Synergy of enediyne antibiotic lidamycin and temozolomide in suppressing glioma growth with potentiated apoptosis induction.

The present work evaluated the synergistic efficacy of an enediyne antibiotic lidamycin (LDM) plus temozolomide (TMZ) against glioma in vitro and in vivo. LDM plus TMZ inhibited the proliferations of rat glioma C6 cells and human glioma U87 cells more efficiently than the single usage of LDM or TMZ. In addition, LDM also potentiated the apoptosis inductions by TMZ in rat C6 cells and human U87 cells. Meanwhile, the results of TdT-mediated dUTP Nick End Labeling assay for subcutaneous U87 tumor sections indicated an enhanced apoptosis induction in vivo by LDM plus TMZ, which confirmed the high potency of the combination for glioma therapy. As determined by Western blot, apoptosis signal pathways in C6 cells and U87 cells were markedly affected by the synergistic alteration of P53, bax, procaspase 3, and bcd-2 expression. In both subcutaneous U87 xenograft and C6 intracerebral orthotopic implant model, TMZ-induced glioma growth suppression was dramatically potentiated by LDM. As shown, the combination therapy efficiently reduced the tumor volumes and tumor weights of the human glioma U87 xenograft. Kaplan-Meier assay revealed that LDM plus TMZ dramatically prolonged the life span of C6 intracerebral tumor-bearing rats with decreased tumor size. This study indicates that the combination of LDM with TMZ might be a promising strategy for glioma therapy.

[Effect of drainage on microbial transformation processes of soil organic carbon in two typical wetlands of China]. / æŽ’æ°´å¯¹æˆ‘å›½ä¸¤ç§å ¸åž‹æ¹¿åœ°åœŸå£¤æœ‰æœºç¢³å¾®ç”Ÿç‰©è½¬åŒ–è¿‡ç¨‹çš„å½±å“.

Wetlands store one third of global soil organic carbon (SOC) and are strongly affected by artificial drainage. The impact of drainage-induced water-table decline on carbon cycling in different wetlands, particularly microbial transformation processes, remains unclear. To address this knowledge gap, we collected soil samples from two typical wetlands of China (a nutrient-poor bog located in Dajiuhu and a nutrient-rich fen in Hongyuan) and conducted an incubation experiment with the addition of 13C-labeled glucose to analyze the effects of short- and long-term drainage on SOC decomposition, extracellular enzyme activity, microbial carbon use efficiency (CUE), and microbial carbon accumulation efficiency (CAE). The results showed that both short- and long-term drainage significantly increased SOC decomposition rates in both wetlands (from 1.47 µg C·g-1·h-1 in submerged soils to 2.47 µg C·g-1·h-1 in drained soils), microbial biomass carbon derived from glucose (from 0.21 mg C·g-1 to 1.00 mg C·g-1) and CAE (from 0.29 to 0.73), but did not alter CUE (ranging from 0.34 to 0.86). Long-term drainage increased α-glucosidase activity in the Dajiuhu wetland and decreased ß-glucosidase and phenol oxidase activities in the Hongyuan wetland. In conclusion, drainage enhanced the 'microbial carbon pump' and its efficiency in wetlands mainly via increasing microbial intracellular metabolism (including respiration), but also acce-lerated SOC decomposition.

[Intraductal tubulopapillary neoplasm of the pancreas: a clinicopathologic study of 6 cases].

OBJECTIVE: To study the pathologic features, diagnosis, differential diagnosis and molecular characteristics of intraductal tubulopapillary neoplasm of the pancreas (ITPN). METHODS: The clinical findings, morphologic features, immunophenotype (by EnVision method) and KRAS gene alterations (by reverse transcriptase-polymerase chain reaction) of 6 cases of ITPN encountered during the period from January, 2001 to June, 2010 were analyzed. RESULTS: There were altogether 2 males and 4 females. The mean age of the patients was 64 years. Gross examination showed that the tumors were located in large pancreatic ducts and appeared as polypoid nodules with ductal obstruction. Solid tumor nodules associated with adjoining dilated ducts were identified in one case. Histologically, the tumors were characterized by tubulopapillary growth pattern without luminal mucin. The tumor cells showed high-grade nuclear atypia with scanty intracytoplasmic mucin. Intraductal necrotic foci were frequently observed. Immunohistochemical study showed that the tumor cells expressed CK7 and CK19. Focal positivity for MUC5AC was demonstrated. Two cases expressed MUC1. The staining for MUC2 was negative. KRAS gene mutations were identified in 2 cases, with a single-amino-acid substitution in codon 12 (35G > A and 35G > T/34G > A). CONCLUSIONS: ITPN is a newly described pancreatic intraductal neoplasm and different from intraductal papillary mucinous neoplasm. ITPN is characterized by intraductal tubulopapillary growth pattern, severe cytologic atypia and scanty mucin secretion.

Identification of a new Bombyx mori nucleopolyhedrovirus and analysis of its bro gene family.

The highly pathogenic Bombyx mori nucleopolyhedrovirus (BmNPV) has caused severe damages to sericulture in many countries, and the relationship between the pathogenicity of various BmNPV strains and their geographical evolution has been the topic of our interest. In this study, we isolated a new BmNPV strain from Thailand (BmNPV-Thai), based on the sequences of its conservative genes p10, p35, polh, egt and vp39. The BmNPV-Thai appears to have baculovirus repeated ORF (bro) genes different from four other well-known BmNPV strains of China (GD, CQ1), Japan (T3), and France (SC7); It only has bro-a, bro-c, and bro-d, but not bro-b and bro-e genes. These bro genes are localized only in the two subgroups highly homologous to their counterparts and their encoded BRO proteins differ mainly at their N-terminal amino acid residues. Phylogenetic analysis indicates that the evolution of the bro genes of the five BmNPV strains is not obviously associated with their geographic locations.

Math1 gene transfer based on the delivery system of quaternized chitosan/Na-carboxymethyl-beta-cyclodextrin nanoparticles.

Mammalian cochlear hair cells don't regenerate naturally after injury, which usually leave permanent hearing loss. Math1 gene is a positive regulator of hair cell differentiation during cochlear development and was proved to be very critical in hair cell regeneration in deaf animals. Generating new cochlear hair cells by forced Math1 expression may be a cure for hearing loss. However, satisfying gene delivering vectors in gene therapy are not available. We combined quaternized chitosan (QCS) with Na-carboxymethyl-beta-cyclodextrin (CM-beta-CD) as novel non-viral vector, which adsorbs pRK5-Math1-EGFP perfectly at the mass ratio of 4:1. In vitro cell transfection can reach a 40% transfect efficiency and relatively low cytotoxity than liposomes. These results suggest that QCS/CM-beta-CD nanoparticle complexes could be a novel non-viral gene carrier in further clinical application.

Enediyne lidamycin enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib, in epidermoid carcinoma A431 cells and lung carcinoma H460 cells.

Gefitinib, a low-molecular-weight epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is effective in a wide variety of tumor types. Preclinical studies have shown potentiated antitumor efficacies of this agent in combination with chemotherapy or radiotherapy. The antitumor antibiotic lidamycin (LDM) showed extremely potent cytotoxicity in vitro and marked therapeutic effect in vivo. In this report, the cytotoxic and biochemical activity of LDM and gefitinib on human epidermoid carcinoma A431 cells and human large cell lung cancer H460 cells as a single agent or in combination has been evaluated. In the MTT assay, LDM showed much more potent cytotoxicity than gefitinib to both cell lines. A431 cells with a highly EGFR-expressing level were more sensitive to gefitinib than H460 cells, which expressed EGFR at an intermediate level. LDM plus gefitinib showed potentiation of antiproliferative activity and apoptosis induction, which were associated with downregulation of EGFR signaling pathway and nuclear factor-kappa B expression, and the increase of cleaved poly (adenosine diphosphate-ribose) polymerase in the two cell lines, although to a lesser degree in H460 cells. Combined treatment induced G1 phase arrest similar to that of gefitinib alone in A431 cells and intensified G2/M phase accumulation in H460 cells. The above results indicate that LDM potentiates the effects of gefitinib in both gefitinib sensitive and less sensitive cells in association with enhanced inhibition of EGFR-dependent signaling.

Administration of adrenomedullin into subfornical organ inhibits Na(+),K(+)-ATPase activity in single proximal renal tubule of rats.

The present study was designed to investigate the effect of administration of adrenomedullin (ADM) into subfornical organ (SFO) on renal tubular Na(+),K(+)-ATPase activity in rats. Rats under anesthesia were injected with ADM 0.1 mL (20 ng/mL) via an implanted cannula into SFO (n=6). Plasma ADM and serum endogenous digitalis-like factor (EDLF) levels were assayed with radioimmunoassay, and urine samples were collected via a canoula intubated in bladder. Urinary sodium concentration was assayed with flame spectrophotometry. Single proximal renal tubule segments were obtained by hand under stereomicroscope and its Na(+),K(+)-ATPase activity was measured by liquid scintillation counting. In addition, single proximal renal tubule segments from normal rats (n=6) were incubated with serum from animals administered with ADM into SFO, and then the Na(+),K(+)-ATPase activity was determined. The results showed that both urinary volume and sodium excretion amounted to the peak value at 30 min after ADM administration, and sustained a significant high level at 60 min (P<0.01). At 30 min after ADM administration, there was a significant increase in serum EDLF and a decrease in Na(+),K(+)-ATPase activity of proximal tubule (P<0.01, respectively), but not in plasma ADM level. Na(+),K(+)-ATPase activity was decreased significantly in single proximal renal tubule segments from normal rats incubated with serum from rats administered with ADM into SFO (P<0.01). These results suggest that the diuretic and natriuretic responses following administration of ADM into SFO are associated with the inhibition of renal tubule Na(+),K(+)-ATPase activity. The inhibition of renal tubule Na(+),K(+)-ATPase activity is related to the increase in the serum level of EDLF.

[Inhibitory effect of lidamycin upon vasculogenic mimicry and its induction of apoptosis in glioma cells].

OBJECTIVE: To evaluate the in vitro effects of lidamycin upon vasculogenic mimicry and apoptosis induction in glioma cells. METHODS: Tube formation assay was performed to estimate the inhibitory effects of lidamycin upon vasculogenic mimicry in C6 and U87 glioma cells. The vasculogenic mimicry of glioma cells was photographed and enumerated. Annexin V-FITC/PI was used for determination of glioma cell apoptosis with flow cytometry. RESULTS: Vasculogenic mimicry assay indicated that 0.1 nmol/L, 0.5 nmol/L and 1 nmol/L lidamycin showed significant inhibition of vasculogenic mimicry in C6 and U87 cells. Comparing with C6 control group (14.7 +/- 1.2), 0.1 nmol/L (12.7 +/- 0.6), 0.5 nmol/L (9.0 +/- 1.7) and 1 nmol/L (4.7 +/-0.6) lidamycin inhibited vasculogenic mimicry in C6 cells with statistical significances (P = 0.013, P = 0.005 and P = 0.0002 respectively). Comparing with U87 control group (14.7 +/- 1.2), the vasculogenic mimicry of 0.1 nmol/L (10.0 +/- 2.0), 0.5 nmol/L (8.3 +/- 1.5) and 1 nmol/L lidamycin (4.3 +/- 0.6) treated U87 cells showed statistical significances (P = 0.025, P = 0.00 and P = 0.0009 respectively). The apoptotic ratios of same dosa ges lidamycin treated C6 cells and U87cells showed a similar tendency as vasculogenic mimicry inhibition (P < 0.001). Lidamycin was more potent than neocarzinostatin in vasculogenic mimicry inhibition and apoptosis induction of C6 cells and U87 cells. Conclusion Lidamycin can inhibit vasculogenic mimicry and promote apoptosis of glioma cells. Thus it is a promising drug in glioma treatment. Further researches on the therapeutic efficacy of enediyne antibiotics in glioma are needed.

Tetra-aqua-(1,10-phenanthroline)nickel(II) 3,6-dicarboxy-bicyclo-[2.2.2]oct-7-ene-2,5-dicarboxyl-ate.

In the title compound, [Ni(C(12)H(8)N(2))(H(2)O)(4)](C(12)H(10)O(8)), the Ni(II) ion is six-coordinated by two N atoms from one phenanthroline ligand and by the O atoms of four water mol-ecules in a distorted octa-hedral geometry. In the crystal, inter-molecular O-H⋯O hydrogen bonds form an extensive three-dimensional network, which consolidates the crystal packing.

Poly[[(µ(3)-5,6-dicarboxy-bicyclo-[2.2.2]oct-7-ene-2,3-dicarboxyl-ato)(1,10-phenanthroline)copper(II)] monohydrate].

In the title compound, {[Cu(C(12)H(10)O(8))(C(12)H(8)N(2))]·H(2)O}(n), the Cu(II) ion is five-coordinated by two N atoms from one phenanthroline ligand and three O atoms from three different H(2)L(2-) anions (H(4)L is bicyclo-[2.2.2]oct-7-ene-2,3,5,6-tetra-carboxylic acid) in a distorted square-pyramidal geometry. Each H(2)L(2-) ion bridges three Cu(II) atoms to form a zigzag sheet parallel to the ab plane. The crystal structure is consolidated by O-H⋯O hydrogen bonds.

[Protective effect of nitric oxide against hydrogen peroxide-induced hearing loss].

Previous research showed that reactive oxygen species (ROS) play an important role in ototoxity. The present research was to investigate whether nitric oxide, an important neurotransmitter in the inner ear, could prevent hydrogen peroxide-induced hearing loss through the nitric oxide/cyclic GMP pathway in guinea pig cochlea. Fifty adult pigmented guinea pigs (250~350 g) of either sex with positive prier reflex were randomly divided into five groups. All of the animals underwent whole cochlear perfusion for two hours. The solution that was perfused into the cochlear of different group was artificial perilymph (AP) for group 1200 micromol/L H2O2 for group 2100 micromol/L L-Arg for group 3, H2O2+L-Arg for group 4 and H2O2+L-Arg+L-NNA for group 5 respectively. Compound action potential (CAP, evoked by click) and cochlear microphonic (CM, evoked by tone burst) were recorded every thirty minutes to show the effects of different reagents on cochlear function. In order to assess cell viability after perfusion, the fluorescent dyes Hoechst that stains all cell nuclei and propidium iodide (PI) that specifically stains nuclei of dead cells, were used. The CAP threshold shifts and CM amplitude decreased after perfusion with H2O2+L-Arg. They were significantly lower than those of H2O2 group. No obvious cell death was noticed after H2O2+L-Arg perfusion, while only 54% of hair cells were alive after H2O2 perfusion. There were no significant differences between the group of H2O2 and that of H2O2+L-Arg+L-NNA group. Our results suggest that nitric oxide may partly be able to protect guinea pigs from hydrogen peroxide-induced hearing loss.

[Activating effect of ATP on NO/cGMP pathway in guinea pig cochlea].

The present investigation was to study the relationship between ATP and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway. Forty healthy purebred albino guinea pigs with sensitive pryer's reflex were randomly divided into five groups. Their cochleae were dissected and perfused immediately with different solutions. For the control group, the cochleae (group 1) were perfused with artificial perilymph basal solution (APBS, containing 100 micromol/L dipyridamole, 100 micromol/L L-Arg and 1 mmol/L IBMX). Other groups were respectively perfused group 2 with 330 micromol/L ATP, group 3 with 100 micromol/L L-NNA+330 micromol/L ATP, group 4 with 10 micromol/L ODQ+330 micromol/L ATP and group 5 with 10 micromol/L A-23187. All these reagents were freshly dissolved in artificial perilymph basal solution (APBS). The cochlear tissue specimens were collected and the average cGMP content was measured with (125)I-cGMP RIA kit. The results showed that there was no significant difference in the average cochlear tissue weights among different groups. The concentration of cGMP in the cochlear tissue of the groups perfused with ATP (59.541+/-8.744 fmol/mg) and A-23187 (55.416+/-7.018 fmol/mg) was significantly higher than those of the control group (30.089+/-4.876 fmol/mg), the groups perfused with L-NNA+ATP (28.761+/-5.019 fmol/mg) and ODQ+ATP (34.209+/-13.658 fmol/mg). No significant difference was observed between the group perfused with ATP and the one with A-23187, as well as among the control group and the groups perfused respectively with L-NNA+ATP and ODQ+ATP. These results suggest that ATP elevated the concentration of cGMP in cochlear tissue while administration of nonselective nitric oxide synthase inhibitor L-NNA and soluble guanylate cyclase inhibitor ODQ could prevent the increase of cGMP concentration induced by ATP. It is indicated that ATP is involved in the activation of NO/cGMP pathway by elevating concentration in the cytoplasm of the cochlea. In turn, NO/cGMP pathway may exert a negative action on the effects of ATP. It is suggested that there is an ATP/Ca(2+)-NO/cGMP pathway in the guinea pig cochlea. ATP and NO/cGMP pathway jointly regulate the function of the cochlea.

Synergistic inhibition of angiogenesis and glioma cell-induced angiogenesis by the combination of temozolomide and enediyne antibiotic lidamycin.

Present work mainly evaluated the inhibitory effects of lidamycin (LDM), an enediyne antibiotic, on angiogenesis or glioma-induced angiogenesis in vitro and in vivo, especially its synergistic anti-angiogenesis with temozolomide (TMZ). LDM alone efficiently inhibited proliferations and induced apoptosis of rat brain microvessel endothelial cells (rBMEC). LDM also interrupted the tube formation of rat brain microvessel endothelial cells (rBMEC) and rat aortic ring spreading. The blockade of rBMEC invasion and C6 cell-induced rBMEC migration by LDM was associated with decrease of VEGF secretion in a co-culture system. TMZ dramatically potentiated the effects of LDM on anti-proliferation, apoptosis induction, and synergistically inhibited angiogenesis events. As determined by western blot and ELISA, the interaction of tumor cells and the rBMEC was markedly interrupted by LDM plus TMZ with synergistic regulations of VEGF induced angiogenesis signal pathway, tumor cell invasion/migration, and apoptosis signal pathway. Immunofluorohistochemistry of CD31 and VEGF showed that LDM plus TMZ resulted in synergistic decrease of microvessel density (MVD) and VEGF expression in human glioma U87 cell subcutaneous xenograft. This study indicates that the high efficacy of LDM and the synergistic effects of LDM plus TMZ against glioma are mediated, at least in part, by the potentiated anti-angiogenesis.

Lidamycin up-regulates the expression of thymidine phosphorylase and enhances the effects of capecitabine on the growth and pulmonary metastases of murine breast carcinoma.

PURPOSE: Capecitabine (CAP), a prodrug, needs to be converted to 5-fluorouracil by several key enzymes, including thymidine phosphorylase (TP). To improve the therapeutic index, potentiation of antitumor activity of CAP is required. In this study, we explored whether lidamycin (LDM), an enediyne anticancer antibiotic, can induce synergistic antitumor effects in combination with CAP in murine breast cancer in vitro and in vivo. METHODS: Using MTT, cell migration and invasion, siRNA knockdown, and Western blot assays, the in vitro synergistic effects of LDM plus CAP on 4T1(LUC) cells were evaluated, and the mechanism of this synergy was explored. For in vivo model of orthotopic implantation model of 4T1(LUC) cells, optical molecular imaging system was utilized to evaluate the growth of primary tumor and metastasis. To further understand the mechanism of action of the LDM/CAP combination, immunohistochemistry analysis was carried out to detect thymidine phosphorylase induction and ERK signaling. RESULTS: As determined by MTT and transwell assay, LDM enhanced the inhibitory effects of CAP on cancer cell proliferation, migration, and invasion. Western blot showed that this synergistic effect was attributed to the up-regulated expression of TP induced by LDM. Knocking down TP impaired the synergistic anti-proliferative effect of LDM and CAP. Furthermore, our data suggested that LDM-induced up-regulation of TP both in vitro and in vivo is associated with ERK activation, because the inhibition of ERK activity by ERK inhibitor U0126 abrogated LDM-induced TP up-regulation. In animal models, LDM plus CAP potently inhibited primary tumor growth as well as lung metastasis compared with control or single-agent-treated group. CONCLUSIONS: LDM can potentiate the antitumor effects of CAP on breast cancer line. The synergistic effects suggest that the combination of LDM and CAP is an innovative antitumor strategy for breast cancer therapy.

Interaction of a calcium channel blocker with noise in cochlear function in guinea pig.

CONCLUSIONS: Both nifedipine and noise exposure had damaging effects on cochlear function. These damaging effects were subtractive rather than additive, suggesting that calcium channel blockers may have a protective role in noise-induced hearing loss. OBJECTIVE: We assessed the interaction of nifedipine, a calcium channel blocker, with noise in cochlear function by evaluating changes in the compound action potential (CAP) threshold after the administration of nifedipine with or without noise exposure. METHODS: Eighty guinea pigs were randomly assigned to eight groups based on those with cochlear perfusion with nifedipine only (0, 0.15, 0.5, and 3 µM, groups 1-4) and noise exposure (groups 5-8). CAP thresholds were recorded using a round window electrode before and 120 min after cochlear perfusion. RESULTS: Cochlear perfusion of different concentrations of nifedipine caused 2.5, 5.5, 28, and 21.5 dB SPL threshold shift, respectively, at 0, 0.15, 0.5, and 3 µM concentrations (groups 1-4). In comparison, the CAP thresholds after nifedipine perfusion with noise exposure were 43.5, 46.5, 20, and 21.5 dB SPL, respectively, in groups 5-8.

Characteristics of cochlear microphonics in infants and young children with auditory neuropathy.

CONCLUSIONS: Cochlear microphonics (CMs) play an important role in the diagnosis of auditory neuropathy (AN). It is necessary and helpful to diagnose the sites-of-lesion in infants and children with AN by analyzing the patterns of CM amplitudes and I/O functions together. OBJECTIVES: To investigate the characteristics and clinical significance of CMs in the diagnosis of AN among infants and children. METHODS: A total of 36 infants and children (16 males and 20 females) were divided into two groups. Group A included 15 children (30 ears) with auditory brainstem response (ABR) absent and distortion product otoacoustic emissions (DPOAEs) present and group B included 21 children (30 ears) with ABR absent and DPOAEs absent. Fifteen normal-hearing infants (30 ears) made up the control group. Click eliciting CMs were recorded at stimulus levels of 100, 90, 80, and 70 dB nHL for each ear using a button electrode placed at the top of the forehead. A tube-clamping method was used to distinguish CMs from artifacts, and an averaging algorithm was used to obtain a clear CM waveform. The time delay and amplitude of CMs were measured in both children with AN and normal-hearing infants on (C-R)/2 waveforms, and an I/O function curve for each group was plotted with the stimulating level as input and the CM amplitude as output. RESULTS: The largest identifiable CMs were generally found between 0.5 and 0.8 ms after stimulation with mean delay of 0.63 ± 0.04 ms in both group A and the control group, and 0.63 ± 0.07 ms in group B. There was no significant difference between the AN group and the control group in CM time delay. There was no significant difference (p > 0.05) between group A (AN with OAEs present, 0.47 ± 0.15 µV) and the control group (0.45 ± 0.13 µV) in CM amplitude, while CM amplitudes in children with AN with DPOAEs absent (0.24 ± 0.08 µV) were significantly lower than those in either the control group or group A (p < 0.01). The amplitude of CMs reduced with stimulus intensity in all the subjects. There was obvious nonlinearity in group A and the control group, while there was a more linear tendency in amplitude increasing on the I/O function curve in group B.

Excimer laser atherectomy combined with drug-eluting balloon angioplasty for the treatment of chronic ischemia of lower limbs: preliminary results in three patients / 介入放射学杂志

Objective To evaluated the safety and feasibility of excimer laser atherectomy (ELA) combined with drug-eluting balloon angioplasty in treating chronic ischemia of lower limbs.Methods ELA combined with paclitaxel-eluting balloon angioplasty was adopted to treat chronic ischemia of lower limbs caused by arteriosclerosis occlusive disease of lower extremity in three patients.All three patients had arteriosclerosis occlusive disease of superficial femoral artery;in two of them the disease was primary occlusive lesion and in another patient the disease was in-stent re-occlusion lesion after sten implantation.Results After the treatment,the blood flow in the diseased arteries was unobstructed,the blood supply of the lower limbs was obviously improved.No procedure-related complications occurred.Two weeks after the treatment,no recurrence of ischemic symptoms was observed,the blood flow in superficial femoral artery kept unobstructed.The patients recovered smoothly.Conclusion For the treatment of chronic ischemia of lower limbs,which are caused by the primary arteriosclerosis occlusive disease of lower extremity or by the in-stent re-occlusion lesion after sten implantation,ELA combined with paclitaxel-eluting balloon angioplasty is clinically safe and feasible,although its long-term effect needs to be clarified with more studies.

Endostar, a modified recombinant human endostatin, exhibits synergistic effects with dexamethasone on angiogenesis and hepatoma growth.

We evaluated the efficacy of a combination strategy, Endostar, a modified recombinant human endostatin, plus dexamethasone, against angiogenesis and hepatoma growth. By colony formation assay, synergistic effects of the combination of Endostar and dexamethasone were observed on the proliferations of human umbilical endothelial cells and hepatoma Bel-7402 cells. Endostar plus dexamethasone inhibited angiogenesis events in vitro. Examined with transwell assay, HUVECs invasion was more efficiently suppressed by combination of Endostar and dexamethasone than by the respective single drug. But the combination treatment of Endostar and dexamethasone to Bel-7402 cells did not alter the migration of HUVECs. The migration of HUVEC tended to coincident with VEGF secretion as determined by ELISA. Tube formation assay, rat aortic ring assay and chick embryo chorioallantoic membrane (CAM) assay indicated that the anti-angiogenesis effects of Endostar were significantly enhanced by dexamethasone. In mouse hepatoma H22 and human hepatoma Bel-7402 subcutaneous xenograft, Endostar plus dexamethasone presented more potent efficacy in tumor growth suppression than the single drug treatments. The above confirms the synergism of Endostar and dexamethasone on anti-angiogenesis and suppression of hepatoma growth. The potentiation effects of the combination indicate that Endostar plus dexamethasone might be a positive strategy for cancer therapy.

[Analysis of improper pattern of Mandarin monosyllable recognition test among the patients with auditory neuropathy].

OBJECTIVE: To analyze the improper pattern in mandarin monosyllable recognition test among the patients with Auditory Neuropathy (AN) in order to work out the common characteristics in speech recognition which might be suitable for diagnosis of AN. METHODS: Sixteen AN patients (32 ears) were studied and 22 patients (32 ears) with sensorineural hearing loss (SNHL) were set for control. In accordance with audiogram pattern, all subjects were then divided into the up-type hearing (15 ears) and non up-type hearing (17 ears) groups. All 64 ears were tested in high intensity by mandarin monosyllable test material which we have developed before. Monosyllable performance scores from testing ears and improper patterns were recorded respectively. Eight improper patterns were then defined as follows: consonant only, vowel only, tone only, consonant and vowel, consonant and tone, vowel and tone, all phonemes and no response. RESULTS: The score of patients with AN was lower than those patients with SNHL in monosyllable recognition test (P < 0.001). No significant difference was found between subgroup of up-type hearing loss and SNHL group in percentage correct scores of monosyllables, consonants, vowels, and tones statistically (P > 0.05), but significant lower score was found in subgroup of non up-type hearing loss compared with SNHL group in these 4 percentage scores concerned (P < 0.001). Chi square test presented a significant difference in improper pattern proportion between AN and SNHL groups (P < 0.001), which could be related to more proportional tone recognition in the former's incorrect items. Improper pattern proportions between two AN subgroups presented a significant difference statistically (P < 0.001), which could be related to a larger proportional recognition of tones and vowels in subgroup of up-type hearing loss compared with subgroup of non up-type hearing loss. CONCLUSIONS: A poor performance might be a major clinical feature identified AN from SNHL in mandarin tone recognition. There are significant differences between AN patients with up-type hearing loss and patients with non up-type hearing loss in performance of monosyllable recognition and improper pattern proportion of tones and vowels. A psychophysical testing may be a key potential in diagnosis of AN in further clinical application.

[Tone-pip auditory brainstem response and auditory steady-state response of infants with normal hearing.].

OBJECTIVE: To estimate tone-pip auditory brainstem response (tone-pip ABR) and auditory steady-state response (ASSR) thresholds to follow the development of hearing in four groups of normal babies through the first 6 month of life and to make a comparison between the tone-pip ABR and ASSR for 0.25 - 8 kHz frequency range at different groups. METHODS: The tone-pip ABR and ASSR were recorded in four groups of normal hearing infants (160 ears) at the age of 2 - 4 day, 6 weeks, 3-month and 6-month. Tone-pip ABR and ASSR thresholds were established in 0.25, 0.5, 1, 2, 4 and 8 kHz stimuli. RESULTS: For click ABR, the wave latency of I, III, V and inter-wave latency of I-III, III-V and I-V decreased as the age increase. The developmental changes were obvious in wave I and III before 6 weeks and 3 months respectively. Tone-pip ABR had the similar waveform as the click ABR. With the frequency increasing, their waveforms and wave latencies of I, III and V were getting better and shorter respectively. There was significant difference between the thresholds of tone-pip ABR and ASSR (all P < 0.05). The tone-pip ABR thresholds were significantly lower than those of ASSR from 0.5 to 8 kHz. Both ASSR and tone-pip ABR had similar audiograms for different age of infants with normal hearing. CONCLUSIONS: The longitudinal findings presented in this study suggest that with the maturational development, the wave latency of I, III, V and inter-wave latency of I-III, III-V and I-V of tone-pip ABR decrease as the age increase, while the hearing sensitivity have no changes. Both tone-pip ABR and ASSR have stable frequency specificity. Compared to the ASSR, tone-pip ABR have lower response threshold and maybe nearer to the hearing level of the infant.