Αρχειοθήκη ιστολογίου

Τετάρτη 22 Δεκεμβρίου 2021

Pathological complete response following cisplatin or carboplatin-based neoadjuvant chemotherapy for triple-negative breast cancer: A systematic review and meta-analysis

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Exp Ther Med. 2022 Jan;23(1):91. doi: 10.3892/etm.2021.11014. Epub 2021 Nov 26.

ABSTRACT

The addition of platinum compounds to standard neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) is highly controversial. Platinum agents, such as cisplatin and carboplatin, are DNA-damaging agents which exhibit activity in breast cancer, particularly in the TNBC subgroup. In order to assess the efficacy of each most representative platinum agent (cisplatin and carboplatin) in patients with TNBC treated with NACT, the present study performed a systematic review and meta-analysis of all available published studies on TNBC. A search of PubMed was performed to identify studies that investigated platinum-based NACT in patients with TNBC. The primary endpoints were the pooled rate of the pathological complete response (pCR) between cisplatin vs. carboplatin-based NACT. A total of 24 studies were selected (17 studies for carboplati n and 6 studies for cisplatin and 1 study with both carboplatin and cisplatin, with 20 prospective studies) for the analysis of 1,711 patients with TNBC. Overall, the pooled rate of pCR in patients treated with platinum-based NACT was 48%. No significant differences were observed between the rates of pCR obtained under carboplatin vs cisplatin treatment. The carboplatin pCR rate was 0.470 [95% confidence interval (CI), 0.401-0.539], while the cisplatin pCR rate was 0.473 (95% CI, 0.379-0.568). The comparison between these two categories revealed no significant differences (P=0.959). In the whole, the present study demonstrates that neoadjuvant platinum-based chemotherapy improves the pCR rate in patients with TNBC, regardless of the platinum agent used. Carboplatin may thus represent a viable option due to its more favorable toxicity profile.

PMID:34934456 | PMC:PMC8652390 | DOI:10.3892/etm.2021.11014

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Stomatin-knockdown effectively attenuates sepsis-induced oxidative stress and inflammation of alveolar epithelial cells by regulating CD36

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Exp Ther Med. 2022 Jan;23(1):69. doi: 10.3892/etm.2021.10992. Epub 2021 Nov 23.

ABSTRACT

Sepsis-induced acute lung injury is a type of lung disease with a high fatality rate that is characterized by acute inflammation. In the present study, the underlying role and potential mechanism of the stomatin (STOM) protein were investigated in lipopolysaccharide (LPS)-induced oxidative stress and inflammation in a mouse lung epithelial cell line, MLE-12. The expression levels of STOM and CD36 were measured using reverse transcription-quantitative PCR and western blotting. Subsequently, the expression levels of STOM and CD36 in LPS-treated MLE-12 cells were knocked down or overexpressed, respectively, via transfection with a small interfering RNA-STOM or a CD36-overexpression vector. An RNA immunoprecipitation (RIP) assay was used to determine the interaction between STOM and CD36, while Cell Counting Kit-8 assay and ELISA were performed to dete ct cell viability and oxidative stress, respectively. Moreover, western blotting and ELISA kits were used to detect the expression levels of associated inflammatory factors. The results of the present study demonstrated that STOM expression was upregulated in MLE-12 cells treated with LPS compared with the untreated control group. According to the Search Tool for the Retrieval of Interacting Genes/Proteins database, it was predicted that STOM and CD36 had the ability to interact with each other. The predicted binding between STOM and CD36 was verified using a RIP assay. The results demonstrated that STOM positively regulated the expression of CD36. Moreover, in LPS-treated MLE-12 cells, STOM-knockdown reversed the inhibitory effects of LPS on cell viability, and the promoting effects of LPS on oxidative stress and inflammation. These aforementioned changes were alleviated by the overexpression of CD36. To conclude, the results of the present study revealed that STOM may interact wit h CD36 to affect the levels of oxidative stress and inflammation in LPS-treated MLE-12 cells.

PMID:34934440 | PMC:PMC8649852 | DOI:10.3892/etm.2021.10992

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Lumbar Pneumorrhachis Associated With Basilar Skull Fractures

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Cureus. 2021 Nov 18;13(11):e19703. doi: 10.7759/cureus.19703. eCollection 2021 Nov.

ABSTRACT

Lumbar pneumorrhachis following head injury is rare and commonly asymptomatic but can be indicative of skull fracture and cerebrospinal fluid (CSF) leak, which may warrant intervention. A PubMed review of the literature was performed using a keyword search to identify cases examining lumbar pneumorrhachis following head injury. Our case series included two patients who had lumbar pneumorrhachis between September 2019 and May 2020 at our center. The literature review summarizes 16 patients from 14 prior reports of pneumorrhachis. In our two-patient case series, neither patient required direct intervention for either pneumorrhachis or CSF leak. Pneumorrhachis is rare following an isolated head injury and is associated with basilar skull fractures and CSF leak. Pneumorrhachis should alert clinicians to the possibility of a CSF leak, which may require int ervention.

PMID:34934572 | PMC:PMC8684351 | DOI:10.7759/cureus.19703

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In vitro and in vivo effects of AVA4746, a novel competitive antagonist of the ligand binding of VLA-4, in B-cell acute lymphoblastic leukemia

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Exp Ther Med. 2022 Jan;23(1):47. doi: 10.3892/etm.2021.10969. Epub 2021 Nov 15.

ABSTRACT

Treatment of resistant or recurrent acute lymphoblastic leukemia (ALL) remains a challenge. It was previously demonstrated that the adhesion molecule integrin α4, referred to hereafter as α4, mediates the cell adhesion-mediated drug resistance (CAM-DR) of B-cell ALL by binding to vascular cell adhesion molecule-1 (VCAM-1) on bone marrow stroma. In addition, it was previously observed that the blockade of α4 with natalizumab or inhibition using the small molecule antagonist TBC3486 sensitized relapsed ALL cells to chemotherapy. However, α4-targeted therapy is not clinically available for the treatment of leukemia to date. In the present study, the use of a novel non-peptidic small molecule integrin α4 antagonist, AVA4746, as a potential new approach to combat drug-resistant B-ALL was explored. An in vitro co-culture = model of primary B- ALL cells and an in vivo xenograft model of patient-derived B-ALL cells were utilized for evaluation of AVA4746. VLA-4 conformation activation, cell adhesion/de-adhesion, endothelial tube formation, in vivo leukemia cell mobilization and survival assays were performed. AVA4746 exhibited high affinity for binding to B-ALL cells, where it also efficiently blocked ligand-binding to VCAM-1. In addition, AVA4746 caused the functional de-adhesion of primary B-ALL cells from VCAM-1. Inhibition of α4 using AVA4746 also prevented angiogenesis in vitro and when applied in combination with chemotherapy consisting of Vincristine, Dexamethasone and L-asparaginase, it prolonged the survival of ~33% of the mice in an in vivo xenograft model of B-ALL. These data implicate the potential of targeting the α4-VCAM-1 interaction using AVA4746 for the treatment of drug-resistant B-lineage ALL.

PMID:34934426 | PMC:PMC8652384 | DOI:10.3892/etm.2021.10969

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Voluntary Cough Effectiveness and Airway Clearance in Neurodegenerative Disease

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J Speech Lang Hear Res. 2021 Dec 22:1-19. doi: 10.1044/2021_JSLHR-21-00308. Online ahead of print.

ABSTRACT

PURPOSE: Voluntary cough dysfunction is highly prevalent across multiple patient populations. Voluntary cough has been utilized as a screening tool for swallowing safety deficits and as a target for compensatory and exercise-based dysphagia management. However, it remains unclear whether voluntary cough dysfunction is associated with the ability to effectively clear the airwa y.

METHOD: Individuals with neurodegenerative disorders performed same-day voluntary cough testing and flexible endoscopic evaluations of swallowing (FEES). Participants who were cued to cough after exhibiting penetration to the vocal folds and/or aspiration with thin liquids during FEES met inclusion criteria. One-hundred and twenty-three trials were blinded, and the amount of residue before and after a cued cough on FEES was measured with a visual analog scale. Linear and binomial mixed-effects models examined the relationship between cough airflow during voluntary cough testing and the proportion of residue expelled.

RESULTS: Peak expiratory flow rate (p = .004) and cough expired volume from the entire epoch (p = .029) were significantly associated with the proportion of aspiration expelled from the subglottis. Peak expiratory flow rate values of 3.00 L/s, 3.50 L/s, and 5.30 L/s provided high predicted probabilities that ≥ 25%, ≥ 50%, and ≥ 80% asp irate was expelled. Accounting for depth of aspiration significantly improved model fit (p < .001).

CONCLUSIONS: These findings suggest that voluntary cough airflow is associated with cough effectiveness to clear aspiration from the subglottis, although aspiration amount and depth may play an important role in this relationship. These findings provide further support for the clinical utility of voluntary cough in the management of dysphagia.

PMID:34936376 | DOI:10.1044/2021_JSLHR-21-00308

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MiR-194-3p modulates the progression of colorectal cancer by targeting KLK10

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Histol Histopathol. 2021 Dec 22:18413. doi: 10.14670/HH-18-413. Online ahead of print.

ABSTRACT

BACKGROUND: A rich history of studies have manifested the importance of miRNAs to cancer progression, while miR-194-3p has been seldom explored.

OBJECTIVE: The purpose of this study is to unearth the way the KLK10/miR-194-3p axis modulates colorectal cancer (CRC).

METHODS: Differentially expressed genes of CRC in TCGA database were analyzed. Western blot and qRT-PCR were employed to test protein and mRNA expressions of two researched genes. Their targeting was confirmed using dual-luciferase. Biological behaviors of cells were tested by a series of cellular functional assays.

RESULT: Remarkably low miR-194-3p expression and high KLK10 expression were observed in cancer cells. Overexpressing miR-194-3p hindered the progression of CRC cells. Overexpression of miR-194-3p significantly weakened the promoting effect of upregulat ed KLK10 on cell migration, invasion and proliferation. Their targeting was verified by dual -luciferase assay. Therefore, miR-194-3p hindered cell behaviors of CRC through KLK10.

CONCLUSION: This investigation casts new light on the treatment of CRC through the KLK10/miR-194-3p axis.

PMID:34935123 | DOI:10.14670/HH-18-413

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Τρίτη 21 Δεκεμβρίου 2021

Paracrine mechanisms of endothelial progenitor cells in vascular repair

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Via histochem

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Acta Histochem. 2021 Dec 17;124(1):151833. doi: 10.1016/j.acthis.2021.151833. Online ahead of print.

ABSTRACT

Endothelial progenitor cells (EPCs) play an important role in repairing damaged blood vessels and promoting neovascularization. However, the specific mechanism of EPCs promoting vascular repair is still unclear. Currently, there are two different views on the repair of damaged vessels by EPCs, one is that EPCs can directly differentiate into endothelial cells (ECs) a nd integrate into injured vessels, the other is that EPCs act on cells and blood vessels by releasing paracrine substances. But more evidence now supports the latter. Therefore, the paracrine mechanisms of EPCs are worth further study. This review describes the substances secreted by EPCs, some applications based on paracrine effects of EPCs, and the studies of paracrine mechanisms in cardiovascular diseases--all of these are to support the view that EPCs repair blood vessels through paracrine effects rather than integrating directly into damaged vessels.

PMID:34929523 | DOI:10.1016/j.acthis.2021.151833

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What is the impact of mastoid surgery on swimming?

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Abstract

Swimming confers significant physical and mental health benefits to people but there is little evidence regarding the impact of mastoid surgery on this activity.

Almost half of the patients (46.7%) swim less after mastoid surgery. Occasional swimmers are affected mostly. The need to protect the ear and dizziness are the main reasons to discontinue swimming.

Acute incapacitating vertigo occurs in 8.9% patients during swimming.

No difference in swimming frequency between patients with a closed or an open mastoid cavity was observed. The presence of a wet ear after surgery and the use of prophylactic measures did not affect the swimming frequency.

Patients should not be discouraged from swimming on the basis of mastoid surgery. We recommend a trial of swimming with or without protection in shallow waters first, under the supervision of an experience swimmer.

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Efficacy and Safety of External Volume Expansion (EVE) on Fat Grafting: A Systematic Review and Single-Arm Meta-Analysis

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J Plast Reconstr Aesthet Surg. 2021 Nov 16:S1748-6815(21)00576-3. doi: 10.1016/j.bjps.2021.11.032. Online ahead of print.

ABSTRACT

BACKGROUND: The autologous fat grafting is commonly used for reconstructive or aesthetic purposes. However, due to the huge variation in methods, its retention rate varies a lot. External volume expansion (EVE) has been used to treat recipient sites of fat grafting. Concerns have been raised regarding its efficacy and safety.

METHODS: We have searched PubMed, EMBASE, and the Cochrane Library for studies on EVE-assisted fat grafting published from 2000 to 2020. A meta-analysis was conducted to pool the retention rate. The incidence of complications was assessed for reconstructive or aesthetic purposes.

RESULTS: The 11 included studies involved 1152 patients with operations on 1794 breasts. Four studies were included in the meta-analysis. The pooled retention rate was 65% [95%CI 49, 79]. Eight stu dies reported the complications. The total complication incidence was 34%, which is 35% for the aesthetic group and 33% for the reconstructive group. The complication rate was not obviously different between the two groups.

CONCLUSIONS: The study shows that the EVE-assisted fat grafting has better retention rate than traditional fat grafting. However, the data showed that the complication rate was much higher in the EVE-assisted group.

PMID:34930704 | DOI:10.1016/j.bjps.2021.11.032

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Reconstruction of midline abdominal defects with a deep inferior epigastric artery keystone-type perforator flap

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J Plast Reconstr Aesthet Surg. 2021 Dec 7:S1748-6815(21)00650-1. doi: 10.1016/j.bjps.2021.11.103. Online ahead of print.

NO ABSTRACT

PMID:34930700 | DOI:10.1016/j.bjps.2021.11.103

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Knockdown of circular RNA hsa_circ_0062270 suppresses the progression of melanoma via downregulation of CDC45

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Histol Histopathol. 2021 Dec 21:18412. doi: 10.14670/HH-18-412. Online ahead of print.

ABSTRACT

BACKGROUND: Although systemic therapies for melanoma have been improved, the 5-year survival rate of this aggressive cancer remains poor. It has been shown that hsa_circ_0062270 was upregulated in patients with melanoma. However, the relevant mechanism of hsa_circ_0062270 in the progression of melanoma remains unclear.

METHODS: The CCK-8, EdU staining, flow cytometry, and transwell assays were used to determine the viability, proliferation, apoptosis and invasion in melanoma cells. An in vivo animal study was performed finally.

RESULTS: The level of hsa_circ_0062270 was significantly upregulated in melanoma cells. In addition, hsa_circ_0062270 knockdown markedly inhibited the viability, proliferation, invasion and promoted the apoptosis of melanoma cells. Cell division cycle protein 45 (CDC45) is the host gene of hsa_circ_0062270 , and downregulation of hsa_circ_0062270 notably decreased the expression of CDC45 in melanoma cells. Rescue assays confirmed that hsa_circ_0062270 regulated the growth of melanoma cells through CDC45. Moreover, RIP analysis showed that hsa_circ_0062270 interacted with RNA-binding protein (RBP) EIF4A3. Furthermore, in vivo study indicated that knockdown of hsa_circ_0062270 inhibited the melanoma tumor growth in vivo.

CONCLUSIONS: Downregulation of hsa_circ_0062270 can inhibit the progression of melanoma through downregulation of CDC45. Our findings provide biological mechanisms for the use of hsa_circ_0062270 as a biomarker for melanoma and potential therapeutic target.

PMID:34931691 | DOI:10.14670/HH-18-412

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