Browsing by Subject "Biomedicine"

Now showing 1 - 8 of 8
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    Absence of human T-cell lymphotropic virus type I and human foamy virus in thymoma
    (Springer, 2004-06) Li, H.; Loehrer, P. J.; Hisada, M.; Henley, J.; Whitby, D.; Engels, E. A.; Medicine, School of Medicine
    The cause of thymoma, a rare malignancy of thymic epithelial cells, is unknown. Recent studies have reported the detection of DNA from human T-cell lymphotropic virus type I (HTLV-I) and human foamy virus (HFV) in small numbers of thymoma tumours, suggesting an aetiologic role for these retroviruses. In the present study, we evaluated 21 US thymoma patients and 20 patients with other cancers for evidence of infection with these viruses. We used the polymerase chain reaction to attempt to amplify viral DNA from tumour tissues, using primers from the pol and tax (HTLV-I) and gag and bel1 (HFV) regions. In these experiments, we did not detect HTLV-I or HFV DNA sequences in any thymoma or control tissues, despite adequate sensitivity of our assays (one HTLV-I copy per 25 000 cells, one HFV copy per 7500 cells). Additionally, none of 14 thymoma patients evaluated serologically for HTLV I/II infection was positive by enzyme-linked immunoassay (ELISA), while five (36%) had indeterminate Western blot reactivity. In comparison, one of 20 US blood donors was HTLV-I/II ELISA positive, and nine (45%) donors, including the ELISA-positive donor, had indeterminate Western blot reactivity. Western blot patterns varied across individuals and consisted mostly of weak reactivity. In conclusion, we did not find evidence for the presence of HTLV-I or HFV in US thymoma patients.
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    Comprehensive biomedical applications of low temperature plasmas
    (Elsevier, 2020-08-26) Duarte, Simone; Panariello, Beatriz H.D.; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    The main component of plasma medicine is the use of low-temperature plasma (LTP) as a powerful tool for biomedical applications. LTP generates high reactivity at low temperatures and can be activated with noble gases with molecular mixtures or compressed air. LTP reactive species are quickly produced, and are a remarkably good source of reactive oxygen and nitrogen species including singlet oxygen (O2), ozone (O3), hydroxyl radicals (OH), nitrous oxide (NO), and nitrogen dioxide (NO2). Its low gas temperature and highly reactive non-equilibrium chemistry make it appropriate for the alteration of inorganic surfaces and delicate biological systems. Treatment of oral biofilm-related infections, treatment of wounds and skin diseases, assistance in cancer treatment, treatment of viruses’ infections (e.g. herpes simplex), and optimization of implants surfaces are included among the extensive plasma medicine applications. Each of these applications will be discussed in this review article.
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    Inhibition of epidermal growth factor receptor signalling reduces hypercalcaemia induced by human lung squamous-cell carcinoma in athymic mice
    (Springer, 2007-07) Lorch, G.; Gilmore, J. L.; Koltz, P. F.; Gonterman, R. M.; Laughner, R.; Lewis, D. A.; Konger, R. L.; Nadella, K. S.; Toribio, R. E.; Rosol, T. J.; Foley, J.; Biochemistry and Molecular Biology, School of Medicine
    The purpose of this study was to evaluate the role of the epidermal growth factor receptor (EGFR) in parathyroid hormone-related protein (PTHrP) expression and humoral hypercalcaemia of malignancy (HHM), using two different human squamous-cell carcinoma (SCC) xenograft models. A randomised controlled study in which nude mice with RWGT2 and HARA xenografts received either placebo or gefitinib 200 mg kg−1 for 3 days after developing HHM. Effectiveness of therapy was evaluated by measuring plasma calcium and PTHrP, urine cyclic AMP/creatinine ratios, and tumour volumes. The study end point was at 78 h. The lung SCC lines, RWGT2 and HARA, expressed high levels of PTHrP mRNA as well as abundant EGFR protein, but very little erbB2 or erbB3. Both lines expressed high transcript levels for the EGFR ligand, amphiregulin (AREG), as well as, substantially lower levels of transforming growth factor-α (TGF-α), and heparin binding-epidermal growth factor (HB-EGF) mRNA. Parathyroid hormone-related protein gene expression in both lines was reduced 40–80% after treatment with 1 μ M of EGFR tyrosine kinase inhibitor PD153035 and precipitating antibodies to AREG. Gefitinib treatment of hypercalcaemic mice with RWGT2 and HARA xenografts resulted in a significant reduction of plasma total calcium concentrations by 78 h. Autocrine AREG stimulated the EGFR and increased PTHrP gene expression in the RWGT2 and HARA lung SCC lines. Inhibition of the EGFR pathway in two human SCC models of HHM by an anilinoquinazoline demonstrated that the EGFR tyrosine kinase is a potential target for antihypercalcaemic therapy.
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    Laboratory analysis of acylcarnitines, 2020 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG)
    (Elsevier, 2020-02) Miller, Marcus J.; Cusmano-Ozog, Kristina; Oglesbee, Devin; Young, Sarah; Medical and Molecular Genetics, School of Medicine
    Acylcarnitine analysis is a useful test for identifying patients with inborn errors of mitochondrial fatty acid β-oxidation and certain organic acidemias. Plasma is routinely used in the diagnostic workup of symptomatic patients. Urine analysis of targeted acylcarnitine species may be helpful in the diagnosis of glutaric acidemia type I and other disorders in which polar acylcarnitine species accumulate. For newborn screening applications, dried blood spot acylcarnitine analysis can be performed as a multiplex assay with other analytes, including amino acids, succinylacetone, guanidinoacetate, creatine, and lysophosphatidylcholines. Tandem mass spectrometric methodology, established more than 30 years ago, remains a valid approach for acylcarnitine analysis. The method involves flow-injection analysis of esterified or underivatized acylcarnitines species and detection using a precursor-ion scan. Alternative methods utilize liquid chromatographic separation of isomeric and isobaric species and/or detection by selected reaction monitoring. These technical standards were developed as a resource for diagnostic laboratory practices in acylcarnitine analysis, interpretation, and reporting.
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    Lack of EGF receptor contributes to drug sensitivity of human germline cells
    (Springer, 2005-01) Park, S.J.; Armstrong, S.; Kim, C.H.; Yu, M.; Robertson, K.; Kelley, Mark R.; Lee, S.H.; Biochemistry and Molecular Biology, School of Medicine
    Germline mutations have been associated with generation of various types of tumour. In this study, we investigated genetic alteration of germline tumours that affect the drug sensitivity of cells. Although all germline tumour cells we tested were hypersensitive to DNA-damaging drugs, no significant alteration was observed in their DNA repair activity or the expression of DNA repair proteins. In contrast, germline tumours expressed very low level of epidermal growth factor receptor (EGFR) compared to drug-resistant ovarian cancer cells. An immunohistochemical analysis indicated that most of the primary germline tumours we tested expressed very low level of EGFR. In accordance with this, overexpression of EGFR in germline tumour cells showed an increase in drug resistance, suggesting that a lack of EGFR, at least in part, contributes to the drug sensitivity of germline tumours.
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    O6-methylguanine-DNA-methyltransferase expression and gene polymorphisms in relation to chemotherapeutic response in metastatic melanoma
    (Springer, 2003-10) Ma, S.; Egyházi, S.; Ueno, T.; Lindholm, C.; Kreklau, E. L.; Stierner, U.; Ringborg, U.; Hansson, J.; Pharmacology and Toxicology, School of Medicine
    In a retrospective study, O6-methylguanine-DNA-methyltransferase (MGMT) expression was analysed by immunohistochemistry using monoclonal human anti-MGMT antibody in melanoma metastases in patients receiving dacarbazine (DTIC) as single-drug therapy or as part of combination chemotherapy with DTIC–vindesine or DTIC–vindesine–cisplatin. The correlation of MGMT expression levels with clinical response to chemotherapy was investigated in 79 patients with metastatic melanoma. There was an inverse relationship between MGMT expression and clinical response to DTIC-based chemotherapy (P=0.05). Polymorphisms in the coding region of the MGMT gene were also investigated in tumours from 52 melanoma patients by PCR/SSCP and nucleotide sequence analyses. Single-nucleotide polymorphisms (SNPs) in exon 3 (L53L and L84F) and in exon 5 (I143V/K178R) were identified. There were no differences in the frequencies of these polymorphisms between these melanoma patients and patients with familial melanoma or healthy Swedish individuals. Functional analysis of variants MGMT-I143V and -I143V/K178R was performed by in vitro mutagenesis in Escherichia coli. There was no evidence that these variants decreased the MGMT DNA repair activity compared to the wild-type protein. All melanoma patients with the MGMT 53/84 polymorphism except one had tumours with high MGMT expression. There was no significant correlation between any of the MGMT polymorphisms and clinical response to chemotherapy, although an indication of a lower response rate in patients with SNPs in exon 5 was obtained. Thus, MGMT expression appears to be more related to response to chemotherapy than MGMT polymorphisms in patients with metastatic melanoma.
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    Somatic mutations of KIT in familial testicular germ cell tumours
    (Springer, 2004-06) Rapley, E. A.; Hockley, S.; Warren, W.; Johnson, L.; Huddart, R.; Crockford, G.; Forman, D.; Leahy, M. G.; Oliver, D. T.; Tucker, K.; Friedlander, M.; Phillips, K.-A.; Hogg, D.; Jewett, M. A. S.; Lohynska, R.; Daugaard, G.; Richard, S.; Heidenreich, A.; Geczi, L.; Bodrogi, I.; Olah, E.; Ormiston, W. J.; Daly, P. A.; Looijenga, L. H. J.; Guilford, P.; Aass, N.; Fosså, S. D.; Heimdal, K.; Tjulandin, S. A.; Liubchenko, L.; Stoll, H.; Weber, W.; Einhorn, L.; Weber, B. L.; McMaster, M.; Greene, M. H.; Bishop, D. T.; Easton, D.; Stratton, M. R.; Medicine, School of Medicine
    Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT. No germline mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five somatic mutations were identified; four were missense amino-acid substitutions in exon 17 and one was a 12 bp in-frame deletion in exon 11. Two of seven TGCT from cases with bilateral disease carried KIT mutations compared with three out of 116 unilateral cases (P=0.026). The results indicate that somatic KIT mutations are implicated in the development of a minority of familial as well as sporadic TGCT. They also lend support to the hypothesis that KIT mutations primarily take place during embryogenesis such that primordial germ cells with KIT mutations are distributed to both testes.
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    Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function
    (Springer, 2004-02) Bhat-Nakshatri, P.; Campbell, R. A.; Patel, N. M.; Newton, T. R.; King, A. J.; Marshall, M. S.; Ali, S.; Nakshatri, H.; Surgery, School of Medicine
    Oestrogen receptor alpha (ERα) is an oestrogen-activated transcription factor, which regulates proliferation and differentiation of mammary epithelial cells by activating or repressing gene expression. ERα is a critical prognostic indicator and a therapeutic target for breast cancer. Patients with tumours that express higher level of ERα have better prognosis than patients with tumours that are ERα negative or express lower level of ERα. Better prognosis in ERα-positive patients is believed to be due to repression of proinvasive gene expression by ERα. Oestrogen receptor alpha represses gene expression by transrepressing the activity of the transcription factors such as nuclear factor-kappaB or by inducing the expression of transcriptional suppressors such as MTA3. In this report, we show that ERα transrepresses the expression of the proinvasive gene interleukin 6 (IL-6) in ERα-negative MDA-MB-231 breast cancer cells stably overexpressing ERα. Using these cells as well as ERα-positive MCF-7 and ZR-75-1 cells, we show that tumour necrosis factor alpha (TNFα) and the phosphatidylinositol-3-kinase (PI3-kinase) modulate transrepression function of ERα by reducing its stability. From these results, we propose that TNFα expression or PI3-kinase activation lead to reduced levels of ERα protein in cancer cells and corresponding loss of transrepression function and acquisition of an invasive phenotype.