Biomedical subjects

Jian-Hua Tong

Publications and source records attributed to Jian-Hua Tong.

6 recordsLinked to original sources

PubMed2007

A new elastic-wave-based imaging method for scanning the defects inside the structure.

In this paper, a new nondestructive testing method using elastic waves for imaging possible voids or defects in concrete structures is proposed. This method integrates the point-source/point receiver scheme with the synthetic aperture focusing technique (SAFT) process to achieve the effect like scanning with a phase array system. This method also is equipped with large functioning depth because of the high-energy feature that elastic waves usually possess over traditional ultrasound. Both numerical simulations and experimental tests were carried out to explore the capabilities of this method in revealing single or multiple defects implied in a matrix material. The results from numerical simulations indicate that this method can clearly reveal the number of the voids or defects, their locations, and front-end profiles. The influence of the accuracy of the wave velocity determination on the resultant image also was evaluated in this study. Furthermore, the effects of the types of the responses to be recorded and the wavelength of the introduced waves also were evaluated so that very good resultant images may be obtained. Both the results from the numerical simulations and the experimental tests indicate that this elastic-wave-based method exhibits high potential in inspecting the defects of in-situ concrete structures by imaging.

Algorithms↗

PubMed2006

RIG-G as a key mediator of the antiproliferative activity of interferon-related pathways through enhancing p21 and p27 proteins.

The RIG-G gene, originally isolated from an acute promyelocytic leukemia cell line NB4, codes for a 60-kDa cytoplasmic protein that is induced by all-trans retinoic acid (ATRA) treatment along with the induction of morphological differentiation of NB4 cells. Here, we provide evidence that ectopic expression of Rig-G in U937 cells can lead to a significant accumulation of cells at G(1)/S transition. Growth arrest seems to occur by modulating several major cell cycle regulatory players. Interestingly, Rig-G alters JAB1 cellular distribution through interacting with this protein and increases the intracellular level of p27 by preventing it from the JAB-1-dependent and ubiquitin/proteasome-mediated degradation. Furthermore, we demonstrate a role of Rig-G for c-myc down-regulation that results in an up-regulation of p21, tightly associated with cell cycle arrest. In addition, our studies reveal that Rig-G is a direct target of STAT1, a key transcription factor in regulating IFN responses, and may be one of the first experimentally proven molecular mediators for the antiproliferative effect of IFN-alpha. Considering that IFN-alpha and ATRA synergistically inhibit growth along the intracellular pathways triggered by the two compounds in many cell types, we suggest that Rig-G may also represent one of the key molecular nodes of signaling cross-talk between ATRA and IFN-alpha.

Base Sequence↗

PubMed2006

Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths.

The involvement of telomerase in cellular immortalization and senescence has often been assessed by means of telomerase expression at the RNA level and quantification of telomerase activity by the telomeric repeat amplification protocol assay. However, these methods either neglected the existence of various telomerase splice variants, or ignored the nonconventional functions of telomerase independent of its ability to elongate and maintain telomere length. Immunodetection of telomerase is now being recognized as a necessary approach to precisely elucidate its roles in oncogenesis and senescence. A few antibodies directed against the catalytic subunit of the human telomerase (hTERT) are currently used but their specificity is not always demonstrated. A survey of the literature showed inconsistencies and led us to comparatively re-evaluate the most frequently used antibodies. Surprisingly, mass spectrometry, two-dimensional gel analysis and immunofluorescent experiments revealed that the most frequently used hTERT immunoprobe, a mouse monoclonal antibody that was claimed to be directed against an hTERT protein epitope, in fact recognizes nucleolin rather than telomerase. Our findings have interesting implications regarding the biology of nucleolin and telomerase in the context of pathophysiological investigations recently carried out.

Antibodies↗

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

Expanding the use of arsenic trioxide: leukemias and beyond.

Arsenic has a long history of use in Chinese and Western medicine but fell out of use in the mid-20th century because of the unacceptable side effects that occurred at the doses that were thought to be necessary. The re-emergence of arsenic trioxide (ATO) in clinical use is due largely to purification of this compound from traditional mixtures, and the definition of effective, low-dose regimens for the treatment of acute promyelocytic leukemia (APL). ATO was first purified and used in controlled studies in patients with APL in China in the 1970s. Studies have subsequently also been performed in the United States. Complete response (CR) rates reported in patients with relapsed or refractory APL have varied from 52% to 92%, with similar rates reported in patients with newly diagnosed disease. The mechanism of action of ATO suggests it may be active against other malignancies, and ATO has shown some activity in patients with accelerated phase chronic myelogenous leukemia (CML) and multiple myeloma (MM). Clinical trials are ongoing and planned to define the optimal use of this compound in hematologic malignancies. Preliminary results from studies in patients with primary hepatocellular and gallbladder tumors indicate that ATO may also prove active against some solid tumors.

Antineoplastic Agents↗

PubMedDate not supplied

Treatment of acute promyelocytic leukemia with ATRA and As2O3: a model of molecular target-based cancer therapy.

Most acute promyelocytic leukemia (APL) cases have t(15;17)(q22;q21) chromosomal translocation and PML-RARalpha chimeric gene which blocks granulocytic differentiation. The introduction of all-trans-retinoic acid (ATRA) and arsenic compounds, especially arsenic trioxide (As(2)O(3)), has provided good models to study not only differentiation and/or apoptosis therapy but also molecular target-based cancer treatment. In vivo and in vitro investigations have shown that both agents are able to induce differentiation of APL cells: ATRA tends to induce terminal differentiation, while low-dose As(2)O(3) can induce partial differentiation. Significant progress has been made in understanding the molecular mechanisms of APL pathogenesis and differentiation therapy. Pharmacological concentrations (0.1 approximately 1 microM) of ATRA derepresses transcription by releasing CoR from, and recruiting CoA to PML-RARalpha, whereas As(2)O(3) triggers a rapid degradation of PML-RARalpha. In fact, the two drugs act on the same oncoprotein through targeting different moieties and in distinct ways and thereby abrogate its dominant-negative effects on regulatory pathways necessary for granulocytic differentiation. As to apoptosis, it is clear that high-dose As(2)O(3) can induce mitochondria-mediated cell death pathway in a thiol-dependent manner, while the mechanism of ATRA-induced apoptosis needs further elucidation. Transcriptomic and proteomic analysis are also expected to find new molecular targets. It is the hope that what we have learnt from APL will benefit further developments of anti-leukemia therapy.

Animals↗