The Ursinus Weekly, April 13, 1964

WSGA elections Wednesday: Barbara Hultz, Valerie Moritz run for association president • Contenders campaign comments • Ursinus hosts science fair • Sophomores plan weekend outing • Psych Club to hear Grosslight • Alumna to perform at piano dedication • Four charities benefit in Chest drive from campuswide activities: Shorb and Riley co-chairmen of project • Otto C. Lee to speak in PAC forum • MSGA winners announced • New look for SWC • Dr. Allen reads his poetry tonite • Editorial: Weekly policy • Spring, when a young man\u27s fancy turns to pledging • When a Negro hates • Next President: Rockefeller • Changing Ursinus • Ursinus victorious in all Spring sports: Baseball team defeats Dickinson; Lacrosse women 6-4 over Penn foe; Netmen overpower King\u27s College; Cindermen win, defeat Haverford 84-42 • Softball forecast • Women\u27s tennis: Experience is key • Wrestling banquet: Videon elected captain • UC\u27s Sue Harmon chosen Miss Montgomery County • Annual student-faculty show ends first week of activities • Heller & Dawson head Y • Meistersingers • Project Hopehttps://digitalcommons.ursinus.edu/weekly/1270/thumbnail.jp

The Ursinus Weekly, April 27, 1964

Waiters guests at annual banquet • Bohl receives Fullbright to study abroad • Campus organizations conduct Spring elections: MSGA chooses officers; WSGA names class reps • Yocum selected to visit Russia • Mensch Mill site of annual Spring retreat • African trip, PAC forum event • Unadvertised Greek week promised to be one of the best • Cheerleaders • Spirit Committee • Women\u27s dorm officers • Meistersingers • Editorial: Supply and demand? • Next President: Henry Cabot Lodge • Slaves work for freedom with sweat, toil and bridge • Letters to the editor • Lacrosse loses 1st ever; Tennis blanked by Penn • Bears\u27 cindermen crunch Garnets • Penn relays have sad outcome • Winning week in Bears baseball • Softball swamps Penn foes 36-1 • Howard awarded science grant • Choir returns from New York • Greek gleanings • Classical music at Studio Cottage • Dr. Hetzel and American Indianhttps://digitalcommons.ursinus.edu/weekly/1272/thumbnail.jp

The Ursinus Weekly, May 4, 1964

WSGA revises constitution: Women to ratify provisions May 13 • UC wins award for alumni support • Greeks greet the sun with party weekend: Lee Vincent, King Twig, Little Anthony and Earl-J break the bleak week • Spring Festival features weekend of activities: Bye, bye Birdie Saturday • Mr. Pennypacker staged by Curtain Club • Band concert • Meistersingers repeat Spring concert for UC • WAA election and activities • UC students hear final concert • Editorial: Our faculty • Live cheaply and die rich • Fifty years ago • Letters to the editor • Dickinson and Johns Hopkins bow to UC trackmen 89-62-11: Rogart, Cooper, Dunn and Gladstone smash school, meet and field records • Rain doesn\u27t dampen spirits: UC swamps West Chester 15-3; Regester pitches 2nd victory in triumph over arch-rival • UC nine drops two close ones to F&M 4-3 and to Wilkes 3-2 • Dr. Howard named tennis advisor • MACs and PMC pose problems in track • Faculty members receive national science grants: Snyder to teach, Schultz to study in Summer schools • Greek gleaningshttps://digitalcommons.ursinus.edu/weekly/1273/thumbnail.jp

A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men

Background Genetic polymorphisms in the RAS gene family are associated with different diseases, which may include alcohol-related disorders. Previous studies showed an association of the allelic variant rs26907 in RASGRF2 gene with higher alcohol intake. Additionally, the rs61764370 polymorphism in the KRAS gene is located in a binding site for the let-7 micro-RNA family, which is potentially involved in alcohol-induced inflammation. Therefore, this study was designed to explore the association between these two polymorphisms and susceptibility to alcoholism or alcoholic liver disease (ALD). Methods We enrolled 301 male alcoholic patients and 156 healthy male volunteers in this study. Polymorphisms were genotyped by using TaqMan® PCR assays for allelic discrimination. Allelic and genotypic frequencies were compared between the two groups. Logistic regression analysis was performed to analyze the inheritance model. Results The A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis (23.2%) compared to alcoholic patients without ALD (14.2%). This difference remained significant in the group of patients with alcohol dependence (28.8% vs. 14.3%) but not in those with alcohol abuse (15.1% vs. 14.4%). Multivariable logistic regression analysis showed that the A allele of this polymorphism (AA or GA genotype) was associated with alcoholic cirrhosis both in the total group of alcoholics (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.32–4.11; P = 0.002) and in the group of patients with alcohol dependence (OR: 3.1, 95% CI: 1.50–6.20; P = 0.001). Allelic distributions of the KRAS polymorphism (rs61764370) did not differ between the groups. Conclusions To our knowledge, this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with ALD in men, particularly in the subgroup of patients with AD. The findings suggest the potential relevance of the RAS gene family in alcoholism and ALD

Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy

Background: Platinum-based therapy, combined or not with immune checkpoint inhibitors, represents a front-line choice for patients with non-small-cell lung cancer (NSCLC). Despite the improved outcomes in the last years for this malignancy, only a sub-group of patients have long-term benefit. Excision repair cross-complementation group 1 (ERCC1) has been considered a potential biomarker to predict the outcome of platinum-based chemotherapy in NSCLC. However, the ERCC1 gene is transcribed in four splice variants where the isoform 202 was described as the only one active and able to complex Xeroderma pigmentosum group F-complementing protein (XPF). Here, we prospectively investigated if the active form of ERCC1, as assessed by the ERCC1/XPF complex (ERCC1/XPF), could predict the sensitivity to platinum compounds.Patients and methods: Prospectively enrolled, patients with advanced NSCLC treated with a first-line regimen containing platinum were centrally evaluated for ERCC1/XPF by a proximity ligation assay. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were analyzed.Results: The absence of the ERCC1/XPF in the tumor suggested a trend of worst outcomes in terms of both OS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 0.67-2.94, P 0.373] and PFS (HR 1.61, 95% CI 0.88-3.03, P = 0.123). ORR was marginally influenced in ERCC1/XPF-negative and -positive groups [odds ratio (stable disease progressive disease versus complete response partial response) 0.87, 95% a 0.25-3.07, P = 0.832].Conclusion: The lack of ERCC1/XPF complex in NSCLC tumor cells might delineate a group of patients with poor outcomes when treated with platinum compounds. ERCC1/XPF absence might well identify patients for whom a different therapeutic approach could be necessary

Metformin Enhances Cisplatin-Induced Apoptosis and Prevents Resistance to Cisplatin in Co-mutated KRAS/LKB1 NSCLC

Introduction: We hypothesized that activating KRAS mutations and inactivation of the liver kinase B1 (LKB1) oncosuppressor can cooperate to sustain NSCLC aggressiveness. We also hypothesized that the growth advantage of KRAS/LKB1 co-mutated tumors could be balanced by higher sensitivity to metabolic stress conditions, such as metformin treatment, thus revealing new strategies to target this aggressive NSCLC subtype. Methods: We retrospectively determined the frequency and prognostic value of KRAS/LKB1 co-mutations in tissue specimens from NSCLC patients enrolled in the TAILOR trial. We generated stable LKB1 knockdown and LKB1-overexpressing isogenic H1299 and A549 cell variants, respectively, to test the in vitro efficacy of metformin. We also investigated the effect of metformin on cisplatin-resistant CD133+cells in NSCLC patient-derived xenografts. Results: We found a trend towards worse overall survival in patients with KRAS/LKB1 co-mutated tumors as compared to KRAS-mutated ones (hazard ratio: 2.02, 95% confidence interval: 0.94\u20134.35, p = 0.072). In preclinical experiments, metformin produced pro-apoptotic effects and enhanced cisplatin anticancer activity specifically in KRAS/LKB1 co-mutated patient-derived xenografts. Moreover, metformin prevented the development of acquired tumor resistance to 5 consecutive cycles of cisplatin treatment (75% response rate with metformin-cisplatin as compared to 0% response rate with cisplatin), while reducing CD133+cells. Conclusions: LKB1 mutations, especially when combined with KRAS mutations, may define a specific and more aggressive NSCLC subtype. Metformin synergizes with cisplatin against KRAS/LKB1 co-mutated tumors, and may prevent or delay the onset of resistance to cisplatin by targeting CD133+cancer stem cells. This study lays the foundations for combining metformin with standard platinum-based chemotherapy in the treatment of KRAS/LKB1 co-mutated NSCLC

[Molecular analysis of the gene of steroidogenic acute regulatory protein (StAR) in adrenal incidentaloma].

The steroidogenic acute regulatory protein (StAR) plays an essential role in steroidogenesis, facilitating cholesterol entry into the inner compartment of mitochondria. Mutations (either transitions or transversions) of StAR gene have been described as a cause of lethal forms of congenital lipoid adrenal hyperplasia. Adrenal incidentalomas are frequently discovered during radiologic examinations performed in patients with diagnosis for other diagnostic problems. Enzymatic defects along the steroidogenetic cascade are observed with high frequency in these patients. Aim of the present study was to asses the involvement of alteration of the StAR gene in incidentally discovered adrenal masses (incidentalomas). The mutational analysis of 32 incidentalomas demonstrated a "missense" mutation in exon five of the gene in one of the tumors analysed. This is the first evidence of an alteration of the StAR gene in adrenal incidentalomas