eXTReMe Tracker
Gene Therapy Net RSS feed Follow Gene Therapy Net on Twitter LinkedIn - Gene Therapy Net discussion group Facebook - Gene Therapy Net

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.


  • Cutaneous adnexal adenocarcinoma with exquisite sensitivity to trastuzumab.
    Cutaneous adnexal adenocarcinoma with exquisite sensitivity to trastuzumab. [Case Reports]Head Neck 2017 Feb 22.HNBrown TJ, Sher DJ, Nedzi LA, et al. We believe the exquisite sensitivity of the primary carcinoma and subsequent recurrence to trastuzumab therapy was due to strong HER-2 expression both at the protein and gene level. © 2017 Wiley Period...Publisher Full TextCutaneous adnexal adenocarcinoma is a rare cancer that is occasionally human epidermal growth factor receptor-2 (HER-2)-positive, and demonstrates variable response to HER-2 inhibitors.We report a case of adnexal adenocarcinoma of the scalp in a 56-year-old man. He underwent wide local excision with cervical node dissection followed by radiation, but had extensive local recurrence.Pathology demonstrated a poorly differentiated adnexal adenocarcinoma with HER-2 overexpression by immunohistochemistry (IHC) and high HER-2 gene amplification by fluorescence in situ hybridization. The patient was treated with trastuzumab-based therapy with dramatic response and clinical resolution of the tumor. Upon pausing trastuzumab, he developed local relapse, but had an excellent response to restarting trastuzumab monotherapy. He lacks visible disease 43 months after the initial diagnosis.We believe the exquisite sensitivity of the primary carcinoma and subsequent recurrence to trastuzumab therapy was due to strong HER-2 expression both at the protein and gene level. © 2017 Wiley Periodicals, Inc. Head Neck, 2017.

  • [A contribution to the differential diagnostics of sclerosing cholangitides].
    [A contribution to the differential diagnostics of sclerosing cholangitides]. [English Abstract, Journal Article]Vnitr Lek 2017; 63(1):50-55.VLBlaho M, Dítě P, Bojková M, et al. Sclerosing cholangitides represent a group of chronic biliary obstructive diseases which include primary sclerosing cholangitis (PSC), IgG4 associated sclerosing cholangitis (IgG4-SC) and secondary scl...Publisher Full TextSclerosing cholangitides represent a group of chronic biliary obstructive diseases which include primary sclerosing cholangitis (PSC), IgG4 associated sclerosing cholangitis (IgG4-SC) and secondary sclerosing cholangitis (SSC). The manifestations of the diseases are similar, but their asymptomatic course is also frequent. IgG4-SC belongs to the group of IgG4 associated diseases and it is the most frequently related to type 1 autoimmune pancreatitis. Diagnosing of IgG4-SC is based on typical histopathological images, shape changes revealed by diagnostic imaging, serological tests, concurrent impairment of other organs and response to therapy, where IgG4-SC responds well to treatment with corticoids, whereas the only possibility for the remaining units is endoscopic intervention or liver transplantation. Secondary sclerosing cholangitis may develop as a result of many different insults affecting the biliary tree. Among them, the most frequently described include long-lasting biliary obstruction, surgical injury of the biliary tree, and ischemic cholangitis in liver allotransplants or recurrent pancreatitis. We use serological and imaging examination in PSC diagnostics, sometimes we have to resort to liver biopsy. PSC is to a significant degree accompanied by the presence of idiopathic bowel disease, typically ulcerative colitis. As a result, PSC may lead to cirrhosis of the liver and it is a precancerous condition of several malignancies. With regard to variable locations of the biliary tree injuries concerning the aforementioned units, also certain malignancies in subhepatic landscape need to be considered in the differential diagnosis: pancreatic cancer and cholangiogenous carcinoma.Key words: genetic factors - IBD - IgG4 cholangitis - liver transplantation - bile duct cancer - ursodeoxycholic acid - primary sclerosing cholangitis - secondary cholangitis - sclerosing cholangitis.

  • Systematic investigation on the intracellular trafficking network of polymeric nanoparticles.
    Systematic investigation on the intracellular trafficking network of polymeric nanoparticles. [Journal Article]Nanoscale 2017 Feb 22.NZhang J, Chang D, Yang Y, et al. Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymer...Publisher Full TextPolymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis. Then the PLGA nanoparticles were transported to early endosomes (EEs), late endosomes (LEs), and finally to lysosomes. Two novel transport pathways were identified in our research: the macropinocytosis (Rab34 positive)-LE (Rab7 positive)-lysosome pathway and the EE-liposome (Rab18)-lysosome pathway. Moreover, the slow (Rab11 and Rab35 positive), fast (Rab4 positive) and apical (Rab20 and Rab25 positive) endocytic recycling endosome pathways could transport the PLGA nanoparticles to lysosomes. The PLGA nanoparticles were transported out of the cells by GLUT4 transport vesicles (Rab8, Rab10 positive), classic secretory vesicles (Rab3, Rab27 positive vesicles) and melanosomes (Rab32, Rab38 positive vesicles). Besides, the PLGA nanoparticles were observed in autophagosomes (LC3 positive), which means that the nanoparticles can be delivered by the autophagy pathway. Multiple cross-talk pathways were identified connecting autophagy and endocytosis or exocytosis by screening the co-localization of the Rab proteins with the LC3 protein. Degradation of nanoparticles through lysosomes can be blocked by autophagy inhibitors (3 MA and CQ). A better understanding of intracellular trafficking mechanisms involved in polymeric nanoparticle-based drug delivery is a prerequisite to clinical application.

  • fl-Asparaginase-mediated downregulation of c-Myc promotes 1,25(OH)2 D3 -induced myeloid differentiation in acute myeloid leukemia cells.
    fl-Asparaginase-mediated downregulation of c-Myc promotes 1,25(OH)2 D3 -induced myeloid differentiation in acute myeloid leukemia cells. [Journal Article]Int J Cancer 2017 Feb 22.IJSong JH, Park E, Kim MS, et al. Treatment of acute myeloid leukemia (AML) largely depends on chemotherapy, but current regimens have been unsatisfactory for long-term remission. Although differentiation induction therapy utilizing 1,...Publisher Full TextTreatment of acute myeloid leukemia (AML) largely depends on chemotherapy, but current regimens have been unsatisfactory for long-term remission. Although differentiation induction therapy utilizing 1,25(OH)2 D3 (VD3) has shown great promise for the improvement of AML treatment efficacy, severe side effects caused by its supraphysiological dose limit its clinical application. Here we investigated the combinatorial effect of l-asparaginase (ASNase)-mediated amino acid depletion and the latent alternation of VD3 activity on the induction of myeloid differentiation. ASNase treatment enhanced VD3-driven phenotypic and functional differentiation of three-different AML cell-lines into monocyte/macrophages, along with c-Myc downregulation. Using gene silencing with shRNA and a chemical blocker, we found that reduced c-Myc is a critical factor for improving VD3 efficacy. c-Myc-dependent inhibition of mTORC1 signaling and induction of autophagy were involved in the enhanced AML cell differentiation. In addition, in a post-culture of AML cells after each treatment, ASNase supports the anti-leukemic effect of VD3 by inhibiting cell growth and inducing apoptosis. Finally, we confirmed that the administration of ASNase significantly improved VD3 efficacy in the prolongation of survival time in mice bearing tumor xenograft. Our results are the first to demonstrate the extended application of ASNase, which is currently used for acute lymphoid leukemia, in VD3-mediated differentiation induction therapy for AML, and suggest that this drug combination may be a promising novel strategy for curing AML. This article is protected by copyright. All rights reserved.

  • Pyoderma Gangrenosum: An Update on Pathophysiology, Diagnosis and Treatment.
    Pyoderma Gangrenosum: An Update on Pathophysiology, Diagnosis and Treatment. [Journal Article, Review]Am J Clin Dermatol 2017 Feb 21.AJAlavi A, French LE, Davis MD, et al. Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic disorder with prototypical clinical presentations. Its pathophysiology is complex and not fully explained. Recent information regarding the...Publisher Full TextPyoderma gangrenosum (PG) is a rare inflammatory neutrophilic disorder with prototypical clinical presentations. Its pathophysiology is complex and not fully explained. Recent information regarding the genetic basis of PG and the role of auto-inflammation provides a better understanding of the disease and new therapeutic targets. PG equally affects patients of both sexes and of any age. Uncontrolled cutaneous neutrophilic inflammation is the cornerstone in a genetically predisposed individual. Multimodality management is often required to reduce inflammation, optimize wound healing, and treat underlying disease. A gold standard for the management of PG does not exist and high-level evidence is limited. Multiple factors must be taken into account when deciding on the optimum treatment for individual patients: location, number and size of lesion/ulceration(s), extracutaneous involvement, presence of associated disease, cost, and side effects of treatment, as well as patient comorbidities and preferences. Refractory and rapidly progressive cases require early initiation of systemic therapy. Newer targeted therapies represent a promising pathway for the management of PG, and the main focus of this review is the management and evidence supporting the role of new targeted therapies in PG.

  • Evaluation of antimicrobial susceptibility and integron carriage in Helicobacter pylori isolates from patients.
    Evaluation of antimicrobial susceptibility and integron carriage in Helicobacter pylori isolates from patients. [Journal Article]Gastroenterol Hepatol Bed Bench 2016 Dec; 9(Suppl1):S47-S52.GHGoudarzi M, Heidary M, Azad M, et al. The high prevalence of multidrug resistance and frequency of class 2 integron in this survey can be a warning for clinicians. Continuous surveillance is necessary for the development of new treatment p...The purpose of this study was to determine the antibiotic susceptibility pattern and distribution of integron in H. pylori isolates collected from patients referred to private health care centers in Tehran, Iran.Antibiotic resistance is the main reason for failure of Helicobacter pylori therapy. Integrons as genetic reservoirs play main roles in the dissemination of antimicrobial resistance gene.During a 12-month cross-sectional study period, 65 H. pylori isolates were recovered from 124 biopsy specimens. Isolates were subjected to susceptibility testing using by Epsilometer test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. PCR was used to detect different types of integrons.Antimicrobial susceptibility testing revealed that 73.8% of isolates were resistant to metronidazole, 43.1% to clarithromycin, 29.2% to tetracycline, 27.7% to amoxicillin, 23.1% to rifampicin and 13.4% to levofloxacin. Frequency of multidrug resistance among H. pylori isolates was 26.1%. The most predominant resistance profiles among our isolates were included resistance to clarithromycin and metronidazole (20%). Class 1 and 2 integrons were detected in 8 (12.3%) and 15 (23.1%) of the isolates, respectively.The high prevalence of multidrug resistance and frequency of class 2 integron in this survey can be a warning for clinicians. Continuous surveillance is necessary for the development of new treatment protocols to prevent the treatment failures and also further spread of resistant isolates.

  • Evaluation of liver cirrhosis and hepatocellular carcinoma using Protein-Protein Interaction Networks.
    Evaluation of liver cirrhosis and hepatocellular carcinoma using Protein-Protein Interaction Networks. [Journal Article]Gastroenterol Hepatol Bed Bench 2016 Dec; 9(Suppl1):S14-S22.GHEhsani Ardakani MJ, Safaei A, Arefi Oskouie A, et al. In conclusion, this study suggests that there is a common molecular relationship between cirrhosis and hepatocellular cancer that may help with identification of target molecules for early treatment th...In the current study, we analysised only the articles that investigate serum proteome profile of cirrhosis patients or HCC patients versus healthy controls.Increased understanding of cancer biology has enabled identification of molecular events that lead to the discovery of numerous potential biomarkers in diseases. Protein-protein interaction networks is one of aspect that could elevate the understanding level of molecular events and protein connections that lead to the identification of genes and proteins associated with diseases.Gene expression data, including 63 gene or protein names for hepatocellular carcinoma and 29 gene or protein names for cirrhosis, were extracted from a number of previous investigations. The networks of related differentially expressed genes were explored using Cytoscape and the PPI analysis methods such as MCODE and ClueGO. Centrality and cluster screening identified hub genes, including APOE, TTR, CLU, and APOA1 in cirrhosis.CLU and APOE belong to the regulation of positive regulation of neurofibrillary tangle assembly. HP and APOE involved in cellular oxidant detoxification. C4B and C4BP belong to the complement activation, classical pathway and acute inflammation response pathway. Also, it was reported TTR, TFRC, VWF, CLU, A2M, APOA1, CKAP5, ZNF648, CASP8, and HSP27 as hubs in HCC. In HCC, these include A2M that are corresponding to platelet degranulation, humoral immune response, and negative regulation of immune effector process. CLU belong to the reverse cholesterol transport, platelet degranulation and human immune response. APOA1 corresponds to the reverse cholesterol transport, platelet degranulation and humoral immune response, as well as negative regulation of immune effector process pathway.In conclusion, this study suggests that there is a common molecular relationship between cirrhosis and hepatocellular cancer that may help with identification of target molecules for early treatment that is essential in cancer therapy.

  • Therapeutic Potential of Secreted Amyloid Precursor Protein APPsα.
    Therapeutic Potential of Secreted Amyloid Precursor Protein APPsα. [Journal Article, Review]Front Mol Neurosci 2017.:30.FMMockett BG, Richter M, Abraham WC, et al. Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage...Publisher Full TextCleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great potential as a therapeutic target. For example, APPsα is neurotrophic, neuroprotective, neurogenic, a stimulator of protein synthesis and gene expression, and enhances long-term potentiation (LTP) and memory. While most early studies have been conducted in vitro, effectiveness in animal models is now being confirmed. These studies have revealed that either upregulating α-secretase activity, acutely administering APPsα or chronic delivery of APPsα via a gene therapy approach can effectively treat mouse models of Alzheimer's disease (AD) and other disorders such as traumatic head injury. Together these findings suggest the need for intensifying research efforts to harness the therapeutic potential of this multifunctional protein.

  • CUL4A promotes proliferation and metastasis of colorectal cancer cells by regulating H3K4 trimethylation in epithelial-mesenchymal transition.
    CUL4A promotes proliferation and metastasis of colorectal cancer cells by regulating H3K4 trimethylation in epithelial-mesenchymal transition. [Journal Article]Onco Targets Ther 2017.:735-743.OTSui X, Zhou H, Zhu L, et al. Increasing evidence suggests that CUL4A, a ubiquitin ligase, is involved in the promotion of cancer malignancy and correlated with worse clinical prognosis in several kinds of human cancers. Although i...Publisher Full TextIncreasing evidence suggests that CUL4A, a ubiquitin ligase, is involved in the promotion of cancer malignancy and correlated with worse clinical prognosis in several kinds of human cancers. Although its effect and mechanism on the progression of colorectal cancer (CRC) remain unknown. Our clinical data show that CUL4A protein is overexpressed, positively associated with lymph nodes status, differentiation degree, tumor size, and poor prognosis in 80 CRC patients. CUL4A overexpression promotes cell proliferation and colony formation of CRC cells. Knockdown of CUL4A inhibits cell proliferation and migration. CUL4A can significantly promote the in vitro migration of CRC cells via induction of the epithelial-mesenchymal transition process. And the modulation of CUL4A expression altered the level of H3K4 trimethylation at the E-cadherin, N-cadherin, and vimentin gene promoters, which in turn transcriptionally regulated their expression. Moreover, knockdown of CUL4A also decreased the tumor volume and tumor weight in vivo. Together, our results reveal that CUL4A plays as an oncogene in CRC and may become a potential therapeutic target in the treatment of colorectal cancer.

  • FLT3 inhibitors: clinical potential in acute myeloid leukemia.
    FLT3 inhibitors: clinical potential in acute myeloid leukemia. [Journal Article, Review]Onco Targets Ther 2017.:607-615.OTHospital MA, Green AS, Maciel TT, et al. Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy that is cured in as few as 15%-40% of cases. Tremendous improvements in AML prognostication arose from a comprehensive analysis of...Publisher Full TextAcute myeloid leukemia (AML) is an aggressive hematopoietic malignancy that is cured in as few as 15%-40% of cases. Tremendous improvements in AML prognostication arose from a comprehensive analysis of leukemia cell genomes. Among normal karyotype AML cases, mutations in the FLT3 gene are the ones most commonly detected as having a deleterious prognostic impact. FLT3 is a transmembrane tyrosine kinase receptor, and alterations of the FLT3 gene such as internal tandem duplications (FLT3-ITD) deregulate FLT3 downstream signaling pathways in favor of increased cell proliferation and survival. FLT3 tyrosine kinase inhibitors (TKI) emerged as a new therapeutic option in FLT3-ITD AML, and clinical trials are ongoing with a variety of TKI either alone, combined with chemotherapy, or even as maintenance after allogenic stem cell transplantation. However, a wide range of molecular resistance mechanisms are activated upon TKI therapy, thus limiting their clinical impact. Massive research efforts are now ongoing to develop more efficient FLT3 TKI and/or new therapies targeting these resistance mechanisms to improve the prognosis of FLT3-ITD AML patients in the future.

Suggestions