Risk of multiple primary cancers in nasal cancer patients.
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Adult↗
Biomedical subjects
C Dong
Publications and source records attributed to C Dong.
Th1 and Th2 cells.
After activation, CD4 helper T (Th) cells differentiate into Th1or Th2 effector subsets. These two types of cells produce distinct profiles of cytokines and regulate different immune responses. This review summarizes recent progress on different features of co-stimulatory regulation and chemokine-mediated homing of Th1 and Th2 cells. Transcription factors and signaling pathways that are selectively expressed or activated in Th1 and Th2 cells to regulate cytokine gene expression are discussed.
Animals↗
Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs.
Fetal liver intriguingly consists of hepatic parenchymal cells and hematopoietic stem/progenitor cells. Human fetal liver aged 22 wk of gestation (HFL22w) corresponds to the turning point between immigration and emigration of the hematopoietic system. To gain further molecular insight into its developmental and functional characteristics, HFL22w was studied by generating expressed sequence tags (ESTs) and by analyzing the compiled expression profiles of liver at different developmental stages. A total of 13,077 ESTs were sequenced from a 3'-directed cDNA library of HFL22w, and classified as follows: 5819 (44.5%) matched to known genes; 5460 (41.8%) exhibited no significant homology to known genes; and the remaining 1798 (13.7%) were genomic sequences of unknown function, mitochondrial genomic sequences, or repetitive sequences. Integration of ESTs of known human genes generated a profile including 1660 genes that could be divided into 15 gene categories according to their functions. Genes related to general housekeeping, ESTs associated with hematopoiesis, and liver-specific genes were highly expressed. Genes for signal transduction and those associated with diseases, abnormalities, or transcription regulation were also noticeably active. By comparing the expression profiles, we identified six gene groups that were associated with different developmental stages of human fetal liver, tumorigenesis, different physiological functions of Itoh cells against the other types of hepatic cells, and fetal hematopoiesis. The gene expression profile therefore reflected the unique functional characteristics of HFL22w remarkably. Meanwhile, 110 full-length cDNAs of novel genes were cloned and sequenced. These novel genes might contribute to our understanding of the unique functional characteristics of the human fetal liver at 22 wk.
Cloning, Molecular↗
[Ca2+]i as a potential downregulator of alpha2beta1-integrin-mediated A2058 tumor cell migration to type IV collagen.
We have investigated cellular Ca2+ regulation during A2058 human melanoma cell chemotaxis to type IV collagen (CIV). We have identified alpha2beta1-integrin as the primary mediator of A2058 cell response to CIV in vitro. Integrin ligation initiated a characteristic intracellular Ca2+ concentration ([Ca2+]i) response consisting of an internal release and a receptor-mediated Ca2+ entry. Thapsigargin (TG) pretreatment drained overlapping and CIV-inducible internal Ca2+ stores while initiating a store-operated Ca2+ release (SOCR). CIV-mediated Ca2+ entry was additive to TG-SOCR, suggesting an independent signaling mechanism. Similarly, ionophore application in a basal medium containing Ca2+ initiated a sustained influx. Elevated [Ca2+]i from TG-SOCR or ionophore significantly attenuated cell migration to CIV by recruiting the Ca2+/calcineurin-mediated signaling pathway. Furthermore, low [Ca2+]i induced by EGTA application in the presence of ionophore fully restored cell motility to CIV. Together, these results suggest that [Ca2+]i signaling accompanying A2058 cell response to alpha2beta1-integrin ligation is neither necessary nor sufficient and that elevated [Ca2+]i downregulates cell motility via a calcineurin-mediated mechanism in A2058 cell chemotaxis to CIV.
Antibodies, Monoclonal↗
Conjugated equine estrogen improves glycemic control and blood lipoproteins in postmenopausal women with type 2 diabetes.
The objective of this study was to determine the metabolic effects of estrogen replacement therapy in postmenopausal women with type 2 diabetes. Twenty-five postmenopausal, type 2 diabetic women completed a randomized, blinded, cross-over trial of conjugated equine estrogen, 0.625 mg/day, vs. placebo for 8 weeks, separated by a 4-week washout period. When compared with 8 weeks of placebo, estrogen reduced fasting serum glucose (7.2 +/- 0.3 vs. 8.4 +/- 0.4 mmol/L, P = 0.0003), glycated hemoglobin (8.7 +/- 0.4% vs. 9.3 +/- 0.4%, P = 0.04), total cholesterol (5.27 +/- 0.20 vs. 5.50 +/- 0.21 mmol/L, P = 0.04), low-density lipoprotein cholesterol (2.47 +/- 0.13 vs. 2.69 +/- 0.14 mmol/L, P = 0.02), serum apolipoprotein B (114 +/- 6 vs. 121 +/- 5 mg/dL, P = 0.03), and postprandial glucose area under the curve (by 12%, P = 0.015). Estrogen replacement therapy also increased high-density lipoprotein (HDL) cholesterol (1.27 +/- 0.08 vs. 1.1 +/- 0.07 mmol/L, P = 0.0002), high-density lipoprotein(2) cholesterol (0.41 +/- 0.04 vs. 0.30 +/- 0.03 mmol/L, P = 0.0001), and fasting triglyceride (2.17 +/- 0.21 vs. 1.94 +/- 0.16 mg/dL, P = 0.02) concentrations but not postprandial triglyceride area under the curve (P = not significant). We conclude that estrogen replacement therapy improves glycemic control, blood lipoproteins, and apolipoprotein B concentrations while modestly increasing triglyceride levels in postmenopausal, type 2 diabetic women.
Animals↗
Second primary cancers after sporadic and familial colorectal cancer.
Second cancers were studied among 68,104 cases of colorectal cancer (CRC) from the Swedish Family-Cancer Database. A total of 1,113 patients received a diagnosis of second CRC; 25 of them had a family history of CRC. Cases of second CRC with a family history were diagnosed up to 10 years before sporadic cases. The relative risk (RR) of all second CRCs was 2.21 compared with the first CRC. Familial second CRCs had a 2-fold risk compared with the sporadic forms. Age of onset was the most important covariate of second CRCs; the relative risk at ages 15-39 years was 27 compared with the first CRC. Familial CRC was associated with a high risk of small-intestinal, endometrial, and gastric cancers apart from CRC, all typical of hereditary nonpolyposis CRC (HNPCC). Among familial cases, 36% of second CRCs and 100% of endometrial cancers came from families that fulfilled the Bethesda criteria for HNPCC. Only 12 families conformed to the Amsterdam criteria; in family members, the risk of second CRC was 127-fold and that of endometrial cancer 257-fold. Other sites that were in excess among all second cancers were many cancers linked to HNPCC and, additionally, breast, prostate, thyroid and other endocrine, skin, and genital cancers. The high risk of second cancer after early-onset CRC calls for evaluation of family history and clinical surveillance.
Adolescent↗
[Quantitative analysis of the expression of insulin receptor and tyrosine protein kinase of patients with hepatic cirrhosis].
OBJECTIVE: To investigate the relationship between the expression of insulin receptor (IR) and the content of tyrosine protein kinase (TPK) in patients with hepatic cirrhosis. METHODS: Glucose tolerance test (GTT), insulin, c-peptide, insulin antibodies in serum, the expression of IR and TPK were quantitively analysed in patients with hepatic cirrhosis. The amount of IR and TPK was evaluated by immunohistochemical quantitative analysis using image analyzer in 12 patients with positive HBV marks and cirrhosis. Insulin and c-peptide in serum were determined by immunoenzymemetric assay (IEMA) and insulin antibodies in serum determined by RIA. RESULTS: IR amount in normal and abnormal GTT patients with hepatic cirrhosis was signifficantly less than that in control group (P<0.01). TPK amount in liver of patitents with abnormal GTT was less than that of normal GTT (P<0.01). CONCLUSIONS: IR decreases in cirrhotic patients. Abnormal GTT has relation to reducing TPK activity.
Antibodies↗
Improvement of melatonin to the learning and memory impairment induced by amyloid beta-peptide 25 - 35 in elder rats.
AIM: To investigate improvement of melatonin on learning and memory impairment induced by amyloid beta-peptide 25 - 35 (Abeta25-35) in elder rats. METHODS: Step-down type passive avoidance test, shuttle-box test, and Morris water maze were used together to determine effects of Abeta25-35 and melatonin on learning and memory. Pathological changes were observed by HE, Congo red, and Ag staining. RESULTS: The elder rats were injected bilaterally Abeta25-35 20 microg into the hippocampus to induce learning and memory dysfunction. Melatonin administration (0.1, 1, and 10 mg/kg, ig x 8 d) to the Abeta25-35-treated rats prolonged the latency, shortened the total stimulating time, and decreased the number of errors in the step-down test. Shuttle-box test showed that melatonin improved amnesic rats' performance at the same doses. Melatonin (0.1, 1, and 10 mg/kg ), giving for 10 d, could enhance the spatial resolution of amnesic rats in Morris water maze test. Also in Abeta25-35-treated group, a decrease in the number of neurons in cortex and hippocampus, a massive glial reaction, and neurophilic phenomenon were detected by HE staining; the positive vascular amyloidosis by Congo red and fibrils by Ag staining were observed. Melatonin (0.1 and 1 mg/kg)could inhibit above pathological changes in Abeta25-35 group. CONCLUSION: Melatonin improved the impaired learning and memory induced by Abeta25-35 in elder rats.
Amyloid beta-Peptides↗
[Studies on correlation between protonation and tautomerism and luminescence characteristics of quinolone].
The fluorescence characteristics of 8 kinds of quinolone in different pH medium were studied. Rules of wavelength and intensity of the fluorescence in different pH medium were discovered. The correlation between the protonation, tautomerism and luminescence characteristics of quinolone are studied. It is found that in pH 6-8 or 2-4 there are two luminescence species. By this, the new view is represented that the change of luminescence characteristics is arised from the protonation and tautomerism of quinolones in different pH medium and the material point of luminescence developed in equilibrium system of tautomerism. Additionally, the correlation between the protonation, tautomerism and luminescence is further discussed.
Anti-Infective Agents↗
[Transformation of S- (+)-ofloxacin enantiomer in human body and determination by synchronous-derivative fluorimetry].
At pH 3,S,R enantioners of ofloxacin can be well recognized by the synchronous-first derivative fluorimetry. Based on this, a new method for the recognition and determination of enantiomers of ofloxacin, the synchronous-first order derivative fluorimetry has been developed. The linear range is 0.36-2.16 micrograms.mL-1(R), 0.36-2.89 micrograms.mL-1(S), and 3.16-31.6 micrograms.mL-1(S). The detection limit is 0.36 microgram.mL-1, RSD is less than 6.6%, and the recovery is within the range of 97%%-104%. The transformation of S- to R- (+)-ofloxacin enantiomer in human body is founded. In 0-3 h after taking ofloxacin tablets by a healthy subject, R-enantiomer can not be detected. At the 6th hour, remarkable amount of R-enantiomer was detected, and then R-/S-enantiomer ratio increased rapidly to 21.3% at the 24th hour for 2.1% at the 6th hour.
Anti-Infective Agents↗
[Determination of ofloxacin in urine by synchronous-derivative fluorimetry].
The internal hormones in human urine emit strong fluorescence and interfere with the determination of trace ofloxacin. However, the experiments indicate that synchronous-first order derivative fluorimetry can be applied to the determination of trace ofloxacin without interference. The linear range is 0.36-3.6 micrograms.mL-1, detection limit is 0.3 microgram.mL-1, RSD is less than 2.5% and the recovery is within the range of 101%-103%.
Humans↗
Stimulation of the mitogen-activated protein kinase cascade and tyrosine phosphorylation of the epidermal growth factor receptor by hepatopoietin.
Hepatopoietin (HPO) is a novel human hepatotrophic growth factor, which specifically stimulates proliferation of cultured primary hepatocytes in vitro and liver regeneration after liver partial hepatectomy in vivo. Recently, the identification of the mitogenic effect of HPO on hepatoma cell lines and the existence of HPO-specific receptors indicate that HPO acts via its specific cell surface receptor. However, the molecular mechanism of HPO action is not fully elucidated. In this report, we examined the signal transduction events induced by HPO in hepatoma cell line (HepG2). Our results demonstrated that HPO induces phosphorylation of mitogen-activated protein kinase kinase and mitogen-activated protein kinase (MAPK) in a rapid and transient manner. HPO stimulates tyrosine phosphorylation of epidermal growth factor receptor (EGFR). Furthermore, we observed that both MAPK activation and the mitogenic effect of HPO on HepG2 cells were completely blocked by AG1478, a specific inhibitor of EGFR tyrosine kinase activity. However, the effects of HPO were not antagonized by an EGFR-blocking antibody, mAb528, which blocks the interaction between epidermal growth factor and EGFR, indicating that stimulation of tyrosine phosphorylation of EGFR by HPO was not mediated by epidermal growth factor. In contrast, genistein, a general tyrosine kinase inhibitor, significantly attenuated the tyrosine phosphorylation of EGFR in response to HPO. In conclusion, our results suggest that tyrosine phosphorylation of EGFR may play a critical role in MAPK activation and mitogenic stimulation by HPO.
Enzyme Inhibitors↗
Extracellular lipid-mediated signaling in tumor-cell activation and pseudopod protrusion.
We have pioneered an in vitro pseudopod-generation model wherein suspended tumor cells are stimulated to form pseudopods into glass micropipettes in response to soluble collagen type IV (CIV). Pertussis toxin and removing intracellular calcium were found previously to be inhibitory to that process. We now extend those observations to dissect the roles of transmembrane calcium influx and circulating fatty acids on pseudopod extension. Removal of fatty acids from BSA in basal media resulted in abrogation of pseudopod formation, while reconstitution of free fatty acids restored cell pseudopod protrusion. We thus hypothesized that fatty acids may provide necessary pseudopod stimulatory signals. Addition of lysophosphatidic acid (LPA) to the fatty acid-free CIV solution or in an opposite pipette without CIV permitted approximately 50% pseudopod recovery in all pipette directions in a dose-dependent fashion. Thapsigargin (TG), an agent that releases internal calcium stores and causes opening of store-operated calcium channels, restored pseudopod protrusion up to 80% in CIV with fatty acid-free albumin. [Ca(2+)](i) release was non-additive when cells were stimulated by TG and LPA, suggesting overlapping [Ca(2+)](i) stores. The combination of TG and LPA in fatty acid-free albumin fully restored the pseudopod response to CIV. Addition of EGTA to chelate stimulatory media calcium blocked the pseudopod response to CIV in the presence of fatty acids. This indicates that pseudopod protrusion requires transmembrane calcium entry. Thus, extracellular lipids and calcium mobilization are required to complement CIV in pseudopod protrusion from suspended cells.
Calcium↗
Control of T helper cell differentiation--in search of master genes.
Naïve T helper (T(H)0) cells can differentiate into one of two distinct populations: T(H)1 and T(H)2. Each population is characterized by the expression of specific cytokines and their ability to participate in cell-mediated or humoral immune responses. Recent efforts at identifying the molecular mechanisms through which T(H)0 cells become T(H)1 or T(H)2 cells have been promising. A number of transcription factors, including GATA-3 and T-bet, have been identified that promote the differentiation of T(H)0 cells and the maintenance of the differentiated cell phenotype. Dong and Flavell review recent findings on proteins that control the fate of T(H)0 differentiation, whether by promotion or inhibition, and discuss the role of epigenesis in the differentiation process.
Animals↗
JNK1 is required for T cell-mediated immunity against Leishmania major infection.
c-Jun N-terminal kinase (JNK) is a mitogen-activated protein kinase that plays important regulatory roles in helper T cell differentiation. In the current study, we used Jnk1-deficient mice to examine the function of JNK during an in vivo pathogenic infection, leishmaniasis, which is strongly influenced by Th1/Th2 effector mechanisms. The data show that Jnk1-deficient mice, despite their usually genetically resistant background, were unable to resolve Leishmania infections. Jnk1-/- mice displayed reduced delayed-type hypersensitivity in response to the pathogen, which was associated with a T cell defect. We found that, although these mice can direct an apparent Th1-response, there is also simultaneous generation of Leishmania-specific Th2 responses, which possibly down-modulate protective Th1-mediated immune function. These findings demonstrate that the negative regulation of Th2 cytokine production by the JNK1 signaling pathway is essential for generating Th1-polarized immunity against intracellular pathogens, such as Leishmania major.
Animals↗
Lifestyle and cancer: protection from a cancer-free spouse.
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Environmental Exposure↗
JNK is required for effector T-cell function but not for T-cell activation.
The hallmark of T-cell activation is the production of interleukin 2 (IL-2). c-Jun amino-terminal kinase (JNK), a MAP kinase that phosphorylates c-Jun and other components of the AP-1 group of transcription factors, has been implicated in the activation of IL-2 expression. Previously, we found that T cells from mice deficient in the Jnk1 or Jnk2 gene can be activated and produce IL-2 normally, but are deficient in functional differentiation into Th1 or Th2 subsets. However, studies of mice with compound mutations indicate that JNK1 and JNK2 are redundant during mouse development. Here we use three new mouse models in which peripheral T cells completely lack JNK proteins or signalling, to test whether the JNK signalling pathway is crucial for IL-2 expression and T-cell activation. Unexpectedly, these T cells made more IL-2 and proliferated better than wild-type cells. However, production of effector T-cell cytokines did require JNK. Thus, JNK is necessary for T-cell differentiation but not for naive T-cell activation.
Animals↗
Bone sialoprotein and the paradox of angiogenesis versus atherosclerosis.
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Animals↗