262 research outputs found
Improved Killing of Human High-Grade Glioma Cells by Combining Ionizing Radiation with Oncolytic Parvovirus H-1 Infection
Purpose. To elucidate the influence of ionizing radiation (IR) on
the oncolytic activity of Parvovirus H-1 (H-1PV) in human
high-grade glioma cells. Methods. Short term cultures of human
high-grade gliomas were irradiated at different doses and infected
with H-1PV. Cell viability was assessed by determining relative
numbers of surviving cells. Replication of H-1PV was measured by
RT-PCR of viral RNA, fluorescence-activated cell sorter (FACS)
analysis and the synthesis of infectious virus particles. To
identify a possible mechanism for radiation induced change in the
oncolytic activity of H-1PV we performed cell cycle analyses.
Results. Previous irradiation rendered glioma cells fully
permissive to H-1PV infection. Irradiation 24 hours prior to H-1PV
infection led to increased cell killing most notably in
radioresistant glioma cells. Intracellular levels of NS-1, the
main effector of H-1PV induced cytotoxicity, were elevated after
irradiation. S-phase levels were increased one day after
irradiation improving S-phase dependent viral replication and
cytotoxicity. Conclusion. This study demonstrates intact
susceptibility of previously irradiated glioma-cells for H-1PV
induced oncolysis. The combination of ionizing radiation followed
by H-1PV infection increased viral cytotoxicity, especially in
radioresistant gliomas. These findings support the ongoing
development of a clinical trial of H-1PV in patients with
recurrent glioblastomas
Hvorfor falder studerende fra? En opsummering af EVAâs analyser af frafald pĂ„ de videregĂ„ende uddannelser
Frafald er et stÊdigt problem, som optager mange i uddannelsessektoren. Og med god grund. Omkring hver tredje studerende, der optages pÄ en videregÄende uddannelse, ender med at falde fra, og frafald er forbundet med betydelige omkostninger for de studerende, som beslutter sig for at afbryde uddannelsen, for uddannelsesinstitutionerne og for samfundet.
Det er nÊppe hverken Þnskeligt eller muligt at nedbringe frafaldet til nul. Uanset hvor god vejledning og information de unge fÄr, vil nogle unge opleve at have truffet det forkerte studievalg, og i disse tilfÊlde vil det vÊre i alles interesse, at uddannelsesforlÞbene afbrydes. Derudover er en stor del af frafaldet i realiteten studieskift: Kun en ud af otte (12 %) af de optagne falder fra uden at starte pÄ en anden videregÄende uddannelse efterfÞlgende (EVA, 2021a). Det har naturligvis stor betydning for de samlede omkostninger forbundet med frafald, som i et lidt lÊngere perspektiv i hÞj grad hÊnger sammen med de unges karriere pÄ arbejdsmarkedet. Her har en tidligere analyse foretaget af EVA vist, at unge, der ikke fÊrdiggÞr en videregÄende uddannelse, har markant hÞjere risiko for at modtage offentlig forsÞrgelse sammenlignet med unge, som gennemfÞrer. Det gÊlder i Þvrigt ogsÄ for udsatte unge (EVA, 2019f ).
Alligevel giver det god mening at bestrÊbe sig pÄ at nedbringe frafaldet, og her er der meget, man kan interessere sig for. Fx er det oplagt, at de studerendes studievalg og optagelsesprocessen har betydning. Det er ogsÄ oplagt at forhold pÄ uddannelsen som fremmer engagement, motivation og lÊringsudbytte har betydning for de studerendes frafaldssandsynlighed. Endelig er der en rÊkke aspekter ved fx de studerendes baggrund, som uddannelsen ikke umiddelbart kan pÄvirke, men hvor det alligevel kan vÊre vÊrdifuldt at kende til de forhold og karakteristika, der hÊnger sammen med en hÞjere frafaldsrisiko.
PĂ„ EVA har vi siden 2016 gennemfĂžrt en rĂŠkke undersĂžgelser med henblik pĂ„ at kunne belyse faktorer, der hĂŠnger sammen med frafald pĂ„ de videregĂ„ende uddannelser. Vi vil i denne artikel kort introducere EVAâs tilgang til feltet og dernĂŠst opsummere resultaterne fra de analyser af frafald, som EVA har gennemfĂžrt gennem de senere Ă„r.
The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a retrospective study in 107 patients
Background: In metastatic breast cancer (MBC), antigen profiles of metastatic tissue and primary tumor differ in up to 20Â % of patients. Reassessment of predictive markers, including human epidermal growth factor receptor 2 (HER2) expression, might help to optimize MBC treatment. While tissue sampling is invasive and often difficult to repeat, circulating tumor cell (CTC) analysis requires only a blood sample and might provide an easy-to-repeat, real-time âliquid biopsyâ approach. The present retrospective study was conducted to compare HER2 expression in primary tumors, metastatic tissue, and circulating tumor cells (CTCs) from MBC patients and to analyze the potential impact of HER2 overexpression by CTCs on progression-free (PFS) and overall survival (OS) in MBC. Methods: CTC-positive (five or more CTCs/7.5Â mL blood; CellSearchÂź, Janssen Diagnostics) MBC patients starting a new line of systemic treatment were eligible for the study. HER2 status of CTCs was determined by immunofluorescence (CellSearchÂź). HER2 status of primary (PRIM) and metastatic (MET) tumor tissue was determined by immunohistochemistry. Data were analyzed using descriptive statistics and KaplanâMeier plots. Results: One hundred seven patients (median age (range) 57 (33â81) years) were included. 100/107 (93Â %) patients were followed-up for a median [95Â % confidence interval (CI)] of 28.5 [25.1â40.1] months. Of 37/107 (35Â %) CTC-HER2-positive patients only 10 (27Â %) were PRIM-HER2-positive. 6/46 (13Â %) patients were MET-HER2-positive; only 2/10 (20Â %) CTC-HER2-positive patients were MET-HER2-positive. Overall accuracy between CTC-HER2 expression and PRIM-HER2 and MET-HER2 status was 69Â % and 74Â %, respectively. KaplanâMeier plots of PFS and OS by CTC-HER2 status revealed significantly longer median [95Â % CI] PFS of CTC-HER2-positive versus CTC-HER2-negative patients (7.4 [4.7â13.7] versus 4.34 [3.5â5.9] months; pâ=â0.035). CTC-HER2-positive status showed no significant difference for OS (13.7 [7.7â30.0] versus 8.7 [5.9â15.3] months; pâ=â0.287). Conclusions: HER2 status can change during the course of breast cancer. CTC phenotyping may serve as an easy-to-perform âliquid biopsyâ to reevaluate HER2 status and potentially guide treatment decisions. Further, prospective studies are needed
Tumor biomarker conversion between primary and metastatic breast cancer: mRNA assessment and its concordance with immunohistochemistry
ClinOmicsTrailbc: a visual analytics tool for breast cancer treatment stratification
Motivation: Breast cancer is the second leading cause of cancer death among women. Tumors,
even of the same histopathological subtype, exhibit a high genotypic diversity that impedes therapy stratification and that hence must be accounted for in the treatment decision-making process.
Results: Here, we present ClinOmicsTrailbc, a comprehensive visual analytics tool for breast cancer
decision support that provides a holistic assessment of standard-of-care targeted drugs, candidates
for drug repositioning and immunotherapeutic approaches. To this end, our tool analyzes and visualizes clinical markers and (epi-)genomics and transcriptomics datasets to identify and evaluate the
tumorâs main driver mutations, the tumor mutational burden, activity patterns of core cancerrelevant pathways, drug-specific biomarkers, the status of molecular drug targets and pharmacogenomic influences. In order to demonstrate ClinOmicsTrailbcâs rich functionality, we present three
case studies highlighting various ways in which ClinOmicsTrailbc can support breast cancer precision medicine. ClinOmicsTrailbc is a powerful integrated visual analytics tool for breast cancer research in general and for therapy stratification in particular, assisting oncologists to find the best
possible treatment options for their breast cancer patients based on actionable, evidence-based
results.
Availability and implementation: ClinOmicsTrailbc can be freely accessed at https://clinomicstrail.
bioinf.uni-sb.de
Pooled Analysis of the Prognostic Relevance of Disseminated Tumor Cells in the Bone Marrow of Patients With Ovarian Cancer
Objective: Detection of disseminated tumor cells (DTCs) in the bone marrow (BM) of patients with breast cancer is associated with poor outcomes. Recent studies demonstrated that DTCs may serve as a prognostic factor in ovarian cancer. The aim of this 3-center study was to evaluate the impact of BM status on survival in a large cohort of patients with ovarian cancer. Materials and Methods: Four hundred ninety-five patients with primary ovarian cancer were included in this 3-center prospective study. Bone marrow aspirates were collected intraoperatively from the iliac crest. Disseminated tumor cells were identified by antibody staining and by cytomorphology. Clinical outcome was correlated with the presence of DTCs. Results: Disseminated tumor cells were detected in 27% of all BM aspirates. The number of cytokeratin-positive cells ranged from 1 to 42 per 2 x 10(6) mononuclear cells. Disseminated tumor cell status did correlate with histologic subtype but not with any of the other established clinicopathologic factors. The overall survival was significantly shorter among DTC-positive patients compared to DTC-negative patients (51 months; 95% confidence interval, 37-65 months vs 33 months; 95% confidence interval, 23-43 months; P = 0.023). In the multivariate analysis, BM status, International Federation of Gynecology and Obstetrics stage, nodal status, resection status, and age were independent predictors of reduced overall survival, whereas only BM status, International Federation of Gynecology and Obstetrics stage, and resection status independently predicted progression-free survival. Conclusions: Tumor cell dissemination into the BM is a common phenomenon in ovarian cancer. Disseminated tumor cell detection has the potential to become an important biomarker for prognostication and disease monitoring in patients with ovarian cancer
Update breast cancer 2020 part 5: moving therapies from advanced to early breast cancer patients
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