The Grizzly, December 1, 2005

Memorial for Professor McLennan • Fate of The Egg • Jazz Legend Performs at Ursinus • Myrin Renovations • Murderball is Coming to Ursinus • Hot Discounts Warm up the Ski Season • Am I Pregnant? • What\u27s Hot and What\u27s Not This Gift-Giving Season • Wanted: Greek Presidents • Opinions: The Bigger Headache with PA Liquor Laws; How to Avoid Disastrous Holiday Parties; Addicted to Games, Are We? • Bears Ground Flying Dutchmen • Bears Fall Short of NCAA Titlehttps://digitalcommons.ursinus.edu/grizzlynews/1701/thumbnail.jp

The Grizzly, October 27, 2005

Clamer Ghosts at it Again • Henrietta: A Haunting Tale • Spirits Spook BWC and Elliott • Terror Behind the Walls • Lighter Side of Halloween • Senior Halloween Party Promises to Bring Excitement to the Weekend • Opinions: Words that Scare People • Streak Ends as Bears Douse Bullets • Bears Blank Bulletshttps://digitalcommons.ursinus.edu/grizzlynews/1697/thumbnail.jp

The Grizzly, September 15, 2005

Gas Prices Continue to Rise • Campus and Local Community Begin Relief Efforts • Students Share Study Abroad Experiences • The Deal with the Meal Deal • One of Ursinus\u27 Own Performs Professionally • Watch Out, Employers: You Could be Next! • How Much is Too Much? Your Guide to Avoiding Portion Distortion • Excitement Building in Kaleidoscope • Beyond the Condom: Guide to Safe Sex • Opinions: New Price of Driving; Ursinus, U are Worth it • Irony of Work Study • Things They Didn\u27t Teach You at Freshman Orientation • Who Says Division III Players Can\u27t Go Pro?https://digitalcommons.ursinus.edu/grizzlynews/1692/thumbnail.jp

The Grizzly, November 10, 2005

Congress to Campus • Spyware Protection • Honor Code Debate Continues • Human Rights Activist Speaks at UC • Scientific Sexual Healing • Epic Skate Shop • DiBlasio to Perform at Ursinus • Repeat! Dynasty Built in Second CC Crown • Fad Diets: Sometimes it is OK Not to be Trendy • Opinions: My Mouth Runneth Over; Who is Samuel Alito? • No Crown but Earn Bid to ECAC • Women\u27s Rugby Division III Championshttps://digitalcommons.ursinus.edu/grizzlynews/1699/thumbnail.jp

The Grizzly, November 3, 2005

Remembering Professor McLennan: A Passionate Teacher and a Beloved Friend • Renowned Writer Speaks at Ursinus • Building Plans for Spring 2006 and Beyond • Ovarian Cancer Walk • Chikara Wrasslin\u27 • EQ vs. IQ: Hirsh-Pasek on Education • The Many Faces of Muslim Women • Take Heed and Use Your Keys • Escape Velocity\u27s Just the Start is a Great Success • New Oktoberfest Policies Put into Effect • Popping the Pill • RHA Brings Halloween Fun to Ursinus • Opinions: The Right to Write Right; Raising Rates for Resident Assistants; Global Gag Rule and FGM; Harriet Miers: Aftermath; You Snooze, You Lose • Title Hopes Still Alive as Ursinus Upsets #16 Johns Hopkins • Bears Beat Blue Jays, Look to Defend Conference Crownhttps://digitalcommons.ursinus.edu/grizzlynews/1698/thumbnail.jp

The Grizzly, September 29, 2005

Fire Safety on Campus • UC Tuition Series Part I: An Overview • Study Abroad in Madrid Returns • Campus Drive Removal • Upcoming RHA Events • Backed Up Your Computer Lately? • Club Spotlight: Le Cercle Francais • Seven Day Itch • The Drift Away Cafe • Main Street Walks for STD Awareness • Sigma Gamma Rho Walks for Sickle Cell Anemia • Update from Mexico • Heefner Organ Recital Series at Ursinus College • Readjusting: Tulane Students at Ursinus • Oktoberfest: An Ursinus Tradition • How do You Take Your Caffeine? • Opinions: Activities Fair Helps Students Get Involved; Face Off; Gangsta Mentality; This Year\u27s Fringe Festival Lived Up to its Name • Just for Kicks, Lady Bears Win Six • Bears Strand Shorewomen • Breaking the Moldhttps://digitalcommons.ursinus.edu/grizzlynews/1694/thumbnail.jp

Blockade of PDGFRβ circumvents resistance to MEK-JAK inhibition via intratumoral CD8+ T-cells infiltration\ua0in triple-negative breast cancer

BACKGROUND: Despite the increasing progress in targeted and immune based-directed therapies for other solid organ malignancies, currently there is no targeted therapy available for TNBCs. A number of mechanisms have been reported both in pre-clinical and clinical settings that involve inherent, acquired and adaptive resistance to small molecule inhibitors. Here, we demonstrated a novel resistance mechanism in TNBC cells mediated by PDGFRβ in response to JAK2 inhibition. METHODS: Multiple in vitro (subG1, western blotting, immunofluorescence, RT-PCR, Immunoprecipitation), in vivo and publically available datasets were used. RESULTS: We showed that TNBC cells exposed to MEK1/2-JAK2 inhibitors exhibit resistant colonies in anchorage-independent growth assays. Moreover, cells treated with various small molecule inhibitors including JAK2 promote PDGFRβ upregulation. Using publically available databases, we showed that patients expressing high PDGFRβ or its ligand PDGFB exhibit poor relapse-free survival upon chemotherapeutic treatment. Mechanistically we found that JAK2 expression controls steady state levels of PDGFRβ. Thus, co-blockade of PDGFRβ with JAK2 and MEK1/2 inhibitors completely eradicated resistant colonies in vitro. We found that triple-combined treatment had a\ua0significant impact on CD44+/CD24- stem-cell-like cells. Likewise, we found a significant tumor growth inhibition in vivo through intratumoral CD8+ T cells infiltration\ua0in a manner that is reversed by anti-CD8 antibody treatment. CONCLUSION: These findings reveal a novel regulatory role of JAK2-mediated PDGFRβ proteolysis and provide an example of a PDGFRβ-mediated resistance mechanism upon specific target inhibition in TNBC

Proteomic characterization of high-density lipoprotein particles in patients with non-alcoholic fatty liver disease

Abstract Background Metabolic diseases such as obesity and diabetes are associated with changes in high-density lipoprotein (HDL) particles, including changes in particle size and protein composition, often resulting in abnormal function. Recent studies suggested that patients with non-alcoholic fatty liver disease (NAFLD), including individuals with non-alcoholic steatohepatitis (NASH), have smaller HDL particles when compared to individuals without liver pathologies. However, no studies have investigated potential changes in HDL particle protein composition in patients with NAFLD, in addition to changes related to obesity, to explore putative functional changes of HDL which may increase the risk of cardiovascular complications. Methods From a cohort of morbidly obese females who were diagnosed with simple steatosis (SS), NASH, or normal liver histology, we selected five matched individuals from each condition for a preliminary pilot HDL proteome analysis. HDL particles were enriched using size-exclusion chromatography, and the proteome of the resulting fraction was analyzed by liquid chromatography tandem mass spectrometry. Differences in the proteomes between the three conditions (normal, SS, NASH) were assessed using label-free quantitative analysis. Gene ontology term analysis was performed to assess the potential impact of proteomic changes on specific functions of HDL particles. Results Of the 95 proteins identified, 12 proteins showed nominally significant differences between the three conditions. Gene ontology term analysis revealed that severity of the liver pathology may significantly impact the anti-thrombotic functions of HDL particles, as suggested by changes in the abundance of HDL-associated proteins such as antithrombin III and plasminogen. Conclusions The pilot data from this study suggest that changes in the HDL proteome may impact the functionality of HDL particles in NAFLD and NASH patients. These proteome changes may alter cardio-protective properties of HDL, potentially contributing to the increased cardiovascular disease risk in affected individuals. Further validation of these protein changes by orthogonal approaches is key to confirming the role of alterations in the HDL proteome in NAFLD and NASH. This will help elucidate the mechanistic effects of the altered HDL proteome on cardioprotective properties of HDL particles