Programmed Death 1 (PD-1) Expression in Relapsing and Remitting Hodgkin Lymphoma as Prognostic Factor.

BACKGROUND: Programmed death ligand 1 (PD-L1) plays critical role in PD-1-dependent immunity suppress. Abnormal PD-L1 expression has shown to be directly related to poor prognosis and drug resistance in cancer patients. Hence, we aimed to evaluate PD-L1 expression in relapsing and remitting Hodgkin lymphoma (HL) as a prognostic factor. METHODS: In this cross-sectional study, 100 patients with HL between 2007 and 2015, were included. A thin section of tumor tissue fixed and processed on slides, stained by immunohistochemistry (IHC) PD-L1 specific antibodies. The clinical, imaging and pathology information of patients were obtained using case reading and by retrospective follow-up. The status of recurrence or improvement was determined after 5 years of diagnosis. GraphPad Prism v.8 was used for analysis. RESULTS: of 100 HL cases, the mean age of 33 relapsed group cases was significantly higher than remission group (p-value = 0.006), and gender was not significant however majority of cases in both groups were male. The frequency of PD-L1 expression found in 49% of all patients. A significant relationship was found between the expression of PD-L1 and disease progression, HL subtype, stage of tumor (p-value<0.05). High expression of PD-L1 found in majority of relapse group and low expression in remission group. CONCLUSION: PD-L1 expression assessment in HL patients is a valuable tool for prediction of the disease subtype, progression, stage, and treatment outcome. IHC method as an available, simple, rather cheap, and efficient tool could use for evaluation of PD-L1 expression and predicting the prognosis of HL disease, elsewhere.

Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents.

BACKGROUND AND PURPOSE: In this study, some new cytotoxic hybrid structures were synthesized by combining pyrazolinone and imidazolinone rings with quinazoline pharmacophores. EXPERIMENTAL APPROACH: The benzoxazinone, pyrazolo-quinazoline fused ring, and imidazolinone anchored quinazoline derivatives were synthesized by simple ring-opening, ring expansion, and ring closure strategies from oxazolones. The molecular docking studies of the final derivatives were accomplished on the epidermal growth factor receptor enzyme. The cytotoxic effect of the final compounds on the MCF-7 cell line was evaluated by MTT assay. FINDINGS/RESULTS: The docking results confirmed the optimized electrostatic, H-bonding, and hydrophobic interactions of structures with the key residues of the active site (ΔGbin< -9Kcal/mol). The derivatives have been obtained in good yield and purity, and their structures were confirmed by different methods (FT-IR, 1H-NMR, 13C-NMR, and CHNS analysis). The IC50s of all final derivatives against the MCF-7 cell line were lower than 10 µM, and between all, the IXa from pyrazolo-quinazolinone class (IC50: 6.43 µM) with chlorine substitute was the most potent. Furthermore, all derivatives showed negligible cytotoxicity on HUVEC normal cell line which would be a great achievement for a novel cytotoxic agent. CONCLUSION AND IMPLICATIONS: Based on the obtained results, pyrazolo[1,5-c] quinazolin-2-one series were more cytotoxic than imidazolinone methyl quinazoline-4(3H)-ones against MCF-7 cells. Chlorine substitute in the para position of the aromatic ring improved the cytotoxicity effect in both classes. It could be related to the polarizability of a chlorine atom and making better intermolecular interactions. Further pre-clinical evaluations are required for the promising synthesized cytotoxic compounds.