Utility of the psychomotor vigilance task in screening for obstructive sleep apnoea.

PURPOSE: The study aimed to assess the performance of the PVT in patients with suspected OSA, evaluate its role in population screening for OSA. METHODS: The NoSAS, STOP-Bang, ESS scores and PVT tests were performed after suspected OSA patients' admission, followed by PSG. Then we compared the PVT results, calculated the sensitivity, specificity and ROC curve of PVT, and analyzed the accuracy of STOP-Bang and NoSAS questionnaire combined with PVT in predicting OSA. RESULTS: A total of 308 patients were divided into four groups based on AHI: primary snoring (2.74 ± 1.4 events/h, n = 37); mild OSA (9.96 ± 3.25 events/h, n = 65); moderate OSA (22.41 ± 4.48 events/h, n = 76); and, severe OSA (59.42 ± 18.37 events/h, n = 130). There were significant differences in PVT lapses (p < 0.001) and reaction time (RT, p = 0.03) among the four groups. The PVT lapses and RT were positively correlated with AHI (p < 0.001) and ODI (p < 0.001), and negatively correlated with LSpO2 (p < 0.001). When diagnosing OSA (AHI ≥ 5 events/h), the AUCs of PVT, ESS, STOP-Bang, and NoSAS were 0.679, 0.579, 0.727, and 0.653, respectively; the AUCs of STOP-Bang and NoSAS combined with PVT increased. After combined PVT, the diagnostic specificity of STOP-Bang and NoSAS at nodes with AHI ≥ 5, ≥ 15 and ≥ 30 events/h increased to varying degrees. CONCLUSION: Patients with OSA exhibited impairment in the PVT, and the combination of the PVT and STOP-Bang or NoSAS scores can improve the diagnostic efficacy and specificity for OSA.

Effectiveness and safety of radiotherapy plus programmed death-1 inhibitors and lenvatinib in patients with advanced biliary tract carcinoma: a real-world study.

BACKGROUND: Radiotherapy (RT) may function synergistically with immunotherapy and targeted agents (TA). This study aimed to assess the effectiveness and safety of RT combined with programmed death-1 (PD-1) inhibitors and lenvatinib in patients with relapsed or refractory advanced biliary tract carcinoma (BTC). METHODS: This retrospective study included patients with relapsed or refractory advanced BTC who received RT combined with PD-1 inhibitors and lenvatinib at the Peking Union Medical College Hospital (PUMCH). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated. RESULTS: Thirty-one patients who received RT combined with PD-1 inhibitors and lenvatinib as a second- or later-line therapy were analyzed. RT sites were mainly distributed in the liver lesions (64.5%) and lymph nodes (58.1%). The ORR and DCR were 32.3% (10/31; 95% CI: 14.8-49.7) and 87.1% (27/31; 95% CI: 74.6-99.6), respectively. The median PFS (mPFS) and median OS (mOS) were 7.9 (95% CI: 7.1-8.7) and 11.7 (95% CI: 8.3-15.0) months, respectively. Subgroup analyses of this cohort included 12 and 19 patients who received concurrent and salvage (> 6 weeks after commencing PD-1 inhibitor therapy) RT, respectively. The salvage RT group had higher mOS (11.7 vs. 10.5; p = 0.75) and mPFS (7.9 vs. 6.9; p = 0.85) than the concurrent RT group; however, statistical significance was not reached. All patients experienced any-grade adverse events (AEs), and excessive PD-1 inhibitors or RT toxicity were not observed. CONCLUSIONS: RT, PD-1 inhibitors, and lenvatinib may be safely combined and have antitumor effectiveness in patients with advanced BTC.

Evaluation of sensory and safety quality characteristics of "high mountain tea".

High mountain tea (HT) is widely acknowledged as an essential resource of high-quality tea due to its adaptation to superior ecological environments. In this study, the sensory (aroma and taste) and safety (heavy metals and pesticide residues) characteristics of HT were characterized through sensory evaluation, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), flavor activity value, and risk factor analysis. The results elucidated that the aroma sensory characteristics of HT were tender and green, accompanied by sweet and slight chestnut. A total of 8 aroma compounds were identified as the primary substances contributing to the unique aroma characteristics; the difference in the ratio of "green substances" and "chestnut substances" might be the reason for different aroma characteristics in HT and LT (low mountain tea). The taste sensory characteristics of HT were high in freshness and sweetness but low in bitterness and astringency. The high content of soluble sugar (SS), nonester catechins, sweet free amino acids, and low content of caffeine and tea polyphenols were the primary reasons for its taste characteristics. Low temperature stress might be the most fundamental reason for flavor characteristics formation in HT. Furthermore, the pollution risks of 5 heavy metals and 50 pesticide residues in HT were less than 1. The complex ecosystem and low chemical control level were speculated to be the primary reasons for the high safety quality of HT. Overall, these findings provide a more comprehensive understanding of quality characteristics and their formation mechanisms in HT.

Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma.

Background: New and effective chemotherapy or targeted therapy strategies are needed against laryngeal squamous cell carcinoma (LSCC). We aimed to explore the antitumor effect of dual PI3K/mTOR inhibitor combined with autophagy suppression on LSCC and its underlying mechanism. Methods: Hep-2 and AMC-HN-8 cell lines were treated with the Akt inhibitor LY294002, mTOR inhibitor rapamycin, and dual inhibitor NVP-BEZ235 separately. The biological characteristics of in vitro proliferation, cell cycle, apoptosis, migration, invasion, and autophagy were analyzed, and the expression levels of PI3K/Akt/mTOR pathway-related proteins were also measured. The in vivo effects of NVP-BEZ235 combined with inhibition of autophagy using pharmacological inhibitor was further assessed. Results: Compared with Akt or mTOR inhibitor, NVP-BEZ235 had the most significant biological effects on LSCC cells. When combined with various autophagy inhibitors, along with siRNA against ATG7, NVP-BEZ235 showed a synergic antitumor effect in LSCC through increasing cell apoptosis and death both in vitro and vivo. Conclusions: NVP-BEZ235 exerted potent antitumor effects on LSCC, especially when combined with the autophagy inhibitor both in vitro and vivo, providing convincing experimental data for new molecular targeted therapy for LSCC.

Exposure assessment for Cox proportional hazards cure models with interval-censored survival data.

Mixture cure models have been developed as an effective tool to analyze failure time data with a cure fraction. Used in conjunction with the logistic regression model, this model allows covariate-adjusted inference of an exposure effect on the cured probability and the hazard of failure for the uncured subjects. However, the covariate-adjusted inference for the overall exposure effect is not directly provided. In this paper, we describe a Cox proportional hazards cure model to analyze interval-censored survival data in the presence of a cured fraction and then apply a post-estimation approach by using model-predicted estimates difference to assess the overall exposure effect on the restricted mean survival time scale. For baseline hazard/survival function estimation, simple parametric models as fractional polynomials or restricted cubic splines are utilized to approximate the baseline logarithm cumulative hazard function, or, alternatively, the full likelihood is specified through a piecewise linear approximation for the cumulative baseline hazard function. Simulation studies were conducted to demonstrate the unbiasedness of both estimation methods for the overall exposure effect estimates over various baseline hazard distribution shapes. The methods are applied to analyze the interval-censored relapse time data from a smoking cessation study.

Restoration of Deafferentation Reduces Tinnitus, Anxiety, and Depression: A Retrospective Study on Cochlear Implant Patients.

Patients with profound bilateral deafness (BD) are prone to suffering from tinnitus, which further leads to psychological comorbidities and makes it more difficult for patients to communicate with people. This study was aimed at investigating the effect of cochlear implants (CIs) on tinnitus distress and psychological comorbidities in patients with profound BD. This multicenter retrospective study reviewed 51 patients with severe postlingual BD who underwent cochlear implantation; 49 patients underwent unilateral cochlear implantation, and 2 patients underwent bilateral cochlear implantation. The patients were asked to complete all the questionnaires, including the tinnitus handicap inventory (THI), the visual analog scale (VAS) score, the Hospital Anxiety and Depression Scale Questionnaire (HADS), the Categories of Auditory Performance (CAP), and the Speech Intelligibility Rating (SIR), at least 4 months after implantation when the CI was on or off, in approximately May-June 2019. In our study, 94% (48/51) of BD patients suffered from tinnitus before CI, and 77% (37/48) of them suffered from bilateral tinnitus. In addition, 50.9% (26/51) of the CI patients were suffering from anxiety, 52.9% (27/51) of them were suffering from depression (score ≥ 8), and 66.7% (34/51) (27/51) of them were suffering from anxiety or depression. Cochlear implantation could reduce tinnitus more obviously when the CI was on than when the CI was off. Cochlear implantation also reduced anxiety/depression severity. There were significantly positive correlations between tinnitus severity and anxiety/depression severity before and after surgery. Moreover, hearing improvement is positively correlated with reduction level of tinnitus, the better hearing, and the lesser severity of tinnitus. Thus, along with effective restoration of deafferentation, cochlear implantation shows positive therapeutic effects on tinnitus and psychological comorbidities, providing a reference for future clinical and research work.

Transarterial Chemoembolization Followed by Radiotherapy Versus Sandwich Treatment for Unresectable or Ablative Hepatocellular Carcinoma.

OBJECTIVE: Our objective is to assess whether the outcome of intrahepatic unresectable or ablative hepatocellular carcinoma (HCC) could be improved by supplemental transarterial chemoembolization (TACE) following initial treatment of TACE with 3-dimensional conformal radiotherapy (3DCRT), compared to TACE followed by 3DCRT alone. METHODS: We retrospectively analyzed intrahepatic unresectable or ablative HCC patients who underwent TACE, followed by 3DCRT with or without additional TACE, from June 2010 to December 2016 at our institution. Survival was assessed using the Kaplan-Meier method and compared with the log-rank test. Cox regression analyses were used to identify factors that influenced prognosis. Toxicity profiles were evaluated using CTCAE 4.0. RESULTS: 27 patients received TACE with 3DCRT (TR group) and 11 received additional TACE following TACE and 3DCRT (sandwich group), respectively. The median intrahepatic progression-free survival (IPFS), progression-free survival (PFS), and overall survival (OS) in the TR group and sandwich group were 5.4 months vs. 17 months (P = 0.018), 5.4 months vs. 17 months (P = 0.008), and 13.5 months vs. 29.2 months (P = 0.011), respectively. Multivariate Cox regression demonstrated that TACE followed by radiotherapy alone had a shorter IPFS (HR: 2.516, 95% CI (1.136-5.570), P = 0.023) and PFS (HR: 2.637, 95% CI (1.182-5.880), P = 0.018) compared with the sandwich treatment. Hepatitis B virus reactivation occurred in 1 patient in the sandwich group. Myleosuppresion was considered a grade 3/4 adverse event. CONCLUSION: Unresectable or ablative HCC patients possibly benefit from the combination of TACE and 3DCRT followed by additional TACE therapy, compared with TACE followed by 3DCRT alone.

Throat Microbial Community Structure and Functional Changes in Postsurgery Laryngeal Carcinoma Patients.

The microbial community structure in the throat and its shift after laryngectomy in laryngeal squamous cell carcinoma (LSCC) patients were investigated. Thirty swab samples taken prior to laryngectomy (SLC), 18 samples 1 week after laryngectomy (SLCA1w), and 30 samples 24 weeks after laryngectomy (SLCA24w) from 30 LSCC patients were examined. Microbial diversity was profiled through sequencing the V3-V4 variable region of the 16S rRNA gene. Quantitative real-time PCR (qPCR) was used to validate the 16S rRNA sequence data for the V3-V4 region. The community structure and function of throat microbiota were assessed by PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states) analysis. Both alpha and beta diversity results showed significant differences in the throat microbiota of LSCC patients before and after laryngectomy (P < 0.05). The drinking index of the SLC group was positively associated with the genus abundance of Prevotella (P < 0.05). The SLCA1w group had lower abundances of Fusobacterium, Leptotrichia, Lachnoanaerobaculum, and Veillonella than the SLC group (P < 0.05). The SLCA24w group had higher abundances of Streptococcus and Leptotrichia as well as lower abundances of Fusobacterium and Alloprevotella than the SLC group (P < 0.05). The throat microbiomes of the SLC group could be implicated in human cancer signaling pathways, as evidenced by PICRUSt analysis (P < 0.05). Our study clarifies alterations in throat microbial community structure and function in LSCC patients during the perioperative period and postoperative recovery period.IMPORTANCE Laryngeal squamous cell carcinoma greatly impacts patients' lives, and noninvasive means of prognostic assessment are valuable in determining the effectiveness of laryngectomy. We set out to study the microbial structure changes in the throat before and after laryngectomy and found the gene functions of several throat bacteria to be associated with human cancer signaling pathways. Our findings may offer insights into the disease management of patients with laryngeal squamous cell carcinoma. We hope to provide a means of using molecular mechanisms to improve the prognosis of laryngeal cancer treatment and to facilitate relevant research.

The Atoh1 expression levels are correlated with the arrangement, ciliary morphology, and electrophysiological characteristics of ectopic hair cell-like cells.

Previous reports have suggested that the level and duration of Atoh1 expression are correlated with the survival, arrangement and stereociliary bundle-related morphology of hair cells during development, but whether Atoh1 expression levels are correlated with the arrangement, bundle formation and electrophysiological characteristics of newly formed hair cells is unknown. To address this question, cultured cochlear explants obtained from neonatal rats were treated with different titers of a human adenovirus serotype 5 (Ad5) vector encoding Atoh1 and/or EGFP (EGFP-Atoh1+/-). The results showed that higher EGFP-Atoh1 concentrations led to higher initial Atoh1 mRNA expression levels and induced greater numbers of ectopic hair cell-like cells (EHCLCs) in the lesser epithelial ridge (LER). Furthermore, gradual increases in the number of EHCLCs were associated with the progressive conversion of the LER region similarly to that of hair cells during development. Some of the cilia on EHCLCs with higher Atoh1 expression were regularly arranged in a manner similar to that of normal hair bundles. As demonstrated through patch clamp recordings, high Atoh1 expression was associated with significantly decreased proportions of cells with Ih currents, significantly reduced proportions of transient potassium channel currents, and potassium channel currents with a greatly increased mean amplitude, which indicated that EHCLCs with high Atoh1 expression were more mature than those with low Atoh1 expression. Overall, the evidence suggests that the Atoh1 expression levels affect not only the arrangement and ciliary morphology of hair cells but also the electrophysiological characteristics of Atoh1-induced EHCLCs, and these findings provide important guidance for future therapies aimed at treating deafness.

Triptolide induces toxicity in inner ear stem cells via promoting DNA damage.

Emerging evidence and clinical case reports have observed a risk of cytotoxic effects of triptolide in patients. We aimed to investigate the triptolide-induced toxicity in mouse inner ear stem cells. The utricular sensory epithelium from adult BALB/C6 mice was used for the isolation of inner ear stem cells. Sphere formation assay was applied to examine the stemness of the cells. Cell count kit-8 and Bromodeoxyuridine assays were employed to detect the cell proliferation ability. Cell apoptosis was measured with Annexin V-FITC & propidium iodide Apoptosis kit. The relative expression levels of gamma H2A histone family member X (γH2AX), tumor suppressor p53-binding protein 1 (53BP1) and optic atrophy 1 (OPA-1) were measured by Western Blot. Mitochondrial function was analyzed by the MitoGreen green-fluorescent mitochondrial dye kit. Triptolide significantly inhibited the cell viability and proliferation and suppressed the capability of sphere formation. Furthermore, triptolide induced apoptosis as indicated by increased expression of DNA damage repair markers γH2AX and 53BP1. Moreover, triptolide influenced the function of mitochondria by inducing the cleavage of OPA-1. Our work clarifies the toxicity of triptolide in mouse inner ear stem cells, which provides clues of the toxicology mechanism for future studies and basis for clinical use.

Mimic Cochlear Implant Surgery-Induced Cochlear Infection Fails to Further Damage Auditory Pathway in Deafened Guinea Pigs.

BACKGROUND Kanamycin and subsequent furosemide administration was applied to the healthy guinea pigs to induce deafness. MATERIAL AND METHODS Of the deafened guinea pigs, 10 were further infused with anti-infection procedures (Group B) and the other 10 animals did not undergo anti-infection procedures (Group C). In Group B, the deafened animals were able to restore cochlear and middle ear functions following the anti-infection procedure. In Group C, all animals developed cochlear and middle ear infections. RESULTS Compared to the healthy guinea pigs, hair cells and spiral ganglion neurons (SGN) of deafened animals (in Group B and Group C) were severely damaged. SGN density of deafened animals was significantly lower than that of healthy control animals in all ear turns except the basal turn. There was no significant difference between Group B and Group C in SGN density. The average optical density value of neurofilaments of deafened animals was also significantly decreased after the ototoxic drug administration. Notably, the density of the neurons in the cochlear nucleus region (CNR) of the brainstem were not significantly different between the healthy control guinea pigs and deafened animals. CONCLUSIONS Mimic cochlear implant surgery-induced cochlear infection caused no significant damage to the auditory pathway in ototoxic drug-induced deafened guinea pigs.

The Role of the Notch Signal Pathway in Mucosal Cell Metaplasia in Mouse Acute Otitis Media.

Otitis media (OM) is a major cause of morbidity in pediatric and adult patients. This inflammatory condition is characterized by mucous cell hyperplasia that is thought to produce mucins from the middle ear mucosa. We are interested in the role of Notch signalling pathway in this inflammatory process. Using an acute otitis media (AOM) mouse model through injection of Streptococcus Pneumoniae into the middle ear, histopathologic examination and quantitative RT-PCR, acute inflammation with the thickness of mucosa, Goblet cell hyperplasia, and cilia loss were determined and gene expression related to the Notch signaling pathway were evaluated. Upregulation of the mucous cell markers, Argr2 and Muc5AC, and downregulation of the cilia cell marker, Foxj1 and Dnai2, were observed in AOM. In addition, genes encoding Notch receptors and ligands (Notch1, Notch2, Notch3, Notch4 and Dll1) and the Notch target genes (Hes1, Hes5, Hey1, NRARP) in AOM decreased significantly. The expression of the Notch1 and Jagged1 also showed down-regulation throughout the mouse middle ear epithelium. Taken together, this study suggests that downregulation of the Notch signaling pathway is involved in the mucosa hyperplasia during AOM.

MicroRNA-98 acts as a tumor suppressor in hepatocellular carcinoma via targeting SALL4.

MicroRNAs (miRs) are involved in the development and progression of hepatocellular carcinoma (HCC), but the regulatory mechanism of miR-98 in HCC still remains unclear. Here we found that miR-98 was significantly downregulated in HCC tissues compared to matched adjacent normal tissues (ANTs). Low miR-98 expression was associated with tumor size, metastasis, portal vein tumor embolus, and poor overall survival. Ectopic expression of miR-98 decreased the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells. SALL4 was identified as a novel target of miR-98, and the protein expression of SALL4 was inhibited by miR-98 in HCC cells. Overexpression of SALL4 reversed the suppressive effects of miR-98 on the malignant phenotypes of HCC cells. Besides, SALL4, upregulated in HCC tissues compared to the matched ANTs, was inversely correlated to the miR-98 levels in HCC tissues. In addition, overexpression of miR-98 markedly suppressed the tumor growth as well as tumor-induced death in nude mice. In summary, miR-98 plays a suppressive role in the proliferation, migration, invasion and EMT of HCC cells, partly at least, via directly inhibition of SALL4. Therefore, the miR-98/SALL4 axis may become a promising therapeutic target for HCC.

Activation of ETA Receptor by Endothelin-1 Induces Hepatocellular Carcinoma Cell Migration and Invasion via ERK1/2 and AKT Signaling Pathways.

Endothelin-1 (ET-1), a member of endothelins family, binds to ETA receptor (ETAR) and ETB receptor to exert its role in multiple cellular processes. Although ET-1 and its receptors has been reported to be overexpressed in many cancers, and overexpression of ET-1 is able to trigger hepatocarcinogenesis in zebrafish, the functions of ET-1 and its receptors in hepatocellular carcinoma (HCC) cell migration and invasion remain unclear. In the present study, we found that ETAR was greatly expressed in HCC cells and HCC tissues. ETAR expression as well as ET-1 expression was associated with vascular invasion and tumor stage in HCC. Activation of ETAR by ET-1 dose-dependently promoted cell migration and invasion of HCC cells, while silencing of ETAR by siRNA or blocking of ETAR by specific inhibitor resulted in significant reduction in ET-1-mediated migration and invasion. Furthermore, ET-1 induced activation of ERK1/2 and AKT and increased MMP-3 production via ETAR. In addition, using inhibitors of ERK1/2 and AKT, we found that ERK1/2 and AKT pathways were both involved in ETAR-mediated migration, invasion, and MMP-3 production. Taken together, our findings suggest that activation of ETAR by ET-1 promotes HCC cell migration and invasion via activating ERK1/2 and AKT signaling pathways and upregulating MMP-3 expression. Thus, ETAR may play an important role in the progress of HCC.

The hepatitis B virus reactivation after transarterial chemoembolization in Chinese hepatocellular carcinoma patients with low serum hepatitis B virus DNA level.

OBJECTIVE: To investigate the reactivation of the hepatitis B virus (HBV) following transarterial chemoembolization (TACE) in Chinese hepatocellular carcinoma (HCC) patients with low serum HBV DNA level, and to analyze the factors related to HBV reactivation in HCC patients with low serum HBV DNA level. METHODS: From November 2011 to January 2014, 109 patients newly diagnosed with HCC with an HBV DNA level less than 2,000 IU/mL were enrolled in the study. These patients underwent at least two TACE procedures and were followed-up for at least 3 months to assess the reactivation of HBV DNA. Ten variables were compared in patients with and without HBV reactivation to evaluate the factors related to HBV reactivation in HCC patients with low serum HBV DNA level. RESULTS: Of 109 HCC patients with low level HBV DNA, nine patients were HBeAg-positive, the other 100 patients were HBeAg-negative. Twenty-three of 109 (21.1%) patients developed HBV reactivation after TACE. Of nine HBeAg-positive patients, 55.6% (5/9) developed HBV reactivation, while in 100 HBeAg-negative patients, the rate of HBV reactivation was 18% (18/100) (P=0.019). Of ten variables of patients with low level HBV DNA, the levels of AFP and HBeAg status were found to be significantly correlated with HBV reactivation. Nevertheless, on binary logistic regression analysis, only HBeAg-positive status was the independent predictor of HBV reactivation in HCC patients with low serum HBV DNA level (odds ratio, 7.41; P=0.013). CONCLUSION: HCC patients with low serum HBV DNA level still remain associated with risk of viral reactivation after TACE, and HBeAg-positive HCC patients have a higher risk than patients with HBeAg-negative status.

Role of the planar cell polarity pathway in regulating ectopic hair cell-like cells induced by Math1 and testosterone treatment.

Planar cell polarity (PCP) signaling regulates cochlear extension and coordinates orientation of sensory hair cells in the inner ear. Retroviral-mediated introduction of the Math1 transcription factor leads to the transdifferentiation of some mature supporting cells into hair cells. Testosterone, a gonadal sex steroid hormone, is associated with neuroprotection and regeneration in Central Nervous System (CNS) development. Experiments were performed in vitro using Ad5-EGFP-Math1/Ad5-Math1 in neonatal mouse cochleas. Establishment of ectopic hair-cell like cell(HCLC) polarity in the lesser epithelial ridge (LER) with or without testosterone-3-(O-carboxymethyl) oxime bovine serum albumin (testosterone-BSA) treatment was investigated to determine the role of the PCP pathway in regulating ectopic regenerated (HCLCs) through induction by Math1 and testosterone treatment. After Math1 infection, new ectopic regenerated HCLCs were detected in the LER. After the HCLCs developed actin-rich stereocilia, the basal bodies moved from the center to the distal side. Moreover, the narrower, non-sensory LER region meant that the convergent extension (CE) was also established after transfection with Math1. After 9 days of in vitro testosterone-BSA treatment, more Edu(+), Sox2(+), and HCLC cells were observed in the LER with an accompanying downregulation of E-cadherin. Interestingly, the CE of the Ad5-EGFP-math1 treated LER is altered, but the intrinsic cellular polarity of the HCLCs is not obviously changed. In summary, our results indicate that PCP signaling is involved in the development of ectopic HCLCs and the CE of the ectopic sensory region is altered by testosterone-BSA through downregulation of cell-cell adhesion. Testosterone-BSA and Math1 treatment could promote an increase in HCLCs in the LER through proliferation and transdifferentiation.

ABCG2 regulated by MAPK pathways is associated with cancer progression in laryngeal squamous cell carcinoma.

ATP-binding cassette, subfamily G, member 2 (ABCG2) overexpression has been associated with multidrug resistance and cancer progression by promoting proliferation and/or suppressing apoptosis, but how this process happens remains to be determined. In this study, the roles and the mechanisms of ABCG2 in the progression of Laryngeal squamous cell carcinoma (LSCC) were investigated. We found that introduction of ABCG2 siRNA into Hep-2 and Hep-2T cells significantly enhanced the intracellular accumulation of mitoxantrone (MX). Down-regulation of ABCG2 by transient RNAi inhibited cell proliferation and blocked cell cycle progression by regulating the expression of cyclin D3 and p21 Cip1. ABCG2 silence also induced cell apoptosis by regulating the expression of surviving, bcl-2 and the cleavage of poly (ADP-ribose) polymerase (PARP) in Hep-2 and Hep-2T cells. ABCG2-specific inhibitor, fumitremorgin C (FTC), and mitogen-activated protein kinase (MAPK) pathway inhibitor, U0126, inhibited cell proliferation and promoted cell apoptosis by degrading endogenous ABCG2 in Hep-2T cells. Furthermore, inhibition of MAPK pathway by U0126 enhanced anti-cancer effects of MX in vivo. In conclusion, suppression of ABCG2 inhibits the procession of LSCC tumor growth by regulating cell proliferation and apoptosis. Our data also provide more evidence for the importance of the MAPK pathway as a suitable therapeutic target for LSCC.

Association between carcinoembryonic antigen levels and the applied value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in post-operative recurrent and metastatic colorectal cancer.

Positron emission tomography (PET) using 18F-fluorodeoxyglucose has been widely used for analyzing cellular metabolism. The present study aimed to evaluate the association between the diagnostic value of PET/computed tomography (CT) in patients with post-operative recurrent and metastatic colorectal cancer (CRC), and the different levels of carcinoembryonic antigen (CEA). A total of 105 suspected recurrent and metastatic CRC patients (67 males and 38 females; mean age, 48.5 years) were included in this retrospective study. All the patients underwent PET/CT examination. The differences in the PET/CT diagnostic values of CEA-positive and -negative patients with recurrent CRC following surgery were retrospectively analyzed and compared. Among the 105 CRC patients, 87 exhibited recurrence and metastasis, as confirmed by histopathological diagnosis or clinical follow-up data. By contrast, the PET/CT examination results revealed that 85 cases were true positives (a false positive foci was diagnosed in one of the patients), 18 were true negatives and 2 were false negatives. Correspondingly, the sensitivity and degree of accuracy were 97.7 and 97.1%, respectively. The detection rates of PET/CT for the recurrence and metastases were 85.3% in the CEA-positive group and 75.7% in the CEA-negative group. No significant differences were observed between the two groups. Overall, CEA levels do not help improve the detection rate of PET/CT in the recurrence and metastasis of CRC. PET/CT imaging has a high sensitivity and degree of accuracy in detecting recurrence and metastasis following CRC surgery. Therefore, this method is ideal for monitoring relapsed and metastatic foci of post-operative colon cancer cases.

Association between glutathione S-transferase T1, M1, and P1 genotypes and the risk of colorectal cancer.

Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens. Genetic polymorphisms within the genes encoding for GSTs may therefore cause variations in their enzyme activity, which may in turn influence the interindividual susceptibility to cancers. In this study, we aimed to investigate the association between genetic polymorphisms of GSTT1, GSTM1, and GSTP1 and the risk of colorectal cancer (CRC) in 264 cases and 317 controls in a Chinese population. Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Our results showed that individuals with GSTT1 and GSTM1 null genotypes exhibited a higher risk of CRC (GSTT1, OR,1.66; 95% CI, 1.20-2.31, P=0.003; GSTM1, OR,1.57; 95% CI,1.13-2.18, P=0.007), while no association was observed for GSTP1 (P heterozygous=0.790 or P variant=0.261). Furthermore, individuals who simultaneously carried the null genotypes for both GSTT1 and GSTM1 showed a stronger risk association (OR, 1.95; 95% CI, 1.33-2.85; P<0.001). In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.