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31.
Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: identification and characterization using proteomic profiling and mass spectrometry. 总被引:24,自引:0,他引:24
Bin Ye Daniel W Cramer Steven J Skates Steven P Gygi Vanessa Pratomo Lanfei Fu Nora K Horick Larry J Licklider John O Schorge Ross S Berkowitz Samuel C Mok 《Clinical cancer research》2003,9(8):2904-2911
PURPOSE: The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays. Experimental Design: Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens. RESULTS: Using surface enhanced laser desorption and ionization, we found a serum biomarker at approximately 11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the alpha chain of haptoglobin. ELISA indicated that Hp-alpha was =2-fold higher in cancer serum compared with normal, benign tumor, and other gynecological cancers (P < 0.05) and had 64% sensitivity at 90% specificity alone and 91% sensitivity and 95% specificity if combined with CA125. CONCLUSIONS: Haptoglobin-derived alpha subunit is a potential marker for ovarian cancer that is complementary to CA125. MS-based protein profiling is a valuable tool for screening protein markers and useful to detect post-translational modification of tumor-associated proteins or abnormal metabolic products. However, confirmation of protein identity with specific antibodies is crucial for clinical application and functional studies. 相似文献
32.
AIM: To ascertain the psychological, social, and educational needs of children born to mothers with HIV infection. METHODS: Review of case records of 120 children and 86 mothers. RESULTS: The cohort of 120 children were born to 92 women, and followed up for a median duration of 48 months (mean (SD) 51.1 (34.1), range 0.3-132). Sixteen children were infected with HIV, 15 were of indeterminate status, and 89 uninfected. Eighty one children (68%) were cared for by their birth mother, of whom 52% were single women and 23 (38% of 61) known to have symptomatic HIV disease. Twenty five mothers of 32 children had died; the child's mean (SD) age at maternal death was 66.9 months (37.7) (range 4-128). Compared with uninfected children, more infected children knew of their mother's diagnosis (31% v 5%) and mothers were also more likely to disclose their own illness to educational authorities (77% v 13%). A larger proportion of infected children had special educational needs (69% v 13%). Only 33 children (28%) were known not to be receiving any support from the voluntary or statutory agencies. CONCLUSION: The results highlight the multiple needs of children living with maternal HIV infection, which require dedicated resources and commitment from health, education, and social work agencies and the voluntary sector. We propose the model of chronic illness as the standard of care for these children. 相似文献
33.
Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells 总被引:7,自引:5,他引:7
Cell to cell communication via gap junctions is essential in the
maintenance of the homeostatic balance of multicellular organisms. Aberrant
intercellular gap junctional communication (GJIC) has been implicated in
tumor promotion, neuropathy and teratogenesis. Oxidative stress has also
been implicated in similar pathologies such as cancer. We report a
potential link between oxidative stress and GJIC. Hydrogen peroxide, a
known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells
with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible
as indicated by the complete recovery of GJIC with the removal of H2O2 via
a change of fresh media. Free radical scavengers, such as t-butyl alcohol,
propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2,
which indicated that the effects of H2O2 on GJIC was probably not a
consequence of aqueous free radical damage. The depletion of intracellular
GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of
glutathione- sufficient cells with H2O2 resulted in the
hyperphosphorylation of connexin43, which is the basic subunit of the
hexameric gap junction protein, as determined by Western blot analysis.
TPA, a well-known tumor promoter, also inhibits GJIC via
hyperphosphorylation of GJIC, which is a result of protein kinase-C
activation. However, H2O2 also induced hyperphosphorylation in
GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism
of GJIC inhibition must be different from the TPA-pathway and involves GSH.
相似文献
34.
Anthony T. C. Chan Thomas W. T. Leung Wing H. Kwan Tony S. K. Mok Winnie Yeo Maria Lai Philip J. Johnson 《Cancer chemotherapy and pharmacology》1998,42(3):247-249
Purpose: A single-institution phase II trial of Temodal (temozolomide, SCH52365) in Chinese patients with advance nasopharyngeal
carcinoma was undertaken to determine the efficacy and safety of the drug in this population. Methods: A total of 14 patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma were entered into the study.
One patient was unevaluable. Temodal was given at doses of 150 or 200 mg/m2 daily on days 1–5 every 28 days. Results: In all, 30 cycles of Temodal were given with no significant toxicity. All 13 (100%) evaluable patients had progressive disease
after 2 (84.6%) or 4 (15.4%) courses. Conclusion: Temodal given on this schedule has no activity in advanced nasopharyngeal carcinoma.
Received: 9 January 1998 / Accepted: 4 February 1998 相似文献
35.
36.
37.
Speech perception for adults who use hearing aids in conjunction with cochlear implants in opposite ears. 总被引:1,自引:0,他引:1
Mansze Mok David Grayden Richard C Dowell David Lawrence 《J. Speech Lang. Hear. Res.》2006,49(2):338-351
This study aimed to (a) investigate the effect of using a hearing aid in conjunction with a cochlear implant in opposite ears on speech perception in quiet and in noise, (b) identify the speech information obtained from a hearing aid that is additive to the information obtained from a cochlear implant, and (c) explore the relationship between aided thresholds in the nonimplanted ear and speech perception benefit from wearing a hearing aid in conjunction with a cochlear implant in opposite ears.Fourteen adults who used the Nucleus 24 cochlear implant system in 1 ear participated in the study. All participants had either used a hearing aid in the nonimplanted ear for at least 75% of waking hours after cochlear implantation, and/or, hearing loss less than 90 dB HL in the low frequencies in the nonimplanted ear. Speech perception was evaluated in 3 conditions: cochlear implant alone (CI), hearing aid alone (HA), and cochlear implant in conjunction with hearing aid in opposite ears (CIHA). Three speech perception tests were used: consonant-vowel nucleus-consonant (CNC) words in quiet, City University of New York style (CUNY) sentences in coincident signal and noise, and spondees in coincidental and spatially separated signal and noise. Information transmission analyses were performed on the CNC responses.Of the 14 participants tested, 6 showed significant bimodal benefit on open-set speech perception measures and 5 showed benefit on close-set spondees. However, 2 participants showed poorer speech perception with CIHA than CI in at least 1 of the speech perception tests. Results of information transmission analyses showed that bimodal benefit (performance with CIHA minus that with CI) in quiet arises from improved perception of the low frequency components in speech. Results showed that participants with poorer aided thresholds in the mid-to-high frequencies demonstrated greater bimodal benefit. It is possible that the mid-to-high frequency information provided by the hearing aids may be conflicting with the cochlear implants. 相似文献
38.
Mok MH Knight GE Andrews PL Hoyle CH Burnstock G 《Journal of the autonomic nervous system》2000,80(3):130-136
This study has shown that cyclophosphamide treatment of the insectivore Suncus murinus, causes a down regulation in both muscarinic and P2X receptors, together with a reduced responsiveness to exogenous histamine (0.3 mM) in the urinary bladder. Electrical field stimulation (70 V, 0.3 ms, 0.5-16 Hz, 10 s every 5 min) of bladders from both control and cyclophosphamide-treated animals showed identical responses. Since post-junctional alterations have been revealed by the reduced responsiveness to exogenous carbachol (0.1 microM-3 mM) and beta,gamma-methylene ATP (0.3-300 microM), it would appear that in the bladders of cyclophosphamide-treated animals there is also a pre-junctional effect, increased transmitter release compensating for the down regulation of the receptors. As the pattern of neurotransmission of the bladder of suncus more closely resembles that of human detrusor than other commonly studied laboratory animals, this insectivore appears to be a useful animal model for the study of bladder neurotransmission in pathophysiological conditions. 相似文献
39.
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40.
腺病毒载体介导的PML生长抑制因子对前列腺癌细胞生长和致瘤能力的抑制效果 总被引:1,自引:0,他引:1
为探讨用腺病毒载体携带PML(PromyelocyticLeukemia)基因作为前列腺癌基因治疗的可能性,应用重组人携带PML基因腺病毒(AdPML)感染培养的前列腺癌细胞,观察表达PML蛋白的癌细胞与对照组癌细胞的体外生长和裸鼠体内致瘤能力变化,对荷瘤裸鼠瘤体周围注射AdPML,观察治疗组和对照组肿瘤生长的变化。结果显示,感染AdPML的前列腺癌细胞体外生长和裸鼠体内致瘤能力明显下降,荷瘤裸鼠瘤体周围注射AdPML后肿瘤生长速度明显减慢。证实了PML是一种生长抑制因子,提示其可能被应用于前列腺癌的基因治疗研究 相似文献