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Biomedical subjects

S C Wang

Publications and source records attributed to S C Wang.

At least 73 records · Page 4Linked to original sources
PubMed2000

Suppressing HER2/neu-mediated cell transformation by transcriptional repressors.

Breast and ovarian cancer are two of the leading causes of death for women in the United States. HER2/neu overexpression is an unfavorable prognosis factor associated with low patient survival rate of multiple cancer types including breast and ovarian cancer. Downregulation of the HER2/neu gene expression in cancer cells has been shown to be a useful strategy to significantly reverse the malignant characteristics induced by HER2/neu overexpression. It is possible that HER2/neu overexpression can be repressed through inhibiting the promoter activity of the gene. We have identified a number of potent transcriptional regulators, including the adenovirus type 5 E1A, the SV40 large T antigen, and the ets family member PEA3, and have tested their activity to repress HER2/neu overexpression. Ectopic expression of these transcriptional regulators resulted in downregulation of the HER2/neu promoter activity and reversed the transformed phenotype of the cancer cells in vitro. These observations were followed by a series of studies to investigate whether these HER2/neu repressors could act therapeutically as tumor suppressor genes for cancers overexpressing HER2/neu. The results of these preclinical studies clearly indicated that transcriptional repressors, which downregulate HER2/neu overexpression, can be an effective regimen for cancer treatment in a gene therapy format combined with an appropriate gene delivery system such as the cationic liposome DC-Chol or replication-deficient adenovirus vector. Our results have demonstrated that these delivery systems can effectively transfer the therapeutic genes into the cancer cells in vivo and lead to significant suppressive effects on tumor growth. Furthermore, tumor-free survival rate of treated animals is increased dramatically using nontoxic doses, compared with animals without the treatment. A great body of evidence has revealed the potential of using transcriptional repressors to suppress HER2/neu overexpression and abolish tumor growth. Thus, suppression of oncogenic gene expression using transcription factors can be a novel field for cancer treatment and prevention.

Journal Article↗
PubMed2000

The prevalence of betel chewing among the students of the different senior high schools in southern Taiwan.

A cross-sectional study was designed to determine the prevalence of betel chewing and the high-risk groups among the students of the first and second grades in five types of senior high schools in southern Taiwan. The results reveal that more male than female students were betel chewers: the prevalence rate of current chewers is from 0.96% to 16.15% among male students compared with that of 0% to 5.58% among female students. The students in the vocational schools was found have the higher prevalence rate of betel chewing. The students in the agricultural schools are the highest-risk group for betel chewing. The highest odds were found in the agricultural school students when they were compared with the general school students. It is 31.74 for the current chewers and 5.93 for the ex-chewers.

Adolescent↗
PubMed2000

Transcriptional targeting of the HER-2/neu oncogene.

Breast and ovarian cancers are the leading cause of death for women in many areas in the world including the United States. Overexpression of the HER-2/neu gene (also known as c-erbB2) is a frequent event in about 30% of breast as well as ovarian cancers. The overall survival rates of breast and ovarian cancer patients whose tumors overexpress HER-2/neu are significantly lower than those of patients whose tumors do not overexpress HER-2/neu. Overexpression of HER-2/neu leads to elevated tumorigenicity, enhanced metastatic potential, increased resistance to TNF-alpha-induced apoptosis and resistance to treatments such as paclitaxel and tamoxifen. Down-regulation of the HER-2/neu oncogene causes suppression of the cell-transforming phenotype induced by the oncogene. For example, downregulation of the HER-2/neu gene expression by E1A significantly mitigated tumorigenic activity of human breast and ovarian cancer cells in nude mice. These results strongly imply that HER-2/neu mediated cell transformation may be inhibited by transcriptional repressors that target the promoter of the oncogene. In addition to E1A, we recently identified the ets transcription factor PEA3 as a potential HER-2/neu gene inhibitor. PEA3 binds directly to this consensus binding motif and suppresses the HER-2/neu gene promoter activity. Downregulation of HER-2/neu expression led to inhibition of cell transformation and proliferation in vitro. In a preclinical gene therapy setting, in which the PEA3 gene tumor delivery was facilitated by a cationic liposome DC-Chol, blocked HER-2/neu overexpression by PEA3 resulted in prolonged survival of treated animals. These studies demonstrate a promising approach to cancer gene therapy using transcriptional repressors to target expression of oncogenes such as HER-2/neu.

Journal Article↗
PubMed1999

Electrophoretic separation of linear and supercoiled DNA in uncoated capillaries.

We report electrophoretic separation of supercoiled plasmids (2-16 kilo base pairs) and linear double-stranded DNA (0.6-23 kilo base pairs) in uncoated capillaries filled with dilute hydroxyethylcellulose. Because electroosmotic flow reverses the order of elution, long plasmids spend less time in the capillary and their bandwidths are narrower than observed in coated capillaries. However, resolution is similar to that obtained in coated capillaries, because it is governed by the distribution of unresolved topoisomers. In the presence of electroosmotic flow migration of supercoiled plasmids does not follow the elastic rod model that has been observed in coated capillaries.

DNA↗
PubMed1999

Osteogenic sarcoma with skeletal muscle metastases.

Two cases of osteogenic sarcoma with skeletal muscle metastases are described. A 40-year-old woman presented with progressive swelling of both calves and a soft tissue back lump. She had been diagnosed with mandibular chondroblastic osteogenic sarcoma 6 years earlier. Radiographs showed calcified masses. MRI scans and bone scintigraphy revealed multiple soft tissue masses in both calves. Bone scintigraphy also showed uptake in the back lump, right thigh and left lung base. Biopsy confirmed metastatic chondroblastic osteogenic sarcoma, which initially responded well to chemotherapy. However, the metastatic disease subsequently progressed rapidly and she died 21 months after presentation. The second case concerns a 20-year-old man who presented with a pathologic fracture of the humerus, which was found to be due to osteoblastic osteogenic sarcoma. He developed cerebral metastases 17 months later, followed by metastases at other sites. Calcified masses were subsequently seen on radiographs of the abdomen and chest. CT scans confirmed the presence of densely calcified muscle metastases in the abdominal wall, erector spinae and gluteal muscles. The patient's disease progressed rapidly and he died 30 months after presentation.

Adult↗
PubMed1999

Intracellular generation of MDA-LYS epitope in foam cells.

Oxidative stress plays a central role in atherogenesis. Antioxidants, such as probucol, inhibit oxidation of LDL, retard secretion of interleukin-1, growth factors and chemoattractants, and thus inhibit progression of atherosclerosis. Other antioxidants with an ability to inhibit LDL oxidation, however, could not prevent progression of atherosclerosis. The inconsistency between antioxidant potencies indicated oxidative events might have occurred at locations other than LDL. MDA-lysine epitope (MDA-lys) is closely associated with atherogenesis and was recognized as marker for oxidation. We traced formation of MDA-lys during oxidation of LDL and formation of foam cells. The results indicated that thiobarbituric acid reactive substance (TBARS) was primarily present in lipid fraction of ox-LDL not associated with protein fraction after Cu2+ oxidation in vitro. Oxidized LDL did not increase significant immunoreactivity of MDA-lys epitope under our experimental conditions. Foam cells, however, showed the presence of MDA-lys epitope suggesting that intracellular oxidation events occurred to internalized lipids. The uptake of non-oxidatively modified LDL (acetylated LDL) was sufficient to generate MDA-lys epitope in foam cells, consistent with the hypothesis that atherosclerosis is associated with oxidative events in addition to LDL oxidation. We hypothesized that MDA-lys may be generated through intracellular lipid metabolism during the formation of foam cells.

Animals↗
PubMed1999

Joint sonography.

Sonographic evaluation of joint and periarticular pathology clearly has applications in numerous clinical scenarios, not only for diagnosis but in some situations for US-guided biopsy, aspiration, and injections. It is a rapid, inexpensive technique that with adequate equipment, training, and expertise makes it compelling for use as a first-line imaging modality for the assessment of periarticular masses, localized pain, possible infection, joint swelling, as well as posttraumatic articular and periarticular lesions.

Acromioclavicular Joint↗
PubMed1999

CD14 expression and production by human hepatocytes.

BACKGROUND/AIMS: CD14 has been identified as a receptor for LPS and is present both in a membrane-bound and a soluble form. Membrane CD14 (mCD14) is predominantly expressed on monocytes, macrophages and granulocytes. The source of soluble CD14 (sCD14) is as yet unclear. Previous investigation using monocytes has shown that sCD14 can be derived either from the shedding of mCD14 or from direct secretion by monocytes. Whether the monocyte is the sole or even the major source of sCD14 is as yet uncertain. Clearance of LPS from the bloodstream is thought to be primarily mediated by the liver. Production of CD14 by hepatocytes would potentially provide a powerful mechanism by which the liver could clear LPS, and therefore we examined the ability of human hepatocytes to produce CD14. METHODS: Human hepatocytes were isolated using collagenase perfusion. RESULTS: Human hepatocytes were found to have CD14 mRNA by Northern blot analysis. Western blot analysis and immunohistochemical staining confirmed CD14 protein in primary hepatocyte cultures. Further studies showed that a liver epithelial-like cell line AKN-1 is capable of producing CD14. Comparisons of the size of hepatocyte-derived CD14 protein with the sCD14 protein from the human monocytic leukemia cell line HL60 suggested that a slightly larger form of CD14 is expressed by human liver cells. CONCLUSION: This is the first study to demonstrate production of CD14 by human hepatocytes.

Cell Line↗
PubMed1999

Using a direct current electrical field to promote spinal-cord regeneration.

The authors used a direct current electrical field to promote spinal-cord regeneration in a canine model. Thirty-two dogs were randomly divided into four groups. Complete spinal-cord injury was induced, and electrical stimulators were then placed in the animals. Group 1 served as controls; Groups 2 to 4 were experimental groups, with varying stimulator voltages: 0V in Group 1, 12V in Groups 2 and 4, and 6V in Group 3, with the stimulator implanted 6 hr after spinal-cord injury in Group 4. Functional, electrophysiologic and morphometric assessments were carried out 1 to 3 months postoperatively. Results showed that spinal-cord function, cortical somatosensory evoked potentials, number of neurons, sectional area of neurons, and Nissl body density in the experimental groups were much better than those in the control group. In addition, all the indices in Group 2 were better than those in Groups 3 and 4. This indicated that direct current electrical stimulation could effectively promote spinal-cord regeneration and functional recovery in this model. The 12V voltage was safe for the animals. The stimulator was not rejected by the host for a relatively long period of time.

Animals↗
PubMed1999

Blunt thoracic aortic injury: delayed or early repair?

OBJECTIVE: To evaluate the safety and benefit of delayed repair of blunt thoracic aortic injury (BTAI) in trauma patients with multiple injuries and to assess the financial impact of delayed repair. METHODS: A retrospective review of charts was performed on 55 patients with the diagnosis of BTAI from January 1, 1992, through December 31, 1997, at our Level I trauma center. Early repair was defined as operative repair of BTAI within 12 hours of admission. Seven patients were excluded from analysis due to death before BTAI diagnosis (two deaths were from rupture in the emergency department and five were from massive blunt trauma without rupture). The groups were compared by using a McNemar chi2 test, for which p less than or equal to 0.05 is significant. RESULTS: There were 30 patients in the early repair (ER) group repaired at 5.3+/-2.4 hours, and 18 patients in the delayed repair (DR) group repaired at 8.5 days (range, 17 hours-67 days). There were no significant differences between the ER and DR groups in age (37+/-18 years vs. 41+/-19 years), Injury Severity Score (39+/-15 vs. 45+/-14), intensive care unit days (12+/-14 days vs. 18+/-11 days), hospital length of stay (21+/-19 days vs. 28+/-14 days), or mortality rates (7% vs. 6%). There was a trend toward longer lengths of stay in the DR group. Most DR patients required beta-blocker therapy and/or other antihypertensives for systolic BP more than 120 mm Hg during admission. There were no deaths from aortic rupture in either group. By using financial data that was available from July of 1994 onward, we performed a subset analysis of the direct costs associated with BTAI. Total direct and variable direct costs for patients undergoing delayed repair were over two times the costs for early repair patients (p < 0.05). CONCLUSION: The management of trauma patients with multiple injuries requires prioritization of injuries so that the outcomes from these injuries can be optimized. Although delayed aortic repair was safely practiced in this series, there was not an obvious outcome benefit to delayed repair. The patients undergoing late repair required increased attention to hemodynamics, and there was a trend toward increased length of stay. In addition, analysis of the costs associated with delayed repair demonstrated a twofold increase in the direct costs for delayed repair compared with early repair.

Adolescent↗
PubMed1999

Inhibition of focal contact formation in cells transformed by p185neu.

Signaling pathways mediated by adhesive molecules are tightly associated with cytoskeletal organization and cell growth regulation. Focal adhesion kinase (FAK) plays a prominent role in the adhesion signaling pathway through its tyrosine kinase activity and protein-protein interaction with other signaling molecules, including src, paxillin, and p130CAS, and other proteins. We explored the roles of these signaling molecules in the transformation of B104-1-1 cells, an NIH/3T3-derived cell line transformed by activated rat p185neu. The cytoskeletal organization of the p185neu-transformed cells was disrupted, and their morphology was dramatically altered. FAK, paxillin, and p130CAS appeared to be tyrosine phosphorylated in both NIH/3T3 and B104-1-1. However, the phosphorylation levels of paxillin and p130CAS were lower in B104-1-1 cells than in NIH/3T3 cells. Surprisingly, the association between FAK and paxillin was enhanced in B104-1-1 cells, suggesting reorganization of protein-protein interaction modulated by protein phosphorylation. Our results showed that even though cellular transformation by src and neu has similar consequences, such as focal adhesion disassembly and increased metastasis potential, the molecular events underlying the signaling pathways can be dramatically different.

3T3 Cells↗
PubMed1999

[Studies of transgene segregation and integration in maize].

The segregation, integration and stability of the transgene-Bt (Bacillus thuringensis) in eight transformants created by three ways of transformation were studied by means of PCR (Polymerase chain reaction) and DNA molecular hybridization. The results are as follows: (1) The transgene-Bt in most of the progenies of the transformants showed simple Mendelian segregation. Although some deviation from Mendelian fashion existed in the early generations, the normal Mendelian segregation would be found after R3 generations and the transgene could fix in the populations. (2) The integration patterns of the transgene varied to the some extent in the different transformants, but they were characterized by either smaller band and copy numbers or cascade integration or closely linked integration in all transformants. (3) Changes of the Southern land pattern were found in some families of some transformants, especially, in the two families of Ding 4R5.

Blotting, Southern↗
PubMed1999

Leptospirosis: report of one case.

An 8-year-old male aborigine was referred to our hospital with a presumptive diagnosis of Kawasaki disease. The major symptom presented was a persistent fever for six days. Several other symptoms were drowsiness, headache, nausea, vomiting, abdominal pain, diarrhea, nuchal rigidity, lymphadenopathy, subconjunctival hemorrhage, and muscle aching of the calf. During hospitalization, cerebrospinal fluid studies showed pleocytosis. Abdominal sonograms revealed hepatosplenomegaly, moderate ascites and gallbladder wall thickening. These data were suggestive of leptospirosis. The microscopic agglutination test of leptospiral antibodies further confirmed the diagnosis. After treatment with intravenous aqueous penicillin and gentamicin, the clinical course improved significantly.

Child↗
PubMed1999

[Resection of spinal tumor and reconstruction of spinal stability].

OBJECTIVE: Both primary and metastatic tumor of spine can influence spinal stability, spinal cord and nerves. The principles of dealing spinal tumor are resection of tumor decompression on spinal cord and reconstruction of spinal stability. METHODS: Since Aug. 1993 to Oct. 1996, 15 cases with spinal tumor were treated, including 4 primary spinal tumor and 11 metastatic tumor. Tumor foci were mainly in thoracic and lumbar spine. Graded by Frankel classification of spinal injuries, there were 1 case of grade A, 1 of grade B, 3 of grade C, 5 of grade D and 5 of grade E. Tumors of upper lumbar spine and thoracic spine were resected through anterior approach. Posterior approach also was adopted once posterior column was affected. Tumors of lower lumbar spine were resected by two-staged operation: firstly, operation through posterior approach to reconstruct spinal stability: secondly, operation through anterior approach. After resection of tumor, the spines were fixed by Kaneda instrument, Steffee plate or Kirschner pins. To fuse the spine, bone grafting was used in benign tumor and bone cement used in malignant tumor. RESULTS: Except one patient died from arrest of bone marrow, the others were followed up for 3 to 20 months. Postoperatively, 11 patients could sit up on one foot with the help of body supporter, and 9 patients could walk in two weeks under careful monitoring. There was no exacerbation of symptom and failure of fixation. The function of spinal cord was improved: 1 case from grade B to grade E, 1 from A to C, 2 from C to E and 4 from D to E. CONCLUSION: The spine can be reconstructed for weight bearing early by internal fixation. The symptom can be relieved and the nervous function can be improved by resection of tumor and decompression.

Adult↗
PubMed1998

Characterization of BRCA2: temperature sensitivity of detection and cell-cycle regulated expression.

People carrying a mutant BRCA2 gene are susceptible to breast, ovarian, pancreatic and other tumors. Many facets of BRCA2 have been studied, including its mutation in human cancers, its role in mouse embryogenesis and its RNA expression in different tissues and different mouse embryogenesis stages. However, there has been very little characterization of BRCA2 protein. We investigated the biochemical and biological properties of BRCA2 by using a monoclonal antibody we generated against the N-terminal portion of BRCA2. We discovered that the detection of BRCA2 by immunoblot analysis was sensitive to the temperature used to denature the samples before gel electrophoresis. BRCA2 was easily detectable when samples were denatured at low temperature instead of boiling. Although the precise mechanism underlying this observation is not clear yet, this finding will significantly improve our ability to study BRCA2. We examined the expression of BRCA2 using an immunoblot analysis protocol modified according to this observation. We showed that BRCA2 was presented in every human cell lines examined, including Capan-1, which expressed a truncated BRCA2 due to a BRCA2 frameshift mutation. We also showed that the expression of BRCA2 was cell-cycle regulated. Our results suggest that BRCA2 has an important role in cell growth regulation.

Antibodies, Monoclonal↗