ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming.

Abnormalities of FGFR1 have been reported in multiple malignancies, suggesting FGFR1 as a potential target for precision treatment, but drug resistance remains a formidable obstacle. In this study, we explored whether FGFR1 acted a therapeutic target in human T-cell acute lymphoblastic leukemia (T-ALL) and the molecular mechanisms underlying T-ALL cell resistance to FGFR1 inhibitors. We showed that FGFR1 was significantly upregulated in human T-ALL and inversely correlated with the prognosis of patients. Knockdown of FGFR1 suppressed T-ALL growth and progression both in vitro and in vivo. However, the T-ALL cells were resistant to FGFR1 inhibitors AZD4547 and PD-166866 even though FGFR1 signaling was specifically inhibited in the early stage. Mechanistically, we found that FGFR1 inhibitors markedly increased the expression of ATF4, which was a major initiator for T-ALL resistance to FGFR1 inhibitors. We further revealed that FGFR1 inhibitors induced expression of ATF4 through enhancing chromatin accessibility combined with translational activation via the GCN2-eIF2α pathway. Subsequently, ATF4 remodeled the amino acid metabolism by stimulating the expression of multiple metabolic genes ASNS, ASS1, PHGDH and SLC1A5, maintaining the activation of mTORC1, which contributed to the drug resistance in T-ALL cells. Targeting FGFR1 and mTOR exhibited synergistically anti-leukemic efficacy. These results reveal that FGFR1 is a potential therapeutic target in human T-ALL, and ATF4-mediated amino acid metabolic reprogramming contributes to the FGFR1 inhibitor resistance. Synergistically inhibiting FGFR1 and mTOR can overcome this obstacle in T-ALL therapy.

Quercetin-3-O-α-L-arabinopyranosyl-(1→2)-ß-D-glucopyranoside Isolated from Eucommia ulmoides Leaf Relieves Insulin Resistance in HepG2 Cells via the IRS-1/PI3K/Akt/GSK-3ß Pathway.

For nearly 2000 years, Eucommia ulmoides Oliver (EUO) has been utilized in traditional Chinese medicine (TCM) throughout China. Flavonoids present in bark and leaves of EUO are responsible for their antioxidant, anti-inflammatory, antitumor, anti-osteoporosis, hypoglycemic, hypolipidemic, antibacterial, and antiviral properties, but the main bioactive compound has not been established yet. In this study, we isolated and identified quercetin glycoside (QAG) from EUO leaves (EUOL) and preliminarily explored its molecular mechanism in improving insulin resistance (IR). The results showed that QAG increased uptake of glucose as well as glycogen production in the palmitic acid (PA)-induced HepG2 cells in a dose-dependent way. Further, we observed that QAG increases glucose transporters 2 and 4 (GLUT2 and GLUT4) expression and suppresses the phosphorylation of insulin receptor substrate (IRS)-1 at serine612, thus promoting the expression of phosphatidylinositol-3-kinase (PI3K) at tyrosine458 and tyrosine199, as well as protein kinase B (Akt) and glycogen synthase kinase (GSK)-3ß at serine473 and serine9, respectively. The influence posed by QAG on the improvement of uptake of glucose was significantly inhibited by LY294002, a PI3K inhibitor. In addition, the molecular docking result showed that QAG could bind to insulin receptors. In summary, our data established that QAG improved IR as demonstrated by the increased uptake of glucose and glycogen production through a signaling pathway called IRS-1/PI3K/Akt/GSK-3ß.

Exercise for Neuropathic Pain: A Systematic Review and Expert Consensus.

Background: Neuropathic pain (NP), a severe and disruptive symptom following many diseases, normally restricts patients' physical functions and leads to anxiety and depression. As an economical and effective therapy, exercise may be helpful in NP management. However, few guidelines and reviews focused on exercise therapy for NP associated with specific diseases. The study aimed to summarize the effectiveness and efficacy of exercise for various diseases with NP supported by evidence, describe expert recommendations for NP from different causes, and inform policymakers of the guidelines. Design: A systematic review and expert consensus. Methods: A systematic search was conducted in PubMed. We included systematic review and meta-analysis, randomized controlled trials (RCTs), which assessed patients with NP. Studies involved exercise intervention and outcome included pain intensity at least. Physiotherapy Evidence Database and the Assessment of Multiple Systematic reviews tool were used to grade the quality assessment of the included RCTs and systematic reviews, respectively. The final grades of recommendation were based on strength of evidence and a consensus discussion of results of Delphi rounds by the Delphi consensus panel including 21 experts from the Chinese Association of Rehabilitation Medicine. Results: Eight systematic reviews and 21 RCTs fulfilled all of the inclusion criteria and were included, which were used to create the 10 evidence-based consensus statements. The 10 expert recommendations regarding exercise for NP symptoms were relevant to the following 10 different diseases: spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, cervical radiculopathy, sciatica, diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV/AIDS, and surgery, respectively. The exercise recommended in the expert consensus involved but was not limited to muscle stretching, strengthening/resistance exercise, aerobic exercise, motor control/stabilization training and mind-body exercise (Tai Chi and yoga). Conclusions: Based on the available evidence, exercise is helpful to alleviate NP intensity. Therefore, these expert consensuses recommend that proper exercise programs can be considered as an effective alternative treatment or complementary therapy for most patients with NP. The expert consensus provided medical staff and policymakers with applicable recommendations for the formulation of exercise prescription for NP. This consensus statement will require regular updates after five-ten years.

[Metabonomics research on lung tissue of rats with acute exacerbation of chronic obstructive pulmonary disease treated with mineral Chinese medicine Chloriti Lapis].

To study the effect of mineral Chloriti Lapis on pulmonary metabolites and metabolic pathways in lung tissues of rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). The AECOPD rat model of phlegm heat syndrome was replicated by the method of smoking combined with Klebsiella pneumoniae infection. Except for using UPLC-Q-TOF-MS analysis, SPSS 18.0, SIMCA 13.0 and other software were also used for statistical analysis. Through literature search and online database comparison, the differential metabolites were identified, and the possible metabolic pathways were analyzed. After 15 days of administration, PLS-DA analysis was carried out on lung tissue samples of rats in each group. The results showed that the metabolic profiles of lung tissues of rats in each group could be well separated, which indicated that Chloriti Lapis and aminophylline had significant intervention effect on the lung metabolic profile of rats with AECOPD. Moreover, the metabolic profile of Chloriti Lapis group was closer to that of control group, and the intervention effect was better than that of aminophylline group. As a result, 15 potential differential metabolites were identified: phytosphingosine, sphinganine, tetradecanoylcarnitine, L-palmitoylcarnitine, elaidic carnitine, lysoPC[18∶2(9Z,12Z)], lysoPC(16∶0), lysoPC[18∶1(9Z)], lysoPC(18∶0), stearic acid, lysoPC(15∶0), arachidonic acid, docosapentaenoic acid, linoleic acid and palmitic acid. Among them, Chloriti Lapis could significantly improve the levels of 10 differential metabolites of phytosphingosine, tetradecanoylcarnitine, L-palmitoylcarnitine, elaidic carnitine, lysoPC[18∶2(9Z,12Z)], lysoPC(16∶0), lysoPC[18∶1(9Z)], stearic acid, lysoPC(15∶0), and palmitic acid(P<0.05). The intervention effect of Chloriti Lapis group was better than that of aminophylline group. Analysis of metabolic pathways showed that there were 8 possible metabolic pathways that could be affected, and three of the most important metabolic pathways(pathway impact>0.1) were involved: linoleic acid metabolism, arachidonic acid metabolism, and sphingolipid metabolism. Chloriti Lapis had obvious intervention effects on lung tissue-related metabolites and metabolic pathways in rats with AECOPD, and the effect was better than that of aminophyllinne.

[Effects of mineral Chinese medicine Chloriti Lapis on contents of metal elements in plasma and lung tissue of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) rats].

The effects of Chloriti Lapis on metal elements in plasma and lung tissue of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) rats were studied. The rat AECOPD model with phlegm heat syndrome was established by smoking combined with Klebsiella pneumoniae infection. After the rats were treated by Chloriti Lapis,the contents of metal elements in plasma and lung tissue were determined by inductively coupled plasma-optical emission spectroscopy( ICP-OES) and inductively coupled plasma mass spectrometry( ICP-MS). The changes in the contents of metal elements were analyzed by SPSS 18. 0. Further,the correlations of differential metal elements( including Cu/Zn ratio) with differential metabolites in plasma,lung tissue and urine of AECOPD rats treated with Chloriti Lapis were analyzed. The results showed that Chloriti Lapis significantly up-regulated the contents of Fe,Al,Mn,Cu,Zn,Sn( P<0. 05),V,Co( P< 0. 01) and Cu/Zn ratio( P< 0. 05),and significantly down-regulated the contents of Ti( P< 0. 05)and Pb( P<0. 05) in the model rat plasma. It significantly increased the content of Be( P<0. 05) and decreased the contents of Mg,Ti and Al( P<0. 01) in model rat lung tissue. The element profiles of normal group,model group and Chloriti Lapis group can be well separated. Chloriti Lapis group and other groups were clustered into two categories. The taurine in plasma and phytosphingosine in lung tissue had the strongest correlations with differential metal elements. The Fe,Al,Mg,Be,Ti,V,Mn,Cu,Zn,Sn,and Co in Chloriti Lapis may directly or indirectly participate in the intervention of AECOPD rats. This group of metal elements may be the material basis of Chloriti Lapis acting on AECOPD rats,and reduce the Cu/Zn value in vivo. It was further confirmed that Chloriti Lapis could interfere with the metabolic pathways of taurine and hypotaurine in plasma and urine as well as the sphingolipid metabolism pathway in lung tissue of AECOPD rats. In addition,this study confirmed that long-term smoking can cause high-concentration Cd accumulation in the lung and damage the lung tissue.

[Herbal textual research on triditional Chinese medicine "Baihe"( Lilii Bulbus)].

To clarify the species and preparation of " Baihe"( Lilii Bulbus),a traditional Chinese medicine,we investigated the relative ancient Chinese literature on this medicine. The study concluded that Lilium brownii var. viridulum is the authentic lily for medical use. In the Ben Cao Yan Yi and some medical books in the Ming and Qing Dynasties,L. lancifolium( Juandan) was also mistakenly used as genuine lily,but most doctors believe that this variety should not be used for medicinal purposes; L. pumilum( Shandan)began to be used as a medicine from Ri Hua Zi Ben Cao,but mainly for surgery,the effect is also different from L. brownii var. viridulum. We suggested Shandan be used as the species for another medicine as " Hong Bai He( red lily) " due to its red flower. All above three species recorded in the Chinese Pharmacopoeia are not corresponded to the condition of ancient doctors' uses. Therefore,as for developing of traditional classical formula,L. brownii var. viridulum should be chosen and used as Baihe. The birth places for Baihe include Gansu,Hubei,Anhui and Shandong province. The drug preparations of Baihe include crude medicine,roasting and steaming,which preparation should be chosen depends on the formula which contains Baihe.

Cytotoxic indole alkaloids from Nauclea orientalis.

A new indole alkaloid, nauclorienine (1), along with seven known alkaloids (2-8), were isolated from the stems and leaves of Nauclea orientalis. Among them, nauclorienine (1) was a new indole alkaloid holding a rare corynanthe-type skeleton, and the known compounds (2-8) were isolated from N. orientalis for the first time. Their structures were elucidated on the basis of extensive spectroscopic data analyses. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Alkaloids 1-4 exhibited significant inhibitory effects against various human cancer cell lines with IC50 values comparable to those of cisplatin.

Bioactive polyoxygenated seco-cyclohexenes from Artabotrys hongkongensis.

Six new polyoxygenated seco-cyclohexenes, artahongkongenes A-F (1-6), together with six known analogues (7-12) were isolated from the stems and leaves of Artabotrys hongkongensis. Their structures were elucidated by extensive spectroscopic methods. All new compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. New seco-cyclohexenes 1-6 showed significant inhibitory effects against various human cancer cell lines with IC50 values ranging from 0.26 to 16.58 µM.

A new polyoxygenated cyclohexene derivative from Artabotrys hainanensis.

A new polyoxygenated cyclohexene derivative, artahainanol A (1), together with three known analogues (2-4), was isolated from the stems and leaves of Artabotrys hainanensis. Among them, 1 is an unusual polyoxygenated cyclohexene containing 14 carbon atoms on the carbon skeleton. All known compounds (2-4) were isolated from the genus Artabotrys for the first time. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1-4 showed significant inhibitory effects against various human cancer cell lines with IC50 values ranging from 2.68 to 18.32 µM.

A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil.

BACKGROUND: Emergence agitation (EA) is a common phenomenon in preschool children during emergence from general anesthesia. This study evaluated the safety and efficacy of dezocine for emergence agitation in preschool children anesthetized with sevoflurane-remifentanil. METHODS: A total of 100 preschool children, scheduled for elective laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia were randomized into two groups: Group C (n = 50) received Ringer's lactate 10 mL and Group D received Ringer's lactate 10 mL containing dezocine 0.1 mg/kg, postoperatively. RESULTS: Incidence of EA, defined as a score ≥ 3 on Aono's four point scale or Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10 in the PACU (10% vs. 76%) and the percentage of patients with severe EA (PAED score ≥ 13) (12% vs. 76%) were significantly lower in Group D compared to Group C (P < 0.05). Mean Children and Infants Postoperative Pain Scale (CHIPPS) score was significantly lower in Group D compared to Group C (1.2 ± 0.5 vs. 5.2 ± 0.6; P < 0.05). Patients need for fentanyl (18% vs. 4%) or propofol rescue (20% vs. 0) was significantly greater in Group C compared to Group D. No significant differences in other relative aspects after surgery between groups. CONCLUSION: Administration of dezocine 0.1 mg/kg decreased the incidence and severity of EA in preschool children that had undergone laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia. TRIAL REGISTRATION: A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil effectively: A double-blind, prospective, randomized, controlled study, Chinese Clinical Trial Registry (ID: ChiCTR-IOR-16010033), retrospectively registered on November 21, 2016.

Butorphanol suppresses fentanyl-induced cough during general anesthesia induction: A randomized, double-blinded, placebo-controlled clinical trial.

Fentanyl-induced cough (FIC) is unwanted in the patients requiring stable induction of general anesthesia. This study was designed to evaluate the suppressive effects of butorphanol pretreatment on the incidence and severity of FIC during the induction of general anesthesia. A total of 315 patients of American Society of Anesthesiologists physical status I and II, scheduled for elective surgery under general anesthesia were randomized into 3 equally sized groups (n = 0105). Two minutes before fentanyl bolus, group I received intravenously 5 mL normal saline, groups II and III received butorphanol 0.015 and 0.03 mg/kg (diluted with saline to 5 mL), respectively. Patients were then administrated with fentanyl 2.5 µg/kg within 5 s. The incidence and severity of FIC was recorded for 2 minutes after fentanyl bolus. During experimental period, the mean arterial pressure, heart rate, and peripheral capillary oxygen saturation (SpO2) were recorded before the administration of butorphanol or normal saline (T0), 2 minutes (T1) after butorphanol injection, and 2 minutes (T2) after fentanyl injection. The incidence of FIC was 31.4% in group I, 11.4% in group II, and 3.8% in group III. Group III had a lowest incidence of FIC among 3 groups (P < 0.001, vs group I; P < 0.05, vs group II). The severe FIC was not observed in groups II and III, but was recoded from 6 patients in group I. At 2 minutes after fentanyl injection (T2), the mean arterial pressure was significantly higher in group I than that in groups II and III (P < 0.01, vs group II; P < 0.05, vs group III), but the values remained within safe limits. In conclusion, pretreatment with butorphanol could effectively and safely suppress FIC during anesthesia induction.

Stathmin and phospho-stathmin protein signature is associated with survival outcomes of breast cancer patients.

Currently, Stathmin1 (STMN1) and phospho-STMN1 levels in breast cancers and their clinical implications are unknown. We examined the expression of STMN1 and its serine phospho-site (Ser16, Ser25, Ser38, and Ser63) status by immunohistochemistry. Using Cox regression analysis, a STMN1 expression signature and phosphorylation profile plus clinicopathological characteristics (STMN1-E/P/C) was developed in the training set (n = 204) and applied to the validation set (n = 106). This tool enabled us to separate breast cancer patients into high- and low-risk groups with significantly different disease-free survival (DFS) rates (P < 0.001). Importantly, this STMN1-E/P/C model had a greater prognostic value than the traditional TNM classifier, especially in luminal subtype breast cancer (P = 0.002). Further analysis showed that patients in the low-risk group would benefit more from adjuvant paclitaxel-based chemotherapy (P = 0.002). In conclusion, the STMN1-E/P/C signature is a reliable prognostic indicator for luminal subtype breast cancer and may predict the therapeutic response to paclitaxel-based treatments, potentially facilitating individualized management.

Effects of VBMDMP on the reversal of cisplatin resistance in human lung cancer A549/DDP cells.

Tumor drug resistance is a major obstacle to cancer chemotherapy. We previously constructed a fusion protein based on two tumstatin-derived sequences named recombinant VBMDM (rVBMDMP). We preliminarily confirmed its inhibition of HUVEC and colon cancer cell growth. The present study further systematically observed the inhibitory effect of rVBMDMP on lung cancer cell growth and analyzed a possible mechanism to provide a theoretical basis for the development of new antitumor protein drugs. The effect of rVBMDMP on human lung adenocarcinoma (A549) and cisplatin-resistant human lung adenocarcinoma (A549/DDP) cell proliferation was evaluated by MTS assay. Hoechst 33342 staining performed together with fluorescence microscopy and immunoblot analysis were used to examine the effects of rVBMDMP on the apoptosis of A549/DDP cells. A protein phosphorylation chip was used to identify changes in rVBMDMP-induced signaling protein phosphorylation. Changes in the phosphatidylinositol 3 kinase (PI3K)/Akt signal transduction pathway and expression of multidrug resistance protein (MRP-2)-related molecules following rVBMDMP treatment in A549/DDP cells were evaluated by western blot analysis. A lung cancer xenograft model was used to evaluate the reversal effect of rVBMDMP on drug-resistance of A549/DDP cell tumors to cisplatin in vivo. The results demonstrated that rVBMDMP increased the phosphorylation of 79 signaling proteins, including focal adhesion kinase (FAK), caspase-6, Fas, FasL and FAF1 and downregulated 30 signaling proteins, including integrin αV, integrin ß3, PI3K/Akt, NF-κB and MRP-2 compared with the controls. rVBMDMP also increased the sensitivity of A549 and A549/DDP cells to cisplatin and directly induced apoptosis, which may be related to MRP-2 and Bcl-2 downregulation. The effects of growth inhibition and apoptosis induction of rVBMDMP on A549/DDP cells may be related to the inhibition of integrin αVß3 and PI3K/Akt protein phosphorylation. Finally, we observed an increase in cancer cell sensitivity to cisplatin by rVBMDMP using the A549/DDP cell xenograft model in nude mice. Our study suggests that rVBMDMP may be an effective potential chemotherapy sensitizer and may be a viable drug candidate in anticancer therapies.

Expression of CXCR4 is associated with progression and invasion in patients with nasal-surface basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer with an increasing incidence worldwide that imposes a considerable burden on public health. C-X-C chemokine receptor (CXCR4) plays a vital role in initiation, progression and metastasis of several types of cancers. The aim of the present study was to investigate the expression and clinical significance of CXCR4 in BCC. METHODS: In this study, 80 samples of primary BCC were assessed for CXCR4 expression using immunohistochemistry. The mRNA and protein expression levels of CXCR4 were evaluated by real-time reverse transcription polymerase chain reaction and Western blot analysis, respectively. RESULTS: CXCR4-positive staining was detected in 70% of BCC samples. Overexpression of CXCR4 was significantly associated with tumor size (>2 vs. 2 cm, p = 0.002) and pathological type (invasive vs. noninvasive, p = 0.007). CXCR4 was also upregulated at transcriptional and translational levels. CONCLUSION: Our study revealed that the expression of CXCR4 was associated with progression and invasion in patients with BCC. It may be a considerable biomarker to assess invasiveness of nasal-surface BCC and to guide clinical management of such tumors.

Spaceflight alters the gene expression profile of cervical cancer cells.

Our previous study revealed that spaceflight induced biological changes in human cervical carcinoma Caski cells. Here, we report that 48A9 cells, which were subcloned from Caski cells, experienced significant growth suppression and exhibited low tumorigenic ability after spaceflight. To further understand the potential mechanism at the transcriptional level, we compared gene expression between 48A9 cells and ground control Caski cells with suppression subtractive hybridization (SSH) and reverse Northern blotting methods, and analyzed the relative gene network and molecular functions with the Ingenuity Pathways Analysis (IPA) program. We found 5 genes, SUB1, SGEF, MALAT-1, MYL6, and MT-CO2, to be up-regulated and identified 3 new cDNAs, termed B4, B5, and C4, in 48A9 cells. In addition, we also identified the two most significant gene networks to indicate the function of these genes using the IPA program. To our knowledge, our results show for the first time that spaceflight can reduce the growth of tumor cells, and we also provide a new model for oncogenesis study.

[Expression and clinical significance of hypoxia-inducible factor-1alpha and cyclooxygenase-2 in laryngeal squamous cell carcinoma].

OBJECTIVE: To investigate the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and cyclooxygenase-2 (COX-2) in laryngeal squamous cell carcinoma (LSCC), while determine their relationship with clinicopathologic characteristics and prognosis. METHODS: Tumor tissues were obtained from 60 patients who underwent resection of laryngeal carcinoma in Affiliated First People's Hospital of Shanghai Jiaotong University. Immunohistochemistry (Envision DAKO) was used to detect the expressions of HIF-1alpha and COX-2 in the tumor tissues. As control group, 15 cases of atypical hyperplasia, 10 cases of leukoplakia of vocal cord and 10 cases of polyp of vocal cord were studied. All patients were regularly followed up and the clinical data were collected systematically. RESULTS: Positive staining rates of HIF-1alpha and COX-2 were 95.0% (57/60) and 98.3% (59/60), respectively in all 60 specimen of LSCC. The positive expressions in LSCC were significantly higher than those in atypical hyperplasia, leukoplakia and polyp of vocal cord ( Fisher's exact test, P < 0.01). The expression of HIF-1alpha was correlated with COX-2 in LSCC (r = 0.526, P < 0.01). High level expressions of HIF-1alpha and COX-2 were 35.0% (21/60) and 38.3% (23/60) respectively. High level expression of HIF-1alpha was significantly correlated with clinical stages (chi2 = 4.331, P < 0.05) and lymph nodes metastases (Fisher's exact test, P < 0.05). High level expression of COX-2 was significantly correlated with clinical stage (chi2 = 8.539, P < 0.01) and T stages (chi2 = 6.792, P < 0.01). With univariate analysis, high level expressions of HIF-1alpha and COX-2 were significantly associated with a worse overall survival (chi2 = 6.003, P < 0.05 and chi2 = 9.489, P < 0.01, respectively) and disease-free survival (chi2 = 5.010, P < 0.05 and chi2 = 6.102, P < 0.05, respectively). With multivariate analysis, recurrence and high level expression of COX-2 were two unfavorable prognostic factors (RR = 7.104, P = 0.003; RR = 5.714, P = 0.008). CONCLUSIONS: The expressions of HIF-1alpha and COX-2 played an important role in the process of tumorigenesis and development of LSCC, The expression of HIF-1alpha was correlated with COX-2 in LSCC. COX-2 and recurrence were probably significant risk factors for prognosis of LSCC.

Pharmacodynamics of rocuronium in cholestatic patients with or without hepatocellular injury: normal onset time of initial dose and prolonged duration time after repeated doses.

PURPOSE: A prospective controlled study was designed to observe the pharmacodynamics of rocuronium in cholestatic patients with or without hepatocellular injury. METHODS: Sixty patients undergoing abdominal surgery were allocated into three groups: group I had 20 cholestatic patients with hepatocellular injury; group II had 20 cholestatic patients without hepatocellular injury, and group III (control group) had 20 patients without hepatic disease. Anesthetized with propofol and fentanyl, all patients received rocuronium 0.6 mg/kg for initial dose followed by intermittent repeated administration of rocuronium 0.15 mg/kg. The twitch high of adductor pollicis muscle was monitored by acceleromyography. The onset time of the initial dose, the duration time of the initial and the repeated doses, and the recovery index were observed. RESULTS: The onset and the duration time of the initial dose had no significant difference among the three groups (P<0.05). After administration of the 5th dose, the duration time of the repeated doses was significantly prolonged than that of the 2nd dose in group I (31+/-8 versus 22+/-4 min) and group II (28+/-5 versus 21+/-4 min) (P<0.05), but not in group III (P>0.05). The recovery index of rocuronium was longer in group I (48+/-13 min) and group II (46+/-9 min) than that in group III (24+/-5 min) (P<0.05). CONCLUSION: Cholestatic patients experience prolonged duration time and longer recovery index after repeated use of rocuronium, despite normal onset time after the initial dose.

Autoantibodies as potential biomarkers for nasopharyngeal carcinoma.

Autoantibody signatures, as new biomarkers, may improve the early detection of nasopharyngeal carcinoma (NPC). We constructed a T7 phage cDNA library from mixed NPC tissues, and we isolated 31 tumor-associated proteins using biopan enrichment techniques with sera from NPC patients and from healthy population. DNA sequence analysis showed that among 31 phage-displayed proteins, 22 have sequence identity with known or putative tumor-associated proteins. The results of immunochemical reactivity of patients' sera with phage-expressed proteins showed enrichment in the number of immunogenic phage clones in the biopanning process and also confirmed that antibodies were present in the sera of patients but not in the sera of healthy donors. The autoantibody against phage-expressed protein MAGE, HSP70, Fibronectin, and CD44 measured by ELISA had greater predictive value than that against EBNA-1, respectively. The antibody levels against MAGE in sera positively correlated with the clinical stages of NPC, and the antibody levels against other three proteins partly correlated with the clinical stages of NPC. Our studies suggested that the autoantibodies against tumor-associated antigens in the sera of NPC patients could be used as a screening test for NPC. Studies of the corresponding proteins may have significances in tumor biology, novel drug development, and immunotherapy.

[Construction of eukaryotic expression vector encoding human nasopharyngeal carcinoma anti-idiotype antibody single chain fragment gene G22 and its expression].

OBJECTIVE: To construct a eukaryotic expression vector encoding human nasopharyngeal carcinoma anti-idiotype antibody single chain fragment (ScFv) gene G22, and to identify its expression in rectal cancer cells (CMT-93). METHODS: The G22 gene was ligated into the sites of EcoRI and NotI of eukaryotic expression vector pcDNA3.1(+). After the identification and DNA sequencing, the recombinant plasmid pc DNA3.1(+)-G22 was stably transfected into CMT-93 cells, and the expression of G22 was detected by Western blot, flow cytometry and immunofluorescence staining. RESULTS: Restriction enzyme digestion and DNA sequencing showed that the recombinant plasmid contained the human nasopharyngeal carcinoma anti-idiotype antibody ScFv gene G22. Transfection experiment verified that G22 gene could be expressed in CMT-93 cells in the right way. CONCLUSION: The eukaryotic expression vector containing the human nasopharyngeal carcinoma anti-idiotype antibody ScFv gene G22 is successfully constructed and expressed, which is the basis for further study of its DNA vaccine.

[Biological properties of Caski cell lines induced by exposing to the space environment].

OBJECTIVE: To investigate the biological properties of Caski cell lines induced by exposing to the space environment. METHODS: Caski cells were carried in "Shen Zhou IV" airship. After 7 days of spaceflight, cells survived and were monocoloned, and the experimental methods such as cell morphological observation, the cell proliferation assay, flow cytometry cell cycle analysis, the soft agar assay, and tumorigenesis assay were used to analyze cell growth characteristics and malignant phenotypes. RESULTS: Altogether 1440 strains subclonal cell lines were established and 4 strains were screened. Compared with the control group, mutated cells appeared to have multiple cell morphological changes. Strains numbered 44F10 and 17E3 were screened due to their increased cell proliferation and tumorigenesis, and their cell cycles were induced to progress from G(1) to S phase, while strains 48A9 and 31F2 were opposite to 44F10 and 17E3 in cytological events. The average population double time of ground nomal control group, ground simulant control group, strains numbered 44F10, 17E3, 48A9 and 31F2 groups were 56.54, 58.44, 52.96, 51.46, 101.76 and 88.47h, respectively; compared with the control group, the average double time of strains numbered 44F10 and 17E3 was decline, but with no statistical significance. However, compared with the control groups, the average double time of 48A9 and 31F2 was significant increased (P<0.05). The colony formation rates were 9.7%, 9.3%, 14.7%, 12.1%, 0 and 0.1%, respectively, and the difference between the ground control groups and the other groups was significant (P<0.01); 6 groups of above-mentioned Caski cells were inoculated subcutaneously in Babl/c nude mice respectively. Forty-seven days later, the formed tumors in the nude mice were statistically analyzed and tested. The average weight of tumors of the above-mentioned groups was 0.066, 0.066, 0.175, 0.249, 0.011 and 0.018g. The difference between the ground control groups and other groups was significant (P<0.05). CONCLUSION: Spaceflight may affect the physiological characteristics of tumor cells and the variation is complicated.