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Antiviral Drugs as Tools for Nanomedicine
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
In normal cells, during mitosis, cells divide and grow in an interdependent manner, depending on the availability of various stimulants or growth factors and ambient conditions. As the supply is on or off, normal cells switch to proliferation or stop dividing; however, such switch mechanisms are disrupted in transformed cells, due to which they become independent of any signals (Hanahan and Weinberg 2000, 2011). Such transformed cells also lose contact inhibition that is seen in normal cells, where cells stop dividing after attaining a specific threshold. On the contrary, cancer cells do not have any contact inhibition, leading to an uncontrolled mass of cells (Pavel et al. 2018). The life of a normal cell is limited and well-programmed; it dies when function is over, by apoptosis, and is replaced by a new cell. This is due to the limited efficiency of DNA replication, as, at each time, there is a shortening of telomeres. However, cancer cells show the very high activity of telomerase, which keeps restoring the worn-out ends of the telomere, thus granting the cell to proliferate unlimitedly (Trybek et al. 2020). Witsch et al. (2011) has described the stepwise process of cancer development and the role of various growth factors in each step.
MOF-based Electrochemical Sensors for Protein Detection
Published in Ram K. Gupta, Tahir Rasheed, Tuan Anh Nguyen, Muhammad Bilal, Metal-Organic Frameworks-Based Hybrid Materials for Environmental Sensing and Monitoring, 2022
Yang Liu, Juanhua Zhou, Shiyu Zhang, Hongye Wang
Telomerase is an enzyme responsible for maintaining telomere length in cells. Telomerase activity is tightly regulated in normal human cells, but the telomerase activity is always overexpressed in cancer cells. Thus, the measurement of telomerase’s activity is important to tumor screening. Due to the excellent physical and chemical properties of nanomaterials, biosensors based on MOFs combined with nanomaterials for detecting kinase activity has been reported a lot. The nanoscale metalloporphyrin MOF [P-MOF(Fe)] with Pd NPs grown [Pt@P-MOF(Fe)] was used as biomimetic catalyst signal media which was an ideal platform for sensing kinase activity [68]. Moreover, Xiong et al. constructed an electrochemiluminescence biosensor by ZIF-8 doped with ruthenium polyethyleneimine (Ru–PEI) complex which possessed high ECL efficiency [69]. Owing to an enzyme-assisted DNA recycle–amplification strategy, telomerase activity was successfully detected.
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Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Eun-Kyung Lim, Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh, Kwangyeol Lee
Drugs such as cisplatin, the antibiotics daunorubicin and DOX, and etoposide disrupt the replication of the DNA and cause formation of nonsense DNA or RNA by inhibiting telomerase activity or eliminating telomeric DNA. Telomerase as the natural enzyme for elongating telomeres enables cancer cells to divide virtually forever. Immortalization of cancer cells is considered to stem from their activity [354, 360]. Therefore, DOX, which is effective in treatments of acute leukemia, malignant lymphoma, and a variety of solid tumors, acts by intercalating between nucleic acid bases. It also inhibits the action of the enzyme topoisomerase II, thereby interfering with DNA and RNA biosynthesis. The four planar rings of the drug intercalate into DNA, whereas the hydroxyl group on the side chain interacts with topoisomerases II, which causes cleavage of DNA to stop the replication process [372, 373]. However, because it induces common toxicities, including cardiotoxicity [38], attempts to reduce its toxicity have been made by introducing novel carrier systems such as PEGylated liposomes [374–380]. Etoposide does not intercalate into DNA but forms a ternary complex with DNA and topoisomerase II enzyme, thereby preventing religation of the DNA strands, inducing errors in DNA synthesis and apoptosis of cancer cells [372–373].
Efficient expression of recombinant human telomerase inhibitor 1 (hPinX1) in Pichia pastoris
Published in Preparative Biochemistry and Biotechnology, 2018
Yagmur Unver, Melike Yildiz, Deryanur Kilic, Mesut Taskin, Abdulhadi Firat, Hakan Askin
Telomerase participates in malignant tumor development and formation.[4–6] Its expression is repressed in many normal cells. But, it is reactivated in a great majority (85%) of human cancer cells.[7,8] Also, telomeric repeat binding factor 1 (TRF1) and its associated proteins containing PinX1 regulate the telomerase activity.[9] In targeted tumor gene therapy, studying on telomerase inhibitors has become a significant area. PinX1 which is a putative tumor suppressor and a potent telomerase inhibitor was firstly determined as a Pin2/TRF1-binding protein in vivo. However, PinX1 can inhibit telomerase activity by binding directly to hTERT subunit differently from other TRF1-binding proteins.[10] This property makes it unique. Although normal human tissues express this protein, tumor tissues do not or less express it. Studies have reported that the telomerase activity in liver and gastric tumor cells can be inhibited by this protein and their apoptosis can be induced.[11–14] So, this protein has been defined as an endogenous telomerase inhibitor and the gene located in human chromosome 8p23 is known as a versatile tumor suppressor gene.[10] Consequently, PinX1 is a clinically remarkable tumor suppressor according to existent latest evidence from human tumors and mouse models.[15]
Expression of microRNA-155 and human telomerase reverse transcriptase in patients with bladder cancer
Published in Egyptian Journal of Basic and Applied Sciences, 2020
Ahmed Abdelgawad, Ahmed Mosbah, Laila A. Eissa
Telomerase is a ribonucleoprotein enzyme that synthesizes telomeres (repeated sequences of TTAGGG) at the ends of chromosomes to ensure genome stability. BC malignant cells acquire immortality by hyperactivating telomerase. For detecting telomerase efficiency, Eissa et al., found that detection of hTERT mRNA by RT-PCR, in voided urine samples is superior to RTA by TRAP assay and hTR mRNA by RT-PCR. The sensitivity, specificity, PPV, NPV, and accuracy of hTERT in BC diagnosis were 96%, 96%, 97%, 94% and 96% versus 75%, 94%, 96%, 64% and 81% for cytology, respectively [21].
Key characteristics of 86 agents known to cause cancer in humans
Published in Journal of Toxicology and Environmental Health, Part B, 2019
Daniel Krewski, Michael Bird, Mustafa Al-Zoughool, Nicholas Birkett, Mélissa Billard, Brittany Milton, Jerry M. Rice, Yann Grosse, Vincent J. Cogliano, Mark A. Hill, Robert. A. Baan, Julian Little, Jan M. Zielinski
Immortalization refers to a cell evading normal cellular senescence and proliferating indefinitely. In culture, normal cells have a fixed number of replication cycles before entering cellular senescence and stop replicating. Evasion of senescence is frequently associated with activation of telomerase (Willeit et al. 2010) and plays a critical part in carcinogenesis (Reddel 2000). Carcinogenesis may involve activation of a telomerase that prevents loss of telomere length, leading to immortalization of cells (Willeit et al. 2010).