Biomedical subjects

Qiang Qu

Publications and source records attributed to Qiang Qu.

12 recordsLinked to original sources

PubMed2006

Regulation of osteoblast differentiation: a novel function for fibroblast growth factor 8.

Several members of the fibroblast growth factor (FGF) family have an important role in the development of skeletal tissues. FGF-8 is widely expressed in the developing skeleton, but its function there has remained unknown. We asked in this study whether FGF-8 could have a role in the differentiation of mesenchymal stem cells to an osteoblastic lineage. Addition of FGF-8 to mouse bone marrow cultures effectively increased initial cell proliferation as well as subsequent osteoblast-specific alkaline phosphatase production, bone nodule formation, and calcium accumulation if it was added to the cultures at an early stage of osteoblastic differentiation. Exogenous FGF-8 also stimulated the proliferation of MG63 osteosarcoma cells, which was blocked by a neutralizing antibody to FGF-8b. In addition, the heparin-binding growth factor fraction of Shionogi 115 (S115) mouse breast cancer cells, which express and secrete FGF-8 at a very high level, had an effect in bone marrow cultures similar to that of exogenous FGF-8. Interestingly, experimental nude mouse tumors of S115 cells present ectopic bone and cartilage formation as demonstrated by typical histology and expression of markers specific for cartilage (type II and IX collagen) and bone (osteocalcin). These results demonstrate that FGF-8 effectively predetermines bone marrow cells to differentiate to osteoblasts and increases bone formation in vitro. It is possible that FGF-8 also stimulates bone formation in vivo. The results suggest that FGF-8, which is expressed by a great proportion of malignant breast and prostate tumors, may, among other factors, also be involved in the formation of osteosclerotic bone metastases.

Alkaline Phosphatase↗

PubMed2006

Defects in tangential neuronal migration of pontine nuclei neurons in the Largemyd mouse are associated with stalled migration in the ventrolateral hindbrain.

The LARGE gene encodes a putative glycosyltransferase that is required for normal glycosylation of dystroglycan, and defects in LARGE can cause abnormal neuronal migration in congenital muscular dystrophy (CMD). Previous studies have focused on radial migration, which is disrupted at least in part due to breaks in the basal lamina. Through analysis of precerebellar nuclei development in the Large(myd) mouse hindbrain, we show that tangential migration of a subgroup of hindbrain neurons may also be disrupted. Within the precerebellar nuclei, the pontine nuclei (PN) are severely disrupted, whereas the inferior olive (IO), external cuneate nuclei (ECN) and lateral reticular nuclei (LRN) appear unaffected. Large and dystroglycan are widely expressed in the hindbrain, including in the pontine neurons migrating in the anterior extramural migratory stream (AES). BrdU labeling and immunohistochemical studies suggest normal numbers of neurons begin their journey towards the ventral midline in the AES in the Large(myd) mouse. However, migration stalls and PN neurons fail to reach the midline, surviving as ectopic clusters of cells located under the pial surface dorsally and laterally to where they normally would finish their migration near the ventral midline. Stalling of PN neurons at this location is also observed in other migration disorders in mice. These observations suggest that glycan-dependent dystroglycan interactions are required for PN neurons to correctly respond to signals at this important migrational checkpoint.

Amino Acids↗

PubMed2006

[Comparison of different clinical staging systems for hepatocellular carcinoma].

OBJECTIVE: To compare the prognostic efficacy of three clinical staging systems: the Chinese system (CS), CLIP scores, and TNM for hepatocellular carcinoma (HCC). METHODS: 107 cases diagnosed as HCC between January 2000 and October 2003 were retrospectively analyzed. Their clinical stages were decided on the basis of data in CLIP or Chinese staging system when the HCC diagnosis had been confirmed. Fifty-three of the 107 patients underwent surgical resection. The TNM stage was therefore determined according to surgico-pathological results. The survival of those patients with respective to different stages were analyzed and compared using Kaplan-Meier curves and Log rank method. RESULTS: All the patients were followed up after treatment. The 3-year survival rate in the CS Ia, Ib and CLIP 0 group were 100%. The 1- and 2-year survival rates of CS IIIa group was 68% and 51%, respectively. The 1-year survival in CS IIIb group was only 20.9%. The 1-, 2-, and 3-year survival rate in patients with a CLIP score beyond 4 was 57.1%, 49.9%, and 33.5%, respectively. In patients treated with surgical resection, the CS Ia group and TNM I group had a 3-year survival rate of 100%. The 1- and 3-year survival rate in CS IIb were 83.3% and 75.0%, in TNM III group 93.7% and 77.5%. CONCLUSION: The CLIP system may provide accurate prediction of prognosis based on early clinical features. The CS system is comparably efficient in predicting the prognosis of HCC patients, particularly in patients with severe cirrhosis.

Adolescent↗

PubMed2005

Self-inactivating lentiviruses: versatile vectors for quantitative transduction of cerebellar granule neurons and their progenitors.

Cerebellar granule neurons (CGNs) undergo a well-defined, intrinsic differentiation program that is recapitulated in vitro. Thus, homogeneous cultures of CGNs provide an excellent opportunity to define the mechanisms underlying their development. The ability to alter endogenous gene expression in CGNs on a population-wide basis would greatly facilitate the elucidation of these events. In the present study, we show that self-inactivating lentiviruses efficiently infect both dividing progenitors and post-mitotic CGN cultures in a quantitative manner without altering their cellular properties. The time course for protein expression was biphasic for both types of cultures, with the first peak occurring during the initial infection period. Thus, lentiviruses can express proteins in CGNs both acutely and on a long-term basis to study developmental and other processes continuously over an extended time period. These vectors also infected CGNs in cerebellar slice preparations. In addition, lentiviruses harboring a transgene for the mouse GABA(A) receptor alpha6 subunit promoter recapitulated the differentiation-dependent expression of this gene in CGN cultures. Self-inactivating lentiviruses are extremely versatile vectors that offer important advantages for studies of protein function and gene regulation. The ability to alter protein function on a global scale in CGN cultures permits biochemical assessment of its impact on mRNA and protein populations, as well as on protein--protein and protein--DNA interactions. Further, integrated lentiviruses can be used to study chromatin-dependent promoter regulation and transcription factor interactions in CGNs over time in a facile manner.

Animals↗

PubMed2005

[Expression of albumin during hepatocyte differentiation by human bone marrow stem cells].

OBJECTIVE: To observe the expression pattern of albumin during the hepatocyte differentiation by human bone marrow stem cells in vitro. METHODS: Human bone marrow cells were harvested and cultured in the presence of hepatocyte growth factor (HGF), fibroblast growth factor (FGF) and lymphocyte inhibitory factor (LIF). Cells were stained immunohistochemically by albumin specific antibody and examined under a confocal microscope. Supernatant albumin level was measured biochemically on a serial time points of the culture. RESULTS: By this condition, the attached cells became mature morphologically in 1 week of culture. Hepatocyte-specific albumin could be detected in mature cells. The albumin level revealed a time-dependent change during a 4-week culture. CONCLUSION: Human bone marrow cells could be induced to differentiate to mature hepatocytes that produce and secret albumin in vitro. These cells may contribute to a stable source of hepatocytes for clinical hepatocyte transplantation and artificial liver support system.

Albumins↗

PubMed2005

Gene expression profiling of mouse postnatal cerebellar development using oligonucleotide microarrays designed to detect differences in glycoconjugate expression.

Differences in gene expression patterns between adult and postnatal day 7 (P7) mouse cerebellum, at the peak of granule neuron migration, were analyzed by hybridization to the GLYCOv2 glycogene array. This custom designed oligonucleotide array focuses on glycosyl transferases, carbohydrate-binding proteins, proteoglycans and related genes, and 173 genes were identified as being differentially expressed with statistical confidence. Expression levels for 11 of these genes were compared by RT-PCR, and their differential expression between P7 and adult cerebellum confirmed. Within the group of genes showing differential expression, the sialyltransferases (SiaTs) and GalNAc-Ts that were elevated at P7 prefer glycoprotein substrates, whilst the SiaTs and GalNAc-Ts that were elevated in the adult preferentially modify glycolipids, consistent with a role for gangliosides in maintaining neuronal function in the adult. Also within this group, three proteoglycans--versican, bamacan and glypican-2--were elevated at P7, along with growth factor midkine, which is known to bind to multiple types of proteoglycans, and fibroblast growth factor receptor 1, whose activity is known to be influenced by heparan sulfate proteoglycans. Two sulfotransferases that can modify the extent of proteoglycan sulfation were also differentially regulated, and may modify the interaction of a subset of proteoglycans with their binding partners during cerebellar development. Bamacan, glypican-2 and midkine were shown to be expressed in different cell types, and their roles in cerebellar development during granule neuron migration and maturation are discussed.

Aging↗

PubMed2005

Neuronal migration defects in cerebellum of the Largemyd mouse are associated with disruptions in Bergmann glia organization and delayed migration of granule neurons.

The Large gene encodes a putative glycosyltransferase that is required for normal glycosylation of dystroglycan, and defects in either Large or dystroglycan cause abnormal neuronal migration. The mechanism for this effect is not fully understood. This study analyzes the Largemyd mouse cerebellum during postnatal cerebellar development. Large is shown to be expressed most strongly in the Bergmann glial cells and Purkinje cells throughout cerebellar development, which is similar to what is known for dystroglycan expression. Discontinuities of the pial surface of the developing Largemyd mouse cerebellum correlate with disruption of the normal organization of the external granule cell layer and Bergmann glial fibers. At early time points, granule neurons express differentiation markers normally, both temporally and spatially, and show no defects in neurite outgrowth in in vitro assays. However, granule neuron migration is delayed within the external granule and molecular layers, resulting in granule neurons undergoing their intrinsically programmed differentiation in inappropriate locations. Consequently, cells expressing mature granule neuron markers become stranded within these layers. The cause of the less efficient migration is likely due to both physical disruption of the glial-guide scaffolding, as well as to suboptimal neuronal-glial guide interactions during migration.

Animals↗

PubMed2004

Alpha-dystroglycan interactions affect cerebellar granule neuron migration.

The interaction of alpha-dystroglycan (a-DG) with its extracellular binding partners requires glycans attached to its mucin core domain, and defects in the glycosylation of a-DG are associated with both muscular dystrophy and neuronal migration defects. The involvement of a-DG and one of its ligands, agrin, in cerebellar neuronal migration was investigated. Antibodies directed against glycosylated a-DG inhibited granule neuron migration in cerebellar slice cultures. a-DG interactions did not appear to influence neurite outgrowth in cerebellar explant cultures, but enhanced granule neuron binding was observed on cells transfected with a-DG. These results suggest that interactions involving a-DG influence the strength of attachment of granule neurons to the a-DG-expressing Bergmann glial cells that guide granule neuron migration in the cerebellum. Experiments using anti-agrin antibodies suggest that agrin is not involved in these interactions.

Agrin↗

PubMed2004

Liver injury after intermittent or continuous hepatic pedicle clamping and its protection by reduced glutathione.

BACKGROUND: The debate is still going on about selection of several clamping patterns during hepatectomy. The aim of this study was to assess the safety and preference of normothermic intermittent or continuous hepatic pedicle clamping and confirm the protective effect of reduced glutathione (GSH). METHODS: Thirty-two adult male healthy Sprague-Dawley (SD) rats were divided into groups of intermittent clamping and GSH absent (IA), continuous clamping and GSH absent (CA), intermittent clamping and GSH present (IP) and continuous clamping and GSH present (CP). The clamping manners were successively 40 minutes in continuous clamping groups and two cycles of 20 minutes with an interval of 5 minutes in intermittent clamping groups, and reperfusion periods were 60 minutes. Experimental parameters included levels of malonaldehyde (MDA) and Cu/Zn superoxide dismutase (SOD), pathological and ultrastructural changes in liver tissues, activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in sera. RESULTS: In the same group, the activities of ALT and AST were significantly higher in post-clamping rats than in pre-clamping rats (P<0.05), but no significant differences were noted in levels of MDA and Cu/Zn SOD (P>0.05). The differences of all values between post-reperfusion rats and pre-clamping rats were significant (P<0.05). Pathological and ultrastructural changes could be observed, but no irreversible injury was present. The comparison of the groups showed that the values at relevant time points between the intermittent and continuous groups were not significantly different (P>0.05). The values were significantly different between the GSH absent and present groups after reperfusion (P<0.05). The morphological damages were also obviously alleviated in the GSH present group. CONCLUSIONS: Normothermic intermittent or continuous hepatic pedicle clamping could cause reversible liver ischemia/reperfusion injury when the clamping time lasts 40 minutes. The injury extent seems to be similar. Continuous clamping should be regarded as a proper method in liver surgery. GSH has been confirmed as an effective agent in preventing post-clamping liver injury.

Animals↗

PubMed2004

Major hepatectomy without blood transfusion: report of 51 cases.

BACKGROUND: Blood transfusion has been found to be a devastating factor for outcomes of hepatectomy. This study was to assess the value of major hepatectomy without blood transfusion. METHODS: We retrospectively studied 51 patients who had undergone major hepatectomy without blood transfusion, including 29 patients with primary liver cancer, from August 1997 to December 2000. Sixty patients undergoing major hepatectomy with blood transfusion including 48 patients with primary liver cancer served as controls. Hepatectomy was performed through normothermic interruption of the porta hepatis. Intraoperative ultrasonography was performed to define tumor margins, and an ultrasound dissector was used to dissect liver parenchyma. RESULTS: In the study group, the operative mortality and morbidity and 1-, 2-, and 3-year recurrence rates were 0%, 9.8%, 24.1%, 27.6% and 31.0%, respectively. In the control group, they were 3.3%, 28.3%, 43.5%, 54.3% and 58.7%, respectively. Significant differences were seen in morbidity and recurrence rates of patients with liver cancer between the two groups (P < 0.05). CONCLUSION: Major hepatectomy without blood transfusion can reduce postoperative morbidity and recurrence rate of patients with liver cancer.

Adult↗

PubMed2003

Expression of dystroglycan, fukutin and POMGnT1 during mouse cerebellar development.

Dystroglycan (DG) plays a central role in linking the extracellular matrix to cellular cytoskeletal elements, and is required for proper neuromuscular junction organization and neural cell migration in the CNS. DG interactions with laminin and several other extracellular ligands are mediated through carbohydrates located in a densely glycosylated mucin core domain on alpha-DG. A hallmark of a number of congenital muscular dystrophies is abnormal alpha-DG glycosylation and disordered neuronal migration in both the cerebral cortex and cerebellum. The underlying genetic defects in two such diseases have been localized to the POMGnT1 glycosyltransferase and the putative glycosyltransferase fukutin. We report here the spatial expression pattern of DG together with its putative modifying enzymes during the period of peak neuronal migration in the cerebellum. All three genes are broadly expressed in late embryonic and early postnatal cerebellar neurons, including premigratory granule neurons of the external granule cell layer. Expression of POMGnT1 and fukutin is maintained in neurons of the internal granule cell layer after migration is complete, whereas DG mRNA is largely downregulated. Purkinje cells expressed all three genes throughout development at varying levels, ranging from weak expression of DG to a unique pattern of intense fukutin expression in irregularly spaced cell bodies that do not appear to correlate with known parasagittal stripes. Significantly, immunocytochemical analysis reveals that alpha- and beta-DG proteins are also present on the Bergmann glial scaffolds used by granule cells during early postnatal radial migration, and double-label in situ hybridization confirms that these cells also express POMGnT1 and fukutin. These results suggest that abnormal glycosylation of alpha-DG on glial scaffolds and neurons and their processes could affect interactions with alpha-DG ligands expressed by migrating granule cells, and be a potential mechanism through which neuronal migration is compromised in CMD disease.

Animals↗

PubMed2003

[Multi-modal serial therapy for primary liver cancer in senile patients: a report of 153 cases].

OBJECTIVE: To study the feasibility and validity of multi-modal serial therapy for primary liver cancer in senile patients. METHODS: 153 senile primary liver cancer patients (>or= 60 years) were given multi-modal serial therapy from June 1993 to December 2000. Hepatectomy was performed in 37, deep cryosurgery in 32 and non-operative therapy in 84 (intervention as chief therapy in 81, combined local and intervention therapy in 3). The multi-course intervention therapy was given postoperatively in hepatectomy and cryosurgery groups, while bioimmunotherapy and traditional Chinese medicine were used in all groups. RESULTS: The 1-, 3- and 5-year survival rates in the hepatectomy group were 78.4%, 46.4% and 35.7%, without operative mortality. The 1- and 3- and 5-year year survival rates in the cryosurgery group were 64.5%, 40.9% and 25.0% with mortality of 3.1%. Among patients with non-operative therapy, the 1- and 3- and 5-year year survival rates in intervention group were 47.5%, 23.5% and 4.3%. The operative mortality was 1.2%. The 3 patients who received combined local and intervention therapy have survived for 2.5, 3.8 and 7.1 years. CONCLUSION: Multi-modal serial therapy with surgical treatment as the chief means, being precise in the effect and good in safety, is feasible and valid for primary liver cancer in senile patients.

Aged↗