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The information and links in this issue are no longer being updated and are provided for reference purposes only. Kaposi sarcoma is a soft tissue malignancy that affects the skin, the mucous membranes, the lymph nodes and other organs of individuals with compromised immune systems. Most studies of miRNA targets investigate changes to the RNA, but these studies may miss genes regulated at the protein level.
To verify that the miRNAs can reduce the endogenous protein levels of GRB2, ROCK2, STAT3 (I± and I?), and HMGCS1, the scientists expressed the 16 KSHV miRNAs in primary endothelial cells and used quantitative Western blotting to measure protein changes. The data generated by the authors also can be used to address the question of whether miRNA-mediated changes in gene expression are mostly seen at the mRNA or protein level. Finally, the researchers wanted to determine the functional relevance of KSHV miRNA-mediated gene expression changes.
Looking more broadly at the pathways regulated by proteins highly repressed by the KSHV miRNAs, the researchers found that they are involved in translation, the cytoskeleton, the cell cycle, chromatin modification, and angiogenesis. Conventional therapies for transitional cell carcinoma of the bladder often result in poor prognosis. We then examined YP2-induced CPE in various cell lines through light microscope and crystal violet staining. YP2 treatment significantly retarded MBT-2 bladder tumor growth compared with CW1 or PBS treatment. Taken together, our results suggest that YP2 may have therapeutic potential for the treatment of invasive bladder cancer. Board Review Answers Week Of Sept 8thEpstein–Barr virus mononucleosis usually involves exudative pharyngitis, lymphadenopathy, and atypical lymphocytosis. Common Cold – Wikipedia, The Free EncyclopediaThe common cold virus is typically transmitted via airborne droplets (aerosols), direct contact with infected nasal secretions, or fomites (contaminated objects).
Boost Your Immune System Naturally – YouTubeMost people that catch an airborne virus catch it because their immune system has been compromised in some shape or form. Laboratory ????Effective April 1, 2009, Marsh? eld Labs consolidated all Epstein–Barr virus (EBV) serological testing onto one automated platform, the Airborne and blood-borne transmissions are rare.
122701 Serologic Markers Of Epstein Barr Virus InfectionSEROLOGIC MARKERS OF EPSTEIN–BARR VIRUS INFECTION AND NASOPHARYNGEAL CARCINOMA medical consultations by physicians of the National Taiwan Uni-versity Hospital. Robyn Andersen, PhDMember, Public Health Sciences DivisionUnderstanding behavioral issues related to cancer intervention and prevention strategies. Chongzhi DiAssociate Member, Public Health Sciences DivisionResearch focus: Statistical methods in HIV prevention trials and in genetic association studies.
William Grady, MDMember, Clinical Research DivisionMember, Public Health Sciences DivisionRodger C. They combined cells from both conditions and used mass spectrometry to measure the abundance of isotope-labeled amino acids. It is caused by infection with human herpesvirus-8 also known as Kaposi sarcoma-associated herpesvirus or KSHV.
To observe proteins repressed by the KSHV miRNAs, the researchers used a novel method called pulsed stable isotope labeling of amino acids in cell culture (pSILAC) coupled with tandem mass spectrometry (MS).


They used fluorescent reporter genes each containing the 3’UTR from the transcript of one of the six proteins and found that the fluorescence from all six reporter genes was suppressed by at least one KSHV miRNA. All five proteins were inhibited by at least one miRNA, and expression of four of the five was repressed by multiple miRNAs.
The investigators took cells from their pSILAC study and used microarray analysis to look at mRNA changes. They found that repression of ROCK2 and STAT3 by the miRNAs prevented lysophosphatidic acid-induced expression of ICAM1, which recruits white blood cells to sites of inflammation. These results suggest that KSHV miRNAs target important cell functions and are likely to be critical for KSHV pathogenicity.
Proteomic Screening of Human Targets of Viral microRNAs Reveals Functions Associated with Immune Evasion and Angiogenesis. Increased survival was also observed in YP2-treated mice in comparison with CW1-treated or PBS-treated.
These individuals were not on any antiinflammatory drugs at the time Association of Epstein–Barr virus infection with systemic lupus erythematosus in Taiwan. Sonnabend was one of the first physicians to notice among his gay male patients an immune deficiency that would later be named AIDS. Bricker, PhDAssociate Member, Public Health Sciences DivisionAffiliate Associate Professor, Department of Psychology, University of Washington(1) Novel behavioral interventions (e.g. My group is particularly interested in better understanding exposures that influence (both good and bad) a cancer survivor's subsequent risk for developing heart disease and related conditions.
Goodman, MD, MSSenior Investigator, Swedish Medical Center Cancer InstituteMember, Public Health Sciences DivisionLung cancer prevention, cancer prevention clinical trials, biomarkers of cancer risk. Peter Nelson's lab focuses on understanding the molecular, cellular and physiological events that lead to cancer initiation and progression.
Neuhouser, PhD, RDMember, Public Health Sciences DivisionNutritional epidemiology, methods to improve diet and physical activity assessment, diet and physical activity in relation to energy balance, nutritional status and cancer risk.
In this assay, they expressed a collection of 16 KSHV miRNAs or a control miRNA in human endothelial cells then introduced amino acids containing stable medium-heavy or heavy isotopes, respectively, into the cell media to label newly-made proteins. After mapping the specific sites targeted by the miRNAs for two genes, the investigators mutated these sites, which relieved the miRNA-mediated repression. Comparing the protein and mRNA changes, they found that for the six newly-identified targets, the protein changes were stronger than the alterations in mRNA.
KSHV infection alone also strongly repressed ICAM1 levels, suggesting that the miRNAs could enhance viral immune system evasion. TNL dose-dependently lysed all the cell lines examined at 3 days postinfection, whereas YP2 exerted differential cytolytic effects on these cells. Immunofluorescent staining with swine antiserum against PrV demonstrated that PrV proteins were detected within MBT-2 tumors after intratumoral injection with either YP2 or TNL, whereas only background expression was observed with the tumor of PBS-treated animals.
Acceptance and Commitment Therapy) for changing health behavior delivered at the public health level; (2) natural psychoscocial influences on health behavior over the course of the lifespan. The goal of his research program is to understand how microenvironments within distant tissues regulate dormancy and growth of disseminated tumor cells (DTCs), and whether these niches convey chemoresistance to dormant DTCs.


We generate novel genetically engineered mouse models that we use to interrogate the biology underlying major cancer driver genes. While their functions are not well understood, these miRNAs may be a way for the virus to alter the host immune response without producing proteins that could be recognized and targeted by the immune system.
The investigators pooled the samples, extracted the proteins, and analyzed them with MS, which can detect the isotope-labeled amino acids. The strongly repressed proteins were more likely to have at least one predicted 3’UTR matching site. The researchers also wanted to verify that pSILAC-identified proteins are repressed by KSHV infection. These results suggest that examining protein expression can indeed find targets missed by studying mRNA alone. In addition to identifying proteins downregulated by the KSHV miRNAs, the investigators observed enhanced expression of HIF1I± and HMOX1, two genes known to promote angiogenesis, which is a hallmark of Kaposi sarcoma. Furthermore, hematoxylin-eosin staining revealed that the intratumoral infiltrate of mononuclear cells was more pronounced in the tumors injected with YP2 or TNL than those injected with PBS (Figure 5).
In virus infected endothelial cells, they observed significant decreases in the levels of the same five proteins, particularly HMGCS1, validating these targets. The scientists showed that their increased expression was due at least in part to miRNA-mediated repression of the ubiquitin ligase RBX1 and the transcription factor BACH1, respectively. The cytomegalovirus (CMV) early promoter was active in NIH3T3, MBT-2, and HCDB-1 cells, with highest activity found in NIH3T3 cells. Pseudorabies virus (PrV), a herpesvirus of swine, may be exploited as an oncolytic agent for human cancer. Nevertheless, TCC-SUP cells were as susceptible as TSGH-8301 cells to TNL infection, while J82 cells were more resistant to TNL-induced cytolysis. Cell were infected with varying doses of TNL or YP2, and monitored for CPE by crystal violet staining at 3 days postinfection. Interestingly, CPE in HCDB-1 cells infected with YP2 appeared more pronounced than that infected with TNL. After 24 h, cells were treated with TPA and retinoic acid and their luciferase activities were determined. In human bladder cancer cells, the ratio in TSGH-8301 cells was higher compared with that in J82 and TCC-SUP cells. In a separate experiment, cell viability was also measured by trypan blue exclusion 4 days after infection with YP2, TNL or CW1 at 2 ? 104 TCID50.
The viability of YP2- or CW1-infected NIH3T3 cells did not differ significantly from that of the mock-infected counterpart, whereas viable cells in TNL-infected cells were scarcely detected.
By contrast, the viability of MBT-2 cells decreased dramatically after YP2 or TNL infection, but remained unchanged after CW1 infection when compared with mock-infected cells (Figure 3).



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