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Biomedical subjects

Ji Wu

Publications and source records attributed to Ji Wu.

7 recordsLinked to original sources
PubMed2007

Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells.

Imatinib mesylate (Gleevec) is effective therapy against Philadelphia chromosome-positive leukemia, but resistance develops in all phases of the disease. Bcr/Abl point mutations and other alterations reduce the kinase inhibitory activity of imatinib mesylate; thus, agents that target Bcr/Abl through unique mechanisms may be needed. Here we describe the activity of WP1130, a small molecule that specifically and rapidly down-regulates both wild-type and mutant Bcr/Abl protein without affecting bcr/abl gene expression in chronic myelogenous leukemia (CML) cells. Loss of Bcr/Abl protein correlated with the onset of apoptosis and reduced phosphorylation of Bcr/Abl substrates. WP1130 did not affect Hsp90/Hsp70 ratios within the cells and did not require the participation of the proteasomal pathway for loss of Bcr/Abl protein. WP1130 was more effective in reducing leukemic versus normal hematopoietic colony formation and strongly inhibited colony formation of cells derived from patients with T315I mutant Bcr/Abl-expressing CML in blast crisis. WP1130 suppressed the growth of K562 heterotransplanted tumors as well as both wild-type Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells transplanted into nude mice. Collectively, our results demonstrate that WP1130 reduces wild-type and T315I mutant Bcr/Abl protein levels in CML cells through a unique mechanism and may be useful in treating CML.

Animals↗
PubMed2006

Noninvasive evaluation of hepatic fibrosis in children with infant hepatitis syndrome.

AIM: To elucidate the impact of hemodynamic para-meters on ultrasonography and serum fibrosis markers for the assessment of liver fibrosis in the children with infant hepatitis syndrome (IHS). METHODS: Forty-one children with IHS and 46 healthy infants were examined by ultrasonography, and several hemodynamic indices such as peak systolic velocity (PSV) and resistant index (RI) of proper hepatic artery (PHA) were measured. Serum fibrosis markers including hyaluronic acid (HA), pre-collagen type-III (PC-III), collagen type IV (C-IV), and laminin (LN) were assayed by radioimmunoassays. In children with IHS, liver tissues were obtained either by ultrasound-guided liver biopsy (n = 35) or in the course of operation (n = 6). The stages of hepatic fibrosis were scored as mild (S1 and S2), moderate (S3), or severe (S4) according to liver histological diagnosis. Multiple groups comparative and Spearman correlative analyses were carried out. RESULTS: Histopathologically, 39 children (95.1%) were found to have hepatic fibrosis, 12 of them stage S1 or S2, 12 stage S3, and 15 stage S4. PSV, RI of the PHA, and serum HA showed a consecutive increase from mild to severe hepatic fibrosis and a close positive correlation with hepatic fibrosis in IHS group (r = 0.717, 0.745 and 0.712, respectively, P = 0.001). The Doppler waveform of HV was also positively correlated with the degree of hepatic fibrosis in IHS group (r = 0.783, P < 0.001). CONCLUSION: Combination of ultrasonic studies on the hepatic hemodynamics with the evaluation of serum HA may provide an indicator for hepatic fibrosis in patients with IHS. This may be a useful noninvasive method for the diagnosis and evaluation of the prognosis of IHS.

Biomarkers↗
PubMed2006

Small RNAs and development.

Small RNAs, including microRNAs (miRNAs), short interfering RNAs (siRNAs), and siRNA-like scan RNAs (scnRNAs), are known to be crucial for regulatory functions in diverse species, with special focus on their interference in the development of plants as well as of C. elegans, Drosophila, and other animals. The functions of small RNAs on the complex regulatory network of metazoan embryonic development are presented in this article. In addition, indirect evidence is summarized here for those miRNAs which are important regulators controlling the biological processes of germ-cell development.

Animals↗
PubMed2006

[Semi-joint prosthesis replacement in treatment of malignant tumors around children's knees].

OBJECTIVE: To investigate the effect of the semi-joint prosthesis replacement in treating malignant tumors around the children's knees. METHODS: Five children (aged 8-12 years) with malignant tumors around the proximal end of the tibia underwent the semi-joint prostheses replacement from March 2000 to June 2005. All the children had been diagnosed with osteosarcoma, which was graded as II B by the Enneking staging system. The pathologic changes involved the upper segment of the tibia 9-11 cm in length. Before operation all the patients underwent puncture biopsy and standard chemotherapy. The lesion extent was determined by X-ray, CT and MRI, and then the size of the prosthesis was determined. The length of the prosthesis was 1-2 cm longer than that of the excised bone. After operation the patients were given neoadjuvant chemotherapy for 2 courses and they could walk with the help of a special brace 4 weeks postoperatively. RESULTS: All the 5 patients had a successful semi-joint prosthesis replacement except one patient who had a skin flap necrosis, and the wound healed after a flap grafting. The remaining patients had their wounds healed by first intention. The 12-36 months' follow-up revealed that all the patients had no metastasis or recurrence of the tumor and they were living and well except one patient who died of lung metastasis 8 months after operation. CONCLUSION: The semi-joint prosthesis replacement in the limb salvage surgery for malignant tumors around the children's knees has advantages of avoiding a damage to the normal osteoepiphysis, stabilizing the knee joint, and facilitating elongation of the limb in future. It also creates the condition for total knee replacement in adults.

Arthroplasty, Replacement, Knee↗
PubMed2005

Short-type PB-cadherin promotes survival of gonocytes and activates JAK-STAT signalling.

Neonatal development of the rat testis involves a number of critical events including re-entry of gonocytes into the cell cycle and eventual loss of many of these cells and their progeny via apoptosis. Since surviving gonocytes give rise to subsequent generations of germ cells, regulation of their fate is critical for adult testicular function. Here, we have identified a role for short-type PB-cadherin (STPB-C) in promoting survival of gonocytes in neonatal rats and we have linked its expression to the JAK-STAT signaling pathway. These findings were obtained with varied approaches including use of transgenic rats overexpressing STPB-C which were studied with protein microarrays and other techniques, direct examination of germ cell apoptosis and survival in gonocyte-Sertoli cell co-cultures, and direct study of the JAK-STAT pathway in these models and in L cells transfected with STPB-C. These data provide new information on the regulation of gonocyte fate and exciting new evidence supporting a link between the JAK-STAT pathway and cadherin-based cell-cell interactions.

Animals↗
PubMed2002

Expression of Fas, p53 and AFP in development of human fetal germ cells in vitro.

In the present study we employed a two-step culture system to study the expression of Fas, p53 and alpha-fetoprotein (AFP) in the development in vitro of human fetal germ cells. p53 mRNA was determined by Northern blotting, and Fas content was assessed by western blotting. RT-nested polymerase chain reaction (RT-nPCR) analysis was performed to determine the expression of AFP mRNA in different stages of fetal follicular development. Follicular cell apoptosis was evaluated by DNA fragmentation analyses (DNA ladder). The results showed that by day 7 of culture approximately one-sixth of fetal germ cells grew to class C oocytes (primary oocytes) from class B oocytes (primordial oocytes) or class A oocytes. On day 45 of culture, one-third of these primary follicles doubled in size. In the meantime, there was a high proportion apoptosis of follicular cells on days 35 or 45 of culture, as evident by a clear ladder pattern of DNA fragmentation upon electrophoretic analysis. Expression of Fas antigen and p53 mRNA increased in a time-dependent manner, while AFP mRNA was expressed on days 10 to 35, and disappeared on day 45. These results indicate that human fetal germ cells can develop in a two-step culture system and AFP may play an active role in the proliferation of these germ cells. At the late stage of follicular development in vitro, a number of follicular cells became apoptotic. Moreover, apoptosis may be the mechanism responsible for fetal germ cell regression and the Fas antigen and/or p53-mediated death pathway may be central in the induction of germ cell regression.

Female↗