Τετάρτη 26 Ιανουαρίου 2022

Sensitizing TRAIL response via differential modulation of anti- and pro-apoptotic factors by AZD5582 combined with ER nanosomal TRAIL in neuroblastoma

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Via histochem

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Acta Histochem. 2022 Jan 22;124(2):151856. doi: 10.1016/j.acthis.2022.151856. Online ahead of print.

ABSTRACT

Neuroblastoma is a metastatic brain tumor particularly common in children. The cure rate is below 50% for patients of high-risk condition. Novel therapeutic agents and approaches are needed to improve the cure rate. Tumor necrosis factor-related and apoptosis-inducing ligand (TRAIL) is a promising proapoptotic factor that rapidly induces apoptosis preferentially in t ransformed and cancerous cells. Unfortunately, the common TRAIL resistance in cancers has hampered the clinical application of the ligand. Previously we prepared a novel TRAIL-armed ER derived nanosomal agent (ERN-T) that overcomes TRAIL resistance in some cancer lines when combined with a synthetic antagonist of inhibitors of apoptosis proteins (IAPs), AZD5582. However, how AZD5582 sensitizes cancer cells to ERN-T remains not well understood. In this study we continued to test the therapeutic efficacy of the combinatory therapy of ERN-T and AZD5582 on neuroblastoma, aiming to reveal the molecular mechanism underlying the synergism between AZD5582 and ERN-T. The obtained data revealed that ERN-Ts overcame TRAIL resistance and showed significant cytotoxicity on the resistant neuroblastoma line SH-SH5Y when combined with AZD5582 whilst sparing normal cells. The combination of low doses of ERN-Ts and AZD5582 induced intensive apoptosis in SH-SY5Y but not in normal skin fibroblasts (NSF s). Importantly we discovered that TRAIL sensitization in SH-SY5Y was associated with the concomitant downregulation of antiapoptotic factors cFLIP, MCL-1 and IAPs and upregulation of proapoptotic protein BAX and the death receptor 5 (DR5) by the cotreatment of ERN-T and AZD5582. In vivo study demonstrated that the combination of ERN-T and AZD5582 constituted a highly effective and safe therapy for subcutaneous SH-SY5Y xenograft neuroblastoma in nude mice. In conclusion, we identified that the concomitant regulation of both antiapoptotic and proapoptotic factors and DR5 is an essential molecular mechanism for overcoming TRAIL resistance in SH-SY5Y and the combination of ERN-T and AZD5582 potentially constitutes a novel therapeutic strategy, which is highly effective and safe for neuroblastoma.

PMID:35077998 | DOI:10.1016/j.acthis.2022.151856

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Chinese guidelines for diagnosis and treatment of allergic rhinitis (2022, revision)

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Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022 Jan 21;57:8-31. doi: 10.3760/cma.j.cn115330-20211228-00828. Online ahead of print.

NO ABSTRACT

PMID:35078291 | DOI:10.3760/cma.j.cn115330-20211228-00828

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Endoscopic Posterior Rotation Flap for Posterior Glottic Insufficiency

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Τρίτη 25 Ιανουαρίου 2022

Morphology of the ligaments located on the medial side of the ankle and on the plantar surface of the foot

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Surg Radiol Anat. 2022 Jan 25. doi: 10.1007/s00276-021-02872-w. Online ahead of print.

ABSTRACT

To have biodynamic features, the feet have bones located in a special posture, the joints that keep together those bones, the ligaments that provide linkage to those joints, and tendons of muscles particularly which end the foot. This study aimed to research the morphology of the medial side and plantar ligaments. The study was conducted on a total of 30 feet belonging to 2 women and 13 men cadavers that exist at the Anatomy Department of the Medical Faculty of Uludag University. After the dissections, 61 parameters that belonging to the ligaments and general features of the foot, were evaluated. The statistical analysis of the collected data was evaluated by SPSS 20.0. According to the findings, while the descriptive statistics of the foot and the ligaments related to the foot, the statistically significant difference of any of the parameters wasn't observed when they were compared between the right and left sides of the foot. In terms of the correlative relations, the parameters that showed high correlation were chosen and 28 formulas were developed using regression analysis. We foresee that our findings of the features belonging to normal anatomic structures will deepen our knowledge besides providing important benefits before or during orthopedic and plastic surgery operations related to the region. Also, our findings were discussed by comparing the find ings of similar studies belonging to many other researchers in literature, and our study's contribution to the literature was evaluated.

PMID:35075567 | DOI:10.1007/s00276-021-02872-w

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Effectiveness of submucosal turbinoplasty in refractory obstructive rhinitis: a prospective comparative trial

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Eur Arch Otorhinolaryngol. 2022 Jan 25. doi: 10.1007/s00405-022-07267-0. Online ahead of print.

ABSTRACT

OBJECTIVE: Refractory inferior turbinate hypertrophy requires a surgical approach to address symptomatic complaints. Submucosal approaches demonstrated their efficacy in restoring respiratory function and respecting the nasal mucosa. Microdebrider-assisted turbinoplasty (MAT) tools effectively reduces the soft tissue, exploiting a very different principle from the kinetic energy of radiofrequency. Thus, we aimed to compare the microdebrider-assisted turbinoplasty and the quantum molecular resonance (QMR) to assess patients' perspectives and respiratory outcomes.

METHODS: Subjects with persistent bilateral nasal blockage due to inferior turbinates hypertrophy were prospectively recruited from the University Medical Center. We randomly assigned the patients to each treatment and performed symptom evaluation via the visual analog score and endoscopic assessment at baseline and 30-, 90-, and 180-day post-treatment.

RESULTS: Seventy participants completed the evaluations, 35 in MAT and 35 in the QMR group. Nasal complaints were significantly reduced after 1 month using both methods. Although the MAT group reported higher postoperative bleeding and edema than QMR group, similar significant reductions were seen for turbinate size at long-term follow-up. Conversely, the MAT group reported greater VAS outcomes than QMR from the first postoperative month. In addition, MAT showed a longer operating time, although this difference was not statistically significant (p < 0.05).

CONCLUSION: MAT allows effective control of nasal symptoms by reducing the size of turbinates in patients with lower turbinate hypertrophy. Although QMR may cause fewer postoperative complications, functional results are comparable to long-term follow-up.

PMID:35076746 | DOI:10.1007/s00405-022-07267-0

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The differences in distant metastatic patterns and their corresponding survival between thyroid cancer subtypes

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Abstract

Introduction

This study aimed to systematically elucidate the metastatic patterns and their corresponding survival of each thyroid cancer subtype at time of diagnosis.

Methods

We accessed the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2018 to search for primary thyroid cancers with DM at presentation (M1).

Results

We included 2787 M1 thyroid cancers for statistical analyses and the incidence of DM at presentation was 2.4%. Lung was the most common metastatic site for anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), papillary thyroid carcinoma (PTC), and oncocytic (Hurthle) cell carcinoma (HCC) whereas bone is the favorable disseminated site of follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC). Patients with multi-organ metastases had the worst survival whereas bone metastases were associated with a favorable outcome (p < 0.001).

Conclusion

There are significant differences in DM patterns of thyroid cancer subtypes and their corresponding survival.

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A study of 285 cases of cranial vault suture closure in Chinese adults

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Surg Radiol Anat. 2022 Jan 25. doi: 10.1007/s00276-021-02854-y. Online ahead of print.

ABSTRACT

PURPOSE: To examine the presence and characteristics of cranial vault suture closure in Chinese adults and to explore whether craniosacral therapy (CST) manipulation is rational from the anatomical perspective.

METHODS: Anthropological non-metric observation and craniometry were used to study 285 dry skull specimens of Chinese adults.

RESULTS: A total of 91 specimens w ith closed extracranial sutures were observed, with an occurrence rate of 31.93%. Based on the mode of closure, there were 32 cases of single type closure, with sagittal suture closure predominating with 20 cases (21.98%); 59 cases of composite closure, with a partial closure of coronal suture + sagittal suture + lambdoid suture predominating with 26 cases (28.57%). In terms of the degree of closure, there were 13 cases (14.28%) of sagittal suture grade 0 closure and 78 cases (85.72%) of grade 1 - 4 closure; 34 cases (37.36%) of coronal suture grade 0 closure and 57 cases (62.64%) of grade 1 - 4 closure; 47 cases (51.65%) of lambdoid suture grade 0 closure and 44 cases (48.35%) of grade 1 - 4 closure. The segment and degree of coronal suture closure (46, 80.7%) and lambdoid suture (31, 70.45%) were mostly left-right symmetrical. The bone surfaces on either side of the cranial vault sutures are embedded in each other, forming a rough, complex and interlocking bone-suture-bone structu re.

CONCLUSION: This study observed the closure of the cranial vault suture, summarized its characteristics, and explored the irrationality of the CST manipulation. The anatomical characteristics of the cranial suture dictate that manipulation cannot push the cranial suture at will.

PMID:35076751 | DOI:10.1007/s00276-021-02854-y

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