Molecular Diagnosis & Therapy最新文献

{"title":"Acknowledgement to Referees.","authors":"","doi":"10.1007/s40291-024-00763-5","DOIUrl":"https://doi.org/10.1007/s40291-024-00763-5","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878357","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":"Inner Ear Gene Therapy: An Overview from Bench to Bedside.","authors":"Anselm Joseph Gadenstaetter, Paul Emmerich Krumpoeck, Lukas David Landegger","doi":"10.1007/s40291-024-00759-1","DOIUrl":"https://doi.org/10.1007/s40291-024-00759-1","url":null,"abstract":"<p><p>Hearing loss represents a highly prevalent and debilitating sensory disorder affecting roughly one in five people worldwide. In a majority of patients with congenital hearing loss, genetic mutations cause the disease. Up until recently, therapeutic options for individuals with hearing loss were limited to hearing aids and different types of auditory implants. However, after numerous years of intensive basic and translational research, gene therapy strategies are now being investigated in clinical trials. First results show significant hearing improvement in treated patients, highlighting gene therapy's role as a promising treatment for certain forms of genetic hearing loss. In this article, we provide an overview of genetic hearing loss and inner ear gene therapy research including relevant strategies that have been established in animal models and will likely be investigated in human patients soon. Furthermore, we summarize and contextualize the novel findings of recently completed and ongoing clinical trials, and discuss future hurdles needed to be overcome to allow for a broad and safe clinical application of inner ear gene therapy.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774106","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":"Advancing Rabies Diagnosis: Time for a New \"Gold Standard\"?","authors":"Lonika Lodha, Ashwini Manoor Ananda, Reeta S Mani","doi":"10.1007/s40291-024-00758-2","DOIUrl":"10.1007/s40291-024-00758-2","url":null,"abstract":"<p><p>Rabies, a neglected zoonosis, claims approximately 60,000 lives globally each year. One of the significant challenges in rabies control efforts is the lack of surveillance data and underreporting, stemming from inadequate diagnostic facilities, particularly in low- and middle-income countries. At present, the World Health Organization recognizes the fluorescent antibody test (FAT) on postmortem brain specimens as the \"gold standard\" for confirming rabies in humans and animals. In this opinion article, we highlight several limitations of FAT and advocate for superior alternatives to replace it as the reference diagnostic technique for rabies. We argue that molecular techniques, specifically PCR-based methods, offer rapid, accurate, and convenient means of laboratory confirmation for rabies. Their implementation is now feasible due to the expanded technical and logistical capabilities achieved during the COVID-19 pandemic.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669736","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":"Leveraging Multi-omics to Disentangle the Complexity of Ovarian Cancer.","authors":"Shijuan Lin, Lily L Nguyen, Alexandra McMellen, Michael S Leibowitz, Natalie Davidson, Daniel Spinosa, Benjamin G Bitler","doi":"10.1007/s40291-024-00757-3","DOIUrl":"10.1007/s40291-024-00757-3","url":null,"abstract":"<p><p>To better understand ovarian cancer lethality and treatment resistance, sophisticated computational approaches are required that address the complexity of the tumor microenvironment, genomic heterogeneity, and tumor evolution. The ovarian cancer tumor ecosystem consists of multiple tumors and cell types that support disease growth and progression. Over the last two decades, there has been a revolution in -omic methodologies to broadly define components and essential processes within the tumor microenvironment, including transcriptomics, metabolomics, proteomics, genome sequencing, and single-cell analyses. While most of these technologies comprehensively characterize a single biological process, there is a need to understand the biological and clinical impact of integrating multiple -omics platforms. Overall, multi-omics is an intriguing analytic framework that can better approximate biological complexity; however, data aggregation and integration pipelines are not yet sufficient to reliably glean insights that affect clinical outcomes.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669737","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":"Selecting Targets for Molecular Imaging of Gastric Cancer: An Immunohistochemical Evaluation.","authors":"Ruben D Houvast, Maurice van Duijvenvoorde, Kira Thijse, Wobbe O de Steur, Lioe-Fee de Geus-Oei, A Stijn L P Crobach, Jacobus Burggraaf, Alexander L Vahrmeijer, Peter J K Kuppen","doi":"10.1007/s40291-024-00755-5","DOIUrl":"https://doi.org/10.1007/s40291-024-00755-5","url":null,"abstract":"<p><strong>Purpose: </strong>Tumor-targeted positron emission tomography (PET) and fluorescence-guided surgery (FGS) could address current challenges in pre- and intraoperative imaging of gastric cancer. Adequate selection of molecular imaging targets remains crucial for successful tumor visualization. This study evaluated the potential of integrin α_vβ₆, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM) and human epidermal growth factor receptor-2 (HER2) for molecular imaging of primary gastric cancer, as well as lymph node and distant metastases.</p><p><strong>Methods: </strong>Expression of α_vβ₆, CEACAM5, EGFR, EpCAM and HER2 was determined using immunohistochemistry in human tissue specimens of primary gastric adenocarcinoma, healthy surrounding stomach, esophageal and duodenal tissue, tumor-positive and tumor-negative lymph nodes, and distant metastases, followed by quantification using the total immunostaining score (TIS).</p><p><strong>Results: </strong>Positive biomarker expression in primary gastric tumors was observed in 86% for α_vβ₆, 72% for CEACAM5, 77% for EGFR, 93% for EpCAM and 71% for HER2. Tumor expression of CEACAM5, EGFR and EpCAM was higher compared to healthy stomach tissue expression, while this was not the case for α_vβ₆ and HER2. Tumor-positive lymph nodes could be distinguished from tumor-negative lymph nodes, with accuracy ranging from 82 to 93% between biomarkers. CEACAM5, EGFR and EpCAM were abundantly expressed on distant metastases, with expression in 88-95% of tissue specimens.</p><p><strong>Conclusion: </strong>Our findings show that CEACAM5, EGFR and EpCAM are promising targets for molecular imaging of primary gastric cancer, as well as visualization of both lymph node and distant metastases. Further clinical evaluation of PET and FGS tracers targeting these antigens is warranted.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631431","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":"Sensitive and Specific Droplet Digital PCR Assays for Circulating Tumor HPV DNA: Development, Validation, and Clinical Application in HPV-Associated Cancers.","authors":"Alvida Qvick, Elin Andersson, Anna Oldaeus Almerén, Max Waenerlund, Bianca Stenmark, Christina Karlsson, Mats G Karlsson, Gisela Helenius","doi":"10.1007/s40291-024-00743-9","DOIUrl":"10.1007/s40291-024-00743-9","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus (HPV) has emerged as a significant contributor to cancer incidence globally, particularly in the context of oropharyngeal squamous cell carcinoma (OPSCC) and cancer of unknown primary (HNCUP). This study aimed to develop and validate droplet digital PCR (ddPCR) assays for the detection of circulating tumor HPV DNA (ctHPV-DNA) in plasma, focusing on high-risk HPV genotypes associated with these cancers.</p><p><strong>Methods: </strong>ddPCR assays for HPV16, 18, 33, 35, 56, and 59 were developed and tested using gBlocks, HPV cell-free DNA, fragmented tumor HPV+ DNA, and plasma samples from patients with HPV+ OPSCC (n = 110) and HNCUP (n = 9).</p><p><strong>Results: </strong>Assays demonstrated robust technical sensitivity across all tested HPV genotypes. Clinical application of the assays on a cohort of patients with HPV+ OPSCC and HNCUP revealed high sensitivity (91.6%) and wide variability in ctHPV-DNA levels. Analyses revealed correlations between ctHPV-DNA levels and TNM stage and tumor viral load. The association between ctHPV-DNA and tumor viral load persisted even after adjusting for TNM stage. At posttreatment, 72.5% of samples had reached undetectable ctHPV-DNA levels. Having detectable ctHPV-DNA posttreatment was associated with a higher ctHPV-DNA level at diagnosis and higher viral load at diagnosis.</p><p><strong>Conclusion: </strong>The findings underscore the potential of ctHPV-DNA as a biomarker for monitoring HPV+ cancers and offer insights into tumor dynamics. Implementation of these assays in clinical practice could enhance no-invasive treatment monitoring and recurrence detection in HPV-associated cancers.</p><p><strong>Clinical trials: </strong>NCT05904327.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"835-845"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331121","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":"Diagnosis of Lung Cancer Through Exhaled Breath: A Comprehensive Study.","authors":"Elina Gashimova, Azamat Temerdashev, Dmitry Perunov, Vladimir Porkhanov, Igor Polyakov","doi":"10.1007/s40291-024-00744-8","DOIUrl":"10.1007/s40291-024-00744-8","url":null,"abstract":"<p><strong>Objectives: </strong>Exhaled breath analysis is an attractive lung cancer diagnostic tool. However, various factors that are not related to the disease status, comorbidities, and other diseases must be considered to obtain a reliable diagnostic model.</p><p><strong>Methods: </strong>Exhaled breath samples from 646 individuals including 273 patients with lung cancer (LC), 90 patients with cancer of other localizations (OC), 150 patients with noncancer lung diseases (NLD), and 133 healthy controls (HC) were analyzed using gas chromatography-mass spectrometry (GC-MS). The samples were collected in Tedlar bags. Volatile organic compounds (VOCs) were preconcentrated on Tenax TA sorbent tubes with subsequent two-stage thermal desorption followed by GC-MS analysis. The influence of age, gender, smoking status, time since last food consumption, and comorbidities on exhaled breath were evaluated. Also, the effect of histology, TNM, tumor localization, treatment status, and the presence of a tumor on VOC profile of patients with lung cancer were assessed. Intergroup statistics were estimated, diagnostic models were created using artificial neural networks (ANNs) and gradient boosted decision trees (GBDTs).</p><p><strong>Results: </strong>Smoking status and food consumption affect exhaled breath VOC profile: benzene, ethylbenzene, toluene, 1,3-pentadiene 1,4-pentadiene acetonitrile, and some ratios are significantly different in exhaled breath of smokers and nonsmokers; the ratios 2,3-butandione/2-pentanone, 2,3-butandione/dimethylsulfide, and 2-butanone/2-pentanone are affected by time since last food consumption. Exhaled breath of LC is affected by the form of the disease and comorbidities. One-pentanol and 2-butanone were different in exhaled breath of patients with various tumor localization; 2-butanone was different in exhaled breath of patients before and during treatment. Diabetes as a comorbidity affects the pentanal level in exhaled breath; obesity affects the ratios of 2,3-butanedione/dimethylsulfide and 2-butanone/isoprene. Sensitivity and specificity of diagnostic models aimed to discriminate LC and HC, OC, and NLD were 78.7% and 51.0%, 62.2% and 53.4%, and 60.4% and 58.0%, respectively. HC and patients, regardless of the disease, can be classified with sensitivity of 76.6% and specificity of 68.2%.</p><p><strong>Conclusions: </strong>The models created to diagnose lung cancer can also classify OC and NLD as patients with lung cancer. Additionally, the influence of comorbidities and factors not related to the disease status must be considered before the creation of diagnostic models to avoid false results.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"847-860"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299596","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 Progresses and Challenges of Bispecific Antibodies for the Treatment of Solid Tumors.","authors":"Yuheng Gu, Qi Zhao","doi":"10.1007/s40291-024-00734-w","DOIUrl":"10.1007/s40291-024-00734-w","url":null,"abstract":"<p><p>In recent years, bispecific antibodies (BsAbs) have emerged as a promising therapeutic strategy against tumors. BsAbs can recruit and activate immune cells, block multiple signaling pathways, and deliver therapeutic payloads directly to tumor sites. This review provides a comprehensive overview of the recent advances in the development and clinical application of BsAbs for the treatment of solid tumors. We discuss the different formats, the unique mechanisms of action, and the clinical outcomes of the most advanced BsAbs in solid tumor therapy. Several studies have also analyzed the clinical progress of bispecific antibodies. However, this review distinguishes itself by exploring the challenges associated with bispecific antibodies and proposing potential solutions. As the field progresses, BsAbs hold promise to redefine cancer treatment paradigms and offer new hope to patients with solid tumors.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"669-702"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019337","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":"Developing a DNA Methylation Signature to Differentiate High-Grade Serous Ovarian Carcinomas from Benign Ovarian Tumors.","authors":"Douglas V N P Oliveira, Edyta Biskup, Colm J O'Rourke, Julie L Hentze, Jesper B Andersen, Claus Høgdall, Estrid V Høgdall","doi":"10.1007/s40291-024-00740-y","DOIUrl":"10.1007/s40291-024-00740-y","url":null,"abstract":"<p><strong>Introduction: </strong>Epithelial ovarian cancer (EOC) represents a significant health challenge, with high-grade serous ovarian cancer (HGSOC) being the most common subtype. Early detection is hindered by nonspecific symptoms, leading to late-stage diagnoses and poor survival rates. Biomarkers are crucial for early diagnosis and personalized treatment OBJECTIVE: Our goal was to develop a robust statistical procedure to identify a set of differentially methylated probes (DMPs) that would allow differentiation between HGSOC and benign ovarian tumors.</p><p><strong>Methodology: </strong>Using the Infinium EPIC Methylation array, we analyzed the methylation profiles of 48 ovarian samples diagnosed with HGSOC, borderline ovarian tumors, or benign ovarian disease. Through a multi-step statistical procedure combining univariate and multivariate logistic regression models, we aimed to identify CpG sites of interest.</p><p><strong>Results and conclusions: </strong>We discovered 21 DMPs and developed a predictive model validated in two independent cohorts. Our model, using a distance-to-centroid approach, accurately distinguished between benign and malignant disease. This model can potentially be used in other types of sample material. Moreover, the strategy of the model development and validation can also be used in other disease contexts for diagnostic purposes.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"821-834"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479161","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":"Advances in Pompe Disease Treatment: From Enzyme Replacement to Gene Therapy.","authors":"Pasqualina Colella","doi":"10.1007/s40291-024-00733-x","DOIUrl":"10.1007/s40291-024-00733-x","url":null,"abstract":"<p><p>Pompe disease is a neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), hydrolyzing glycogen to glucose. Pathological glycogen storage, the hallmark of the disease, disrupts the metabolism and function of various cell types, especially muscle cells, leading to cardiac, motor, and respiratory dysfunctions. The spectrum of Pompe disease manifestations spans two main forms: classical infantile-onset (IOPD) and late-onset (LOPD). IOPD, caused by almost complete GAA deficiency, presents at birth and leads to premature death by the age of 2 years without treatment. LOPD, less severe due to partial GAA activity, appears in childhood, adolescence, or adulthood with muscle weakness and respiratory problems. Since 2006, enzyme replacement therapy (ERT) has been approved for Pompe disease, offering clinical benefits but not a cure. However, advances in early diagnosis through newborn screening, recognizing disease manifestations, and developing improved treatments are set to enhance Pompe disease care. This article reviews recent progress in ERT and ongoing translational research, including the approval of second-generation ERTs, a clinical trial of in utero ERT, and preclinical development of gene and substrate reduction therapies. Notably, gene therapy using intravenous delivery of adeno-associated virus (AAV) vectors is in phase I/II clinical trials for both LOPD and IOPD. Promising data from LOPD trials indicate that most participants met the criteria to discontinue ERT several months after gene therapy. The advantages and challenges of this approach are discussed. Overall, significant progress is being made towards curative therapies for Pompe disease. While several challenges remain, emerging data are promising and suggest the potential for a once-in-a-lifetime treatment.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"703-719"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972146","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}