Presented in this paper is an assessment of the applicability of Raman spectroscopy and microspectrophotometry (MSP) in visible and ultraviolet light (UV-Vis) in the examination of textile fibers dyed with mixtures of synthetic dyes. Fragments of single polyester fibers, stained with ternary mixtures of disperse dyes in small mass concentrations, and fragments of single cotton fibers, dyed with binary or ternary mixtures of reactive dyes, were subjected to the study. Three types of excitation sources, 514, 633, and 785 nm, were used during Raman examinations, while the MSP study was conducted in the 200 to 800 nm range. The results indicate that the capabilities for discernment of dye mixtures are similar in the spectroscopic methods that were employed. Both methods have a limited capacity to distinguish slightly dyed polyester fiber; additionally, it was found that Raman spectroscopy enables identification of primarily the major components in dye mixtures. The best results, in terms of the quality of Raman spectra, were obtained using an excitation source from the near infrared. MSP studies led to the conclusion that polyester testing should be carried out in the range above 310 nm, while for cotton fibers there is no limitation or restriction of the applied range. Also, MSP UV-Vis showed limited possibilities for discriminatory analysis of cotton fibers dyed with a mixture of reactive dyes, where the ratio of the concentration of the main dye used in the dyeing process to minor dye was higher than four. The results presented have practical applications in forensic studies, inter alia.

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Forensic evidence in the form of fibres is recovered in cases involving sexual offenses, assault, murder and road accidents. In the event when a connection between persons is determined, fibres transferred from an offender’s to a victim’s clothing and vice versa are sought for. Colour is the first physico-chemical property verified during forensic analysis. Any colour differences between materials recovered at the crime scene and those originating from a suspect's clothing suggestthat fibres cannot have come from the same source. The aim ofthis article is to introduce the colour-related issues as they pertain to forensic fibre evidence.

Homozygous deletions of p16/CDKN2a (cyclin dependent kinase inhibitor 2A) locus are prevalent in cancer and often involve co-deletion of adjacent genes. Metabolic gene MTAP (methylthioadenosine phosphorylase) is localized at the 9p21 chromosome in the close proximity to p16/CDKN2A tumor-suppressor locus. Co-deletion of MTAP may be observed in 80-90% of all tumors harboring homozygous deletion of CDKN2A, which represents 10 - 15% of all human tumors. Many of these tumor types, such as non-small cell lung cancer, pancreatic adenocarcinoma, glioblastoma or mesothelioma are associated with poor prognosis, representing a significant unmet medical need. MTAP deletion results in a massive accumulation of methylthioadenosine (MTA) in cells. MTA in high concentrations is a very selective inhibitor of PRMT5 methyltransferase, competitive for the substrate: S-adenosylmethionine (SAM). Accumulation of MTA in cells with MTAP deletion causes partial inhibition of the methylation activity of PRMT5, which in turn reduces the level of symmetric arginine dimethylation of the whole proteome, and thus an increased sensitivity of cells to modulation of methylosome activity. Therapeutic targeting of PRMT5 in homozygous MTAP-deleted cancers constitute a promising strategy of selective killing of genetically defined cancer cells. Ryvu has identified a series of MTA-cooperative PRMT5 inhibitors which have good drug-like physicochemical properties and block methyltransferase activity with nanomolar IC50 values. Structurally enabled hit generation and optimization allowed quick expansion and delivery of several generations of compounds with novel IP, high target engagement in cells and selective potency in MTAP-deleted cell lines. Ryvu compounds selectively inhibit growth of MTAP-deleted cancer cells in prolonged 3D culture, which strongly correlates with inhibition of PRMT5-dependent protein symmetric dimethylation (SDMA) in those cells. Selectivity between effects observed in MTAP-deleted and WT cells exceeds 100-fold both for SDMA and growth inhibition. The DMPK profile of these compounds allows for oral administration, which enables testing antitumor activity in MTAP null tumor xenograft-bearing mice. Efficacy studies with our lead compound resulted in demonstration of tumor growth inhibition in MTAP -/- model, accompanied by significant inhibition of target proximal PD biomarker.  Overall, these studies provide a rationale for further optimization of our chemical series of MTA-cooperative PRMT5 inhibitors towards a clinical candidate.  Citation Format: Anna Bartosik, Adam Radzimierski, Aneta Bobowska, Oleksandr Levenets, Agata Stachowicz, Kamil Kuś, Kinga Michalik, Katarzyna Banaszak, Monika Madej, Marta Skoda, Kamila Kozłowska-Tomczyk, Igor Tomczyk, Karolina Pyziak, Dobrosława Krzemień, Mirosława Gładysz, Paulina Podkalicka, Aniela Gołas, Karolina Gluza, Grzegorz Satała, Andrzej Gondela, Marta Sowińska, Nicolas Boutard, Agata Chłopek, Aleksandra Więckowska, Daria Szukiel, Grzegorz Ćwiertnia, Iana Levenets, Karol Zuchowicz, Klara Korta-Piątek, Marcin Nowogródzki, Marek Wronowski, Marianna Girardi, Mateusz Świrski, Oleksandr Popika, Paulina Niedziejko-Ćwiertnia, Pierpaolo Cordone, Przemysław Wyrębek, Quỳnh Vũ, Sujit Sasmal, Svitlana Sukhomlinova, Magdalena Miodek, Jacek Faber, Anna Kowal-Chwast, Róża Starczak, Sanja Novak Ratajczak, Agnieszka Świrska, Dawid Gogola, Paweł Guzik, Martin Swarbrick, Mateusz Nowak. Discovery of novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP-deleted cancers  [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 449.