Biomedical subjects

Qi Zhu

Publications and source records attributed to Qi Zhu.

27 records · Page 2Linked to original sources

PubMed2003

[In vitro study of the effects of arsenic trioxide combined with 8-CPT-cAMP on differentiation induction in retinoic acid resistant acute promyelocytic leukemia cells].

OBJECTIVE: To investigate the potential effects of arsenic trioxide (As(2)O(3)) combined with 8-(4-chlorophenylthio) adenosine 3', 5'-cyclic monophosphate (8-CPT-cAMP) on the retinoic acid (RA)-resistant acute promyelocytic leukemia (APL) cells. METHODS: The RA resistant APL cell lines NB4-R1 and NB4-R2 were used as in vitro models. The effect of As(2)O(3) and/or 8-CPT-cAMP was evaluated according to cellular morphology, cell surface antigen and nitroblue-tetrazolium (NBT) assay. Meanwhile, immunofluorescence analysis and Western blot assay were used to detect the degradation of PML-RAR alpha fusion protein and the change of several key cell cycle regulatory proteins in these cells before and after the treatment. RESULTS: Low dose of As(2)O(3) (0.25 micromol/L) synergized with 8-CPT-cAMP (200 micromol/L) in inducing differentiation of NB4-R1 and NB4-R2 cells, while neither of these two drugs alone could induce differentiation of these cells. In addition, 8-CPT-cAMP was able to inhibit the cell growth by modulating the expression of some important cell cycle regulators and to facilitate the As(2)O(3)-mediated degradation of PML-RAR alpha fusion protein. CONCLUSIONS: As(2)O(3) combined with 8-CPT-cAMP could induce differentiation of RA-resistant APL cells.

Antineoplastic Agents↗

PubMed2003

[A preliminary study of endoscopic ultrasonography in the preoperative staging of early gastric carcinoma].

OBJECTIVE: To study the clinical value of endoscopic ultrasonography (EUS) in the preoperative staging of early gastric carcinoma. METHODS: EUS was performed in 149 gastric carcinoma patients proved by biopsy (including 33 patients with early gastric cancer), of which the results were compared with postoperative pathologic findings. RESULTS: The accuracy of EUS in determining the T stage of gastric carcinoma was 80.3% (T1 81.8%, T2 70.4%, T3 88.9%, T4 71.4%). The accuracy of EUS in differentiating early gastric carcinoma from advanced ones was 95.1%, and the accuracy of EUS in differentiating mucosal cancer from submucosal cancer was only 63.6%. The diagnostic accuracy of EUS for mucosal and submucosal cancer was 52.9% and 75%, with positive predictive value of 90% and 70.6%, respectively. The accuracy of invasion depth of EUS for the bulging and flat type of early gastric carcinoma was 100%, whereas the accuracy was only 58.6% for the depressed type. The accuracy of invasion depth of the differentiated and undifferentiated early cancer was 71.4%and 57.9%, without any significant difference (P > 0.05). The accuracy of invasion depth of EUS for early gastric carcinoma decreased as tumor size increased. The diagnostic accuracy of lymph node status of early gastric carcinoma by EUS was 90.9%, and the sensitivity and specificity of lymph node metastasis was 66.7% and 96.3%, respectively. CONCLUSION: The clinical value of endoscopic ultrasonography in the preoperative staging of early gastric carcinoma is relatively high.

Adenocarcinoma↗

PubMed2003

[Effects of yanlieping formula on mice with chronic nonbacterial prostatitis].

OBJECTIVES: To study the mechanism of Yanlieping Formula in treating chronic nonbacterial prostatitis. METHODS: Thirty-two C57BL/6 mice were divided into Chinese Traditional Medicine group(Yanlieping group, 10 mice), treatment control group(Cernilton group, 10 mice), model group(6 mice) and normal group(6 mice). The animal model was created by using immunologic adjuvant, and Yanlieping (0.84 g per mouse), Cernilton (7.5 mg per mouse), distilled water(1.05 ml per mouse) and distilled water (0.5 ml per mouse) were respectively administered to the four groups every day for one month. The prostate weight, pathological changes, TNF-alpha and IL-2 in serum were observed. RESULTS: The prostate weight in Yanlieping group and Cernilton group became significantly lower than in the model group(P < 0.05). Pathologic sign of chronic inflammation became better significantly(Yanlieping group showed more significant improvement). The expression of IL-2 in Yanlieping group and Cernilton group were downregulated significantly. And the expression of TNF-alpha in Yianlieping group was higher than that of the model group and the normal group (P < 0.05). CONCLUSIONS: The mechanism of Yanlieping Formula in treating chronic prostatitis may lie in the max urethral close pressure reduction, anti-inflammation, local blood circulation improvement.

Animals↗

PubMed2002

Role of disulfide bonds in folding and activity of leiurotoxin I: just two disulfides suffice.

The aim of this study is to investigate the contribution of each disulfide bond in the folding and function of leiurotoxin I, a short scorpion toxin that blocks small conductance K(+) channels. The structure of leiurotoxin I contains a motif conserved in all scorpion toxins, formed by a helix and a double-stranded beta-sheet and stabilized by three disulfide bridges. We synthesized three analogues, each presenting two alpha-aminobutyric acid (Abu) moieties replacing two bridged cysteine residues: LeTx1 ([Abu 3,21] Leiurotoxin I), LeTx2 ([Abu 8,26] Leiurotoxin I), and LeTx3 ([Abu 12,28] Leiurotoxin I). All three analogues fold into a major product containing two native disulfide bonds, while LeTx3 forms an additional isomer, containing non-native disulfides. In denaturing conditions, analogues LeTx2 and LeTx3 yield non-native isomers, while LeTx1 only forms the isomer with native disulfides. All isomers with native disulfides contain nativelike alpha-helical conformations and bind to synaptosomal membranes with affinities within a log of that shown by the native toxin. By contrast, the non-native LeTx3A analogue exhibits a disordered conformation and a decreased biological potency. Our results indicate that the "CxxxC, CxC" cysteine spacing, conserved in all scorpion toxins and preserved in LeTx1, may play an active role in folding, and that only two native disulfide bonds in leiurotoxin I are sufficient to preserve a nativelike and active conformation. Thus, in the scorpion toxin scaffold, modifications of conserved and interior cysteine residues may permit modulation of function, without significantly affecting folding efficiency and structure.

Amino Acid Sequence↗

PubMed2002

Publication bias in editorial decision making.

CONTEXT: Studies with positive results are more likely to be published than studies with negative results (publication bias). One reason this occurs is that authors are less likely to submit manuscripts reporting negative results to journals. There is no evidence that publication bias occurs once manuscripts have been submitted to a medical journal. We assessed whether submitted manuscripts that report results of controlled trials are more likely to be published if they report positive results. METHODS: Prospective cohort study of manuscripts submitted to JAMA from February 1996 through August 1999. We classified results as positive if there was a statistically significant difference (P<.05) reported for the primary outcome. Study characteristics and indicators for quality were also appraised. We included manuscripts that reported prospective studies in which participants were assigned to an intervention or comparison group and statistical tests compared differences between groups. RESULTS: Among 745 manuscripts, 133 (17.9%) were published: 78 (20.4%) of 383 with positive results, 51 (15.0%) of 341 with negative results, and 4 (19.0%) of 21 with unclear results. The crude relative risk for publication of studies with positive results compared with negative results was 1.36 (95% confidence interval [CI], 0.99-1.88). After being adjusted simultaneously for study characteristics and quality indicators, the odds ratio for publishing studies with positive results was 1.30 (95% CI, 0.87-1.96). CONCLUSIONS: Among submitted manuscripts, we did not find a statistically significant difference in publication rates between those with positive vs negative results.

Biomedical Research↗

PubMed2002

Association between time interval to publication and statistical significance.

CONTEXT: Studies have shown that reports from clinical trials with statistically significant results tend to be submitted and published more rapidly than reports from studies with null or insignificant findings. METHODS: We wanted to determine whether manuscripts reporting positive results from controlled clinical trials are published more quickly than those reporting negative results. We tracked manuscripts from submission to JAMA until the publication decision. We classified results as positive if a statistically significant difference was reported for the primary outcome. Manuscripts were further classified according to indicators of methodologic quality and other study characteristics. We included manuscripts if they were submitted from February 1996 through August 1999, reported results of a prospective study in which participants were assigned to a treatment or comparison group, used statistical tests to compare differences between groups, and were accepted for publication. RESULTS: One hundred thirty-three manuscripts met our inclusion criteria, 78 (59%) reported positive results, 51 (38%) reported negative results. We were unable to classify the direction of results for 4 articles (3%). The time interval between submission and publication was not associated with positive results: median time between submission and publication was 7.8 months for reports with positive vs 7.6 months for reports with negative results (P =.44). Time to publication also was not associated with any marker of study quality or study characteristic. CONCLUSIONS: Among 133 published controlled trials, time to publication was not associated with statistical significance, methodologic quality, or other study characteristics.

Controlled Clinical Trials as Topic↗

PubMed2002

Synergic effects of arsenic trioxide and cAMP during acute promyelocytic leukemia cell maturation subtends a novel signaling cross-talk.

Acute promyelocytic leukemia (APL) is characterized by the specific chromosome translocation t(15;17) with promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) fusion gene and the ability to undergo terminal differentiation as an effect of all-trans retinoic acid (ATRA). Recently, arsenic trioxide (As(2)O(3)) has been identified as an alternative therapy in patients with both ATRA-sensitive and ATRA-resistant APL. At the cellular level, As(2)O(3) triggers apoptosis and a partial differentiation of APL cells in a dose-dependent manner; both effects are observed in vivo among patients with APL and APL animal models. To further explore the mechanism of As(2)O(3)-induced differentiation, the combined effects of arsenic and a number of other differentiation inducers on APL cell lines (NB4 and NB4-R1) and some fresh APL cells were examined. The data show that a strong synergy exists between a low concentration of As(2)O(3) (0.25 microM) and the cyclic adenosine monophosphate (cAMP) analogue, 8-CPT-cAMP, in fully inducing differentiation of NB4, NB4-R1, and fresh APL cells. Furthermore, cAMP facilitated the degradation of As(2)O(3)-mediated fusion protein PML-RARalpha, a process considered to play a key role in overcoming the differentiation arrest of APL cells. On the other hand, cAMP could significantly inhibit cell growth by modulating several major players in G(1)/S transition regulation. Interestingly, H89, an antagonist of protein kinase A, could block the differentiation-inducing effect of As(2)O(3) potentiated by cAMP. These results thus support the existence of a novel signaling cross-talk for APL maturation, which may deepen understanding of As(2)O(3)-induced differentiation in vivo, and thus furnish insights for new therapeutic strategies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

[Experimental study of low dose arsenic trioxide in treatment of patients with acute promyelocytic leukemia].

BACKGROUND & OBJECTIVE: Low dose arsenic trioxide(As2O3) is one of the effective treatments for patients with acute promyelocytic leukemia (APL). As2O3 could induce complete remission in de novo APL patients as well as in relapsed APL patients who have been resistant to all-trans retinoic acid (ATRA). However, the underlying mechanisms of As2O3-induced remission remain obscure. Therefore, we designed this study to explore the possible mechanism of low dose As2O3 in treatment of the patients with APL. METHODS: The APL cell line NB4 and primary malignant cells isolated from APL patients were used as in vitro models. Cell differentiation was determined by cell morphology, NBT reduction test and cytometry assay of cell differentiation antigens. The change of PML-RAR alpha fusion protein was analyzed by immunofluorescence and Western blot. RESULTS: The 0.25 mumol/L As2O3 combined with cyclic adenosine monophosphate(cAMP) analogue, 8-(4-chlorophenylthio) adenosine 3', 5'-cyclic monophosphate (8-CPT-cAMP), had induced differentiation in NB4 cell line and primary cells. It was also found that this effect could be attenuated by H89, a specific PKA inhibitor. Moreover, 8-CPT-cAMP was able to facilitate the As2O3-mediated degradation of PML-RAR alpha. CONCLUSIONS: The 8-CPT-cAMP could enhance As2O3-induced differentiation in APL cells.

Antineoplastic Agents↗

PubMed2002

[Transforming growth factor beta(1) and bone morphogenetic protein 2 induce the differentiation of odontoblasts in vitro].

OBJECTIVE: To investigate the effects of transforming growth factor beta(1) (TGF-beta(1)) and bone morphogenetic protein 2 (BMP2) combined with heparin on odontoblast differentiation. METHODS: Trypsin-isolated dental papillae from day 17 mandibular first molar were cultured in semisolid-agar medium for 6d. Recombinant human TGF-beta(1) and BMP2 combined with heparin were added to the medium. RESULTS: TGF-beta(1) and BMP2 combined with heparin induced differentiation of odontoblasts and promoted matrix secretion. Odontoblast differentiation never occurred when TGF-beta(1) or BMP2 were added alone to the medium, whereas an increase in extracellular matrix production was observed. CONCLUSION: These results demonstrate that both TGF-beta(1) and BMP2 stimulate the cytological and functional differentiation of preodontoblasts, and that heparin might play important role as a substrate.

Animals↗