Whole-Genome Sequencing to Identify the Genetic Etiology of a Spontaneous Thymoma Mouse Model |
Author : Milan Radovich |
Abstract | Full Text |
Abstract :Background: A mouse model for thymoma was previously created serendipitously by the random introduction of a transgene consisting of a mouse a-cardiac promoter, a constitutively active human transforming growth factor-ß, and a simian virus 40 integration sequence into C3HeB/FeJ mice. Previous data demonstrated that the likely cause of thymomas in the thymoma mouse model was due to insertional mutagenesis by the transgene. At the time, fluorescence in situ hybridization was used to localize the transgene to the short arm of chromosome 2 (Chr2qF2-G region). In this exploratory study, we aimed to identify the exact insertion site of the transgene as this could provide clues to the genetic causation of thymomas in humans.
Materials and Methods: To identify the insertion site of the transgene, germline DNA from the thymoma mouse model was sequenced using low-pass, fragment-library, whole genome sequencing. Long-insert mate pair whole genome sequencing was employed to traverse the repetitive regions of the mouse’s genome and identify the integration site.
Results: The transgene was found to be integrated into a repetitive area of the mouse genome, specifically on Chr2qF1 within the intron of the FAM227B gene. Tandem integration of the transgene was observed with enumeration of an estimated 30 copies. Initial results suggested that a nearby gene, fibroblast growth factor 7 (Fgf7), could be affected by the gene insertion.
Conclusions: Whole genome sequencing of this thymoma mouse model identified the region of tandem integration of a transgene on Chr2qF1 that may have potential translational implications in helping to understand the genomic etiology of thymoma in humans. |
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Sphingomonas paucimobilis complicating vaginal fluid cultivation. A rare case |
Author : Chrisostomos Sofoudis |
Abstract | Full Text |
Abstract :Sphingomonas paucimobilis represents an aerobic Gram-negative bacillus that is gaining recognition as an important human pathogen.
These species are widely distributed in both natural environment and hospitals.
They appear as opportunistic pathogen that take advantage of underlying conditions and diseases.
Regardless of the clinical significance, pathogenic mechanism varies throughout current bibliography.
Aim of our study, reflects presentation of a rare case of an out-patient clinical asymptomatic, with vaginal culture positive for this rare microorganism, S. paucimobilis.
Assiduous diagnosis and therapeutic mapping consist necessary conditions of effective treatment. |
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Prostate cancer presented with de novo brain metastases as initial manifestation: A case report with review of the literature |
Author : Konstantinos Tsapakidis and Ioannis Litos |
Abstract | Full Text |
Abstract :Prostate cancer is the most common cancer and among the leading causes of cancer death in men and its clinical symptoms vary a lot. The most common metastatic site is the bones, but rarely prostate cancer can metastasize to brain in very advanced stages of the disease. However, brain metastases giving neurological symptoms as first manifestation of prostate cancers have been reported. Research of international literature revealed only seventeen patients (including our own) that were diagnosed with prostate cancer presented with neurological symptoms. |
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Calcitriol Revises Aromatase Gene Expression in Ehrlich Solid Tumor Bearing Mice Exposed to Low Dose Gamma Radiation |
Author : Nermeen M El Bakary |
Abstract | Full Text |
Abstract :Background: Dysregulation of aromatase expression had been monitored in many types of cancer. Our study aimed to evaluate the possible role of calcitriol (Cal; Vit D3-OH) or/and low dose of gamma radiation in regulation of aromatase gene expression and the regression of tumor proliferation in murine model (EST; Ehrlich solid tumor bearing mice).
Methods: Mice with ˜1 cm3 EST were received (i.p. injection) day after day repeated doses of Calcitriol (Cal) (0.05µg/mouse) for 14day or/and exposed to 0.5 Gy gamma radiation (low dose) delivered as one shot at dose rate 0.48 Gy/min.
Results: Our results demonstrated that, mRNA expression of aromatase, levels of cyclooxygenase (COX2) and prostaglandin (PGE2) in addition to volume of the tumor are significantly decreased while caspase 3 level is significantly increased in EST mice treated with Cal or/and exposed to 0.5 Gy gamma ray compared to untreated EST bearing mice. However, the most pronounced improvements in all of the measured parameters were obviously indicated in EST mice group treated with Cal and exposed to gamma radiation. This was accomplished by suppression of inflammatory markers which cause down regulation in aromatase mRNA expression as well as augmenting apoptosis by inducing Caspase3 concentration.
Conclusion: It could be concluded that the exposure to low dose gamma radiation potentiate the action of Calcitriol against tumor growth in the subjected murine model which represent a prospective policy for the management of solid tumor and decreasing the possibilities of tumor drug resistance. |
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