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Selective Antimicrobial Agents from Terrestrial Plants A Hope in the Battle of Infection
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Fadia S. Youssef, Mohamed L. Ashour
The development of bacterial resistance against many antibiotics has been seriously reducing the success in curing such infections. There are many reported mechanisms involved in this resistance that include the inactivation of the antibiotic directly by changing important functional groups in the antimicrobial agents or even altering the dimensions or stereochemistry of the target enzymes. Moreover, the modification of the targeted site of action, the modification in the metabolic pathways, inhibition of drug uptake and reduction of the intracellular amount of the drug via its exist out of the infected cell by ABC transporters are other possible mechanisms (Wink et al. 2012). In addition, mechanisms for antimicrobial resistance comprise an effective efflux of the antimicrobial agent, reduction of drug entry into the microbial cells, degradation of antimicrobial drugs enzymatically in addition to the effective formation of biofilm (Varela et al. 2021).
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
ABC transporters comprise 49 members, which are classified into seven gene subfamilies (ABCA-G). Most of these act as active transporters (ATP dependent) and mediate the transport of substances through the plasma membrane and intracellular membrane. Several transporters are involved in the efflux of certain chemotherapeutic drugs leading to multidrug resistance (MDR) of CSC population. The most well studied MDR family members include ABCB1, ABCC1, and ABCG2. Those cells, which efflux Hoechst 33342 dye through ABCB1 and ABCG2 transporters, were identified as drug-resistant side population (SP) or CSCs [11, 12]. Primarily, four pathways regulate drug resistance genes in CSCs: HH, Wnt/β-catenin, EGFR, and Notch signaling pathways [13, 14].
Companion Animals Models of Human Disease
Published in Rebecca A. Krimins, Learning from Disease in Pets, 2020
Canine lymphoma (cL) is a common type of neoplasia in dogs with an estimated incidence rate of 20–100 cases per 100,000 dogs and is in many respects comparable to non-Hodgkin lymphoma in humans(75–77). Although the exact cause is unknown, environmental factors and genetic susceptibility are thought to play an important role. cL is not a single disease, and a wide variation in clinical presentations and histological subtypes is recognized. Despite this potential variation, most dogs present with generalized lymphadenopathy (multicentric form) and intermediate to high-grade lymphoma, more commonly of B-cell origin. The most common paraneoplastic sign is hypercalcemia that is associated with the T-cell immunophenotype. Chemotherapy is the treatment of choice and a doxorubicin-based multidrug protocol is currently the standard of care. A complete remission is obtained for most dogs and lasts for a median period of 7–10 months, resulting in a median survival of 10–14 months. Many prognostic factors have been reported, but stage, immunophenotype, tumor grade, and response to chemotherapy appear of particular importance. Failure to respond to chemotherapy suggests drug resistance, which can be partly attributed to the expression of drug transporters of the ABC-transporter superfamily, including P-gp and BCRP. Ultimately, most lymphomas will become drug resistant and the development of treatments aimed at reversing drug resistance or alternative treatment modalities (e.g. immunotherapy and targeted therapy) are of major importance.
ABC transporters in breast cancer: their roles in multidrug resistance and beyond
Published in Journal of Drug Targeting, 2022
Anupama Modi, Dipayan Roy, Shailja Sharma, Jeewan Ram Vishnoi, Puneet Pareek, Poonam Elhence, Praveen Sharma, Purvi Purohit
But newer research areas have emerged that hold the promise for carrying the investigation forward and making it more impactful in real-world outcomes. In particular, cholesterol homeostasis and membrane lipid trafficking are closely interlinked with ABC transporters, and they regulate pivotal processes regarding cellular signalling, communication, migration, and proliferation. Exploring the roles of these lipid molecules can increase our knowledge and aid us in the fine-tuned modulation of the different ABC transporters. Although, these transporters are not only found as the components of cellular membranes but in subcellular compartments such as Golgi apparatus and endoplasmic reticulum as well. Studies on the intracellular mechanisms of the regulation of ABC transporters in cancer are few, and fewer yet in BC. This is also an exciting arena to explore.
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
Biedler et al. pointed out that a cell surface protein could mediate the potential existence of MDR phenomenon[7]. MDR is one of the problems in the drug treatment process and may occur in many fungal diseases, bacteria, and cancer. In some bacteria, enzyme inactivation mechanisms like phosphorylation arrest aminoglycosides’ activity [8]. Some fungi develop drug resistance to fluconazole by changing the direction of ergosterol [9]. Common mechanisms of MDR between different organisms are efflux pumps or ABC transporters, which are naturally present in cells and play a significant role in maintaining their homeostasis [10]. ABC transporters are the significant components of the membrane protein superfamily that translocate different molecules like drugs across extra/intracellular membranes, which need to consume ATP to mediate the movement of their substrates across cell membranes. They are separated into subfamilies that in humans are ABCA to ABCG. On the other hand, plants possess ABCI in addition to ABCA to ABCG but do not have ABCH [11].
Different effects of lysophosphatidic acid receptor-2 (LPA2) and LPA5 on the regulation of chemoresistance in colon cancer cells
Published in Journal of Receptors and Signal Transduction, 2021
Kaichi Ishimoto, Akito Minami, Kanako Minami, Nanami Ueda, Toshifumi Tsujiuchi
In conclusion, the present results indicate that LPA2 positively and LPA5 negatively regulate the acquisition of chemoresistance in colon cancer cells. The cause of opposite effects between LPA2 and LPA5 on the cell survival to anticancer drugs is unclear. Since LPA5 is not coupled to Gi protein [1,2], the intracellular signaling via Gi protein may play important roles in the modulation of cells survival to anticancer drugs. Gi protein inhibits the activity of adenylyl cyclase [1]. On the other hand, LPA signaling via LPA5 promotes the intracellular cAMP level [18]. cAMP is synthesized from ATP by the activity of adenylyl cyclase, resulting in the intracellular cAMP accumulation [19]. It is known that some phosphodiesterase (PDE) inhibitors suppress ABC transporter functions. The enzyme PDE degrades the phosphodiester bond in cAMP and cGMP [20]. ABC transporters act as the efflux pumps of anticancer drugs and cytotoxic compounds through cell membranes [21]. To better understand the mechanisms underlying the acquisition of chemoresistance via LPA signaling, we are currently investigating the roles of LPA2 downstream effectors in the regulation of chemoresistance of colon cancer cells.