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Gang Chen

Publications and source records attributed to Gang Chen.

At least 73 records · Page 4Linked to original sources

Lesion-induced neurogenesis in the hypothalamus is involved in behavioral recovery in adult ring doves.

Although neurogenesis in the brain of adult vertebrates is region dependent, lesion induces generation of new neurons in non-neurogenic brain regions. These findings raise the question of the role of new neurons in brain repair and functional recovery. We addressed this question by applying previous observations that electrolytic lesion induced neurogenesis in the ventromedial nucleus (VMN) of the hypothalamus in adult ring doves. Such lesions disrupted the male's courtship behavior, which could be reinstated after rehabilitation with a female. We investigated whether lesion-induced newborn neurons in the VMN facilitate the recovery of courtship behavior in the lesioned birds. We conducted systematic observations of cytological, morphological, and neuroanatomical changes in the lesioned VMN, and concurrently we monitored behavioral changes. Using a multitude of specific cell markers, we found a well-circumscribed cellular zone that proliferated actively. This highly proliferative zone initially appeared along the periphery of the lesion site, where cells had high levels of expression of neuronal, glial, and neurovascular markers. As newborn neurons matured at the lesion site, the necrosis gradually decreased, whereas a downsized proliferative zone relocated to a region ventral to the VMN. Some of the mature neurons were found to project to the midbrain vocal nuclei. Restoration of these projection neurons coincided with the recovery of courtship vocalization. Finally, we found that a social factor, that is, when the male doves were cohoused with a mate, facilitated neurogenesis and behavioral recovery. These results suggest that lesion-induced neurogenesis contributes to behavioral recovery in adult animals.

Aging↗

Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells.

The G2/M checkpoint is an attractive pathway for targeting and sensitizing tumor cells to cancer treatment. Abrogation of the G2/M checkpoint by targeting molecules, such as checkpoint kinase 1 (chk1), increases DNA breakage and sensitizes tumor cells to anti-tumoral agents. However, most of the previously described G2/M abrogators are actually targeting the G2-M border checkpoints rather than mitotic checkpoints. This prompted us to test the effects of combined targeting of chk1 and a critical regulator of mitosis, polo-like kinase 1 (plk1). Chk1 and plk1 were found to be co-expressed in 70% of primary neoplastic tissues we examined. Asynchronized tumor cells were treated with different DNA damaging-agents to activate G1/S, S or G2/M checkpoints. Either chk1 or plk1-specific antisense oligodeoxynucleotides (ASODN) enhanced DNA damaging agent-induced apoptosis. When used in combination, however, chk1- plus plk1-specific ASODN failed to produce synergistic effects. Moreover, selective targeting of plk1 or chk1 in tumor xenografts of mice by oncolytic adenovirus mutants demonstrated potent anti-tumoral efficacy in the presence of low dose cisplatin. Again, combined targeting of chk1 and plk1 did not further enhance anti-tumoral efficacy. We concluded that combined targeting of chk1 and plk1 was not superior to either targeting chk1 or plk1 alone, which suggested that chk1 and plk1 silencing might overlap in their mechanism of action. Whether combined targeting of chk1 with other, more specific mitotic regulators would synergistically sensitize tumor to anti-neoplastic therapeutics needs to be further clarified.

Animals↗

A ratio test in active control non-inferiority trials with a time-to-event endpoint.

There are essentially two kinds of non-inferiority hypotheses in an active control trial: fixed margin and ratio hypotheses. In a fixed margin hypothesis, the margin is a prespecified constant and the hypothesis is defined in terms of a single parameter that represents the effect of the active treatment relative to the control. The statistical inference for a fixed margin hypothesis is straightforward. The outstanding issue for a fixed margin non-inferiority hypothesis is how to select the margin, a task that may not be as simple as it appears. The selection of a fixed non-inferiority margin has been discussed in a few articles (Chi et al., 2003; Hung et al., 2003; Ng, 1993). In a ratio hypothesis, the control effect is also considered as an unknown parameter, and the noninferiority hypothesis is then formulated as a ratio in terms of these two parameters, the treatment effect and the control effect. This type of non-inferiority hypothesis has also been called the fraction retention hypothesis because the ratio hypothesis can be interpreted as a retention of certain fraction of the control effect. Rothmann et al. (2003) formulated a ratio non-inferiority hypothesis in terms of log hazards in the time-to-event setting. To circumvent the complexity of having to deal with a ratio test statistic, the ratio hypothesis was linearized to an equivalent hypothesis under the assumption that the control effect is positive. An associated test statistic for this linearized hypothesis was developed. However, there are three important issues that are not addressed by this method. First, the retention fraction being defined in terms of log hazard is difficult to interpret. Second, in order to linearize the ratio hypothesis, Rothmann's method has to assume that the true control effect is positive. Third, the test statistic is not powerful and thus requires a huge sample size, which renders the method impractical. In this paper, a ratio hypothesis is defined directly in terms of the hazard. A natural ratio test statistic can be defined and is shown to have the desired asymptotic normality. The demand on sample size is much reduced. In most commonly encountered situations, the sample size required is less than half of those needed by either the fixed margin approach or Rothmann's method.

Clinical Trials as Topic↗

Applied radioactivity in radiation synovectomy with [188Re]rhenium sulfide suspension.

BACKGROUND: Early experience demonstrated absorbed dose in radiation synovectomy is about 100 Gy. For reaching this dose, the applied radioactivity should be calculated. METHOD: Twenty-nine synovitic models of rabbit were treated by intra-articular injection of [(188)Re]rhenium sulfide and histological changes of synovium and cartilage were examined. The applied radioactivity was calculated by method of absorbed dose factor. In clinical, eleven haemophilic patients with haemarthrosis were performed radiation synovectomy with treated [(188)Re]rhenium sulfide. The synovial thickness was evaluated by MR and its value was used to calculate the applied radioactivity. After radiation synovectomy, all patients were followed up by synovial thickness, regional inflammation, and clinical course including bleeding frequency. RESULTS: In rabbit models, the synovitic membrane can be eliminated by calculated radioactivity as planed without damaging the joint cartilage. In patients study, all patients exhibited significant reductions in synovial thickness and inflammation after radiation synovectomy with the planed radioactivities of [(188)Re]rhenium sulfide. Post-procedure bleeding frequency reduction in excellent and good reached to 63.6% by 18 months. In the cases of joint bleeding, the need for antihaemophilic factor treatment decreased immensely. Most of the recurrent episodes of bleeding were mild, subsiding with local means. CONCLUSION: The applied radioactivity in radiation synovectomy could be calculated according to thickness of inflamed synovium. Further study including comparison therapeutic results from calculated individual activities with results from fixed activities and long-term follow-up is warranted.

Adult↗

Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder.

OBJECTIVE: While adolescent anxiety disorders represent prevalent, debilitating conditions, few studies have explored their brain physiology. Using event-related functional magnetic resonance imaging (fMRI) and a behavioral measure of attention to angry faces, the authors evaluated differences in response between healthy adolescents and adolescents with generalized anxiety disorder. METHOD: In the primary trials of interest, 18 adolescents with generalized anxiety disorder and 15 comparison subjects of equivalent age/gender/IQ viewed angry/neutral face pairs during fMRI acquisition. Following the presentation of each face pair, subjects pressed a button to indicate whether a subsequent asterisk appeared on the same (congruent) or opposite (incongruent) side as the angry face. Reaction time differences between congruent and incongruent face trials provided a measure of attention bias to angry faces. RESULTS: Relative to the comparison subjects, patients with generalized anxiety disorder manifested greater right ventrolateral prefrontal cortex activation to trials containing angry faces. Patients with generalized anxiety disorder also showed greater attention bias away from angry faces. Ventrolateral prefrontal cortex activation differences remained evident when differences in attention bias were covaried. Finally, in an examination among patients of the association between degree of anxiety and brain activation, the authors found that as ventrolateral prefrontal cortex activation increased, severity of anxiety symptoms diminished. CONCLUSIONS: Adolescents with generalized anxiety disorder show greater right ventrolateral prefrontal cortex activation and attentional bias away from angry faces than healthy adolescents. Among patients, increased ventrolateral prefrontal cortex activation is associated with less severe anxiety, suggesting that this activation may serve as a compensatory response.

Adolescent↗

Characterization of tamoxifen and 4-hydroxytamoxifen glucuronidation by human UGT1A4 variants.

INTRODUCTION: Tamoxifen (TAM) is an antiestrogen widely used in the treatment and prevention of breast cancer in women. One of the major mechanisms of metabolism of TAM and one of its major active metabolites, 4-hydroxytamoxifen (4-OH-TAM), is via glucuronidation. In the present study, the glucuronidating activities of three common variant isoforms encoded by the human UDP-glucuronosyltransferase (UGT) 1A4 gene were examined against TAM, trans-4-OH-TAM and cis-4-OH-TAM. METHODS: HPLC was used to detect glucuronide conjugates in microsomes from UGT1A4-overexpressing HK293 cells. The UGT1A4 wild-type cDNA was synthesized by RT-PCR using normal human liver total RNA. The UGT1A424Thr/48Leu and UGT1A424Pro/48Val variants were generated by site-directed mutagenesis of the pcDNA3.1/V5-His-TOPO plasmid expressing wild-type UGT1A424Pro/48Leu. Levels of UGT1A4 expression in UGT-overexpressing cell lines were measured by western blot analysis. RESULTS: Microsomes from wild-type UGT1A424Pro/48Leu-overexpressing HK293 cells exhibited significant levels of activity against TAM, trans-4-OH-TAM and cis-4-OH-TAM, forming exclusively the tamoxifen quaternary ammonium glucuronide (TAM-N+-glucuronide) and the 4-hydroxytamoxifen quaternary ammonium glucuronides (trans-4-OH-TAM-N+-glucuronide and cis-4-OH-TAM-N+-glucuronide) with apparent Km values of 2.0 microM, 2.2 microM, and 2.1 microM, respectively. Higher glucuronidation activities were found by kinetic analysis for microsomes from the variant UGT1A424Pro/48Val-overexpressing cell line as compared with microsomes from wild-type UGT1A424Pro/48Leu-overexpressing cells against TAM and against both the trans and cis isomers of 4-OH-TAM. A significantly (P < 0.02) lower Km value (approximately 1.6-fold to 1.8-fold) was observed for both 4-OH-TAM isomers, while a near-significant (P = 0.053) decrease in Km was observed for TAM for the UGT1A424Pro/48Val variant as compared with wild-type UGT1A4. The Vmax/Km ratio for the UGT1A424Pro/48Val variant was significantly (P < or = 0.005) higher than that observed for the wild-type UGT1A4 isoform for both the trans and cis isomers of 4-OH-TAM after normalization for UGT1A4 expression by western blotting. No significant effect on enzyme kinetics was observed for the UGT1A424Thr/48Leu variant against either isomer of 4-OH-TAM or with TAM. CONCLUSION: These data suggest that the UGT1A4 codon 48 Leu>Val polymorphism significantly alters glucuronidation rates against TAM and its active hydroxylated metabolites, and that this polymorphism may play an important role in individual pharmacological response to TAM therapy.

Glucuronates↗

Expression analysis of a mouse orthologue of HSFY, a candidate for the azoospermic factor on the human Y chromosome.

Heat shock transcription factor on Y (HSFY) is located in one of three candidate regions for azoospermic factor (AZF), AZFb on the Y chromosome. We and others have already revealed that some azoospermic males are missing the regions of the Y chromosome including HSFY. Previously, we showed that murine HSFY-like sequence [mHSFYL (Riken cDNA 4933413G11Rik)], which is the mouse orthologue of HSFY, is exclusively expressed in testis. The sequences encoding the presumed DNA-binding domain in HSFY and mHSFYL were found in other mammals such as dogs, cows and chickens. To elucidate mHSFYL expression in the testes in detail, we carried out in situ hybridization. mHSFYL was predominantly expressed in round spermatids. Furthermore, we clarified the intracellular distribution of mHSFYL in COS1 cells with HA- or GFP-tagged proteins. Both HA-mHSFYL and GFP-mHSFYL were located in the nucleus. Our results suggest that HSFY/mHSFYL may have evolutionarily conserved functions for spermatogenesis.

Amino Acid Sequence↗

Determination of bioactive constituents in traditional Chinese medicines by CE with electrochemical detection.

This paper reviews the recent advances and the key strategies in capillary electrophoresis (CE) with electrochemical detection (ECD) for separating and detecting a variety of bioactive constituents in traditional Chinese medicines (TCMs). The subjects covered include the separation modes for the CE analysis of the constituents in TCMs, the CE-ECD system, the sample preparations of TCMs, the ECD of TCMs, the applications of CE-ECD in the determination of various bioactive constituents in Chinese medicinal materials and their preparations, the identification and differentiation of TCMs by CE-ECD, and future prospects. It is expected that CE-ECD will become a powerful tool in the herbal medicinal fields and will lead to the creation of truly routine devices for TCM analysis.

Drugs, Chinese Herbal↗

[Recurrence patterns of esophageal cancer after Ivor-Lewis esophagectomy--a report of 196 cases].

BACKGROUND & OBJECTIVE: About one half of the patients with esophageal cancer may recur within 3 years after operation, but the recurrence pattern is still unclear. This study was to investigate the recurrence patterns of esophageal cancer after Ivor-Lewis esophagectomy. METHODS: Clinical data of 196 patients with squamous cell carcinoma of the middle third thoracic esophagus, who underwent Ivor-Lewis esophagectomy with two-field lymph node dissection from Jan. 1997 through Jan. 2001, were reviewed. The risk factors of postoperative recurrence within 3 years were analyzed with Logistic regressive model. RESULTS: Recurrence was recognized in 96 (48.9%) patients within 3 year after operation. The median time to recurrence was 12.2 months. Of the 96 cases of recurrence, 52 (54.1%) were locoregional, including 41 cases (78.8%) of mediastinal lymph node metastasis, and 8 cases (15.3%) of single cervical lymph node metastasis; 44 (45.8%) were hematogenous, including 10 cases of locoregional-hematogenous recurrence, and mainly located at liver, bone, and lung (39, 88.6%). The locoregional recurrence rate was significantly lower in the patients who received postoperative radiotherapy than in the patients have not received postoperative radiotherapy (23.3% vs. 41.3%, P<0.05). Logistic analysis showed that T3 and N1 tumor were independent risk factors of postoperative tumor recurrence. CONCLUSIONS: About one half of the patients would develop recurrent disease within 3 years after Ivor-Lewis esophagectomy, and most of them were with mediastinal lymph node, liver, bone, or lung metastasis. Postoperative radiotherapy is helpful to control locoregional recurrence.

Adult↗

Physiological and biochemical characteristics and molecular-biological identification of a gigantic tobacco mutant.

A new gigantic late-flowering tobacco mutant was isolated in tobacco field in Xunyang county, Shaanxi province, in 2001. It was rescued through tissue culture and a large amount of regenerated plantlets were obtained. The results of the comparison between the regenerated plants from this mutant and the wild type plant (K346) were as follows: (1) Morphological observation showed that the leaf number of the mutant was 3.3 times as many as that of the wild type, the height of mutant was 2.2 folds that of the wild type, and the mutant had the late-flowering character. (2) Cytological examination showed that the mutant was a normal diploid, and the number of chloroplasts in a guard cell of mutant was 1.3 times that of the wild type. (3) Both chlorophyll a and b content of the mutant were larger than that of the wild type; soluble protein content of the mutant was 1.18 times as much as that of the wild type. Peroxidase isozyme and cytochrome-oxidase isozyme electrophoresis analyses indicated differences between the mutant and the wild type. The soluble protein SDS-PAGE patterns showed the absence of four bands [P1 (114.6 kD), P2 (103 kD), P3 (66.2 kD), P4 (24 kD)] in the mutant. (4) RAPD analysis showed that the similarity index of the mutant and the wild type was 0.612. This suggested that there were changes at DNA level. The mRNA of mutant leaves at flowering stage was isolated; DDRT-PCR was carried out using 10 random primers, using OligodT(15)M (M=A/G/C) as anchor primer. It has been proved that gene expression at anthesis was different between the mutant and the wild type. (5) Genetic observation showed that the mutant was homozygotic and bred true. And the mutant was a late-flowering one.

Chlorophyll↗

[The influence of nanometer inorganic filling carrying silver on the properties of composite resin].

PURPOSE: To observe the mechanical performance's effects of nanometer inorganic filling carrying silver on the properties of composite resin and find the perfect dose of the mixture. METHODS: The resin was mixed with inorganic filling whose doses were 0.5%, 1.0%, 1.5% and 2.0%, and then the compressive strength, flexure strength and wear-resistance were measured in the five groups. One-way ANOVA and Student's t test were used for statistical analysis in SPSS 10.0. RESULTS: The results showed that in the compressive strength tests, the 1.5% dose was perfect which was (264.93+/-12.48) MPa (P>0.05) and the 2.0% dose was bad which was (94.54+/-17.42) MPa (P<0.01); in the flexure strength tests, 0.5%, 1.0% and 1.5% dose didn't change significantly which were (86.25+/-12.76) MPa, (99.49+/-16.47) MPa and (108.69+/-10.35) MPa (P>0.05) respectively, and 2.0% dose went down significantly which was (79.79+/-8.10) MPa (P<0.01); in the wear-resistance tests, 1.5% and 2.0% worked very well which were (2.73+/-0.53) MPa (P<0.05), (2.70+/-1.25) MPa (P<0.01) respectively. CONCLUSION: Nanometer inorganic filling had no significant influence on the composite resin, and 1.5% dose of nanometer inorganic filling is perfect for the resin's mechanical properties.

Composite Resins↗

Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2.

Vascular endothelial growth factor (VEGF) has been identified to be important in tumor angiogenesis, which is essential for the growth, invasion, and metastasis of solid tumors. The aim of this study was to determine the effect of VEGF overexpression on the invasion of human epithelial ovarian cancer cells in vitro and the possible mechanism involved. The VEGF165 cDNA was transfected into ovarian tumor cell lines CAOV3 and COC1 to promote the expression of VEGF. The VEGF expression and matrix metalloproteinase (MMP)-2 activity were examined by RT-PCR, Western blot analysis and gelatin zymography. A modified Boyden chamber assay was used to test tumor cell invasion in vitro. All cells overexpressing VEGF displayed an enhanced in vitro invasiveness through Matrigel-coated filters with Boyden chamber invasion assay. MMP-2 mRNA and protein were significantly increased during VEGF165 cDNA transfection; MMP-2 activity was also increased. The invasion property of ovarian cancer cells was abrogated with VEGF neutralizing antibody. Our data indicated that the expression of VEGF gave impetus to the in vitro invasion of ovarian cancer cells by stimulating the production and functional activities of MMP-2, which may be a key component of VEGF in promoting ovarian cancer cell invasion. VEGF may constitute a novel therapeutic target for antiangiogenic cancer therapy.

Antibodies, Monoclonal↗

[Changes in the activities of enzymes involved in starch synthesis and accumulation in caryopsis of transgenic rice with antisense Wx gene].

The amylose content of rice caryopsis is determined by Wx protein, one kind of granule-bound starch synthetase which is encoded by Wx gene. Different rice types and species have different levels of Wx gene expression and have different amylose contents in their caryopsis. Wuyunjing No.7 (2200), the japonica rice with an amylose content 17% and its transgenic rice lines with antisense Wx gene (2201 and 2203, with amylose contents 8.5% and 2% respectively), and Longtefu (LP03), the indica rice with a high amylose content (28%) and its transgenic rice with antisense Wx gene (A199, with an amylose content 9%) were used to investigate the effects of Wx protein content decrease on the activities of enzymes involved in starch synthesis and thereby starch accumulation. The results indicated that with the decrease in Wx protein, the amylose content in transgenic caryopsis was reduced accordingly, whereas the amylopectin content per caryopsis (mg/grain) was not affected, and made the total starch content in transgenic caryopsis markedly lower than their parents. With the development of caryopsis, the amylose/total starch ratio was not changed significantly in the two parent caryopses, LP03 and 2200, but it went down gradually in their transgenic caryopses. The amylose/total starch ratio in transgenic caryopses was very significantly lower than their parents in the same period. The activities of ADP-glucose pyrophosphorylase (ADPG-PPase), granule-bound starch synthase (GBSS), soluble starch synthase (SSS) and starch branching enzyme (SBE) rose rapidly in early periods of grain filling, and soon reached their maximum, then reduced quickly until the middle and later periods of grain filling. Compared with the parents, the GBSS activity in transgenic caryopsis was significantly lowered, and correlated with the amylose reduction. Besides, the maximum activity of GBSS appeared earlier, and the range of the activity was smaller. In transgenic caryopsis, the activities of ADPG-PPase and SSS were higher than their parents in early and middle periods of grain filling, while the SBE activity was higher than their parents in middle and late periods.

1,4-alpha-Glucan Branching Enzyme↗

[Immunological screening for multiple myeloma-associated antigens and their bioinformatics analysis].

This study was aimed to screen the cell cDNA expression library of multiple myeloma HMy2 (MM HMy2) by using "serological analysis of cDNA expression library (SEREX)" technique. The obtained 30 positive clones were all sequenced, and analyzed by BLAST (basic local alignment search tool). The results indicated that 6 known genes and 12 new MM-associated genes were obtained, part of which sequences were spliced by EST (expressed sequence tag) splicing. 6 known genes such as for ring finger protein 167, KLF10, TPT1 protein, p02 protein, cDNA FLJ46859 fis, DNMT1 methyltrasferase etc. have been demonstrated a certain relationship with other tumor's formation, progress and prognosis. The structures and functions of the new genes preliminarily analyzed and predicted by means of bioinformatics showed that MMSA-3, MMSA-8 and MMSA-11 encoding 215, 160 and 122 amino acid residues respectively had the full open reading frames (ORF). All the new genes might be located at euchromosomes but MMSA-1 at sex chromosome. MMSA-4 was highly similar to the protein controlling the transcription of tumor antigen, MMSA-5 might take part in cell phagocytosis, MMSA-7 might inactivated NF-kappaB, and MMSA-12 might be a lymphocytic cytoplasmic protein. The specificity of new genes such as MMSA-3 and MMSA-7 were higher, by a preliminary analysis using CrELISA. It is concluded that tumor antigens screened by this study can be used for early immunological diagnosis, surveillance of minor residual foci, assessment of prognosis, and preparation of tumor vaccine and so on.

Antigens, Neoplasm↗

Effects of taohong siwu decoction II in the chick chorioallantoic membrane (CAM) assay and on B16 melanoma in mice and endothelial cells ECV304 proliferation.

OBJECTIVE: To investigate the anti-angiogenesis action of Taohong Siwu Decoction II (THSWD II). METHODS: The chick chorioallantoic membrane (CAM) assay was adopted to study the anti-angiogenesis action of THSWD II; the MTT test was used to investigate its effect on proliferation of the human umbilical vein endothelial cells ECV304; and the immunohistochemical method was used to observe the effect of THSWD II on the expression of kinase insert domain containing receptor/fetal liver kinase 1 (KDR/Flk-1) and the microvessel density (MVD) of B16 melanoma in mice. RESULTS: After treatment with THSWD II, the blood vessel index of CAM and the absorbency of ECV304 in the THSWD II 1 mg/ml group and the 2 mg/ml group decreased significantly (P < 0.01); the weight, the expression of KDR/Flk-1 and the MVD of B16 melanoma in mice reduced significantly in the THSWD II 5 g/kg group, the 10 g/kg group and the TSHSWD 10g/kg plus cyclophosphamide group (P < 0.01). CONCLUSION: THSWD II has the actions of anti-angiogenesis, and inhibiting the proliferation of ECV304 cells and the growth of B16 melanoma. The clinical anti-tumour mechanism is considered to berelated possibly to its anti-angiogenesis action by inhibiting the expression of KDR/FIK-1.

Angiogenesis Inhibitors↗

[Inverse correlation between Snail and E-cadherin expression in carcinoma cell lines and invasive ability in vitro].

OBJECTIVE: Malignant transformation of epithelial cell frequently coincides with loss of E-cadherin. Here we study the expression of Snail and E-cadherin and correlate their expression with cell differentiation and in vitro invasion. METHODS: The expression and localization of Snail and E-cadherin were studied by Northern blot and laser confocal microscopy in two normal cell lines (MDCK, NIH 3T3) and six carcinoma cell lines (A431, MCF-7, MDA-MB-453, HepG2, MDA-MB-435s, MDA-MB-231). Boyden chamber assay was done to detect the invasive ability of cells in vitro. RESULTS: Snail mRNA and protein were detected in fibroblasts NIH 3T3 and poorly differentiated carcinoma cell lines HepG2, MDA-MB-435s and MDA-MB-231. On the contrary, E-cadherin mRNA and protein were detected in normal epithelial cell line MDCK and well differentiated carcinoma cell lines A431 and MDA-MB-453. In MCF-7 cells, Snail and E-cadherin expressions were revealed both at mRNA and protein levels. The cells with higher expression of Snail had stronger ability of invasion than those with lower expression of Snail. CONCLUSION: There is an inverse correlation between Snail and E-cadherin expressions and their expressions are correlated with cell differentiation and tumor invasiveness.

3T3 Cells↗

[In vivo distribution and pharmacokinetics of dexamethasone sodium phosphate thermosensitive in situ gel following intratympanic injection].

OBJECTIVE: To investigate the absorption and distribution of DSP (Dexamethasone sodium phosphate)-loaded thermosensitive in situ gel following IT (intratympanic injection) in guinea pig and provide rationale for clinical application. METHODS: DSP-loaded thermosensitive in situ gel was prepared by using poloxamer 407 as matrix. The HPLC assays for the determination of DSP and dexamethasone (Dex) in perilymph (PL), cerebrospinal fluid (CSF) and plasma were developed, respectively. DSP-loaded gel and solution were administered after IT or IV (intravenous injection). PL, CSF and plasma were collected periodically. The concentrations of DSP and Dex were measured by HPLC, and were used to estimate in vivo distribution and pharmacokinetic parameters of Dex in the inner ear. RESULTS: The AUC (area under curve) and t1/2 of Dex in PL following IT DSP-loaded gel were 593.7- and 28.6-fold higher than those following IV DSP solution. Moreover, DSP-loaded gel following IT extended the mean residence time (MRT) by nearly 5 times, compared with the solution. After IT, the concentration levels of Dex in CSF and plasma were much lower than that in PL. CONCLUSION: DSP thermosensitive in situ gel following IT has significant cochlea-oriented and sustained-release effect.

Administration, Topical↗

[Study on preparation of konjac glucomannan-hydroxypropyl methyl cellulose compression coated tablets for colonic delivery and in vitro release].

OBJECTIVE: Prepare konjac glucomannan-hydroxypropyl methyl cellulose (HPMC) compression coated tablets and study the effects of the formulation, technics and in vitro dissolution condition on drug release behavior to elevate the colon-specific effects of preparation. METHOD: Berberine hydrochloride core tablets were prepared by wet granulation technique and konjac glucomannan-HPMC mixture as the coating layer were used with compression coated technique. The effects of the formulation and technics on drug release behavior were investigated by dissolution test. The erosion of coat layer during dissolution test was investigated. RESULT: Drug almost not released in dissolution medium stimulating gastric and intestinal condition, and released completely by coating layer erosion and rupture by enzyme in stimulating colonic condition. Drug release decreased with decreasing the ratio of konjac glucomannan-HPMC and increasing coat weight (P < 0.05), compression force was not found to be a significant factor on drug release. Drug release increased with increasing the concentration of beta-mannase in dissolution medium (P < 0.05), rotation speed has no effect on drug release. The release of drug was correlative with erosion of coat layer. The mechanism of drug release were diffusion and erosion. CONCLUSION: The konjac glucomannan-HPMC compression coated tablets was a promising delivery system for drugs to be delivered to the colon.

Administration, Oral↗