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Δευτέρα 13 Φεβρουαρίου 2023

Exosomes: Mediators in Microenvironment of Colorectal Cancer

AlexandrosSfakianakis shared this article with you from Inoreader

Abstract

Tumor microenvironment, the soil where tumor thrives, plays a critical role in the development and progression of colorectal cancer (CRC). Various cell signaling molecules in the environment promote tumor angiogenesis, immune tolerance and facilitate immune escape. Exosomes, as messengers between tumor and host cells, are considered key mediators involved in the tumor-accelerating environment. However, the exosome-mediated communication networks in the CRC microenvironment are still largely unclear. In this review, we summarized the relationship between TME and CRC based on recent literature. Then, we revealed the unique impacts and signal molecules of exosomes on account of their regulatory role in the flora, hypoxia, inflammatory, and immunological microenvironment of CRC. Finally, we summarized the therapeutically effective of exosomes in CRC microenvironment and discussed their current status and prospects, aiming to provide new molecular targets and a theoretical basis for th e CRC treatment.
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Effectiveness and Accuracy of MRI‐Ultrasound Fusion Targeted Biopsy Based on PI‐RADS v2.1 Category in Transition/Peripheral Zone of the Prostate

AlexandrosSfakianakis shared this article with you from Inoreader

Background

MRI-ultrasound fusion targeted biopsy (MRI-TBx) improves the clinically significant prostate cancer (csPCa) detection with fewer cores. However, whether systematic biopsy-guided by transrectal ultrasound (TRUS-SBx) can be omitted when undergoing MRI-TBx in transition zone (TZ) and peripheral zone (PZ) remains unclear.

Purpose

To assess the performance and effectiveness of MRI-TBx based on PI-RADS v2.1 for csPCa diagnosis in TZ and PZ, respectively.

Study Type

Retrospective.

Subjects

A total of 309 selected cases (median age 70 years) with 356 lesions who underwent both MRI-TBx and TRUS-SBx were enrolled.

Field Strength/Sequence

A 3.0 T, multiparametric MRI (mp-MRI) including T2-weighted turbo-spin echo imaging (T2WI), diffusion-weighted spin-echo echo planar imaging (DWI), dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging (DCE).

Assessment

Mp-MRI was assessed by two radiologists using PI-RADS v2.1. The csPCa detection rates provided by MRI-TBx, TRUS-SBx and combined biopsy in TZ and PZ were calculated, respectively.

Statistical Tests

McNemar test was used to compare the csPCa detection rates in TZ and PZ, respectively. The frequencies and distribution of all detected prostate cancers by different biopsy methods were also compared. P < 0.05 was considered statistically significant.

Results

Among 356 lesions in 309 patients, 208 (68 in TZ, 140 in PZ) were pathologically confirmed as csPCa. In TZ, there were significant differences for csPCa detection with PI-RADS 3 between combined biopsy and TRUS-SBx (23.5% vs. 15.3%), MRI-TBx (23.5% vs. 16.3%), respectively. MRI-TBx detected 23% (19/83) cases missed by TRUS-SBx in which 68% (13/19) were csPCa. In PZ, there were no statistical differences between MRI-TBx and combined biopsy with PI-RADS 3–5 (P = 0.21, 0.25, 0.07, respectively). In 9% (14/152) cases only detected by MRI-TBx, 86% (12/14) were clinically significant. Five percent (7/152) of cases only detected by TRUS-SBx were completely nonclinically significant.

Data Conclusion

MRI-TBx played a positive role on csPCa diagnosis in TZ, but combined biopsy might be the best choice especially in the subgroup PI-RADS 3. In PZ, MRI-TBx had an advantage over TRUS-SBx for csPCa detection.

Evidence Level

2.

Technical Efficacy

Stage 2.
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WHOLE‐GENOME SINGLE MOLECULE REAL‐TIME SEQUENCING OF SARS‐CoV‐2 OMICRON

AlexandrosSfakianakis shared this article with you from Inoreader

ABSTRACT

New variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome can only be identified using accurate sequencing methods. Single molecule real-time (SMRT) sequencing has been used to characterize Alpha and Delta variants, but not Omicron variants harbouring numerous mutations in the SARS-CoV-2 genome. This study assesses the performance of a target capture SMRT sequencing protocol for whole genome sequencing (WGS) of SARS-CoV-2 Omicron variants and compared it to that of an amplicon SMRT sequencing protocol optimized for Omicron variants. The failure rate of the target capture protocol (6%) was lower than that of the amplicon protocol (34%, p<0.001) on our dataset, and the median genome coverage with the target capture protocol (98.6% [IQR: 86-99.4]) was greater than that with the amplicon protocol (76.6% [IQR: 66-89.6], (p<0.001)). The percentages of samples with >95% whole genome coverage were 64% with the target capture pro tocol and 19% with the amplicon protocol (p<0.05). The clades of 96 samples determined with both protocols were 93% concordant and the lineages of 59 samples were 100% concordant. Thus, target capture SMRT sequencing appears to be an efficient method for WGS, genotyping and detecting mutations of SARS-CoV-2 Omicron variants.

This article is protected by copyright. All rights reserved.
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Autophagy: A challengeable paradox in cancer treatment

AlexandrosSfakianakis shared this article with you from Inoreader

Abstract

Objective

Autophagy is an intracellular degradation pathway conserved in all eukaryotes from yeast to humans. This process plays a quality-control role by destroying harmful cellular components under normal conditions, maintaining cell survival, and establishing cellular adaptation under stressful conditions. Hence, there are various studies indicating dysfunctional autophagy as a factor involved in the development and progression of various human diseases, including cancer. In addition, the importance of autophagy in the development of cancer has been highlighted by paradoxical roles, as a cytoprotective and cytotoxic mechanism. Despite extensive research in the field of cancer, there are many questions and challenges about the roles and effects suggested for autophagy in cancer treatment. The aim of this study was to provide an overview of the paradoxical roles of autophagy in different tumors and related cancer treatment options.

Methods

In this study, to find articles, a search was made in PubMed and Google scholar databases with the keywords Autophagy, Autophagy in Cancer Management, and Drug Design.

Results

According to the investigation, some studies suggest that several advanced cancers are dependent on autophagy for cell survival, so when cancer cells are exposed to therapy, autophagy is induced and suppresses the anti-cancer effects of therapeutic agents and also results in cell resistance. However, enhanced autophagy from using anti-cancer drugs causes autophagy-mediated cell death in several cancers. Because autophagy also plays roles in both tumor suppression and promotion further research is needed to determine the precise mechanism of this process in cancer treatment.

Conclusion

We concluded in this article, autophagy manipulation may either promote or hinder the growth and development of cancer according to the origin of the cancer cells, the type of cancer, and the behavior of the cancer cells exposed to treatment. Thus, before starting treatment it is necessary to determine the basal levels of autophagy in various cancers.
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Intelligent Headband System for Evaluating Rehabilitation Effectiveness

AlexandrosSfakianakis shared this article with you from Inoreader

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Stroke is an acute cerebrovascular condition causing damage to cranial nerves and requires subsequent rehabilitation treatment. In clinical practice, the effectiveness of rehabilitation is usually subjectively assessed by experienced physicians or using global prognostic scales. Several brain imaging techniques, such as positron emissio n tomography, functional magnetic resonance imaging, and computed tomography angiography, can be applied in rehabilitation effectiveness evaluation, but their complexity and long measurement times limit the activity of patients during measurement. This paper proposes an intelligent headband system based on near-infrared spectroscopy. An optical headband continuously and noninvasively monitors changes in hemoglobin parameters in the brain. The system's wearable headband and wireless transmission provide convenience of use. According to the change of hemoglobin parameters during rehabilitation exercise, several indexes were also defined to evaluate the state of cardiopulmonary function and further build the neural network model of the cardiopulmonary function evaluation. Finally, the relationship between the defined indexes and the cardiopulmonary function state were investigated and the neural network model for the cardiopulmonary function evaluation was also applied in the rehabil itation effect evaluation. The experimental results show the cardiopulmonary function state could reflect on most of the defined indexes and the output of neural network model, and the rehabilitation therapy could also improve the cardiopulmonary function.
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Combined proliferation and apoptosis index provides better risk stratification in breast cancer

AlexandrosSfakianakis shared this article with you from Inoreader
Combined proliferation and apoptosis index provides better risk stratification in breast cancer


Introduction

Breast cancer (BC) risk stratification is critical for predicting behaviour and guiding management decision-making. Despite the well-established prognostic value of cellular proliferation in BC, the interplay between proliferation and apoptosis remains to be defined. In this study, we hypothesised that the combined proliferation and apoptosis indices can provide a more accurate in vivo growth rate measure and a precise prognostic predictor.

Methods and Results

Apoptotic and mitotic figures were counted in whole slide images (WSI) generated from haematoxylin and eosin-stained sections of 1545 BC cases derived from two well-defined BC cohorts. Counts were carried out visually within defined areas. There was a significant correlation between mitosis and apoptosis scores. High apoptotic counts were associated with features of aggressive behaviour including high grade, high pleomorphism score, and hormonal receptor negativity. Although the mitotic index (MI) and apoptotic index (AI) were independent prognostic indicators, the prognostic value was synergistically higher when combined. BC patients with a high combined AI and MI had the shortest survival. Replacing the mitosis score with the mitosis-apoptosis index, in the Nottingham grading system, revealed that the modified grade with the new score had a higher significant association with BC-specific survival with a higher hazard ratio.

Conclusion

Apoptotic figures count provides additional prognostic value in BC when combined with MI, such a combination can be implemented to assess the behaviour of BC and provides an accurate prognostic indicator. This can be considered when using artificial intelligence algorithms to assess proliferation in BC.
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Improving trunk postural control facilitates walking in children with cerebral palsy: a pilot study

AlexandrosSfakianakis shared this article with you from Inoreader

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Objective The aim of this study was to determine the effects of bilateral trunk support during walking on trunk and leg kinematics and neuromuscular responses in children with cerebral palsy (CP). Design Fourteen children with spastic CP (GMFCS level I to III) participated in this study. Children walked on a treadmill under 4 different conditions, i.e., without support (BASELINE), with bilateral support applied to the upper trunk (UTS), the lower trunk (LTS), and combined upper and lower trunk (CTS). The trunk and leg kinematics and muscle activity were recorded. Results Providing bilateral support to the trunk had a significant impact on the displacement of the pelvis and trunk (p
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Plasma Biomarkers and Positron Emission Tomography Tau Pathology in Progressive Supranuclear Palsy

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Plasma Biomarkers and Positron Emission Tomography Tau Pathology in Progressive Supranuclear Palsy

Plasma neurofilament light chain (NfL) is a promising biomarker of progressive supranuclear palsy (PSP) to assist in PSP diagnosis and differential diagnosis from Parkinson's disease (PD) and to monitor disease severity. Pending replication in independent cohorts, plasma glial fibrillary acidic protein (GFAP) holds promise for a PSP diagnosis and a differential diagnosis with multiple system atrophy with predominant parkinsonism (MSA-P) and for detecting brainstem atrophy and tau deposition in PSP.


ABSTRACT

Background

Development of disease-modifying therapeutic trials of progressive supranuclear palsy (PSP) urges the need for sensitive fluid biomarkers.

Objectives

The objectives of this study were to explore the utility of plasma biomarkers in the diagnosis, differential diagnosis, and assessment of disease severity, brain atrophy, and tau deposition in PSP.

Methods

Plasma biomarkers were measured using a single-molecule array in a cohort composed of patients with PSP, Parkinson's disease (PD), multiple system atrophy with predominant parkinsonism (MSA-P), and healthy controls (HCs).

Results

Plasma neurofilament light chain (NfL) outperformed other plasma makers (ie, glial fibrillary acidic protein [GFAP], phosphorylated-tau 181 [p-tau181], amyloid-β 1–40, amyloid-β 1–42) in identifying PSP from HC (area under the curve [AUC] = 0.904) and from MSA-P (AUC = 0.711). Plasma GFAP aided in distinguishing PSP from HC (AUC = 0.774) and from MSA-P (AUC = 0.832). It correlated with brainstem atrophy and higher regional tau accumulation. However, plasma p-tau181 neither helped in diagnosis nor was it associated with clinical or neuroimaging measures.

Conclusions

Plasma NfL and GFAP showed different values in differentiating PSP from HC or controls with other forms of neurodegenerative parkinsonism and detecting disease severity, brain atrophy, or tau deposition in PSP. © 2023 International Parkinson and Movement Disorder Society.
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