China
Africa
Explore chapters and articles related to this topic
Targeted Therapy for Cancer Stem Cells
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Rama Krishna Nimmakayala, Saswati Karmakar, Garima Kaushik, Sanchita Rauth, Srikanth Barkeer, Saravanakumar Marimuthu, Moorthy P. Ponnusamy
The canonical Wnt/β-catenin signaling pathway is crucial for the regulation of normal development and stem cell maintenance, and studies show that mutations in these pathway molecules could make this pathway constitutively active leading to the drug resistance and uncontrolled proliferation of CSCs in various cancers [15]. Another drug resistance signaling mechanism, Hh signaling is required for normal embryonic development and tissue homeostasis. However, the pathway also regulates drug resistance genes in various cancers. For example, the Hh signaling transcription factor, Gli2 increases the expression of ABCC1 drug-resistant transporter leading to increased therapy resistance in hepatoma cells [16]. Moreover, aberrant activation of Notch signaling, which is required for normal development and tissue homeostasis, increases the expression levels of major CSC genes such as Myc, Nanog, OCT-4 and Sox2 [17]. EGFR mediated signaling is also known to regulate drug resistance in CSCs. Studies report that EGFR signaling is constitutively active in CSCs, and the inhibition of the signaling sensitizes glioma stem cells to radiation mediated cytotoxicity [18]. Also, OCT-4, a pluripotent transcription factor, regulates the genes of ABC transporters, especially ABCG2 drug resistant protein [19]. Myc driven signaling also induces ABC transporter genes such as ABCC1 [20].
Retinal stem cell research
Published in A Peyman MD Gholam, A Meffert MD Stephen, D Conway MD FACS Mandi, Chiasson Trisha, Vitreoretinal Surgical Techniques, 2019
Henry Klassen, Michael J Young, Robert Ritch, Julia E Richards, Teresa Borrάs, Leonard A Levin
Markers present on the cell surface are of particular interest, because their epitopes are accessible to antibody binding in the living cell. Surface markers therefore provide potential targets for cell selection during CNS stem cell isolation, as well as targets for pharmacologic manipulation. In the latter case, antibody or ligand binding can be useful for influencing key processes such as proliferation, migration, and differentiation. Surface markers present on primitive neuroepithelial cells include the notch receptor, CD133, the carbohydrate moiety CD15 (Lewis X), and the membrane glycolipid GD2 ganglioside (Fig. 68.1).5 GD2 ganglioside and CD15 have the distinction of being nonprotein epitopes. In addition, certain surface molecules can be exploited indirectly for cell sorting. For example, expression of the ABCG2 transporter has been associated with stem cell populations. The protein extrudes the vital dye Hoechst 33342, allowing selective isolation of these cells from the larger Hoechst-positive population.
Cytotoxic Phenanthridone Alkaloid Constituents of the Amaryllidaceae
Published in Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri, Plants That Fight Cancer, 2019
Jerald J. Nair, Johannes van Staden
The P-glycoprotein (P-gp) is an efflux pump which plays a crucial physiological role in protecting cells from toxic xenobiotics and endogenous metabolites (Sharom 2011). It forms a major component of the blood–brain barrier, restricting the uptake of drugs from the small intestine (Sharom 2011). P-gp has also been detected in many human cancers where it is thought to contribute to chemotherapeutic resistance (Sharom 2011). With an excellent Pearson correlation coefficient of 0.447 pancratistatin was identified amongst the top 26 compounds in the NCI library whose cytotoxicity profiles had the highest positive correlations with the ABCG2 transporter (Deeken et al. 2009). ABCG2 has multiple anticancer compounds as its substrates and is known to regulate oral bioavailability and serves a protective role in the blood–brain barrier, the maternal–fetal barrier, and in hematopoietic stem cells (Deeken et al. 2009).
ABCG2 and SLCO1B1 gene polymorphisms in the Croatian population
Published in Annals of Human Biology, 2022
Tamara Božina, Lana Ganoci, Ena Karačić, Livija Šimičević, Majda Vrkić-Kirhmajer, Iva Klarica-Domjanović, Tena Križ, Zrinka Sertić, Nada Božina
The ABCG2 is considered the major determinant of renal and extrarenal urate secretion, and reduced-function ABCG2 variants are linked to the risk for developing gout and hyperuricaemia (Matsuo et al. 2011; Fohner 2017). In addition, it is proven that ABCG2 has a crucial protective role in lowering cadmium’s intracellular concentration, which could be negatively altered by the Q141K genetic variant (Wen et al. 2021). At first, it was thought that ABCG2 substrates include a wide range of cytostatics, such as mitoxantrone, irinotecan, methotrexate and tyrosine kinase inhibitors (TKIs) such as imatinib, gefitinib and nilotinib. However, BCRP substrates are not limited to chemotherapeutics but include different drugs like erlotinib, prazosin, rosuvastatin, cimetidine, apixaban, sulfasalazine, etc. (Giacomini et al. 2013; Mao and Unadkat 2015; Hira and Terada 2018; Heyes et al. 2018; Safar et al. 2019; Toyoda et al. 2019; Svedberg et al. 2020).
Overcoming multidrug resistance through targeting ABC transporters: lessons for drug discovery
Published in Expert Opinion on Drug Discovery, 2022
Mohammad Feyzizadeh, Ashkan Barfar, Zeinab Nouri, Muhammad Sarfraz, Parvin Zakeri-Milani, Hadi Valizadeh
ABCG2 is the latest efflux pump reviewed in this section which has the lightest weight compared to the previous cases. It is a 72-kDa protein that consists of 665 amino acid units. ABCG2 is the half ABC transporter, and its functional figure is a homodimerized form that assembles in the plasma cell membrane. This protein consists of an N-terminal-NBD and a C-terminal-TMD. The presence of coupling TMDs plus coupling NBDs in its structure makes a unique conformation. Its special feature is that it is about half the size of other ABCs and has an inverted configuration compared to the majority of other ABC transporter proteins. Followed by six transmembrane helices (THs), ABCG2 is formed. The topology studies indicated that all extracellular loops are stunted, excluding the EL3, the loop which is among TH5 and TH6 [35]. The elevated amounts of ABCG2 were seen in the various organs such as the central nervous system, liver, adrenal gland, placenta, prostate, testes, and uterus [36]. Specified analysis expression of ABCG2 in the human gastrointestinal tract (GI) was explicitly tested. The results showed that the highest amounts of ABCG2 were lowered alongside the GI tract in the duodenum and ABCG2 levels. This pattern of ABCG2 expression in the GI tract pointed out that it may have a function in restricting the absorption of the oral drugs and substrates [35]. For the first time, Jonker et al. demonstrated in a study that ABCG2 can save the fetus from xenobiotic substances. Several researchers reported that ABCG2 could inhibit the fetal penetration of the antidiabetic c drug glyburide [37].
Optisol-GS Storage of Cultured Human Limbal Epithelial Cells at Ambient Temperature Is Superior to Hypothermic Storage
Published in Current Eye Research, 2020
Catherine Joan Jackson, Lara Pasovic, Sten Raeder, Amer Sehic, Borghild Roald, Maria F. de la Paz, Kim Alexsander Tønseth, Tor Paaske Utheim
Expression of cytokeratin CK3 indicated that differentiation was decreased in storage at 4°C and 23°C compared to the non-stored control. Expression of the putative limbal stem cell marker ΔNp63α, which is associated with clinical success,19 was low in all groups, including the non-stored control. However, the P63 antibody, which identifies both stem and transient amplifying non-differentiated cells, showed high expression in the non-stored control group and this was unaltered after storage at either temperature. ABCG2 is associated with stem cells in a number of cell types.18,29 Selver et al. used flow cytometry to show that export of dye is performed by ABCG2-positive cells and these cells undergo a large expansion in explant culture.17 Furthermore, they showed that high dye-excluding cells were found to have a high colony-forming ability, where each colony represents a stem cell. The results suggested that culture conditions activate proliferative function in stem cells, which may be useful in regeneration following transplantation. We found reduced ABCG2 staining in cells stored at 4°C compared to non-stored control. The decrease in ABCG2 cells may have been due to loss through cell death and detachment, as reflected in the cell viability results and morphological observations. Alternatively, the decrease in staining may indicate that stem cells in the HLEC sheet kept at 4°C were not activated.17 On the other hand, maintenance of ABCG2 at 23°C suggested that proliferative capability was maintained in this group, which was also supported by our analysis of PCNA expression.