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Biomedical subjects

Hong Ding

Publications and source records attributed to Hong Ding.

At least 37 records · Page 2Linked to original sources
PubMed2005

Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse.

Endothelial dysfunction plays a role in the development of atherosclerosis and diabetes-associated vascular disease and, in the streptozotocin (STZ)-induced apoE-deficient diabetic mouse, we report that, when compared to the citrate (CIT)-treated nondiabetic apoE-deficient control, acetylcholine (Ach)-mediated endothelium-dependent relaxation was reduced in the small mesenteric arteries (SMA) and the plaque-prone regions of the aorta from the STZ-diabetic mouse. In the SMA the component of Ach-mediated relaxation that was attributed to nitric oxide (NO) from STZ-treated diabetic apoE-deficient mice was enhanced; however, the endothelium-derived hyperpolarizing factor (EDHF)-mediated component was reduced. The EDHF component was assessed by determining the component of the Ach-mediated response that was resistant to the combination of the NO synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester, cyclooxygenase inhibitor, indomethacin, and soluble guanylate cyclase inhibitor, ODQ, and inhibited by the combination of the intermediate conductance KCa (IKCa) inhibitor TRAM-34 and the small-conductance KCa (SKCa) inhibitor apamin. Endothelial NOS was increased but SK2, SK3 and connexin (Cx) 37 mRNA expressions were significantly (P<0.05) decreased in the SMA from STZ-treated apoE-deficient mice compared to the CIT-treated controls. There was no difference in the IKCa expression or in Cx 40, 43 and 45 mRNA levels between STZ- and CIT-treated mice. The microvasculature of STZ-induced apoE-deficient mice developed endothelial dysfunction, which may be linked to a decrease in the contribution of the EDHF component due to a decrease in SK2 and 3 and Cx 37 expression.

Acetylcholine↗
PubMed2005

Imaging of focal liver lesions: low-mechanical-index real-time ultrasonography with SonoVue.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of a contrast-enhanced contrast-specific ultrasonographic technique with a low mechanical index for characterization of focal liver lesions. METHODS: Contrast-specific ultrasonography was used to assess 144 patients with 147 focal liver lesions: 87 primary liver carcinomas, 27 hemangiomas, 16 focal nodular hyperplasias, 5 hepatic abscesses, 3 inflammatory pseudotumors of the liver, and 9 metastases. A sulfur hexafluoride gas-based contrast agent was used with a mechanical index of 0.08 to 0.11. RESULTS: On contrast-enhanced ultrasonography, the typical hemodynamic pattern of primary liver carcinoma was the whole-lesion enhancement or mosaic enhancement in the arterial phase with an enhancement defect in the late phase (sensitivity, 92.0%; specificity, 86.7%). The most common enhancement pattern of hemangioma was that enhancement appeared in the periphery first and progressively filled into the lesion center (sensitivity, 96.3%; specificity, 97.5%). The enhancement pattern of focal nodular hyperplasia was that the whole lesion enhanced early and rapidly in the arterial phase with a centrifugal radiating configuration and appeared isoechoic or hyperechoic until the late phase (sensitivity, 87.6%; specificity, 94.5%). The central scar was detected in 31.3% of cases in the late phase. The specific enhancement of a hepatic abscess was the honeycomblike enhancement in all phases (sensitivity, 80.0%; specificity, 100%). No enhancement of a lesion in all phases was specific for an inflammatory pseudotumor of the liver. CONCLUSIONS: Contrast-enhanced real-time ultrasonography is a promising approach in the noninvasive characterization of focal liver lesions and can be useful as a first-line imaging technique clinically when a focal liver lesion is detectable on ultrasonography.

Adult↗
PubMed2005

Overexpression of the N-terminal end of the p55gamma regulatory subunit of phosphatidylinositol 3-kinase blocks cell cycle progression in gastric carcinoma cells.

pRb and its family members p130 and p107 regulate cell cycle progression and direct G1/S transition in mammalian cells through interaction with the transcription factor E2F. Phosphatidylinositol 3-kinase (PI3K) is an essential component of growth factor-regulated pathways and plays a crucial role in the regulation of cellular proliferation and differentiation. It has been demonstrated that PI3K can regulate cell cycle progression via Akt-mediated pathway. However, the possible interactions between PI3K and Rb pathways remain to be defined. It was reported that the unique 24-amino-acid N-terminal end of the p55 regulatory subunits of PI3K is an Rb-binding domain and affects Rb action or Rb-E2F interaction. The 24 N-terminal amino acids of p55gamma encoded by a cDNA construct could compete with the endogenous p55gamma for binding to Rb, which influences Rb-mediated signaling and blocks cell cycle progression. In the current study, we investigated the effects of this 24-peptide on cell proliferation in human gastric carcinoma MKN-28 cells by means of cell cycle analysis, BrdU incorporation, and determining the levels of cell cycle regulatory molecule expression. Our results showed that p55gammaPI3K and the Rb family members p130 and p107 exist in MKN-28 cells, while the p110PI3K was not detected. Moreover, p55gammaPI3K was found binding to p130/p107 in these cells. We demonstrated that the introduction of the plasmid N24p55-GFP (harboring the cDNA for the 24 N-terminal amino acids of p55gamma) into MKN-28 cells caused cell cycle arrest at G1. Furthermore, we showed that the over-expression of the 24-peptide in MKN-28 cells decreased the population of cells incorporating BrdU and reduced the levels of cyclin D1 and cyclin A. These observations suggest that PI3K can regulate cell cycle progression and cell proliferation in human gastric tumor cells via Rb-mediated pathway, and that this effect of PI3K is mediated through a direct association with Rb via the N-terminal end of its p55 kDa regulatory subunits and modulating Rb-E2F interactions. Taken together with previous studies, our data provide a new therapeutic target in human stomach cancer. Strategies targeting PI3K signal transduction or the association of PI3K with Rb, or regulating PI3K-Rb interactions could be employed for gene therapy or chemotherapy of gastric cancer and other tumors.

Carcinoma↗
PubMed2005

Demonstration of differential gene expression between sensitive and resistant ovarian tumor cells by fluorescence differential display-PCR analysis.

Chemotherapy plays a major role in cancer management; however, acquired drug resistance remains a significant problem for ovarian cancer treatment. Chemoresistance is regulated by the coordinated expression of a set of genes. Thus, the identification of genes specifically modulated in the process provides an important step toward the discovery of underlying molecular mechanisms in drug resistance events. We recently developed five drug-resistant human ovarian carcinoma cell lines, including two cisplatin (cis) resistant cell lines, two carboplatin (car) resistant cell lines and one taxol (tax) resistant cell line. In this study, we investigated differential gene expression between these resistant cell lines and their parental cell lines by the fluorescence differential display-polymerase chain reaction (FDD-PCR) technique. We first screened and identified differentially expressed genes in the resistant ovarian cancer cell lines, and we then sequenced and analyzed these genes by bioinformatics software. A total of 33 fragments were displayed in the two resistant cell lines (S-cis and S-car) derived from the sensitive SKOV-3 cell line, and 36 fragments were displayed in the three resistant cell lines (A-cis, A-car and A-tax) derived from the sensitive A2780 cell line. After purification, cloning, sequencing, and homology analysis on the NCBI BLAST GenBank, 12 gene fragments were identified from the resistant S-cis and S-car cells, and 23 gene fragments were identified from the resistant A-cis, A-car and A-tax cells. Although a homolog search of the NIH GenBank revealed that most of the gene fragments were not significantly associated with the known drug resistance-related genes, our study conclusively demonstrates that FDD-PCR is a useful tool for analyzing the differential gene expression between resistant and sensitive tumor cells and for identifying novel chemoresistance-associated genes and potential biological markers or genetic markers of drug resistance.

Base Sequence↗
PubMed2005

[Characteristics of blood dynamic parameters in pregnant women with anticardiolipin antibodies and history of adversely pregnant complications].

OBJECTIVE: To study the characteristics of blood dynamic parameters in pregnant women with anticardiolipin antibody (aCL) and a history of adversely pregnant complications. METHODS: The study included a prospective cohort of pregnant women with (272 cases) and without (186 cases) aCL. Among the aCL positive pregnant women, 91 cases had the history of adversely pregnant complications including spontaneous abortion, still fetus. Serum antibodies to cardiolipin (CL) were measured by a specific enzyme linked immunosorbent assay. Blood dynamics parameters were measured by non-invasive cardiovascular parameters surveyor (TP-CBS). RESULTS: The women were divided into three groups: group A (91 cases)included women with both the history of adversely pregnant complications and positive aCL, group B (181 cases) with positive aCL alone and group C (186 cases) without either of them. In group A maximum blood viscosity (Vmax) was (4.7 +/- 0.5) mPa x s and in group B it was (4.6 +/- 0.7) mPa x s. Both was higher than normal. In group B the Vmax was higher (P < 0.05) than in group C [(4.4 +/- 0.4) mPa x s]. The wave form coefficient(K) was different in three groups: group A was 0.41 +/- 0.04, group B was 0.39 +/- 0.05 and group C was 0.39 +/- 0.04. In group A their wave form coefficient was higher than in group B (P < 0.05). Their total peripheral resistance (TPR) was higher (P < 0.05) in group A [(1.3 +/- 0.4) mm Hg x s x ml(-1)] than in group B [(1.2 +/- 0.4) mm Hg x s x ml(-1)]. The cardiac index (CI) was in group A [(43 +/- 15) ml/(s x m(2))], in group B [(48 +/- 16) ml/(s x m(2))] and in group C [(48 +/- 14) ml/(s x m(2))], lower in group A than in group B (P < 0.05). CONCLUSIONS: An important change of blood dynamic parameters of pregnant women with aCL is the increase of Vmax. If Vmax, K and TPR were increased and CI was decreased simultaneously in women with aCL, it would result in more chances of adversely pregnant complications. Measuring the blood dynamics parameters will help us discover the sub-clinical hypercoagulable state of patients with aCL and guide us to treat them promptly, so that to improve successful pregnancy rate.

Adult↗
PubMed2005

Differential expression of cyclins A, B1, D3 and E in G1 phase of the cell cycle between the synchronized and asynchronously growing MOLT-4 cells.

The use of 'double-thymidine block' was the first widely accepted method for inducing cell synchrony and remains one of the most effective and frequently used techniques for analyzing the cell cycle today. While thymidine is in itself an inhibitor of DNA replication, thymidine blocks are typically used to generate cell synchrony at the G1/S boundary. We have previously presented the first evidence that shows the growth imbalance and altered expression levels of cyclins A, B1, D3 and E in MOLT-4 cells synchronized in the cell cycle by thymidine. The major objective of the present study was to compare the levels of cyclins A, B1, D3 and E in G1 phase of the cell cycle between synchronized and unperturbed asynchronously growing human lymphocyte leukemia MOLT-4 cells. Here, we demonstrate that the sorted, asynchronously growing MOLT-4 cells had considerably lower levels of cyclins A, B1, D3 and E than their counterparts of the cells arrested in G1/S phase, as assessed by flow cytometry. In addition, we confirmed these results by using post-sorting Western blotting, a new method we recently developed for examining protein expression in specific phases of sorted, synchronized or asynchronously growing cells. Our findings revealed that the levels of cyclins D3 and E in the asynchronously growing MOLT-4 cells were significantly lower than those in synchronized cultures. Interestingly, protein expression levels of cyclins A and B1 in the asynchronously growing MOLT-4 cells were barely measurable, suggesting that these proteins were either not expressed or under detectable levels. These studies indicate that our synchronization protocol may have disturbed cell proliferation and metabolism as evidenced by significant differences in the expression of cyclins between asynchronously growing and synchronized cells, and further suggest that the levels of cyclins A, B1, D3 and E in synchronized cultures cannot represent those in unperturbed, asynchronously growing cells. Thus, it appears that thymidine-treated, synchronized cells may not be suitable experimental models for the study of normal cell cycle.

Blotting, Western↗
PubMed2005

[Management of heart failure and timing of delivery in pregnancy].

OBJECTIVE: To explore the management of heart failure, the timing of delivery in pregnancy, and the influence on pregnant prognosis. METHODS: We retrospectively analyzed the incidence of heart failure, treatment results, pattern of termination, and time of termination in 356 cases of pregnancy with heart disease. RESULTS: One hundred and thirty-six (38.20%) cases were diagnosed as heart failure and 76 (55.88%) were moderate or severe heart failure. Heart failure tends to occur more easily in rheumatic heart diseases than in congenital heart diseases. Heart failure occurred more frequently in pregnancy with rheumatic heart diseases without the heart operation before pregnancy than that of pregnancy with congenital heart diseases. The occurence of the moderate and severe heart failure in pregnancy decreased in rheumatic heart diseases with surgical therapies compared with those without surgical therapies (P <0.05). Compared with pregnancy with heart failure controlled inadequately, pregnancy with effectively controlled heart failure had better tolerance during delivery and through the pregnancy, and puerperium. CONCLUSION: Congenital heart diseases and rheumatic heart diseases are the chief causes of heart failure during the gestation. Therapy before pregnancy, especially surgery to the rheumatic heart diseases, may improve the cardiac function during pregnancy. Monitoring heart function and selecting the proper timing to terminate pregnancy after controlling the heart failure in late pregnant period will be helpful to improve the prognosis of pregnant and perineonate.

Adult↗
PubMed2004

Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer.

Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogues that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small molecule XIAP antagonists as a potential therapy for cancers that overexpress XIAP.

Animals↗
PubMed2004

Modulation of Kupffer cells on hepatic drug metabolism.

AIM: To observe the effects of Kupffer cells on hepatic drug metabolic enzymes. METHODS: Kunming mice were i.p. injected with GdCl310, 20, 40 mg/kg to decrease the number and block the function of kupffer cells selectively. The contents of drug metabolic enzymes, cytochrome P450, NADPH-cytochrom C redutase (NADPH-C), aniline hydroxylase (ANH), aminopyrine N-demethylase (AMD), erythromycin N-demethylase (EMD), and glutathione s-transferase (mGST) in hepatic microsome and S9-GSTpi, S9-GST in supernatant of 9 000 g were accessed 1 d after the injection. The time course of alteration of drug metabolic enzymes was observed on d 1, 3, and 6 treated with a single dose GdCl3. Mice were treated with Angelica sinensis polysaccharides (ASP) of 30, 60, 120 mg/kg, i.g., qd x 6 d, respectively and the same assays were performed. RESULTS: P450 content and NADPH-C, ANH, AMD, and EMD activities were obviously reduced 1 d after Kupffer cell blockade. However, mGST and S9-GST activities were significantly increased. But no relationship was observed between GdCl3 dosage and enzyme activities. With single dose GdCl3 treatment, P450 content, NADPH-C, and ANH activities were further decreased following Kupffer cell blockade lasted for 6 d, by 35.7%, 50.3%, 36.5% after 3 d, and 57.9%, 57.9%, 63.2% after 6 d, respectively. On the contrary, AMD, EMD, mGST, and S9-GST activities were raised by 36.5%, 71.9%, 23.1%, 35.7% after 3 d, and 155%, 182%, 21.5%, 33.7% after 6 d, respectively. Furthermore, the activities of drug metabolic enzymes were markedly increased after 30 mg/kg ASP treatment, and decreased significantly after 120 mg/kg ASP treatment. No change in activity of S9-GSTpi was observed in the present study. CONCLUSION: Kupffer cells play an important role in the modulation of drug metabolic enzymes. The changes of drug metabolic enzyme activities depend on the time of kupffer cell blockade and on the degree of Kupffer cells activated. A low concentration of ASP increases the activities of drug metabolic enzymes, but a high concentration of ASP decreases the activities of drug metabolic enzymes.

Angelica sinensis↗
PubMed2004

[C6N2H14]0.5.[MnAl3(PO4)4(H2O)2]: a manganese(II)-substituted aluminophosphate with AFN topology.

A new manganese(II)-substituted aluminophosphate, [C(6)N(2)H(14)]0.5.[MnAl(3)(PO(4))(4)(H(2)O)(2)], denoted as MnAPO-14, has been synthesized hydrothermally in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as the structure-directing agent. Its structure is determined by single-crystal X-ray diffraction analysis and further characterized by X-ray powder diffraction, ICP, and TG analyses. The structure of MnAPO-14 is built up by MnO(4)(H(2)O)(2) octahedra, AlO(4) tetrahedra, and PO(4) tetrahedra via Al-O-P and Mn-O-P linkages. Its framework is analogous to that of aluminophosphate zeotype AFN in which 25% of the aluminum sites are replaced by Mn(II) atoms. The diprotonated DABCO cations reside in the eight-membered ring channels. Computational simulations indicate that the substitution site of Mn to Al is determined by the host-guest interaction. Crystal data: [C(6)N(2)H(14)]0.5.[MnAl(3)(PO(4))(4)(H(2)O)(2)], triclinic P1 (No. 2), a = 9.5121(4) A, b = 9.8819(3) A, c = 12.1172(4) A, alpha = 70.533(2) degrees, beta = 73.473(2) degrees, gamma = 82.328(2) degrees, Z = 2, R(1) = 0.0586 (I > 2 sigma(I)), and wR(2) = 0.1877 (all data).

Journal Article↗
PubMed2004

Resistance index in differential diagnosis of liver lesions by color doppler ultrasonography.

AIM: To investigate the specific value of resistance index (RI) in color Doppler ultrasonography in the diagnosis of focal hepatic lesions. METHODS: Eight hundred patients with 893 hepatic solid lesions were studied with color Doppler flow imaging (CDFI) and pulsed Doppler, including 644 malignant cases (596 primary malignant liver tumors, and 48 metastatic liver tumors), 156 benign cases. All were confirmed by operation and pathology. RESULTS: The detection rate of arterial flow in malignant tumors was 92%, and 52% in benign lesions. Doppler spectrum analysis showed that the resistance index in primary malignant tumors was 0.75+/-0.12, 0.73+/-0.09 in metastatic tumors, and was below 0.6 in benign lesions. The difference was significant (P<0.001). This difference was related with its histopathologic structure. CONCLUSION: The arterial flow with RI > or =0.6 identified by CDFI within the liver lesion can be regarded as a criterion of malignant tumors, RI<0.6 can be regarded as benign disorders. RI is useful in differential diagnosis of liver neoplasms.

Adolescent↗
PubMed2004

Characterization of hepatic tumors: value of contrast-enhanced coded phase-inversion harmonic angio.

OBJECTIVE: Our purpose was to evaluate the value of contrast-enhanced coded phase-inversion harmonic imaging in showing the characteristic intranodular hemodynamics of hepatic tumors. SUBJECTS AND METHODS. Using a microbubble contrast agent we performed coded harmonic angio in 163 patients with 192 hepatic tumor nodules: 153 hepatocellular carcinomas, 13 metastases, 14 hemangiomas, eight dysplastic nodules, and four focal nodular hyperplasias. After injecting Levovist, we performed real-time scanning, interval-delay fast low-angle shot imaging, and sweep scanning in the early arterial phase, late vascular phase, and postvascular phase, respectively. RESULTS: On contrast-enhanced coded harmonic angio, the typical hemodynamic pattern of hepatocellular carcinomas was shown as abundant tumor vessels supplied from the periphery to the center of the tumor and dense parenchymal tumor staining with fast washout (sensitivity, 92.8%; specificity, 92.3%). The characteristic hemodynamic pattern of metastases was peripheral tumor vessels with a rim parenchymal stain in the vascular phase followed by a perfusion defect in the postvascular phase (sensitivity, 69.2%; specificity, 100%). Hemangiomas were hypovascular in the early arterial phase with gradual spotty or cotton-wool pooling continuing to the late vascular phase (sensitivity, 92.9%; specificity, 100%). Dysplastic nodules were shown as having no early arterial supply with isovascularity in the late vascular phase (sensitivity, 75%; specificity, 100%). Focal nodular hyperplasias were shown to have a spoked wheel pattern of blood vessels accompanied by dense staining in interval-delay scanning (sensitivity, 100%; specificity, 100%). CONCLUSION: Contrast-enhanced coded harmonic angio is a promising method to provide useful information for the differential diagnosis of hepatic tumors.

Adult↗
PubMed2004

[Research advances on tumor therapy via nitric oxide].

Nitric oxide (NO) is a short-lived pleiotropic molecule involved in many physiological and pathological processes in the organism. As an important biologic mediator, nitric oxide has been focused in tumor study and therapy for its function in the process of tumor genesis, progression,and death. It is documented that nitric oxide plays a dual role:induction or suppression of tumorigenesis, which is dependent on different conditions, such as the concentration, time,and position of NO products. Tumor growth can be promoted by continuous low NO concentration, while cytotoxicity and apoptosis to tumor cells can be induced by quite high NO concentration. Currently, the concentration-dependent principle is the theoretical basis of tumor therapy mediated by NO. These tumor therapies can be classified into several types: firstly, drug treatments including chemotherapy, nitric oxide synthase inducer and inhibitor, together with related research from Chinese traditional medicine; secondly, radiotherapy and photodynamic therapy; thirdly, genic level therapy; and so on. Thus, the paper states the relationship and mechanism between NO and tumor, and summarizes research advances on tumor therapy via nitric oxide.

Animals↗
PubMed2004

Mechanisms underlying the synergistic effect of SU5416 and cisplatin on cytotoxicity in human ovarian tumor cells.

SU5416 is a selective inhibitor of vascular endothelial growth factor (VEGF) receptors with anti-angiogenesis activity for human cancers. We have previously reported that SU5416 sensitizes ovarian cancer cells to cisplatin via suppression of nucleotide excision repair activity. This study sought to gain further insights into the mechanisms underlying the synergistic effect of SU5416 and cisplatin on cytotoxicity in human ovarian tumor cells. Here, we show that SU5416 inhibited the expression of G1 cell cycle checkpoint regulators, p53, p21, p27 and MDM2 in ovarian carcinoma cells. We also demonstrate that SU5416 triggered the apoptosis of these cells, in addition to augmenting the apoptosis induced by cisplatin, as determined by a Sub-G1 profile analysis using a flow cytometer. Furthermore, we show that SU5416-induced apoptosis is associated with a decrease in the expression of the apoptosis inhibitors, MDM2 and Bcl-2, and an increase in the level of NF-kappaB inhibitor, IkappaBalpha. NF-kappaB is an anti-apoptotic transcription factor, which induces the apoptosis inhibitors, Bcl-XL and IAPs (inhibitor of apoptosis proteins), and IkappaBalpha is an inhibitor of NF-kappaB, which binds to the NF-kappaB and retains it in the cytoplasm. Finally, the compound was found to block cisplatin-induced increases in AP-1 expression and JNK activity, as well as Raf-1 protein level in these cells. Together, these results suggest that the chemosensitizing effect of SU5416 on ovarian tumor cells may be mediated, at least in part, through inhibiting G1 checkpoint control and up-regulating the apoptotic response to cisplatin.

Angiogenesis Inhibitors↗
PubMed2004

Development and characterization of five cell models for chemoresistance studies of human ovarian carcinoma.

Platinum agents and paclitaxel (taxol) are among the most effective drugs currently available for treatment of ovarian cancer. One of the hurdles with taxol and platinum- based therapy is the clinical development of resistance to these agents. To investigate the mechanism of drug resistance in human ovarian cancer, we developed and characterized 5 cell models for chemoresistance studies of cisplatin, carboplatin and taxol. We report in this study that these human ovarian carcinoma cell model systems include 2 models for cisplatin resistance, 2 models for carboplatin resistance, and 1 model for taxol resistance. The biological and biochemical characteristics of the models showed that (i), the IC50 values of the drugs for all these resistant cell models were 3 times (or more) higher than those for the parental tumor cells. There also exist varying degrees of cross-resistance to several other chemotherapeutic agents in these systems. Moreover, the intracellular drug accumulations in these cells were significantly reduced as compared to those in the parental cells. (ii), The proliferation rates of these resistant cells were markedly decreased. However, there were no obvious changes in cell cycle distribution in these model systems. (iii), Our results for the expression of a few major drug resistance-related genes revealed that the expression of p53, lrp-1 and mrp-1 was decreased, while the expression of pkc, topo I and topo II beta was increased in the resistant tumor cells as compared with the parental cells. In contrast, no significant alterations in gst-pi and topo II alpha expression were found. Interestingly, the levels of mdr-1 expression were elevated in some models, but were reduced in others, thus suggesting that different pathways are involved in the formation of drug resistance in different cell model systems, and that different mechanisms are responsible for the development of different drug resistances in tumor cells. Taken together, our findings indicate that these models may be potentially used to assess the biochemical and genetic mechanisms of drug resistance in human ovarian cancer and to identify new drug resistance-related genes.

Antineoplastic Agents↗
PubMed2004

The endothelium in health and disease: a discussion of the contribution of non-nitric oxide endothelium-derived vasoactive mediators to vascular homeostasis in normal vessels and in type II diabetes.

Endothelial dysfunction is considered as a major risk factor of cardiovascular complications of type I and types II diabetes. Impaired endothelium-dependent vasodilatation can be directly linked to a decreased synthesis of the endothelium-derived nitric oxide (NO) and/or an increase in the production of reactive oxygen species such as superoxide. Administration of tetrahydrobiopterin, an important co-factor for the enzyme nitric oxide synthase (NOS), has been demonstrated to enhance NO production in prehypertensive rats, restore endothelium-dependent vasodilatation in coronary arteries following reperfusion injury, aortae from streptozotocin-induced diabetic rats and in patients with hypercholesterolemia. Tetrahydrobiopterin supplementation has been shown to improve endothelium-dependent relaxation in normal individuals, patients with type II diabetes and in smokers. These findings from different animal models as well as in clinical trials lead to the hypothesis that tetrahydrobiopterin, or a precursor thereof, could be a new and an effective therapeutic approach for the improvement of endothelium function in pathophysiological conditions. In addition to NO, the endothelium also produces a variety of other vasoactive factors and a key question is: Is there also a link to changes in the synthesis/action of these other endothelium-derived factors to the cardiovascular complications associated with diabetes? Endothelium-derived hyperpolarizing factor, or EDHF, is thought to be an extremely important vasodilator substance notably in the resistance vasculature. Unfortunately, the nature and, indeed, the very existence of EDHF remains obscure. Potentially there are multiple EDHFs demonstrating vessel selectivity in their actions. However, until now, identity and properties of EDHF that determine the therapeutic potential of manipulating EDHF remains unknown. Here we briefly review the current status of EDHF and the link between EDHF and endothelial dysfunction associated with diabetes.

Animals↗
PubMed2004

[A review of methods for measuring plant programmed cell death (PCD)].

Programmed cell death (PCD) is an active way for plant cells marching to death, which plays an important role in plant development and stress responses. Cytological, biochemical, molecular and physiological methods for measuring plant PCD were reviewed. Application of flow cytometer to plant PCD research was also covered.

Apoptosis↗