Curcumin inhibits propofol-induced autophagy of MN9D cells via Akt/mTOR/p70S6K signaling pathway.

The rapid rise in propofol dependency and abuse has highlighted limited resources for addressing substance abuse-related cognitive impairment, prompting the development of novel therapies. Dysregulated autophagy flow accelerates neuronal cell death, and interventions countering this dysregulation offer an appealing strategy for neuronal protection. Curcumin, a potent natural polyphenol derived from turmeric rhizomes, is renowned for its robust antineurotoxic properties and enhanced cognitive function. Utilizing CCK-8 and Ki67 fluorescent staining, our study revealed that curcumin treatment increased cell viability and proliferative potential in MN9D cells exposed to propofol-induced neurotoxicity. Furthermore, enzyme-linked immunosorbent assay and western blot analysis demonstrated the partial restoration of dopamine synthesis, secretion levels, and TH expression in damaged MN9D cells treated with curcumin. Scanning electrode microscope images displayed reduced autolysosomes and phagosomes in curcumin-treated cells compared to the propofol group. Immunoblotting revealed that curcumin mitigated the degradation of LC3I to LC3II and p62 induced by propofol stimulation, with green fluorescence expression of LC3 postcurcumin treatment resembling that following autophagy inhibitor HCQ treatment, indicating that modulating autophagy flow can alleviate propofol's toxic effects. Moreover, curcumin treatment upregulated the Akt/mTOR/p70S6K signaling pathway, suggesting that curcumin potentially curtails autophagy dysregulation in nerve cells by activating Akt/mTOR/p70S6K. In conclusion, our findings suggest that curcumin can ameliorate propofol abuse-induced neurotoxicity, partially through autophagy regulation and Akt/mTOR/p70S6K signaling activation.

Stage IIB-IVA cervix carcinoma in elderly patients treated with radiation therapy: a longitudinal cohort study by propensity score matching analysis.

OBJECTIVE: We aimed to evaluate the treatment modality and prognostic impact of the age at diagnosis on stage IIB-IVA cervix carcinoma (CC) patients who received radiotherapy (RT).The evaluation was performed using the Surveillance, Epidemiology, and End Results (SEER) database. PATIENTS AND METHODS: From the SEER database, we included the patients with a histopathological diagnosis of CC between 2004 and 2016. Subsequently, we compared the treatment outcomes between patients aged ≥ 65 years (OG) and < 65 years (YG) by propensity score matching (PSM) analysis and Cox proportional hazard regression models. RESULTS: The data of 5,705 CC patients were obtained from the SEER database. We observed that the OG patients were significantly less likely to receive chemotherapy, brachytherapy, or combination treatment compared to the YG (P < 0.001). Further, the advanced age at diagnosis was an independent prognostic factor associated with decreasing overall survival (OS) before and after PSM. Even in the subgroup analysis of patients who received trimodal therapy, an advanced age had a significant negative impact on OS compared to their younger counterparts. CONCLUSION: Advanced age is associated with less aggressive treatment regimens and is independently associated with impaired OS for stage IIB-IVA CC patients who received RT. Hence, future studies should incorporate geriatric assessment into clinical decision-making to select appropriate and effective treatment strategies for elderly CC patients.

Trends and predictors of survival for small cell carcinoma of the cervix uteri: A SEER population study.

OBJECTIVE: Small cell carcinoma of the cervix uteri (SCCC) is an uncommon cancer associated with unsatisfactory survival outcomes. We aimed to investigate the incidence and prognostic factors of survival in SCCC patients using the Surveillance, Epidemiology, and End Results database. METHODS: Eligible patients with histopathologic diagnoses of SCCC were identified between 2004 and 2015. Overall survival (OS) and cause-specific survival (CSS) for the included patients were calculated using the Kaplan-Meier method. Univariate and multivariate analyses of clinical factors were performed using Cox proportional hazard regression models. RESULTS: We identified 272 SCCC patients based on predefined criteria. The average incidence of SCCC was 1.01 % per year between 2004 and 2015. The median OS and CSS were 17.0 and 19.0 months, respectively, accompanying with 5-year OS rate was 26.3 % and 5-year CSS rate was 30.1 %. In the multivariate analysis, advanced age (age ≥ 65 years old), late FIGO stage, surgery at the primary site, radiotherapy (RT) and chemotherapy (CT) were strong prognostic factors for OS. The corresponding variables for CSS were: advanced age, late FIGO stage, RT and CT. In the subgroup analysis for nonsurgical management of SCCC, the combination of RT and CT provided the best survival outcomes when compared with other therapeutic modalities. Again, advanced age was interrelated to worse survival outcomes for both OS and CSS. CONCLUSIONS: SCCC is an infrequent disease with aggressive nature, which lead to poor survival outcomes. In addition to other known parameters, advanced age is a strong predictive factor for OS and CSS. The combination of RT and CT was the best therapeutic strategy for patients who received nonsurgical management.

High-sensitivity modified Glasgow prognostic score (HS-mGPS) Is superior to the mGPS in esophageal cancer patients treated with chemoradiotherapy.

The present study compared the prognostic value of the modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) in unresectable locally advanced esophageal squamous cell carcimona (LAESCC) patients treated with concurrent chemoradiotherapy (CCRT). The baseline data of 163 eligible patients were retrospectively collected. Patients with a C-reactive protein (CRP) ≤ 10 mg/l and albumin ≥ 35 g/l were allocated to mGPS-0 group. Patients with only elevated CRP (> 10 mg/l) were assigned to mGPS-1 group. Patients who had both elevated CRP (> 10 mg/l) and hypoalbuminurea (< 35 g/l) were assigned to mGPS-2 group. The HS-mGPS was calculated based on cutoff values of 3mg/l for CRP and the same value (35 g/l) for albumin. Prognostic significance for both tumor response and overall survival (OS) was analyzed by univariate and multivariate analysis. The mGPS was 0 in 95 patients, 1 in 28 patient and 2 in 40 patients. In contrast, the HS-mGPS was 0 in 66 patients, 1 in 47 patients and 2 in 50 patients. In multivariate analysis, the HS-mGPS was the only positive factor for tumor response (P = 0.015). Both the mGPS (P < 0.001) and HS-mGPS (P < 0.001) were good prognostic predictors for OS. However, the HS-mGPS was found to be a superior prognostic predictor compared to the mGPS in a multivariate analysis (P = 0.006). In conclusion, the pretreatment HS-mGPS is a strong prognosticator superior to the mGPS for both tumor response and OS in LAESCC patients who received CCRT.

Pretreatment nutritional risk scores and performance status are prognostic factors in esophageal cancer patients treated with definitive chemoradiotherapy.

This study evaluated the prognostic effects of nutritional risk scores and performance status (PS) on unresectable locally advanced esophageal cancer (LAEC) patients who were treated with definitive concurrent chemoradiotherapy (dCRT). A total of 202 LAEC patients from four different cancer centers were retrospectively reviewed. Nutritional risk and PS were measured using the Nutritional Risk Screening 2002 (NRS-2002) scores and Eastern Cooperative Oncology Group (ECOG) scales. Outcomes were clinical response rate, overall survival (OS) and progression-free survival (PFS). Multivariate analysis of predictive factors of response to dCRT and survival were performed using a logistic regression and a Cox model, respectively. The majority of patients (71.8%) had an ECOG PS score of 0-1, and 52.5% (n=106) of patients were identified as having nutritional risk (NRS-2002 ≥3) upon treatment initiation. There was no correlation between NRS-2002 scores and ECOG PS (Spearman's ρ=0.046; P=0.516). In multivariate analysis, NRS-2002 scores (P=0.002, HR 2.805, 95%CI: 1.445-5.446) and ECOG PS (P=0.015, HR 2.719, 95%CI: 1.218-6.067) were independent prognostic factors for the response to dCRT. NRS-2002 scores (OS: HR 1.530, 95%CI 1.059-2.209; P=0.023; PFS: HR 1.517, 95%CI 1.105-2.082; P=0.010) and ECOG PS (OS: HR 1.729, 95%CI 1.185-2.522; P=0.005; PFS: HR 1.678, 95%CI 1.179-2.387; P=0.004) were both independent prognostic factors for OS and PFS. In conclusions, NRS-2002 scores and ECOG PS scales both have prognostic effects on clinical response and survival in LAEC, but a significant association of NRS-2002 scores and ECOG PS were not observed.

Comparative transcriptome analysis of the global circular RNAs expression profiles between SHEE and SHEEC cell lines.

Esophageal squamous cell carcinoma (ESCC) is widely regarded as one of the most lethal types of cancer around the world. The fact that early detection of ESCC could dramatically improve the treatment outcome of the patients has sparked considerable interest in searching for reliable and accurate diagnostic biomarkers. Recently, circular RNAs (circRNA) have emerged as a new type of non-coding RNAs with significant RNase resistance, wide abundance and remarkable internal diversity. There is also increasing evidence suggesting that circRNAs could be implicated in the pathogenesis of cancer and other diseases. In this study, we performed a comparative analysis of the global circRNA expression profiles in normal and malignant esophageal epithelial cell lines by a combination of RNA sequencing and bioinformatics analysis. We identified 813 significantly up-regulated and 445 down-regulated circRNA candidates, of which 32 were subsequently validated by quantitative real-time reverse transcription polymerase chain reaction analysis. The differentially expressed circRNAs were found to be associated with pathways involved in metabolism, cell apoptosis, proliferation and migration, which are commonly altered in cancer cells. Based on the obtained data, we constructed a circRNA-miRNA interaction network, in which circRNA9927-NBEAL1 represented the biggest node. Our study could lay the groundwork for further investigation concerning the pathological roles of circRNAs in ESCC.

Sequence variations of mitochondrial DNA D-loop region are associated with familial nasopharyngeal carcinoma.

Mitochondrial DNA (mtDNA) D-loop has been identified as a frequent hot spot of mutations in various tumors. The aim here was to investigate the sequence variations of mitochondrial D-loop region in familial nasopharyngeal carcinoma (FNPC) and their possible associations with cancer risk. 29 subjects from 4 Chinese NPC families and 20 sporadic NPC as well as 122 cases of normal control were recruited. mtDNA extracted from peripheral blood was examined by PCR-based assay for D-loop sequence variations, followed by sequencing analysis. Compared with normal control, four high variations and 6 unrepoted novel polymorphisms were found. Particularly, the np16362 and 16519T to C variants show significantly higher (100%, 81.8%) and lower (0, 22.7%) frequencies in FNPC and unaffected pedigree members, respectively. The occurrence of mitochondrial microsatellite instability (mtMSI) at D310 in experimental groups was statistically significantly higher than in normal control (53.3%). Likewise, in Base Variation Rate consistent with the result, there was a statistically significant difference compared with NC (6.05%). Our results indicated that mtDNA exhibited a high rate of sequence variants in patients with NPC and pedigree members and the mtDNA np16362, np16519 variants and mtMSI at D310 are associated with an increased risk of familial nasopharyngeal carcinoma in pedigree members from families with NPC, which might be involved in the NPC carcinogenesis.

The role of replanning in fractionated intensity modulated radiotherapy for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Anatomic changing frequently occurred during fractionated radiotherapy. The aims of this study were to model the potential benefit of adaptive IMRT replanning during fractionated radiotherapy and its potential advantage over clinical outcome in patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: Thirty-three patients with repeat CT imaging and replanning were retrospectively analyzed. 66 case-matched control patients without replanning were identified by matching for AJCC stage, gender, and age. Hybrid IMRT plans were generated to evaluate the dosimetric changing. Mann-Whitney-Wilcoxon tests were used to evaluate the effect of replanning on volumetric and dosimetric outcomes within individuals. Kaplan-Meier estimators were used to estimate the survival function of patients with or without replanning. RESULTS: The mean volume of the ipsilateral and contralateral parotid glands decreased during the treatment. The hybrid IMRT plans showed decreased doses to target volumes and increased doses to normal structures in replanning. The clinical outcome comparison indicated that the IMRT replanning improved the 3 years local progression-free survival for patients who had AJCC staged more than T(3) (T(3,4)N(x)) and ease the late effects for patients who had large lymph nodes (AJCC stage T(x)N(2,3)). CONCLUSION: Repeat CT imaging and IMRT replanning were recommendatory for specific nasopharyngeal carcinoma patients.