Elin Andersson

Bio: Elin Andersson is an academic researcher from University of Gothenburg. The author has contributed to research in topics: Cervical intraepithelial neoplasia & Tripeptide. The author has an hindex of 8, co-authored 11 publications receiving 193 citations.

Glycine-Amide Is an Active Metabolite of the Antiretroviral Tripeptide Glycyl-Prolyl-Glycine-Amide

Abstract: The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH 2 ) inhibits replication of human immunodeficiency virus (HIV) type 1 (HIV-1) in vitro, probably by interfering with capsid formation. The aim of the present study was to determine whether the metabolites glycyl-proline (GP-OH), glycine (G-OH), prolyl-glycine-amide (PG-NH 2 ), proline (P-OH), and glycine-amide (G-NH 2 ) from proteolytic cleavage may inhibit the replication of HIV-1 in vitro. PG-NH 2 has previously been shown to have a modest effect on HIV-1 replication. In the present study we show that G-NH 2 exhibits a pronounced inhibitory effect on HIV-1. This effect was not due to a decrease in cell proliferation or viability and could not be shown for herpes simplex virus type 1. The G-NH 2 concentration that inhibited virus replication by 50% (IC 50 ) was equimolar to that of GPG-NH 2 and ranged from 3 to 41 μM. Transmission electron microscopy revealed that the effect of G-NH 2 on HIV-1 morphology was equivalent to that of GPG-NH 2 and showed disarranged capsid structures, indicating interference with capsid formation. Serial passage of HIV-infected cells with G-NH 2 for more than 20 subcultivations did not decrease the susceptibility to the compound. The results from this study suggest that GPG-NH 2 might act as a prodrug and that G-NH 2 is an active antiretroviral metabolite.

Type-Specific Human Papillomavirus E6/E7 mRNA Detection by Real-Time PCR Improves Identification of Cervical Neoplasia

Abstract: DNA-based human papillomavirus (HPV) assays show high sensitivity but poor specificity in detecting high-grade cervical lesions. Assays detecting mRNA of the oncoproteins E6 and E7 show higher specificity but lack either detection of all high-risk HPV genotypes or the capacity to specify the detected genotypes. Therefore, a real-time PCR assay detecting type-specific E6/E7 mRNA was developed and the clinical performance evaluated. A total of 210 cervical LBC (liquid-based cytology) samples from 204 women were analyzed for HPV DNA and mRNA with the in-house real-time PCR as well as PreTect HPV-Proofer. The sensitivity of real-time PCR mRNA detection to identify histologically confirmed CIN2+ (cervical intraepithelial neoplasia, grade 2 or higher) was 0.91, compared to 0.95 for DNA analysis. The specificity was 0.68 compared to 0.38, and the positive predictive value (PPV) was higher for mRNA (0.67 versus 0.52) without any loss in negative predictive value (NPV). The sensitivity of the real-time PCR mRNA test was somewhat higher than that for PreTect HPV-Proofer (0.83 versus 0.75) in analyses for the same genotypes. The specificities were similar (0.76 versus 0.77). In analyses for mRNA of the eight most common genotypes in cervical cancer (HPV16, -18, -31, -33, -35, -45, -52, and -58), the sensitivity of detection of CIN2+ lesions was 0.87 and the specificity 0.74, with a PPV of 0.70. In conclusion, real-time PCR for detection of HPV E6/E7 mRNA transcripts can be a sensitive and specific tool in screening and investigation of cervical neoplasia. The composition of HPV types in mRNA testing needs to be further investigated to optimize sensitivity and specificity.

Detection of transcriptionally active high risk HPV in patients with head and neck squamous cell carcinoma as visualized by a novel E6/E7 mRNA in situ hybridization method

Abstract: Evidence for transcriptional activation of the viral oncoproteins E6 and E7 is regarded as the gold standard for the presence of clinically relevant human papillomavirus (HPV), but detection of E6/E7 mRNA requires RNA extraction and polymerase chain reaction amplification-a challenging technique that is restricted to the research laboratory. The development of RNA in situ hybridization (ISH) probes complementary to E6/E7 mRNA permits direct visualization of viral transcripts in routinely processed tissues and has opened the door for accurate HPV detection in the clinical care setting. Tissue microarrays containing 282 head and neck squamous cell carcinomas from various anatomic subsites were tested for the presence of HPV using p16 immunohistochemistry, HPV DNA ISH, and an RNA ISH assay (RNAscope) targeting high-risk HPV E6/E7 mRNA transcripts. The E6/E7 mRNA assay was also used to test an additional 25 oropharyngeal carcinomas in which the HPV status as recorded in the surgical pathology reports was equivocal due to conflicting detection results (ie, p16 positive, DNA ISH negative). By the E6/E7 mRNA method, HPV was detected in 49 of 282 (17%) HNSCCs including 43 of 77 (56%) carcinomas from the oropharynx, 2 of 3 (67%) metastatic HNSCCs of an unknown primary site, 2 of 7 (29%) carcinomas from the sinonasal tract, and 2 of 195 (1%) carcinomas from other head and neck sites. p16 expression was strongly associated with the presence of HPV E6/E7 mRNA: 46 of 49 HPV-positive tumors exhibited p16 expression, whereas only 22 of 233 HPV-negative tumors were p16 positive (94% vs. 9%, P<0.0001). There was also a high rate of concordance (99%) between the E6/E7 mRNA method and HPV DNA ISH. For the selected group of discordant HNSCCs (p16/HPV DNA), the presence of E6/E7 transcripts was detected in 21 of 25 (84%) cases. The E6/E7 mRNA method confirmed the presence of transcriptionally active HPV-related HNSCC that has a strong predilection for the oropharynx and is strongly associated with high levels of p16 expression. Testing for HPV E6/E7 transcripts by RNA ISH is ideal because it confirms the presence of integrated and transcriptionally active virus, permits visualization of viral transcripts in tissues, and is technically feasible for routine testing in the clinical laboratory.

Human Papillomavirus Genotyping and p16 Expression As Prognostic Factors for Patients With American Joint Committee on Cancer Stages I to III Carcinoma of the Anal Canal

Abstract: Purpose Carcinomas of the anal canal are strongly associated with the human papillomavirus (HPV). Expression of p16 is used as a surrogate marker of HPV infection. In a retrospective study, we evaluated HPV genotyping and p16 expression as prognostic markers of overall survival (OS) and disease-specific survival (DSS) in patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to III carcinoma of the anal canal. Patients and Methods HPV genotyping polymerase chain reaction (high-risk subtypes 16, 18, 31, 33, 45, 52, and 58) and immunohistochemical expression of p16 were analyzed by using paraffin-embedded tumor biopsies from 143 anal carcinomas. The patients were treated with combined chemoradiotherapy or radiotherapy alone. Results HPV16 was detected in 81.0% of the tumors, followed by HPV33 (5.1%), HPV18 (2.2%), and HPV58 (0.7%). p16 positivity was found in 92.9% of the tumors. In univariable survival analysis, HPV positivity was significantly correlated with improved OS (74% v 52%; P .036) and DSS (84% v 52%; P .002), and p16 positivity was significantly correlated with improved OS (76% v 30%; P .001) and DSS (85% v 30%; P .001). In multivariable COX analysis that included HPV status, p16 status, sex, T stage, N stage, and treatment, p16 positivity remained an independent prognostic factor for OS (hazard ratio [HR], 0.07; 95% CI, 0.01 to 0.61; P .016) and DSS (HR, 0.07; 95% CI, 0.01 to 0.53; P .011). Conclusion p16 positivity is an independent prognostic factor for OS and DSS in patients with AJCC stages I to III carcinoma of the anal canal. J Clin Oncol 32:1812-1817. © 2014 by American Society of Clinical Oncology

Emerging anti-HIV drugs.

Abstract: There are now exactly 20 anti-HIV drugs licenced (approved) for clinical use, and > 30 anti-HIV compounds under (pre)clinical development. The licensed anti-HIV drugs fall into five categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine); nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir disoproxil fumarate); non-nucleoside reverse transcriptase inhibitors (NNRTIs: nevirapine, delavirdine and efavirenz); protease inhibitors (PIs: saquinavir, indinavir, ritonavir, nelfinavir, amprenavir, lopinavir, atazanavir and fosamprenavir); and fusion inhibitors (FIs: enfuvirtide). The compounds that are currently under clinical (Phase I, II or III) or preclinical investigation are either targeted at the same specific viral proteins as the licensed compounds (i.e., reverse transcriptase [NRTIs: PSI-5004, (-)-dOTC, DPC-817, elvucitabine, alovudine, MIV-210, amdoxovir, DOT; NNRTIs: thiocarboxanilide, UC-781, capravirine, dapivirine, etravirine, rilpivirine], protease [PIs: tipranavir, TMC-114]) or other specific viral proteins (i.e., gp120: cyanovirin N; attachment inhibitors: AIs, such as BMS-488043; integrase: L-870,812, PDPV-165; capsid proteins: PA-457, alpha-HCG); or cellular proteins (CD4 downmodulators: CADAs; CXCR4 antagonists: AMD-070, CS-3955; CCR5 antagonists: TAK-220, SCH-D, AK-602, UK-427857). Combination therapy is likely to remain the gold standard for the treatment of AIDS so as to maximise potency, minimise toxicity and diminish the risk for resistance development. Ideally, pill burden should be reduced to once-daily dosing so as to optimise the patient's compliance and reduce the treatment costs.

Global comparison of the membrane subproteomes between a multidrug-resistant Acinetobacter baumannii strain and a reference strain.

Abstract: Acinetobacter baumannii causes severe infections in compromised patients. We combined SDS-PAGE, two-dimensional gel electrophoresis and mass spectrometry (LC-MS/MS and MALDI-TOF) to separate and characterize the proteins of the cell envelope of this bacterium. In total, 135 proteins (inner and outer membrane proteins) were identified. In this analysis, we described the expression by this bacterium of RND-type efflux systems and some potential virulence factors. We then compared the membrane subproteome of a clinical multidrug-resistant (MDR) isolate with that of a reference strain. We found that the MDR strain expressed lower levels of the penicillin-binding-protein 1b, produced a CarO protein having different primary and quaternary structures to that of the reference strain, and expressed OmpW isoforms. We also showed that the clinical strain has a high ability to form biofilms consistent with the accumulation of some outer membrane proteins (OMPs) such as NlpE or CsuD that have already been described as involved in bacterial adhesion. These features may partly explain the MDR emergence of the clinical isolate.