DigitalUM :: Browsing by Subject "Gene therapy"

Browsing by Subject "Gene therapy"

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Open Access
Gene therapy strategies in neurodegenerative diseases
(Murcia : F. Hernández, 2001) Giménez y Ribotta, M.
Treatment of neurodegenerative diseases by classical pharmacotherapy is restricted by blood-brain barrier which prevents access to the brain of potentially therapeutic molecules. Recent progress in the knowledge of pathophysiological molecular processes, and in the development of molecular biotechnology have opened the way to new therapeutic interventions for these disorders. This chapter reviews the most recent gene therapy strategies using experimental models for neurodegenerative diseases.
Open Access
Gene therapy using herpes simplex virus-based vectors
(Murcia : F. Hernández, 2000) Latchman, D.S.
Gene therapy involves the use of specific genes to treat human diseases and is thus critically dependent on efficient gene delivery systems. Although a variety of systems for such gene delivery are under development, HSV has unique advantages in terms of its large genome size and for gene delivery in the nervous system because of its ability to enter a latent state in neuronal cells. Considerable progress has been made in the effective disablement of this virus whilst retaining its ability to deliver genes and in producing long term expression of the foreign gene. Although much remains to be achieved in the further disablement of the virus and its testing in rodent and primate models of human diseases, it is likely that these viruses may ultimately be of use in human gene therapy procedures particularly for otherwise intractable neurological diseases.
Open Access
KRT80 expression works as a biomarker and a target for differentiation in gastric cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Shi, Kai hang; Xue, Hang; Zhao, En hong; Xiao, Li jun; Sun, Hong zhi; Zheng, Hua Chuan
. Keratin 80 (KRT80) is a filament protein that participates in cell differentiation and the integrity of the epithelial barrier. Here, KRT80 expression was higher in gastric cancer compared with normal mucosa at both mRNA and protein levels by bioinformatic analysis, qRT-PCR and Western blot (p<0.05), however, the methylation of KRT80 was lower than in normal mucosa (p<0.05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in gastric cancer (p<0.05). KRT80 mRNA and protein expression was positively correlated with the differentiation of gastric cancer (p<0.05), while KRT80 methylation was negatively associated with gastric cancer differentiation and p53 mutation (p<0.05). The expression of KRT80 mRNA was positively linked to the short survival time of gastric cancers (p<0.05). The differential genes of KRT80 mRNA were involved in ligand-receptor interaction, estrogen signal pathway, peptidase, filament and cytoskeleton, keratinocyte differentiation, vitamin D receptor, muscle contraction, and B cell-mediated immunity (p<0.05). KRT80-related genes were classified into cell adhesion and junction, cadherin binding, skin and epidermis development, and so forth (p<0.05). KRT80 knockdown suppressed proliferation, anti-apoptosis, anti-pyroptosis, migration, invasion and epithelial-mesenchymal transition in gastric cancer cells (p<0.05). These findings indicated that upregulated expression of KRT80 played a crucial part in gastric carcinogenesis, and might be considered as a biological marker for aggressive behaviors and poor prognosis. Its silencing might be used as an approach of target therapy for gastric cancer patients.
Open Access
Perspectives in gene therapy
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 1998) Martín Duque, Mª del P.; Sánchez Prieto, R.; Lleonart, M.; Ramón y Cajal, S.
Gene therapy is understood to be both the restitution of genetic alterations caused by mutation or deletion and the control of overexpressed genes. The concept of gene therapy can also encompass molecular strategies to induce cell death in tumor cell by either the so-called "suicided genes" or by certain viral genes that induce a more selective cell dea th among th e transformed cells. The prospect for the clinical application of gene therapy are enormous and, at least theoretically. its utilization can be extended to a number of diseases known to have a genetic basis, and to neoplastic processes. This review summarizes some of the projects that are currently underway involving neopla stic dise ases. liver disease s, hematopoi e tic cells and respiratory tract cells. The results of most of the ongoing protocols are not yet conclusive, and presumibly, their clinical application is still some years away. One of the major limitations is the method of introducing the ge ne tic sequences into the cells and achieving their constitutive expression by the cells. For ethical reasons, this approach should not be done in germ cells, but at the leve l of the tissue or cells most closely involved in the deve lopment of each gene-based disease. The methods employed in gene therapy are discussed, focusing on those med iated by the application of viral vectors, as well as those requiring the use of liposomes and others.
Open Access
Salivary gland bioengineering - yesterday, today, tomorrow!
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Iyer, Janaki; Pillai, Sangeeth; Munguia Lopez, Jose G.; Zhang, Yuli; Mielkozorova, Mariia; Tran, Simon D.
Salivary glands are specialized structures developed as an extensively compact, arborized design through classical embryogenesis, accompanied by a cascade of events channelized by numerous growth factors and genetic regulatory pathways. Salivary secretions maintain oral homeostasis and, when diminished in certain conditions, present as xerostomia or salivary hypofunction, adversely impacting the patient’s quality of life. The current available treatments primarily aim at tackling the immediate symptoms providing temporary relief to the patient. Despite scientific efforts to develop permanent and effective solutions to restore salivation, a significant permanent treatment is yet to be established. Tissue engineering has proven as a promising remedial tool in several diseases, as well as in xerostomia, and aims to restore partial loss of organ function. Recapitulating the physiological cellular microenvironment to in vitro culture conditions is constantly evolving. Replicating the dynamic multicellular interactions, genetic pathways, and cytomorphogenic forces, as displayed during salivary gland development have experienced considerable barriers. Through this review, we endeavour to provide an outlook on the evolution of in vitro salivary gland research, highlighting the key bioengineering advances and the challenges faced with the current therapeutic strategies for salivary hypofunction, with an insight into our team’s scientific contributions.
Open Access
Skin gene therapy for acquired and inherited disorders
(Murcia : F. Hernández, 2006) Carretero, M.; Escámez, M.J.; Prada, F. A.; Mirones, I.; García, M.; Holguín, A.; Duarte, B.; Podhajcer, O.; Jorcano, J.L.; Larcher, F.; Del Río, M.
The rapid advances associated with the Human Genome Project combined with the development of proteomics technology set the bases to face the challenge of human gene therapy. Different strategies must be evaluated based on the genetic defect to be corrected. Therefore, the re-expression of the normal counterpart should be sufficient to reverse phenotype in single-gene inherited disorders. A growing number of candidate diseases are being evaluated since the ADA deficiency was selected for the first approved human gene therapy trial (Blaese et al., 1995). To cite some of them: sickle cell anemia, hemophilia, inherited immune deficiencies, hyper-cholesterolemia and cystic fibrosis. The approach does not seem to be so straightforward when a polygenic disorder is going to be treated. Many human traits like diabetes, hypertension, inflammatory diseases and cancer, appear to be due to the combined action of several genes and environment. For instance, several wizard gene therapy strategies have recently been proposed for cancer treatment, including the stimulation of the immune system of the patient (Xue et al., 2005), the targeting of particular signalling pathways to selectively kill cancer cells (Westphal and Melchner, 2002) and the modulation of the interactions with the stroma and the vasculature (Liotta, 2001; Liotta and Kohn, 2001).
Open Access
Telomerase activity in cancer as a diagnostic and therapeutic target
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Kyo, S.; Takakura, M.; Inoue, M.
Major advances have been made in understanding the role of telomerase in cellular immortalization and carcinogenesis. Human telomeres undergo progressive shortening with cell division, and critical shortening of telomeres with cellular aging triggers a signal for cells to stop dividing and senesce. Telomerase is an enzyme that adds telomeric-repeated sequences to the ends of human chromosome DNA. Telomerase is active in the vast majority of tumors, but not in normal somatic tissues, and prevents progressive shortening of telomeres with cell division, probably giving tumor cells a growth advantage over normal cells. Highly-sensitive PCR-based TRAP (telomeric repeat amplification protocol) assay provided the means to analyze telomerase in a wide variety of tissues. Evidence has been accumulated that this assay may be useful as a potential diagnostic tool for cancer. The constituents of telomerase complex have recently been identified, and human telomerase reverse transcriptase (hTERT) has been found to be responsible for the enzymatic activity of telomerase. Detection of hTERT mRNA may therefore be useful for the screening and diagnosis of cancers. The mechanisms regulating hTERT expression have been extensively analyzed, and transcriptional regulation of hTERT has been found to be essential for hTERT expression, in which several nuclear factors including c-Myc play crucial roles. Understanding of such mechanisms might provide insight into molecular basis of human carcinogenesis and contributes to the development of novel cancer gene therapy targeting telomerase.
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Terapia génica en la enfermedad de Parkinson
(Elsevier España, 2007-02) Fernández Barreiro, Andrés; Gómez Gallego, María; Atención Sociosanitaria
La enfermedad de Parkinson es un trastorno crónico y progresivo cuyo tratamiento no impide a medio plazo la aparición de complicaciones motoras y psíquicas invalidantes. Las técnicas de terapia génica de aplicación cada vez mayor en el campo de las enfermedades neurodegenerativas se suman a las posibilidades de tratamiento de esta patología. Entre las modalidades existentes, las estrategias in vivo que emplean potentes vectores virales son las que mejores resultados han obtenido en los distintos modelos existentes de la enfermedad. Este artículo pretende revisar la información referente al empleo de estas últimas técnicas, los ensayos terapéuticos que se han llevado a cabo y las ventajas e inconvenientes que tiene la utilización de los diferentes vectores.----------------------
Open Access
The function and significance of SERA2a in congestive heart failure: an analysis of gene therapy trials
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Wu, Pei; Zhai, Yuting; Li, Dongye
Congestive heart failure (CHF) is a widespread disease that has a negative impact on health, worldwide. Despite advances in therapies, morbidity, mortality and hospital discharges due to CHF remain high. Advances in the understanding of the pathophysiological mechanisms of CHF and the development of gene transfer technology have made gene therapy a realistic potential therapeutic method for CHF. Among the various potential targets, sarco-endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a), which is an important protein in the regulation of Ca2+ cycling, has piqued the interest of many researchers. Restoring decreased SERCA2a activity in CHF could improve cardiac contractions and energetics, as well as reducing myocardial fibrosis and ventricular arrhythmias, and these benefits have been confirmed by studies using both in vivo and in vitro models. Following these promising preclinical results, SERCA2a gene therapy advanced to clinical trials. However, results of the clinical trials were controversial, leading some to question whether SERCA2a is the right target for CHF treatment. In this review, we illustrate the function and significance of SERCA2a in CHF, and more importantly, analyze possible causes of the controversial clinical trials results, with the aim of stimulating future research on the relationship between SERCA2a and CHF.
Open Access
The promoting effects of Grin2d expression in tumorigenesis and the aggressiveness of esophageal cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Wang, Lin Lin; Li, Jun; Xue, Hang; Zhang, Li; Yu, Da yong; Yang, Ning; Yun, Wen jing; Zhao, Ming Zhen; Zheng, Hua Chuan
Grin2d is an ionotropic NMDA receptor, a subunit of glutamate-dependent, and a facilitator of cellular calcium influx in neuronal tissue. In this study, we found that Grin2d expression was higher in esophageal cancer than in normal mucosa at both the mRNA and protein level using RT-PCR, bioinformatics analysis, and western blotting (p<0.05). Grin2d mRNA expression was positively correlated with old age, white race, heavy weight, distal location, adenocarcinoma, cancer with Barrett’s lesion, or high-grade columnar dysplasia (p<0.05). The differential genes associated with Grin2d mRNA were involved in fat digestion and absorption, cholesterol metabolism, lipid transfer, lipoproteins, synaptic membranes, and ABC transporters (p<0.05). The Grin2d-related genes were classified into the following categories: metabolism of glycerolipids, galactose, and O-glycan, cell adhesion binding, actin binding, cadherin binding, the Hippo signaling pathway, cell-cell junctions, desmosomes, DNA-transcription activator binding, and skin development and differentiation (p<0.05). Grin2d immunoreactivity was positively correlated with distal metastasis and unfavorable overall survival in esophageal cancer (p<0.05). Grin2d overexpression promoted proliferation, migration, and invasion in esophageal cancer cells but blocked apoptosis (p<0.05) and increased the expression of PI3K, Akt and p-mTOR. Grin2d knockout caused the opposite effects. These findings indicated that upregulated Grin2d expression played an important role in esophageal carcinogenesis via the PI3K/Akt/mTOR pathway and might be a biological marker for aggressive tumor behavior and poor prognosis. Its silencing might represent a targeted therapy approach against esophageal cancer.

Browsing by Subject "Gene therapy"

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