Molecular Diagnosis & Therapy最新文献

{"title":"Genotype and Phenotype of Renal Hypouricemia: A Single-Center Study from China.","authors":"Lijun Mou, Lina Zhu, Xujiao Chen, Ying Hu, Hong Zhu, Ying Xu","doi":"10.1007/s40291-023-00683-w","DOIUrl":"10.1007/s40291-023-00683-w","url":null,"abstract":"<p><strong>Background: </strong>Renal hypouricemia (RHUC), a rare inherited disorder characterized by impaired uric acid reabsorption and subsequent profound hypouricemia, occurs mainly due to variants in SLC22A12 or SLC2A9. Only anecdotal cases and one small-scale RHUC screening study have been reported in the Chinese population.</p><p><strong>Methods: </strong>A total of 19 patients with RHUC from 17 unrelated families were recruited from our center. The medical history, clinical manifestations, biochemical exam, and clinical outcomes were collected. Next-generation sequencing-based targeted gene sequencing or whole exon sequencing was performed.</p><p><strong>Results: </strong>A total of 22 variants in SLC22A12 or SLC2A9 were found in 19 patients. The variant c.944G>A (p.W315X) in SLC2A9 was identified in three patients. Three variants c.165C>A (p.D55E), c.1549_1555delGAGACCC (p.E517Rfs*17), and c.1483T>C (p.W495R) in SLC22A12 and three variants c.1215+1G>A (splicing variant), c.643A>C (p.T215P), and c.227C>A (p.S76X) in SLC2A9 were novel. A proportion of 10 out of 19 patients presented with exercise-induced acute kidney injury (EIAKI). The renal outcome was favorable. Five patients had nephrolithiasis, in whom three had hypercalciuria.</p><p><strong>Conclusion: </strong>The current study reported six novel variants in SLC22A12 and SLC2A9 genes of Chinese patients with RHUC. The variant c.944G>A (p.W315X) in SLC2A9 may be common in Chinese patients. EIAKI is the main clinical phenotype associated with RHUC in our cohort, with a favorable outcome. Hypercalciuria presented in some RHUC patients is a new finding.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"87-99"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136400049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Do Molecular Classifications Affect the Neoadjuvant Treatment of Muscle-Invasive Urothelial Carcinoma?","authors":"Nicole Conci, Elisa Tassinari, Valentina Tateo, Matteo Rosellini, Andrea Marchetti, Costantino Ricci, Francesco Chessa, Matteo Santoni, Enrique Grande, Veronica Mollica, Francesco Massari","doi":"10.1007/s40291-023-00679-6","DOIUrl":"10.1007/s40291-023-00679-6","url":null,"abstract":"<p><p>Despite the significant improvements in the field of oncological treatments in recent decades, and the advent of targeted therapies and immunotherapy, urothelial carcinoma of the bladder remains a highly heterogeneous and difficult-to-treat neoplasm with a poor prognosis. In this context, owing to the new methods of genomic sequencing, numerous studies have analyzed the genetic features of muscle-invasive bladder cancer, providing a consensus set of molecular classes, to identify malignancies that may respond better to specific treatments (standard chemotherapy, immunotherapy, target therapy, local-regional treatment, or combinations) and improve the survival. The aim of the current review is to provide an overview of the current status of the molecular landscape of muscle-invasive bladder cancer, focusing our attention on therapeutic and prognostic implications in order to select the most effective and tailored therapeutic regimen for the individual patient.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"37-51"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Genetics of Inflammatory Bowel Disease.","authors":"Jasmina El Hadad, Philipp Schreiner, Stephan R Vavricka, Thomas Greuter","doi":"10.1007/s40291-023-00678-7","DOIUrl":"10.1007/s40291-023-00678-7","url":null,"abstract":"<p><p>The genetic background of inflammatory bowel disease, both Crohn's disease and ulcerative colitis, has been known for more than 2 decades. In the last 20 years, genome-wide association studies have dramatically increased our knowledge on the genetics of inflammatory bowel disease with more than 200 risk genes having been identified. Paralleling this increasing knowledge, the armamentarium of inflammatory bowel disease medications has been growing constantly. With more available therapeutic options, treatment decisions become more complex, with still many patients experiencing a debilitating disease course and a loss of response to treatment over time. With a better understanding of the disease, more effective personalized treatment strategies are looming on the horizon. Genotyping has long been considered a strategy for treatment decisions, such as the detection of thiopurine S-methyltransferase and nudix hydrolase 15 polymorphisms before the initiation of azathioprine. However, although many risk genes have been identified in inflammatory bowel disease, a substantial impact of genetic risk assessment on therapeutic strategies and disease outcome is still missing. In this review, we discuss the genetic background of inflammatory bowel disease, with a particular focus on the latest advances in the field and their potential impact on management decisions.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"27-35"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41240335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: \"Steps to Improve Precision Medicine in Epilepsy\": Are we all Agreed on the Definition?","authors":"Raffaele Falsaperla, Vincenzo Sortino, Giovanna Vitaliti, Martino Ruggieri","doi":"10.1007/s40291-023-00688-5","DOIUrl":"10.1007/s40291-023-00688-5","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"129-130"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocarrier-Mediated Delivery of MicroRNAs for Fibrotic Diseases.","authors":"Yanfang Guo, Hanying Wang, Rumin Lyu, Juan Wang, Ting Wang, Jingpei Shi, Lechun Lyu","doi":"10.1007/s40291-023-00681-y","DOIUrl":"10.1007/s40291-023-00681-y","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are endogenous noncoding RNAs that mediate the fibrotic process by regulating multiple targets. MicroRNA-based therapy can restore or inhibit miRNA expression and is expected to become an effective approach to prevent and alleviate fibrotic diseases. However, the safe, targeted, and effective delivery of miRNAs is a major challenge in translating miRNA therapy from bench to bedside. In this review, we briefly describe the pathophysiological process of fibrosis and the mechanism by which miRNAs regulate the progression of fibrosis. Additionally, we summarize the miRNA nanodelivery tools for fibrotic diseases, including chemical modifications and polymer-based, lipid-based, and exosome-based delivery systems. Further clarification of the role of miRNAs in fibrosis and the development of a novel nanodelivery system may facilitate the prevention and alleviation of fibrotic diseases in the future.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"53-67"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66784508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanded Alternatives of CRISPR-Cas9 Applications in Immunotherapy of Colorectal Cancer.","authors":"Rubén Arroyo-Olarte, Aranza Mejía-Muñoz, Sonia León-Cabrera","doi":"10.1007/s40291-023-00680-z","DOIUrl":"10.1007/s40291-023-00680-z","url":null,"abstract":"<p><p>Immunotherapy for colorectal cancer (CRC) is limited to patients with advanced disease who have already undergone first-line chemotherapy and whose tumors exhibit microsatellite instability. Novel technical strategies are required to enhance therapeutic options and achieve a more robust immunological response. Therefore, exploring gene analysis and manipulation at the molecular level can further accelerate the development of advanced technologies to address these challenges. The emergence of advanced genome editing technology, particularly of clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9, holds promise in expanding the boundaries of cancer immunotherapy. In this manuscript, we provide a comprehensive review of the applications and perspectives of CRISPR technology in improving the design, generation, and efficiency of current immunotherapies, focusing on solid tumors such as colorectal cancer, where these approaches have not been as successful as in hematological conditions.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"69-86"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10786962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral Vector-Based Gene Therapy for Epilepsy: What Does the Future Hold?","authors":"Barbara Bettegazzi, Stefano Cattaneo, Michele Simonato, Silvia Zucchini, Marie Soukupova","doi":"10.1007/s40291-023-00687-6","DOIUrl":"https://doi.org/10.1007/s40291-023-00687-6","url":null,"abstract":"<p>In recent years, many pre-clinical studies have tested gene therapy approaches as possible treatments for epilepsy, following the idea that they may provide an alternative to conventional pharmacological and surgical options. Multiple gene therapy approaches have been developed, including those based on anti-sense oligonucleotides, RNA interference, and viral vectors. In this opinion article, we focus on translational issues related to viral vector-mediated gene therapy for epilepsy. Research has advanced dramatically in addressing issues like viral vector optimization, target identification, strategies of gene expression, editing or regulation, and safety. Some of these pre-clinically validated potential gene therapies are now being tested in clinical trials, in patients with genetic or focal forms of drug-resistant epilepsy. Here, we discuss the ongoing translational research and the advancements that are needed and expected in the near future. We then describe the clinical trials in the pipeline and the further challenges that will need to be addressed at the clinical and economic levels. Our optimistic view is that all these issues and challenges can be overcome, and that gene therapy approaches for epilepsy will soon become a clinical reality.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"71 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138685728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Novel Internally Controlled HrpB1 Gene-Based Real-Time qPCR Assay for Detection of Burkholderia pseudomallei","authors":"Pranjal Kumar Yadav, Moumita Paul, Suchetna Singh, Sanjay Kumar, S. Ponmariappan, Duraipandian Thavaselvam","doi":"10.1007/s40291-023-00686-7","DOIUrl":"https://doi.org/10.1007/s40291-023-00686-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Melioidosis, caused by category B bioterrorism agent <i>Burkholderia pseudomallei</i>, is a seasonal disease of tropical and subtropical regions with a high mortality rate. An early and culture-independent detection of <i>B. pseudomallei</i> is required for the appropriate disease management and prevention. The present study is designed to identify novel and unique sequences of <i>B. pseudomallei</i> and development of quantitative polymerase chain reaction (qPCR) assay.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A novel <i>B. pseudomallei</i>-specific target sequence was identified by in silico analysis for the qPCR assay development. The specificity of the developed assay was assessed using purified DNA of 65 different bacterial cultures, and the sensitivity was estimated using a cloned target gene. Further, a type III secretion protein <i>Hrp</i>B1 (<i>Hrp</i>B1) gene-based duplex qPCR assay incorporating suitable extraction and amplification control was developed, and its viability was assessed in different clinical and environmental matrices for the detection of <i>B. pseudomallei</i>.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In this study, an 80-nucleotide-long <i>B. pseudomallei</i>-specific region within the gene <i>Hrp</i>B1 was identified by computational analysis. The developed <i>Hrp</i>B1-based qPCR assay was highly specific for <i>B. pseudomallei</i> detection when evaluated with 65 different bacterial cultures. The sensitivity of the qPCR assay with the <i>Hrp</i>B1-recombinant plasmid was found to be five copies per qPCR reaction. The assay’s detection limit was found to be 5 × 10² CFU/mL for human blood and urine, 5 × 10¹ CFU/mL in river water, and 2 × 10³ CFU/gm in paddy field soil.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The results of the study showed the applicability of a novel <i>Hrp</i>B1-based qPCR assay for sensitive and specific detection of <i>B. pseudomallei</i> in diverse clinical and environmental samples.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"12 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138573595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equecabtagene Autoleucel: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40291-023-00673-y","DOIUrl":"10.1007/s40291-023-00673-y","url":null,"abstract":"<p><p>Equecabtagene autoleucel (Fucaso^®), an autologous anti-B cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR)-T cell therapy that uses lentivirus as a gene vector to transfect autologous T cells, is being developed by IASO Biotechnology and Innovent Biologics, Inc. for the treatment of multiple myeloma (MM) and autoimmune diseases of the nervous system, including neuromyelitis optica spectrum disorder (NMOSD). Equecabtagene autoleucel was granted conditional approval in China in June 2023 for the treatment of adults with relapsed or refractory MM (RRMM) who have progressed after ≥ 3 lines of therapy (≥ 1 proteasome inhibitor and an immunomodulator). This article summarizes the milestones in the development of equecabtagene autoleucel leading to this first approval in patients with RRMM who have progressed after multiple lines of therapy.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"781-787"},"PeriodicalIF":4.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Potential of Expanded Noninvasive Prenatal Testing for Detection of Aneuploidies and Microdeletion/Microduplication Syndromes.","authors":"Chunyan Li, Menghua Xiong, Ying Zhan, Jianfang Zhang, Guyuan Qiao, Jia Li, Hong Yang","doi":"10.1007/s40291-023-00674-x","DOIUrl":"10.1007/s40291-023-00674-x","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to evaluate the clinical performance of expanded noninvasive prenatal testing (NIPT-Plus) for the detection of aneuploidies and microdeletion/microduplication syndromes.</p><p><strong>Methods: </strong>A total of 7177 pregnant women were enrolled in the study from June 2020 to March 2022 at Xijing Hospital, China. Cases with NIPT-Plus-positive results were further confirmed by chromosomal karyotyping and a chromosomal microarray analysis.</p><p><strong>Results: </strong>A total of 112 positive cases (1.56%) were identified by NIPT-Plus, including 60 chromosome aneuploidies and 52 microdeletion/microduplication syndromes. Ninety-five cases were validated by amniocentesis, and 57 were confirmed with true-positive results, comprising 18 trisomy 21, 4 trisomy 18, 1 trisomy 13, 17 sex chromosome aneuploidies, 1 other aneuploidy, and 16 microdeletion/microduplication syndromes. The positive predictive value of total chromosomal abnormalities was 60% (57/95). For trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, other aneuploidies and microdeletion/microduplication syndromes, the sensitivity was all 100%, the specificity was 100, 99.986, 100, 99.888, 99.958, and 99.636%, and the positive predictive value was 100, 80, 100, 68, 25, and 38.10%, respectively. For all clinical characteristics, the abnormal maternal serum screening group was found to have the highest prevalence of chromosomal abnormalities (1.54%), and the ultrasound abnormality group presented the highest positive predictive value (73.33%).</p><p><strong>Conclusions: </strong>NIPT-Plus has great potential for the detection of aneuploidies and microdeletion/microduplication syndromes owing to its high sensitivity, safety, and specificity, which greatly reduces unnecessary invasive procedures and the risk of miscarriage and allows informed maternal choice.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"769-779"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10188752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}