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Biomedical subjects

He Wang

Publications and source records attributed to He Wang.

At least 19 recordsLinked to original sources
PubMed2026

The transcription factor SbWRKY6 confers cadmium tolerance via activating SbPLAC8-17 expression in sorghum.

Cadmium (Cd) is a widespread environmental pollutant that severely threatens crop productivity and food safety. However, the regulatory mechanisms underlying Cd detoxification and tolerance in sorghum remain largely elusive. Herein, we functionally characterized SbWRKY6, a Cd‑induced WRKY transcription factor that localizes to the nucleus and functions as a transcriptional activator. Stable overexpression of SbWRKY6 significantly enhanced Cd tolerance in sorghum, as evidenced by improved growth performance, mitigated oxidative damage, and decreased Cd concentration in plant tissues, whereas silencing of SbWRKY6 resulted in a Cd-hypersensitive phenotype with exacerbated toxicity symptoms. Mechanistically, we identified SbPLAC8-17, a member of the Plant Cadmium Resistance (PCR)/PLAC8 family, as a critical downstream target of SbWRKY6. Heterologous expression of SbPLAC8-17 functionally complemented the Cd‑sensitive phenotype of the yeast mutant ∆ycf1 and reduced intracellular Cd accumulation. Further yeast one-hybrid (Y1H), electrophoretic mobility shift assay (EMSA), and dual-luciferase reporter (Dual-LUC) assays confirmed that SbWRKY6 directly binds to the SbPLAC8-17 promoter and transcriptionally activates its expression. In vivo silencing of SbPLAC8-17 significantly impaired cellular Cd²⁺ efflux and aggravated Cd toxicity in sorghum. Additionally, the rapid Cd-induced transcriptional upregulation of SbMPK3 and its direct physical interaction with SbWRKY6 suggest a potential upstream regulatory module that remains to be functionally validated. Collectively, this study elucidates a novel SbWRKY6‑SbPLAC8-17 transcriptional cascade that positively regulates Cd tolerance by facilitating Cd²⁺ efflux, providing promising genetic targets for phytoremediation and molecular breeding of safe sorghum cultivars for Cd-contaminated fields.

Sorghum↗
PubMed2005

Enhancement of cancer radiation therapy by use of adenovirus-mediated secretable glucose-regulated protein 94/gp96 expression.

Tumor-derived glucose-regulated protein 94 (GRP94/gp96) has shown great promise as a tumor vaccine. However, current protein-based approaches require the availability of large quantities of tumor tissue, which are often not possible. In addition, the efficacy of immunotherapy is often not ideal when used alone. In this study, we explored the therapeutic efficacy of a combined GRP94/gp96-based genetic immunotherapy and radiation therapy strategy in the weakly immunogenic and highly metastatic 4T1 murine mammary cancer model. An adenovirus encoding a modified, secretable form of GRP94 gene (AdsGRP94) was constructed and evaluated in various antitumor experiments. Lethally irradiated, virus-infected cells were used as vaccines. Adenoviral vectors were also injected directly into tumors in conjunction with tumor irradiation. Vaccination with lethally irradiated, AdsGRP94-infected 4T1 cells completely prevented subsequent tumor growth from challenge inoculations of as many as 10(7) cells per mouse. In established tumor models, vaccinations alone had minimal effect on local and metastatic tumor growth. However, when vaccination was combined with radiation therapy and i.t. AdsGRP94 injections, local tumor growth and pulmonary metastasis were markedly inhibited. In some cases, complete tumor regression was observed. In these cases, the mice were resistant to subsequent tumor challenge and remain tumor free up to 10 months after initial therapy. Our results indicate that combined AdsGRP94-based immunotherapy and radiation therapy may be a potentially effective strategy for cancer treatment.

Adenoviridae↗
PubMed2005

Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A.

A G-protein coupled receptor to niacin (nicotinic acid) was identified recently but the physiological/pharmacological role of the receptor remains poorly defined. We present our studies to demonstrate that HM74A, but not HM74, binds niacin at high affinities and effectively mediates Gi signaling events in human embryonic kidney HEK293 cells as well as in 3T3L1 adipocytes expressing HM74A. Furthermore, HM74A, but not HM74, expressed in differentiated 3T3L1 adipocytes effectively mediated inhibition of lipolysis by niacin. Our results provided direct evidence indicating that HM74A, but not HM74, was sufficient to mediate anti-lipolytic effect of niacin in adipose tissue.

3T3-L1 Cells↗
PubMed2005

Cloning and functional characterization of the rabbit C-C chemokine receptor 2.

BACKGROUND: CC-family chemokine receptor 2 (CCR2) is implicated in the trafficking of blood-borne monocytes to sites of inflammation and is implicated in the pathogenesis of several inflammatory diseases such as rheumatoid arthritis, multiple sclerosis and atherosclerosis. The major challenge in the development of small molecule chemokine receptor antagonists is the lack of cross-species activity to the receptor in the preclinical species. Rabbit models have been widely used to study the role of various inflammatory molecules in the development of inflammatory processes. Therefore, in this study, we report the cloning and characterization of rabbit CCR2. Data regarding the activity of the CCR2 antagonist will provide valuable tools to perform toxicology and efficacy studies in the rabbit model. RESULTS: Sequence alignment indicated that rabbit CCR2 shares 80 % identity to human CCR2b. Tissue distribution indicated that rabbit CCR2 is abundantly expressed in spleen and lung. Recombinant rabbit CCR2 expressed as stable transfectants in U-937 cells binds radiolabeled 125I-mouse JE (murine MCP-1) with a calculated Kd of 0.1 nM. In competition binding assays, binding of radiolabeled mouse JE to rabbit CCR2 is differentially competed by human MCP-1, -2, -3 and -4, but not by RANTES, MIP-1alpha or MIP-1beta. U-937/rabbit CCR2 stable transfectants undergo chemotaxis in response to both human MCP-1 and mouse JE with potencies comparable to those reported for human CCR2b. Finally, TAK-779, a dual CCR2/CCR5 antagonist effectively inhibits the binding of 125I-mouse JE (IC50 = 2.3 nM) to rabbit CCR2 and effectively blocks CCR2-mediated chemotaxis. CONCLUSION: In this study, we report the cloning of rabbit CCR2 and demonstrate that this receptor is a functional chemotactic receptor for MCP-1.

Amino Acid Sequence↗
PubMed2005

Validation of an accelerated 'demons' algorithm for deformable image registration in radiation therapy.

A greyscale-based fully automatic deformable image registration algorithm, originally known as the 'demons' algorithm, was implemented for CT image-guided radiotherapy. We accelerated the algorithm by introducing an 'active force' along with an adaptive force strength adjustment during the iterative process. These improvements led to a 40% speed improvement over the original algorithm and a high tolerance of large organ deformations. We used three methods to evaluate the accuracy of the algorithm. First, we created a set of mathematical transformations for a series of patient's CT images. This provides a 'ground truth' solution for quantitatively validating the deformable image registration algorithm. Second, we used a physically deformable pelvic phantom, which can measure deformed objects under different conditions. The results of these two tests allowed us to quantify the accuracy of the deformable registration. Validation results showed that more than 96% of the voxels were within 2 mm of their intended shifts for a prostate and a head-and-neck patient case. The mean errors and standard deviations were 0.5 mm+/-1.5 mm and 0.2 mm+/-0.6 mm, respectively. Using the deformable pelvis phantom, the result showed a tracking accuracy of better than 1.5 mm for 23 seeds implanted in a phantom prostate that was deformed by inflation of a rectal balloon. Third, physician-drawn contours outlining the tumour volumes and certain anatomical structures in the original CT images were deformed along with the CT images acquired during subsequent treatments or during a different respiratory phase for a lung cancer case. Visual inspection of the positions and shapes of these deformed contours agreed well with human judgment. Together, these results suggest that the accelerated demons algorithm has significant potential for delineating and tracking doses in targets and critical structures during CT-guided radiotherapy.

Algorithms↗
PubMed2005

An automatic CT-guided adaptive radiation therapy technique by online modification of multileaf collimator leaf positions for prostate cancer.

PURPOSE: To propose and evaluate online adaptive radiation therapy (ART) using in-room computed tomography (CT) imaging that detects changes in the target position and shape of the prostate and seminal vesicles (SVs) and then automatically modifies the multileaf collimator (MLC) leaf pairs in a slice-by-slice fashion. METHODS AND MATERIALS: For intensity-modulated radiation therapy (IMRT) using a coplanar beam arrangement, each MLC leaf pair projects onto a specific anatomic slice. The proposed strategy assumes that shape deformation is a function of only the superior-inferior (SI) position. That is, there is no shape change within a CT slice, but each slice can be displaced in the anteroposterior (AP) or right-left (RL) direction relative to adjacent slices. First, global shifts (in SI, AP, and RL directions) were calculated by three-dimensional (3D) registration of the bulk of the prostate in the treatment planning CT images with the daily CT images taken immediately before treatment. Local shifts in the AP direction were then found using slice-by-slice registration, in which the CT slices were individually registered. The translational shift within a slice could then be projected to a translational shift in the position of the corresponding MLC leaf pair for each treatment segment for each gantry angle. Global shifts in the SI direction were accounted for by moving the open portal superiorly or inferiorly by an integral number of leaf pairs. The proposed slice-by-slice registration technique was tested by using daily CT images from 46 CT image sets (23 each from 2 patients) taken before the standard delivery of IMRT for prostate cancer. A dosimetric evaluation was carried out by using an 8-field IMRT plan. RESULTS: The shifts and shape change of the prostate and SVs could be separated into 3D global shifts in the RL, AP, and SI directions, plus local shifts in the AP direction, which were different for each CT slice. The MLC leaf positions were successfully modified to compensate for these global shifts and local shape variations. The ART method improved geometric coverage of the prostate and SVs compared with the couch-shift method, particularly for the superior part of the prostate and all the SVs, for which the interfraction shape change was the largest. The dosimetric comparison showed that the ART method covered the target better and reduced the rectal dose more than a simple couch-translation method. CONCLUSIONS: ART corrected for interfraction changes in the position and shape of the prostate and SVs and gave dose distributions that were considerably closer to the planned dose distributions than could be achieved with simple alignment strategies that neglect shape change. The ART proposed in this investigation requires neither contouring of the daily CT images nor extensive calculations; therefore, it may prove to be an effective and clinically practical solution to the problem of interfraction shape changes.

Algorithms↗
PubMed2005

Use of deformed intensity distributions for on-line modification of image-guided IMRT to account for interfractional anatomic changes.

PURPOSE: Recent imaging studies have demonstrated that there can be significant changes in anatomy from day to day and over the course of radiotherapy as a result of daily positioning uncertainties and physiologic and clinical factors. There are a number of strategies to minimize such changes, reduce their impact, or correct for them. Measures to date have included improved immobilization of external and internal anatomy or adjustment of positions based on portal or ultrasound images. Perhaps the most accurate way is to use CT image-guided radiotherapy, for which the possibilities range from simple correction of setup based on daily CT images to on-line near real-time intensity modulated radiotherapy (IMRT) replanning. In addition, there are numerous intermediate possibilities. In this paper, we report the development of one such intermediate method that takes into account anatomic changes by deforming the intensity distributions of each beam based on deformations of anatomy as seen in the beam's-eye-view. METHODS AND MATERIALS: The intensity distribution deformations are computed based on anatomy deformations discerned from the changes in the current image relative to a reference image (e.g., the pretreatment CT scan). First, a reference IMRT plan is generated based on the reference CT image. A new CT image is acquired using an in-room CT for every fraction. The anatomic structure contours are obtained for the new image. (For this article, these contours were manually drawn. When image guided IMRT methods are implemented, anatomic structure contours on subsequent images will likely be obtained with automatic or semiautomatic means. This could be achieved by, for example, first deforming the original CT image to match today's image, and then using the same deformation transformation to map original contours to today's image.) The reference intensity distributions for each beam are then deformed so that the projected geometric relationship within the beam's-eye-view between the anatomy (both target and normal tissues) extracted from the reference image and the reference intensity distribution is the same as (or as close as possible to) the corresponding relationship between anatomy derived from today's image and the newly deformed intensity distributions. To verify whether the dose distributions calculated using the deformed intensity distributions are acceptable for treatment as compared to the original intensity distributions, the deformed intensities are transformed into leaf sequences, which are then used to compute intensity and dose distributions expected to be delivered. The corresponding dose-volume histograms and dose-volume and dose-response indices are also computed. These data are compared with the corresponding data derived (a) from the original treatment plan applied to the original image, (b) from the original treatment plan applied to today's image, and (c) from a new full-fledged IMRT plan designed based on today's image. RESULTS: Depending on the degree of anatomic changes, the use of an IMRT plan designed based on the original planning CT for the treatment of the current fraction could lead to significant differences compared to the intended dose distributions. CT-guided setup compared to the setup based on skin marks or bony landmarks may improve dose distributions somewhat. Replanning IMRT based on the current fraction's image yields the best physically deliverable plan (the "gold standard"). For the prostate and head-and-neck examples studied as proof of principle, the results of deforming intensities within each beam based on the anatomy seen in the beam's-eye-view are a good approximation of full-fledged replanning compared with other alternatives. CONCLUSIONS: Our preliminary results encourage us to believe that deforming intensities taking into account deformation in the anatomy may be a rapid way to produce new treatment plans on-line in near real-time based on daily CT images. The methods we have developed need to be applied to a group of patients for both prostate and head-and-neck cases to confirm the validity of our approach.

Algorithms↗
PubMed2005

Implementation and validation of a three-dimensional deformable registration algorithm for targeted prostate cancer radiotherapy.

PURPOSE: Daily prostate deformation hinders accurate calculation of dose, especially to intraprostatic targets. We implemented a three-dimensional deformable registration algorithm to aid dose tracking for targeted prostate radiotherapy. METHODS AND MATERIALS: The algorithm registers two computed tomography (CT) scans by iteratively minimizing their differences in image intensity. For validation, we measured the accuracy in registering (a) a pelvic CT set to its mathematically deformed counterpart, (b) CT scans of a deformable pelvic phantom with and without an endorectal balloon inflated, to simulate intraprostatic targets, 23 CT-opaque seeds were embedded in the prostate, and (c) two pelvic CT scans of a patient obtained on 2 separate days. RESULTS: The mean (SD) error in registering the pelvic CT set to its transformed set was 0.5 mm (1.5), with correlation coefficient improvement from 0.626 to 0.991. Using the deformable pelvic phantom, the correlation coefficient improved from 0.543 to 0.816 after registration. The mean (SD) error in tracking the intraprostatic seeds was 0.8 mm (0.5). The correlation coefficient improved from 0.610 to 0.944 after registration of the two patient CT sets. CONCLUSION: The algorithm had an accuracy of about 1 mm. It could be used for optimizing dose calculation and delivery for prostate radiotherapy.

Algorithms↗
PubMed2005

[Study on p53 tetramerization domain in improving functional affinity and biological activity of antibody].

OBJECTIVE: To fuse the genes of p53 tetramerization domain and anti-CD3/anti-prostate-cancer bispecific single-chain antibody (BsAb), and exploit a new way to improve the functional affinity and biological activity of antibody. METHODS: Genes of p53 tetramerization domain and anti-CD3/anti-prostate-cancer BsAb was fused by technique of DNA sub-cloning. The fusion gene confirmed by sequencing was subcloned into the pSectag2-B plasmid. Then the recombinant plasmid was transfected into HeLa cells. The expression products, which were analyzed by both SDS-PAGE and western blotting, were purified with Ni(2+)-NTA superflow affinity chromatography. mBsAb-pSectag2-B plasmid was added into the suspensions of human peripheral blood mononuclear cells (PBMCs) and PC-3 cells respectively. Flow cytometry was used to examine the binding rate of multivalent anti-prostate-cander/anti-CD3 bispecific scFv with PBMCs and PC-3 cells. T cells were isolated from the PBMCs. PC-3 cells were labeled with Na(2)[(51)Cr]O(4) used as target cells. Labeled PC-3 cells, T cells, and different concentrations of mBsAb were mixed. Natural release control well with labeled target cells only and maximum release control well with labeled target cells and 10% SDS were prepared. The supernatants were extracted. gamma calculator was used to calculate the counts per minute (cpm) values to calculate the specific release rate of (51)Cr. RESULTS: Sequencing showed a fragment from mBsAb-pSectag2-B with the size of 1.7 kb corresponding to the predicted value. SDS-PAGE and Western blotting showed expression of 67 000 D protein in the supernatant of culture fluid of HeLa cells transfected with MBsAb-pSectag2-B plasmid. The binding rates of multivalent anti-prostate-cancer/anti-CD3 bispecific scFv with PBMC and PC-3 cells were 70.4% and 81% respectively, significantly higher than those of anti-prostate-cancer/anti-CD3 bispecific scFv. In the presence of mBsAb the activated T cells lysed PC-3 cells in positive correlation with the antibody concentration and effective cell/target cell ratio and with a lysis rate significantly higher than those of the control groups. CONCLUSION: Multivalent anti-CD3 x anti-prostate-cancer BsAb exhibits much higher functional affinity and biological activity than anti-CD3 x anti-prostate-cancer BsAb, which may break a new path to the improvement of functional affinity and biological activity of antibody.

Antibodies, Bispecific↗
PubMed2005

Redox potential and equilibria in the reductive half-reaction of Vibrio harveyi NADPH-FMN oxidoreductase.

Vibrio harveyi NADPH:FMN oxidoreductase P (FRP(Vh)) is a homodimeric enzyme having a bound FMN per enzyme monomer. The bound FMN functions as a cofactor of FRP(Vh) in transferring reducing equivalents from NADPH to a flavin substrate in the absence of V. harveyi luciferase but as a substrate for FRP(Vh) in the luciferase-coupled bioluminescent reaction. As part of an integral plan to elucidate the regulation of functional coupling between FRP(Vh) and luciferase, this study was carried out to characterize the equilibrium bindings, reductive potential, and the reversibility of the reduction of the bound FMN in the reductive half-reaction of FRP(Vh). Results indicate that, in addition to NADPH binding, NADP(+) also bound to FRP(Vh) in either the oxidized (K(d) 180 microM) or reduced (K(d) 230 microM) form. By titrations with NADP(+) and NADPH and by an isotope exchange experiment, the reduction of the bound FMN by NADPH was found to be readily reversible (K(eq) = 0.8). Hence, the reduction of FRP(Vh)-bound FMN is not the committed step in coupling the NADPH oxidation to bioluminescence. To our knowledge, such an aspect of flavin reductase catalysis has only been clearly established for FRP(Vh). Although the reductive potentials and some other properties of a R203A variant of FRP(Vh) and an NADH/NADPH-utilizing flavin reductase from Vibrio fischeri are quite similar to that of the wild-type FRP(Vh), the reversal of the reduction of bound FMN was not detected for either of these two enzymes.

FMN Reductase↗
PubMed2005

The relationship of exhaled nitric oxide to airway inflammation and responsiveness in children.

Exhaled nitric oxide (eNO) is a potential tool in epidemiological studies of asthma. It was hypothesized that in a cross-sectional survey of asthma in adolescent children, eNO may contribute to the detection of this disease. A cohort of Australian school children in two educational years (n = 107, aged 14.7 +/- 2.3 years, 42.9% female) were surveyed in terms of exhaled nitric oxide (eNO), which was compared with other indicators of asthma: asthma symptoms, atopy [skin prick tests (SPT)], hypertonic saline bronchial reactivity, sputum inflammatory cells and eosinophilic cationic protein. Significant positive correlations were found with eNO and number of positive skin prick tests (p = 0.001; n = 98), symptoms (p = 0.05; n = 107), sputum eosinophils (p = 0.025; n = 83), and sputum eosinophilic cationic protein (p = 0.009; n = 83). There was no significant relationship with airway hyperresponsiveness (p = 0.3; n = 15). eNO had a negative predictive value for asthma of 83%, and a positive predictive value of 54%, which is comparable with most current tests for diagnosing asthma. eNO appears to be a useful indicator of atopy and airway inflammation, but in this population it was not closely related to airway hyperresponsiveness.

Adolescent↗
PubMed2005

Localization of haptoglobin in normal human skin and some skin diseases.

BACKGROUND: Haptoglobin (Hp) is an acute-phase reactant, known to be produced mainly in the liver. Haptoglobin can also be detected in the cytoplasm of normal epidermal Langerhans cells (LCs), and can prevent their functional maturation. The synthesis of Hp in skin cells has not been well studied. METHODS: We examined Hp expression at mRNA and protein levels by in situ hybridization and immunohistochemistry, respectively, in normal human skin and in the skin of patients with psoriasis, lichen planus, erythroderma, seborrheic keratosis, verruca vulgaris, basal cell carcinoma, systemic lupus erythematosus, pemphigus and bullous pemphigoid. RESULTS: (1) Haptoglobin mRNA was expressed in the epidermal keratinocytes (KCs), the epithelial cells of hair follicles, sebaceous glands and eccrine glands in normal skin and all dermatoses investigated. (2) Whereas compared with normal skin, the Hp mRNA in KCs of patients with psoriasis, lichen planus, erythroderma, seborrhoea keratosis and verruca vulgaris was significantly intensified, it was weaker in patients with systemic lupus erythematosus, pemphigus and bullous pemphigoid. (3) Haptoglobin protein only stained positively in some KCs of patients with psoriasis, lichen planus and erythroderma. (4) Although some but not all epidermal LCs were positively stained with anti-Hp antibody in normal skin and in skin samples from all patients, the ratios of Hp-positive LCs/total LCs were significantly higher in those diseases with intensified Hp mRNA in KCs. CONCLUSIONS: Skin is another extrahepatic organ where Hp can be synthesized by KCs. The expression of Hp mRNA in KCs and the Hp protein in both LCs and KCs appears to be correlated with the amount of inflammation, which might indicate that skin itself is involved in down-regulating the local inflammatory reaction by KC-synthesized Hp.

Haptoglobins↗
PubMed2005

A novel engineered peptide, a narrow-spectrum antibiotic, is effective against vancomycin-resistant Enterococcus faecalis.

A novel antienterococcal peptide was prepared by fusing the enterococcal cCF10 pheromone to the channel-forming domain of colicin Ia, forming Enterococcus faecalis pheromonicin (PMC-EF). This peptide was bactericidal against vancomycin-resistant Enterococcus faecalis (VRE) organisms. Electron microscopy and vital dyes confirmed increased membrane permeability. All mice made bacteremic with VRE strains survived when they were treated with PMC-EF, while all controls died.

Anti-Bacterial Agents↗
PubMed2005

The use of three-dimensional ultrasound micro-imaging to monitor prostate tumor development in a transgenic prostate cancer mouse model.

Longitudinal studies of mouse cancer models required large cohorts since autopsy was the only reliable method to evaluate treatment efficacy. This paper reports the use of high-resolution three-dimensional ultrasound micro-imaging to monitor prostate tumor development in genetically engineered mice. Twenty-nine genetically engineered prostate cancer mice, including castrated and uncastrated mice, were imaged by three-dimensional ultrasound. Qualitative comparisons of three-dimensional ultrasound images with histology sections of prostate tumors demonstrate the ability of ultrasound to accurately depict the size and shape of malignant masses in live mice. The correlation coefficient of tumor diameter measurements performed in vivo with three-dimensional ultrasound and at autopsy was 0.997. Prospective tumor detection sensitivity and specificity were 91.7% and 100%. Representative exponential growth curves constructed via longitudinal ultrasound imaging indicated diameter doubling times from 10 to 37 days for four prostate tumors during an initial period of rapid progression. Three-dimensional ultrasound will likely become the micro-imaging modality most readily adopted for mouse pre-clinical trial studies.

Animals↗
PubMed2005

[The solving and simulation of cable equation under the stimulation of point electrical source].

The character of the membrane of fiber can be simulated by nonpower RC network on condition that the offset of distance between the transmembrane potential of unmyelinated nerve fiber and the resting potential of nerve fiber cell is small enough. Thus, it is possible to found the successive cable equation with external stimulation under subthreshold linear state. So far, most scholars use time-domain analysis method. In this paper are reported the method of integral transform and the analytical expression of cable equation under the stimulation of point electrical source firstly. And at the same time, computer-aided simulation of transmembrane potential of nerve fiber and analysis of the possibility of activating action potential are presented.

Action Potentials↗
PubMed2005

[Relation between the expression of hypoxia inducible factor-1alpha and angiogenesis in ovarian cancer using tissue microarray].

OBJECTIVE: To study the relation between the expression of hypoxia inducible factor-1alpha (HIF-1alpha)and angiogenesis in ovarian cancer. METHODS: The expressions of HIF-1alpha mRNA, vascular endothelial growth factor (VEGF), and CD(34) in 295 patients with epithelial ovarian tumors were analyzed by tissue microarray technology, in situ hybridization and immunohistochemistry, and compared with those of 13 normal ovarian tissue samples. RESULTS: The expressions of HIF-1alpha mRNA were observed in 0, 13.2%, 42.1% and 81.9% of normal ovarian tissue, benign, borderline and malignant ovarian tumors respectively. Expression rates of HIF-1alpha mRNA in borderline and invasive tumors were significantly higher than those in normal ovarian tissues and benign tumors (P < 0.01). Statistical analysis revealed that the expression of HIF-1alpha mRNA was not related to surgical stages and histological subtypes. Close positive relation was observed between the expression of HIF-1alpha mRNA and tumor histological grade (r = 0.246, P < 0.01). There were significant correlations between the expression of HIF-1alpha mRNA and VEGF (r = 0.206, P = 0.01) and microvessel density (MVD) level (r = 0.451, P < 0.01). CONCLUSION: HIF-1alpha may play a role in angiogenesis of ovarian carcinoma, and may promote the development of the carcinoma.

Adenocarcinoma↗
PubMed2005

Mutation analysis of HOXD13 gene in a Chinese pedigree with synpolydactyly.

OBJECTIVE: To study the clinical features and to identify homeobox D13 (HOXD13) gene mutation of the affected individuals in a Chinese synpolydactyly (SPD) kindred. METHODS: Clinical data and peripheral blood samples of SPD family members were obtained through field investigation. For every member of this pedigreeìthe fragment containing mutational hot spots of HOXD13 was amplified by PCR for mutation screening. To examine whether there is any other mutation within coding sequence of HOXD13, exon 1 and exon 2 of HOXD13 were also amplified by PCR. All the amplified fragments were electrophoresed on 2% agarose gels and then the mutant fragments were electrophoresed on 5% polyacrylamide gels to be separated. Purified PCR products of normal and selected mutant alleles were directly sequenced. RESULTS: Comparing the HOXD13 coding sequence of the affected individuals with HOXD13 sequence in the GenBank and with that of the unaffected, an inserted segment coding 8 alanine residues within HOXD13 was found segregating with the disorder. This mutation is also termed polyalanine expansion. The 8-alanine expansion can be interpreted as a reduplication of normal alanines 5-12. CONCLUSION: The results suggest that synpolydactyly in this kindred may be caused by polyalanine expansion in HOXD13.

Base Sequence↗