Biologics : Targets & Therapy最新文献

{"title":"The Cancer Driver Genes IDH1 and IDH2 and CD204 in WHO-Grade 4 Astrocytoma: Crosstalk Between Cancer Metabolism and Tumour Associated Macrophage Recruitment in Tumour Microenvironment.","authors":"Maher Kurdi,&nbsp;Nasser Mulla,&nbsp;Yousef Katib,&nbsp;Taghreed Alsinani,&nbsp;Sahar Hakamy,&nbsp;Bassam Mj Addas,&nbsp;Husam Malibary,&nbsp;Taher F Halawa,&nbsp;Marwa S Farhan,&nbsp;Eyad Faizo,&nbsp;Saleh Baeesa","doi":"10.2147/BTT.S394556","DOIUrl":"https://doi.org/10.2147/BTT.S394556","url":null,"abstract":"<p><strong>Purpose: </strong>IDH1 and IDH2 are hotspot mutations commonly identified in WHO-grade 4 astrocytomas. Their association with TAMs has never been investigated. We aim to explore the crosstalk between the IDH1/2 mutation metabolic effect and TAMs in tumour microenvironment and how this relationship affects the tumour recurrence.</p><p><strong>Patients and methods: </strong>The study included 20 samples of patients with WHO-grade 4 astrocytoma. The alteration hotspot in codon IDH1^R132 and IDH2^R172 was examined using direct sequencing. The protein expression of CD204 on TAM was detected through immunohistochemistry.</p><p><strong>Results: </strong>IDH1^R132 and IDH2^R172 were symmetrically identified as wildtype in 18/20 tumours (90%) and the remaining 2 tumours (10%) showed synonymous mutations on both codons. Tumours with IDH1/2-wildtype showed high expression of CD204⁺TAMs in 10 cases and low expression in 8 cases. Typical expression was seen equally in IDH1/2 mutant tumours. There was no significant association between IDH1/2 and CD204⁺TAM expression (p= 0.999). The association between the two groups was significantly observed among IDH-wildtype tumours (p=0.027). Highly expressed CD204 in IDH-wildtype tumours showed a median recurrence at 10 months compared to low CD204 expression, showed a median recurrence interval at 24 months.</p><p><strong>Conclusion: </strong>IDH1^R132 or IDH^R172 has the same impact on the classification and prognosis of WHO-grade 4 astrocytoma. There was no crosstalk between IDH1/2 metabolic effect and CD204⁺TAM. However, IDH-wildtype glioblastomas with dense CD204⁺TAM are associated with early recurrence. Because the sample size is small, a larger study is recommended to determine the impact of IDH1/2 on TAMs.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"15-22"},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b7/d8/btt-17-15.PMC9912343.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9275805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypereosinophilic Dermatitis: Successful Treatment with Dupilumab.","authors":"Chenyu Wu,&nbsp;Jianzhong Zhang,&nbsp;Yan Zhao","doi":"10.2147/BTT.S400073","DOIUrl":"https://doi.org/10.2147/BTT.S400073","url":null,"abstract":"<p><p>Hypereosinophilic dermatitis (HED) is a subtype of hypereosinophilic syndrome. HED is characterized by eosinophilic granulocytes increased in peripheral blood and bone marrow and infiltrated in skin. The clinical manifestations of HED are diffussed by erythema, papule and maculopapule with severe itching. The etiology of HED is unknown. At present, in addition to HED with FIP1L1-PDGFRA fusion gene positive, whose treatment is tyrosine kinase inhibitor, other types of HED first-line treatment are oral glucocorticoids, supplemented by antihistamines and immunosuppressants. Dupilumab is a human monoclonal antibody, which inhibits the IL-4 and IL-13 signaling by binding to the IL-4R-α and IL-13R-α-1 subunits of the receptor. We report a 76-year-old male patient with HED whose peripheral blood eosinophils decreased from 20.7% to 4.1% after 8 weeks of dupilumab, and his pruritus was completely relieved. Dupilumab was discontinued after 6 months of treatment. It is exciting that the patient has not experienced relapse for 17 months after the discontinuation. No adverse event was reported.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"57-60"},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/fe/btt-17-57.PMC10124617.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9356810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary Assessment of Safety and Tolerability of Avacopan During the Early Access Program for ANCA-Associated Vasculitis.","authors":"Jolijn R van Leeuwen,&nbsp;Tamara Popov,&nbsp;Achim Obergfell,&nbsp;Ton J Rabelink,&nbsp;Y K Onno Teng","doi":"10.2147/BTT.S394843","DOIUrl":"https://doi.org/10.2147/BTT.S394843","url":null,"abstract":"Introduction Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a heterogeneous group of rare, life-threatening, systemic autoimmune disorders characterized by necrotizing vasculitis that predominantly affects the small bloodto medium-sized vessels. Patients with ANCA vasculitis experience side effects from immunosuppression used to achieve disease remission, notably from long-term use of glucocorticoids. Both a Phase 2 trial (CLEAR) and a Phase 3 pivotal trial (ADVOCATE) have demonstrated the potential for avacopan to reduce steroid use in patients with newly diagnosed or relapsing severe ANCA-associated vasculitis while maintaining efficacy and safety. Avacopan is an orally administered small-molecule C5a receptor (C5aR) antagonist that selectively blocks the effects of C5a through the C5aR, including blocking neutrophil chemoattraction and activation. Most recently, avacopan has been approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of ANCAassociated vasculitis. In between the completion of the ADVOCATE study (2019) and the approval of regulatory agencies, 30 patients with a high unmet medical need have been treated with avacopan through the Early Access Program (EAP). Eligible for the EAP were patients with new or relapsing lifeor organ-threatening ANCA-associated vasculitis, requiring an induction treatment, who also had a high risk of steroid-related complications.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"11-14"},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/03/btt-17-11.PMC9884459.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10602784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Uracil Analog with Exocyclic Methylidene Group Can Reverse Resistance to Taxol in MCF-7 Cancer Cells.","authors":"Angelika Długosz-Pokorska,&nbsp;Renata Perlikowska,&nbsp;Tomasz Janecki,&nbsp;Anna Janecka","doi":"10.2147/BTT.S405080","DOIUrl":"https://doi.org/10.2147/BTT.S405080","url":null,"abstract":"<p><strong>Introduction: </strong>Taxol (Tx), a microtubule-stabilizing drug, has been widely used as a chemotherapeutic in several types of cancer. However, the development of resistance limited its application. One of the strategies used to prevent the emergence of drug resistance is combination treatment, involving at least two drugs. The aim of the current study was to assess if a new uracil analog, 3-<i>p</i>-bromophenyl-1-ethyl-5-methylidenedihydrouracil (U-359) can prevent the development of Tx resistance in breast cancer cells.</p><p><strong>Methods: </strong>The cytotoxicity of the new drug was tested in MCF-7 (hormone receptor (ER, PR) positive cell-line) and MCF-10A cell lines using MTT method. For the detection of apoptosis and necrosis, the Wright and Giemsa staining was used. Gene expression was measured by real-time PCR, and changes in the protein levels were evaluated by ELISA and bioluminescent method.</p><p><strong>Results: </strong>We investigated the effect of Tx and U-359 on cancer MCF-7 and normal MCF-10A cells alone and in combination. Tx co-administered with U-359 inhibited proliferation of MCF-7 cells to 7% while the level of ATPase drastically decreased to 14%, compared with effects produced by Tx alone. The apoptosis process was induced through the mitochondrial pathway. These effects were not seen in MCF-10A cells, showing the wide safety margin. The obtained results have shown that U-359 produced a synergistic effect with Tx probably by reducing Tx resistance in MCF-7 cells. To elucidate the possible mechanism of resistance, expression of tubulin III (TUBIII), responsible for microtubule stabilization and tau and Nlp proteins, responsible for microtubule dynamics, was assessed.</p><p><strong>Conclusion: </strong>Combination of Tx with U-359 reduced overexpression of TUBIII and Nlp. Thus, U-359 may stand for a potential reversal agent for the treatment of MDR in cancer cells.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"69-83"},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/6c/btt-17-69.PMC10198386.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9495864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Serum Vinculin in Patients with HBV/HCV-Associated Liver Cirrhosis and Hepatocellular Carcinoma: A Pilot Study.","authors":"Abdallah Essa,&nbsp;Enas Said Essa,&nbsp;Sara Mahmoud El-Deeb,&nbsp;Hossam Eldin Mostafa Seleem,&nbsp;Muthana Al Sahlawi,&nbsp;Omar Ahmed Al-Omair,&nbsp;Somaia Shehab-Eldeen","doi":"10.2147/BTT.S405500","DOIUrl":"https://doi.org/10.2147/BTT.S405500","url":null,"abstract":"<p><strong>Background: </strong>The stiffness of the extracellular matrix (ECM) controls many cellular processes, such as migration and differentiation. Cells detect stiffness through adhesion structures termed focal adhesions (FAs). Vinculin, an actin-binding FA protein, plays a pivotal role in FA-mediated mechanotransduction.</p><p><strong>Aim: </strong>This study aimed to explore the role of vinculin in the development of HBV/HCV-induced hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>Vinculin levels in a total number of 100 serum samples from patients with HBV/HCV-induced liver cirrhosis and HCC, as well as healthy controls, were analyzed using an enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>In patients with HCC and liver cirrhosis, the serum vinculin levels were significantly greater than in controls (503.8±242.2 and 728.4±1044.8 vs 77.7±36.1 respectively, p<0.001). However, results showed no link between serum vinculin and the clinicopathological features of HCC.</p><p><strong>Conclusion: </strong>Patients with HBVor HCV-induced liver cirrhosis and HCC have significantly higher serum levels of vinculin than do controls. This might point to a potential role for vinculin in the development of HCC. More research into how this protein affects the development of HCC at the molecular level could lead to better clinical treatments and the development of new molecular therapies.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"23-32"},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/7a/btt-17-23.PMC10035354.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9560616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treating Alpelisib-Induced Hyperinsulinemia in Patients with Advanced Breast Cancer - A Real-Life Experience.","authors":"Ruth Percik,&nbsp;Cecilie Oedegaard Smith,&nbsp;Anca Leibovici,&nbsp;Ayelet Shai","doi":"10.2147/BTT.S395817","DOIUrl":"https://doi.org/10.2147/BTT.S395817","url":null,"abstract":"<p><p>PIK3CA activating mutations are found in 40% of advanced breast cancer and are associated with worse prognosis. PI3K blockage is associated with insulin resistance, leading to hyperglycemia and hyperinsulinemia. Alpelisib is the first PI3K inhibitor used in cancer treatment. Laboratory evidence indicated that alpelisib-induced hyperinsulinemia offsets the drug's efficacy, but insulin levels were not tested in the clinical trials that evaluated alpelisib for breast cancer. Hyperglycemia could also interfere with anti-tumor effects of PI3K inhibitors by inducing Immune tolerance and altered mitochondrial metabolism. We have monitored insulin levels in 4 breast cancer patients with concomitant metabolic syndrome treated with alpelisib, and pre-treated patients with baseline increased insulin levels with pioglitazone, a potent insulin sensitizer, to target both hyperinsulinemia and hyperglycemia, and we report the treatment course of these patients. All patients achieved glycemic control and were able to maintain alpelisib dose intensity. Duration of response to alpelisib was longer than anticipated in this treatment setting. Insulin dynamics confirmed the efficacy of pioglitazone as a specific on-target hypoglycemic and hypo-insulinemic agent in the unique setting of PI3K blockade. Our experience suggests that targeting hyperinsulinemia in patients with is safe and feasible and results in good metabolic and oncologic outcomes.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"61-67"},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/64/btt-17-61.PMC10164376.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why and How Should Ethiopia Establish a Stem Cell Transplant Service? A Review Article.","authors":"Sintayehu Mekonnen,&nbsp;Hawi Farris","doi":"10.2147/BTT.S401289","DOIUrl":"https://doi.org/10.2147/BTT.S401289","url":null,"abstract":"<p><p>Ethiopia is attempting to reduce cancer-related morbidity and mortality through a strategic national cancer control plan but according to Globocan 2020, hematologic malignancies particularly leukemia and non-Hodgkin's lymphoma rank among the top five leading causes of new cancer incidence and cause of death among all age groups in both sexes. Hematopoietic stem-cell transplantation (HSCT) is an advanced treatment modality that makes the only effective treatment for cancer and non-cancer-related hematologic diseases unresponsive to conventional therapy. Patients who need stem cell transplants must travel to abroad countries to get the treatment. Meanwhile, the Ethiopian National Specialty and Subspecialty Roadmap sets the goal of establishing HSCT centers in 2020-2029 GC, yet leaders and planners must start taking steps to put the setup in place. Setting up an HSCT facility is challenging for developing countries due to the high costs, limited infrastructure, and need for intensive medical staff training; however, several nations have been able to start successful stem cell transplant programs. This review summarizes the basic steps and requirements of the program in light of guidelines recommendations and lessons learned from other developing countries. It also highlights possible cost-effective opportunities, bottlenecks, and areas that will require work and investment to make the objective reality in Ethiopia. Provides key information to assist administrators and policymakers to set priorities in planning and making informed decisions to establish and maintain the service.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"33-40"},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/8c/btt-17-33.PMC10038007.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9545572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adherence to Subcutaneous Anti-Tumour Necrosis Factor Treatment in a Cohort of Patients with Rheumatoid Arthritis Before and After the Implementation of a Comprehensive Care Model.","authors":"Pedro Santos-Moreno,&nbsp;Guillermo Sánchez-Vanegas,&nbsp;Angélica Monterrosa-Blanco,&nbsp;Gabriel-Santiago Rodríguez-Vargas,&nbsp;Manuel Rivero,&nbsp;Pedro Rodriguez,&nbsp;Omar-Javier Calixto,&nbsp;Adriana Rojas-Villarraga,&nbsp;Carlos Alberto Castro","doi":"10.2147/BTT.S385422","DOIUrl":"https://doi.org/10.2147/BTT.S385422","url":null,"abstract":"<p><strong>Purpose: </strong>To assess, in a cohort of patients with rheumatoid arthritis (RA) treated with subcutaneous antitumor necrosis factor drugs (anti-TNFs), the levels of treatment adherence before and after implementing a comprehensive care model (CCM).</p><p><strong>Patients and methods: </strong>An observational study including RA patients under treatment with subcutaneous anti-TNFs (adalimumab, etanercept, and golimumab) selected at convenience was performed; a sample size of 125 patients was calculated. The outcome variable was adherence assessed with the Compliance Questionnaire on Rheumatology (CQR19), measured before and after implementing a CCM. Descriptive and bivariate analyses were performed comparing adherence before and after applying the model (Wilcoxon and McNemar's Chi² test). For multivariate analysis, a generalized linear model adjusted for covariates was performed, where the difference in the proportion of adherence was the outcome measure.</p><p><strong>Results: </strong>A total of 131 RA patients were followed-up for 24 months; average age was 62 years, and 83.9% were women. The median of DAS28 at the beginning of the follow-up was 2.32, and the HAQ was 0.25. At baseline, 87.8% were adherent; after 24 months, 96.2% were adherent according to CQR19. At the end of follow-up, adherence increased with the three types of anti-TNFs treatment. In a matched model adjusted for clinical variables, the CCM was estimated to produce a 9.4% increase in the total percentage of adherent patients. Additionally, a statistically significant increase of 4.5% in the percentage of adherent patients treated with golimumab compared with etanercept and adalimumab was found.</p><p><strong>Conclusion: </strong>A CCM produced an important increase in the percentage of patients with rheumatoid arthritis adherent to treatment after 24 months of follow-up. It is noteworthy that Golimumab patients were more adherent when compared with other current anti-TNFs treatments.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"199-209"},"PeriodicalIF":4.0,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/34/btt-16-199.PMC9699109.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40515015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNF Inhibitors Exert a \"Hidden\" Beneficial Effect in the Cardiovascular Lipoprotein Profile of RA Patients.","authors":"Jaime Calvo Alén,&nbsp;Bernardo Alio Lavin-Gomez,&nbsp;Elena Aurrecoechea,&nbsp;Armando Raul Guerra Ruiz,&nbsp;Víctor Martínez Taboada,&nbsp;Juan Gómez Gerique","doi":"10.2147/BTT.S364191","DOIUrl":"https://doi.org/10.2147/BTT.S364191","url":null,"abstract":"<p><strong>Purpose: </strong>A high cardiovascular risk has been described in patients with rheumatoid arthritis (RA); the effects of different biological agents have also been described in these patients. The aim of the present study is to examine the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of RA patients using a broad laboratory assessment including a large number of non-routine tests.</p><p><strong>Patients and methods: </strong>RA patients treated with and without TNFi (70 patients in each group) were cross-sectionally compared regarding a broad spectrum of lipoprotein parameters including serum levels of total and HDL, LDL and VLDL cholesterol triglycerides, lipoprotein A (LpA), apolipoprotein A1 (Apo A), B100 (Apo B) and paroxonase. For each lipoprotein subfraction (HDL, LDL and VLDL), we assess specific concentrations of cholesterol, triglycerides, phospholipids and proteins and total mass of each one. Additionally, HDL Apo A, LDL and VLDL Apo B concentrations and number of particles of LDL and VLDL were also determined. Exploratory univariate and multivariate analyses of the different variables were performed.</p><p><strong>Results: </strong>Seventy patients in each subset were enrolled. Patients on treatment with TNFi showed a trend to be younger and to have a longer disease duration. Regarding the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed.</p><p><strong>Conclusion: </strong>TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in the VLDL-related parameters consistent with a reduction of the atherogenic risk.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"187-197"},"PeriodicalIF":4.0,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4c/8d/btt-16-187.PMC9587304.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40680083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phage Therapy: A Different Approach to Fight Bacterial Infections.","authors":"Zigale Hibstu,&nbsp;Habtamu Belew,&nbsp;Yibeltal Akelew,&nbsp;Hylemariam Mihiretie Mengist","doi":"10.2147/BTT.S381237","DOIUrl":"https://doi.org/10.2147/BTT.S381237","url":null,"abstract":"<p><p>Phage therapy is one of the alternatives to treat infections caused by both antibiotic-sensitive and antibiotic-resistant bacteria, with no or low toxicity to patients. It was started a century ago, although rapidly growing bacterial antimicrobial resistance, resulting in high levels of morbidity, mortality, and financial cost, has initiated the revival of phage therapy. It involves the use of live lytic, bioengineered, phage-encoded biological products, in combination with chemical antibiotics to treat bacterial infections. Importantly, phages will be removed from the body within seven days of clearing an infection. They target specific bacterial strains and cause minimal disruption to the microbial balance in humans. Phages for medication must be screened for the absence of resistant genes, virulent genes, cytotoxicity, and their interaction with the host tissue and organs. Since they are immunogenic, applying a high phage titer for therapy exposes them and activates the host immune system. To date, no serious side effects have been reported with human phage therapy. In this review, we describe phage-phagocyte interaction, bacterial resistance to phages, how phages conquer bacterial resistance, the role of genetic engineering and other technologies in phage therapy, and the therapeutic application of modified phages and phage-encoded products. We also highlight the comparison of antibiotics and lytic phage therapy, the pros and cons of phage therapy, determinants of human phage therapy trials, phage quality and safety requirements, phage storage and handling, and current challenges in phage therapy.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"173-186"},"PeriodicalIF":4.0,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/58/btt-16-173.PMC9550173.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33502647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}