Nonpharmacological Interventions for Management of the Pain-Fatigue-Sleep Disturbance Symptom Cluster in Breast Cancer Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: The pain-fatigue-sleep disturbance symptom cluster is commonly experienced by breast cancer patients, and a variety of nonpharmacological interventions are used to treat this symptom cluster. Objective: To compare the efficacy of nonpharmacological interventions in improving the symptoms of the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients. Methods: A comprehensive literature search was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL, CNKI, and Wanfang databases to identify randomized controlled studies from database inception to May 2022. Two reviewers independently performed data retrieval and risk of bias assessments. The consistency model was used to conduct network meta-analyses (NMA) based on the frequentist framework to assess the interventions, which were ranked by the surface under the cumulative ranking curve (SUCRA). Finally, the CINeMA application was used to evaluate the results of the NMA and the evidence of quality. The results Twenty-three eligible studies assessing 14 interventions were included. According to SUCRA values, among the management effects of the three symptoms, the effect of progressive muscle relaxation (PMR) ranked first, followed by mindfulness-based stress reduction (MBSR). The overall evidence quality of our study ranges from very low to moderate. Conclusion: PMR and MBSR were effective interventions for the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients. Clinical recommendations prioritize PMR for symptom management, followed by MBSR. However, this should be interpreted cautiously, as the confidence in the evidence was not high.

Nomogram models for the prognosis of cervical cancer: A SEER-based study.

Background: Cervical cancer (CC) is one of the most common cancers in women. This study aimed to investigate the clinical and non-clinical features that may affect the prognosis of patients with CC and to develop accurate prognostic models with respect to overall survival (OS) and cancer-specific survival (CSS). Methods: We identified 11,148 patients with CC from the SEER (Surveillance, Epidemiology, and End Results) database from 2010 to 2016. Univariate and multivariate Cox regression models were used to identify potential predictors of patients' survival outcomes (OS and CSS). We selected meaningful independent parameters and developed nomogram models for 1-, 3-, and 5-year OS and CSS via R tools. Model performance was evaluated by C-index and receiver operating characteristic curve. Furthermore, calibration curves were plotted to compare the predictions of nomograms with observed outcomes, and decision curve analysis (DCA) and clinical impact curves (CICs) were used to evaluate the clinical effectiveness of the nomograms. Results: All eligible patients (n=11148) were randomized at a 7:3 ratio into training (n=7803) and validation (n=3345) groups. Ten variables were identified as common independent predictors of OS and CSS: insurance status, grade, histology, chemotherapy, metastasis number, tumor size, regional nodes examined, International Federation of Obstetrics and Gynecology stage, lymph vascular space invasion (LVSI), and radiation. The C-index values for OS (0.831 and 0.824) and CSS (0.844 and 0.841) in the training cohorts and validation cohorts, respectively, indicated excellent discrimination performance of the nomograms. The internal and external calibration plots indicated excellent agreement between nomogram prediction and actual survival, and the DCA and CICs reflected favorable potential clinical effects. Conclusions: We constructed nomograms that could predict 1-, 3-, and 5-year OS and CSS in patients with CC. These tools showed near-perfect accuracy and clinical utility; thus, they could lead to better patient counseling and personalized and tailored treatment to improve clinical prognosis.

Lidocaine Ameliorates Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats through Modulating the c-Jun Signaling Pathway.

As one of the common complications of diabetes mellitus (DM), Diabetic Peripheral Neuropathy (DPN) threatens human lives seriously. Emerging evidences have confirmed the protective effects of lidocaine on DPN. However, the possible role and underlying mechanisms of lidocaine in DPN have not been clarified. In this study, the potential role of lidocaine in DPN is explored, and the possible mechanisms are investigated. The rat DPN model is constructed through administration of streptozotocin (STZ, 60 mg/kg). All rats are randomly divided into four groups, including the control group, DPN group, lidocaine (3.78 mg/time) group, and lidocaine combined with the SP600125 (15 mg/kg) group. Mechanical threshold, thermal latency, and blood glucose of rats before and after treatment are detected, and Nerve Conduction Velocity (NCV) is assessed. Moreover, qRT-PCR and western blot assays are carried out to determine the expressions of the c-Jun signaling pathway. The experimental results demonstrate that lidocaine remarkably downregulates the mRNA and protein expressions of the c-Jun signaling pathway in serum and DRGs induced with DPN. Besides, lidocaine combined with SP600125 can obtain better effects than lidocaine alone. It is clearly evident that lidocaine has a certain therapeutic effect on DPN.

Predicted CD4+ T cell infiltration levels could indicate better overall survival in sarcoma patients.

OBJECTIVE: The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations. METHODS: Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined. RESULTS: Levels of CD4+ T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4+ T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4+ T cell infiltration levels. CONCLUSIONS: This data mining study indicated that CD4+ T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4+ T cells infiltration indicated a better chance of survival.

Comparison of the survival outcome of neoadjuvant therapy followed by radical surgery with that of concomitant chemoradiotherapy in patients with stage IB2-IIIB cervical adenocarcinoma.

PURPOSE: To compare the survival outcome of neoadjuvant therapy (NAT) (chemotherapy or chemotherapy and intracavitary brachytherapy (ICBT) followed by radical surgery and of concomitant chemotherapy and radiotherapy (CCRT) in patients with locally advanced cervical adenocarcinoma and identify predictors of cervical adenocarcinoma. METHODS: We retrospectively reviewed our medical records of cervical adenocarcinoma patients treated with either NAT + surgery or CCRT in our institution from January 2013 to December 2017. The patients were treated with two-dimensional radiotherapy or three-dimensional-conformal or intensity-modulated radiotherapy combined with intracavitary brachytherapy. The regimen of concomitant chemotherapy was weekly cisplatin. The neoadjuvant chemotherapy (NACT) was paclitaxel plus cisplatin. The primary end points were overall survival (OS) and progression-free survival (PFS). RESULTS: We enrolled 121 patients. There were 42 (34.7%) patients in the NAT + surgery group and 79 (65.3%) in the CCRT group. After univariate multivariate analysis, NAT was an independent predictor of OS (p = 0.008) and PFS (p = 0.006). After propensity score matching, the 5-year OS rates in the NAT + surgery and CCRT groups were 25% and 4%, respectively (p = 0.00014), and the 5-year PFS rates were 25% and 4%, respectively (p = 0.00015). Subgroup analysis showed that the 5-year OS and PFS rates in the NACT + surgery and CCRT groups were both 20% and 8%, respectively (p = 0.015). CONCLUSION: Compared with CCRT, NAT followed by radical surgery had better OS and PFS in locally advanced cervical adenocarcinoma. In subgroup analysis, OS and PFS were longer for NACT + surgery than for CCRT.

Comparison of survival outcomes of locally advanced cervical cancer by histopathological types in the surveillance, epidemiology, and end results (SEER) database: a propensity score matching study.

BACKGROUND: There has been limited research on the comparison of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of cervical cancer and that lack of information may have significant bearing on the treatment of patients. We compared survival outcomes between squamous cell carcinoma and adenocarcinoma in locally advanced cervical cancer patients and examined factors related to the prognosis of cervical cancer. METHODS: We identified 4131 patients with stage IB2-IVA cervical cancer patients diagnosed between 2010 and 2015 by using the Surveillance, Epidemiology, and End Results (SEER) database. Variables related to the prognosis of cervical cancer were compared using both univariate and multivariate Cox models and log-rank method before and after propensity score matching. We compared the efficacy of radiotherapy alone to radiotherapy combined with chemotherapy or/and surgery in overall survival of SCC and AC. RESULTS: Our sample included 3385 patients with SCC (81.9%) and 746 patients with AC (18.1%). The 5-year overall survival on comparing the squamous cell carcinoma group and adenocarcinoma group was not significant (P > 0.05). Using propensity score matching, 676 pairs of patients were selected. The 5-year overall survival of matched patients did not differ significantly (P > 0.05). Histology was not independently associated with overall survival in multivariate Cox model (P > 0.05). Factors affecting overall survival included FIGO stage IVA (P < 0.05), chemotherapy (P < 0.05), and external radiation combined with brachytherapy (P < 0.05). Patients with SCC that were treated with radiation alone had significantly worse OS than AC patients receiving radiation only (P < 0.05). CONCLUSIONS: The OS in AC of the cervix is similar to that SCC in when treated with radiotherapy combined with chemotherapy and/or surgery but better when treated with radiation alone.

Long Noncoding RNA CRNDE/PRC2 Participated in the Radiotherapy Resistance of Human Lung Adenocarcinoma Through Targeting p21 Expression.

Long noncoding RNAs (lncRNAs), a new class of functional regulators involved in human tumorigenesis, have been attracting the increasing attention of researchers. The lncRNA colorectal neoplasia differentially expressed (CRNDE) gene, transcribed from chromosome 16 on the strand opposite the adjacent IRX5 gene, was originally found to be increased in CRC and was reported to be abnormally expressed in many cancers. However, its potential role and the molecular mechanism underlying the radioresistant phenotype formation of lung adenocarcinoma (LAD) remain unclear. In our present study, we identified that CRNDE was significantly upregulated in LAD tissue and radioresistant LAD cell lines. A high level of CRNDE expression was significantly correlated with poor differentiation, TNM stage, lymph node metastasis, radiotherapy response, and a significantly shorter overall survival. Gain- and loss-of-function tests revealed that CRNDE could influence the radiosensitivity of LAD cells by affecting the G1/S transition and causing apoptosis of LAD cells in vitro. Additionally, the mechanistic investigations showed that CRNDE could interact with PRC2 and recruit its core component EZH2 to p21 (CDKN1A) promoter regions and repress its transcription. Furthermore, rescue experiments were performed to confirm that CRNDE oncogenic function was partly through regulating p21. In conclusion, our data suggest that CRNDE may function as an oncogene by modulating p21, finally contributing to the radioresistant phenotype formation of LAD cells.

Microarray Analysis of Circular RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells.

Preoperative 5-fluorouracil- (5-FU-) based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, the effect of 5-FU-based chemoradiotherapy on CRC is limited due to the development of chemoradiation resistance (CRR), and the molecular mechanisms underlying this resistance are yet to be investigated. Recently, circular RNAs (circRNAs), which can function as microRNA sponges, were found to be involved in the development of several cancers. In this study, we focused on clarifying the modulation of the expression profiles of circRNAs in CRR. Microarray analysis identified 71 circRNAs differentially expressed in chemoradiation-resistant CRC cells. Among them, 47 were upregulated and 24 were downregulated by more than twofold. Furthermore, expression modulation of five representative circRNAs was validated by quantitative reverse transcription PCR (qRT-PCR). Moreover, these modulated circRNAs were predicted to interact with 355 miRNAs. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most modulated circRNAs regulate several cancers and cancer-related pathways, and the possible mechanism underlying CRR was discussed. This is the first report revealing the circRNA modulations in 5-FU chemoradiation-resistant CRC cells by microarray. The study provided a useful database for further understanding CRR and presents potential targets to overcome CRR in CRC.

MiR-424 Promotes Non-Small Cell Lung Cancer Progression and Metastasis through Regulating the Tumor Suppressor Gene TNFAIP1.

BACKGROUND/AIMS: This study aimed to investigate the potential roles of miR-424 expression in non-small cell lung cancer (NSCLC) metastasis and growth and its underlying mechanism. METHODS: The expression of miR-424 in two NSCLC cell lines (A549 and H1975) was altered by transfection with miR-424 mimic and inhibitor. Effects of miR-424 overexpression and suppression on cells migration, invasion and colony formation were analyzed. Target genes for miR-424 were predicted using bioinformatics method and then verified using luciferase assay. Effects of miR-424 expression on cell migration, invasion and proliferation were reanalyzed on the condition of TNFAIP1 was silenced. Moreover, TNFAIP1 silencing and miR-424 modified A549 cells were subcutaneous injected into node BALB/c mice to confirm the regulation of miR-424 on TNFAIP1 in regulating tumor growth. RESULTS: Compared with the control, miR-424 overexpression significantly increased the migrated and invaded cells, as well as the proliferated colonies. TNFAIP1 was a predicted target gene for miR-424, and was negatively regulated by miR-424. TNFAIP1 silence significantly increased the migrated and invaded cells compared to that in control, while these increases were abolished by miR-424 suppression. Animal experiment further evidenced miR-424 affected tumor growth by regulating TNFAIP1. CONCLUSIONS: These data demonstrate that miR-424 may be a contributor for NSCLC progression and metastasis through involving in cell migration, invasion and proliferation via inhibiting TNFAIP1. This study may provide theoretical basis for miR-424 in NSCLC target therapeutic treatment.

MDK Protein Overexpression Correlates with the Malignant Status and Prognosis of Non-small Cell Lung Cancer.

BACKGROUND AND AIMS: Midkine (MDK) is a heparin-binding growth factor and is overexpressed in various types of human cancer. However, little is known about the clinical significance of MDK in non-small cell lung cancer (NSCLC). The aim of this study was to measure MDK protein levels in patients with NSCLC and to explore its clinical significance. METHODS: The expression status of MDK in NSCLC at Gene Expression Omnibus (GEO accession number: GSE19804) was observed. The expression of MDK mRNA and protein was examined in NSCLC tissues and normal lung tissues through real-time PCR and Western blot. Meanwhile, the relationship of MDK protein expression levels with clinical characteristics of 186 NSCLC patients was analyzed by immunohistochemistry. RESULTS: MDK expression was increased in NSCLC tissues compared with paired normal lung tissues in microarray data (GSE19804). MDK mRNA and protein expression were obviously increased in NSCLC tissues than in paired adjacent normal lung tissues. Using immunohistochemistry, MDK protein overexpression was positively correlated with status of clinical stage, T classification, N classification, and M classification in NSCLC patients. In survival analysis, patients with higher MDK protein expression had a significantly shorter overall survival time than did patients with lower MDK protein expression. Multivariate analysis indicated that the MDK protein overexpression was an independent poor prognostic indicator for patients with NSCLC. CONCLUSIONS: MDK plays an important role in NSCLC progression and prognosis and may act as a convincing prognostic indicator for NSCLC patients.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells.

BACKGROUND: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. MATERIALS AND METHODS: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. RESULTS: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak- STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. CONCLUSIONS: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

Parecoxib: an enhancer of radiation therapy for colorectal cancer.

BACKGROUND: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. MATERIALS AND METHODS: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. RESULTS: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. CONCLUSIONS: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.

[The relationship between the expression of EGFR NF-kappaB and radiosensitivity in human nasopharyngeal carcinoma].

OBJECTIVE: To detect the expression of EGFR and NF-kappaB and the relationship between the two factors and radiosensitivity in human nasopharyngeal carcinoma. METHOD: The expression of EGFR and NF-kappaB were detected with immunohistochemical staining SP methods in forty-one patients. The radiotherapy effect was assessed by follow up visit and clinical judgement. All of the forty-one patients were divided into three groups: the complete response group, the partial response (or the stable disease) group and the progressive disease group. RESULT: The expression of EGFR and NF-kappaB were detected in human nasopharyngeal carcinoma tissues, which were not in normal ones. EGFR and NF-kappaB were significant difference of the radiosensitivity in nasopharyngeal carcinoma tissues (P<0.05). The expression of EGFR and NF-kappaB in the complete response-group and the partial response (or the stable disease)-group were lower than the progressive disease-group (P<0.05), and there was no significant difference between the complete response-group and the partial response (or the stable disease)-group (P>0.05). The two factors' expression had negative correlation with radiosensitivity. CONCLUSION: EGFR and NF-kappaB, as important targets, could predict the radiosensitivity of NPC, which could be helpful for targeting treatment and promote the effect of radiotherapy of NPC.