Background. Cancer stem cells (CSCs) use their stemness properties such as self renewal, toxicity... more Background. Cancer stem cells (CSCs) use their stemness properties such as self renewal, toxicity, plasticity, and communication with the tumor microenvironment (TME) to perpetuate their lineage and survive chemotherapy. Learning how to interrupt the self renewal ability or modulate the interaction of CSCs with the TME signaling will dramatically improve therapeutic impact on patient’s remission. Anti-tumor properties of mesenchymal stem cells (MSCs) are currently under investigations and different approaches have been applied to gain beneficial effects However, different types of MSCs yielded different conflicting results. In order to investigate if different types of MSCs preconditioned in the same culture conditions can exert alike anti oncogenic effect on glioma stem cells, we planned this study. Methods. GSCs were isolated from U87 cell line by FACS cell sorter, characterized and established as gliospheres. Condition media from MSCs of Wharton Jelly (WJ-MSCs) and bone marrow (B...
Combinatorial therapeutic strategies using siRNA and small molecules to eradicate tumors are emer... more Combinatorial therapeutic strategies using siRNA and small molecules to eradicate tumors are emerging. Targeting multiple signaling pathways decreases the chances of cancer cells switching and adapting new signaling processes that may occur when using a single therapeutic modality. Aberrant functioning of Notch-1, Wnt/β-catenin, and STAT3 proteins and their crosstalk signaling pathways have been found to be involved in tumor survival, drug resistance, and relapse. In the current study, we describe a therapeutic potential of single and combinations of siRNA designed for silencing Notch-1, Wnt/β-catenin, and STAT3 in MCF7_DoxS (wild type) and MCF7_DoxR (doxorubicin resistant) breast cancer cells. The MCF7_DoxR cells were developed through treatment with a gradual increase in doxorubicin concentration, the expression of targeted genes was investigated, and the expression profiling of CD44/CD24 of the MCF7_DoxS and MCF7_DoxR cells were detected by flow cytometry. Both MCF7_DoxS and MCF7...
Adiponectin is an adipokine involved in the regulation of body metabolism and immune response. Ci... more Adiponectin is an adipokine involved in the regulation of body metabolism and immune response. Circulating levels and/or activity of adiponectin were reported to influence susceptibility to several diseases, including type 2 diabetes mellitus, cardiovascular disease, and metabolic syndrome. In this study, serum adiponectin levels and the association of adiponectin gene (ADIPQO) single-nucleotide polymorphism (G276T SNP) with hypertension in type 2 diabetic patients were examined. Type 2 diabetic patients (n = 449) were recruited and divided into two groups, normotensive (n = 199) and hypertensive (n = 250). Results demonstrated that serum adiponectin levels were significantly higher in normotensive subjects compared with hypertensive subjects (P < .05). When these results were compared according to gender, only female hypertensive diabetic patients showed significantly higher levels of adiponectin (P < .05). In addition, no significant difference in the genotypes and alleles frequencies of ADIPQO G276T SNP was observed between the two groups (P > .05). In conclusion, high circulating levels of adiponectin were found to be associated with hypertension only in type 2 diabetic female patients which might indicate a gender preference.
Journal of Drug Delivery Science and Technology, 2021
Abstract Triple negative breast cancer is an aggressive type of cancer with limited therapeutic o... more Abstract Triple negative breast cancer is an aggressive type of cancer with limited therapeutic options. Aptamer-functionalized liposomes to deliver short interference RNAs (siRNAs) offer a promising therapeutic option. The current study aimed at preparing an aptamer functionalized liposome loaded with siRNA-protamine polyplexes for selective delivery of Notch 1 siRNA into cancer cells. The aptamer functionalized liposomes were characterized by Dynamic Light Scattering (DLS) and electron microscopy. In vitro silencing and antiproliferative efficiency were conducted using the triple negative breast cancer cell line MDA-MB-231. The unfunctionalized loaded liposomes had a Z-average size of 153.1 ± 6.481 nm and a charge of −17.5 ± 0.265 mV, while the functionalized liposomes had a higher Z-average size of 285 ± 12.33 nm and a charge of −23.8 ± 0.924 mV with an encapsulation efficiency (EE%) of 60%. The presence of the nucleolin aptamer on the surface of the liposomes increased the cellular uptake of liposomes by almost 2 folds. Confocal images showed the co-localization of liposomes and aptamer in the cytoplasm where the siRNA must be released. The functionalized loaded liposomes produced a higher antiproliferative and silencing effect compared to the unfunctionalized liposomes. In conclusion, this formulation represents a novel promising vehicle to deliver siRNA effectively to the MDA-MB-231 cell line.
Background: Earlier diagnosis and advances in treatment strategies have increased the average sur... more Background: Earlier diagnosis and advances in treatment strategies have increased the average survival of cancer patients over the last decades. Despite the increased number of new anti-neoplastic agents, there has been no adequate therapy for intricate malignancies such as pancreatic cancer. Cancer metabolism is the main building block standing behind cancer promotion and progression even in the presence of a harsh environment. Targeting metabolic pathways, such as glycolysis and pentose phosphate pathway, is regarded as a promising new strategy for cancer treatment. Objective: The current study is to investigate the effect of knocking-down pancreatic cancer glycolytic and pentose phosphate pathway's regulators (HIF-1α, ARNT, PFKFB4, and RBKS), on cell’s viability and resistance to gemcitabine and doxorubicin, using small interference RNA. Methodology: The human pancreatic ductal adenocarcinoma cell line, Panc-1, was used to study the anti-proliferative activity of targeting HI...
Background. Cancer stem cells (CSCs) use their stemness properties such as self renewal, toxicity... more Background. Cancer stem cells (CSCs) use their stemness properties such as self renewal, toxicity, plasticity, and communication with the tumor microenvironment (TME) to perpetuate their lineage and survive chemotherapy. Learning how to interrupt the self renewal ability or modulate the interaction of CSCs with the TME signaling will dramatically improve therapeutic impact on patient’s remission. Anti-tumor properties of mesenchymal stem cells (MSCs) are currently under investigations and different approaches have been applied to gain beneficial effects However, different types of MSCs yielded different conflicting results. In order to investigate if different types of MSCs preconditioned in the same culture conditions can exert alike anti oncogenic effect on glioma stem cells, we planned this study. Methods. GSCs were isolated from U87 cell line by FACS cell sorter, characterized and established as gliospheres. Condition media from MSCs of Wharton Jelly (WJ-MSCs) and bone marrow (B...
Combinatorial therapeutic strategies using siRNA and small molecules to eradicate tumors are emer... more Combinatorial therapeutic strategies using siRNA and small molecules to eradicate tumors are emerging. Targeting multiple signaling pathways decreases the chances of cancer cells switching and adapting new signaling processes that may occur when using a single therapeutic modality. Aberrant functioning of Notch-1, Wnt/β-catenin, and STAT3 proteins and their crosstalk signaling pathways have been found to be involved in tumor survival, drug resistance, and relapse. In the current study, we describe a therapeutic potential of single and combinations of siRNA designed for silencing Notch-1, Wnt/β-catenin, and STAT3 in MCF7_DoxS (wild type) and MCF7_DoxR (doxorubicin resistant) breast cancer cells. The MCF7_DoxR cells were developed through treatment with a gradual increase in doxorubicin concentration, the expression of targeted genes was investigated, and the expression profiling of CD44/CD24 of the MCF7_DoxS and MCF7_DoxR cells were detected by flow cytometry. Both MCF7_DoxS and MCF7...
Adiponectin is an adipokine involved in the regulation of body metabolism and immune response. Ci... more Adiponectin is an adipokine involved in the regulation of body metabolism and immune response. Circulating levels and/or activity of adiponectin were reported to influence susceptibility to several diseases, including type 2 diabetes mellitus, cardiovascular disease, and metabolic syndrome. In this study, serum adiponectin levels and the association of adiponectin gene (ADIPQO) single-nucleotide polymorphism (G276T SNP) with hypertension in type 2 diabetic patients were examined. Type 2 diabetic patients (n = 449) were recruited and divided into two groups, normotensive (n = 199) and hypertensive (n = 250). Results demonstrated that serum adiponectin levels were significantly higher in normotensive subjects compared with hypertensive subjects (P < .05). When these results were compared according to gender, only female hypertensive diabetic patients showed significantly higher levels of adiponectin (P < .05). In addition, no significant difference in the genotypes and alleles frequencies of ADIPQO G276T SNP was observed between the two groups (P > .05). In conclusion, high circulating levels of adiponectin were found to be associated with hypertension only in type 2 diabetic female patients which might indicate a gender preference.
Journal of Drug Delivery Science and Technology, 2021
Abstract Triple negative breast cancer is an aggressive type of cancer with limited therapeutic o... more Abstract Triple negative breast cancer is an aggressive type of cancer with limited therapeutic options. Aptamer-functionalized liposomes to deliver short interference RNAs (siRNAs) offer a promising therapeutic option. The current study aimed at preparing an aptamer functionalized liposome loaded with siRNA-protamine polyplexes for selective delivery of Notch 1 siRNA into cancer cells. The aptamer functionalized liposomes were characterized by Dynamic Light Scattering (DLS) and electron microscopy. In vitro silencing and antiproliferative efficiency were conducted using the triple negative breast cancer cell line MDA-MB-231. The unfunctionalized loaded liposomes had a Z-average size of 153.1 ± 6.481 nm and a charge of −17.5 ± 0.265 mV, while the functionalized liposomes had a higher Z-average size of 285 ± 12.33 nm and a charge of −23.8 ± 0.924 mV with an encapsulation efficiency (EE%) of 60%. The presence of the nucleolin aptamer on the surface of the liposomes increased the cellular uptake of liposomes by almost 2 folds. Confocal images showed the co-localization of liposomes and aptamer in the cytoplasm where the siRNA must be released. The functionalized loaded liposomes produced a higher antiproliferative and silencing effect compared to the unfunctionalized liposomes. In conclusion, this formulation represents a novel promising vehicle to deliver siRNA effectively to the MDA-MB-231 cell line.
Background: Earlier diagnosis and advances in treatment strategies have increased the average sur... more Background: Earlier diagnosis and advances in treatment strategies have increased the average survival of cancer patients over the last decades. Despite the increased number of new anti-neoplastic agents, there has been no adequate therapy for intricate malignancies such as pancreatic cancer. Cancer metabolism is the main building block standing behind cancer promotion and progression even in the presence of a harsh environment. Targeting metabolic pathways, such as glycolysis and pentose phosphate pathway, is regarded as a promising new strategy for cancer treatment. Objective: The current study is to investigate the effect of knocking-down pancreatic cancer glycolytic and pentose phosphate pathway's regulators (HIF-1α, ARNT, PFKFB4, and RBKS), on cell’s viability and resistance to gemcitabine and doxorubicin, using small interference RNA. Methodology: The human pancreatic ductal adenocarcinoma cell line, Panc-1, was used to study the anti-proliferative activity of targeting HI...
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Papers by Suha Whaibi