Journal of genetic syndromes & gene therapy最新文献

{"title":"Treatment of Pulmonary Hypertension in Downs Syndrome","authors":"S. Herbert, Tulloh Rmr","doi":"10.4172/2157-7412.1000273","DOIUrl":"https://doi.org/10.4172/2157-7412.1000273","url":null,"abstract":"Down’s Syndrome(DS) is the most common chromosomal abnormality associated with multiple comorbidities including congenital heart disease and respiratory disease typically with airway obstruction. These comorbidities have been documented to contribute to pulmonary arterial hypertension (PAH) within months if left untreated. It is therefore of paramount importance to identify congenital abnormalities to prevent the progression of PAH in such people. Since people with DS have a higher risk of developing PAH in comparison to the normal population, they must be both monitored for symptoms of disease as categorized by WHO functional class and be actively treated in order to halt or slow the disease process.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"161 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2015-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80171852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cooperative Interaction between the Alpha1-Adrenoceptors (ñ1-AR) andTransient Receptor Potential (TRP) Triggers a Proliferative Cell Signal inProstate Cancer Cell Lines","authors":"G. Santoni, M. Morelli, C. Amantini, M. Santoni, M. Nabissi, C. Cardinali, F. Bello, Aless, R. Piergentili, W. Quaglia","doi":"10.4172/2157-7412.1000275","DOIUrl":"https://doi.org/10.4172/2157-7412.1000275","url":null,"abstract":"Calcium (Ca2+) increases the proliferation of human advanced prostate cancer (PCa) cells but the ion channels involved are unknown. Santoni and Quaglia groups investigated the correlation between alpha1D-adrenergic receptor (α1D-AR) and the transient receptor potential vanilloid type 1 (TRPV1) ion channel expression in PCa cells. The α1D-AR and TRPV1 mRNAs are increased in PCa compared to BPH. α1D-AR and TRPV1 are co-expressed in PCa cells. Norepinephrine (NE) induced α1D-AR- and TRPV1-dependent protons release, Ca2+ flux in PC3 cells and activation of PLC, PKC and ERK path-ways that stimulated PC3 cell proliferation. Similarly, a role for TRPC6 or GPR55 in α1-AR-dependent proliferation of mesangial cells and PCa cells was reported. Overall, a crosstalk between α1-AR and TRPs in PCa cells, involved in the control of cell proliferation has been demonstrated. These data strongly promote a putative novel pharmacological approach in the treatment of PCa by targeting both α1-AR and TRP channels.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"17 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2015-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90563551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribosome Inactivating Proteins: Exploiting Plant Weapons to Fight Human Cancer","authors":"R. Vago","doi":"10.4172/2157-7412.1000272","DOIUrl":"https://doi.org/10.4172/2157-7412.1000272","url":null,"abstract":"Ribosomeinactivating proteins (RIPs) are potent toxins from plant or bacterial origin that work by irreversibly block ribosomes of target cells, causing apoptotic cell death. Their noteworthy activity has been exploited to therapeutic purpose in the treatment of cancer. The specificity for malignant cells has been addressed by using targeting domains such as antibodies to form immunotoxins or ligands to get chimeric fusions. These therapeutics have shown encouraging preliminary results in hematological tumors as well as in solid tumors with the most effective ones currently undergoing clinical trials. Denileukin diftitox, a fusion between the catalytic domain of the diphtheria toxin and human cytokine interleukin-2, was the first toxin-derived drug approved by the FDA. Another, more recent way to take advantage of RIPs is to utilize their DNA in the suicide gene therapy. Toxin DNA can be delivered trough a vector to or complexed and directly injected in the tumor. In the future RIPs are expected in to give a significant contribution in the treatment of the cancer, also in combination with traditional therapies. The scope of this review is to highlight advantages and drawbacks of RIP based biomedical applications, by evaluating their employment as either targeted proteins or genes as effectors.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"148 Pt 8 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2015-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84088385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Let-7 Family miRNAs Represent Potential Broad-Spectrum Therapeutic Molecules for Human Cancer","authors":"J. Guan, S. Guo, M. Liu","doi":"10.4172/2157-7412.1000271","DOIUrl":"https://doi.org/10.4172/2157-7412.1000271","url":null,"abstract":"miRNAs are a class of small non-coding RNAs that modulate gene expression. Let-7 was first discovered in Caenorhabditis elegans and is one of the most extensively studied miRNAs. The human let-7 family contains 13 miRNAs. The expression of these miRNAs is decreased in most human cancers and contributes to carcinogenesis and progression. Thus, the let-7 family of miRNAs has attracted the attention of researchers in various fields. Exogenous let-7 restoration has been confirmed to show antitumor efficacy in many human cancers. Let-7 functions as a tumor suppressor by acting upon several multi-signaling pathways and multiple downstream target oncogenes that are involved in most human cancers. Let-7 shows potential for modulation of chemoresistance and radiation sensitivity in human cancers. miRNAs in the let-7 family represent potential broad-spectrum antitumor molecules for human cancer therapy, and miRNAs in this family have been studied intensively for their therapeutic potential. However, most previous studies have been limited to a single functional aspect or focused on a single effect in a particular type of cancer. Here, we review the latest research on let-7 and discuss its potential value as a broadspectrum antitumor molecule.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"34 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2015-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82173820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folate Metabolism and Genetic Variant in Down Syndrome: A Meta-Analysis","authors":"A. Asim, S. Agarwal, Sakil Kulkarni, I. Panigrahi","doi":"10.4172/2157-7412.1000270","DOIUrl":"https://doi.org/10.4172/2157-7412.1000270","url":null,"abstract":"Objectives: Studies investigating the association between gene polymorphisms involved in homocysteine/folate metabolism and Down syndrome (DS) have reported contradictory or inconclusive results. A meta- analysis of 25 studies on association between MTHFR and MTRR polymorphism and DS including 1, 934/2,081/ cases/controls for MTHFR C677T polymorphism, 1,404/1,632/ cases/control for MTHFR A1298C polymorphism and 859 /1,132/cases/ control for MTRR A66G polymorphism was carried out. Study design: Studies were identified by searching the PubMed database for relevant articles published. Case – control studies were chosen, and odds ratio (OR) with confidence interval (CI) were used to assess the strength of association. Results: The overall results suggested that the variant genotypes MTHFR C677T were associated with DS risk (homozygote, TT vs. CC: OR=2.991; 95% CI: 1.321-3.558; P=0.001 and co dominant model, CT vs. CC: OR=1.1616 (1.216-1.845; P=0.0001). The result of the variant genotypes MTHFR A1298C showed its association with the DS risk (homozygote, AA vs. CC: OR=1.428; 95% CI: 1.016-1.849; P=0.0067).In the stratified analysis, results obtained in variant genotype of MTHFR C677T A66G had increased risk of DS in Caucasian subjects in codominant and dominant model while the increased risk was found in dominant models for Brazilian and Asian subjects. Again, for MTHFR A1298C variant, increased risk was found in Caucasian subject in co-dominant, dominant and recessive models and in co-dominant model for Brazilian population. The results also show that in A66G variant of MTRR had increased risk of DS in both Caucasian and Brazilian subjects in dominant model. Conclusion: This meta-analysis supports the idea that MTHFR C677T and MTHFR A1298C genotype is associated with increased risk for DS.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"74 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2015-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73429199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Commentary on WNT7A Implication in Cervical Cancer Development","authors":"Cristina Artaza-Irigaray, A. Aguilar-Lemarroy, L. Jave-Suárez","doi":"10.4172/2157-7412.1000267","DOIUrl":"https://doi.org/10.4172/2157-7412.1000267","url":null,"abstract":"","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73472410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hallermann Streiff Syndrome-The Oral Manifestations in a Child","authors":"Sonu Acharya, Mamta Mohanty, Sheetal Acharya","doi":"10.4172/2157-7412.1000268","DOIUrl":"https://doi.org/10.4172/2157-7412.1000268","url":null,"abstract":"Hallermann-Streiff syndrome (HSS) is a rare genetic disorder that is primarily characterized by distinctive malformations of the skull and facial region, sparse hair, eye abnormalities, dental defects, atrophic skin changes and a proportionate short stature. Here we discuss a case of 9 years-old female child who presented with abnormal facial features, dental problems and associated cardiac problems.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"58 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2015-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88747214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel mutation-deletion in the PHOX2B gene of the patient diagnosed with Neuroblastoma, Hirschsprung's Disease, and Congenital Central Hypoventilation Syndrome (NB-HSCR-CCHS) Cluster.","authors":"Izabela Szymońska, Thore L Borgenvik, T. M. Karlsvik, Anders Halsen, B. Malecki, S. Saetre, M. Jagła, P. Kruczek, Anna Madetko Talowska, G. Drabik, M. Zasada, M. Małecki","doi":"10.4172/2157-7412.1000269","DOIUrl":"https://doi.org/10.4172/2157-7412.1000269","url":null,"abstract":"INTRODUCTION\u0000Neuroblastoma (NB), Hirschsprung disease (HSCR), Congenital Central Hypoventilation Syndrome (CCHS), clinically referred as the NB-HSCR-CCHS cluster, are genetic disorders linked to mutations in the PHOX2B gene on chromosome 4p12.\u0000\u0000\u0000SPECIFIC AIM\u0000The specific aim of this project is to define the PHOX2B gene mutations as the genomic basis for the clinical manifestations of the NB-HSCR-CCHS cluster.\u0000\u0000\u0000PATIENT\u0000A one day old male patient presented to the Jagiellonian University Medical College (JUMC), American Children Hospital, neonatal Intensive Care Unit (ICU) due to abdominal distention, vomiting, and severe apneic episodes. With the preliminary diagnosis of the NB-HSCR-CCHS, the blood and tissue samples were acquired from the child, as well as from the child's parents. All procedures were pursued in accordance with the Declaration of Helsinki, with the patient's Guardian Informed Consent and the approval from the Institutional Review Board.\u0000\u0000\u0000GENETIC/GENOMIC METHODS\u0000Karyotyping was analyzed based upon Giemsa banding. The patient's genomic DNA was extracted from peripheral blood and amplified by polymerase chain reaction. Direct microfluidic Sanger sequencing was performed on the genomic DNA amplicons. These procedures were pursued in addition to the routine clinical examinations and tests.\u0000\u0000\u0000RESULTS\u0000G-banding showed the normal 46 XY karyotype. However, genomic sequencing revealed a novel, heterozygous deletion (8 nucleotides: c.699-706, del8) in exon 3 of the PHOX2B gene on chromosome 4. This led to the frame-shift mutation and malfunctioning gene expression product.\u0000\u0000\u0000CONCLUSION\u0000Herein, we report a novel PHOX2B gene mutation in the patient diagnosed with the NB-HSCR-CCHS cluster. The resulting gene expression product may be a contributor to the clinical manifestations of these genetic disorders. It adds to the library of the mutations linked to this syndrome. Consequently, we suggest that screening for the PHOX2B mutations becomes an integral part of genetic counseling, genomic sequencing of fetal circulating nucleic acids and / or genomes of circulating fetal cells prenatally, while preparing supportive therapy upon delivery, as well as on neonates' genomes of intubated infants, when breathing difficulties occur upon extubation. Further, we hypothesize that PHOX2B may be considered as a potential target for gene therapy.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2157-7412.1000269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72527971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal Liver-Derived Stem Cells Ameliorate Adipocyte Functions in Obese Mice","authors":"Ming Li, Ke-quan Guo, Yunze Cui, Y. Adachi, S. Ikehara","doi":"10.4172/2157-7412.1000263","DOIUrl":"https://doi.org/10.4172/2157-7412.1000263","url":null,"abstract":"Fetal liver (FL) contains hepatic stem cells, hematopietic stem cells, and mesenchymal stem cells, as well as pluripotent stem cells and very small embryonic-like stem cells. FL has thus been available as a source of stem cells for regenerative medicine. Our previous report suggested that combining FL cell transplantation with the transplantation of fetal thymus prevented tumor growth in tumor-bearing mice. Moreover, in animal models, intra bone marrow-bone marrow transplantation (IBM-BMT) has proven to be the best approach for allogenic BMT. We here propose that transplanting FL cells by IBM-BMT can improve adipocyte functions in obese mice. FL cells were collected from FLs of C57BL/6 mice at 16 days post coitum, and then transplanted by IBM-BMT to db/db mice, an animal model of type 2 diabetes with obesity. Our results showed that the body weight was significantly lower in the treated db/db mice than in the sham-treated db/db mice. The plasma IL-6 level significantly decreased and adiponectin level significantly increased after the transplantation of FL cells. Blood glucose levels also significantly decreased although not to within the normal range. This is the first report that the transplantation of FL cells may improve adipocyte functions, resulting in decreased body weight in obese mice.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"22 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2015-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82499678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autosomal Dominant Corneal Dystrophy with TGFBI Mutations: Lessons Learned from a Chinese Pedigree","authors":"An-li Shu, Zheng Wei, Yibin Hao, Hai Luo, F. Tian, F. Biddle, Wei Wu, Min Liu, W. Cao","doi":"10.4172/2157-7412.1000264","DOIUrl":"https://doi.org/10.4172/2157-7412.1000264","url":null,"abstract":"Corneal dystrophies are rare autosomal dominant genetic diseases with diverse anatomic classification. The complexity of this disease reflects both the heterogeneity of causative gene mutations and the diversity of clinical presentations. Here, we studied and report a four-generation Chinese pedigree with corneal dystrophy, in which the clinical symptoms resemble Meesmann corneal dystrophy without the characteristic gene mutations of either KRT3 or KRT12. Targeted exon sequencing with PCR methods identified an Arg124Cys mutation in the TGFBI gene that concordant with phenotype in all affected individuals. This TGFBI mutation has been associated with multiple subtypes of corneal dystrophy. We reviewed the global reported TGFBI mutations in different ethnic groups and geographically mapped TGFBI mutations previously reported in China. The distribution of TGFBI allelic mutations may assist the clinical diagnosis of the heterogeneous, autosomal dominant corneal dystrophies.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"8 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2015-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81991883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}