Background:
Laryngeal carcinoma is one of the most common malignant tumors of the head and neck. Researchers have refined the study of surgical margin in the anatomical subarea of the larynx to ...determine the most appropriate distance of the surgical margin for laryngeal carcinoma, to achieve accurate resection of laryngeal carcinoma and to improve the possibility of retention of laryngeal function.
Methods:
A comprehensive review of the primary literature was performed from 2009 to 2019 utilizing keywords laryngeal carcinoma, surgical margin, molecular margin, and prognostic factor. Articles were included at the discretion of the authors based on novel and/or contributions to the literature.
Results:
The prognosis of laryngeal carcinoma significantly correlates with the status of surgical margins. Patients with positive surgical margins have higher recurrence and metastasis rates and worse prognosis. Patients with negative pathological surgical margin but with the expression or altered expression levels of one or more tumor-related molecular biomarkers had high rates of recurrence and metastasis, and poor prognosis.
Conclusions:
Clinical intervention can improve the prognosis of patients with positive surgical margins. Patients with close margins should be followed closely. Among patients with negative surgical margins, patients with abnormal molecular margin results should be closely followed up. However, the specific selection of one or several molecular biomarkers as the detection index of molecular margin currently requires multicenter prospective or retrospective large sample study as guidance.
Metastasis and chemoresistance are major causes of poor prognosis in patients with esophageal squamous cell carcinoma (ESCC), manipulated by multiple factors including deubiquitinating enzyme (DUB). ...DUB PSMD14 is reported to be a promising therapeutic target in various cancers. Here, we explored the antitumor activity of Thiolutin (THL), the PSMD14 inhibitor, as a new therapy strategy in ESCC.
Through 4-NQO-induced murine ESCC model, we investigated the expression of PSMD14 in esophageal tumorigenesis. Ubiquitin-AMC assay was performed to evaluate DUB activity of PSMD14 with THL treatment. The effect of THL on epithelial-to-mesenchymal transition (EMT), invasion, stemness and chemosensitivity was detected by using
and
experiments. Immunoprecipitation and
ubiquitination assay were conducted to examine whether THL could impair the deubiquitination and stability of SNAIL regulated by PSMD14.
Compared with normal esophageal epithelium, PSMD14 was upregulated in 4-NQO-induced murine esophageal epithelium dysplasia and ESCC tissues. THL could significantly weaken DUB activity of PSMD14. Furthermore, the results of
and
assays showed that THL efficiently suppressed motility and stemness and increased sensitivity to cisplatin in ESCC. Mechanically, THL impaired the interaction between PSMD14 and SNAIL, then promoted the ubiquitination and degradation of SNAIL to inhibit EMT which plays a crucial role in ESCC metastasis, stemness and chemosensitivity. TCGA database analysis revealed that high concomitant PSMD14/SNAIL expression predicted shorter overall survival in esophageal cancer.
Our findings demonstrate for the first time that suppression of PSMD14/SNAIL axis by THL could be a novel and promising therapeutic approach for ESCC clinical therapy.
Based on the comprehensive analysis of optically stimulated luminescence (hereinafter referred to as OSL) dating, paleomagnetic dating, and lithological characteristics of the Guoyongzhuang ...(hereinafter referred to as GYZ) borehole in the Xinji area of Hebei Plain, the Quaternary chronostratigraphic sequence was divided and determined. The grain size characteristics of sediments, hydrodynamic conditions, and evolution process of the sedimentary environment since 1.22 Ma BP were discussed in a chronological sequence by analyzing the grain size parameters, frequency distribution curves, and probability accumulative curves, combined with the lithologic characteristics of the section. The results showed that the sediments were composed of fine particles, also they followed a trend toward better sortability, the skewness was positive, and the kurtosis was generally sharp. Thus, it also can determine that the hydrodynamic condition firstly enhanced increased and then weakened. The frequency distribution curves were dominated by a single peak, whereas the probability accumulative curve was mainly a two-stage curve and was supplemented by three-stage curves. In the early period of the 1.22–0.78 Ma BP, the sedimentary phase transitioned from a shallow lake to a depressional environment with an entrained fluvial environment, alternating between lakeside and fluvial environment in the middle stage and a depressional environment in the late part. During 0.78–0.13 Ma BP, the depressional environment was transformed into a fluvial one. Also, the lakeside environment was developed in the early period of 0.13–0.01 Ma BP, and the hydrodynamic conditions changed from weak to medium in the late period, with the development of a depressional environment and river environment successively. Besides, the period during 0.01–0 Ma BP was mainly a flood plain.
Surimi-based products with elasticity and specific shapes have received considerable notice in recent years. To ascertain the effects of inulin, microbial transglutaminase (MTGase) and the ...combination of inulin/MTGase on gel formation of silver carp surimi, the gel strength, textural properties, water-holding capacity (WHC), dynamic rheological measurements, Raman spectroscopy, light microscopy of gel structure and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of gels from different groups were analyzed. The results showed that addition of inulin, MTGase and MTGase + inulin improved gel strength (increased by 7.7%, 26.8% and 38.56% compared with control group), textural properties and WHC. Raman spectroscopy proven that MTGase + inulin promoted the conversion of α-helixes to β-sheets and β-turns compared with other experimental and control groups. Pure surimi gelation contained a loose and non-heterogeneous network via light microscopy. With the addition of MTGase and inulin, the microstructure of surimi gelation became more compact and homogeneous, particularly the MTGase + inulin groups. Moreover, The SDS-PAGE pattern further disclosed that the MTGase + inulin had a weakened myosin heavy chain band, indicating that inulin could enhance the cross-linking effects of MTGase on myosin heavy chains. These data demonstrated inulin incorporating with MTGase may be a new and effective strategy to improve the gel properties of fish surimi.
Long non-coding RNAs (LncRNAs) are implicated in malignant progression of human cancers. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-known lncRNA, has been reported to ...play crucial roles in multiple malignancies including head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of MALAT1 in HNSCC progression remain to be further investigated. Here, we elucidated that compared with normal squamous epithelium, MALAT1 was notably upregulated in HNSCC tissues, especially in which was poorly differentiated or with lymph nodes metastasis. Moreover, elevated MALAT1 predicted unfavorable prognosis of HNSCC patients. The results of in vitro and in vivo assays showed that targeting MALAT1 could significantly weaken the capacities of proliferation and metastasis in HNSCC. Mechanistically, MALAT1 inhibited von Hippel-Lindau tumor suppressor (VHL) by activating EZH2/STAT3/Akt axis, then promoted the stabilization and activation of β-catenin and NF-κB which could play crucial roles in HNSCC growth and metastasis. In conclusion, our findings reveal a novel mechanism for malignant progression of HNSCC and suggest that MALAT1 might be a promising therapeutic target for HNSCC treatment.
The invasion-metastasis cascade in head and neck squamous cell carcinoma (HNSCC) is predominantly caused by the interaction between tumor cells and tumor microenvironment, including hypoxia as well ...as stromal cells. However, the mechanism of hypoxia-activated tumor-stroma crosstalk in HNSCC metastasis remains to be deciphered. Here, we demonstrated that HIF1α was upregulated in HNSCC specimens compared with adjacent normal tissues, whose overexpression was associated with lymph node metastasis and predicted unfavorable prognosis. HIF1α expression correlated positively with the levels of miR-5100 as well as α-SMA, the marker of CAFs. Hypoxia/HIF1α regulated transcriptionally miR-5100 to promote the degradation of its target gene QKI, which acts as a tumor suppressor in HNSCC. Hypoxic HNSCC-derived exosomal miR-5100 promoted the activation of CAFs by orchestrating QKI/AKT/STAT3 axis, which further facilitated HNSCC metastasis. Additionally, miR-5100 derived from plasma exosomes indicated HNSCC malignant progression. In conclusion, our findings illuminate a novel HIF1α/miR-5100/QKI pathway in HNSCC metastasis, and suggest that miR-5100 might be a potential biomarker and therapeutic target for HNSCC.
In conventional geochemical exploration work, the samples of the same particle size range are used to eliminate the interference of foreign substances. However, the influence of topography on element ...migration is not considered in the anomaly delineation, and only a unified anomaly lower limit is used to delineate anomalies, which may result in false anomaly or hide some weak mining-induced anomaly information. This research proposes to introduce elevation elements into the processing of geochemical data, divides elevation data groups at equal intervals according to the relative elevation differences, and analyzes the vertical migration characteristics of elements under different landscape conditions. The present study has shown that summarizing the superficial vertical migration of elements can finely divide the geochemical background area, shield the influence of high background values on weak and small anomalies, and have a greater reality in screening, identifying weak and false anomaly information, and guiding actual fieldwork significance.
Ubiquitination is a reversible process that not only controls protein synthesis and degradation, but also is essential for protein transport, localization and biological activity. Deubiquitinating ...enzyme (DUB) dysfunction leads to various diseases, including cancer. In this study, we aimed to explore the functions and mechanisms of crucial DUBs in head and neck squamous cell carcinoma (HNSCC). Based on bioinformatic analysis and immunohistochemistry detection, YOD1 was identified to be significantly downregulated in HNSCC specimens compared with adjacent normal tissues. Further analysis revealed that reduced YOD1 expression was associated with the malignant progression of HNSCC and indicated poor prognosis. The results of the in vitro and in vivo experiments verified that YOD1 depletion significantly promoted growth, invasion, and epithelial-mesenchymal transition in HNSCC. Mechanistically, YOD1 inhibited the activation of the ERK/β-catenin pathway by suppressing the ubiquitination and degradation of TRIM33, leading to the constriction of HNSCC progression. Overall, our findings reveal the molecular mechanism underlying the role of YOD1 in tumor progression and provide a novel potential therapeutic target for HNSCC treatment.
Cervical lymph node metastasis from unknown primary sites is a challenging clinical issue with a changing therapy model and unpredictable outcomes, which leads to the difficulty in selecting optimal ...treatments. Thus, it is valuable to analyze the clinical characteristics and outcomes of the patients who receive different management styles.
All patients with cervical lymph node metastasis from unknown primary sites were reviewed and no primary lesions were found. In addition, this work was funded by the Clinical Trial Fund Project of Tianjin Medical University Cancer Institute and Hospital (No. C1716). Specifically, we used univariate, multiple regression analysis to evaluate the factors associated with prognosis.
365 patients met the inclusion criteria, and the 2- and 5-year survival rates were 77.0% and 33.4%, respectively, with a median survival of 45 months. Gender, age, pathological type, nodal status, and necessary cervical lymph node dissection affected locoregional control. Distant metastasis was common in individuals with a pathological type of adenocarcinoma, poor differentiation, and advanced nodal status. Furthermore, patients who received induction chemotherapy had a better prognosis than those treated with postoperative chemotherapy. Multiple regression analysis showed that pathological grade, treatment models, and distant metastasis were associated with overall survival (OS) and progression-free survival (PFS). In addition, local recurrence exerted a significant influence on OS. Induction chemotherapy and postsurgical radiotherapy seemed to improve the prognosis of patients at the advanced stage compared with simple surgery and postsurgical chemotherapy.
Pathological grade, treatment models, and distant metastasis were independent risk factors for prognosis. Induction chemotherapy or postoperative radiotherapy benefited patients at the advanced stage, and patients with adenocarcinoma, poor differentiation, and advanced nodal status should undergo induction chemotherapy in light of the increased risk of distant metastasis.
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