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1.
Oral Oncol ; 156: 106908, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38936007

ABSTRACT

BACKGROUND: This retrospective study aimed to determine the optimal metronomic chemotherapy duration (MTCD) as adjuvant therapy for patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: This study involved LANPC patients treated with metronomic chemotherapy (MTC) using a 5-FU prodrug (S1, capecitabine, or tegafur) from May 2013 to September 2020. The optimal MTCD threshold was established using X-tile Bioinformatics software. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were compared between short-term and long-term groups using propensity score matching (PSM). RESULTS: A total of 546 patients were analyzed. MTCD was an independent prognostic factor for OS, PFS, and DMFS (all P < 0.05). Patients were categorized into long-term (>3 months) and short-term (≤3 months) MTCD groups. After a median follow-up of 48 months, significant differences were observed in 4-year OS (97.0 % vs. 87.1 %; P < 0.01), PFS (84.6 % vs. 70.9 %; P < 0.01), DMFS (87.3 % vs. 78.8 %; P < 0.01), and LRRFS (95.3 % vs. 87.4 %; P < 0.01) between the long-term and short-term groups. In the PSM-matched cohort of 196 patients per group, the long-term group demonstrated superior 4-year OS and LRRFS (97.3 % vs. 87.1 %, P < 0.01; 95.2 % vs. 90.0 %, P < 0.05). No significant differences in acute toxicities were observed between the groups (P > 0.05). CONCLUSION: Extended MTC with a 5-FU prodrug (>3 months) may benefit NPC patients. Further prospective studies are needed to validate these findings.

2.
BMJ ; 385: e077890, 2024 06 19.
Article in English | MEDLINE | ID: mdl-38897625

ABSTRACT

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.


Subject(s)
Albumins , Antineoplastic Combined Chemotherapy Protocols , Capecitabine , Cisplatin , Deoxycytidine , Gemcitabine , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Recurrence, Local , Paclitaxel , Humans , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Cisplatin/adverse effects , Male , Middle Aged , Female , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/mortality , Deoxycytidine/analogs & derivatives , Deoxycytidine/administration & dosage , Deoxycytidine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/therapeutic use , Capecitabine/administration & dosage , Adult , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/mortality , Neoplasm Recurrence, Local/drug therapy , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use , Paclitaxel/adverse effects , Albumins/administration & dosage , Albumins/adverse effects , Albumins/therapeutic use , Aged , Progression-Free Survival , China , Neoplasm Metastasis
3.
Nat Commun ; 15(1): 1029, 2024 Feb 03.
Article in English | MEDLINE | ID: mdl-38310101

ABSTRACT

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.


Subject(s)
Antibodies, Monoclonal, Humanized , Induction Chemotherapy , Nasopharyngeal Neoplasms , Pyridines , Humans , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/pathology , Induction Chemotherapy/adverse effects , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/therapeutic use , Chemoradiotherapy/adverse effects
4.
Sci Rep ; 14(1): 1768, 2024 01 20.
Article in English | MEDLINE | ID: mdl-38242940

ABSTRACT

To assess the efficacy and safety of the combination of immune checkpoint inhibitors (ICIs) and target therapy (anti-angiogenesis or EGFR inhibitors) as a second-line or subsequent treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC), we conducted a retrospective study. In this study, previously treated R/M NPC patients were administered one of the following treatment: ICIs combined with target therapy and chemotherapy (ITC), ICIs combined with target therapy alone (IT), ICIs combined with chemotherapy (IC), or chemotherapy alone (C). The primary endpoint under consideration was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety measures. A total of 226 patients participated in this study, with 70 receiving the ITC regimen, 48 receiving IT, 48 treated with IC, and 60 undergoing C alone. The median PFS for the four cohorts was 20.67, 13.63, 12.47, and 7.93 months respectively. Notably, ITC regimen yielded the most favorable PFS among these cohorts. The ITC cohort exhibited a comparable tumor response and safety profile to the IT and IC cohorts (p > 0.05), but superior tumor response compared to the C cohort (p < 0.05). The ITC regimen also conferred a significant improvement in OS when comparing to C alone (HR 0.336, 95%CI 0.123-0.915, p = 0.033). The IT and IC regimens achieved a nearly identical PFS (HR 0.955, 95%CI 0.515-1.77, p = 0.884), although the IT regimen was associated with a lower occurrence of SAEs in contrast to the IC regimen (p < 0.05). In addition, the IT regimen demonstrated superior PFS (HR 0.583, 95%CI 0.345-0.985, p = 0.044) and fewer SAEs when compared to C alone (p < 0.05). These findings collectively support the notion that the combination of ICIs, target and chemotherapy exhibits robust antitumor activity in previously treated R/M NPC patients, without a significant increase in adverse events.


Subject(s)
Nasopharyngeal Neoplasms , Neoplasm Recurrence, Local , Humans , Nasopharyngeal Carcinoma/drug therapy , Retrospective Studies , Neoplasm Recurrence, Local/drug therapy , Irinotecan , Immunotherapy , Nasopharyngeal Neoplasms/drug therapy
5.
Crit Rev Oncol Hematol ; 190: 104113, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37633346

ABSTRACT

We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with anti-angiogenesis or anti-EGFR treatment in recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) patients who progressed to previous anti-PD1 therapy. Enrolled patients were divided into a combination group and a chemotherapy only group. A total of 145 patients were enrolled. The median progress-free survival (mPFS) was 7.9 months and 4.4 months, respectively for the two groups. The combination group exhibited significantly longer PFS (HR=0.363, p < 0.001), and better disease control ratio (DCR, p = 0.022) compared with the chemotherapy group. Among the combination group, longer PFS was found in those patients who received different PD1 inhibitor from prior therapy, reached object response rate (ORR) from prior anti-PD1 therapy, and EBV DNA ≤ 1500 copy/ml before therapy, comparing to the corresponding other patients. R/M NPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with anti-angiogenesis or anti-EGFR agents.


Subject(s)
Immunotherapy , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/drug therapy , Immune Checkpoint Inhibitors , Nasopharyngeal Neoplasms/drug therapy
6.
EClinicalMedicine ; 62: 102136, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37593221

ABSTRACT

Background: There are limited treatment options for patients with metastatic nasopharyngeal carcinoma (mNPC) after failure of platinum-based chemotherapy. In this trial, we assessed the efficacy and safety of sintilimab plus bevacizumab in patients with mNPC where platinum-based chemotherapy has been ineffective. Methods: This was a single-centre, open-label, single-arm, phase 2 trial in Guangzhou, China for patients with mNPC progressed after at least one line of systemic therapy. Eligible patients were between 18 and 75 years old, were histologically confirmed differentiated or undifferentiated non-keratinized NPC, were ineffective after platinum-based chemotherapy, and they had at least one measurable metastatic lesion assessed with Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V.1.1) by investigators and unsuitable for local surgery or radiotherapy. Key exclusion criterion was previous treatment with anti-PD-1/PD-L1 antibodies plus anti-VEGF antibodies and high risk of hemorrhage or nasopharyngeal necrosis. Patients were enrolled and received sintilimab (200 mg) plus bevacizumab (7.5 mg/kg) intravenously every 3 weeks. Intention-to-treat population was included in primary endpoint analyses and safety analyses. The primary endpoint was objective response rate (ORR) assessed by investigators following the guidelines of RECIST V1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. This trial is registered with ClinicalTrials.gov (NCT04872582). Findings: Between July 29, 2021 and August 16, 2022, 33 patients were enrolled. Median age was 46 years (range, 18-64 years), and 63.6% of patients had previously received two or more lines of chemotherapy for metastatic disease. Median follow-up was 7.6 months (range, 4.1-17.5 months). ORR was 54.5% (95% CI, 36.4-71.9%) with 3 complete responses (9.1%) and 15 partial responses (45.5%). Median PFS was 6.8 months (95% CI, 5.2 months to not estimable). Median DOR was 7.2 months (95% CI, 4.4 months to not estimable). Median OS was not reached. The most common potential immune-related adverse event (AE) was Grade 1-2 hypothyroidism (42.4%). Treatment-related grade 3 or 4 AEs occurred in 7 patients (21.2%), including nasal necrosis (3/33), hypertension (1/33), pruritus (1/33), total bilirubin increased (1/33) and anaphylactic shock (1/33). No treatment-related deaths and severe epistaxis occurred. Interpretation: This phase 2 trial showed that sintilimab plus bevacizumab demonstrated promising antitumour activity and manageable toxicities in patients with mNPC after failure of platinum-based chemotherapy. Further trials are warranted, and the detailed mechanisms need to be elucidated. Funding: The Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, and the Science and Technology Planning Project of International Cooperation of Guangdong Province.

7.
Front Immunol ; 14: 1124066, 2023.
Article in English | MEDLINE | ID: mdl-36860875

ABSTRACT

Background: Epstein-Barr virus (EBV) DNA seronegative (Sero-) and seropositive (Sero+) nasopharyngeal carcinoma (NPC) are distinctly different disease subtypes. Patients with higher baseline EBV DNA titers seem to benefit less from anti-PD1 immunotherapy, but underlying mechanisms remain unclear. Tumor microenvironment (TME) characteristics could be the important factor affecting the efficacy of immunotherapy. Here, we illuminated the distinct multicellular ecosystems of EBV DNA Sero- and Sero+ NPCs from cellular compositional and functional perspectives at single-cell resolution. Method: We performed single-cell RNA sequencing analyses of 28,423 cells from ten NPC samples and one non-tumor nasopharyngeal tissue. The markers, function, and dynamics of related cells were analyzed. Results: We found that tumor cells from EBV DNA Sero+ samples exhibit low-differentiation potential, stronger stemness signature, and upregulated signaling pathways associated with cancer hallmarks than that of EBV DNA Sero- samples. Transcriptional heterogeneity and dynamics in T cells were associated with EBV DNA seropositivity status, indicating different immunoinhibitory mechanisms employed by malignant cells depending on EBV DNA seropositivity status. The low expression of classical immune checkpoints, early-triggered cytotoxic T-lymphocyte response, global activation of IFN-mediated signatures, and enhanced cell-cell interplays cooperatively tend to form a specific immune context in EBV DNA Sero+ NPC. Conclusions: Collectively, we illuminated the distinct multicellular ecosystems of EBV DNA Sero- and Sero+ NPCs from single-cell perspective. Our study provides insights into the altered tumor microenvironment of NPC associated with EBV DNA seropositivity, which will help direct the development of rational immunotherapy strategies.


Subject(s)
Epstein-Barr Virus Infections , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma , Ecosystem , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , DNA , Nasopharyngeal Neoplasms/genetics , Tumor Microenvironment
8.
Cancer Sci ; 113(11): 3838-3851, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35912545

ABSTRACT

Liver metastases still remain a major cause of colorectal cancer (CRC) patient death. MYO10 is upregulated in several tumor types; however, its significance and the underlying mechanism in CRC are not entirely clear. Here, we found that MYO10 was highly expressed in CRC tumor tissues, especially in liver metastasis tissues. MYO10 knockout reduced CRC cell proliferation, invasion, and migration in vitro and CRC metastasis in vivo. We identified RACK1 by LC-MS/MS and demonstrated that MYO10 interacts with and stabilizes RACK1. Mechanistically, MYO10 promotes CRC cell progression and metastasis via ubiquitination-mediated RACK1 degradation and integrin/Src/FAK signaling activation. Therefore, the MYO10/RACK1/integrin/Src/FAK axis may play an important role in CRC progression and metastasis.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Myosins , Humans , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Chromatography, Liquid , Colorectal Neoplasms/pathology , Integrins/genetics , Liver Neoplasms/genetics , Myosins/genetics , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Phenotype , Receptors for Activated C Kinase/genetics , Tandem Mass Spectrometry , Animals
9.
Eur J Histochem ; 65(2)2021 Apr 28.
Article in English | MEDLINE | ID: mdl-33908744

ABSTRACT

Condyloma acuminata (CA) are benign anogenital warts caused by human papillomavirus (HPV) infection with a high recurrence rate. Despite its high contagiousness, high recurrence rate and potential for malignant transformation, effective treatments for CA have not yet been developed. Accordingly, it is necessary to clarify the mechanisms underlying CA development. Zinc (Zn) is stably maintained in the weight of human body. Skin is the third most Zn-abundant tissue in the body. Zn is present as a divalent ion (Zn2+) in cells and does not need a redox reaction upon crossing the cellular membrane. Zn transporters (ZnTs; SLC30A) and Irt-like proteins (ZIPs; SLC39A) are involved in Zn2+ efflux and uptake, respectively. ZnT1 is one of the ZnTs, which associates with the development of HPV. However, the role of ZnT1 regulation in the CA caused by HPV infection remains unknown. A multigroup case-control study was designed to investigate the expression and significance of the ZnT1 in patients with CA infected with HPV and in normal vulva controls. ZnT1 was assessed by immunohistochemistry in 44 patients with CA at Zhongnan Hospital of Wuhan University 2019-2020. Samples were analyzed by paraffin embedding and sectioning and hematoxylin-eosin and immunohistochemical staining. Immunohistochemical methods detected specific, dark brown, positive staining of ZnT1 in the keratinocytes of epidermis. We verified that the expression levels of ZnT1 that interact with HPV were upregulated in the CA groups independently of genotype compared with the control group. And then we found that the HPV risk grade in CA patients has a certain correlation with ZnT1 expression. These findings showed that HPV infection upregulated the expression of ZnT1 in CA. Additionally, there were obvious differences in the expression of ZnT1 between the different HPV risk grade infection groups. The higher the HPV risk grade, the stronger the ZNT1 protein expression. This study provided new insights into the sign pathway to HPV infection.


Subject(s)
Cation Transport Proteins/metabolism , Condylomata Acuminata/metabolism , Adult , Biomarkers/metabolism , Case-Control Studies , Humans , Immunohistochemistry , Middle Aged , Risk Assessment , Up-Regulation , Young Adult
10.
Comb Chem High Throughput Screen ; 24(8): 1197-1204, 2021.
Article in English | MEDLINE | ID: mdl-32981498

ABSTRACT

AIM AND OBJECTIVE: Fatty acid desaturase 1 (FADS1) has been reported to be a potential biomarker in various cancers. However, no study has explored the relationship between FADS1 expression and bladder cancer. Our study aimed to investigate the role of FADS1 in bladder cancer prognosis via The Cancer Genome Atlas (TCGA). MATERIALS AND METHODS: RNA-Seq expression of 414 tumor tissues and 19 paired normal tissues, as well as corresponding clinical data, were downloaded from the TCGA database. Two cancer cases were excluded due to a lack of clinical information. The association between FADS1 and the clinicopathological features of bladder cancer was analyzed. This study was conducted in October 2019 in China. RESULTS: The high expression of FADS1 in bladder cancer was significantly related to histological grade (OR = 0.155 for low vs. high), clinical stage (OR=2.074 for III or IV vs. I or II), T classification (OR=2.326 for T3 or T4 vs. T1 or T2), lymphatic metastasis (OR=1.923 for N1 or N2 or N3 vs. N0) and distant metastasis (OR=4.883 for yes vs. no) (all p-values <0.05). Bladder cancer with high FADS1 levels was related to a worse prognosis than bladder cancer with low FADS1 levels (p= 1.626*10-5), according to median expression value 3.622. FADS1 was an independent factor of overall survival in bladder cancer, with a hazard ratio of 1.048 (95%CI: 1.020-1.077, p = 0.001). CONCLUSION: Increased FADS1 expression in bladder cancer is associated with advanced clinicopathological features and may be a potential biomarker for poor prognosis.


Subject(s)
Urinary Bladder Neoplasms , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Humans , Lymphatic Metastasis , Prognosis , Proportional Hazards Models , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/genetics
11.
Ann Clin Lab Sci ; 50(6): 717-725, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33334785

ABSTRACT

OBJECTIVE: Sine oculis homeobox homolog 2 (Six2), a developmental transcription factor, is known to be correlated with the development and prognosis of various cancers. In this study, we explored the prognostic value of Six2 in colon adenocarcinoma (COAD). METHODS: Wilcoxon signed-rank test and logistic regression were applied to identify relationship between clinical features and Six2 expression. The effect of Six2 expression and clinical features on the survival of COAD patients was explored using Kaplan-Meier and Cox regression analyses. Gene Set Enrichment Analysis (GSEA) was performed utilizing TCGA dataset. RESULTS: Compared to adjacent normal tissues, Six2 was highly expressed in COAD. Overexpression of Six2 in COAD was significantly associated with M classification (OR=2.557, positive vs. negative), N classification (OR=2.636, N2 vs. N0), and stage (OR=1.864, III vs. I) (all p-values<0.05). Patients with higher Six2 expression had significantly poor overall survival (OS, p=0.003). The univariate analysis showed that high expression of Six2 was significantly correlated with a poor OS (HR=1.135, 95%Cl 1.038-1.241; p=0.005). The multivariate analysis demonstrated that Six2 was an independent predictor of OS (HR=1.107, 95%Cl 1.007-1.216; p=0.036). According to GSEA, differentially enriched pathways in the Six2 high expression phenotype, included the TGF- ß and Wnt signaling pathway. CONCLUSIONS: Six2 may be a valuable biomarker and potential therapeutic target for the treatment of COAD.


Subject(s)
Colonic Neoplasms/genetics , Homeodomain Proteins/genetics , Nerve Tissue Proteins/genetics , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Colon/pathology , Colonic Neoplasms/metabolism , Databases, Genetic , Female , Gene Expression/genetics , Homeodomain Proteins/metabolism , Humans , Male , MicroRNAs/genetics , Middle Aged , Nerve Tissue Proteins/metabolism , Prognosis , Transcription Factors/genetics
12.
Cancer Manag Res ; 12: 13043-13049, 2020.
Article in English | MEDLINE | ID: mdl-33376398

ABSTRACT

BACKGROUND: No study has reported the risk factors associated with the prognosis of patients with transverse colon cancer. Therefore, we aimed to demonstrate the long-term outcomes of transverse colon cancer patients undergoing radical surgery and explore the prognostic factors. MATERIALS AND METHODS: The clinical data of a total of 366 patients with transverse colon cancer staged from I to IIIC undergoing radical surgery from February 1992 to May 2017 were retrospectively analyzed. Clinicopathological features were recorded, and univariate and multivariate analyses were conducted to evaluate the association between the factors and overall survival (OS) as well as disease-free survival (DFS). Kaplan-Meier curves were generated to assess the association between TNM stage and OS and DFS, respectively. RESULTS: The median follow-up time was 62 months, and the 5-year OS and DFS rates were 87.5% and 86.5%, respectively. In addition, a significant difference was also found in the OS and DFS curves according to TNM stage. The N classification, vascular invasion, differentiation, preoperative CA199, preoperative CA125 and preoperative AFP were significantly associated with OS according to univariate analysis, while N classification and differentiation were independent prognostic factors for OS according to multivariate analysis (both P < 0.05). Similarly, N classification, vascular invasion, differentiation, preoperative CA199, preoperative CA125, and preoperative AFP were statistically correlated with DFS according to univariate analysis, while N classification and preoperative CA199 were independent prognostic factors for DFS according to multivariate analysis (both P < 0.05). CONCLUSION: N classification was an independent factor for both OS and DFS, while differentiation and CA199 were independent prognostic factors only for OS and DFS, respectively.

13.
Biomed Res Int ; 2020: 5848493, 2020.
Article in English | MEDLINE | ID: mdl-32884943

ABSTRACT

With recent advances in immunooncology and tumor microenvironment, the treatment landscape of bladder urothelial carcinoma has been changing dramatically. We aim to construct an immune gene-related signature which can predict BLCA patients' overall survival. Transcriptomic data of BLCA patients was downloaded from The Cancer Genome Atlas database, and immune-related genes were downloaded from the Immunology Database and Analysis Portal database. Prognostic immune-related genes were identified. We then constructed and validated an immune gene-related signature. Tumor-related transcription factors were downloaded from the Cistrome database, and a network between them and prognostic immune-related genes was generated. Cox's proportional hazards model and the Kaplan-Meier survival analysis were performed to assess our signature's prognostic ability. Relationship between the signature and patients' clinicopathologic features was then explored to validate its clinical value. We further downloaded concentration of six types of immune cells from the Tumor Immune Estimation Resource database to explore immune-related potential mechanisms of the signature.


Subject(s)
Databases, Nucleic Acid , Gene Expression Regulation, Neoplastic , Neoplasm Proteins , Transcriptome , Urinary Bladder Neoplasms , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Survival Rate , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/mortality
14.
Biomed Res Int ; 2020: 7974034, 2020.
Article in English | MEDLINE | ID: mdl-32802874

ABSTRACT

Long noncoding RNAs (lncRNAs) have been confirmed to play a crucial role in human disease, especially in tumor development and progression. Small nucleolar RNA host gene (SNHG3), a newly identified lncRNA, has been found dysregulated in various cancers. Nevertheless, the results remain controversial. Thus, we aim to analyze the comprehensive data to elaborate the association between SNHG3 expression and clinical outcomes in multiple cancers. We searched PubMed, Web of Science, Cochrane Library, Embase, and MEDLINE database to identify eligible articles. STATA software was applied to calculate the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (95% CI) for survival outcomes and clinical parameters, respectively. Besides, the data from The Cancer Genome Atlas (TCGA) dataset was extracted to verify the results in our meta-analysis. There were thirteen studies totaling 919 cancer patients involved in this meta-analysis. The results demonstrated that high SNHG3 expression was significantly associated with poor overall survival (OS) (HR = 2.53, 95% CI: 1.94-3.31) in cancers, disease-free survival (DFS) (HR = 3.89, 95% CI: 1.34-11.3), and recurrence-free survival (RFS) (HR = 2.42, 95% CI: 1.14-5.15) in hepatocellular carcinoma. Analysis stratified by analysis method, sample size, follow-up time, and cancer type further verified the prognostic value of SNHG3. Additionally, patients with high SNHG3 expression tended to have more advanced clinical stage, higher histological grade, earlier distant metastasis, and earlier lymph node metastasis. Excavation of TCGA dataset valuated that SNHG3 was upregulated in various cancers and predicted worse OS and DFS. Overexpressed SNHG3 was strongly associated with poor survival and clinical outcomes in human cancers and therefore can serve as a promising biomarker for predicting patients' prognosis.


Subject(s)
Databases, Nucleic Acid , Neoplasms , RNA, Long Noncoding , RNA, Neoplasm , Disease-Free Survival , Female , Humans , Male , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/mortality , RNA, Long Noncoding/biosynthesis , RNA, Long Noncoding/genetics , RNA, Neoplasm/biosynthesis , RNA, Neoplasm/genetics , Survival Rate
15.
Minerva Chir ; 75(3): 193-202, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32550728

ABSTRACT

INTRODUCTION: Thyroid surgery, which is usually followed by moderate postoperative pain, has gained increasing attention in recent years. A systematic review and meta-analysis was conducted to assess the effect of prophylactic bupivacaine on postoperative pain following thyroidectomy. EVIDENCE ACQUISITION: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases for specific keywords. RevMan 5.0 and Stata 12.0 software were used to perform meta-analyses. The endpoints were postoperative pain, rescue analgesic requirement, and postoperative nausea and vomiting (PONV) during the immediate 24 h postoperative period. EVIDENCE SYNTHESIS: A total of 18 randomized controlled trials (RCTs) with 1308 patients were included in the meta-analysis. A significant reduction of pain according to the postoperative pain scale at 1 hour (P<0.05) and rescue analgesic requirement (P<0.05) was observed following local infiltration with bupivacaine. A bilateral superficial cervical plexus block (BSCPB) with bupivacaine also significantly reduced postoperative pain at 1 hour (P<0.01) and 24 hours (P<0.01), as well as rescue analgesic requirement (P<0.00001) and PONV (P<0.01). Compared with BSCPB, local infiltration with bupivacaine provides a better effect in terms of postoperative analgesia (P<0.05). CONCLUSIONS: We recommend local infiltration with bupivacaine ranged from 20 to 75 mg before or after skin closure or BSCPB with bupivacaine ranged from 25 to 100 mg to reduce postoperative pain after thyroidectomy.


Subject(s)
Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Pain, Postoperative/prevention & control , Thyroidectomy/adverse effects , Analgesics/therapeutic use , Cervical Plexus Block/methods , Humans , Postoperative Nausea and Vomiting , Randomized Controlled Trials as Topic/statistics & numerical data , Salvage Therapy , Time Factors
16.
Cancer Biol Ther ; 20(11): 1380-1388, 2019.
Article in English | MEDLINE | ID: mdl-31387444

ABSTRACT

Background The prognostic value of Chemokine (C-X-C motif) ligand 1 (CXCL1) in various types of cancer remains controversial. Here we aimed to evaluate the prognostic role of CXCL1 for cancer. Methods A comprehensively search of the PubMed, Embase, Web of Science, Wanfang and China National Knowledge Internet databases was conducted to retrieve eligible studies meeting the inclusion criteria. Overall survival (OS), progression-free survival (PFS) and various clinicopathological parameters were defined as endpoints. Stata SE12.0 software was used for quantitative meta-analysis. Results A total of 17 studies encompassing 2265 cancer patients were included. Our meta-analysis showed that patients with higher CXCL1 expression had significantly shorter OS, according to both multivariate (HR 1.51, 95% CI 1.19-1.83, P < .01) and univariate analysis (HR 2.08, 95% CI 1.62-2.54, P < .01). Furthermore, higher CXCL1 expression was significantly correlated with advanced TNM stage and lymph node metastasis (both P < .05). Conclusions High CXCL1 expression is a risk factor for cancer prognosis indicating a poor OS, and advanced TNM stage and lymph node metastasis, demonstrating that it may be a promising prognostic biomarker for different cancers.


Subject(s)
Biomarkers, Tumor/genetics , Chemokine CXCL1/genetics , Lymphatic Metastasis/genetics , Neoplasms/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Lymphatic Metastasis/pathology , Neoplasms/pathology , Progression-Free Survival , Risk Factors
17.
Cancer Biol Ther ; 20(12): 1409-1415, 2019.
Article in English | MEDLINE | ID: mdl-31411522

ABSTRACT

Malignant peritoneal mesothelioma is a very rare tumor originating from the peritoneal serous mesothelium. Meningeal metastasis of malignant peritoneal is even more rare. Here, we reported a case of a 60-year-old female patient with a history of exposure to asbestos for 10 years who presented with massive peritoneal effusion followed by disorder of consciousness and symptoms of cranial nerve injury. The patient was diagnosed as peritoneal mesothelioma with meningeal metastasis through neurological symptoms, cytological finding of cerebrospinal fluid combined with cranial magnetic resonance imaging (MRI). The patient received systemic chemotherapy and total craniospinal irradiation. The follow up visits showed that the survival time of patient after diagnosis of meningeal metastasis from peritoneal mesothelioma was 5 months. To our knowledge, this is the first case of menigeal metastasis of peritoneal mesothelioma. We hope this particular case may be helpful in providing some experience to the treatment of peritoneal mesothelioma with meningeal metastasis.


Subject(s)
Lung Neoplasms/pathology , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/secondary , Mesothelioma/pathology , Peritoneal Neoplasms/pathology , Asbestos/adverse effects , Biomarkers, Tumor , Biopsy , Disease Progression , Fatal Outcome , Female , Genetic Testing , Humans , Immunohistochemistry , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/etiology , Meningeal Neoplasms/therapy , Mesothelioma/diagnostic imaging , Mesothelioma/etiology , Mesothelioma, Malignant , Middle Aged , Multimodal Imaging/methods , Occupational Exposure/adverse effects , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/etiology , Radiotherapy, Intensity-Modulated
18.
J Cell Mol Med ; 23(8): 4891-4899, 2019 08.
Article in English | MEDLINE | ID: mdl-31251476

ABSTRACT

Recently, increasing studies have reported that long non-coding RNA (lncRNA) gastric carcinoma highly expressed transcript 1 (GHET1) is highly expressed in variety of cancers and relevant to poor prognosis of cancer patients. Nevertheless, the results were inconsistent and the systematic analysis of lncRNA GHET1 in cancers has not been inspected. Thus, we aim to evaluate the relationship between lncRNA GHET1 expression and clinical outcomes in human cancers. We searched keywords in PubMed, Web of Science, Embase, Cochrane Library and ClinicalTrial.gov. Stata SE12.0 software was used in the quantitative meta-analysis. Pooled hazard ratio (HR) and odds ratio with 95% confidence interval (95% Cl) were calculated to evaluate the clinical significance of lncRNA GHET1. Twelve studies totalling 761 patients with cancers were included for analysis. The pooled results of this study indicated that high lncRNA GHET1 expression level was significantly associated with poor overall survival (OS, HR = 2.30, 95% CI: 1.75-3.02) in human cancers. The statistical significance was also detected in subgroup analysis stratified by analysis method, cancer type, sample size and follow-up time respectively. In addition, the elevated lncRNA GHET1 expression was also significantly related to more advanced clinical stage, earlier lymph node metastasis, earlier distant metastasis and bigger tumour size. LncRNA GHET1 may serve as a promising biomarker for prognosis in Asians with cancers.


Subject(s)
Biomarkers, Tumor/metabolism , Neoplasms/mortality , RNA, Long Noncoding/metabolism , Biomarkers, Tumor/genetics , China , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Odds Ratio , Prognosis , RNA, Long Noncoding/genetics
19.
J Pain Res ; 11: 2463-2475, 2018.
Article in English | MEDLINE | ID: mdl-30425559

ABSTRACT

BACKGROUND/AIMS: An updated systematic review and meta-analysis was conducted to assess the effect of prophylactic dexamethasone for tracheal intubation of general anesthesia on postoperative sore throat (POST). METHODS: Comprehensive literature search of databases for randomized controlled trials (RCTs), including Embase, PubMed, and Cochrane Library, which evaluate the effect of prophylactic dexamethasone on POST was conducted. RevMan 5.0 and STATA 12.0 software were used to perform meta-analyses. RESULTS: Fourteen RCTs totaling 1,837 patients were included for analysis. Compared with placebo, a significant reduction in the incidence of POST (OR 0.44, 95% CI 0.33-0.58, P<0.00001), hoarseness (OR 0.42, 95% CI 0.31-0.58, P<0.00001), and postoperative nausea and vomiting (PONV) (OR 0.06, 95% CI 0.03-0.14, P<0.00001) and a comparable incidence of cough (OR 0.59, 95% CI 0.19-1.89, P=0.38) was described in patients receiving dexamethasone, with or without concomitant drugs. Dexamethasone ≥0.2 mg/kg had a statistically greater impact on reducing the incidence of POST than dexamethasone 0.1-0.2 mg/kg, while dexamethasone ≤0.1 mg/kg did not. Dexamethasone was as effective as other drugs such as ondansetron, magnesium sulfate, ketamine gargle, betamethasone gel, and ketorolac for reducing POST (OR 0.70, 95% CI 0.46-1.07, P=0.10). Dexamethasone plus a different drug was more effective than dexamethasone alone for reducing the incidence of POST at 24 hours (OR 0.40, 95% CI 0.21-0.77, P=0.006). Compared with controls, a statistically higher blood glucose level was the only adverse event during the immediate postoperative period in patients receiving dexamethasone. CONCLUSIONS: Intravenous dexamethasone ≥0.2 mg/kg within 30 minutes before or after induction of general anesthesia should be recommended as grade 1A evidence with safety and efficacy in reducing the incidence of POST, hoarseness, and PONV in patients without pregnancy, diabetes mellitus, or contraindications for corticosteroids.

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