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Biomedical subjects

Liang Hu

Publications and source records attributed to Liang Hu.

35 records · Page 2Linked to original sources

Physical activity, self-efficacy, and self-esteem: longitudinal relationships in older adults.

We examined the structure of the expanded version of the Exercise and Self-Esteem Model in a sample of older adults (N = 174; age, M = 66.7 years) across a 4-year period. A panel analysis revealed support for the indirect effects of physical activity (PA) and self-efficacy (SE) on physical self-worth and global esteem through subdomain levels of esteem. These relationships were consistent across the 4-year period. Over time, older adults reporting greater reductions in SE and PA also reported greater reductions in subdomain esteem. This is one of the first studies to examine these relationships longitudinally in the PA domain and offers further support for the hierarchical and multidimensional nature of self-esteem at the physical level. We recommend further testing of the Exercise and Self-Esteem Model, with special attention being paid to assessing multiple aspects of PA and SE.

Aged↗

Physical activity enhances long-term quality of life in older adults: efficacy, esteem, and affective influences.

BACKGROUND: Physical activity has been effective in enhancing quality of life (QOL) of older adults over relatively short periods of time. However, little is known about the long-term effects of physical activity and even less about the possible mediators of this relationship. PURPOSE: We examined the mediating effects of psychological variables on the relationship between physical activity and global QOL (satisfaction with life) in older adults over a 4-year period. METHODS: Participants (N = 174, M age = 66.7 years) completed a battery of psychosocial measures at 1 and 5 years following enrollment in a 6-month randomized controlled exercise trial. RESULTS: Panel analysis conducted within a covariance modeling framework indicated that physical activity was related to self-efficacy, physical self-esteem, and positive affect at 1 year, and in turn, greater levels of self-efficacy and positive affect were associated with higher levels of QOL. Analyses indicated that changes in physical activity over the 4-year period were related to increases in physical self-esteem and positive affect, but only positive affect directly influenced improvements in QOL. CONCLUSIONS: The findings lend support to the position that physical activity effects on QOL are in part mediated by intermediate psychological outcomes and that physical activity can have long-term effects on well-being.

Affect↗

[Comparative genomic hybridization: the profile of chromosomal imbalances in esophageal squamous cell carcinoma].

OBJECTIVE: To characterize the profile of chromosomal imbalances of esophageal squamous cell carcinoma (SCC) in Linzhou, the high prevalence area of Henan province. METHODS: Comparative genomic hybridization (CGH) was used to examine 52 cases of primary SCC of esophagus. RESULTS: Gains in part or in whole of chromosome 3q, 8q, 5p, 1q, 6q, 18p, 20q and losses of 3p, 1p, 9q, 19p, 4p, 8p were detected frequently in SCC (> 20%). Gain of 3q, 5p, 1q, 11q13-14 and loss of 4pq, 13q were all significantly correlated with pathologic staging (P < 0.05). Gains of 8q, loss of 4p were linked to nodal metastasis (P < 0.05). Gains of 2p and loss of 4pq, 11q14-qter were associated with distant organ metastasis (P < 0.05). CONCLUSION: These observations suggest that 3q, 8q, 5p, 1q, 6q, 18p, and 20q may contain SCC-related oncogenes; 3p, 1p, 9q, 19p, 4p and 8p may contain SCC-related tumor suppressor genes. It is likely that gain of 3q, 5p, 1q, 11q13-14 and loss of 4pq, 13q are the genetic aberrations critical for the development of esophageal carcinoma, whereas gains of 8q, 2p and loss of 4pq, 11q14-qter are considered later events associated with tumor progression and are thought to confer metastatic potential to esophageal carcinoma. Furthermore, nodal and distant organ metastases involve different genes.

Carcinoma, Squamous Cell↗

Establishment and characterization of a human non-small cell lung cancer cell line.

Lung cancer is one of the most common causes of cancer death worldwide. Although many efforts have been made to explore the mechanisms involved in the development of lung cancer, the genetic events involved in the pathogenesis of lung cancer are still unclear. For a better mechanistic scope of study, a well-established cellular model is essential. We report the establishment of a squamous cell carcinoma (SCC) cell line of human lung, SCC-37. Chromosomal abnormalities and global genomic alterations of SCC-37 were studied by spectral karyotyping (SKY) and comparative genomic hybridization (CGH), respectively. Results showed that SCC-37 was a hypodiploid with complex chromosomal rearrangements. Some of the alterations, such as the gain of 1q25-qter in SCC-37, have been correlated to the tumor recurrence of non-small cell lung cancer (NSCLC). Other interesting findings include the amplification of 3q25-qter and 12q13, suggesting the existence of important oncogenes in the amplicons. This cell line may thus provide a useful cellular resource for studying the pathogenesis of SCC of the lung in the future.

Aged↗

[Behavioral changes of rats under rotation stimulation].

OBJECTIVE: To assess the specification and efficiency of rotation sickness indices by monitoring changes of behaviors in rats under rotation stimulation. METHOD: SD rats were stimulated by Crampton model with different time courses. Pica or kaolin consumption (KC), conditioned taste aversion (CTA) or saccharine water ingestion (SWI), 2 h food ingestion (2hFI), and open-field test (OFT) scores were observed. RESULT: Apparent changes of the four indices were observed after rotation stimulation. SWI, OFT scores and 2hFI decreased exponentially with increase of duration of the motion stimulation. KC increased linearly with the increase of time within 12 h stimulation. After 18 h stimulation, KC decreased to a level even lower than that after 6 or 12 h stimulation. The adjusted correlation between changes of the indices and duration of stimulation within 12 h are: 0.94 for KC, 0.54 for SWI, 0.44 for 2hFI and 0.34 for OFT. The maximum efficiency of the four indices appeared at 6-hour stimulation: 70% for KC, 90% for SWI, 80% for 2hFI and 95% for OFT. CONCLUSION: It is found that pica and CTA were more specific than the other indices. They may serve as primary indices and can be combined with the secondary indices such as 2hFI or OFT. Six hours is the optimal duration of stimulation by Crampton model for rotation sickness studies.

Animals↗

Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis.

Tumor/host-generated thrombin (endogenous thrombin) was investigated with tumor growth and metastasis experiments in mice by the use of hirudin, a highly potent specific inhibitor of thrombin. Pretreatment with hirudin inhibited tumor implantation in nude or syngeneic mice, following subcutaneous injection of 2 human and 2 murine tumors. Hirudin induced a considerable lag period in the appearance of tumor growth, compared with phosphate-buffered saline (PBS) treatment, but had no effect on established tumor nodule growth in vivo or on tumor growth in vitro. Hirudin treatment induced central necrosis of the tumor nodule compared with no effect with PBS treatment. Greater protection was noted with longer duration of treatment. Tumor seeding into blood was examined with green fluorescent protein (GFP)-labeled tumor cells. Hirudin inhibited seeding into the blood as well as systemic organs which varied from complete protection to 15- to 32-fold in the blood and 17- to 395-fold in the lung. Hirudin inhibited spontaneous metastases from subcutaneously implanted tumor by reducing the number of tumor nodules in the lungs. Mouse survival in animals injected subcutaneously with highly aggressive 4T1 cells revealed 5 of 5 deaths of PBS-treated animals on day 40 compared with no deaths with hirudin treatment, with prolongation of survival with hirudin treatment of 16 days to more than 31 days. Thus, endogenous thrombin contributes to tumor implantation, seeding, and spontaneous metastasis. A potent antithrombin agent should be of clinical benefit to patients with cancer.

Animals↗

Oncogenic role of eIF-5A2 in the development of ovarian cancer.

Amplification of 3q26 is one of the most frequent chromosomal alterations in many solid tumors, including ovarian, lung, esophageal, prostate, breast, and nasopharyngeal cancers. A candidate oncogene to eukaryotic initiation factor 5A2 (eIF-5A2), a member of eukaryotic initiation factor 5A subfamily, has been isolated from a frequently amplified region at 3q26.2. In this work, the tumorigenic ability of eIF-5A2 was demonstrated by anchorage-independent growth in soft agar and tumor formation in nude mice. Furthermore, antisense DNA against eIF-5A2 could inhibit cell growth in ovarian cancer cell line UACC-1598 with amplification of eIF-5A2 in form of double minutes. Cell growth rate in UACC-1598 was also inhibited when the expression level of EIF-5A2 was decreased by the reduction of the copy number of double minutes. The correlation of EIF-5A2 overexpression and clinical features of ovarian cancer was investigated using tissue microarray, and the result showed that eIF-5A2 overexpression was significantly associated with the advanced stage of ovarian cancer. These findings suggest that eIF-5A2 plays important roles in ovarian pathogenesis.

Animals↗

Association of Vimentin overexpression and hepatocellular carcinoma metastasis.

The poor prognosis of hepatocellular carcinoma (HCC) has been associated with recurrence and metastasis. Recently, we established a pair of HCC cell lines from a primary (H2-P) and its matched metastatic (H2-M) HCC tumors. A high density of cDNA microarray with 9184 human cDNA was used to identify the differentially expressed genes between H2-P and H2-M. Comparing with H2-P, eight upregulated and six downregulated genes were detected in H2-M. One interesting finding is the overexpression of Vimentin (VIM), a well-defined intermediate filament, which has been linked to a more aggressive status in various tumors. The correlation of overexpression of VIM and HCC metastasis was studied by immunohistochemistry using a tissue microarray with 200 primary HCCs and 60 pairs of primary and matched metastatic HCC samples. Tissue microarray demonstrated that the overexpression of VIM was significantly associated with HCC metastasis (P<0.01). This finding strongly suggests that the overexpression of VIM may play an important role in the metastasis of HCC.

Adult↗

Establishment of cell lines from a primary hepatocellular carcinoma and its metastatis.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world with a very poor prognosis that has been associated with tumor metastasis. The molecular mechanism of HCC metastasis is still unclear. In this study, we established cell lines from a primary tumor (H2-P) and its metastasis (H2-M). G-banding karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization were applied to study these two cell lines and the results demonstrated that they are of the same origin. These cell lines provide a very useful tool to identify genetic alterations associated with HCC metastasis.

Adult↗

Generation of a complete set of human telomeric band painting probes by chromosome microdissection.

Chromosomal rearrangements involving telomeric bands have been frequently detected in many malignancies and congenital diseases. To develop a useful tool to study chromosomal rearrangements within the telomeric band effectively and accurately, a whole set of telomeric band painting probes (TBP) has been generated by chromosome microdissection. The intensity and specificity of these TBPs have been tested by fluorescence in situ hybridization and all TBPs showed strong and specific signals to target regions. TBPs of 6q and 17p were successfully used to detect the loss of the terminal band of 6q in a hepatocellular carcinoma cell line and a complex translocation involving the 17p terminal band in a melanoma cell line. Meanwhile, the TBP of 21q was used to detect a de novo translocation, t(12;21), and the breakpoint at 21q was located at 21q22.2. Further application of these TBPs should greatly facilitate the cytogenetic analysis of complex chromosome rearrangements involving telomeric bands.

Cell Line, Tumor↗

Complement-independent Ab-induced peroxide lysis of platelets requires 12-lipoxygenase and a platelet NADPH oxidase pathway.

Antiplatelet GPIIIa49-66 Ab of HIV-related thrombocytopenic patients induces thrombocytopenia and platelet fragmentation by the generation of peroxide and other reactive oxygen species (ROS). Here we report the presence of a functional platelet NADPH oxidase pathway that requires activation by the platelet 12-lipoxygenase (12-LO) pathway to fragment platelets. A new Ab-mediated mechanism is described in which the platelet 12-LO product, 12(S)-HETE activates the NADPH oxidase pathway to generate ROS.

Antibodies↗

[Comparative genomic hybridization analysis of nasopharyngeal carcinoma drug-resistant cell CNE2/DDP and its parent cell CNE2].

BACKGROUND & OBJECTIVE: Developed from fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH) is a new molecular and cellular technique,used to examine the genomic imbalances,especially the loss and amplification of chromosomes,and to locate these alterations in certain chromosome regions. For a comprehensive understanding of the possible differences in genomic DNA between nasopharyngeal carcinoma drug-resistant and drug-sensitive cells, we analyzed the genomic DNA of a nasopharyngeal carcinoma drug-resistant cell line CNE2/DDP and its parent cell line CNE2 with CGH. METHODS: Genomic DNA was extracted from CNE2/DDP and CNE2 cells, as well as from normal placenta tissue. Fluorescent random primed labeling method was used to label the DNA probes (CNE2 and CNE2/DDP cells with green fluorescein-12-dUTP and normal placenta tissue with red tetramethylrhodamine-5-dUTP). The labeled DNA probes were then co-hybridized with normal lymphocyte metaphase chromosomes. Signals were taken by charge coupled device (CCD) and processed with Quips CGH Program after fluorescent hybridization. The green-to-red fluorescent ratio was calculated automatically and showed with graphs. RESULTS: There were extensive chromosome changes in CNE2, mainly the gain of 1q, 3q, 5p, 6p, 7p, 8q, 9q, 11p, 12q and 19q, and the loss of 4q, 12p, 13p, 14p, 15p, 18, 20q, 21p and 22. However, the CNE2/DDP cells, which come from the CNE2, showed a relatively normal karyotype except loss of 8p and gain of 8q and 19q. Consistent result was achieved after the CNE2/DDP cells were cultured in the medium free of any drugs for over one month. It appears that the CNE2/DDP cell has relative normal and much more stable chromosome constitution than its parent CNE2 cell. CONCLUSION: The CNE2/DDP is a single drug-resistant clone selected from CNE2,which is a blend of sub-clones that have different sorts of chromosome number and structure. It strongly suggests that the appearance of tumor drug-resistance is mainly a select process in which the would-be drug-resistant cell clone be selected from unfavorable survival condition.

Cell Line, Tumor↗

Heterogeneous expression and association of beta-catenin, p16 and c-myc in multistage colorectal tumorigenesis and progression detected by tissue microarray.

Most colorectal carcinomas (CRCs) arise from adenomas through an archetypal pathogenic pathway, the adenoma-carcinoma-metastasis sequence. Aberrant expression of beta-catenin, p16, E-cadherin and c-myc appears to have played important roles in the development and/or progression of CRC, but their precise distribution pattern and associations in different pathologic loci along CRC's pathogenic pathway have not been thoroughly examined. In this study, a tissue microarray (TMA) containing 85 advanced CRCs in different Dukes stages was constructed. In each of 85 cases, tissue specimens from normal mucosa and primary carcinomas in different layers of the bowel wall were included in the TMA. Tissue specimens from matched adenoma, lymph node metastases and distant metastases were obtained from 22, 21 and 21 cases, respectively. Expression patterns of beta-catenin, p16, E-cadherin and c-myc were evaluated by immunohistochemistry. The results revealed that nuclear expression of beta-catenin, p16 and c-myc was quantitatively increased from normal mucosa to premalignant adenoma, primary carcinoma and lymph node metastatic carcinoma; the frequency of nuclear overexpression of beta-catenin and p16 in lymph node metastases was significantly higher than that in distant metastases (p < 0.05). These results suggest an association between nuclear overexpression of beta-catenin and/or p16 and CRC lymph node metastasis but not distant metastasis. The results also showed that correlative high nuclear expression of beta-catenin and c-myc was observed in primary carcinomas involving the serosa and lymph node metastases (p < 0.05) but not in other pathologic regions of CRCs, suggesting that the tumor microenvironment in different pathologic loci of colorectal tumorigenesis and progression may influence c-myc responsiveness to beta-catenin/Tcf activation.

Colorectal Neoplasms↗

Genetic changes in human fetuses from spontaneous abortion after in vitro fertilization detected by comparative genomic hybridization.

The in vitro fertilization (IVF) technique is becoming a very important approach for infertile disease therapy, but approximately 30% of pregnancies are spontaneously aborted in the first trimester. It is believed that chromosomal abnormality is the major reason for early spontaneous abortion. Although some reports have mentioned cytogenetic changes in spontaneously aborted embryos after IVF, little is known about the comprehensive cytogenetic alterations in these aborted embryos. Here we use the comparative genomic hybridization (CGH) technique to analyze the genetic alterations in 41 spontaneously aborted human specimens after IVF. In this study, 25 of 41 cases (61%) showed chromosomal changes. Among them, autosomes and sex chromosomes were involved in 16 and 11 cases, respectively. Several nonrandom chromosomal changes were identified, including loss of one sex chromosome (six cases) and gains of 22 (four cases), Y (four cases), 21 (three cases), 4 (two cases), and 13 (two cases). Our data support the opinion that chromosome abnormality is one of the major causes of early spontaneous abortion after IVF. The association between chromosome changes in these spontaneously aborted fetuses and maternal age, infertility patterns, infertility causes, and IVF patterns (routine IVF and other methods, including intracytoplasmic sperm injection, egg donation, and embryo donation) were also studied. No significant correlation was found.

Abortion, Spontaneous↗

Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells.

Angiogenesis is required for tumor growth and metastasis. It has recently been suggested that thrombin is a potent promoter of angiogenesis. We therefore examined the possibility that thrombin could be inducing the expression of angiopoietin-2 (Ang-2), necessary for remodeling. Human umbilical vein endothelial cells were incubated with or without thrombin (1 U/mL) for 1 to 24 hours and then examined for messenger RNA (mRNA) by Northern analysis. Enhanced mRNA expression (about 4-fold over baseline) was noted at 4 hours. Enhanced expression of Ang-2 mRNA was secondary to enhanced transcription (about 4-fold), with no effect on stabilization. Enhanced Ang-2 mRNA transcription was inhibited by H7 and PD98059, indicating the requirement of serine/threonine kinases as well as the mitogen-activated protein kinase pathway. Up-regulation of mRNA was associated with enhanced Ang-2 protein synthesis and secretion as assayed by immunoblot. Thrombin-induced secreted Ang-2 inhibited the binding of recombinant (35)S-Ang-1 to its Tie-2-Fc receptor, demonstrating functionality. Hirudin reversed this effect, demonstrating thrombin specificity. Thus, thrombin-induced tumorigenesis and metastasis is associated with enhanced Ang-2 protein synthesis and secretion via enhanced transcription of Ang-2. This could help explain how thrombin promotes angiogenesis.

Angiopoietin-2↗

Establishment and characterization of human metastatic hepatocellular carcinoma cell line.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with a poor prognosis. Recently, we established a HCC cell line from a metastatic HCC tumor. GTG banding analysis was performed and the karyotype showed that this metastatic HCC cell line is a hypertriploid (71-78 chromosomes) with a large marker chromosome containing a long homogeneously staining region (hsr). Comparative genomic hybridization was applied to characterize the chromosomal alterations in this metastatic HCC cell line. The results showed that the hsr was composed of amplified DNA sequences from 11q13. Further characterization of the hsr may lead to the isolation of the putative amplified oncogene at 11q13.

Aneuploidy↗

[Establishment and cytogenetic characterization of a human hepatocellular carcinoma cell strain from the embolus in portal vein].

BACKGROUND & OBJECTIVE: Poor prognosis of hepatocellular carcinoma (HCC) is due to its high recurrent rate after operation and early metastasis through portal vein. This study was designed to establish a metastatic HCC cell line and to investigate its molecular and cytogenetic characterization. METHODS: Cell culture was performed using the tissue obtained from a metastatic lesion in portal vein of a patient with HCC. After G-banding staining, karyotype, and comparative genomic hybridization (CGH) of the cultured H4M cells were characterized and cyclin D1 gene CCND1 was detected by differential PCR. RESULTS: The karyotype of metastatic HCC cell strain is a hypertriploid (71-78 chromosomes) with a huge marker chromosome containing a long homogeneously staining region (hsr). The main genetic alterations in H4M cells were a high copy number amplification of 11q13 and loss of 8p. Cyclin D1 gene CCND1 was also amplified significantly in the cells. CONCLUSIONS: The loss of chromosome 8p and high copy number amplification of 11q13 are associated with the metastatic characteristics of H4M cells. The amplification of cyclin D1 gene CCND1 in H4M cells may be the cause of the amplification of chromosome 11q13.

Aneuploidy↗