy, and as a platform to combine multiple therapies. The aim of this review is to introduce the latest scientific achievements in the field of innovative composite graphene materials as potentially applied in cancer therapy. The “Technology and Innovation Roadmap” published in the Graphene Flagship indicates, that the first anti-cancer drugs using graphene and graphene-derived materials will have appeared on the market by 2030. However, it is necessary to broaden understanding of graphene-based material interactions with cellular metabolism and signaling at the functional level, as well as toxicity. The main aspects of further research should elucidate how treatment methods (e.g., photothermal therapy, photodynamic therapy, combination therapy) and the physicochemical properties of graphene materials influence their ability to modulate autophagy and kill cancer cells. Interestingly, recent scientific reports also prove that graphene nanocomposites modulate cancer cell death by inducing precise autophagy dysfunctions caused by lysosome damage. It turns out as well that developing photothermal oncological treatments, it should be taken into account that near-infrared-II radiation (1000– 1500 nm) is a better option than NIR-I (750– 1000 nm) because it can penetrate deeper into tissues due to less scattering at longer wavelengths radiation.