Κυριακή 7 Μαρτίου 2021

Relationship between tumor cell infiltration and 5-aminolevulinic acid fluorescence signals after resection of MR-enhancing lesions and its prognostic significance in glioblastoma

alkiviadis.1961 shared this article with you from Inoreader

Abstract

Purpose

This study investigated the degree of tumor cell infiltration in the tumor cavity and ventricle wall based on fluorescent signals of 5-aminolevulinic acid (5-ALA) after removal of the magnetic resonance (MR)-enhancing area and analyzed its prognostic significance in glioblastoma.

Methods

Twenty-five newly developed isocitrate dehydrogenase (IDH)-wildtype glioblastomas with complete resection both of MR-enhancing lesions and strong purple fluorescence on resection cavity were retrospectively analyzed. The fluorescent signals of 5-ALA were divided into strong purple, vague pink, and blue colors. The pathologic findings were classified into massively infiltrating tumor cells, infiltrating tumor cells, suspicious single-cell infiltration, and normal-appearing cells. The pathological findings were analyzed according to the fluorescent signals in the resection cavity and ventricle wall.

Results

There was no correlation between fluorescent signals and infiltrating tumor cells in the resection cavity (p = 0.199) and ventricle wall (p = 0.704) after resection of the MR-enhancing lesion. The median progression-free survival (PFS) and median overall survival (OS) were 12.5 (± 2.1) and 21.1 (± 3.5) months, respectively. In univariate analysis, the presence of definitive infiltrating tumor cells in the resection cavity and ventricle wall was significantly related to the PFS (p = 0.002) and OS (p = 0.027). In multivariate analysis, the absence of definitive infiltrating tumor cells improved PFS (hazard ratio: 0.184; 95% CI: 0.049–0.690, p = 0.012) and OS (hazard ratio: 0.124; 95% CI: 0.015–0.998, p = 0.050).

Conclusions

After resection both of the MR-enhancing lesions and strong purple fluorescence on resection cavity, there was no correlation between remnant fluorescent signals and infiltrating tumor cells. The remnant definitive infiltrating tumor cells in the resection cavity and ventricle wall significantly influenced the prognosis of patients with glioblastoma. Aggressive surgical removal of infiltrating tumor cells may improve their prognosis.

View on the web

Patterns of treatment failure in patients with prostate cancer treated with 76–80 Gy radiotherapy to the prostate and seminal vesicles ± hormonotherapy

alkiviadis.1961 shared this article with you from Inoreader

Abstract

Purpose

To assess the pattern of treatment failure in patients with prostate cancer (PCa) treated with radiotherapy (76–80 Gy) ± hormone therapy (HT). We also evaluated the influence of treatment failure on survival outcomes.

Methods

Retrospective study of patients with PCa (n = 302) treated with radiotherapy (RT) ± HT at our centre between November 1999 and July 2007. The mean patient age was 70.2 years (range 51–87). Distribution by NCCN risk group was low (n = 80, 26.5%), intermediate (n = 86, 28.5%), high (n = 77, 25.5%), and very high (n = 49, 16.2%). Most patients (n = 273, 90.4%) received IMRT at a dose of 76–80 Gy. HT was administered in 237 patients (78.5%), in most cases (n = 167, 55.3%) for < 7 months

Results

Survival rates at 10 years were: overall survival (OS), 64.3%; biochemical disease-free survival, 83.9%; disease-free survival, 92.5%; and metastasis-free survival (MFS), 94.3%. Biochemical failure (BF) was observed in 55 cases (18.2%), 32 of whom subsequently developed clinical recurrence: metastasis (n = 17, 5.6%), local failure (n = 11, 3.6%), and regional failure (n = 4, 1.3%). The cause of death (n = 159) was intercurrent disease in 115 cases (72.3%), second cancer in 27 (17.0%), and PCa in 17 (10.7%). Biochemical failure-free survival ≤ 24 months was significantly associated with worse OS and MFS (p = 0.0001). Late genitourinary and gastrointestinal toxicity grade ≥ 3 (RTOG) was observed in 18 (6.0%) and 7 (2.3%) patients, respectively.

Conclusions

The main type of treatment failure after 76–80 Gy of radiotherapy ± HT is local or metastatic. In all cases, biochemical failure occurred prior to treatment failure. BF within 24 months of treatment completion was significantly associated with worse OS and MFS.

View on the web

Influence of glioblastoma contact with the subventricular zone on survival and recurrence patterns

alkiviadis.1961 shared this article with you from Inoreader

Abstract

Background

There is growing evidence that the subventricular zone (SVZ) may be involved in both the initiation and progression of glioblastoma (GB). We aimed to assess tumor proximity to the SVZ as a potential prognostic factor in GB.

Method

Retrospective study of 133 patients diagnosed with primary GB who underwent surgery followed by temozolomide-based chemoradiation between 2010 and 2016. All lesions were classified according to their anatomic relation with the SVZ. We determined the effect of tumor contact with the SVZ on progression-free survival (PFS), overall survival (OS), type, and patterns of recurrence.

Results

At a median follow-up of 18.6 months (95% CI 15.9–21.2), PFS and OS were 7.5 (95% CI 6.7–8.3) and 13.9 (95% CI 10.9–16.9) months, respectively. On the univariate analyses, initial contact with the SVZ was a factor for poor prognosis for both PFS (6.1 vs. 8.7 months; p = 0.006) and OS (10.6 vs. 17.9 months; p = 0.037). On the multivariate analysis, tumor contact with the SVZ remained statistically significant for PFS, but not OS. Patients with SVZ-contacting tumors presented a higher rate of aggressive clinical progression (30.9% vs. 11.3%; p = 0.007) and contralateral relapse patterns (23.4% vs. 9.1%; p = 0.048).

Conclusions

Our results suggest that glioblastoma contact with the SVZ appears to be an independent prognostic factor for poor PFS. The presence of an SVZ-contacting tumor was associated with more aggressive recurrences and a higher rate of contralateral relapses. These findings suggest that this variable may be a new prognostic factor in glioblastoma.

View on the web

SMARCA4 promotes benign skin malignant transformation into melanoma through Adherens junction signal transduction

alkiviadis.1961 shared this article with you from Inoreader

Abstract

Purpose

Melanoma is a malignant skin tumor, and its incidence is rising. To explore the specific differences in benign and malignant melanoma at the genetic level, we performed a series of bioinformatics analyses, including differential gene analysis, co-expression analysis, enrichment analysis, and regulatory prediction.

Methods

The microarray data of benign and malignant melanocytes were downloaded from GEO, and 1917 differential genes were obtained by differential analysis (p < 0.05). Weighted gene co-expression network analysis obtained three functional barrier modules. The essential genes of each module are SMARTA4, HECA, and C1R.

Results

The results of the enrichment analysis showed that the dysfunctional module gene was mainly associated with RNA splicing and Adherens junction. Through the pivotal analysis of ncRNA, it was found that miR-448, miR-152-3p, and miR-302b-3p essentially regulate three modules, which we consider to be critical regulators. In the pivot analysis of TF, more control modules include ARID3A, E2F1, E2F3, and E2F8.

Conclusions

We believe that the regulator (miR-448, miR-152-3p, miR-302b-3p) regulates the expression of the core gene SMARCA4, which in turn affects the signal transduction of the Adherens junction. It eventually leads to the deterioration of benign skin spasms into melanoma.

View on the web

Identifying a novel 5-gene signature predicting clinical outcomes in acute myeloid leukemia

alkiviadis.1961 shared this article with you from Inoreader

Abstract

Background

Acute myeloid leukemia (AML) is the most common type of acute leukemia and biologically heterogeneous diseases with poor prognosis. Thus, we aimed to identify prognostic markers to effectively predict the prognosis of AML patients and eventually guide treatment.

Methods

Prognosis-associated genes were determined by Kaplan–Meier and multivariate analyses using the expression and clinical data of 173 AML patients from The Cancer Genome Atlas database and validated in an independent Oregon Health and Science University dataset. A prognostic risk score was computed based on a linear combination of 5-gene expression levels using the regression coefficients derived from the multivariate logistic regression model. The classification of AML was established by unsupervised hierarchical clustering of CALCRL, DOCK1, PLA2G4A, FCHO2 and LRCH4 expression levels.

Results

High FCHO2 and LRCH4 expression was related to decreased mortality. While high CALCRL, DOCK1, PLA2G4A expression was associated with increased mortality. The risk score was predictive of increased mortality rate in AML patients. Hierarchical clustering analysis of the five genes discovered three clusters of AML patients. The cluster1 AML patients were associated with lower cytogenetics risk than cluster2 or 3 patients, and better prognosis than cluster3 patients (P values < 0.05 for all cases, fisher exact test or log-rank test).

Conclusion

The gene panel comprising CALCRL, DOCK1, PLA2G4A, FCHO2 and LRCH4 as well as the risk score may offer novel prognostic biomarkers and classification of AML patients to significantly improve outcome prediction.

View on the web

Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells in vitro and in vivo

alkiviadis.1961 shared this article with you from Inoreader

Abstract

Purpose

Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy.

Methods

We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells.

Results

CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells.

Conclusion

We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer.

View on the web

Head-to-head comparison of two rapid high-throughput automated electrochemiluminescence immunoassays targeting total antibodies to the SARS-CoV-2 nucleoprotein and spike protein receptor binding domain

alkiviadis.1961 shared this article with you from Inoreader

1-s2.0-S1386653220X00138-cov150h.gif

Publication date: Available online 5 March 2021

Source: Journal of Clinical Virology

Author(s): Mario Poljak, Anja Oštrbenk Valenčak, Tina Štamol, Katja Seme

View on the web

Midazolam for sedation before procedures in adults and children: a systematic review update

alkiviadis.1961 shared this article with you from Inoreader

13643.jpg

Midazolam is used for sedation before diagnostic and therapeutic medical procedures by several routes including oral, intravenous, intranasal and intramuscular. This is an update of a Cochrane review published...
View on the web

COVID-19 related increase in childhood tics and tic-like attacks

alkiviadis.1961 shared this article with you from Inoreader

3.cover-source.jpg

Explosion of tics

Since the onset of the COVID-19 pandemic, paediatricians and child mental health practitioners have noticed an increase in tic symptoms in some children and adolescents already diagnosed with tic disorders.1 Interestingly, clinicians have also seen a marked increase in presentations of sudden and new onset of severe tics and 'tic-like' attacks.

There is an urgent need to collate systematic data on this group as this is a rare and unusual subtype of tics and Tourette syndrome , differing in age and type of onset and expected patterns of tics. Typically, childhood tics start around 5–7 years and show a waxing and waning course of predominantly motor tics, more commonly affecting boys in a ratio of 4:1. The new surge of referrals consists of adolescent girls with sudden onset of motor and phonic tics of a complex and bizarre nature. In London, UK specialist tic clinics at each...

View on the web

Longitudinal assessment of anti-SARS-CoV-2 immune responses for six months based on the clinical severity of COVID-19

alkiviadis.1961 shared this article with you from Inoreader

pdf.svg

Abstract
There is insufficient data on the longevity of immunity acquired following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to evaluate the duration of SARS-CoV-2-specific humoral and cellular immunity according to the clinical severity of coronavirus disease 2019 (COVID-19). The study population comprised asymptomatic (n=14), symptomatic/non-pneumonic (n=42), and pneumonic (n=41) patients. The anti-SARS-CoV-2 IgG and neutralizing antibody (NAb) titers lasted until six mont hs after diagnosis, with positivity rates of 66.7% and 86.9%, respectively. Older age, prolonged viral shedding and accompanying pneumonia were more frequently found in patients with sustained humoral immunity. SARS-CoV-2 specific T-cell response was strongly observed in pneumonic patients and prominent in individuals with sustained humoral immunity. In conclusion, most (> 85%) patients carries NAb until six months after diagnosis of SARS-CoV-2 infection, providing insights for establishing vaccination strategies against COVID-19.
View on the web

Sex differences in the evolution of neutralizing antibodies to SARS-CoV-2

alkiviadis.1961 shared this article with you from Inoreader

pdf.svg

Abstract
We measured Anti-Spike (S), Nucleoprotein (N) and neutralizing antibodies (NAbs) in sera from 308 RT-qPCR + healthcare workers with mild disease, collected at two time-points up to 6 months after symptom onset. At Month 1 (M1), anti-S and N antibody levels were higher in males > 50 years or with a body mass index (BMI) > 25. At M3-6, anti-S and anti-N antibodies were detected in 99% and 59% of individuals, respectively. Anti-S antibodies and NAbs declined faster in males than in females, independently of age and BMI, suggesting an association of sex with evolution of the humoral response.
View on the web

Shedding of culturable virus, seroconversion, and 6-month follow-up antibody responses in the first 14 confirmed cases of COVID-19 in the United States

alkiviadis.1961 shared this article with you from Inoreader

pdf.svg

Abstract
We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to six months post-onset, among 14 early US COVID-19 patients. We isolated viable SARS-CoV-2 from rRT-PCR-positive respiratory specimens collected during days 0-8 post-onset, but not after. All 13 patients with two or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodie s. Eight participants provided serum at six months post-onset; all retained detectable anti-spike IgG, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at six months.
View on the web