Κυριακή 6 Μαρτίου 2022

PKM2 Is Overexpressed in Glioma Tissues, and Its Inhibition Highly Increases Late Apoptosis in U87MG Cells With Low-density Specificity

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In Vivo. 2022 Mar-Apr;36(2):694-703. doi: 10.21873/invivo.12755.

ABSTRACT

BACKGROUND/AIM: Pyruvate kinase M2 (PKM2) functions as an important rate-limiting enzyme in aerobic glycolysis and is involved in tumor initiation and progression. However, there are few studies on the correlation between PKM2 expression and its role in glioma.

MATERIALS AND METHODS: PKM2 expression was immunohistochemically examined in human brain tumor samples. Furthermore, we studied the effects of two PKM2 inhibitors (shikonin and compound 3K) on the U87MG glioma cell line.

RESULTS: PKM2 was overexpressed in most glioma tissues when compared to controls. Interestingly, glioma-adjacent tissues from showed slight PKM2 overexpression. This suggests that PKM2 overexpression maybe an important trigger factor for glioma tumorigenesis. We found that the PKM2 inhibitor shikonin was effective against U87MG cells at a relatively low dose and was largely dep endent on low cellular density compared to the effects of the anticancer drug vincristine. Shikonin highly increased late-apoptosis of U87MG cells. We also demonstrated that autophagy was involved in the increase in late-apoptosis levels caused by shikonin. Although vincristine treatment led to a high level of G2-phase arrest in U87MG cells, shikonin did not increase G2 arrest. Co-treatment with two PKM2 inhibitors, shikonin and compound 3K, increased the inhibitory effects.

CONCLUSION: Combination therapy with PKM2 inhibitors together might be more effective than combination therapy with anticancer drugs. Our findings encourage the application of PKM2-targeting in gliomas, and lay the foundation for the development of PKM2 inhibitors as promising antitumor agents for glioma.

PMID:35241524 | DOI:10.21873/invivo.12755

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A Deep Learning Framework for Real‐Time 3D Model Registration in Robot‐Assisted Laparoscopic Surgery

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Abstract

Introduction

The current study presents a Deep Learning framework to determine, in real-time, position and rotation of a target organ from an endoscopic video. These inferred data are used to overlay the 3D model of patient's organ over its real counterpart. The resulting augmented video flow is streamed back to the surgeon as a support during laparoscopic Robot-Assisted procedures.

Methods

This framework exploits semantic segmentation and, thereafter, two techniques, based on Convolutional Neural Networks and motion analysis, were used to infer the rotation.

Results

The segmentation shows optimal accuracies, with a mean IoU score greater than 80% in all tests. Different performance levels are obtained for rotation, depending on the surgical procedure.

Discussion

Even if the presented methodology has various degrees of precision depending on the testing scenario, this work sets the first step for the adoption of Deep Learning and Augmented Reality to generalize the automatic registration process.

This article is protected by copyright. All rights reserved.

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Submandibular gland transfer for the prevention of radiation‐induced xerostomia in oropharyngeal cancer: Dosimetric impact in the intensity modulated radiotherapy era

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Abstract

Background

Submandibular gland (SMG) transfer decreased radiation-associated xerostomia in the 2/3-dimensional radiotherapy era. We evaluated the dosimetric implications of SMG transfer on modern intensity modulated radiotherapy (IMRT) plans.

Methods

Eighteen oropharynx cancer patients underwent SMG transfer followed by IMRT; reoptimized plans using the baseline SMG location were generated. Mean salivary gland, oral cavity, and larynx doses were compared between clinical plans and reoptimized plans.

Results

No statistically significant difference in mean SMG dose (27.53 Gy vs. 29.61 Gy) or total salivary gland dose (26.12 Gy vs. 26.41 Gy) was observed with or without SMG transfer (all p > 0.05). Mean oral cavity and larynx doses were not statistically different. Neither tumor site, target volume crossing midline, stage, nor salivary gland volumes were associated with mean doses.

Conclusions

Salivary gland doses were similar with or without SMG transfer. IMRT likely decreases the benefit of SMG transfer on the risk of radiation-associated xerostomia.

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Endonasal Acoustic Doppler Sonography in Predicting the Survival of Nasoseptal Flap Following Previous Irradiation

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Objective

Blood supply to the nasoseptal flap may be compromised in patients who had previous irradiation to the head and neck region, hence, affecting its viability. Here, we evaluate the role of an endonasal acoustic Doppler sonography in predicting the survival of the nasoseptal flap in this group of patients.

Study Design

Retrospective cohort.

Methods

Retrospective review of patients with previous irradiation to the head and neck region who had undergone endoscopic endonasal surgeries requiring nasoseptal flap as reconstruction. Survival rates of nasoseptal flap were compared between groups where endonasal Doppler was used.

Results

A total of 28 patients were identified with previous irradiation to the head and neck region who had undergone endoscopic endonasal surgeries requiring nasoseptal flap as reconstruction. The overall survival rate of nasoseptal flap is 67.8% (19 out of 28). Endonasal acoustic Doppler was used in 17 of these patients, of which 13 patients had a positive signal. The flap survival rate in the Doppler-positive group compared to the non-Doppler group was significantly better at 100% vs 45.4% (P = .003). Among those where the endonasal Doppler was used, the flap survival rate with a negative doppler signal was significantly worse at 25%, compared with 100% flap survival in those with positive doppler signal (P = .006). The positive predictive value of a positive endonasal Doppler signal with flap survival is 100%.

Conclusion

The use of endonasal acoustic Doppler may be useful in predicting the viability of nasoseptal flap in postirradiated patients who need a local mucosal flap coverage.

Level of Evidence

Level 3 Laryngoscope, 2022

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Smoothed Cepstral Peak Analysis

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Childhood and adolescence are essential stages in the development of voice and speech quality; therefore, it is essential to understand the vocal changes that occur during this period. Frequency-based measurement methods like cepstral measurements stand out among the methods described, which are able to identify fo and estimate the periodicity and noise in the acoustic wave without establishing individual cycles of the sound wave.
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Computational Study of the Impact of Dehydration-Induced Vocal Fold Stiffness Changes on Voice Production

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Systemic vocal fold dehydration is known to increase vocal fold stiffness, which has been hypothesized to have important effect on voice production. However, it remains unclear whether the dehydration-induced vocal fold stiffness changes can have a noticeable impact on phonation, particularly in normal phonation conditions. The goal of this study was to investigate the impact of vocal fold stiffness changes due to vocal fold systemic dehydration and its significance in daily communication.
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Whole‐transcriptome sequencing identifies postzygotic ATP2A2 mutations in a patient misdiagnosed with herpes zoster, confirming the diagnosis of very late‐onset segmental Darier disease

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ABSTRACT

An 82-year-old female patient presented with a recent onset of painful skin lesions in unilateral distribution on the abdominal area following the lines of Blaschko; the initial diagnosis of Varicella-zoster infection was made. However, because the individual lesions appeared as hyperkeratotic papules and were unresponsive to antiviral therapy, a skin biopsy was performed, which revealed hyperkeratosis, suprabasal acantholysis and dyskeratosis with corps ronds and grains, consistent with acantholytic dyskeratotic acanthoma. Since this entity has been associated with Darier disease, whole transcriptome sequencing by RNA-Seq was performed on RNA isolated from a lesion as well as from adjacent normal appearing skin, and a recently developed bioinformatics pipeline that can identify both genomic sequence variants and the presence of any of over 900 viruses was applied. Two pathogenic missense mutations in the ATP2A2 gene were identified in the lesional but not in normal appeari ng skin, and no evidence of Varicella-Zoster infection was obtained. These findings confirm the diagnosis of segmental Darier disease due to postzygotic mutations in the ATP2A2 gene, and attest to the power of a novel single-step application of RNA-Seq in providing correct diagnosis in this rare genodermatosis.

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