Triple-negative breast cancer (TNBC) is the most aggressive and heterogeneous cancer subtypes. High rates of metastasis, poor prognosis, and drug resistance are the major problems associated with TNBC. The current chemotherapeutics eliminate only the bulk tumor cells (non-BCSCs) and do not affect breast cancer stem cells (BCSCs). The BCSCs which are left behind after chemotherapy is reported to promote recurrence and metastasis of TNBC. Death receptor-5 (DR-5) is exclusively expressed in TNBCs and mediates the extrinsic pathway of apoptosis. DR-5, therefore, can be exploited for targeted drug delivery and to induce apoptosis. Gammasecretase mediated Notch signaling in BCSCs regulates its proliferation, differentiation, and metastasis. The endogenous ligand, Delta-like ligand 4 ((DLL4)), is reported to activate this Notch signaling in TNBC. Blocking this signaling pathway using both gamma-secretase inhibitors (GSIs) and (DLL4) monoclonal antibody (mAb) may produce synergistic benefits. Further, the GSIs (DAPT, LY-411575, RO4929097, MK0752, etc. ) suffer from poor bioavailability and off-target side effects such as diarrhea, suppression of lymphopoiesis, headache, hypertension, fatigue, and ventricular dysfunctions. In this hypothesis, we discuss solid lipid nanoparticles (SLNs) based drug delivery systems containing GSIs and surface modified with DR-5 and (DLL4) monoclonal antibodies (mAb) to effectivity target and treat TNBC. The delivery system is designed to deliver the drug cargo precisely to TNBCs through its DR-5 receptors and hence expected to reduce the off-target side effects of GSIs. Further, (DLL4) mAb and GSIs are expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis.

Aim & Background: Multiple Sclerosis is one of the most common inflammatory central nervous system diseases. In patients, there is a defect in apoptotic pathway making T auto reactive cells nonapoptotic and entering to blood stream. Among the genes related to this disease, there is a gene named CD95L involved in apoptosis pathway.Material & Method: In this survey, we included 30 MS patients and 30 healthy controls which were matched by sex and age. Blood was taken from cases and controls with consent. Next, total RNA was extracted and cDNA was synthesized. Then, by TaqMan Real-time PCR technique, the expression level of CD95L and HGPRT genes was evaluated. The results obtained were analyzed by Linreg and Rest softwares.Result: In this study, CD95L expression in MS patients did not show any significant decrease compared to healthy controls (p Value: 0.197). In addition, in comparison of CD95L expression level between men and women no significant decrease was seen (p Value (M): 0.142, p Value (F): 0.156).Conclusion: In this study, no significant difference of CD95L gene expression between multiple sclerosis patients and healthy controls was seen.