Статті в журналах: "Therapeutic repositioning"

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Banno, Kouji, Miho Iida, Megumi Yanokura, Haruko Irie, Kenta Masuda, Yusuke Kobayashi, Eiichiro Tominaga, and Daisuke Aoki. "Drug Repositioning for Gynecologic Tumors: A New Therapeutic Strategy for Cancer." Scientific World Journal 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/341362.

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The goals of drug repositioning are to find a new pharmacological effect of a drug for which human safety and pharmacokinetics are established and to expand the therapeutic range of the drug to another disease. Such drug discovery can be performed at low cost and in the short term based on the results of previous clinical trials. New drugs for gynecologic tumors may be found by drug repositioning. For example, PPAR ligands may be effective against ovarian cancer, since PPAR activation eliminates COX-2 expression, arrests the cell cycle, and induces apoptosis. Metformin, an antidiabetic drug, is effective for endometrial cancer through inhibition of the PI3K-Akt-mTOR pathway by activating LKB1-AMPK and reduction of insulin and insulin-like growth factor-1 due to AMPK activation. COX-2 inhibitors for cervical cancer may also be examples of drug repositioning. PGE2 is induced in the arachidonate cascade by COX-2. PGE2 maintains high expression of COX-2 and induces angiogenic factors including VEGF and bFGF, causing carcinogenesis. COX-2 inhibitors suppress these actions and inhibit carcinogenesis. Combination therapy using drugs found by drug repositioning and current anticancer drugs may increase efficacy and reduce adverse drug reactions. Thus, drug repositioning may become a key approach for gynecologic cancer in drug discovery.

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Yan, Ran, Jiahao He, Ge Liu, Jianfeng Zhong, Jiapeng Xu, Kai Zheng, Zhe Ren, Zhendan He, and Qinchang Zhu. "Drug Repositioning for Hand, Foot, and Mouth Disease." Viruses 15, no. 1 (December 27, 2022): 75. http://dx.doi.org/10.3390/v15010075.

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Hand, foot, and mouth disease (HFMD) is a highly contagious disease in children caused by a group of enteroviruses. HFMD currently presents a major threat to infants and young children because of a lack of antiviral drugs in clinical practice. Drug repositioning is an attractive drug discovery strategy aimed at identifying and developing new drugs for diseases. Notably, repositioning of well-characterized therapeutics, including either approved or investigational drugs, is becoming a potential strategy to identify new treatments for virus infections. Various types of drugs, including antibacterial, cardiovascular, and anticancer agents, have been studied in relation to their therapeutic potential to treat HFMD. In this review, we summarize the major outbreaks of HFMD and the progress in drug repositioning to treat this disease. We also discuss the structural features and mode of action of these repositioned drugs and highlight the opportunities and challenges of drug repositioning for HFMD.

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Cuéllar Rodríguez, Santiago. "Therapeutic repositioning: importance of new therapeutic indications approved for old medicines." Anales de la Real Academia Nacional de Farmacia, no. 90(02) (July 1, 2024): 239–56. http://dx.doi.org/10.53519/analesranf.2024.90.02.06.

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In the field of health and, particularly in biomedicine, continuous reevaluation has allowed us to see with a different attitude what was apparently known; A large part of the medicines from synthetic chemistry, biotechnology and advanced therapies (genetics, somatics, tissue engineering, etc.) are a clear example of this. The search and investigation of new applications for drugs already approved and in clinical use – and even for compounds that did not reach the clinical research phases at the time – is usually called “repositioning”, which makes it possible to have drugs with a profile of safety and efficacy already known, which represents a significant saving in time and development costs and, sometimes, is the only way to develop therapies for rare diseases, as orphan indications. In fact, it is estimated that a substantial part of the known drugs may have new therapeutic uses and that drugs currently in clinical use could be used for numerous applications other than those for which they were originally approved. The high number of authorizations of new indications or their extensions or modifications by the EMA and the FDA, in relation to that of medicines with new active ingredients, highlights that pharmacological research – basic and clinical – does not end with the marketing authorization of a medicine but, on the contrary, there are many that continue to be the subject of extensive and intensive research by their titular laboratories in order to extract the maximum knowledge and health results from products whose development has a very high economic cost and requires large and multidisciplinary human research teams. In order to examine the current innovative activity in the field of new indications for medicines previously authorized in the European Union, we have proceeded to systematically collect and study the contents of all the summaries of the 36 plenary meetings of the Committee for Medicinal Products for Human Use (CHMP) published by the EMA between January 2021 and March 2024, in which 258 positive recommendations for extension of indications were made, for a total of 181 medicines from 74 laboratories. Keywords: Pharmacology; therapeutic repositioning; clinical research; drug authorization; drug evaluation

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Kwon, Minsu. "Drug Repositioning for Treatment of Head and Neck Cancers." Korean Journal of Otorhinolaryngology-Head and Neck Surgery 66, no. 8 (August 25, 2023): 505–13. http://dx.doi.org/10.3342/kjorl-hns.2023.00731.

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Head and neck cancer (HNC) is a complex disease that poses significant therapeutic challenges. Traditional treatment options such as surgery, radiation, and chemotherapy have limited efficacy and often result in significant side effects. In recent years, drug repositioning has emerged as a promising strategy to identify new therapeutic options for HNC. Drug repositioning involves repurposing existing drugs, already approved for other indications, for the treatment of HNC. This approach takes advantage of existing knowledge about drug safety and efficacy, reducing the time and cost needed to develop new drugs. By leveraging the known safety profiles, pharmacokinetic, and pharmacodynamic properties of these drugs, drug repositioning can accelerate the drug development process and reduce costs. In this review, the current status of drug repositioning efforts for HNC and the challenges and opportunities associated with this approach are discussed. We also highlight some of the most promising drug candidates that have emerged from recent studies and clinical trials. Overall, drug repositioning has the potential to significantly improve the treatment landscape for HNC and offer new hope for patients with this challenging disease.

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Perwitasari, Olivia, Abhijeet Bakre, S. Tompkins, and Ralph Tripp. "siRNA Genome Screening Approaches to Therapeutic Drug Repositioning." Pharmaceuticals 6, no. 2 (January 28, 2013): 124–60. http://dx.doi.org/10.3390/ph6020124.

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Ruckenstein, Michael J. "Therapeutic Efficacy of the Epley Canalith Repositioning Maneuver." Laryngoscope 111, no. 6 (June 2001): 940–45. http://dx.doi.org/10.1097/00005537-200106000-00003.

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Hu, Qingkai, Xianfang Wang, Yifeng Liu, Yu Sang, and Dongfang Zhang. "Application of artificial intelligence in drug repositioning." Gene & Protein in Disease 1, no. 3 (November 7, 2022): 201. http://dx.doi.org/10.36922/gpd.v1i3.201.

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The use of artificial intelligence technologies in biology, pharmacy, and medicine has brought about a dramatic change in these industries. Drug repositioning is a method of drug development in the process of applying existing therapeutic agents to new diseases. This paper first outlines the use of artificial intelligence technology in the field of drug repositioning, then reviews a variety of application methods of artificial intelligence in the realm of drug repositioning, and finally summarizes the advantages and disadvantages of these methods, and proposes the difficulties faced by artificial intelligence in drug repositioning in the future and the corresponding suggestions to achieve the goal of helping researchers to develop more effective methods of drug repositioning.

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Marrazzo, Pasquale, and Cian O’Leary. "Repositioning Natural Antioxidants for Therapeutic Applications in Tissue Engineering." Bioengineering 7, no. 3 (September 2, 2020): 104. http://dx.doi.org/10.3390/bioengineering7030104.

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Although a large panel of natural antioxidants demonstrate a protective effect in preventing cellular oxidative stress, their low bioavailability limits therapeutic activity at the targeted injury site. The importance to deliver drug or cells into oxidative microenvironments can be realized with the development of biocompatible redox-modulating materials. The incorporation of antioxidant compounds within implanted biomaterials should be able to retain the antioxidant activity, while also allowing graft survival and tissue recovery. This review summarizes the recent literature reporting the combined role of natural antioxidants with biomaterials. Our review highlights how such functionalization is a promising strategy in tissue engineering to improve the engraftment and promote tissue healing or regeneration.

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Lee, Soojung, Judee Grace E. Nemeño, and Jeong Ik Lee. "Repositioning Bevacizumab: A Promising Therapeutic Strategy for Cartilage Regeneration." Tissue Engineering Part B: Reviews 22, no. 5 (October 2016): 341–57. http://dx.doi.org/10.1089/ten.teb.2015.0300.

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Shibata, Kyoko, Toshinori Endo, and Yoshikazu Kuribayashi. "Computational Drug-repositioning Approach Identifying Sirolimus as a Potential Therapeutic Option for Inflammatory Dilated Cardiomyopathy." Drug Research 69, no. 10 (June 25, 2019): 565–71. http://dx.doi.org/10.1055/a-0950-9608.

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Abstract Objective The aim of this study was to determine promising treatment options for human inflammatory dilated cardiomyopathy using a computational drug-repositioning approach (repurposing established drug compounds for new therapeutic indications). Background If the myocardial tissue is detected to be infiltrated with inflammatory cells, primarily of lymphocytes, and if the virus is confirmed using genetic examination (PCR) or immunostaining, the infection is suspected. However, there is no specific treatment (i. e., an antiviral drug) even if the virus is identified; therefore, we used Connectivity Map to identify compounds showing inverse drug–disease signatures, indicating activity against inflammatory dilated cardiomyopathy. Results Potential drug-repositioning candidates for the treatment of inflammatory dilated cardiomyopathy were explored through a systematic comparison of the gene expression profiles induced by drugs using Gene Expression Omnibus and Connectivity Map databases. Conclusion Using a computational drug-repositioning approach based on the integration of publicly available gene expression signatures of drugs and diseases, sirolimus was suggested as a novel therapeutic option for inflammatory dilated cardiomyopathy.

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Xie, Yuhan. "The Relationship Between Reelin and Sphingosine-1-Phosphate in the Repositioning of Adult-Generated Dentate Granule Cells." Theoretical and Natural Science 73, no. 1 (January 8, 2025): 76–81. https://doi.org/10.54254/2753-8818/2024.19363.

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Reelin and sphingosine-1-phosphate (S1P) are important in adult neurogenesis, particularly in the repositioning of newly formed dentate granule cells (DGCs). The relationship between Reelin and S1P in the repositioning of new DGCs is investigated in this study, with a specific focus on their functioning pathways and upstream/downstream relationships. Applying gene knockdown and immunostaining methods, this research discovers that Reelin and S1P function in the same signaling pathway during the new DGC's repositioning process, and it appears that Reelin works upstream of S1P. The results could potentially inform therapeutic measures for cognitive disorders associated with neurogenesis impairment

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Hay Mele, Bruno, Federica Rossetti, Maria Vittoria Cubellis, Maria Monticelli, and Giuseppina Andreotti. "Drug Repurposing and Lysosomal Storage Disorders: A Trick to Treat." Genes 15, no. 3 (February 25, 2024): 290. http://dx.doi.org/10.3390/genes15030290.

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Rare diseases, or orphan diseases, are defined as diseases affecting a small number of people compared to the general population. Among these, we find lysosomal storage disorders (LSDs), a cluster of rare metabolic diseases characterized by enzyme mutations causing abnormal glycolipid storage. Drug repositioning involves repurposing existing approved drugs for new therapeutic applications, offering advantages in cost, time savings, and a lower risk of failure. We present a comprehensive analysis of existing drugs, their repurposing potential, and their clinical implications in the context of LSDs, highlighting the necessity of mutation-specific approaches. Our review systematically explores the landscape of drug repositioning as a means to enhance LSDs therapies. The findings advocate for the strategic repositioning of drugs, accentuating its role in expediting the discovery of effective treatments. We conclude that drug repurposing represents a viable pathway for accelerating therapeutic discovery for LSDs, emphasizing the need for the careful evaluation of drug efficacy and toxicity in disease-specific contexts.

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Adasme, Melissa F., Sarah Naomi Bolz, Lauren Adelmann, Sebastian Salentin, V. Joachim Haupt, Adriana Moreno-Rodríguez, Benjamín Nogueda-Torres, et al. "Repositioned Drugs for Chagas Disease Unveiled via Structure-Based Drug Repositioning." International Journal of Molecular Sciences 21, no. 22 (November 20, 2020): 8809. http://dx.doi.org/10.3390/ijms21228809.

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Chagas disease, caused by the parasite Trypanosoma cruzi, affects millions of people in South America. The current treatments are limited, have severe side effects, and are only partially effective. Drug repositioning, defined as finding new indications for already approved drugs, has the potential to provide new therapeutic options for Chagas. In this work, we conducted a structure-based drug repositioning approach with over 130,000 3D protein structures to identify drugs that bind therapeutic Chagas targets and thus represent potential new Chagas treatments. The screening yielded over 500 molecules as hits, out of which 38 drugs were prioritized following a rigorous filtering process. About half of the latter were already known to have trypanocidal activity, while the others are novel to Chagas disease. Three of the new drug candidates—ciprofloxacin, naproxen, and folic acid—showed a growth inhibitory activity in the micromolar range when tested ex vivo on T. cruzi trypomastigotes, validating the prediction. We show that our drug repositioning approach is able to pinpoint relevant drug candidates at a fraction of the time and cost of a conventional screening. Furthermore, our results demonstrate the power and potential of structure-based drug repositioning in the context of neglected tropical diseases where the pharmaceutical industry has little financial interest in the development of new drugs.

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Jamir, Esther, Himakshi Sarma, Lipsa Priyadarsinee, Kikrusenuo Kiewhuo, Selvaraman Nagamani, and G. Narahari Sastry. "Polypharmacology guided drug repositioning approach for SARS-CoV2." PLOS ONE 18, no. 8 (August 9, 2023): e0289890. http://dx.doi.org/10.1371/journal.pone.0289890.

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Drug repurposing has emerged as an important strategy and it has a great potential in identifying therapeutic applications for COVID-19. An extensive virtual screening of 4193 FDA approved drugs has been carried out against 24 proteins of SARS-CoV2 (NSP1-10 and NSP12-16, envelope, membrane, nucleoprotein, spike, ORF3a, ORF6, ORF7a, ORF8, and ORF9b). The drugs were classified into top 10 and bottom 10 drugs based on the docking scores followed by the distribution of their therapeutic indications. As a result, the top 10 drugs were found to have therapeutic indications for cancer, pain, neurological disorders, and viral and bacterial diseases. As drug resistance is one of the major challenges in antiviral drug discovery, polypharmacology and network pharmacology approaches were employed in the study to identify drugs interacting with multiple targets and drugs such as dihydroergotamine, ergotamine, bisdequalinium chloride, midostaurin, temoporfin, tirilazad, and venetoclax were identified among the multi-targeting drugs. Further, a pathway analysis of the genes related to the multi-targeting drugs was carried which provides insight into the mechanism of drugs and identifying targetable genes and biological pathways involved in SARS-CoV2.

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Padhy, BM, and YK Gupta. "Drug repositioning: Re-investigating existing drugs for new therapeutic indications." Journal of Postgraduate Medicine 57, no. 2 (2011): 153. http://dx.doi.org/10.4103/0022-3859.81870.

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Tjioe, Kellen Cristine, Denise Tostes Oliveira, and Julie Gavard. "Drug Repositioning Identifies Luteolin as an Oral Cancer Therapeutic Agent." Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 126, no. 3 (September 2018): e167. http://dx.doi.org/10.1016/j.oooo.2018.02.667.

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Wasim, Rufaida, Tarique Mahmood Ansari, Mohammed Haris Siddiqui, Farogh Ahsan, Arshiya Shamim, Aditya Singh, Mohammad Shariq, Aamir Anwar, Aquib Rehanullah Siddiqui, and Saba Parveen. "Repurposing of Drugs for Cardiometabolic Disorders: An Out and Out Cumulation." Hormone and Metabolic Research 55, no. 01 (January 2023): 7–24. http://dx.doi.org/10.1055/a-1971-6965.

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AbstractCardiometabolic disorders (CMD) is a constellation of metabolic predisposing factors for atherosclerosis such as insulin resistance (IR) or diabetes mellitus (DM), systemic hypertension, central obesity, and dyslipidemia. Cardiometabolic diseases (CMDs) continue to be the leading cause of mortality in both developed and developing nations, accounting for over 32% of all fatalities globally each year. Furthermore, dyslipidemia, angina, arrhythmia, heart failure, myocardial infarction (MI), and diabetes mellitus are the major causes of death, accounting for an estimated 19 million deaths in 2012. CVDs will kill more than 23 million individuals each year by 2030. Nonetheless, new drug development (NDD) in CMDs has been increasingly difficult in recent decades due to increased costs and a lower success rate. Drug repositioning in CMDs looks promising in this scenario for launching current medicines for new therapeutic indications. Repositioning is an ancient method that dates back to the 1960s and is mostly based on coincidental findings during medication trials. One significant advantage of repositioning is that the drug’s safety profile is well known, lowering the odds of failure owing to undesirable toxic effects. Furthermore, repositioning takes less time and money than NDD. Given these facts, pharmaceutical corporations are becoming more interested in medication repositioning. In this follow-up, we discussed the notion of repositioning and provided some examples of repositioned medications in cardiometabolic disorders.

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Bellera, Carolina L., Lucas N. Alberca, María L. Sbaraglini, and Alan Talevi. "In Silico Drug Repositioning for Chagas Disease." Current Medicinal Chemistry 27, no. 5 (March 16, 2020): 662–75. http://dx.doi.org/10.2174/0929867326666191016114839.

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: Chagas disease is an infectious tropical disease included within the group of neglected tropical diseases. Though historically endemic to Latin America, it has lately spread to high-income countries due to human migration. At present, there are only two available drugs, nifurtimox and benznidazole, approved for this treatment, both with considerable side-effects (which often result in treatment interruption) and limited efficacy in the chronic stage of the disease in adults. : Drug repositioning involves finding novel therapeutic indications for known drugs, including approved, withdrawn, abandoned and investigational drugs. It is today a broadly applied approach to develop innovative medications, since indication shifts are built on existing safety, ADME and manufacturing information, thus greatly shortening development timeframes. Drug repositioning has been signaled as a particularly interesting strategy to search for new therapeutic solutions for neglected and rare conditions, which traditionally present limited commercial interest and are mostly covered by the public sector and not-for-profit initiatives and organizations. : Here, we review the applications of computer-aided technologies as systematic approaches to drug repositioning in the field of Chagas disease. In silico screening represents the most explored approach, whereas other rational methods such as network-based and signature-based approximations have still not been applied.

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Spinas, Enrico, Laura Pipi, and Claudia Dettori. "Extrusive Luxation Injuries in Young Patients: A Retrospective Study with 5-Year Follow-Up." Dentistry Journal 8, no. 4 (December 16, 2020): 136. http://dx.doi.org/10.3390/dj8040136.

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(1) Background: The purpose of this study was to analyze the influence of the chosen diagnostic and therapeutic approach (repositioning and splinting methods) on the risk, frequency and timing of the onset of pulp canal obliteration and pulp necrosis following extrusive luxation in young patients with permanent dentition. (2) Methods: From an initial sample of 50 subjects affected by extrusive luxation, were selected the clinical data of 13 patients presenting extrusive luxation but no other type of injury to the dental hard tissue. All teeth were examined according to a standardized protocol. Follow-up examinations were performed at regular intervals for 5 years. Statistical associations between pulp consequences and several covariates were assessed using the Mann–Whitney test and Fisher’s exact test. (3) Results: Among the 13 studied teeth, only 1 healed completely, whereas 9 showed pulp obliteration and 3 developed pulp necrosis. No tooth with obliteration developed pulp necrosis. The average time to treatment was 11.9 h. The treatment approaches used were manual repositioning, orthodontic repositioning and stabilization splinting. “Time to treatment” was the only covariate that showed a weak statistical association with the onset of pulp consequences. (4) Conclusions: There is still uncertainty over the most appropriate therapeutic approach to adopt in young patients with extrusive luxation injuries, particularly for repositioning of the injured tooth. Extruded teeth should be treated as soon as possible after the traumatic event. This study highlighted the value of orthodontic repositioning of the extruded tooth, which does not seem to aggravate the conditions of the dental pulp. In addition, the study confirmed that prophylactic endodontic treatment is not appropriate for immature teeth affected by extrusive luxation injuries, given the extreme rarity of pulp necrosis in teeth already affected by pulp obliteration.

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Yin, Zheng, and Stephen T. C. Wong. "Converging multi-modality datasets to build efficient drug repositioning pipelines against Alzheimer’s disease and related dementias." Medical Review 2, no. 1 (February 1, 2022): 110–13. http://dx.doi.org/10.1515/mr-2021-0017.

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Abstract Alzheimer’s disease and related dementias (AD/ADRD) affects more than 50 million people worldwide but there is no clear therapeutic option affordable for the general patient population. Recently, drug repositioning studies featuring collaborations between academic institutes, medical centers, and hospitals are generating novel therapeutics candidates against these devastating diseases and filling in an important area for healthcare that is poorly represented by pharmaceutical companies. Such drug repositioning studies converge expertise from bioinformatics, chemical informatics, medical informatics, artificial intelligence, high throughput and high-content screening and systems biology. They also take advantage of multi-scale, multi-modality datasets, ranging from transcriptomic and proteomic data, electronical medical records, and medical imaging to social media information of patient behaviors and emotions and epidemiology profiles of disease populations, in order to gain comprehensive understanding of disease mechanisms and drug effects. We proposed a recursive drug repositioning paradigm involving the iteration of three processing steps of modeling, prediction, and validation to identify known drugs and bioactive compounds for AD/ADRD. This recursive paradigm has the potential of quickly obtaining a panel of robust novel drug candidates for AD/ADRD and gaining in-depth understanding of disease mechanisms from those repositioned drug candidates, subsequently improving the success rate of predicting novel hits.

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Papacharalampous, George X., P. V. Vlastarakos, G. P. Kotsis, D. Davilis, and L. Manolopoulos. "The Role of Postural Restrictions after BPPV Treatment: Real Effect on Successful Treatment and BPPV’s Recurrence Rates." International Journal of Otolaryngology 2012 (2012): 1–5. http://dx.doi.org/10.1155/2012/932847.

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Background. Canalith repositioning techniques are adequately established in the literature, as the treatment of choice for benign paroxysmal positional vertigo. However, the role of the posttreatment instructions is still not clearly defined.Patients and Methods. A retrospective chart review of 82 patients was conducted in order to determine the efficacy of postural restrictions, when combined with the classic canalith repositioning techniques, in terms of successful treatment and recurrence rates. Follow-up period reached at least 12 months after the initial treatment.Results. In this study, postural restrictions did not appear to significantly affect the outcomes of repositioning maneuvers, as well as the recurrence rate.Conclusions. Although this study, as well as most recent control studies, states that there is no significant effect of postmaneuver postural restrictions on both treatment and recurrence rates, larger multicentric research projects, adopting improved methodology, are still necessary in order to determine the contribution of such restrictions to both the therapeutic results and the prevention of recurrence. Adequate followup, focusing on the first six months after the initially successful repositioning maneuver, is also of paramount importance.

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Zhang, Cheng, Mengnan Shi, Woonghee Kim, Muhammad Arif, Martina Klevstig, Xiangyu Li, Hong Yang, et al. "Discovery of therapeutic agents targeting PKLR for NAFLD using drug repositioning." eBioMedicine 83 (September 2022): 104214. http://dx.doi.org/10.1016/j.ebiom.2022.104214.

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Tano, Sho, Tomomi Kotani, Takafumi Ushida, Noriyuki Nakamura, Yukako Iitani, Masato Yoshihara, Kenji Imai, and Hiroaki Kajiyama. "Developing of a novel therapeutic agent for FGR through Drug repositioning." Placenta 128 (October 2022): 124. http://dx.doi.org/10.1016/j.placenta.2022.08.018.

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Shameer, Khader, Ben Readhead, and Joel T. Dudley. "Computational and Experimental Advances in Drug Repositioning for Accelerated Therapeutic Stratification." Current Topics in Medicinal Chemistry 15, no. 1 (January 14, 2015): 5–20. http://dx.doi.org/10.2174/1568026615666150112103510.

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Choung, Boyoung, Dongil Lee, Shinki Ahn, Moonhyoung Lee, Myounhee Kim, Suyoung Kim, and Sungsoon Kim. "Repositioning of Pacemaker Generator due to Therapeutic Radiation: A Tunneling Method." Korean Circulation Journal 28, no. 9 (1998): 1620. http://dx.doi.org/10.4070/kcj.1998.28.9.1620.

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Simmons, H. Clifton. "Temporomandibular Joint Orthopedics With Anterior Repositioning Appliance Therapy and Therapeutic Injections." Journal of the California Dental Association 42, no. 8 (August 1, 2014): 537–48. http://dx.doi.org/10.1080/19424396.2014.12221400.

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Rivas, Sarah R., Mynor J. Mendez Valdez, Jay S. Chandar, Jelisah F. Desgraves, Victor M. Lu, Leo Ampie, Eric B. Singh, et al. "Antiretroviral Drug Repositioning for Glioblastoma." Cancers 16, no. 9 (April 30, 2024): 1754. http://dx.doi.org/10.3390/cancers16091754.

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Outcomes for glioblastoma (GBM) remain poor despite standard-of-care treatments including surgical resection, radiation, and chemotherapy. Intratumoral heterogeneity contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. Drug repositioning studies on antiretroviral therapy (ART) have shown promising potent antineoplastic effects in multiple cancers; however, its efficacy in GBM remains unclear. To better understand the pleiotropic anticancer effects of ART on GBM, we conducted a comprehensive drug repurposing analysis of ART in GBM to highlight its utility in translational neuro-oncology. To uncover the anticancer role of ART in GBM, we conducted a comprehensive bioinformatic and in vitro screen of antiretrovirals against glioblastoma. Using the DepMap repository and reversal of gene expression score, we conducted an unbiased screen of 16 antiretrovirals in 40 glioma cell lines to identify promising candidates for GBM drug repositioning. We utilized patient-derived neurospheres and glioma cell lines to assess neurosphere viability, proliferation, and stemness. Our in silico screen revealed that several ART drugs including reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs) demonstrated marked anti-glioma activity with the capability of reversing the GBM disease signature. RTIs effectively decreased cell viability, GBM stem cell markers, and proliferation. Our study provides mechanistic and functional insight into the utility of ART repurposing for malignant gliomas, which supports the current literature. Given their safety profile, preclinical efficacy, and neuropenetrance, ARTs may be a promising adjuvant treatment for GBM.

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Frohman, E. M., P. D. Kramer, R. B. Dewey, L. Kramer, and T. C. Frohman. "Benign paroxysmal positioning vertigo in multiple sclerosis: diagnosis, pathophysiology and therapeutic techniques." Multiple Sclerosis Journal 9, no. 3 (June 2003): 250–55. http://dx.doi.org/10.1191/1352458503ms901oa.

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Objective: To report on the most common causes of vertigo in patients with multiple sclerosis (MS) and emphasize appro priate diagnostic techniques and treatment interventions. Background: True vertigo is estimated to occur in about 20% of MS patients. Lesions within the vestibular nuclei and in the root entry zone of cranial nerve VIII represent the most common locations where demyelinating activity can provoke vertigo in patients with MS. However, other causes of vertigo should be explored in MS patients in order to avoid unnecessar y treatment with corticosteroids and vestibular suppressants. Recently, we reviewed our four-year experience with new onset vertigo in our university-based MS population and found that benign paroxysmal positioning vertigo (BPPV) to be the most common cause. A ll patients diagnosed with BPPV were treated successfully with particle repositioning maneuvers. The remaining patients were treated with conventional therapies appro priate for the specific diagnosis. Conclusions: Empiric treatments with corticosteroids and/or vestibular suppressants should not be employed until all MS patients undergo a careful bedside examination, which includes diagnostic positional and, if indicated, particle repositioning maneuvers. Here we emphasize the pathophysiology of BPPV and illustrate the proper techniques for the diagnostic and therapeutic maneuvers.

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Thorsteinsdottir, Jun, Torleif Sandner, Annamaria Biczok, Robert Forbrig, Sebastian Siller, Patricia Bernasconi, Andrea Szelényi, Thomas Liebig, Jörg-Christian Tonn, and Christian Schichor. "Detection of impending perfusion deficits by intraoperative computed tomography (iCT) in aneurysm surgery of the anterior circulation." Acta Neurochirurgica 163, no. 12 (October 13, 2021): 3501–14. http://dx.doi.org/10.1007/s00701-021-05022-8.

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Abstract Background The aim of our study was to evaluate the additional benefit of intraoperative computed tomography (iCT), intraoperative computed tomography angiography (iCTA), and intraoperative computed tomography perfusion (iCTP) in the intraoperative detection of impending ischemia to established methods (indocyanine green videoangiography (ICGVA), microDoppler, intraoperative neuromonitoring (IONM)) for initiating timely therapeutic measures. Methods Patients with primary aneurysms of the anterior circulation between October 2016 and December 2019 were included. Data of iCT modalities compared to other techniques (ICGVA, microDoppler, IONM) was recorded with emphasis on resulting operative conclusions leading to inspection of clip position, repositioning, or immediate initiation of conservative treatment strategies. Additional variables analyzed included patient demographics, aneurysm-specific characteristics, and clinical outcome. Results Of 194 consecutive patients, 93 patients with 100 aneurysms received iCT imaging. While IONM and ICGVA were normal, an altered vessel patency in iCTA was detected in 5 (5.4%) and a mismatch in iCTP in 7 patients (7.5%). Repositioning was considered appropriate in 2 patients (2.2%), where immediate improvement in iCTP could be documented. In a further 5 cases (5.4%), intensified conservative therapy was immediately initiated treating the reduced CBP as clip repositioning was not considered causal. In terms of clinical outcome at last FU, mRS0 was achieved in 85 (91.4%) and mRS1-2 in 7 (7.5%) and remained mRS4 in one patient with SAH (1.1%). Conclusions Especially iCTP can reveal signs of impending ischemia in selected cases and enable the surgeon to promptly initiate therapeutic measures such as clip repositioning or intraoperative onset of maximum conservative treatment, while established tools might fail to detect those intraoperative pathologic changes.

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Johnson, Karen L., and Tim Meyenburg. "Physiological Rationale and Current Evidence for Therapeutic Positioning of Critically Ill Patients." AACN Advanced Critical Care 20, no. 3 (July 1, 2009): 228–40. http://dx.doi.org/10.4037/15597768-2009-3005.

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Prolonged bed rest is common in critically ill patients, and therapeutic positioning is important to prevent further complications and to improve patient outcomes. Nurses use therapeutic positioning to prevent complications of immobility. This article reviews therapeutic positions including stationary positions (supine, semirecumbent with head of bed elevation, lateral, and prone) and active repositioning (manual, continuous lateral rotation, and kinetic therapy). The physiological rationale and current evidence for each position are described. Applicable evidence-based practice guidelines are summarized. Special considerations for therapeutic positioning of critically ill obese and elderly patients are also discussed.

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Bolognino, Isabella, Marco Catto, Leonardo Pisani, Saverio Cellamare, Cosimo D. Altomare, and Nicola Giangregorio. "Repositioning of Dantrolene as a Multitarget Agent for Neurodegenerative Diseases." Proceedings 22, no. 1 (August 7, 2019): 7. http://dx.doi.org/10.3390/proceedings2019022007.

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Kushchayeva, Yevgeniya, Kirk Jensen, Kenneth D. Burman, and Vasyl Vasko. "Repositioning therapy for thyroid cancer: new insights on established medications." Endocrine-Related Cancer 21, no. 3 (January 20, 2014): R183—R194. http://dx.doi.org/10.1530/erc-13-0473.

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Repositioning of established non-cancer pharmacotherapeutic agents with well-known activity and side-effect profiles is a promising avenue for the development of new treatment modalities for multiple cancer types. We have analyzed some of the medications with mechanism of action that may have relevance to thyroid cancer (TC). Experimentalin vitroandin vivoevidences, as well as results of clinical studies, have indicated that molecular targets for medications currently available for the treatment of mood disorders, sexually transmitted diseases, metabolic disorders, and diabetes may be active and relevant in TC. For instance, the derivatives of cannabis and an anti-diabetic agent, metformin, both are able to inhibit ERK, which is commonly activated in TC cells. We present here several examples of well-known medications that have the potential to become new therapeutics for patients with TC. Repositioning of established medications for the treatment of TC could broaden the scope of current therapeutic strategies. These diverse treatment choices could allow physicians to provide an individualized approach to optimize treatment for patients with TC.

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Xu, Manyi, Wan Li, Jiaheng He, Yahui Wang, Junjie Lv, Weiming He, Lina Chen, and Hui Zhi. "DDCM: A Computational Strategy for Drug Repositioning Based on Support-Vector Regression Algorithm." International Journal of Molecular Sciences 25, no. 10 (May 12, 2024): 5267. http://dx.doi.org/10.3390/ijms25105267.

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Computational drug-repositioning technology is an effective tool for speeding up drug development. As biological data resources continue to grow, it becomes more important to find effective methods to identify potential therapeutic drugs for diseases. The effective use of valuable data has become a more rational and efficient approach to drug repositioning. The disease–drug correlation method (DDCM) proposed in this study is a novel approach that integrates data from multiple sources and different levels to predict potential treatments for diseases, utilizing support-vector regression (SVR). The DDCM approach resulted in potential therapeutic drugs for neoplasms and cardiovascular diseases by constructing a correlation hybrid matrix containing the respective similarities of drugs and diseases, implementing the SVR algorithm to predict the correlation scores, and undergoing a randomized perturbation and stepwise screening pipeline. Some potential therapeutic drugs were predicted by this approach. The potential therapeutic ability of these drugs has been well-validated in terms of the literature, function, drug target, and survival-essential genes. The method’s feasibility was confirmed by comparing the predicted results with the classical method and conducting a co-drug analysis of the sub-branch. Our method challenges the conventional approach to studying disease–drug correlations and presents a fresh perspective for understanding the pathogenesis of diseases.

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Potenza, Rosa Luisa, Monica Armida, and Patrizia Popoli. "Can Some Anticancer Drugs Be Repurposed to Treat Amyotrophic Lateral Sclerosis? A Brief Narrative Review." International Journal of Molecular Sciences 25, no. 3 (February 1, 2024): 1751. http://dx.doi.org/10.3390/ijms25031751.

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Amyotrophic lateral sclerosis (ALS) is a rare progressive motor neuron disease that, due to its high complexity, still lacks effective treatments. Development of a new drug is a highly costly and time-consuming process, and the repositioning of approved drugs can represent an efficient strategy to provide therapeutic opportunities. This is particularly true for rare diseases, which are characterised by small patient populations and therefore attract little commercial interest. Based on the overlap between the biological background of cancer and neurodegeneration, the repurposing of antineoplastic drugs for ALS has been suggested. The objective of this narrative review was to summarise the current experimental evidence on the use of approved anticancer drugs in ALS. Specifically, anticancer drugs belonging to different classes were found to act on mechanisms involved in the ALS pathogenesis, and some of them proved to exert beneficial effects in ALS models. However, additional studies are necessary to confirm the real therapeutic potential of anticancer drugs for repositioning in ALS treatment.

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KANEKO, Shuji. "3. Drug Repositioning and Novel Therapeutic Target Search Based on Clinical Evidence." Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics 52, no. 2 (March 31, 2021): 50. http://dx.doi.org/10.3999/jscpt.52.50.

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Miranda, Mariana R., and Melisa M. Sayé. "Chagas Disease Treatment: From New Therapeutic Targets to Drug Discovery and Repositioning." Current Medicinal Chemistry 26, no. 36 (December 13, 2019): 6517–18. http://dx.doi.org/10.2174/092986732636191202125919.

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Bot, Adrian, Francesco Marincola, and Kent A. Smith. "Repositioning therapeutic cancer vaccines in the dawning era of potent immune interventions." Expert Review of Vaccines 12, no. 10 (October 2013): 1219–34. http://dx.doi.org/10.1586/14760584.2013.836908.

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Re, Matteo, and Giorgio Valentini. "Network-Based Drug Ranking and Repositioning with Respect to DrugBank Therapeutic Categories." IEEE/ACM Transactions on Computational Biology and Bioinformatics 10, no. 6 (November 2013): 1359–71. http://dx.doi.org/10.1109/tcbb.2013.62.

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Alfedi, Giulia, Riccardo Luffarelli, Ivano Condò, Giorgia Pedini, Liliana Mannucci, Damiano S. Massaro, Monica Benini, et al. "Drug repositioning screening identifies etravirine as a potential therapeutic for friedreich's ataxia." Movement Disorders 34, no. 3 (January 9, 2019): 323–34. http://dx.doi.org/10.1002/mds.27604.

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Blankenship, James C., and Alan C. Ford. "Therapeutic repositioning of a Gianturco-Roubin II coronary stent after initial deployment." Catheterization and Cardiovascular Diagnosis 45, no. 1 (September 1998): 57–60. http://dx.doi.org/10.1002/(sici)1097-0304(199809)45:1<57::aid-ccd13>3.0.co;2-i.

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Yoshida, Kosuke, Eri Watanabe, Takuya Imagawa, Yuko Yasui, Yuki Nishiko, Mayu Shibata, Yukari Oda, et al. "Identification of novel therapeutic agents for choriocarcinoma based on drug repositioning strategies." Placenta 141 (September 2023): 94. http://dx.doi.org/10.1016/j.placenta.2023.08.010.

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Zhou, Xu, Enyu Dai, Qian Song, Xueyan Ma, Qianqian Meng, Yongshuai Jiang, and Wei Jiang. "In silico drug repositioning based on drug-miRNA associations." Briefings in Bioinformatics 21, no. 2 (February 11, 2019): 498–510. http://dx.doi.org/10.1093/bib/bbz012.

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Abstract Drug repositioning has become a prevailing tactic as this strategy is efficient, economical and low risk for drug discovery. Meanwhile, recent studies have confirmed that small-molecule drugs can modulate the expression of disease-related miRNAs, which indicates that miRNAs are promising therapeutic targets for complex diseases. In this study, we put forward and verified the hypothesis that drugs with similar miRNA profiles may share similar therapeutic properties. Furthermore, a comprehensive drug–drug interaction network was constructed based on curated drug-miRNA associations. Through random network comparison, topological structure analysis and network module extraction, we found that the closely linked drugs in the network tend to treat the same diseases. Additionally, the curated drug–disease relationships (from the CTD) and random walk with restarts algorithm were utilized on the drug–drug interaction network to identify the potential drugs for a given disease. Both internal validation (leave-one-out cross-validation) and external validation (independent drug–disease data set from the ChEMBL) demonstrated the effectiveness of the proposed approach. Finally, by integrating drug-miRNA and miRNA-disease information, we also explain the modes of action of drugs in the view of miRNA regulation. In summary, our work could determine novel and credible drug indications and offer novel insights and valuable perspectives for drug repositioning.

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Kitsiranuwat, Satanat, Apichat Suratanee, and Kitiporn Plaimas. "Integration of various protein similarities using random forest technique to infer augmented drug-protein matrix for enhancing drug-disease association prediction." Science Progress 105, no. 3 (July 2022): 003685042211092. http://dx.doi.org/10.1177/00368504221109215.

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Identifying new therapeutic indications for existing drugs is a major challenge in drug repositioning. Most computational drug repositioning methods focus on known targets. Analyzing multiple aspects of various protein associations provides an opportunity to discover underlying drug-associated proteins that can be used to improve the performance of the drug repositioning approaches. In this study, machine learning models were developed based on the similarities of diversified biological features, including protein interaction, topological network, sequence alignment, and biological function to predict protein pairs associating with the same drugs. The crucial set of features was identified, and the high performances of protein pair predictions were achieved with an area under the curve (AUC) value of more than 93%. Based on drug chemical structures, the drug similarity levels of the promising protein pairs were used to quantify the inferred drug-associated proteins. Furthermore, these proteins were employed to establish an augmented drug-protein matrix to enhance the efficiency of three existing drug repositioning techniques: a similarity constrained matrix factorization for the drug-disease associations (SCMFDD), an ensemble meta-paths and singular value decomposition (EMP-SVD) model, and a topology similarity and singular value decomposition (TS-SVD) technique. The results showed that the augmented matrix helped to improve the performance up to 4% more in comparison to the original matrix for SCMFDD and EMP-SVD, and about 1% more for TS-SVD. In summary, inferring new protein pairs related to the same drugs increase the opportunity to reveal missing drug-associated proteins that are important for drug development via the drug repositioning technique.

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Chellappa, Roopakunthavai Kunthavai. "Non-surgical repositioning of dentoalveolar fracture – A case report." International Journal of Oral Health Dentistry 9, no. 4 (January 15, 2024): 307–9. http://dx.doi.org/10.18231/j.ijohd.2023.057.

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Trauma is the one of the leading causes of morbidity and mortality in children. Although less, maxillofacial fractures contribute to an important part of morbidity in children. Here is a case of severe dento-alveolar fracture with intruded and displaced anterior teeth which was treated conservatively by heavy orthodontic wires. The greater osteogenic potential and faster healing rate in children help us to treat with conservative therapeutic procedures and with minimal displacement of fractures.

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Perales-Patón, Javier, Tomás Di Domenico, Coral Fustero-Torre, Elena Piñeiro-Yáñez, Carlos Carretero-Puche, Héctor Tejero, Alfonso Valencia, Gonzalo Gómez-López, and Fátima Al-Shahrour. "vulcanSpot: a tool to prioritize therapeutic vulnerabilities in cancer." Bioinformatics 35, no. 22 (June 7, 2019): 4846–48. http://dx.doi.org/10.1093/bioinformatics/btz465.

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Abstract Motivation Genetic alterations lead to tumor progression and cell survival but also uncover cancer-specific vulnerabilities on gene dependencies that can be therapeutically exploited. Results vulcanSpot is a novel computational approach implemented to expand the therapeutic options in cancer beyond known-driver genes unlocking alternative ways to target undruggable genes. The method integrates genome-wide information provided by massive screening experiments to detect genetic vulnerabilities associated to tumors. Then, vulcanSpot prioritizes drugs to target cancer-specific gene dependencies using a weighted scoring system based on well known drug-gene relationships and drug repositioning strategies. Availability and implementation http://www.vulcanspot.org. Supplementary information Supplementary data are available at Bioinformatics online.

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Nemeno, Judee Grace E., Soojung Lee, Wojong Yang, Kyung Mi Lee, and Jeong Ik Lee. "Applications and Implications of Heparin and Protamine in Tissue Engineering and Regenerative Medicine." BioMed Research International 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/936196.

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Drug repositioning is one of the most rapidly emerging fields of study. This concept is anchored on the principle that diseases have similar damaged or affected signaling pathways. Recently, drugs have been repositioned not only for their alternative therapeutic uses but also for their applications as biomaterials in various fields. However, medical drugs as biomaterials are rarely focused on in reviews. Fragmin and protamine have been recently the sources of increasing attention in the field of tissue engineering and regenerative medicine. Fragmin and protamine have been manufactured primarily as a safe antidote for the circulating heparin. Lately, these drugs have been utilized as either micro- or nanoparticle biomaterials. In this paper, we will briefly describe the concept of drug repositioning and some of the medical drugs that have been repurposed for their alternative therapeutic uses. Also, this will feature the historical background of the studies focused on fragmin/protamine micro/nanoparticles (F/P M/NPs) and their applications as biomaterials in tissue engineering, stem cell therapy, and regenerative medicine.

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Porta, Exequiel O. J. "The crucial role of drug repositioning in tackling Chagas disease, sleeping sickness, and leishmaniasis." INNOSC Theranostics and Pharmacological Sciences 7, no. 4 (October 15, 2024): 3721. http://dx.doi.org/10.36922/itps.3721.

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Neglected tropical diseases (NTDs), such as Chagas disease, human African trypanosomiasis (sleeping sickness), and leishmaniasis, disproportionately affect low-income populations in tropical and subtropical regions, leading to high morbidity and mortality rates. Consequently, these diseases, historically overlooked in global health agendas, perpetuate cycles of poverty and impede economic development. Drug repositioning, the repurposing of existing drugs for new therapeutic uses presents a promising strategy by reducing drug development time and cost while leveraging known safety profiles. However, despite its success in other therapeutic areas, this approach remains underutilized for NTDs due to challenges such as a limited drug pool, intellectual property barriers, regulatory complexities, and ethical concerns. Essential strategies to overcome these obstacles include expanding approved drug libraries, fostering multi-sector collaborations, streamlining regulatory processes, and adopting innovative funding models. Collaborative efforts among governments, pharmaceutical companies, research institutions, and non-profit health organizations are crucial to fully unlock the potential of drug repositioning. By working together as a united front, these stakeholders can ultimately transform NTD treatment and improve global health outcomes.

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Gościniak, Anna, Anna Stasiłowicz-Krzemień, Bożena Michniak-Kohn, Piotr Fiedor, and Judyta Cielecka-Piontek. "One Molecule, Many Faces: Repositioning Cardiovascular Agents for Advanced Wound Healing." Molecules 29, no. 12 (June 20, 2024): 2938. http://dx.doi.org/10.3390/molecules29122938.

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Chronic wound treatments pose a challenge for healthcare worldwide, particularly for the people in developed countries. Chronic wounds significantly impair quality of life, especially among the elderly. Current research is devoted to novel approaches to wound care by repositioning cardiovascular agents for topical wound treatment. The emerging field of medicinal products’ repurposing, which involves redirecting existing pharmaceuticals to new therapeutic uses, is a promising strategy. Recent studies suggest that medicinal products such as sartans, beta-blockers, and statins have unexplored potential, exhibiting multifaceted pharmacological properties that extend beyond their primary indications. The purpose of this review is to analyze the current state of knowledge on the repositioning of cardiovascular agents’ use and their molecular mechanisms in the context of wound healing.

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Kim, Yoonbee, and Young-Rae Cho. "Predicting Drug–Gene–Disease Associations by Tensor Decomposition for Network-Based Computational Drug Repositioning." Biomedicines 11, no. 7 (July 14, 2023): 1998. http://dx.doi.org/10.3390/biomedicines11071998.

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Drug repositioning offers the significant advantage of greatly reducing the cost and time of drug discovery by identifying new therapeutic indications for existing drugs. In particular, computational approaches using networks in drug repositioning have attracted attention for inferring potential associations between drugs and diseases efficiently based on the network connectivity. In this article, we proposed a network-based drug repositioning method to construct a drug–gene–disease tensor by integrating drug–disease, drug–gene, and disease–gene associations and predict drug–gene–disease triple associations through tensor decomposition. The proposed method, which ensembles generalized tensor decomposition (GTD) and multi-layer perceptron (MLP), models drug–gene–disease associations through GTD and learns the features of drugs, genes, and diseases through MLP, providing more flexibility and non-linearity than conventional tensor decomposition. We experimented with drug–gene–disease association prediction using two distinct networks created by chemical structures and ATC codes as drug features. Moreover, we leveraged drug, gene, and disease latent vectors obtained from the predicted triple associations to predict drug–disease, drug–gene, and disease–gene pairwise associations. Our experimental results revealed that the proposed ensemble method was superior for triple association prediction. The ensemble model achieved an AUC of 0.96 in predicting triple associations for new drugs, resulting in an approximately 7% improvement over the performance of existing models. It also showed competitive accuracy for pairwise association prediction compared with previous methods. This study demonstrated that incorporating genetic information leads to notable advancements in drug repositioning.

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Fan, Shiyong, Dian Xiao, Yanming Wang, Lianqi Liu, Xinbo Zhou, and Wu Zhong. "Research progress on repositioning drugs and specific therapeutic drugs for SARS-CoV-2." Future Medicinal Chemistry 12, no. 17 (September 2020): 1565–78. http://dx.doi.org/10.4155/fmc-2020-0158.

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SARS-CoV-2 has been widely spread around the world and COVID-19 was declared a global pandemic by the WHO. Limited clinically effective antiviral drugs are available now. The development of anti-SARS-CoV-2 drugs has become an urgent work worldwide. At present, potential therapeutic targets and drugs for SARS-CoV-2 are continuously reported, and many repositioning drugs are undergoing extensive clinical research, including remdesivir and chloroquine. On the other hand, structures of many important viral target proteins and host target proteins, including that of RdRp and Mpro were constantly reported, which greatly promoted structure-based drug design. This paper summarizes the current research progress and challenges in the development of anti-SARS-CoV-2 drugs, and proposes novel short-term and long-term drug research strategies.

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