Biomedical subjects

Zhen Chen

Publications and source records attributed to Zhen Chen.

At least 37 records · Page 2Linked to original sources

PubMed2005

Current preventive treatment for recurrence after curative hepatectomy for liver metastases of colorectal carcinoma: a literature review of randomized control trials.

To review the preventive approaches for recurrence after curative resection of hepatic metastases from colorectal carcinoma, we have summarized all available publications reporting randomized control trials (RCTs) covered in PubMed. The treatment approaches presented above include adjuvant intrahepatic arterial infusion chemotherapy, systemic chemotherapy, neoadjuvant chemotherapy, and immunotherapy. Although no standard treatment has been established, several approaches present promising results, which are both effective and tolerable in post-hepatectomy patients. Intrahepatic arterial infusion chemotherapy should be regarded as effective and tolerable and it increases overall survival (OS) and disease-free survival (DFS) of patients, while 5-fluorouracil-based systemic chemotherapy has not shown any significant survival benefit. Fortunately chemotherapy combined with hepatic arterial infusion and intravenous infusion has shown OS and DFS benefit in many researches. Few neoadjuvant RCT studies have been conducted to evaluate its effect on prolonging survivals although many retrospective studies and case reports are published in which unresectable colorectal liver metastases are downstaged and made resectable with neoadjuvant chemotherapy. Liver resection supplemented with immunotherapy is associated with optimal results; however, it is also questioned by others. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence after hepatectomy for liver metastases from colorectal cancer (CRC), but multi-centric RCT is still needed for further evaluation on their efficacy and systemic or local toxicities. In addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with resectable hepatic metastases from CRC.

Colonic Neoplasms↗

PubMed2005

ZNRD1 gene suppresses cell proliferation through cell cycle arrest in G1 phase.

ZNRD1, a transcription-associated gene, was recently found in our laboratory significantly suppress the cell proliferation of stomach cancer cells in vitro and in vivo. In this study, we firstly characterized ZNRD1 expression in a wide spectrum of gastric diseases by immunohistochemistry and RT-PCR. We also investigated its antiproliferative effects and associated molecular alterations in human gastric cancer cell line AGS and mouse fibroblast cell line NIH3T3. Anti-ZNRD1 monoclonal antibody H6 was found to react with 38 (63%) of normal gastric tissues, and 51 (81%) of gastritis. In contrast, no positive expression was found in gastric adenocarcinomas. Thus, the expression of ZNRD1 in normal gastric tissues was significantly higher than that in gastric adenocarcinomas. Compared with the control clones, ZNRD1-transfected cells exhibited significant inhibition of cell growth with G1 cell cycle arrest mediated by the suppression of cyclin D1 expression. These results showed that ZNRD1 may play an important role in the regulation of gastric carcinogenesis and could be used as a new target in treatment of stomach cancer.

Adenocarcinoma↗

PubMed2005

Comparative study of subxiphoid versus video-thoracoscopic pericardial "window".

BACKGROUND: It remains undefined whether surgical subxiphoid drainage or thoracoscopic pericardial "window" is the optimal operative approach to pericardial effusion. We hypothesized that the true window into the pleural space created by the latter might improve the duration of freedom from recurrent effusion. METHODS: We conducted a retrospective chart review of indications, preoperative and intraoperative variables, morbidity, recurrence, and survival. RESULTS: Fifty-six patients underwent the subxiphoid procedure and 15 underwent the thoracoscopic procedure. Echocardiographic evidence of tamponade was present before 8 of 10 thoracoscopic procedures (80%) and 43 of 56 subxiphoid procedures (81%) for which descriptions of hemodynamics were available. In addition, non-pericardial procedures were performed in 10 (67%) and 18 (32%) patients, respectively (p = 0.020). Anesthesia time was longer at thoracoscopy (117.1 +/- 32.4 vs 81.1 +/- 25.5 minutes; p < 0.001). Procedural morbidity was higher after thoracoscopy (4 [27%] vs 1 [2%]; p = 0.006), but was generally minor. Hospital mortality tended to be higher after the subxiphoid procedure (7 [13%] vs 0 [0%]; p = 0.332), but none of the deaths was procedure-related. Follow-up was complete for 65 patients (92%). Recurrence occurred in 1 thoracoscopy patient (8%) and 5 subxiphoid patients (10%) (p = 1.000). Mean time to recurrence by Kaplan-Meier analysis trends were longer after thoracoscopy (36.1 vs 11.4 months; p = 0.16), and multivariate analysis identified the thoracoscopic approach as an independent predictor of freedom from recurrence (relative risk, 0.41; p = 0.014). CONCLUSIONS: Operative time and minor procedural morbidity are higher with thoracoscopic pericardial window, but long-term control of effusion seemed to be better than after subxiphoid surgical drainage.

Female↗

PubMed2005

Maternal serum level of the DDT metabolite DDE in relation to fetal loss in previous pregnancies.

Use of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) continues in about 25 countries. This use has been justified partly by the belief that it has no adverse consequences on human health. Evidence has been increasing, however, for adverse reproductive effects of DDT, but additional data are needed. Pregnant women who enrolled in the Collaborative Perinatal Project (United States, 1959-1965) were asked about their previous pregnancy history; blood samples were drawn and the serum frozen. In 1997-1999, the sera of 1717 of these women who had previous pregnancies were analyzed for 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the major breakdown product of DDT. The odds of previous fetal loss was examined in relation to DDE level in logistic regression models. Compared with women whose DDE level was <15 microg/L, the adjusted odds ratios of fetal loss according to category of DDE were as follows: 15-29 microg/L, 1.1; 30-44 microg/L, 1.4; 45-59 microg/L, 1.6; and 60+ microg/L, 1.2. The adjusted odds ratio per 60 microg/L increase was 1.4 (95% confidence interval 1.1-1.6). The results were consistent with an adverse effect of DDE on fetal loss, but were inconclusive owing to the possibility that previous pregnancies ending in fetal loss decreased serum DDE levels less than did those carried to term.

Abortion, Spontaneous↗

PubMed2005

Multihydroxylated [Gd@C82(OH)22]n nanoparticles: antineoplastic activity of high efficiency and low toxicity.

[Gd@C82(OH)22]n particles (22 nm in a saline solution) of a dose level as low as 10(-7) mol/kg exhibit a very high antineoplastic efficiency ( approximately 60%) in mice. A dose increment of 1 x 10(-7) mol/kg increases the tumor inhibition rate 26%. [Gd@C82(OH)22]n particles have a strong capacity to improve immunity and interfere with tumor invasion in normal muscle cells, nearly without toxicity in vivo and in vitro. Unlike conventional antineoplastic chemicals, the high antitumor efficiency of nanoparticles is not due to toxic effects to cells because they do not kill the tumor cells directly and only about 0.05% of the used dose is found in the tumor tissues. Results suggest that fullerene derivatives with proper surface modifications and sizes may help realize the dream of tumor chemotherapeutics of high-efficacy and low-toxicity.

Animals↗

PubMed2005

Zinc ribbon domain-containing 1 (ZNRD1) mediates multidrug resistance of leukemia cells through regulation of P-glycoprotein and Bcl-2.

Here, we investigated the role of zinc ribbon domain-containing 1 (ZNRD1) in multidrug resistance (MDR) of leukemia cells and the possible underlying mechanisms. ZNRD1 was found overexpressed in the vincristine-induced MDR leukemia cell HL-60/vincristine moreso than its parental cell HL-60. Up-regulation of ZNRD1 expression could confer resistance of both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs on HL-60 cells and suppress Adriamycin-induced apoptosis accompanied by decreased accumulation and increased releasing amount of Adriamycin. ZNRD1 could significantly up-regulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene but not alter the expression of MDR-associated protein, glutathione S-transferase activity, or intracellular glutathione content in leukemia cells. In addition, inhibition of ZNRD1 expression by RNA interference or P-gp inhibitor could partially reverse ZNRD1-mediated MDR. The further study of the biological functions of ZNRD1 may be helpful for understanding the mechanisms of MDR of leukemia and developing possible strategies to treat leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

[Experimental study on effects of shengmai injection: enhancing 5-FU anti-tumor efficacy and reducing its toxicity].

OBJECTIVE: To observe the effects of Shengmai Injection on enhancing efficacy and reducing toxicity of 5-fluorouracil (5-FU). METHODS: Fifty hepatoma 22 bearing mice were randomly divided into five groups: control group, 5-Fu group, Shengmai Injection (low, medium and high dose) combined with 5-FU groups. There were 10 mice in each group. Mice in the five groups were injected introperitoneally the same amount of normal saline, 5-FU (20 mg.kg(-1).d(-1)) and Shengmai Injection (3.5 ml.kg(-1).d(-1), 7 ml.kg(-1).d(-1) and 14 ml.kg(-1).d(-1)) combined with 5-FU respectively, once a day for 14 days. After that, all mice were killed and the tumor inhibiting rates, index of immunological function, liver and kidney function and the blood cells in the peripheral blood were observed. RESULTS: The tumor inhibiting rates were higher in each Shengmai Injection combined with 5-FU group than that in the 5-FU group (P<0.05). The levels of CD3, CD4, CD4/CD8, IgG, IgM in 5-FU group were lower (P<0.05), while those in the three Shengmai Injection combined with 5-FU groups were higher than those in the control group (P<0.05). The level of serum alanine aminotransferase (ALT) was higher and the WBC and PLT counts in the peripheral blood were lower in 5-FU group than those in the control group (P<0.05). But the levels of serum ALT in the three Shengmai Injection combined with 5-FU groups were consistent with that in the control group and the amounts of WBC decreased slightly. CONCLUSION: Shengmai Injection can enhance the anti-tumor effect of 5-FU. It can also improve the immunological function and reduce the adverse reactions of chemotherapy.

Animals↗

PubMed2004

Selective and sensitive fluorescent sensors for metal ions based on manipulation of side-chain compositions of poly(p-phenyleneethynylene)s.

The syntheses and metal-responsive properties of poly(p-phenyleenethynylene)s with grafted new pseudo-crown-ether groups are reported. These polymers exhibit high sensitivities to alkali ions because of their collective optical properties, which are very sensitive to ion-induced conformational changes. The quenching of polymer fluorescence caused by the conformational changes is proportional to the ion concentration. The selectivity of the sensing materials toward Li(+) ions is significantly enhanced by controlling the size of the binding site via manipulation of the polymer side-chain compositions. The polymers are very stable for their six-month solid-state storage at room temperature.

Letter↗

PubMed2004

Dielectric analysis of macroporous anion-exchange resin beads suspensions.

Dielectric measurements were carried out for suspensions of D354 anion-exchange beads dispersed in electrolyte solutions at different concentrations, and distinct Maxwell-Wagner dielectric relaxations were observed around 10(6) Hz. Through fitting the experimental data we obtained the dielectric parameters of the suspensions, and then we calculated the phase parameters from the dielectric parameters and the measured volume fractions by Hanai's method. In light of the present understanding of the interfacial properties, and with the information obtained from the phase parameters, we satisfactorily interpreted the concentration dependences of the dielectric parameters. It is concluded that Hanai's method is an effective tool for obtaining the properties of dispersed particles; the properties of the electrical double layer, which are mainly decided by the properties of the electrolyte solution, predict the dielectric behavior of suspensions with conducting particles. The dielectric relaxation spectroscopy (DRS), based on the M-W mechanism, is also a very sensitive tool for probing the properties of the liquid/solid interface.

Journal Article↗

PubMed2004

Bioavailability and pharmacokinetics of cyclosporine A-loaded pH-sensitive nanoparticles for oral administration.

The pH-sensitive cyclosporine A (CyA) nanoparticles were prepared by the solvent displacement method with enteric dissolved polymer of hydroxypropyl methylcellulose phthalate (HPMCP; including HP50 and HP55). The CyA nanoparticles were analyzed by HPLC for yield and encapsulation efficiency, dynamic light scattering for particle size and transmission electron microscopy (TEM) for morphology. The bioavailability of CyA-HP50 and CyA-HP55 nanoparticle colloids were evaluated in rats, compared with the current available CyA microemulsion (Neoral). The bioavailability of CyA-HP55 nanoparticle colloids with various suspending agents was also investigated. The results obtained demonstrated that the pH-sensitive CyA nanoparticles with a particle size of 50-60 nm and encapsulation efficiency over 95% could be reproducibly prepared. The bioavailability of CyA-HP50 and CyA-HP55 nanoparticle colloids calculated by the AUC(0-72) were 82.3% and 119.6%, similar to the reference of Neoral, while the bioavailability of CyA-HP55 nanoparticle colloids was found to be higher than that of CyA-HP50 nanoparticle colloids. The increase of mean residence time (MRT) and the decrease of elimination constant of the central compartment (K10) for both CyA-HP50 and CyA-HP55 nanoparticle colloids compared with the reference indicated significant sustained release of CyA from the nanoparticles. The effects of the suspending agents on the bioavailability of CyA-HP55 nanoparticles were observed, and the bioavailability decreased as the concentration of suspending agents or the viscosity of the nanoparticle colloids increased.

Administration, Oral↗

PubMed2004

[Influence of suspending agents on relative bioavailability of cyclosporine A-loaded HPMCP nanoparticles for oral administration to rats].

OBJECTIVE: To study the influence of suspending agents on the relative bioavailability of Cyclosporine A-loaded HPMCP(HP55) nanoparticles for oral administration. METHODS: Suspending agents such as Vanzan, HPMC, Carbopol were added into cyclosporine A-loaded HP55 nanoparticles. The suspended nanoparticle formulations and Neoral were administered orally in a dosage of 15 mg/kg to rats. The CyA concentrations in the blood sample were determined by HPLC. Pharmacokinetic parameters were calculated by 3P97. RESULTS: The concentration-time data of these preparations were best fit by two compartment model with a weight of 1/C(2). Compared with the reference Neoral microemulsion, the relative bioavailability of 2 g/L Carbopol, 5 g/L Vanzan, 8, 5, 3 g/L HPMC suspended nanoparticles were 70.2%, 84.3%, 90.0%, 94.5% and 97.7%, respectively. Their viscosity values were 550, 362, 105, 30 and 15 mPaxs, respectively. CONCLUSION: With the increase in viscosity, the relative bioavailability of nanoparticle formulations decreased. So, it is important to select the appropriate viscosity of suspending agents in the formulation design.

Administration, Oral↗

PubMed2004

Bayesian estimation of survival functions under stochastic precedence.

When estimating the distributions of two random variables, X and Y, investigators often have prior information that Y tends to be bigger than X. To formalize this prior belief, one could potentially assume stochastic ordering between X and Y, which implies Pr(X < or = z) > or = Pr(Y < or = z) for all z in the domain of X and Y. Stochastic ordering is quite restrictive, though, and this article focuses instead on Bayesian estimation of the distribution functions of X and Y under the weaker stochastic precedence constraint, Pr(X < or = Y) > or = 0.5. We consider the case where both X and Y are categorical variables with common support and develop a Gibbs sampling algorithm for posterior computation. The method is then generalized to the case where X and Y are survival times. The proposed approach is illustrated using data on survival after tumor removal for patients with malignant melanoma.

Bayes Theorem↗

PubMed2004

Selecting factors predictive of heterogeneity in multivariate event time data.

In multivariate survival analysis, investigators are often interested in testing for heterogeneity among clusters, both overall and within specific classes. We represent different hypotheses about the heterogeneity structure using a sequence of gamma frailty models, ranging from a null model with no random effects to a full model having random effects for each class. Following a Bayesian approach, we define prior distributions for the frailty variances consisting of mixtures of point masses at zero and inverse-gamma densities. Since frailties with zero variance effectively drop out of the model, this prior allocates probability to each model in the sequence, including the overall null hypothesis of homogeneity. Using a counting process formulation, the conditional posterior distributions of the frailties and proportional hazards regression coefficients have simple forms. Posterior computation proceeds via a data augmentation Gibbs sampling algorithm, a single run of which can be used to obtain model-averaged estimates of the population parameters and posterior model probabilities for testing hypotheses about the heterogeneity structure. The methods are illustrated using data from a lung cancer trial.

Algorithms↗

PubMed2003

Prenatal exposure to low-level polychlorinated biphenyls in relation to mental and motor development at 8 months.

The relation between exposure to low levels of polychlorinated biphenyls (PCBs), a class of persistent organic pollutants, and cognitive and motor development in young children has been examined in several studies, and results have varied. The authors evaluated the association between prenatal exposure to PCBs and children's neurodevelopment using data from the Collaborative Perinatal Project. Pregnant women were enrolled from 1959 to 1965 from 12 sites across the United States. PCBs were measured in maternal serum taken during pregnancy. To measure children's mental and psychomotor development at 8 months of age, the authors administered the Bayley Scales of Infant Development (means, 87 (standard deviation, 15) and 88 (standard deviation, 18), respectively). Overall, they did not observe a relation between prenatal PCB exposure and children's mental or psychomotor scores (n = 1,207; multivariate adjusted beta = 0.1 point per micro g/liter increase of PCB, p = 0.71, and beta = 0.5, p = 0.14, respectively). The PCB-psychomotor score relation varied by study center (p < 0.05): The association was direct in some centers, inverse in others. This could not be attributed to variation in the timing or measurement of the child's neurodevelopment or analysis of PCBs because these were standardized across centers. The reasons for variation in results within this study and across other studies remain unclear.

Adult↗

PubMed2003

A Bayesian approach for joint modeling of cluster size and subunit-specific outcomes.

In applications that involve clustered data, such as longitudinal studies and developmental toxicity experiments, the number of subunits within a cluster is often correlated with outcomes measured on the individual subunits. Analyses that ignore this dependency can produce biased inferences. This article proposes a Bayesian framework for jointly modeling cluster size and multiple categorical and continuous outcomes measured on each subunit. We use a continuation ratio probit model for the cluster size and underlying normal regression models for each of the subunit-specific outcomes. Dependency between cluster size and the different outcomes is accommodated through a latent variable structure. The form of the model facilitates posterior computation via a simple and computationally efficient Gibbs sampler. The approach is illustrated with an application to developmental toxicity data, and other applications, to joint modeling of longitudinal and event time data, are discussed.

Animals↗

PubMed2003

Random effects selection in linear mixed models.

We address the important practical problem of how to select the random effects component in a linear mixed model. A hierarchical Bayesian model is used to identify any random effect with zero variance. The proposed approach reparameterizes the mixed model so that functions of the covariance parameters of the random effects distribution are incorporated as regression coefficients on standard normal latent variables. We allow random effects to effectively drop out of the model by choosing mixture priors with point mass at zero for the random effects variances. Due to the reparameterization, the model enjoys a conditionally linear structure that facilitates the use of normal conjugate priors. We demonstrate that posterior computation can proceed via a simple and efficient Markov chain Monte Carlo algorithm. The methods are illustrated using simulated data and real data from a study relating prenatal exposure to polychlorinated biphenyls and psychomotor development of children.

Algorithms↗

PubMed2003

[Correlation between TXB2, 6-Keto-PGF1alpha and liver metastasis in rats model with blood stasis].

OBJECTIVE: To observe the correlation between serum level of TXB2, 6-Keto-PGF1alpha and liver metastasis. METHODS: The metastatic model was made by injection of W256 carcinosarcoma. Rats were randomly divided into two groups: rats with blood stasis group and control group. Rats in control group were given normal saline via abdominal cavity once a day. Rats in blood stasis group were injected adrenalin in the fourteenth day. Tumor size and liver metastasis were observed. Serum TXB2 and 6-Keto-PGF1alpha were tested by radioimmunoassay. RESULTS: Tumor size in rats with blood stasis was significantly smaller than that of the control group (P<0.01). Occurrence of liver metastasis in rats with blood stasis was significantly lower than that of the control group (P<0.01). The values of 6-Keto-PGF1alpha, TXB2, and TXB2/6-Keto-PGF1alpha were higher in the group with blood stasis. CONCLUSION: In the status of blood stasis, W256 carcinosarcoma grows slowly, and liver metastasis increases insignificantly, with the elevations of 6-Keto-PGF1alpha, TXB2 and TXB2/6-Keto-PGF1alpha.

6-Ketoprostaglandin F1 alpha↗

PubMed2003

Comparison between chemoembolization combined with radiotherapy and chemoembolization alone for large hepatocellular carcinoma.

AIM: To investigate the efficacy of transcatheter arterial chemoembolization (TACE) combined with radiotherapy for unresectable large hepatocellular carcinoma (HCC). METHODS: From June 1994 to June 1999, a total of 76 patients with large unresectable HCC were treated with TACE followed by external-beam irradiation. 89 patients with large HCC, who underwent TACE alone during the same period, served as the control group. Clinical features, therapeutic modalities, acute effects and survival rates were analyzed and compared between TACE plus irradiation group and TACE alone group. A multivariate analysis of nine clinical variables and one treatment variable (irradiation) was performed by the Cox proportional hazards model. RESULTS: The clinical features and therapeutic modalities except irradiation between the two groups were comparable (P>0.05). The objective response rate (RR) in TACE plus irradiation group was higher than that in TACE alone group (47.4 % vs 28.1 %, P<0.05). The overall survival rates in TACE plus irradiation group (64.0 %, 28.6 %, and 19.3 % at 1, 3, 5 years, respectively) were significantly higher than those in TACE alone group (39.9 %, 9.5 %, and 7.2 %, respectively, P=0.0001). Cox proportional hazards model analysis showed that tumor extension and Child grade were significant and were independent negative predictors of survival, while irradiation was an independent positive predictor of survival. CONCLUSION: TACE combined with radiotherapy is more effective than TACE alone, and is a promising treatment for unresectable large HCC.

Carcinoma, Hepatocellular↗