Natural products reverse cisplatin resistance in the hypoxic tumor microenvironment.

Cisplatin is one of the most commonly used drugs for cancer treatment. Despite much progress in improving patient outcomes, many patients are resistant to cisplatin-based treatments, leading to limited treatment efficacy and increased treatment failure. The fact that solid tumors suffer from hypoxia and an inadequate blood supply in the tumor microenvironment has been widely accepted for decades. Numerous studies have shown that a hypoxic microenvironment significantly reduces the sensitivity of tumor cells to cisplatin. Therefore, understanding how hypoxia empowers tumor cells with cisplatin resistance is essential. In the fight against tumors, developing innovative strategies for overcoming drug resistance has attracted widespread interest. Natural products have historically made major contributions to anticancer drug research due to their obvious efficacy and abundant candidate resources. Intriguingly, natural products show the potential to reverse chemoresistance, which provides new insights into cisplatin resistance in the hypoxic tumor microenvironment. In this review, we describe the role of cisplatin in tumor therapy and the mechanisms by which tumor cells generate cisplatin resistance. Subsequently, we call attention to the linkage between the hypoxic microenvironment and cisplatin resistance. Furthermore, we summarize known and potential natural products that target the hypoxic tumor microenvironment to overcome cisplatin resistance. Finally, we discuss the current challenges that limit the clinical application of natural products. Understanding the link between hypoxia and cisplatin resistance is the key to unlocking the full potential of natural products, which will serve as new therapeutic strategies capable of overcoming resistance.

Preparation of Biochar with Developed Mesoporous Structure from Poplar Leaf Activated by KHCO3 and Its Efficient Adsorption of Oxytetracycline Hydrochloride.

The effective removal of oxytetracycline hydrochloride (OTC) from the water environment is of great importance. Adsorption as a simple, stable, and cost-effective technology is regarded as an important method for removing OTC. Herein, a low-cost biochar with a developed mesoporous structure was synthesized via pyrolysis of poplar leaf with potassium bicarbonate (KHCO3) as the activator. KHCO3 can endow biochar with abundant mesopores, but excessive KHCO3 cannot continuously promote the formation of mesoporous structures. In comparison with all of the prepared biochars, PKC-4 (biochar with a poplar leaf to KHCO3 mass ratio of 5:4) shows the highest adsorption performance for OTC as it has the largest surface area and richest mesoporous structure. The pseudo-second-order kinetic model and the Freundlich equilibrium model are more consistent with the experimental data, which implies that the adsorption process is multi-mechanism and multi-layered. In addition, the maximum adsorption capacities of biochar are slightly affected by pH changes, different metal ions, and different water matrices. Moreover, the biochar can be regenerated by pyrolysis, and its adsorption capacity only decreases by approximately 6% after four cycles. The adsorption of biochar for OTC is mainly controlled by pore filling, though electrostatic interactions, hydrogen bonding, and π-π interaction are also involved. This study realizes biomass waste recycling and highlights the potential of poplar leaf-based biochar for the adsorption of antibiotics.

Human microbiomes in cancer development and therapy.

Colonies formed by bacteria, archaea, fungi, and viral groups and their genomes, metabolites, and expressed proteins constitute complex human microbiomes. An increasing evidences showed that carcinogenesis and disease progression were link to microbiomes. Different organ sources, their microbial species, and their metabolites are different; the mechanisms of carcinogenic or procancerous are also different. Here, we summarize how microbiomes contribute to carcinogenesis and disease progression in cancers of the skin, mouth, esophagus, lung, gastrointestinal, genital, blood, and lymph malignancy. We also insight into the molecular mechanisms of triggering, promoting, or inhibiting carcinogenesis and disease progress induced by microbiomes or/and their secretions of bioactive metabolites. And then, the strategies of application of microorganisms in cancer treatment were discussed in detail. However, the mechanisms by which human microbiomes function are still poorly understood. The bidirectional interactions between microbiotas and endocrine systems need to be clarified. Probiotics and prebiotics are believed to benefit human health via a variety of mechanisms, in particular, in tumor inhibition. It is largely unknown how microbial agents cause cancer or how cancer progresses. We expect this review may open new perspectives on possible therapeutic approaches of patients with cancer.

Circ_0108942 Regulates the Progression of Breast Cancer by Regulating the MiR-1178-3p/TMED3 Axis.

BACKGROUND: Breast cancer (BC) has posed a fatal threat to women's lives and the search for new methods of diagnosis and treatment is an important way to break the bottleneck of high mortality in BC. Circular RNAs (circRNAs) have been confirmed to be aberrantly expressed in several types of cancers, and this study is intended to elucidate the role and mechanism of circ_0108942 in BC. MATERIALS AND METHODS: The levels of circ_0108942, microRNA-1178-3p (miR-1178-3p), and transmembrane p24 trafficking protein 3 (TMED3) were measured using real-time quantitative polymerase chain reaction (RT-qPCR) or western blot. Meanwhile, the cell proliferation, migration, invasion, angiopoiesis, and apoptosis were analyzed using 5-ethynyl-2'-deoxyuridine (EdU), transwell, tubule formation, and flow cytometry assays. Protein levels were determined by western blot. In addition, we used dual-luciferase reporter and RNA pull-down assays to identify the interplay between miR-1178-3p and circ_0108942 or TMED3. Lastly, the impact of circ_0108942 on the growth of BC tumors in vivo was analyzed by xenograft models. RESULTS: Circ_0108942 and TMED3 were notably upregulated in BC, and the miR-1178-3p was downregulated. Functionally, silencing circ_0108942 suppressed cell proliferation, migration, invasion and promoted apoptosis in BC cells. In mechanism, circ_0108942 regulated TMED3 expression by sponging miR-1178-3p. Meanwhile, circ_0108942 knockdown also greatly constrained tumor growth in vivo. CONCLUSION: Circ_0108942 boosted BC progression by regulating miR-1178-3p and thus upregulating TMED3.

Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways.

Drug resistance is still an obstacle in cancer therapy, leading to the failure of tumor treatment. The emergence of tumor drug resistance has always been a main concern of oncologists. Therefore, overcoming tumor drug resistance and looking for new strategies for tumor treatment is a major focus in the field of tumor research. Natural products serve as effective substances against drug resistance because of their diverse chemical structures and pharmacological effects. We reviewed the signaling pathways involved in the development of tumor drug resistance, including Epidermal growth factor receptor (EGFR), Renin-angiotensin system (Ras), Phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), Wnt, Notch, Transforming growth factor-beta (TGF-ß), and their specific signaling pathway inhibitors derived from natural products. This can provide new ideas for the prevention of drug resistance in cancer therapy.

Development of a model for predicting mortality of breast cancer admitted to Intensive Care Unit.

Background: There is still not a mortality prediction model built for breast cancer admitted to intensive care unit (ICU). Objectives: We aimed to build a prognostic model with comprehensive data achieved from eICU database. Methods: Outcome was defined as all-cause in-hospital mortality. Least absolute shrinkage and selection operator (LASSO) was conducted to select important variables which were then taken into logistic regression to build the model. Bootstrap method was then conducted for internal validation. Results: 448 patients were included in this study and 79 (17.6%) died in hospital. Only 5 items were included in the model and the area under the curve (AUC) was 0.844 (95% confidence interval [CI]: 0.804-0.884). Calibration curve and Brier score (0.111, 95% CI: 0.090-0.127) showed good calibration of the model. After internal validation, corrected AUC and Brier score were 0.834 and 0.116. Decision curve analysis (DCA) also showed effective clinical use of the model. The model can be easily assessed on website of https://breastcancer123.shinyapps.io/BreastCancerICU/. Conclusions: The model derived in this study can provide an accurate prognosis for breast cancer admitted to ICU easily, which can help better clinical management.

MALAT1 Promotes Tumorigenesis and Increases Cellular Sensitivity to Herceptin in HER2-positive Breast Cancer.

BACKGROUND: The function of MALAT1, a long non-coding RNAs (lncRNA), in HER2- positive breast cancer remains largely unexplored. OBJECTIVES: This study aimed to investigate the effect of MALAT1 on tumor development in HER2-positive breast cancer. METHODS: We detected MALAT1 expression in HER2-positive breast cancer cells and tissues, and analyzed the effects of MALAT1 on cell proliferation in HER2-positive breast cancer cells lines (BT-474 and SKBR3). A mouse xenograft model was established for detecting the function of MALAT1 in HER2-positive breast cancer. RESULTS AND DISCUSSION: As a result, MALAT1 was remarkably up-regulated in HER2-positive breast cancer both in cells and tissues. In addition, the silencing of MALAT1 inhibited the proliferation of HER2-positive breast cancer cells both in vitro and in vivo. Furthermore, knockdown of MALAT1 by shRNA down-regulated DNMT1, DNMT3a, and DNMT3b, while up-regulated BRCA1 and PTEN in HER2-positive breast cancer both in cell lines and mouse xenograft models. CONCLUSION: In short, MALAT1 might be a potential biomarker and therapeutic target for HER2- positive breast cancer therapy.

Downregulation of hsa_circRNA_0001400 Helps to Promote Cell Apoptosis Through Disruption of the circRNA_0001400-miR-326 Sponge in Cervical Cancer Cells.

Background: In recent years, circular RNAs (circRNAs) have been reported to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of circRNAs in cervical cancer remain elusive. Methods: Flow cytometry assays were performed to measure cell apoptosis and cell cycle. Colony Formation and transwell chamber were performed to measure cell migration and invasion. Double luciferase reporter for gene analysis was used to detect the interaction between hsa-circRNA_0001400, miR-326, and Akt. Relative protein levels were determined by immunoblotting and relative gene levels were determined by quantitative real-time PCR. Tumor Xenograft Modeling was used to evaluate the effect of hsa_circRNA_0001400_siRNA in vivo. Results: In the present study, we showed that hsa_circRNA_0001400 was highly expressed in cervical cancer tissues relative to in matched normal tissue. We found that hsa_circRNA_0001400_siRNA significantly promoted the apoptosis of cervical cancer cells and arrested the cell cycle and migration of cervical cancer cells. We showed that hsa_circRNA_0001400_siRNA can inhibit the protein expression of Akt and that the inhibition of miR-326 could rescue the inhibition of Akt in cervical cancer cells. We found that has-miR-326 was downregulated in cervical cancer tissues and hsa_circRNA_0001400_siRNA could increase the gene expression of has-miR-326. We also observed that hsa_circRNA_0001400_siRNA inhibited the growth and angiogenesis of SiHa xenografts in nude mice. Conclusion: In conclusion, this study provides evidence that the hsa_circRNA_0001400-miR-326-Akt network promotes cervical cancer progression. Notably, our findings demonstrate the novel antitumor effects of hsa_circRNA_0001400_siRNA in cervical cancer.

CDK12 Promotes Breast Cancer Progression and Maintains Stemness by Activating c-myc/ß -catenin Signaling.

BACKGROUND: CDK12 is a promising therapeutic target in breast cancer with an effective ability of maintaining cancer cell stemness. OBJECTIVE: We aim to investigate the mechanism of CDK12 in maintaining breast cancer stemness. METHODS: CDK12 expression level was accessed by using RT-qPCR and IHC. CDK12-altered breast cancer cell lines MDA-MB-231-shCDK12 and SkBr-3-CDK12 were then established. CCK8, colony formation assays, and xenograft model were used to value the effect of CDK12 on tumorigenicity. Transwell assay, mammosphere formation, FACS, and lung metastasis model in vivo were determined. Western blot further characterized the mechanism of CDK12 in breast cancer stemness through the c-myc/ß-catenin pathway. RESULTS: Our results showed a higher level of CDK12 exhibited in breast cancer samples. Tumor formation, cancer cell mobility, spheroid forming, and the epithelial-mesenchymal transition will be enhanced in the CDK12high group. In addition, CDK12 was associated with lung metastasis and maintained breast cancer cell stemness. CDK12high cancer cells presented higher tumorigenicity and a population of CD44+ subset compared with CDK12low cells. Our study demonstrated c-myc positively expressed with CDK12. The c-myc/ß-catenin signaling was activated by CDK12, which is a potential mechanism to initiate breast cancer stem cell renewal and may serve as a potential biomarker of breast cancer prognosis. CONCLUSION: CDK12 overexpression promotes breast cancer tumorigenesis and maintains the stemness of breast cancer by activating c-myc/ß-catenin signaling. Inhibiting CDK12 expression may become a potential therapy for breast cancer.

RNA sequencing discloses the genome­wide profile of long noncoding RNAs in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a common type of non­ischemic cardiomyopathy, of which the underlying mechanisms have not yet been fully elucidated. Long noncoding RNAs (lncRNAs) have been reported to serve crucial physiological roles in various cardiac diseases. However, the genome­wide expression profile of lncRNAs remains to be elucidated in DCM. In the present study, a case­control study was performed to identify expression deviations in circulating lncRNAs between patients with DCM and controls by RNA sequencing. Partial dysregulated lncRNAs were validated by reverse transcription­polymerase chain reaction. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and lncRNA­messenger RNA (mRNA) co­expression network analyses were employed to probe potential functions of these dysregulated lncRNAs in DCM. Comparison between 8 DCM and 8 control samples demonstrated that there were alterations in the expression levels of 988 lncRNAs and 1,418 mRNAs in total. The dysregulated lncRNAs were found to be mainly associated with system development, organ morphogenesis and metabolic regulation in terms of 'biological processes'. Furthermore, the analysis revealed that the gap junction pathway, phagosome, and dilated and hypertrophic cardiomyopathy pathways may serve crucial roles in the development of DCM. The lncRNA­mRNA co­expression network also suggested that the target genes of the lncRNAs were different in patients with DCM as compared with those in the controls. In conclusion, the present study revealed the genome­wide profile of circulating lncRNAs in DCM by RNA sequencing, and explored the potential functions of these lncRNAs in DCM using bioinformatics analysis. These findings provide a theoretical foundation for future studies of lncRNAs in DCM.

Low glucose metabolism in hepatocellular carcinoma with GPC3 expression.

AIM: To investigate the relationship between glucose metabolism and glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC). METHODS: Immunohistochemical staining of pathological samples for GPC3 and glucose transporter 1 (GLUT1), and whole-body 18F-FDG PET/CT for measuring tumour glucose uptake were performed in 55 newly diagnosed HCC patients. The maximum standard uptake value (SUVmax) and tumour-to-non-tumourous liver uptake (T/NT) ratio were used to quantify 18F-FDG uptake. In vitro18F-FDG uptake assay of GPC3-expressing HepG2 and non-GPC3-expressing RH7777 cells was used to examine the effect of GPC3 in cellular glucose metabolism. The relationships between GPC3 expression and 18F-FDG uptake, GLUT1 expression, tumour differentiation, and other clinical indicators were analysed using Spearman rank correlation, univariate and multiple logistic regression analyses. RESULTS: Positive GPC3 expression was observed in 67.3% of HCC patients, including 75.0% of those with well or moderately differentiated HCC and 36.4% of those with poorly differentiated HCC. There was an inverse relationship between GPC3 expression and SUVmax (Spearman correlation coefficient = -0.281, P = 0.038) and a positive relationship between GLUT1 expression and SUVmax (Spearman correlation coefficient = 0.681, P < 0.001) in patients with HCC. Univariate analysis showed that two glucose metabolic parameters (SUVmax and T/NT ratio), tumour differentiation, lymph node metastasis, and TNM stage were all significantly associated with GPC3 expression (P < 0.05), whereas GLUT1 expression, sex, age, tumour size, intrahepatic lesion number, and distant metastasis showed no statistical association (P > 0.05). Further multivariate analysis revealed that only the T/N ratio was significantly correlated with GPC3 expression in patients with HCC (P < 0.05). In vitro assay revealed that the uptake of 18F-FDG in GPC3-expressing HepG2 cells was significantly lower than that of non-GPC3-expressing RH7777 cells (t = -20.352, P < 0.001). CONCLUSION: The present study demonstrated that GPC3 expression is inversely associated with glucose metabolism, suggesting that GPC3 may play a role in regulating glucose metabolism in HCC.

Convergence results on iteration algorithms to linear systems.

In order to solve the large scale linear systems, backward and Jacobi iteration algorithms are employed. The convergence is the most important issue. In this paper, a unified backward iterative matrix is proposed. It shows that some well-known iterative algorithms can be deduced with it. The most important result is that the convergence results have been proved. Firstly, the spectral radius of the Jacobi iterative matrix is positive and the one of backward iterative matrix is strongly positive (lager than a positive constant). Secondly, the mentioned two iterations have the same convergence results (convergence or divergence simultaneously). Finally, some numerical experiments show that the proposed algorithms are correct and have the merit of backward methods.

Effect of primary percutaneous coronary intervention on serum collagen biomarkers following acute myocardial infarction.

OBJECTIVE: The aim of this study was to investigate the effect of primary percutaneous coronary intervention (PCI) on serum collagen biomarkers following acute myocardial infarction (AMI). METHODS AND RESULTS: Thirty-eight patients were enrolled into a primary PCI (n = 16) and a control (n = 22) group. The PCI group received successful PCI within 6 h of MI, whereas the control group received no PCI or thrombolytic therapy. Serum type I procollagen (PICP) and type III procollagen (PIIINP) were measured by enzyme-linked immunosorbent assay (ELISA). The baseline characteristics were similar between the PCI and control groups. There was no significant difference in left ventricular end-systolic, end-diastolic volume or ejection fraction between the two groups 30 min after MI (P > 0.05). A significant increase in PICP and PIIINP was noted in both groups 3 days after MI (P < 0.01). PICP and PIIINP in the PCI group declined overtime to the pre-PCI level, whereas they remained high in the control group. In the PCI group, the mean serum PICP and PIIINP on day 7, 14 and 30 was lower than in the control group (P < 0.01). CONCLUSIONS: AMI is associated with an increase in serum biomarkers of collagen synthesis. Early and successful PCI is associated with a reduction in serum collagen biomarkers.

Effects of adrenomedullin on the cell numbers and apoptosis of endothelial progenitor cells.

PURPOSE: To investigate the effect of adrenomedullin on the cell numbers and apoptosis of endothelial progenitor cells (EPCs). METHODS: Mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation. The cells were stimulated with adrenomedullin, before and after the treatment of adrenomedullin-receptor antagonist, adrenomedullin 22-52, or a PI3K inhibitor LY294002. RESULTS: Adrenomedullin dose-dependently increased the number of EPCs (P < 0.05). Adrenomedullin also significantly decreased apoptosis rate of EPCs in a concentration-dependent manner (P < 0.05). In the isolated human mononuclear cells pretreated with adrenomedullin 22-52 or LY294002, adrenomedullin failed to increase the number of EPCs or to reduce the level of apoptosis. CONCLUSIONS: Adrenomedullin increases the number of EPCs and decreases their apoptosis. These actions are likely mediated by PI3K signaling pathways. The clinical importance of these favourable effects on EPCs remains to be determined.

[Childhood thyroid carcinoma: clinical analyses of 22 cases].

BACKGROUND & OBJECTIVE: Thyroid carcinoma is rarely occurred in children. Clinicopathologic characteristics, therapy and prognosis of childhood thyroid carcinoma patients are different from those of adult patients, and the treatment of this disease is controversial. This study was to explore the clinicopathologic characteristics, diagnosis and therapy of thyroid carcinoma in children. METHODS: Clinical data of 22 children under the age of 14, diagnosed as thyroid carcinoma between Jan. 1980 and Dec. 2000, were reviewed. RESULTS: According to UICC clinical and histopathologic classification(2002), 19 cases were classified as stageI (2 cases of T1-4N0M0 and 17 cases of T1-4N1M0) and 3 cases as stage II (T1-4N1-4M1). Of the 22 patients, 8 (36.4%) had papillary carcinoma, 8 (36.4%) had follicular carcinoma, 5(22.7%) had mixed papillary-follicular carcinoma, and 1 (4.5%) had medullary carcinoma. All patients had received operation and postoperative thyroxin therapy. Unilateral and bilateral neck dissection had been performed in 12 and 7 patients, respectively; 19 patients had cervical lymph node metastasis. The follow-up period was 6 to 26 years (median, 14.83 years). The 5-and 10-year survival rates were 100% and 95.5%, respectively. CONCLUSIONS: Childhood thyroid carcinomas are mostly differentiated carcinomas, with high frequency of cervical lymph node metastases. The optimal treatment for thyroid carcinoma in children may improve the quality of life and decrease the incidence of complications.

[Treatment and prognosis of stage IV glottic laryngeal cancer].

BACKGROUND & OBJECTIVE: The prognosis of stage IV glottic cancer is poor. This study was to explore the impacts of different treatment modalities, cervical lymph node status and surgical margin on the prognosis of stage IV glottic cancer. METHODS: Clinical data of 88 patients with stage IV glottic cancer were reviewed. The correlations of different treatment modalities, cervical lymph node status, and surgical margin to the prognosis of stage IV glottic cancer were analyzed. RESULTS: The overall 3-and 5-year survival rates of the 88 patients were 71.6% and 63.0%. There was no significant difference in survival rate among the patients received operation, operation plus postoperative radiotherapy, chemoradiotherapy, and operation plus chemotherapy (P=0.729). The overall survival rate was significant lower in patients with lymph node metastasis than in those without lymph node metastasis (P=0.015); for stage cN0 patients, there was no significant difference between the patients with and without occult lymph node metastasis (P=0.474). There was no significant difference between the patients with positive surgical margin and those with negative surgical margin (P=0.016). CONCLUSIONS: N stage is the important prognostic factor for stage IV glottic cancer. The prognosis of patients with lymph node metastasis is poor. The survival rate of the patients with positive surgical margin is lower than that of those with negative surgical margin.

[Prognostic factors of medullary thyroid carcinoma].

OBJECTIVE: To investigate prognostic factors of medullary thyroid carcinoma. METHODS: By using univariate analysis and multivariate analysis, the prognostic factors were investigated in 102 patients with medullary thyroid carcinoma treated at this hospital. RESULTS: Overall survival rates of 5-year, 10-year and 15-year were 87.4%, 74.6% and 54.2% respectively by Kaplan-Meier method analysis. In univariate analysis, gender, age, bilateral thyroid lobe tumors, tumor size > 4 cm, invasion of thyroid capsule, distant metastasis, and non-radical tumor resection were significant poor prognostic factors. In multivariate analysis, tumor size > 4 cm (chi(2) = 7.43, P = 0.0035), distant metastasis (chi(2) = 23.50, P = 0.0000), and non-radical tumor resection (chi(2) = 25.90, P = 0.0000) remained as independent prognostic factors. CONCLUSIONS: Tumor size > 4 cm, distant metastasis, and non-radical tumor resection are the independent predictors of patients survival. Early diagnosis and early therapy can improve significantly the prognosis of medullary thyroid carcinoma.

[Correlation of cervical lymphatic metastasis to prognosis of glottic carcinoma: a report of 333 cases].

BACKGROUND & OBJECTIVE: Cervical lymph node metastasis rate of glottic carcinoma is low. How to deal with cervical adenopathy remains controversial. This study was to explore the factors relate to cervical lymphatic metastasis of glottic carcinoma. METHODS: Clinical data of 333 patients with glottic carcinoma, treated at Cancer Center of Sun Yat-sen University from Jan. 1, 1992 to Dec. 31, 2000, were reviewed. Distribution of cervical adenopathy, prognosis, and neck management were analyzed. RESULTS: The overall lymphatic metastasis rate was 9.61% (32/333); the occult lymphatic metastasis rate was 6.24% (20/321). Most metastatic lymph nodes located at ipsilateral levels II, III and IV (28/32). The pathologic grade had no correlation to the overall lymphatic metastasis rate (P=0.092), and occult lymphatic metastasis rate (P=0.067). The overall lymphatic metastasis rate (P=0.002) and occult lymphatic metastasis rate (P=0.015) rose up following with increased T stage. Neck selective radiotherapy for the patients at stage cN0 had no significant impact on occult lymph node metastasis rate (P=0.363). The 3-and 5-year survival rates were significantly lower in cN+ patients than in cN0 patients (56.25% vs. 88.70%, 46.67% vs. 85.37%, P<0.001), significantly lower in the cN+ patients with occult lymph node metastasis than in the cN+ patients without lymph node metastasis (68.18% vs. 89.00%, 63.31% vs. 85.55%, P=0.005), and significantly lower in naive cN+ patients than in the naive cN0 patients with occult lymph node metastasis (41.67% vs. 68.18%, 16.67% vs. 63.31%, P=0.004). CONCLUSIONS: Most metastatic lymph nodes of glottic carcinoma locate at ipsilateral levels II, III and IV, especially at level II. Cervical lymphatic metastasis affects the prognosis of glottic carcinoma.