Prognostic value of body mass index before treatment for laryngeal squamous cell carcinoma

Objective: Patients with head and neck cancer often suffer from malnutrition. This study aims to investigate the influence of body mass index(BMI) on the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods: A total of 473 patients with LSCC initially treated at Sun Yat-sen University Cancer Center between January 2005 and July 2009 were retrospectively reviewed. Survival analysis was performed by the Kaplan-Meier method and Cox regression model.Results: Low BMI before treatment was significantly associated with poor overall survival in patients with LSCC(P<0.001). BMI was an independent prognostic factor for patients with LSCC.Conclusion: Leanness before treatment was associated with poor prognosis in patients with LSCC. Good nutritional status is favorable to improve survival in patients with LSCC.

The Prognostic Value of Pathological and Molecular Margins Marked by p53 and eIF4E in Laryngeal Carcinoma

Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was studied in 253 cases and 67 cases respectively, the latter were pathological negative margin chosen from the former. Immunohistochemisty was used to detect the expression of eIF4E and p53 proteins. Results: The rate of pathological, p53 and eIF4E positive margins was 20.2%, 19.4% and 32.8% respectively. The recurrent rate of those with positive margins was higher than that of negative margins, which including pathological margin (70.6% vs 35.1%, P =0.0000), p53 margin (69.2% vs 33.3%, P =0.018) and eIF4E margin (63.6% vs 28.9%, P =0.018); The survival rate of those with negative margins was higher than those with positive margins, including pathological margin (the 5-year cumulative survival rate was 37.52% and 64.37% respectively, P =0.0023), p53 margin (the 5-year cumulative survival rate was 24.62% and 75.69% respectively, P =0.0012) and eIF4E margin (the 5-year cumulative survival rate was 43.31% and 77.52% respectively, P =0.0006). Conclusion: The prognosis of those with both pathological and molecular positive margins was worse than that of the negative margins; Both the eIF4E and p53 were useful markers to pick out the poor prognostic patients from those with pathological negative margin, and the former seemed to be more potential.

Relation between the Expression of K-ras in Hep-2 Cells and Development of Laryngeal Carcinoma~*

Objective： To investigate the expression of K-ras in human laryngeal squamous cell carcinoma cell lines （Hep-2） and its significance for establishing a solid foundation for further study of the relationship between human laryngeal squamous cell carcinoma and K-ras gene point mutations. Methods： The expression of K-ras in human laryngeal squamous cell carcinoma cell lines （Hep-2） and human pancreatic carcinoma cell lines （MIAPaCa-2） was detected by using RT-PCR. Results： The expression of K-ras mRNA in Hep-2 and MIAPaCa-2 was strong and positive. Conclusion： The expression of K-ras mRNA in human laryngeal squamous cell carcinoma cell lines （Hep-2） is positive. Development of laryngeal carcinoma might be related to the activation of K-ras gene point mutation.

Regulation of the cell cycle gene, BTG2, by miR-21 in human laryngeal carcinoma

MicroRNAs are short regulatory RNAs that negatively modulate gene expression at the post-transcriptional level, and are deeply involved in the pathogenesis of several types of cancers. To investigate whether specific miRNAs and their target genes participate in the molecular pathogenesis of laryngeal carcinoma, oligonucleotide microarrays were used to assess the differential expression profiles of microRNAs and mRNAs in laryngeal carcinoma tissues compared with normal tissues. The oncogeuic miRNA, microRNA-21 （miR-21）, was found to he npregulated in laryngeal carcinoma tissues. Knockdown of miR-21 by specific antisense oligonucleotides inhibited the proliferation potential of HEp-2 cells, whereas overexpression of miR-21 elevated growth activity of the cells, as detected by the colony formation assay. The cell number reduction caused by miR-21 inhibition was due to the loss of control of the G1-S phase transition, instead of a noticeable increase in apoptosis. Subsequently, a new target gene of miR- 21, BTG2, was found to be downregulated in laryngeal carcinoma tissues. BTG2 is known to act as a pan-cell cycle regulator and tumor suppressor. These findings indicate that aberrant expression of miR-21 may contribute to the malignant phenotype of laryngeal carcinoma by maintaining a low level of BTG2. The identification of the oneogenic miR-21 and its target gene, BTG2, in laryngeal carcinoma is potentially valuable for cancer diagnosis and therapy.

Expression of Hypoxia Inducible Factor-1α and Its Relationship to Apoptosis and Proliferation in Human Laryngeal Squamous Cell Carcinoma

Summary: To investigate the expression of hypoxia inducible factor-1 alpha (HIF-1α) and its relationship to apoptosis and proliferation in laryngeal squamous cell carcinoma (LSCC), immunohistochemical method was used to detect the expression of HIF-1α and PCNA. Tunnel technique was used to detect in situ cell apoptosis in LSCC. Our results showed that the expression of HIF-1α was related to the clinical stages of cancer and lymph node metastasis (P<0.05). The relationship between HIF-1α and PCNA was statistically significant (P<0.05) and no relationship was found between HIF-1α and apoptosis (P>0.05) It is concluded that HIF-1α plays a role in the carcinogenesis of laryngeal carcinoma and is correlated with proliferation, but bears no relationship with the apoptosis of tumor cells in LSCC.

Effect and mechanism of miR-34a on proliferation, apoptosis and invasion of laryngeal carcinoma cells

Objective: To discuss the effect and mechanism of miR-34 a on the proliferation, apoptosis and invasion of laryngeal carcinoma cells. Methods: The laryngeal squamous carcinoma Hep2 cells were transiently transfected with miR-34 a mimics and miR-34 a NC. The MTT, colony-forming assay, Hoechst staining and Annexin V-PI double staining flow cytometry were employed to detect the effect of miR-34 a on the viability and apoptosis of laryngeal squamous carcinoma Hep2 cells; Transwell assay to defect the effect of miR-34 a on the migration and invasion of laryngeal squamous carcinoma Hep2 cells; western blot and RTPCR assay to defect the effect of miR-34 a mimics on the expression of survivin and Ki-67 m RNA in laryngeal squamous carcinoma Hep2 cells. Results: Compared with miR-34 a NC group, the cell viability in miR-34 mimics group was significantly decreased(P<0.01), the cell apoptosis rate was significantly increased(P<0.01), the abilities of cell migration and invasion were significantly reduced(P<0.01) and the expression of survivin and Ki-67 m RNA was significantly decreased(P<0.01). Conclusions: The increased expression of miR-34 a can induce the apoptosis of Hep2 laryngeal carcinoma cells and inhibit the cell proliferation and invasion, which is related to the down-regulated expression of survivin and Ki-67.

Expression of Vascular Endothelial Growth Factor and Cyclooxygenase-2 in Laryngeal Squamous Cell Carcinoma and Its significance

n order to study the expressions of vascular endothelial growth factor （VEGF） and cyclooxygenase-2 （COX-2） in human laryngeal squamous cell carcinoma （LSCC） and its significance, the expression of VEGF mRNA and COX-2 mRNA in 62 cases of LSCC and 54 adjacent noncancerous laryngeal tissues and 9 normal human laryngeal mucous tissues was detected by using techniques of semi-quantitative RT-PCR. It was found that the expression level of VEGF and COX-2 mRNA was significantly increased in LSCC as compared with that in the normal human laryngeal mucous tissues （both P〈0. 01）, and the expression level of VEGF and COX-2 mRNA were significantly increased in stage Ⅲ＋ Ⅳtissues of LSCC as compared with the stage Ⅰ ＋ Ⅱ tissues of LSCC （P 〈0.01）. There was a high positive correlation between VEGF and COX-2 expression in LSCC （r= 0. 756,P〈0.01）. These data raise the possibility that VEGF and COX-2 may play key roles in the growth, invasion and metastasis of LSCC.

DETECTION OF HUMAN PAPILLOMAVIRUS L1 -16 AND -18 DNA AND EPSTEIN-BARR VIRUS DNA IN LARYNGEAL CARCINOMA

Objective: To look for the further evidence for HPV L1 HPV16 E6, HPV 18 E6 and EBV as carcinogenic factors in laryngeal carcinoma. Method: we examined representative numbers of specimens from laryngeal cancer with highly sensitive PCR technique for the presence of HPV L1 and high-risk types HPV16 E6, HPV18 E6 and EBV LMP1. Results: Using PCR detection, 7.3% samples were HPV L1 positive, 52.03% were HPV16 E6 positive, 30.89% were HPV18 E6 positive and 9.13% were EBV LMP1 positive. The low incidence of HPV L1 and high incidence of HPV-16 E6 and HPV18 E6 genes suggest that HPV might be integrated into tumor cells. Our results support a role of HPV-16 and HPV-18 infection in the pathogenesis of laryngeal carcinoma in China. Conclusion: Integration of E6 into host genome and stable expression of these genes may be associated with the carcinogenesis of laryngeal carcinoma. HPV-16 and HPV-18 may synergistically function on the pathogenesis of laryngeal carcinoma. Our results suggest an association of laryngeal carcinogenesis and infection with the high-risk HPV types 16, HPV 18 and EBV.

CORRELATION ANALYSIS BETWEEN STK15 GENE AND LARYNGEAL CARCINOMA

To explore the relationship between STK15 gene abnormal expression and laryngeal carcinoma. Methods: Tumor tissues and matched normal tissues were taken from 55 LSCC patients. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect STK15 expression in 110 specimens. Results: In 38 of the 55 cases (69.1%), the STK15 expression at the mRNA levels was higher than that of the paired normal tissue. The ratio of ADV (average density value) of STK15 gene to ADV of b-actin gene was 1.220.49 in the cancer tissue, and 0.990.54 in the paired normal tissue with a significant difference (t=4.539, P<0.01). Conclusion: There was obvious association between the STK15 overexpression and laryngeal carcinoma. It may serve as an alternative mechanism of activating the pathogenesis of human laryngeal squamous cell carcinoma.

Correlation between Survivin Expression and Laryngeal Carcinoma:A Meta-analysis

In order to provide evidence for evidence-based medicine in the treatment and prognosis of laryngeal cancer in China, the meta-analysis electronically retrieved the case-control studies published in China about the Survivin expression and its association with clinical pathological features in the tissues of laryngeal carcinoma. The results showed that a total of 25 case-control studies were finally included with 1333 cases of laryngeal cancer and 528 cases of controls. The difference in the expression of Survivin between the two groups was statistically significant [OR=18.34, 95% CI（11.82, 28.47）, P〈0.00001]. The difference in the expression of Survivin between laryngeal carcinoma patients with lymph node metastasis or not was statistically significant [OR=0.25, 95% CI（0.17, 0.37）, P〈0.00001]. The expression of Survivin in clinical Ⅰ–Ⅱ stage group was significantly lower than in the clinical stage Ⅲ–Ⅳ group [OR=0.24, 95% CI（0.18, 0.32）, P〈0.00001]. The expression of Survivin in patients with low/medium differentiation was significantly lower than that in those with high differentiation [OR=0.33, 95% CI（0.26, 0.43）, P〈0.00001]. The difference in the expression of Survivin among different T stages of laryngeal carcinoma was statistically significant [OR=0.35, 95% CI（0.21, 0.58）, P〈0.00001]. In conclusion, Survivin may play an important role in the occurrence and development of laryngeal carcinoma, and its high expression is related to the poor prognosis of patients with laryngeal cancer.

Studies on the interrelationship of Chinese laryngeal carcinoma and human papillomavirus

The studies described herein emphasize HPVDNA detection by applying consensus primers and multiple primers of modified polymerase chain reaction (PCR) to 124 cases of fresh tissue samples with different lesions of larynx. The consensus primers used were able to detect 9 types of HPVsDNAs ( HPV 6 , 11 , 16 , 18, 31 , 33,35, 42, and 583 , from which the positive cases were picked out for further identification of their genometypes of HPV-DNA by using multiple primers PCR. The results areas follows : (1)In the group of laryngeal carcinoma,the total positive rate of HPV infection was 49. 1 %(28/57) : 15. 8%(9/57)for HPV18, 12. 3%(7/57)for HPV16,5. 3 %(3/57) dual infection for HPV16 and HPV18 , 3. 5%(2/57) for mixed infection of HPV6/11 and HPV18 , and 12. 3%(7/57)for the other types. (2) In the cervical metastatic lymphnode group, 3 of the 14 cases (21. 4%) of cervical metastatic lymphnode showed positive HPV, among which there was 1 case of HPV16 infection , 1 case of HPV18 infection ,and 1 case of HPV16 and HPV18 dual infection, resulting in a rate at 7. 1% for the respective cases immediately above. (3) In the pecarcinomatous lesion group ,the positive rate of HPV infection tmixed infection of HPV6/11 and HPV18) was 11. 1 %(1/9). (4)In the vocal cord polypus group , the rate of positive reaction (HPV6/11) was 7.1% (1/14). (5) In the nomal laryngeal tissue group , 15 cases of normal laryngeal tissue adjacent to the carcinoma and 15 cases of normal laryngeal tissue opposite to the carcinoma were HPV-DNA negative.The results showed that the occurrence and development of laryngeal carcinoma were closely related to HPV infection. The distribution of genometypes of HPV varied in different lesions of larynx. The carcinogenic action of HPV in laryngeal carcinoma is also discussed in this paper.

Promoter Hypermethylation of DNA Repair Gene MGMT in Laryngeal Squamous Cell Carcinoma

The relationship between hypermethylation of CpG islands in the promoter regions of O^6- methylguanine DNA methyhransferase （MGMT） genes and laryngeal squamous cell carcinoma was explored. Methylation-specific PCR and semi-quantitative RT-PCR were used to study the promoter methylation and mRNA expression of the MGMT gene in laryngeal carcinoma tissues, tissues adjacent to the tumor and normal laryngeal tissues. Hypermethylation of MGMT gene was detected in 16 samples of 46 （34.8 %） laryngeal squamous cell carcinoma samples. However, the MGMT hypermethylation was not detected in all tissues adjacent to the tumors and normal tissues. No significant difference in MGMT gene hypermethylation was found in samples with different histological grades （χ^2= 3. 130, P=0. 077） or in samples from patients with different TNM status （χ^2= 3. 957, P=0. 138）. No expression of MGMT mRNA was detected in all hypermethylated laryngeal carcinoma tissues. The expression of MGMT mRNA was detected in all unmethylated laryngeal carcinoma tissues, tissues adjacent to the tumors and normal tissues. It suggests that MGMT gene promoter hypermethylation is associated with MGMT gene transcription loss in laryngeal carcinoma tissues and possibly plays an important role in carcinogenesis of laryngeal tissues.

Lenvatinib,sintilimab combined interventional treatment vs bevacizumab,sintilimab combined interventional treatment for intermediate-advanced unresectable hepatocellular carcinoma

BACKGROUND Bevacizumab and sintilimab combined interventional treatment(BeSiIT)and L envatinib and sintilimab combined interventional treatment(LeSiIT)are two commonly used therapeutic regimens for intermediate-advanced hepatocellular carcinoma(HCC)in clinical practice.AIM To compare the clinical efficacy and safety of BeSiIT and LeSiIT for the treatment of intermediate and advanced HCC.METHODS Patients diagnosed with intermediate-advanced HCC and initially treated with BeSiIT or LeSiIT in the Tianjin Medical University Cancer Institute and Hospital between February 2020 and July 2021 were included.The primary endpoint was progression-free survival(PFS),and the secondary endpoints were overall survival(OS),objective response rate(ORR),disease control rate(DCR),conversion rate,and treatmentrelated adverse events.RESULTS Total 127 patients met the inclusion criteria and were divided into BeSiIT and LeSiIT groups.Twenty-eight and fifty patients in the BeSiIT and LeSiIT groups,respectively,were assessed after 1:2 propensity score matching.PFS and OS rates were not significantly different between the two groups.No significant variations were noted in ORRs or DCRs according to the Response Evaluation Criteria in Solid Tumors(RECIST),and modified RECIST.BeSiIT group showed a better conversion rate than the LeSiIT group(P=0.043).Both groups showed manageable toxicity profiles.Multivariate analysis showed that the independent factors associated with PFS were alphafetoprotein levels and carcinoembryonic antigen score.CONCLUSION In intermediate-to-advanced HCC,the BeSiIT and LeSiIT groups exhibited acceptable toxicities and comparable PFS,OS,and ORR.

Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Post-hepatectomy liver failure(PHLF)is a common consequence of radical partial hepatectomy in hepatocellular carcinoma(HCC).AIMS To investigate the relationship between preoperative antiviral therapy and PHLF,as well as assess the potential efficacy of hepatitis B virus(HBV)DNA level in predicting PHLF.METHODS A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy.Receiver operating characteristic(ROC)analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses.Logistic regression analyses were performed to assess the independent risk factors of PHLF.The increase in the area under the ROC curve,categorical net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were used to quantify the efficacy of HBV DNA level for predicting PHLF.The P<0.05 was considered statistically significant.RESULTS Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF(P<0.05).HBV DNA level with an optimal cutoff value of 269 IU/mL(P<0.001)was an independent risk factor of PHLF.All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve,categorical NRI,and IDI,particularly for the fibrosis-4 model,with values of 0.729(95%CI:0.705-0.754),1.382(95%CI:1.341-1.423),and 0.112(95%CI:0.110-0.114),respectively.All the above findings were statistically significant.CONCLUSION In summary,preoperative antiviral treatment can reduce the incidence of PHLF,whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

Prognostic and Predictive Protein Biomarkers in Laryngeal Squamous Cell Carcinoma—A Systematic Review

Background: Despite recent advances in clinical management of laryngeal squamous cell carcinoma (LSCC), the overall 5-year survival continues to be poor. Consequently, biomarkers of treatment response will need to be identified. Proteomic strategies are one way to attempt to identify such biomarkers. Methods: The Medline, Embase and Cochrane Library databases were systematically searched until 1st March 2014 using the terms “larynx”, “squamous cell carcinoma”, “proteomic”, and “biomarker”. Articles which met inclusion criteria were assessed for the type of biomarker investigated, the proteomic technique used, and whether any validation had been performed. Results: Six studies identified biomarkers, including UCRP, ceramides, uPA, MT1-MMP, stratifin, transferrin, albumin, S100 calcium-binding protein A9, stathmin, enolase, PLAU, IGFBP7, MMP14, THBS1, and transthyretin. Transferrin was the only biomarker to appear in more than one study. Conclusions: Our review identified several potential biomarkers of outcome in LSCC. Well designed studies will need to further validate their use in the future.

Clinical significance of tumor-associated macrophage infiltration in supraglottic laryngeal carcinoma

Tumor-associated macrophages(TAMs) can elicit contrasting effects on tumor progression,depending on different tumor microenvironment.This study aimed to explore the correlation between TAM infiltration and clinicopathologic characteristics,metastasis,and prognosis of supraglottic laryngeal carcinoma.TAMs in intratumoral and peritumoral regions of 84 specimens of supraglottic laryngeal carcinoma tissues were detected by immunohistochemical staining with monoclonal CD68 antibody.The density of peritumoral CD68+ TAMs in recurrence cases(9/11) and in dead cases(17/23) were significantly higher than those in non-recurrence cases(33/73) and in survival cases(25/61),with significant differences(P = 0.024 and 0.007,respectively).The Kaplan-Meier survival analysis showed a significant relationship between the infiltration of both intratumoral and peritumoral CD68 + TAMs and the overall survival of patients.The 5year survival rate was significantly lower in the group with a high density of intratumoral CD68+ TAMs than in the group with a low density(39.6% vs.82.5%,P < 0.05).Similarly,the 5-year survival rate was significantly lower in the group with a high density of peritumoral CD68+ TAMs than in the group with a low density(50.6% vs.73.1%,P < 0.05).Cox regression analysis revealed that T classification,distant metastasis,and intratumoral or peritumoral CD68 + TAMs were independent factors for disease-free survival,whereas T classification and intratumoral CD68 + TAMs were independent factors for overall survival.The results indicate that TAM infiltration in supraglottic laryngeal carcinoma can be used to predict metastasis and prognosis and is an independent factor for prognosis.

Neoadjuvant chemotherapy with pingyangmycin can inhibit the amplification and metastasis of laryngeal squamous cell carcinoma

Objective:To evaluate the short-term effects of neoadjuvant chemotherapy with pingyangmycin(PYM)in the treat-ment of laryngeal squamous cell carcinoma.Methods:24 cases of laryngeal squamous cell carcinoma were treated with PYM before the operation,and the surgeries were undergone within one week after neoadjuvant chemotherapy.PCNA,p53,Bcl-2 and CD44v6 were detected in the specimens of tumor,retreated tumor and normal tissue using immunohistochemical methods.Results:Apoptosis could be detected more often in specimens with tumor and retreated tumor after chemotherapy than that before.The expression of PCNA,p53,Bcl-2 and CD44v6 in tumor tissue after neoadjuvant chemotherapy with PYM was weaker than that before the chemotherapy.There was significant difference in the positive ratio of PCNA,p53,Bcl-2 and CD44v6 be-tween retreated tumor and tumor.Conclusion:After neoadjuvant chemotherapy with PYM,a large number of tumor cells died.The amplification and metastasis of tumor were suppressed by neoadjuvant chemotherapy with PYM.

Prognostic Value of Ki67 and VE6F Expression in Laryngeal Squamous Cell Carcinoma

OBJECTIVE To investigate the prognostic value of measuring Ki67 and VEGF expression in laryngeal squamous cell carcinoma (LSCC). METHODS The expression of Ki67 and VEGF in 32 LSCC tissues was studied by immunohistochemical staining. Of these cases, 5 recurred (recurrent group), 3 cases metastasized (metastatic group), 8 cases died (deceased group) and 24 cased survived (survival group) over a 3 year period of follow-up after their operation. RESULTS The expression of Ki67 and VEGF in the deceased group was higher compared to that in the survival group (P<0.01). Overexpression of Ki67 was found in the recurrent group and in the metastatic group (P< 0.05). VEGF expression was higher in the recurrent group than in the non recurrent group (P<0.05). With Cox-regression of multivariate analysis, Ki67 (RR:3.236; P=0.001), the clinical T stage (RR: 1.382; P=0.029) and metastasis in lymph nodes (RR:0.316; P=0.033) were shown to be independent prognostic factors for survival of LSCC patients. CONCLUSION Ki67 and VEGF expression is related to the prognosis of LSCC. Overexpression of the 2 markers indicated poor prognosis of the disease, a finding which might be helpful for the treatment of laryngocar-cinoma.

Changing the paradigm：the potential for targeted therapy in laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.

Extensive laryngeal infiltration from a neglected papillary thyroid carcinoma: A case report

Papillary carcinoma of the thyroid is the commonest type of thyroid cancer. Laryngeal infiltration from papillary thyroid carcinoma is extremely rare, with only a few cases of partial invasion described in the literature. We present a very unusual case of complete infiltration of both thyroid and cricoid cartilages from a neglected papillary thyroid carcinoma in a 59-year-old male. This sequel resulted from refusal of the patient to undergo treatment when initially diagnosed. An invasion to such an extent has not been described in the literature before, and in this case warranted a total laryngectomy followed by radioactive iodine. Prompt management of papillary carcinomas is crucial for avoiding such complications. Future guidelines should include management options for the patients who deny treatment initially.