Cervical Cancer in Women Aged 35 Years and Younger

AbstractPurposeAge has been evaluated as a prognostic factor in cervical cancer in both hospital- and population-based studies. Results regarding the relation of age and cervical cancer prognosis are conflicting. This study pursued a contemporary assessment of the association of extreme young age at the time of a cervical cancer diagnosis on survival.MethodsInstitutional review board approval was obtained, and retrospective data collection at 2 academic institutions was performed. Inclusion criteria involved women ≤35 years diagnosed with cervical cancer between 1990 and 2012. Data included demographic and prognostic information pertinent to survival and progression. Characteristics of very young (≤25 years) and young (>25–35 years) women were compared. Kaplan-Meier estimates, the log-rank test, and Cox proportional hazards modeling were used to assess the association of age, tumor histology, grade, stage, and parametrial involvement with progression-free survival (PFS) and overall survival (OS).FindingsIncident cases (n = 126) of cervical cancer in patients ≤35 years of age were identified of which complete clinical information was available for 114 women. Fifteen percent (17 of 114) were ≤25 years, with the remaining 85% (97 of 114) being 26 to 35 years of age. Race, smoking status, and marital status were comparable between the 2 groups. Squamous histology dominated overall (77 of 114; 68%) with adenocarcinoma contributing ~25% (30 of 114; 26%) of cases. The majority (96 of 114, 84%) had either stage 1A (31 of 114, 27%) or 1B (65 of 114, 57%) disease. A log-rank test revealed no evidence to infer a difference in either PFS or OS among the age groups (P = 0.511 and P = 0.340). In a univariate analysis, grade and stage significantly affected OS (P < 0.0001, P = 0.045), and stage significantly affected PFS (P < 0.0001). In multivariate modeling, presence of parametrial involvement and histologic cancer type significantly affected both PFS (P = 0.002, P = 0.001) and OS (P = 0.001, P = 0.001).ImplicationsTumor histology, parametrial involvement, and stage continue to be strong prognosticators for PFS and OS. Progression and survival outcomes are age independent in women with cervical cancer ≤35 years of age. Further study of a larger young cohort may potentially yield different outcomes

The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer

Ovarian cancer is the 5th leading cause of cancer death among women in the United States. The mevalonate pathway is thought to be a potential oncogenic pathway in the pathogenesis of ovarian cancer. Simvastatin, a 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) inhibitor, is a widely used drug for inhibiting the synthesis of cholesterol and may also have anti-tumorigenic activity. Our goal was to evaluate the effects of simvastatin on ovarian cancer cell lines, primary cultures of ovarian cancer cells and in an orthotopic ovarian cancer mouse model. Simvastatin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, and caused cellular stress via reduction in the enzymatic activity of HMGCR and inhibition of the MAPK and mTOR pathways in ovarian cancer cells. Furthermore, simvastatin induced DNA damage and reduced cell adhesion and invasion. Simvastatin also exerted anti-proliferative effects on primary cell cultures of ovarian cancer. Treatment with simvastatin in an orthotopic mouse model reduced ovarian tumor growth, coincident with decreased Ki-67, HMGCR, phosphorylated-Akt and phosphorylated-p42/44 protein expression. Our findings demonstrate that simvastatin may have therapeutic benefit for ovarian cancer treatment and be worthy of further exploration in clinical trials

Simvastatin, an HMG-CoA reductase inhibitor, exhibits anti-metastatic and anti-tumorigenic effects in endometrial cancer

Our goal was to evaluate the effects of simvastatin on endometrial cancer cell lines and primary cultures of endometrial cancer cells

Atorvastatin exhibits anti-tumorigenic and anti-metastatic effects in ovarian cancer in vitro

Ovarian cancer is the 8th most common cancer in women, and the 5th leading cause of cancer-related deaths among women in the United States. Statins have been shown to have promising anti-tumorigenic activity in many types of cancers. We sought to determine the effects of atorvastatin (ATO) on cell proliferation in ovarian cancer and identify the mechanisms by which ATO inhibits cell growth in this disease. ATO inhibited cell proliferation of both the Hey and SKOV3 ovarian cancer cells in a dose-dependent manner. The anti-proliferative activity of ATO in the ovarian cancer cell lines was associated with induction of apoptosis, autophagy, cellular stress and cell cycle G1 arrest via inhibition of AKT/mTOR and activation of the MAPK pathways. Moreover, ATO inhibited cell adhesion and invasion as well as decreased expression of VEGF and MMP9. c-Myc was downregulated in ovarian cancer cells exposed to ATO. Inhibition of c-Myc by JQ1 synergistically increased the sensitivity of ovarian cancer cells to ATO. This data suggests that ATO may have a therapeutic role in the treatment of ovarian cancer and warrant further exploration in clinical trials

Evaluation of the anti-tumor effects of lactate dehydrogenase inhibitor galloflavin in endometrial cancer cells

High rates of aerobic glycolysis represent a key mechanism by which endometrial cancer cells consume glucose as its primary energy source. The up-regulated glycolytic pathway is a common therapeutic target whose inhibition has implications for anti-tumor activity in cancer cells. The present study was aimed at evaluating the potential of a novel lactate dehydrogenase (LDH) inhibitor, Galloflavin, as a therapeutic agent for endometrial cancer. Our results revealed that Galloflavin effectively inhibited cell growth in endometrial cancer cell lines and primary cultures of human endometrial cancer through its involvement in multiple signaling pathways that regulate metabolism, cell cycle, apoptosis, cell stress and metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-014-0097-x) contains supplementary material, which is available to authorized users

Glutamine promotes ovarian cancer cell proliferation through the mTOR/S6 pathway

Glutamine is one of the main nutrients used by tumor cells for biosynthesis. Therefore, targeted inhibition of glutamine metabolism may have anti-tumorigenic implications. In the present study, we aimed to evaluate the effects of glutamine on ovarian cancer cell growth. Three ovarian cancer cell lines, HEY, SKOV3, and IGROV-1, were assayed for glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis, cell stress, and glucose/glutamine metabolism. Our results revealed that administration of glutamine increased cell proliferation in all three ovarian cancer cell lines in a dose dependent manner. Depletion of glutamine induced reactive oxygen species and expression of endoplasmic reticulum stress proteins. In addition, glutamine increased the activity of glutaminase (GLS) and glutamate dehydrogenase (GDH) by modulating the mTOR/S6 and MAPK pathways. Inhibition of mTOR activity by rapamycin or blocking S6 expression by siRNA inhibited GDH and GLS activity, leading to a decrease in glutamine-induced cell proliferation. These studies suggest that targeting glutamine metabolism may be a promising therapeutic strategy in the treatment of ovarian cancer

Forskningsintegritet og åpen vitenskap i ph.d.undervisningen: Praktiske spørsmål og etisk refleksjon.

Academic presentation at the Virak conference 08. - 09.06.22, Trondheim, Norway

Kunnskapsstatus for bruk av molekylære verktøy i kartlegging og overvåkning av biologisk mangfold i marine miljø

Source at https://www.miljodirektoratet.no/publikasjoner/2021/juni-2021/kunnskapsstatus-for-bruk-av-molekylare-verktoy-i-kartlegging-og-overvakning-av-biologisk-mangfold-i-marine-miljo/Denne rapporten er bestilt av Miljødirektoratet fra NorBOL (Norwegian Barcode of Life), et nasjonalt nettverk av forskningsinstitusjoner som koordineres av NTNU Vitenskapsmuseet. Universitetsmuseet i Bergen har hatt prosjektledelsen. Rapporten gir en oppsummering av dagens status på DNA-basert metodikk som verktøy i kartlegging og overvåking av biologisk mangfold i det marine miljø. Fokus har vært på innsamlingsmetodikk og protokoller for DNA-analyser av arter og artsgrupper. Metodikken er evaluert opp mot kartleggings- og overvåkingsaktivitet i regi av Miljødirektoratet, og kommer med anbefalinger for videre framdrift for å ta metodikken i bruk i nasjonal kartlegging og overvåking. Rapporten har også en gjennomgang og evaluering av eksisterende referansemateriale og referansesekvenser for relevante arter og artsgrupper som inngår i Miljødirektoratets kartleggings- og overvåkingsaktivitet

Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke

Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.Peer reviewe

Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

: Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success