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Τετάρτη 2 Ιουνίου 2021

Clinical and surgical factors affecting the prognosis and survival rates in patients with mucormycosis

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Eur Arch Otorhinolaryngol. 2021 Jun 1. doi: 10.1007/s00405-021-06910-6. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the factors affecting disease specific mortality (DSM) in patients with mucormycosis.

METHODS: This retrospective study included 24 patients diagnosed with mucormycosis and who had undergone surgical and medical treatment between 2010 and 2020. There were 14 male and 10 female patients whose mean age was 53.70 ± 16.87 years, range 18-83. We reviewed the factors affecting DSM, including the extent of disease (paranasal sinus, palatal, orbital or intracranial involvement) and blood parameters (BP) that are serum glucose level (SGL), white blood cell, neutrophil, lymphocyte counts, C-reactive protein and hemoglobulin levels. Also, the effect of SGL in diabetes mellitus and BP in hematological malignancies on DSM was additionally evaluated.

RESULTS: Orbital (p = 0.001) and intracranial (p < 0.01) i nvolvement had statistically significant effect on DSM but not the palatal involvement. When Cox regression analysis was employed to analyze the effect of multiple independent factors on DSM, only the extent of disease (p = 0.023) had statistically significant effect. Receiver operating characteristic analysis of SGL for diabetic patients demonstrated that the area under the curve was 0.917 (p = 0.016). A cut-off SGL of 360 mg/dl revealed an 83.3% sensitivity and 83.3% specificity for mortality outcome for diabetic patients having mucormycosis.

CONCLUSION: Orbital or cerebral involvement is related to a poor prognosis, so early endoscopic nasal examination, diagnosis and treatment are of vital importance for DSM in mucormycosis. Serum glucose level over 360 mg/dl in uncontrolled diabetic patients with fever, ophthalmological findings and facial hypoesthesia should necessitate a consultation to an otolaryngologist and an endoscopic careful nasal examination.

PMID:34075487 | DOI:10.1007/s00405-021-06910-6

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Risk factors of lymphovascular invasion in hypopharyngeal squamous cell carcinoma and its influence on prognosis

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Eur Arch Otorhinolaryngol. 2021 Jun 2. doi: 10.1007/s00405-021-06906-2. Online ahead of print.

ABSTRACT

PURPOSE: Lymphatic vascular invasion (LVI) is a poor prognostic factor for hypopharyngeal squamous cell carcinoma (HPSCC), but the risk factors of LVI and its relationship with clinicopathological of HPSCC remain unclear. This study aims to explore these issues.

METHODS: We retrospectively analyzed the clinicopathological data of 170 patients with HPSCC from January 2011 to December 2015. The relationship between LVI and clinicopathologic was analyzed by Chi-square test or Fisher's exact test. The risk factors of LVI were examined using a logistic regression model, while risk factors of survival rate were carried out using the Cox regression model.

RESULTS: LVI occurred in 59 cases (34.7%). In multivariate analysis, T3-4 stage (HR = 2.877; 95% CI: 1.379-6.004; p = 0.005), N2-3 stage (HR = 2.325; 95% CI: 1.120-4.824; p = 0 .024), and poor differentiation (HR = 2.983; 95% CI: 1.229-7.242; p = 0.016) were independent risk factors for LVI; positive LVI was an independent risk factor for local recurrence (HR = 2.488; 95% CI: 1.150-5.383; p = 0.021), poor 5-year OS (HR = 0.375; 95% CI: 0.232-0.606; p < 0.000), DSS (HR = 0.374; 95% CI: 0.235-0.595; p < 0.000), and DFS (HR = 0.454; 95% CI:0.254-0.813; p = 0.008).

CONCLUSION: T3-4 stage, N2-3 stage and poor differentiation are independent risk factors for LVI of HPSCC; LVI increases the local recurrence and regional recurrence rate, and decreases 5-year OS, DFS and DSS of HPSCC.

PMID:34076727 | DOI:10.1007/s00405-021-06906-2

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Δευτέρα 31 Μαΐου 2021

Cascades between miRNAs, lncRNAs and the NF-κB signaling pathway in gastric cancer (Review)

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Exp Ther Med. 2021 Jul;22(1):769. doi: 10.3892/etm.2021.10201. Epub 2021 May 17.

ABSTRACT

Gastric cancer is a common digestive tract malignancy that is mainly treated with surgery combined with perioperative adjuvant chemoradiotherapy and biological targeted therapy. However, the diagnosis rate of early gastric cancer is low and both postoperative recurrence and distant metastasis are thorny problems. Therefore, it is essential to study the pathogenesis of gastric cancer and search for more effective means of treatment. The nuclear factor-κB (NF-κB) signaling pathway has an important role in the occurrence and development of gastric cancer and recent studies have revealed that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are able to regulate this pathway through a variety of mechanisms. Understanding these interrelated molecular mechanisms is helpful in guiding improvements in gastric cancer treatment. In the present review, the functional associations between miRNAs, lncRNAs and the NF-κB signaling pathway in the occurrence, development and prognosis of gastric cancer were discussed. It was concluded that miRNAs and lncRNAs have complex relations with the NF-κB signaling pathway in gastric cancer. miRNAs/target genes/NF-κB/target proteins, signaling molecules/NF-κB/miRNAs/target genes, lncRNAs/miRNAs/NF-κB/genes or mRNAs, lncRNAs/target genes/NF-Κb/target proteins, and lncRNAs/NF-κB/target proteins cascades are all important factors in the occurrence and development of gastric cancer.

PMID:34055068 | PMC:PMC8145527 | DOI:10.3892/etm.2021.10201

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Etomidate attenuates hyperoxia-induced acute lung injury in mice by modulating the Nrf2/HO-1 signaling pathway

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Exp Ther Med. 2021 Jul;22(1):785. doi: 10.3892/etm.2021.10217. Epub 2021 May 19.

ABSTRACT

The present study aimed to investigate the protective effects of etomidate on hyperoxia-induced acute lung injury in mice, particularly on the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. Fifty specific pathogen-free mice were randomly divided into the blank control, model, high oxygen exposure + low etomidate dose (0.3 mg·kg-1), a high oxygen exposure + moderate etomidate dose (3 mg·kg-1), and a high oxygen exposure + high etomidate dose (10 mg·kg-1) groups, with ten mice allotted per group. After 72 h, the mice were sacrificed and the lung tissues were harvested, and the wet-to-dry (W/D) ratio of the tissues was calculated. Hematoxylin-eosin staining was performed to observe the pathological changes in the lung tissues, and the lung injury score (LIS) was calculated. The mRNA and protein expression levels of Nrf2 and HO-1 were measured. The malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) levels were also measured, and interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α) and IL-10 concentrations in the bronchoalveolar lavage fluid were determined. At low and moderate doses, etomidate decreased pathological damage in the lung tissue, decreased the LIS and W/D ratio, upregulated Nrf2 and HO-1 mRNA and protein expression, decreased IL-1β, IL-6, and TNF-α concentrations, increased MPO activity and IL-10 levels, suppressed the production of the oxidation product MDA, and enhanced the activities of the antioxidant enzymes CAT and SOD. Within a certain dose range, etomidate enhanced antioxidant and anti-inflammatory effects in mice, thereby decreasing lung injury induced by the chronic inhalation of oxygen at high concentrations. Furthermore, the underlying mechanism may be associate with the upregul ation of the Nrf2/HO-1 signaling pathway.

PMID:34055084 | PMC:PMC8145798 | DOI:10.3892/etm.2021.10217

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Inhibition of the Wnt/β-catenin signaling pathway reduces autophagy levels in complement treated podocytes

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Exp Ther Med. 2021 Jul;22(1):737. doi: 10.3892/etm.2021.10169. Epub 2021 May 9.

ABSTRACT

In idiopathic membranous nephropathy, the complement membrane attack complex, more commonly referred to as complement 5b-9 (C5b-9), induces glomerular epithelial cell injury and proteinuria. C5b-9 can also activate numerous mechanisms that restrict or facilitate injury. Recent studies suggest that autophagy and the canonical Wnt signaling pathway serve an important role in repairing podocyte injury. However, the effect of C5b-9 on these pathways and the relationship between them remains unclear. The aim of the present study was to show the effect of C5b-9 on the Wnt/β-catenin signaling pathway and autophagy in podocytes in vitro. Levels of relevant indicators were detected by immunofluorescence staining and capillary western immunoassay. C5b-9 serum significantly activated the Wnt/β-catenin signaling pathway and promoted autophagy. Treatme nt with Dickkopf-related protein 1 (DKK1), a Wnt/β-catenin pathway blocker, protected podocytes from injury and significantly inhibited autophagy. The results indicated that inhibition of the Wnt/β-catenin pathway physiologically activated autophagy. The results indicated that C5b-9 resulted in a decrease in Akt in podocytes. However, the podocytes preincubated with DKK1 and then attacked by C5b-9 showed an increase in Akt levels. This may explain the observation that blocking the Wnt/β-catenin signaling pathway attenuated C5b-9 podocyte damage, while inhibiting autophagy. The results of the present study also suggest that regulation of these two pathways may serve as a novel method for the treatment of idiopathic membranous nephropathy.

PMID:34055054 | PMC:PMC8138266 | DOI:10.3892/etm.2021.10169

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Comparison of modified corneal cross-linking with intrastromal voriconazole for the treatment of fungal corneal ulcer

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Exp Ther Med. 2021 Jul;22(1):786. doi: 10.3892/etm.2021.10218. Epub 2021 May 21.

ABSTRACT

The present study aimed to evaluate the efficacy of modified corneal cross-linking (CXL) for the treatment of fungal corneal ulcers compared with that following intrastromal voriconazole injection. In total, 31 patients with fungal corneal ulcers treated at The General Hospital of Northern Theater Command between October 2017 and October 2019 were enrolled. Among them, 10 eyes were treated with ultraviolet A (UV-A)/riboflavin CXL (CXL group), whilst 21 eyes were treated with debridement combined with intrastromal voriconazole (stromal injection group). Preoperative microbiological examination was performed in both groups, and evaluated using Fisher's exact test. Postoperatively, infection control and total efficacy rates, localized lesion, ulcer healing rate 1 week after surgery, visual acuity and complications were evaluated using Fisher's exact test, however visual acuity was analyzed by mixed-model ANOVA. The results showed that the pre-operative species distribution between the CXL and stromal injection groups did not significantly differ. The infection control rate in the CXL group was notably higher compared with that in the stromal injection group (P=0.04). Furthermore, the total efficacy rate in the CXL group was also markedly higher compared with that in the stromal injection group, though no statistically significant differences were observed. Localized lesions were observed in nine eyes (90.0%) in the CXL group and nine eyes (42.9%) in the stromal injection group (P=0.02). However, the rate of ulcer healing at 1 week postoperatively and the logarithm of the minimum angle of resolution (logMAR) of visual acuity were not found to be significantly different between the two groups. In terms of complications, with the exception of one patient in the CXL group exhibiting loss of corneal transparency and one patient in t he stromal injection group presenting with partial corneal thinning, no other forms of complications were observed. In conclusion, the present study suggested that CXL could have a beneficial impact for treating fungal corneal ulcers in the aspects of infection control, localized lesions and accelerated epithelialization. In addition, except the loss of corneal transparency, this treatment approach could be applied with reduced risks of adverse events.

PMID:34055085 | PMC:PMC8145909 | DOI:10.3892/etm.2021.10218

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Comparative hematological profiles for dose-dense vs. regular anthracycline-based neoadjuvant chemotherapy in non-metastatic breast cancer

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Exp Ther Med. 2021 Jul;22(1):747. doi: 10.3892/etm.2021.10179. Epub 2021 May 11.

ABSTRACT

The aim of the present study was to examine both the feasibility and toxicity of neoadjuvant dose-dense chemotherapy in women with non-metastatic breast cancer. A search within the OncoHelp Association breast cancer database has been performed in order to identify all non-metastatic breast cancer patients who underwent an initial consultation with a medical oncologist between March 2016 and April 2020. The inclusion criteria used were: i) Age, ii) follow-up care obtained at OncoHelp Association, iii) the intent to treat with a neoadjuvant dose-dense anthracycline every two weeks for four cycles (C1-C4) followed by paclitaxel every two weeks for four cycles, with white blood cell growth factor support, and iv) regular anthracycline-based chemotherapy every three weeks for four cycles, followed by paclitaxel every three weeks for four cycles, v) wei ght, vi) height, vii) Eastern Cooperative Oncology Group (ECOG) performance status, viii) hemoglobin (Hb) level, ix) Platelet count and x) neutrophil count.

PMID:34055062 | PMC:PMC8138269 | DOI:10.3892/etm.2021.10179

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Modulated electro-hyperthermia with weekly paclitaxel or cisplatin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: The KGOG 3030 trial

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Exp Ther Med. 2021 Jul;22(1):787. doi: 10.3892/etm.2021.10219. Epub 2021 May 21.

ABSTRACT

The present study (KGOG 3030) aimed to evaluate the safety of modulated electro-hyperthermia (mEHT) therapy with weekly administration of paclitaxel or cisplatin in female patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma. A total of 12 patients were randomized into the paclitaxel or cisplatin arm at a 1:1 ratio. Patients received weekly administration of paclitaxel (70 mg/m2) or cisplatin (40 mg/m2) intravenously on days 1, 8 and 15, and underwent mEHT therapy for 1 h on days 1, 4, 8, 11, 15, 18, 21 and 24 for each 4-week cycle. The primary endpoint was the occurrence of dose-limiting toxicity (DLT). The secondary endpoints were treatment-emergent adverse events (TEAEs), objective response rate, carbohydrate antigen 125 (CA125) response rate, progression-free survival (P FS) and overall survival (OS). In total, 16 patients were recruited, but four patients dropped out. None of the 12 remaining patients (6 each in the two arms) experienced DLT. Overall, 0 and 4 grade 3 TEAEs (anemia, nausea, neutrophil count decreased and platelet count decreased) occurred in the paclitaxel and cisplatin arm, respectively. Furthermore, one confirmed partial response and two CA125 responses were observed in the cisplatin arm. The median PFS time in the paclitaxel and cisplatin arms was 3.0 months (range, 1.7-4.6 months) and 6.8 months (range, 3.9-11.8 months), respectively, while the median OS time was 11.5 months (range, 8.4-28.8+ months) and not reached (range, 3.9-38.5+ months), respectively. In conclusion, mEHT therapy with weekly paclitaxel or cisplatin appeared safe and warrants further investigation. The present trial was registered with www.clinicaltrials.gov on January 22, 2015 (trial registration no. NCT02344095).

PMID:34055086 | PMC:PMC8145814 | DOI:10.3892/etm.2021.10219

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Effects of propofol on the proliferation and migration of liver cancer cells

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Exp Ther Med. 2021 Jul;22(1):733. doi: 10.3892/etm.2021.10165. Epub 2021 May 9.

ABSTRACT

Liver cancer is a malignant cancer with worldwide prevalence. It has been reported that cancer cells are usually exposed to a hypoxic microenvironment, which is associated with a poor prognosis in patients with cancer. Propofol is an intravenous anesthetic that is widely used in cancer surgery. The present study aimed to determine the effects of propofol stimulation on the viability, proliferation and migration of liver cancer cells under normoxia and cobalt chloride (CoCl2)-induced hypoxia. Under normoxia, HepG2 and HCCLM3 cells were randomly divided into six groups as follows: i) Control group; ii) 10 µM propofol group; iii) 25 µM propofol group; iv) 50 µM propofol group; v) 100 µM propofol group; and vi) DMSO group. Cell viability and proliferation were analyzed using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays, respectively, following 24 or 48 h of propofol treatment. In addition, wound healing and Transwell migration assays were used to determine the changes in cell migration. Under CoCl2-induced hypoxia, the protein levels of hypoxia inducible factor-1α (HIF-1α) of HepG2 cells were analyzed using western blotting. Subsequently, CCK-8 and wound healing assays were used to determine the effect of propofol on cell viability and migration. The results of the present study revealed that propofol stimulation had no significant effect on the viability, proliferation and migration of HepG2 and HCCLM3 cells under normoxia. The protein levels of HIF-1α were significantly upregulated following the treatment with 200 µM CoCl2 for 12 h. However, no significant differences were found in the viability and migration of HepG2 cells following the stimulation with propofol in the presence of CoCl2. In conclusion, the findings of the present study revealed that propofol exerted no effect on the viability, proliferation and migration of HepG2 and HCCLM3 cells under normoxic and hypoxic conditions.

PMID:34055050 | PMC:PMC8138278 | DOI:10.3892/etm.2021.10165

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Oncogenic role of epithelial cell transforming sequence 2 in lung adenocarcinoma cells

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Exp Ther Med. 2021 Jul;22(1):788. doi: 10.3892/etm.2021.10220. Epub 2021 May 21.

ABSTRACT

[This retracts the article DOI: 10.3892/etm.2016.3584.].

PMID:34055087 | PMC:PMC8145908 | DOI:10.3892/etm.2021.10220

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