Neoadjuvant therapy with chemotherapy and immune checkpoint inhibitor for laryngeal function preservation in locally advanced hypopharyngeal cancer.

Purpose: To evaluate the efficacy and laryngeal function preservation of neoadjuvant treatment with chemotherapy and immune checkpoint inhibitor for locally advanced hypopharyngeal cancer (LAHPC). Methods: We retrospectively collected LAHPC patients who were diagnosed between February 2022 and June 2023. The patients received a combination of chemotherapy and immune checkpoint inhibitors as the neoadjuvant therapy. The response to treatment, laryngeal function preservation rate, and short-term survival were assessed. Results: A total of 20 patients were included. Of these patients, 17 (85.0%) had stage IVA-B disease. Ten (50%) and four (20%) patients achieved pathological complete response (PCR) and major pathological response (MPR) to the primary tumor, respectively. In addition, 6 patients had incomplete pathological response (IPR). In the neck, 19 patients had node-positive disease before treatment, and only 5 patients (26.4%) had PCR to regional lymph nodes. Pathologically positive lymph nodes were still observed in 14 (73.6%) patients. Significant downgrading on narrow-band imaging assessment in primary tumors was associated with a higher probability of PCR or MPR than those with IPR (92.9% vs. 33.3%, P=0.014). The overall rate of laryngeal preservation was 95.0%. No severe perioperative complications or perioperative death were found. All patients completed the recommended postoperative radiotherapy/chemoradiotherapy. The median follow-up period was 12.1 months. The 1-year progression-free survival and overall survival were 94.1% and 92.9%, respectively. During the follow-up period, all 19 patients who underwent laryngeal preservation surgery had their laryngeal function preserved. Conclusion: The addition of an immune checkpoint inhibitor to neoadjuvant chemotherapy effectively preserves laryngeal function without increasing complications related to surgery and postoperative radiotherapy in LAHPC.

Anti-oncogenic activity of Chibby in the development of human nasopharyngeal carcinoma.

The Wnt/ß-catenin pathway serves important roles in cancer development. The expression and function of Chibby (Cby), as a direct antagonist of ß-catenin, in nasopharyngeal carcinoma (NPC) has not been fully investigated. The present study revealed that the mRNA and protein expression of Cby was significantly lower in NPC tissue than in the adjacent normal tissue. Low expression of Cby was significantly associated with the tumor and the clinical staging. Furthermore, Cby overexpression inhibited the proliferation of human NPC SUNE1 cells and induced cell cycle arrest. In addition, Cby overexpression also significantly enhanced the susceptibility of SUNE1 cells to apoptosis. These results indicated that Cby might serve as an anti-oncogenic gene in the development of NPC and could represent a potential therapeutic target for the human NPC therapy.

Association between underlying medical conditions and fatality risk in H7N9-infected patients: a meta-analysis / 预防医学

Objective The objective of our study was to conduct meta-analyses that examined the association between H7N9-infected case-fatality risk (CFR) and underlying medical conditions (UMCs) by adjusting some potential factors variables. Methods The articles of observational studies and randomized controlled clinical trials (RCT) on the association between UMCs and the CFR of H7N9-infected patients were collected and selected according to inclusion and exclusion criteria. Meta-analysis was performed to calculate odds ratio (OR) or adjusted OR (AOR) and 95％ confidence interval (CI) to assess the association between H7N9-infected CFR and UMCs. Results Among 1934 screened articles, we identified 14 articles reporting the CFR of H7N9-infected patients based on UMCs data. The pooled summary estimates from these studies indicated that UMCs significantly increased the risk of death in H7N9 patients (OR=2.20, 95％CI: 1.76-2.76) . Subgroup analyses showed chronic respiratory diseases (CRD, OR=4.43, 95％CI: 1.73-11.31), immuno-suppressive disorders (ISD, OR=4.65, 95％ CI:1.48-44.70), and two UMCs and above (OR=2.13, 95％ CI: 1.26-5.97) were significantly associated with H7N9-infected CFR; while 60 years old and above (AOR=4.83, 95％CI: 1.29-18.09), male (AOR=2.35, 95％CI: 1.03-5.39), time intervals to oseltamivir treatment (over 5 days) (AOR=5.74, 95％ CI: 1.15-28.66) and hospitalization (over 8 days) (AOR=2.72, 95％CI: 1.20-6.15), and initially bilateral lungs infection (AOR=7.95, 95％CI: 1.56-40.41) of UMCs patients who died from H7N9 infection are much greater compared with non-UMCs. Stratification analyses confirmed statistically significant increasing effects of CFR were observed in 60 years old and above (AOR=2.20, 95％ CI: 1.12-4.30) , time intervals to oseltamivir treatment (over 5 days) (AOR=3.19, 95％CI: 1.56-6.53), and initially bilateral lungs infection (AOR=3.48, 95％CI: 1.74-6.95) compared with 0-59 years old, time intervals to oseltamivir treatment (5 days and below), and initially single lung infection respectively in H7N9-infected patients with UMCs. Conclusions We find that only CRD, ISD, and two UMCs and above are associated with increased risk of death in H7N9-infected patients. We also suggest that a high CFR is associated with 60 years old and above, delayed antiviral treatment, and initially bilateral lungs infection in H7N9-infected patients with UMCs.

An oncogenic function of retinoic acid receptor-α in the development of laryngeal squamous cell carcinoma.

The aberrant expression of retinoic acid receptor-α (RARα) has been reported in various types of cancer. However, its association with the prognosis and development of laryngeal squamous cell carcinoma (LSCC) has not yet been determined. Therefore, the present study aimed to examine the expression and function of RARα in patients with LSCC. The expression of RARα in LSCC tissues was investigated using immunostaining. An MTT assay and flow cytometry analysis were also performed to investigate the function of RARα in the proliferation and cell cycle of LSCC cells. The expression of RARα was significantly elevated in LSCC tissues compared with adjacent noncancerous tissues (78.1 vs. 6.3%, P<0.05). The overexpression of RARα was associated with poorly differentiated features of LSCC (P<0.05). Furthermore, the downregulation of RARα inhibited the proliferation of LSCC cells, and arrested the cell cycle at the G1 phase via upregulation of cyclin dependent kinase inhibitor 1A, which may be associated with inhibition of the protein kinase B signaling pathway. Therefore, the overexpression of RARα may contribute to the development of LSCC through the regulation of the cell cycle. The results of the present study provide evidence that RARα serves an important function in LSCC development and may be a potential therapeutic target or prognostic predictor for LSCC.

An analysis on non-medical cost contributed by smoking of smoking related diseases in main urban districts of Hangzhou / 预防医学

Objective The paper aims to leavn the direct non-medical costs of the major diseases associated with smoking in Hangzhou. Methods We investigated four general hospitals and a cancer hospital in Hangzhou by typical sampling method. The survey included fee of transportation, nutrition, care, travel and so on. Six major Smoking-related diseases were identified through literature review, and the attributable risk (AR) and the price index were obtained. Results In 2013, the direct non-medical costs of tobacco-related diseases in Hangzhou were as follows: lung cancer, gastric cancer, breast cancer, cerebrovascular diseases cost 427.1, 243.1, 71.6 , 1564.6 thousand yuan, respec tively and coronary heart disease cost 92632.3 thousand yuan and COPD cost 11252.0 thousand yuan. Conclusion The direct non-medical cost contributed by smoking is an important part of the burden of Smoking-related diseases and should be taken seriously.

Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells.

Despite recent advances in the therapy of non-small cell lung cancer (NSCLC), the chemotherapy efficacy against NSCLC is still unsatisfactory. Previous studies show the herbal antimalarial drug dihydroartemisinin (DHA) displays cytotoxic to multiple human tumors. Here, we showed that DHA decreased cell viability and colony formation, induced apoptosis in A549 and PC-9 cells. Additionally, we first revealed DHA inhibited glucose uptake in NSCLC cells. Moreover, glycolytic metabolism was attenuated by DHA, including inhibition of ATP and lactate production. Consequently, we demonstrated that the phosphorylated forms of both S6 ribosomal protein and mechanistic target of rapamycin (mTOR), and GLUT1 levels were abrogated by DHA treatment in NSCLC cells. Furthermore, the upregulation of mTOR activation by high expressed Rheb increased the level of glycolytic metabolism and cell viability inhibited by DHA. These results suggested that DHA-suppressed glycolytic metabolism might be associated with mTOR activation and GLUT1 expression. Besides, we showed GLUT1 overexpression significantly attenuated DHA-triggered NSCLC cells apoptosis. Notably, DHA synergized with 2-Deoxy-D-glucose (2DG, a glycolysis inhibitor) to reduce cell viability and increase cell apoptosis in A549 and PC-9 cells. However, the combination of the two compounds displayed minimal toxicity to WI-38 cells, a normal lung fibroblast cell line. More importantly, 2DG synergistically potentiated DHA-induced activation of caspase-9, -8 and -3, as well as the levels of both cytochrome c and AIF of cytoplasm. However, 2DG failed to increase the reactive oxygen species (ROS) levels elicited by DHA. Overall, the data shown above indicated DHA plus 2DG induced apoptosis was involved in both extrinsic and intrinsic apoptosis pathways in NSCLC cells.

Prognostic value of SATB2 expression in patients with esophageal squamous cell carcinoma.

SATB2, a member of the family of special AT-rich binding proteins, has been shown to affect numerous tumorigenesis. However, the role of SATB2 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, the SATB2 expression was examined at mRNA and protein levels by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry in ESCC tissues and adjacent non-cancerous tissues. Statistical analyses were applied to test the associations between SATB2 expression, clinicopathologic factors, and prognosis. Western blotting and qRT-PCR showed that the expression levels of SATB2 mRNA and protein were both significantly lower in SATB2 tissues than those in non-cancerous tissues. Immunohistochemistry analysis showed that SATB2 expression was significantly correlated with clinical stage and Histological differentiation. The results of Kaplan-Meier analysis indicated that a low expression level of SATB2 resulted in a significantly poor prognosis of ESCC patients. Importantly, multivariate analysis showed that low SATB2 expression was an independent prognostic factor for ESCC patients. In sum, our data suggest that SATB2 plays an important role in ESCC progression, and that decreased expression of SATB2 in tumor tissues could be used as a potential prognostic marker for patients with ESCC.

Downregulated Chibby in laryngeal squamous cell carcinoma with increased expression in laryngeal carcinoma Hep-2 cells.

Chibby (Cby) inhibits Wnt/ß-catenin-mediated transcriptional activation by competing with Lef-1 (the transcription factor and target of ß-catenin) to bind to ß-catenin. This suggests that Cby could be a tumor suppressor protein. In the present study, we examined Cby expression in laryngeal squamous cell carcinoma (LSCC) and its function and mechanism in laryngeal carcinoma cell lines. Cby expression levels were investigated by immunohistochemistry in a panel of 36 LSCC patient cases. The expression of ß-catenin, c-myc and cyclin D1 in Hep-2 were determined through RT-PCR and western blot analysis. Activity of Wnt/ß-catenin signaling pathway after overexpression of Cby was measured by TCF/LEF luciferase reporter gene assay. Proliferation, clone forming ability, cell cycle distribution and cell apoptosis of Hep-2 cells were detected by MTT assay, plate colony forming assay, flow cytometry and TUNEL assay, respectively. This study showed that expression of Cby protein was strongly downregulated in LSCC tumor tissues in comparison to normal laryngeal mucosa samples. No significant correlation was found between the expression of Cby in tumor tissue and gender, age, clinical stage and tumor differentiation of laryngeal cancer patients. When Cby was overexpressed in Hep-2 cells, the expression of cyclin D1 was reduced and ß-catenin activity was inhibited. Proliferation and plate colony forming assays revealed a significant inhibitory effect of Cby on growth and colony formation ability of Hep-2 cells after Cby overexpression in comparison to control and mock-infected cells. In addition, we also found that upregulated expression of Cby resulted in accumulation of numbers of cells in G0/G1 phase with concomitant decrease in S phase by cell cycle assay. TUNEL staining demonstrated that, compared with the control group, the rate of apoptosis in the plv-cs2.0-Cby group was significantly increased. Taken together, downregulation of Cby was observed in LSCC, but with no significant correlation to the clinicopathological features of LSCC patients. Overexpression of Cby effectively suppressed laryngeal carcinoma cell growth and promoted its apoptosis. A better understanding of the mechanisms of Cby gene activation in LSCC could provide potential novel therapeutic targets for human laryngeal carcinoma.

Expression and distribution of dendritic cells in nasal polyps.

The aim of the present study was to investigate the expression, distribution and function of dendritic cells (DCs) and to study their role in nasal polyps. The study involved 55 participants, 45 of whom had nasal polyps and were the study group and 10 who had normal inferior turbinates and were the control group. Immunohistochemical staining was used to visualize the expression and distribution of the S-100 protein. A double immunostaining method was used to visualize the CD1a and CD40 expression and the images were analyzed with Axioplan 2 microscopy. The expression level of the S-100 protein in the nasal polyps was higher than that in the normal inferior turbinates with a significant difference (P<0.01). The distribution area, number and density of the double stained cells in the nasal polyps were all greater than in the normal inferior turbinates (P<0.01). The S-100 protein and double stained cells were mainly located in the lamina propria below the mucous membrane. The present study demonstrates that DCs are involved in the pathogenesis of nasal polyps and the presence of CD40-positive DCs suggests that this was related to the reciprocal interaction between the DCs and T lymphocytes.

Effects of Ilex latifolia and Camellia sinensis on cholesterol and circulating immune complexes in rats fed with a high-cholesterol diet.

Hypercholesterolaemia is one of the risk factors for atherosclerosis and subsequent cardiovascular disease. Here, we investigated the effects of dietary supplementation with Ilex latifolia or green tea (Camellia sinensis) on the levels of plasma total cholesterol, high-density lipoprotein cholesterol and circulating immune complexes in Sprague Dawley rats fed with a high-cholesterol diet. We demonstrated that daily administration by gavage of I. latifolia or C. sinensis at doses of 1.0 or 2.0 g/kg body weight for 30 days resulted in a significant decrease in plasma total cholesterol levels and circulating immune complexes and an increase in high-density lipoprotein cholesterol in rats fed with a high-cholesterol diet compared with levels in the high-cholesterol diet control group. C. sinensis was more effective than I. latifolia. I. latifolia and C. sinensis could be used as food supplements to protect against the development of hypercholesterolaemia.