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J Cai

Publications and source records attributed to J Cai.

At least 109 records · Page 6Linked to original sources

[The expression of sialyl Lewis-X antigen in LoVo, HT29 cell lines of colorectal cancer and its correlation with metastatic potential].

OBJECTIVE: To study the correlation of sialyl Lewis-X (SLeX) antigen expression with the metastatic potential of human colorectal cancer. METHODS: The expression of biosynthetic enzyme of SLeX antigen--alpha1, 3Fuc-T mRNA in various cell lines of colorectal cancer possessed with different metastatic potentials (LoVo and HT(29)) was investigated by in situ hybridization. The expression of SLeX antigen was studied using immunohistochemistry and fluorescence-activated flow cytometry qualitatively and quantitatively. RESULTS: The expression level of alpha1, 3Fuc-T mRNA and SLeX antigen in highly metastatic LoVo cells was high (21.2 +/- 7.7, 32.8 +/- 10.9, P < 0.05), and the expression level was low in HT(29) cells (10.8 +/- 5.2, 21.9 +/- 8.8) which are known possessed with a lower metastatic potential. CONCLUSION: The expression of SLeX antigen is correlated to the metastatic potentiality of human colorectal cancer.

Cell Line, Tumor↗

[Synthesis and characterization of the oxidation product of the 1, 2, 3-trihydroxybenzene and its metallic complexes].

The oxidation reaction mechanism of the 1,2,3-trihydroxybenzene was studied by the Ab initio calculation of the quantum chemistry. The derivative of the hydrazine and THBO(the reaction product of the 1,2,3-trihydroxybenzene and H2O2) and its metal complexes were synthesized and characterized by the IR, Raman spectrum and thermogravimetric analysis. The composition of these complexes and the possible structure of THBO were confirmed.

Chelating Agents↗

Molecular cloning and mapping of a novel ADAM gene (ADAM29) to human chromosome 4.

Members of the ADAM family (type I integral membrane protein with a disintegrin and metalloprotease domain) have been implicated in many important biological processes involving cell-cell and cell-matrix interactions, such as fertilization and myoblast fusion. We report here the cDNA sequence of a novel human ADAM gene (ADAM29) that contains a putative fusion peptide. Northern blot analysis revealed that the mRNA of ADAM29 is highly expressed in the testis. By radiation hybrid panel mapping, the ADAM29 gene was assigned to human chromosome 4q34.2-qter.

ADAM Proteins↗

Cytochrome c-mediated apoptosis in cells lacking mitochondrial DNA. Signaling pathway involving release and caspase 3 activation is conserved.

Mitochondria serve as a pivotal component of the apoptotic cell death machinery. However, cells that lack mitochondrial DNA (rho(0) cells) retain apparently normal apoptotic signaling. In the present study, we examined mitochondrial mechanisms of apoptosis in rho(0) osteosarcoma cells treated with staurosporine. Immunohistochemistry revealed that rho(0) cells maintained a normal cytochrome c distribution in mitochondria even though these cells were deficient in respiration. Upon staurosporine treatment, cytochrome c was released concomitantly with activation of caspase 3 and loss of mitochondrial membrane potential (Deltapsi(m)). After mitochondrial loss of cytochrome c, rho(0) cells underwent little change in glutathione (GSH) redox potential whereas a dramatic oxidation in GSH/glutathione disulfide (GSSG) pool occurred in parental rho(+) cells. These results show that mitochondrial signaling of apoptosis via cytochrome c release was preserved in cells lacking mtDNA. However, intracellular oxidation that normally accompanies apoptosis was lost, indicating that the mitochondrial respiratory chain provides the major source of redox signaling in apoptosis.

Apoptosis↗

Asymmetric synthesis and antitumor activity of cycloalkanin.

Cycloalkanin was accessible by a practical and efficient asymmetric synthesis. The chiral center of the target is introduced via an asymmetric C-arylation of chiral aldehyde in high de. The synthesized cycloalkanin was shown to be significantly active against P388 cell line as assayed by in vitro MIT method.

Animals↗

Consequences of the use of different measures of effect to determine the impact of age on the association between obesity and mortality.

The impact of using different measures of the effect of obesity on mortality across age groups has not been explored. The authors examined this issue by using mortality data from 62,116 men and 262,965 women in the Cancer Prevention Study-I (1960-1972). Measures of effect were calculated separately, by decade of age, for five groups of participants aged 30-79 years. The rate ratio associated with obesity declined with age, from 2.60 (men) and 1.99 (women) for participants aged 30-39 years to 1.24 (men) and 1.15 (women) for those aged 70-79 years. In contrast, the rate differences between obese and reference-weight participants increased with age, from 201 (men) and 112 (women) deaths per 100,000 person-years for those in the youngest decade to 1,379 (men) and 626 (women) deaths per 100,000 person-years for those in the oldest decade. The years of life lost attributable to obesity tended to increase with age but declined for those in the oldest decade. The rate advancement period declined with decade of age. Standardization of estimates to a population changed some age-associated trends. The direction of trends varied regarding the effect of obesity on mortality across age groups, depending on the measure of effect used.

Adult↗

Clinical significance of spontaneous apoptosis in advanced gastric adenocarcinoma.

BACKGROUND: Spontaneous apoptosis has been detected in gastric carcinoma. However, the clinicopathological significance of this remains unclear. The objective of this study was to investigate the correlation between spontaneous apoptosis and the clinicopathologic and biologic characteristics of advanced gastric carcinoma. In addition, the prognostic significance of spontaneous apoptosis of tumors was evaluated. METHODS: The occurrence of apoptotic cell death (apoptotic index [AI]) in 97 patients with advanced gastric carcinoma was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling method. The Ki-67 labeling index (LI), expression of p53 and p21, DNA ploidy pattern, microvessel density (MVD), density of dendritic cells (DCs) in tumors, and degree of lymphocytic infiltration (LI) of the tumors were compared with the AI for each patient. In addition, the prognostic significance of AI was evaluated in these patients. RESULTS: The mean AI of the 97 tumors was 2.05% (range, 0-11.31%). Statistical analyses revealed significant correlations between the AIs and the Ki-67 LIs (P = 0.0004) and between the AIs and the density of DCs (P = 0.0007), as well as an inverse correlation between the AIs and the intratumoral MVD (P = 0.0064). In addition, the AI of 47 tumors with high grade LI (2.94+/-2.51%) was significantly higher than that of 50 tumors with low grade LI (1.22+/-0.93%) (P<0.0001). However, the authors failed to find a significant correlation between the AIs and expression of p53 and p21 and the DNA ploidy pattern. In 93 surviving patients, the 5-year survival rate of 45 patients who had tumors with high AIs (> or =1.47; 82%) was significantly better than that of 48 patients who had tumors with low AIs (<1.47; 60%) (P = 0.0264). CONCLUSIONS: The findings of the current study suggest that the tumors with low neovascularization and high local immunoreactivity may regulate their progression by apoptosis. Moreover, less extensive apoptosis in gastric adenocarcinoma may contribute to disease progression and could be correlated with a poorer prognosis.

Adenocarcinoma↗

The active site of Serratia endonuclease contains a conserved magnesium-water cluster.

Serratia endonuclease is an important member of a class of magnesium dependent nucleases that are widely distributed in nature. Here, we describe the location and geometry of a magnesium-water cluster within the active site of this enzyme. The sole protein ligand of the magnesium atom is Asn119; this metal ion is also associated with five water molecules to complete an octahedral coordination complex. These water molecules are very well ordered and there is no evidence of rotational disorder or motion. Glu127 and His89 are located nearby and each is hydrogen bonded to water molecules in the coordination sphere. Asp86 is not chelated to the magnesium or its surrounding water molecules. Results of kinetics and site-specific mutagenesis experiments suggest that this metal-water cluster contains the catalytic metal ion of this enzyme. All residues which hydrogen bond to the water molecules that coordinate the magnesium atom are conserved in nucleases homologous to Serratia endonuclease, suggesting that the water cluster is a conserved feature of this family of enzymes. We offer a detailed structural comparison to one other nuclease, the homing endonuclease I-PpoI, that has recently been shown, in spite of a lack of sequence homology, to share a similar active site geometry to Serratia endonuclease. Evidence from both of these structures suggests that the magnesium of Serratia nuclease participates in catalysis via an inner sphere mechanism.

Amino Acid Sequence↗

Inhibition of the expression of VE-cadherin/catenin complex by gamma linolenic acid in human vascular endothelial cells, and its impact on angiogenesis.

Gamma linolenic acid (GLA) has been recently shown to inhibit tumour-induced angiogenesis. The present study investigated the effects of GLA on the HUVEC-specific adhesion. After treatment with GLA, HUVECs decreased the amounts of Triton soluble and insoluble VE-cadherin and beta-catenin and reduced tube formation in matrix in a concentration-dependent manner. An anti-VE-cadherin antibody dissociated HUVECs' colonies and exerted similar inhibitory effects on tube formation of HUVECs. These data indicate that the VE-cadherin/catenins complex is essential for formation and maintenance of new capillaries. It is concluded, therefore, that GLA inhibits tumour-induced angiogenesis partly via the decrease in the expression of VE-cadherin and beta-catenin.

Antigens, CD↗

Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells.

Activation of pro-caspase-3 is a central event in the execution phase of apoptosis and appears to serve as the convergence point of different apoptotic signaling pathways. Recently, mitochondria were found to play a central role in apoptosis through release of cytochrome c and activation of caspases. Moreover, a sub-population of pro-caspase-3 has been found to be localized to this organelle. In the present study, we demonstrate that pro-caspase-3 is present in the mitochondrial fraction of Jurkat T cells in a complex with the chaperone proteins Hsp60 and Hsp10. Induction of apoptosis with staurosporine led to the activation of mitochondrial pro-caspase-3 and its dissociation from the Hsps which were released from mitochondria. The release of Hsps occurred simultaneously with the release of other mitochondrial intermembrane space proteins including cytochrome c and adenylate kinase, prior to a loss of mitochondrial transmembrane potential. In in vitro systems, recombinant Hsp60 and Hsp10 accelerated the activation of pro-caspase-3 by cytochrome c and dATP in an ATP-dependent manner, consistent with their function as chaperones. This finding suggests that the release of mitochondrial Hsps may also accelerate caspase activation in the cytoplasm of intact cells.

Apoptosis↗

Synthesis and biological evaluation of boron-containing polyamines as potential agents for neutron capture therapy of brain tumors.

New boron-containing spermidine/spermine (SPD/SPM) analogues have been synthesized: N5-[4-(2-aminoethyl-o-carboranyl)butyl] and N5-{4-[(2,3-dihydroxypropyl)-o-carboranyl]butyl} SPD/SPM derivatives (ASPD-5, ASPM-5, DHSPD-5, and DHSPM-5) as well as N5-{[4-(dihydroxyboryl)phenyl]methyl}spermidine (BBSPD-5). These boronated polyamines retain their ability to displace ethidium bromide from calf thymus DNA and are rapidly taken up in vitro by F98 rat glioma cells. The in vitro toxicities of ASPD-5, ASPM-5, DHSPD-5, and DHSPM-5 are lower than those previously reported for N5-[4-(o-carboranyl)butyl] SPD/SPM derivatives (SPD-5 and SPM-5) but similar to those of native SPD and SPM. Very low toxicity was also observed for BBSPD-5. In vivo studies of ASPD-5 and BBSPD-5 were performed in mice bearing intracerebral implants of the GL261 glioma and subcutaneous implants of the B16 melanoma. The biodistribution data found in both tumor models suggest that the polyamines synthesized to date do not appear to be suitable boron agents for BNCT.

Animals↗

Nickel enhances telomeric silencing in Saccharomyces cerevisiae.

Certain nickel compounds including crystalline nickel sulfide (NiS) and subsulfide (Ni3S2) are potent human and animal carcinogens. In Chinese hamster embryo cells, an X-linked senescence gene was inactivated following nickel-induced DNA methylation. Nickel also induced the inactivation of the gpt reporter gene by chromatin condensation and a DNA methylation process in a transgenic gpt+ Chinese hamster cell line (G12), which is located near a heterochromatic region. To determine if nickel can cause gene silencing independently of DNA methylation, based only on the induction of changes in chromatin structure, we measured its effect on gene silencing in Saccharomyces cerevisiae. Growth of yeast in the presence of nickel chloride repressed a telomeric marker gene (URA3) and resulted in a stable epigenetic switch. This phenomenon was dependent on the number of cell doubling prior to selection and also on the distance of the marker gene from the end of the chromosome. The level of TPE (telomeric position effect) increased linearly with elevations of nickel concentration. Addition of magnesium inhibited this effect, but magnesium did not silence the reporter gene by itself. The level of silencing was also assessed following treatment with other transition metals: cobalt, copper and cadmium. In the sublethal range, cobalt induced similar effects as nickel, while copper and cadmium did not change the basal level of gene expression. Silencing by copper and cadmium were evident only at concentrations of those metals where the viability was very low.

Cell Survival↗

CT and PET lung image registration and fusion in radiotherapy treatment planning using the chamfer-matching method.

PURPOSE: We present a validation study of CT and PET lung image registration and fusion based on the chamfer-matching method. METHODS AND MATERIALS: The contours of the lung surfaces from CT and PET transmission images were automatically segmented by the thresholding technique. The chamfer-matching technique was then used to register the extracted lung surfaces. Arithmetic means of distance between the two data sets of the pleural surfaces were used as the cost function. Matching was then achieved by iteratively minimizing the cost function through three-dimensional (3D) translation and rotation with an optimization method. RESULTS: Both anatomic thoracic phantom images and clinical patient images were used to evaluate the performance of our registration system. Quantitative analysis from five patients indicates that the registration error in translation was 2-3 mm in the transverse plane, 3-4 mm in the longitudinal direction, and about 1.5 degree in rotation. Typical computing time for chamfer matching is about 1 min. The total time required to register a set of CT and PET lung images, including contour extraction, was generally less than 30 min. CONCLUSION: We have implemented and validated the chamfer-matching method for CT and PET lung image registration and fusion. Our preliminary results show that the chamfer-matching method for CT and PET images in the lung area is feasible. The described registration system has been used to facilitate target definition and treatment planning in radiotherapy.

Aged↗

Antineoplastic urinary protein inhibits Kaposi's sarcoma and angiogenesis in vitro and in vivo.

Kaposi's sarcoma (KS) is the most common tumor in human immunodeficiency virus infection and acquired immune deficiency syndrome. Recent clinical trials with human chorionic gonadotropin (hCG) prepared from early pregnancy urine have shown encouraging results in the resolution of KS lesions. A urinary protein with antitumor activity, ANUP (antineoplastic urinary protein), a dimer of 32 kD, has previously been shown to inhibit the growth of various tumor cell lines in vivo. It was thus studied for its activity in KS cell lines in vitro and in vivo to determine whether it could be a source of the anti-KS activity observed in hCG preparations. ANUP is a strong growth inhibitor for KS cell lines, but has little or no effect on fibroblast, aortic smooth muscle, T- and B-lymphocyte, and monocyte cell lines. ANUP also inhibited the proliferation of endothelial cell lines, suggesting that the in vitro effects were endothelial cell lineage-specific. However, ANUP antibodies did not block the inhibitory effect of certain commercial preparations of hCG, previously shown to be active in KS. Thus, the active protein in these commercial preparations of hCG may be distinct from ANUP. The antitumor activity of ANUP was further confirmed in a chicken allantoic membrane (CAM) assay in which vascular endothelial growth factor (VEGF) and beta fibroblast growth factor (bFGF)-induced angiogenesis was inhibited by ANUP in a dose-dependent manner. In vivo activity of ANUP was demonstrated in the murine model of KS, where ANUP inhibited tumor growth. ANUP is thus a potential candidate for development in the treatment of KS and other diseases in which angiogenesis plays an important role.

Adult↗

Vascular endothelial growth factor chimeric toxin is highly active against endothelial cells.

Angiogenesis is a critical step in a benign tumor's evolution toward malignancy and metastasis. Tumor cells acquire such a phenotype by their ability to secrete angiogenic factors such as vascular endothelial growth factor (VEGF). VEGF receptors (VEGFRs) flt-1/VEGFR-1 and Flk-1/ KDR/VEGFR-2 are restricted to activated endothelial cells, with the highest expression being in the tumor vasculature. The present study was undertaken to target the VEGFRs. Targeted toxins were developed by recombinant methods by fusing VEGF165 or VEGF121 to the diphtheria toxin (DT) translocation and enzymatic domain (DT390-VEGF165 or DT390-VEGF121). Both fusion proteins were found to be highly toxic to proliferating endothelial cells but not to vascular smooth muscle cells. The fusion protein is also active in Kaposi's sarcoma, a tumor type that expresses high levels of VEGFRs. These fusion proteins completely inhibit the basic fibroblast growth factor-induced growth of new blood vessels in the chick chorioallantoic membrane assay. Furthermore, the fusion toxin substantially retards the growth of Kaposi's sarcoma tumors in mice. Because nearly all tumors induce local angiogenesis with high VEGFR expression, VEGF-derived toxins may have wide application in cancer therapy.

Animals↗

Identification and quantitation of N-(carboxymethyl)valine adduct in hemoglobin by gas chromatography/mass spectrometry.

A sensitive, specific and reproducible method was developed for the quantitation of the hemoglobin (Hb) adduct N-(carboxymethyl)valine (CMV). This adduct is one of various products from the Maillard reaction, involving reducing sugars and amino acids, proteins or other molecules with a free amino group. Such adducts, including N epsilon-(carboxymethyl)lysine (CML), are called advanced glycation end products (AGE) and have been correlated with aging and severity of diabetes in human tissues. This method was developed to examine the CMV-Hb adduct as a possible AGE formed by reaction of Hb with glucose or other oxidation products. CMV was cleaved selectively from isolated globin using pentafluorophenyl isothiocyanate (PFPITC) in a modified Edman degradation at pH 9.5. The carboxyl group of the adduct was derivatized to its methyl ester with diazomethane. The resulting derivative, 5-isopropyl-1-(methyl acetate)-3-pentafluorophenyl-2-thiohydantoin, was detected by gas chromatography/mass spectrometry with selected ion monitoring (GC/SIM/MS). Quantitation was based on the response factor of the derivative molecular ion (m/z 396) from synthesized CMV and N-(2-carboxyethyl)valine (molecular ion m/z 410) as internal standard. This method exhibits reproducibility and linearity in the range 0.2-100 ng CMV. The limit of quantitation (0.2 ng CMV) gave a signal-to-noise ratio greater than 5:1 using a 1:30 sample aliquot. The GC/SIM/MS method can detect CMV adduct in 5 mg globin samples with relative standard deviations less than 5%. This approach avoids tedious acid hydrolysis and interference from other amino acids. The molecular ion and other CMV derivative ion assignments from samples were confirmed by accurate mass determinations using GC/high resolution SIM/MS. Measurements from random mouse, rat and human globin samples gave mean CMV levels of about 6, 5 and 14 nmol g-1 Hb in these species, respectively.

Animals↗