Biomedical subjects

Jianhua Chen

Publications and source records attributed to Jianhua Chen.

9 recordsLinked to original sources

PubMed2005

Correction for broadening in Doppler blood flow spectrum estimated using wavelet transform.

The conventionally used spectral estimation technique for Doppler blood flow signal analysis is short-time Fourier transform (STFT). But this method requires stationarity of the signal during the window interval. Wavelet transform (WT), which has a flexible time-frequency window, is particularly suitable for nonstationary signals. In recently years, the WT has been used to investigate its advantages and limitations for the analysis of Doppler blood flow signals. In these studies, the estimated spectral width of Doppler blood flow signals using the WT might include significant window and nonstationarity broadening errors. These broadening errors of the time-varying spectrum were clearly undesirable since it would tend to mask the effect of flow disturbance on the spectra width. In this paper, a closed form expression for window and nonstationary root-mean-squared (rms) spectral width is given when using the WT to estimate the Doppler blood flow spectrum. The increases in the rms spectral width can be calculated and then the spectral width estimation based on the WT can be corrected.

Algorithms↗

PubMed2005

Preclinical evaluation of new and highly potent analogues of octreotide for predictive imaging and targeted radiotherapy.

PURPOSE: Molecular imaging and targeted radiotherapy are emerging fields in nuclear oncology. Five human somatostatin receptors (hsstr1-hsstr5) are known to be overexpressed to some degree on various tumors, sstr2 being the most important one. Clinically used somatostatin based radiopeptides target exclusively sstr2. The aim of this study was to develop novel analogues with a broader sstr profile for diagnostic (positron emission tomography and single-photon emission computed tomography) and radiotherapeutic applications. EXPERIMENTAL DESIGN: The following promising structures emerged from a parallel synthetic approach: [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA(0)),1-Nal(3),Thr(8)]-octreotide (1, DOTA-NOC-ATE) and [DOTA(0),BzThi(3),Thr(8)]-octreotide (2, DOTA-BOC-ATE). The conjugates were labeled with cold and radioactive (111)In. Pharmacologic properties were compared with [(111)In-DOTA,Tyr(3)]-octreotide ([(111)In-DOTA]-TOC). RESULTS: The receptor affinity profile showed high affinity of both peptides to hsstr2, hsstr3, and hsstr5 and some intermediate affinity to hsstr4, whereas [(111)In-DOTA]-TOC shows affinity only to sstr2. The internalization is fast in sstr2 expressing AR4-2J and in transfected sstr3 expressing human embryonic kidney 293 cells. Both radiopeptides internalize much more efficiently than [(111)In-DOTA]-TOC. Animal biodistribution studies showed very high and specific uptake of [(111)In]-1 and [(111)In]-2 in s.c. implanted AR4-2J tumors (Lewis rats) and in somatostatin receptor expressing normal tissues. The uptake was at least 2-fold higher in these tissues and in the tumor compared with [(111)In-DOTA]-TOC. In addition, the kidney uptake was significantly lower for both radiopeptides. CONCLUSIONS: These data suggest that the novel radiopeptides are superior to [(111)In/(90)Y-DOTA]-TOC and show great promise for the clinical application in the imaging of somatostatin receptor-positive tumors and their targeted radiotherapy.

Animals↗

PubMed2005

Evaluation of [99mTc/EDDA/HYNIC0]octreotide derivatives compared with [111In-DOTA0,Tyr3, Thr8]octreotide and [111In-DTPA0]octreotide: does tumor or pancreas uptake correlate with the rate of internalization?

UNLABELLED: Radiolabeled somatostatin analogs are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin receptor-positive tumors. The aim of this study was to compare 3 somatostatin analogs designed for the labeling with (99m)Tc (where HYNIC is 6-hydrazinopyridine-3-carboxylic acid): 6-hydrazinopyridine-3-carboxylic acid(0)-octreotide (HYNIC-OC/(99m)Tc-(1)), [HYNIC(0),Tyr(3)]octreotide (HYNIC-TOC/(99m)Tc-(2)), and [HYNIC(0),Tyr(3),Thr(8)]octreotide (HYNIC-TATE/(99m)Tc-(3)), using ethylenediamine-N,N'-diacetic acid (EDDA) as a coligand. In addition, we compared the (99m)Tc-labeled peptides [(111)In-diethylenetriaminepentaacetic acid(0)]octreotide ([(111)In-DTPA]-OC) and [(111)In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(0),Tyr(3),Thr(8)]octreotide ([(111)In-DOTA]-TATE) with regard to the rate of internalization and the biodistribution in AR4-2J (expressing the somatostatin receptor subtype 2) tumor-bearing rats. The main attention was directed toward a potential correlation between the rate of internalization and the tumor or pancreas uptake. METHODS: Synthesis was performed on solid phase using a standard Fmoc strategy. Internalization was studied in cell culture (AR4-2J) and biodistribution was studied using a Lewis rat tumor model (AR4-2J). RESULTS: The 5 radiopeptides showed a specific internalization into AR4-2J cells in culture (as shown by blocking experiments). The rate of internalization of the 5 radiopeptides differed significantly according to the following order: (99m)Tc-(1) approximately = [(111)In-DTPA]-OC < (99m)Tc-(2) < (99m)Tc-(3) approximately = [(111)In-DOTA]-TATE. All radiopeptides displayed a rapid blood clearance and a fast clearance from all somatostatin receptor-negative tissues predominantly via the kidneys. A receptor-specific uptake of radioactivity was observed for all compounds in somatostatin receptor-positive organs such as the pancreas, the adrenals, and the stomach. After 4 h, the uptake in the AR4-2J tumor was comparable for (99m)Tc-(2) (3.85 +/- 1.0 injected dose per gram tissue (%ID/g)), (99m)Tc-(3) (3.99 +/- 0.58%ID/g), and [(111)In-DOTA]-TATE (4.12 +/- 0.74%ID/g) but much lower for [(111)In-DTPA]-OC (0.99 +/- 0.08%ID/g) and (99m)Tc-(1) (0.70 +/- 0.13%ID/g). The specificity was determined by blocking experiments using a large excess of [Tyr(3)]octreotide. (99m)Tc-(3) displayed the highest tumor-to-kidney ratio (2.5:1), followed by (99m)Tc(2) (1.9:1) and [(111)In-DOTA]-TATE (1.7:1). CONCLUSION: These data show that the 5 radiopeptides are specific radioligands for the somatostatin receptor subtype 2. The rate of internalization correlates with the uptake in the tumor (R(2) = 0.75; P = 0.026) and pancreas (R(2) = 0.98; P = 7.4.10(-5)). [Tyr(3),Thr(8)]octreotide derivatives show superiority over the corresponding octreotide and [Tyr(3)]octreotide derivatives, indicating that [(111)In-DOTA]-TATE and [(99m)Tc/EDDA/HYNIC]-TATE are suitable candidates for clinical studies.

Animals↗

PubMed2004

A RasGAP-derived cell permeable peptide potently enhances genotoxin-induced cytotoxicity in tumor cells.

Treatment of many cancers relies on the combined action of several genotoxins, but the detrimental effect of these drugs on normal cells can cause severe side effects. One major challenge in anticancer therapy is therefore to increase the selectivity of current treatments toward cancer cells in order to spare normal cells. We have recently demonstrated that a RasGAP caspase cleavage fragment is able to sensitize HeLa cells towards cisplatin-induced apoptosis. Here, we extend this observation by showing that this fragment also enhances cell death induced by adriamycin and mitoxantrone, two other widely used genotoxins. Furthermore, we have delineated a short sequence within this fragment that still bears the genotoxin-sensitization property. The peptide encoded by this sequence, when fused to the TAT cell permeation sequence, potently sensitized a number of tumors cells, but not normal cells, towards apoptosis induced by cisplatin, adriamycin and mitoxantrone. This sensitization effect was not mediated through modulation of NFkappaB activity or activation of the JNK and p38 MAPK pathways. Our results demonstrate the feasibility in enhancing the efficacy of currently used drugs to selectively kill cancer cells using peptides derived from pro-apoptotic caspase substrate fragments.

Apoptosis↗

PubMed2004

Synthesis and evaluation of bombesin derivatives on the basis of pan-bombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors.

Bombesin receptors are overexpressed on a variety of human tumors like prostate, breast, and lung cancer. The aim of this study was to develop radiolabeled (Indium-111, Lutetium-177, and Yttrium-90) bombesin analogues with affinity to the three bombesin receptor subtypes for targeted radiotherapy. The following structures were synthesized: diethylenetriaminepentaacetic acid-gamma-aminobutyric acid-[D-Tyr6, beta-Ala11, Thi13, Nle14] bombesin (6-14) (BZH1) and 1,4,7,10-tetraazacyclododecane-N,N',N",N"' -tetraacetic acid-gamma-aminobutyric acid-[D-Tyr6, beta-Ala11, Thi13, Nle14] bombesin (6-14) (BZH2). [111In]-BZH1 and in particular [90Y]-BZH2 were shown to have high affinity to all three human bombesin receptor subtypes with binding affinities in the nanomolar range. In human serum metabolic cleavage was found between beta-Ala11 and His12 with an approximate half-life of 2 hours. The metabolic breakdown was inhibited by EDTA and beta-Ala11-His12 (carnosine) indicating that carnosinase is the active enzyme. Both 111In-labeled peptides were shown to internalize into gastrin-releasing peptide-receptor-positive AR4-2J and PC-3 cells with similar high rates, which were independent of the radiometal. The biodistribution studies of [111In]-BZH1 and [111In]-BZH2 ([177Lu]-BZH2) in AR4-2J tumor-bearing rats showed specific and high uptake in gastrin-releasing peptide-receptor-positive organs and in the AR4-2J tumor. A fast clearance from blood and all of the nontarget organs except the kidneys was found. These radiopeptides were composed of the first pan-bombesin radioligands, which show great promise for the early diagnosis of tumors bearing not only gastrin-releasing peptide-receptors but also the other two bombesin receptor subtypes and may be of use in targeted radiotherapy of these tumors.

Animals↗

PubMed2004

Context modeling based on context quantization with application in wavelet image coding.

Context modeling is widely used in image coding to improve the compression performance. However, with no special treatment, the expected compression gain will be cancelled by the model cost introduced by high order context models. Context quantization is an efficient method to deal with this problem. In this paper, we analyze the general context quantization problem in detail and show that context quantization is similar to a common vector quantization problem. If a suitable distortion measure is defined, the optimal context quantizer can be designed by a Lloyd style iterative algorithm. This context quantization strategy is applied to an embedded wavelet coding scheme in which the significance map symbols and sign symbols are directly coded by arithmetic coding with context models designed by the proposed quantization algorithm. Good coding performance is achieved.

Algorithms↗

PubMed2003

Spatial distribution and specification of mammalian replication origins during G1 phase.

We have examined the distribution of early replicating origins on stretched DNA fibers when nuclei from CHO cells synchronized at different times during G1 phase initiate DNA replication in Xenopus egg extracts. Origins were differentially labeled in vivo versus in vitro to allow a comparison of their relative positions and spacing. With nuclei isolated in the first hour of G1 phase, in vitro origins were distributed throughout a larger number of DNA fibers and did not coincide with in vivo origins. With nuclei isolated 1 h later, a similar total number of in vitro origins were clustered within a smaller number of DNA fibers but still did not coincide with in vivo origins. However, with nuclei isolated later in G1 phase, the positions of many in vitro origins coincided with in vivo origin sites without further change in origin number or density. These results highlight two distinct G1 steps that establish a spatial and temporal program for replication.

Animals↗

PubMed2003

[Study on supercritical CO2 extracting conditions on Phyllanthus urinaria].

The technology for extracting Phyllanthus urinaria L. with supercritical CO2 as a solvent was described. The effect of extraction pressure, extraction temperature, extraction time and 85% ethanol-H2O co-solvent capacity have been studied. The proper technology requirements were determined through orthogonal experiment and the result shows the rate of extraction can be up to 9.0 percent, after extracting for 2.5 hours under the condition of extraction pressure 18 MPa, extraction temperature 50 degrees C, separation temperature 42 degrees C, separation pressure 5.8 +/- 0.2 MPa and CO2 flux 3.0 +/- 0.2 L/h.

Carbon Dioxide↗

PubMedDate not supplied

A novel method for the rational construction of well-defined immunogens: the use of oximation to conjugate cholera toxin B subunit to a peptide-polyoxime complex.

Cholera toxin B subunit (CTB), capable of binding to all mucous membranes in its pentameric form, is a potential carrier of mucosal vaccines. In our previous work we reported that the N-terminus of CTB, a threonine, could in principle undergo oxidation and oximation to form conjugates with a cascade of immunogenic peptides. In this study, we set up a model by chemically coupling CTB to a polyoxime that possessed five copies of influenza virus-derived peptides displayed in comblike form. The construct was reconstituted into pentameric form when eluted from a Superdex column after conjugation, and the pentameric nature of this CTB-viral peptide complex was confirmed by SDS-PAGE. GM(1)-ELISA assay showed that the binding properties of CTB-viral peptide complex were increased 4-5-fold over native CTB.

Cholera Toxin↗