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Latest Articles on Gene Therapy

Overview of latest articles and publications on gene therapy in PubMed, including Human Gene Therapy, Journal of Molecular Medicine and Journal of Gene Medicine. PubMed is a service of the US National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals.


  • [Biomarkers in Diagnosis, Treatment and Prognosis of Infectious Lung Diseases].
    [Biomarkers in Diagnosis, Treatment and Prognosis of Infectious Lung Diseases]. [English Abstract, Journal Article]Pneumologie 2017 Oct 18.PUnnewehr M, Kolditz M, Windisch W, et al. Biomarkers play an important role in the management of infectious pulmonary diseases, even though there is only limited evidence that biomarker-guided therapies are superior to clinical strategies.Well...Publisher Full TextBiomarkers play an important role in the management of infectious pulmonary diseases, even though there is only limited evidence that biomarker-guided therapies are superior to clinical strategies.Well-established indications for the use of biomarkers are the guidance of the duration of antibiotic therapy in community-acquired pneumonia (CAP) by PCT, the decision against the use of antibiotics by CRP or PCT in ambulatory settings, and the evaluation of CAP treatment by CRP or PCT kinetics.In the prognostic assessment of CAP, the standard biomarkers of acute organ dysfunction should be given priority, e. g. leukocyte and platelet counts, creatinine/urea and lactate, in combination with clinical signs and symptoms.MR-pro-ADM could enrich diagnostics in the future. Genetic transcriptome analysis is a completely new and promising concept.

  • [Changes of serum Krebs von den Lungen-6 levels in interstitial lung disease associated with dermatomyositis and secondary Sjögren's syndrome: a case report].
    [Changes of serum Krebs von den Lungen-6 levels in interstitial lung disease associated with dermatomyositis and secondary Sjögren's syndrome: a case report]. [English Abstract, Journal Article]Beijing Da Xue Xue Bao 2017 Oct 18; 49(5):910-914.BDYu JF, Jin YB, He J, et al. Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. The underlying pathogenesis ...Publisher Full TextInterstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. The underlying pathogenesis of ILDs is complex and associated with multiple rheumatologic conditions, such as systemic sclerosis, rheumatoid arthritis, pollymyositis and dermatomyositis, Sjögren's syndrome, and systemic lupus erythematosus. As the disease progresses, excessive pulmonary fibrosis impairs alveolar gas exchange and damages pulmonary function. The common methods to diagnose ILDs, such as clinical manifestations, pulmonary function test, and radiological examinations are not specific for ILDs and not able to diagnose ILDs at the early stage due to their low sensitivity. So, the easy way is important to diagnose ILDs. One important biomarker for ILDs is the high-molecular-weight glycoprotein, Krebs von den Lungen-6(KL-6). KL-6 encoded by the MUC1 gene is a mucin-like glycoprotein with high molecular weight and expressed predominantly on the cell surface of type II alveolar epithelial cells, and is detectable in the serum of patients with ILDs. We here report a case of ILDs associated with dermatomyositis and secondary Sjögren's syndrome. A 60-year-old woman was admitted to our hospital with the chief complaints of debilitation, dry mouth, dyspnea and astasia. ILDs associated with dermatomyositis and secondary Sjögren's syndrome was diagnosed clinically when the following criteria were satisfied: (1) development of dyspnea within 2 months of presentation, (2) pulmonary dispersion dysfunction, (3) bilateral infiltrative shadows on chest high resolution computed tomography (HRCT). She was treated with prednisone 50 mg/d prior to admission, but the result of therapy was not good. In our hospital she was treated with intravenous methylprednisolone and cyclophosphamide and oral hydroxychloroquine sulfate. Subsequently, her serum KL-6 levels gradually decreased after treatment, pulmonary diffuse function improved, and the improvement in the clinical manifestation and HRCT findings were observed. Nevertheless, the combination treatment of glucocorticoid and cyclophosphamide had contributed to the favourable outcomes. In conclusion, detection of serum KL-6 levels in ILDs associated with connective tissue diseases may be beneficial to making a definitive diagnosis, predicting the prognosis and monitoring the disease activity, which would be of great help in clinical practice. However, a well-designed clinical study with more patients and a longer follow-up period are required to arrive at a more conclusive judgment on the role of serum KL-6 in patients with ILDs.

  • [Clinical and genetic characteristics of Williams-Beuren syndrome: 2 cases report].
    [Clinical and genetic characteristics of Williams-Beuren syndrome: 2 cases report]. [English Abstract, Journal Article]Beijing Da Xue Xue Bao 2017 Oct 18; 49(5):899-903.BDWang SQ, Yang ZX, Li H To explore the clinical and genetic characteristics of Williams-Beuren syndrome (WBS) and to raise awareness of the disease. The characteristics of clinical manifestations, personal history, cardiac ul...Publisher Full TextTo explore the clinical and genetic characteristics of Williams-Beuren syndrome (WBS) and to raise awareness of the disease. The characteristics of clinical manifestations, personal history, cardiac ultrasound, brain magnetic resonance imaging (MRI), electroencephalogram (EEG) and chromosome detection results of two cases with WBS were analyzed. The two patients were both male and the age was 11 months and 1 day, and 9 months and 9 days, respectively. They both suffered from cardiovascular malformation: case one presented supravalvular aortic stenosis, and case two showed atrial septal defect and patent ductus arteriosus. Both of the cases were exhibited characteristic facial features of WBS, including full orbital, spherical nose, flat nasal bridge, long philtrum and thick lips. For the mental development, case one displayed moderate to severe developmental retardation, and case two showed severe developmental retardation. In addition, case one presented bilateral indirect inguinal hernia and hydrocele, and case two manifested feeding difficulties, buried penis and infantile spasms. Personal history: case one's mother had tocolytic therapy during pregnancy period, and case one was born at full-term by cesarean section due to amniotic fluid pollution. Supplementary examination: brain MRI of the two cases were no significant abnormalities; the EEG of case two showed hypsarrhythmia, and the epileptic spasms were recorded. Chromosome detection results: case one was identified as 7q11.23 deletion including the fragment deletion mutation of elastin (ELN) gene by multiplex ligation dependent probe amplification method, and case two was found with 7q11.21q11.23 deletion by high resolution G-band method. The two cases with WBS both had cardiovascular malformations, special facial features, mental retardation and connective tissue or urinary system abnormality. The supravalvular aortic stenosis of case one may be associated with the deletion of ELN gene, and the occurrence of epilepsy of case two may be related to the q11.21 deletion beyond the 7q11.23 region.

  • Identification of Genetically Intact HIV-1 Proviruses in Specific CD4(+) T Cells from Effectively Treated Participants.
    Identification of Genetically Intact HIV-1 Proviruses in Specific CD4(+) T Cells from Effectively Treated Participants. [Journal Article]Cell Rep 2017 Oct 17; 21(3):813-822.CRHiener B, Horsburgh BA, Eden JS, et al. Latent replication-competent HIV-1 persists in individuals on long-term antiretroviral therapy (ART). We developed the Full-Length Individual Proviral Sequencing (FLIPS) assay to determine the distribu...Latent replication-competent HIV-1 persists in individuals on long-term antiretroviral therapy (ART). We developed the Full-Length Individual Proviral Sequencing (FLIPS) assay to determine the distribution of latent replication-competent HIV-1 within memory CD4(+) T cell subsets in six individuals on long-term ART. FLIPS is an efficient, high-throughput assay that amplifies and sequences near full-length (∼9 kb) HIV-1 proviral genomes and determines potential replication competency through genetic characterization. FLIPS provides a genome-scale perspective that addresses the limitations of other methods that also genetically characterize the latent reservoir. Using FLIPS, we identified 5% of proviruses as intact and potentially replication competent. Intact proviruses were unequally distributed between T cell subsets, with effector memory cells containing the largest proportion of genetically intact HIV-1 proviruses. We identified multiple identical intact proviruses, suggesting a role for cellular proliferation in the maintenance of the latent HIV-1 reservoir.

  • Enhanced doxorubicin delivery to hepatocellular carcinoma cells via CD147 antibody-conjugated immunoliposomes.
    Enhanced doxorubicin delivery to hepatocellular carcinoma cells via CD147 antibody-conjugated immunoliposomes. [Journal Article]Nanomedicine 2017 Oct 15.NWang J, Wu Z, Pan G, et al. HAb18G/CD147, an important marker in the progression of hepatocellular carcinoma (HCC), is highly expressed on the surface of HCC cells. To increase the therapeutic efficacy of Doxil (PEGylated liposom...Publisher Full TextHAb18G/CD147, an important marker in the progression of hepatocellular carcinoma (HCC), is highly expressed on the surface of HCC cells. To increase the therapeutic efficacy of Doxil (PEGylated liposomal doxorubicin) against HCC, we constructed CD147-targeted doxorubicin-loaded immunoliposomes (Anti-CD147 ILs-DOX) by conjugating F(ab')2 of a CD147-specific monoclonal antibody to DSPE-PEG-MAL, and then inserted the antibody-conjugated polymer to Doxil. Anti-CD147 ILs-DOX delivered DOX to CD147-overexpressing HCC cells specifically and efficiently in vitro and in vivo, resulting in enhanced therapeutic effects than non-targeted controls. Strikingly, Anti-CD147 ILs-DOX reduced the CD133-positive fraction of HCC cells, suggesting its potential in reducing the number of HCC stem cells. Pharmacokinetic and biodistribution studies of Anti-CD147 ILs-DOX confirmed its long circulation time and efficient accumulation in tumors. The superior antitumor effects of Anti-CD147 ILs-DOX than other treatments were demonstrated in both HCC cells and patient-derived HCC xenograft models. Anti-CD147 ILs-DOX represents a novel approach for targeted HCC therapy.

  • Association Between the rs1229984 Polymorphism in the Alcohol Dehydrogenase B (ADH1B) Gene and Risk for Restless Legs Syndrome.
    Association Between the rs1229984 Polymorphism in the Alcohol Dehydrogenase B (ADH1B) Gene and Risk for Restless Legs Syndrome. [Journal Article]Sleep 2017 Oct 16.SJiménez-Jiménez FJ, Gómez-Tabales J, Alonso-Navarro H, et al. These results suggest an association between rs1229984 SNP and the risk for RLS.Publisher Full TextSeveral studies have raised the possibility of an association between alcohol consumption and the risk of developing restless legs syndrome (RLS). Moreover, an important percentage of patients under alcohol detoxification therapy develop RLS symptoms fulfil the criteria for idiopathic RLS during alcohol withdrawal. We have aimed to establish the possible association between 2 common single nucleotide polymorphisms (SNPs) in the alcohol-dehydrogenase 1B (ADH1B) gene, and the risk for RLS.We studied, using specific TaqMan assays, the genotype and allelic variant frequencies of ADH1B rs1229984 and ADH1B rs6413413 SNPs in 205 RLS patients and 505 gender-matched healthy controls using a TaqMan assay.The sum of the frequencies of rs1229984CT and rs1229984TT genotypes, as well as the frequency of the rs1229984T allelic variant, were significantly higher in RLS patients than in controls, both in the whole group and in females. The frequencies of genotypes and allelic variants of the rs6413413 SNP were similar between the two groups. RLS patients with the rs1229984CT genotype were younger, and those with the rs122984TT genotype older, at onset of RLS symptoms than those with the rs1229984CC genotype. None of the studied SNPs were related either with positivity of family history for RLS or with RLS severity.These results suggest an association between rs1229984 SNP and the risk for RLS.

  • The Chimpanzee Model of Viral Hepatitis: Advances in Understanding the Immune Response and Treatment of Viral Hepatitis.
    The Chimpanzee Model of Viral Hepatitis: Advances in Understanding the Immune Response and Treatment of Viral Hepatitis. [Journal Article]ILAR J 2017 Oct 17.:1-18.IJLanford RE, Walker CM, Lemon SM Chimpanzees (Pan troglodytes) have contributed to diverse fields of biomedical research due to their close genetic relationship to humans and in many instances due to the lack of any other animal model...Publisher Full TextChimpanzees (Pan troglodytes) have contributed to diverse fields of biomedical research due to their close genetic relationship to humans and in many instances due to the lack of any other animal model. This review focuses on the contributions of the chimpanzee model to research on hepatitis viruses where chimpanzees represented the only animal model (hepatitis B and C) or the most appropriate animal model (hepatitis A). Research with chimpanzees led to the development of vaccines for HAV and HBV that are used worldwide to protect hundreds of millions from these diseases and, where fully implemented, have provided immunity for entire generations. More recently, chimpanzee research was instrumental in the development of curative therapies for hepatitis C virus infections. Over a span of 40 years, this research would identify the causative agent of NonA,NonB hepatitis, validate the molecular tools for drug discovery, and provide safety and efficacy data on the therapies that now provide a rapid and complete cure of HCV chronic infections. Several cocktails of antivirals are FDA approved that eliminate the virus following 12 weeks of once-per-day oral therapy. This represents the first cure of a chronic viral disease and, once broadly implemented, will dramatically reduce the occurrence of cirrhosis and liver cancer. The recent contributions of chimpanzees to our current understanding of T cell immunity for HCV, development of novel therapeutics for HBV, and the biology of HAV are reviewed. Finally, a perspective is provided on the events leading to the cessation of the use of chimpanzees in research and the future of the chimpanzees previously used to bring about these amazing breakthroughs in human healthcare.

  • Validation of a Metastatic Assay using biopsies to improve risk stratification in patients with prostate cancer treated with radical radiation therapy.
    Validation of a Metastatic Assay using biopsies to improve risk stratification in patients with prostate cancer treated with radical radiation therapy. [Journal Article]Ann Oncol 2017 Oct 10.AOJain S, Lyons CA, Walker SM, et al. BackgroundRadiotherapy is an effective treatment for intermediate/high-risk locally-advanced prostate cancer, however, >30% of patients relapse within five years. Clinicopathological parameters current...Publisher Full TextBackgroundRadiotherapy is an effective treatment for intermediate/high-risk locally-advanced prostate cancer, however, >30% of patients relapse within five years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy (ADT).Patients & MethodsA bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold prior to further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and ADT. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS).ResultsGene expression analysis was performed in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients (HR = 3.21, [1.35-7.67]; p=0.003). On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases (HR = 2.71, [1.11-6.63]; p=0.030). The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) (HR = 3.23 [1.22-8.59]; p=0.019) whilst CAPRA itself was not significant (HR = 1.88, [0.52-6.77]; p=0.332). A high concordance (100% [61.5-100]) for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance.ConclusionsThe Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource.

  • Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer.
    Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer. [Journal Article]Ann Oncol 2017 Oct 04.AOFribbens C, Garcia Murillas I, Beaney M, et al. Cancers progressing on first line AI show high levels of genetic heterogeneity, with frequent sub-clonal mutations. Sub-clonal KRAS mutations are found at high frequency. The genetic diversity of AI re...Publisher Full TextSelection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to first line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer.83 patients on first line AI therapy for metastatic breast cancer were enrolled in a prospective study. Plasma samples were collected every 3 months to disease progression and ctDNA analysed by digital droplet PCR and enhanced tagged-amplicon sequencing (eTAm-Seq). Mutations identified in progression samples by sequencing were tracked back through samples prior to progression to study the evolution of mutations on therapy. The frequency of novel mutations were validated in an independent cohort of available baseline plasma samples in the SoFEA trial, which enrolled patients with prior sensitivity to AI.Of the 39 patients who progressed on first line AI, 56.4%(22/39) had ESR1 mutations detectable at progression, which were polyclonal in 40.9%(9/22) patients. In serial tracking, ESR1 mutations were detectable median 6.7 months (95%CI 3.7-NA) prior to clinical progression. Utilising eTAm-Seq ctDNA sequencing of progression plasma, ESR1 mutations were demonstrated to be sub-clonal in 72.2%(13/18) patients. Mutations in RAS genes were identified in 15.4%(6/39) of progressing patients (4 KRAS, 1 HRAS, 1 NRAS). In SoFEA, KRAS mutations were detected in 21.2%(24/113) patients, although there was no evidence that KRAS mutation status was prognostic for progression free or overall survival.Cancers progressing on first line AI show high levels of genetic heterogeneity, with frequent sub-clonal mutations. Sub-clonal KRAS mutations are found at high frequency. The genetic diversity of AI resistant cancers may limit subsequent targeted therapy approaches.

  • BRAF mutant Colorectal Cancer: prognosis, treatment and new perspectives.
    BRAF mutant Colorectal Cancer: prognosis, treatment and new perspectives. [Journal Article]Ann Oncol 2017 Jul 24.AOSanz-Garcia E, Argiles G, Elez E, et al. The MAPK cascade plays a crucial role in tumor cell proliferation and survival. Accumulating evidence suggests that mutations in the BRAF oncogene are not only associated with poor prognosis but also l...Publisher Full TextThe MAPK cascade plays a crucial role in tumor cell proliferation and survival. Accumulating evidence suggests that mutations in the BRAF oncogene are not only associated with poor prognosis but also linked with less benefit when treated with anti-epidermal growth factor receptor (EGFR) antibodies in metastatic colorectal cancer (mCRC). Targeting this molecular aberration has thus become a matter of particular interest in mCRC drug development. In contrast to other malignances such as BRAF mutant (mt) melanoma, efficacy observed with BRAF inhibitors in mono-therapy in mCRC is poor. Several mechanisms of resistance have been identified leading to the development of different treatment strategies that have shown promising activity in early clinical trials. Hence, rational combination of targeted therapies is expected to further increase the efficacy of selective BRAF inhibitors. Herein, we discuss the main clinical and molecular characteristics of BRAF mt colorectal cancer (CRC) and its translation into the clinic, with a focus on developmental therapeutics and combination strategies. In addition, we contextualize the available data with potential future approaches that include the extended access to next-generation sequencing platforms and gene expression strategies for molecular subtyping. These approaches will facilitate the identification of certain patient profiles providing more therapeutic possibilities.

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