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Biomedical subjects

Andrew C Chang

Publications and source records attributed to Andrew C Chang.

16 recordsLinked to original sources
PubMed2006

Diversity of the angiogenic phenotype in non-small cell lung cancer.

Angiogenesis is crucial for tumor biology. There are many mechanisms by which tumors induce angiogenesis. We hypothesize that each individual tumor develops a unique mechanism to induce angiogenesis, and that activation of a particular angiogenic pathway suppresses the evolution of alternative pathways. We characterized 168 human non-small cell lung cancer (NSCLC) specimens for levels of angiogenic factors (angiogenic CXC chemokines, basic fibroblast growth factor, and vascular endothelial growth factor). We also induced lung tumor formation in A/J mice by injecting the tobacco carcinogen NNK. We dissected individual lung tumors and measured expression of angiogenic factors from three distinct families using real-time PCR. Finally, we controlled the angiogenic milieu using in vivo models to determine the resultant phenotype of the angiogenic factors expressed by NSCLC cells. Human tumors displayed marked variation in the expression of angiogenic factors. Individual mouse tumors, even from within the same mouse, displayed variability in their pattern of expression of angiogenic factors. In a sponge model of angiogenesis using murine lung cancer cells, implanting LLC cells with an angiogenic factor suppressed the expression of other angiogenic factors in implanted sponges. This suppressive effect was not seen in vitro. We conclude that lung cancer tumors evolve a unique and dominant angiogenic phenotype. Once an angiogenic pathway is activated, it may allow for tumor growth to proceed in the absence of a selection pressure to activate a second pathway.

Angiogenic Proteins↗
PubMed2006

Comparative proteomics analysis of Barrett metaplasia and esophageal adenocarcinoma using two-dimensional liquid mass mapping.

Esophageal adenocarcinoma, currently the seventh leading cause of cancer-related death, has been associated with the presence of Barrett metaplasia. The malignant potential of Barrett metaplasia is evidenced by ultimate progression of this condition to invasive adenocarcinoma. We utilized liquid phase separation of proteins with chromatofocusing in the first dimension and nonporous reverse phase HPLC in the second dimension followed by ESI-TOF mass spectrometry to identify proteins differentially expressed in six Barrett metaplasia samples as compared with six esophageal adenocarcinoma samples; all six Barrett samples were obtained from the identical six patients from whom we obtained the esophageal adenocarcinoma tissue. Approximately 300 protein bands were detected by mass mappings, and 38 differentially expressed proteins were identified by microLC-MS/MS. The false positive rates of the peptide identifications were evaluated by reversed database searching. Among the proteins that were identified, Rho GDP dissociation inhibitor 2, alpha-enolase, Lamin A/C, and nucleoside-diphosphate kinase A were demonstrated to be up-regulated in both mRNA and protein expression in esophageal adenocarcinomas relative to Barrett metaplasia. Candidate proteins were examined at the mRNA level using high density oligonucleotide microarrays. The cellular expression patterns were verified in both esophageal adenocarcinomas and in Barrett metaplasia by immunohistochemistry. These differentially expressed proteins may have utility as useful candidate markers of esophageal adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Disposal of domestic sludge and sludge ash on volcanic soils.

Column leaching experiments were conducted to test the ability of Chilean volcanic soils in retaining the mineral constituents and metals in sewage sludge and sludge ash that were incorporated into the soils. Small or negligible amounts of the total content of Pb, Fe, Cr, Mn, Cd, and Zn (0 to <2%), and more significant amounts of mineral constituents such as Na (7-9%), Ca (7-13%), PO4 (4-10%), and SO4 (39-46%) in the sludge and sludge ash were readily soluble. When they were incorporated on the surface layer of the soils and leached with 12 pore volumes of water over a 3 month period of time, less than 0.1% of the total amount of heavy metals and PO4 in the sludge and sludge ash were collected in the drainage water. Cation exchange selectivity, specific anion adsorption and solubility are the processes that cause the reduction of leaching. The volcanic soils were capable of retaining the mineral constituents, P, and metals in applied sewage sludge and sludge ash and gradually released them as nutrients for plant growth.

Chile↗
PubMed2006

Multiple forms of genetic instability within a 2-Mb chromosomal segment of 3q26.3-q27 are associated with development of esophageal adenocarcinoma.

Gene amplification is one of the mechanisms to activate oncogenes in many cancers, including esophageal adenocarcinoma (EA). In the present study, we used two-dimensional restriction landmark genome scanning to clone a NotI/DpnII fragment that showed increased genomic dosage in 1 of 44 EAs analyzed. This fragment maps to 3q26.3-q27, and subsequent experiments identified two intrachromosomal amplicons within a 10-Mb DNA segment in 7 of 75 (9%) EAs. The distal amplified-core region maps centromeric to the PIK3CA locus, and a microsatellite (D3S1754) within this region exhibited significant instability (MSI), in stark contrast to the genomewide microsatellite stability found in EA. D3S1754-MSI arises in premalignant Barrett's dysplastic cells and preceded amplification of the nascent MSI allele in the corresponding EA. Seven ESTs within the amplified-core were overexpressed in amplicon-containing EAs. One of these, EST AW513672, represents a chimeric transcript that initiated from an antisense promoter sequence in the 5'UTR of a full-length LINE-1 element (L1-5'ASP). Similar chimeric transcripts encoding portions of the MET oncogene and the BCAS3 gene also were overexpressed in EAs, suggesting that L1-5'ASP activation may occur at a broad level in primary EAs. Thus, the fine dissection of a 2-Mb amplified DNA segment in 3q26.3-q27 in EA revealed multiple genetic alterations that had occurred sequentially and/or concurrently during EA development.

5' Untranslated Regions↗
PubMed2006

Bridge to transplant using the MicroMed DeBakey ventricular assist device in a child with idiopathic dilated cardiomyopathy.

We report the implantation of the MicroMed DeBakey left ventricular assist device (MDBVAD) in a 10-year-old girl with cardiogenic shock secondary to an idiopathic dilated cardiomyopathy. This was the first pediatric implant of the MDBVAD in the United States and the youngest patient worldwide. The patient recovered well and subsequently underwent successful heart transplantation after 84 days of support.

Cardiac Catheterization↗
PubMed2006

Management of congenital and acquired pulmonary vein stenosis.

BACKGROUND: Pulmonary vein (PV) stenosis, whether congenital or after repair of total anomalous pulmonary venous connection (TAPVC), continues to carry a poor prognosis. METHODS: A retrospective review identified 36 patients who underwent repair of PV stenosis between December 1989 and June 2003. Fourteen with congenital PV stenosis underwent scar excision and primary repair (n = 2), intraoperative stent placement (n = 4), or sutureless pericardial marsupialization (n = 8). Twenty-two with acquired PV stenosis after TAPVC repair underwent anastomotic revision and/or vein repair (n = 11) or sutureless pericardial marsupialization (n = 11). Follow-up ranged from 1 month to 14 years (median, 30 months). RESULTS: Among the 14 patients with congenital PV stenosis, 8 died (3 early deaths, 4 late deaths with restenosis, and 1 late noncardiac death). Among the six survivors, five (4 after marsupialization) have not developed restenosis. Among 11 of 22 patients with acquired PV stenosis undergoing anastomotic revision or vein repair, there were 5 deaths (2 early, 2 late with restenosis, and 1 late noncardiac death) and 1 of the six survivors has developed restenosis. Of the remaining 11 undergoing marsupialization, there was one late death (with restenosis) and 10 survivors have no restenosis. Congenital etiology, use of marsupialization technique, presence of associated defect, and extent of disease were identified as risk factors for poor outcome. CONCLUSIONS: Patients with pulmonary vein stenosis continue to have a guarded prognosis. Sutureless pericardial marsupialization was associated with satisfactory midterm results and appears superior to other conventional techniques.

Heart Defects, Congenital↗
PubMed2006

Tension chylothorax.

Thoracic duct injury resulting in chylothorax is a well-known and documented complication of thoracic surgery. However, chylothorax under tension is a rarely reported complication that results in respiratory and hemodynamic collapse. Early recognition and treatment of this entity are essential for optimal patient outcome. Herein we present two cases of postoperative tension chylothorax followed by a review of the diagnostic work-up and therapy for this complication.

Aged↗
PubMed2006

Awake tracheobronchial dilation without the use of rigid bronchoscopy.

Benign tracheal strictures have been treated by repeated dilations using rigid bronchoscopy and general anesthesia. An alternative approach using conscious sedation, fluoroscopy, flexible bronchoscopy, and Savary-Gilliard esophageal dilators (Cook Endoscopy, Inc, Winston-Salem, NC) is reported. All patients undergoing dilation while awake had lesions due to inflammatory disease or lesions that were not amenable to resection. This method may be less traumatic than rigid bronchoscopy and can be accomplished on an outpatient basis without the use of general anesthesia.

Adult↗
PubMed2006

The volume-performance relationship in esophagectomy.

The current literature demonstrates that both hospital volume and surgeon volume are inversely related to operative mortality for esophageal resection. Given the heterogeneity of the volume-outcome literature, it is difficult to identify minimum volume thresholds at which satisfactory performance is achieved. Both volume-based hospital referral and process improvement provide compelling and sometimes competing strategies for translating evidence about volume-outcome relationships into policy. Each approach has significant limitations that preclude uniform implementation nationwide but nonetheless should be a focus for continued investigation and application, with the goal of providing uniform and high-quality care after esophagectomy.

Clinical Competence↗
PubMed2006

Expression and effect of inhibition of the ubiquitin-conjugating enzyme E2C on esophageal adenocarcinoma.

Ubiquitin-dependent proteolysis of cyclins plays a critical role in cell cycle progression and tumorigenesis. We examined the expression of ubiquitin-conjugating enzyme E2C (UBE2C) during progression from Barrett's metaplasia to esophageal adenocarcinoma (EA) and the effects of targeting this enzyme on EA-derived cell lines. Using oligonucleotide microarrays UBE2C expression was elevated in 73% (11 of 15) of EAs relative to Barrett's metaplasia. Tissue microarray showed elevated UBE2C in 70% (7 of 10) of dysplastic samples and in 87% (58 of 67) of tumors relative to metaplastic samples. Transfection of dominant-negative UBE2C into Seg-1 cells decreased proliferation (P = .04) and increased mitotic arrest compared to vector controls (63.5% vs 6.8%; P < .001). Transfection of UBE2C small interfering RNA also caused inhibiton of cell proliferation and distortion of the cell cycle, with maximal increase of G(2) cells (155% of mock cells) at 72 hours and of S-phase cells (308% of mock cells) at 24 hours. Treatment of Seg-1 cells with the proteasome inhibitor MG-262 (1 nM-1 microM) showed decreased proliferation (P = .02). EA-derived cells expressing UBE2C are sensitive to treatment with MG-262 and to silencing of UBE2C, suggesting that patients with EAs overexpressing UBE2C may benefit from agents targeting this ubiquitin-conjugating enzyme.

Adenocarcinoma↗
PubMed2005

CT-based definition of thoracic lymph node stations: an atlas from the University of Michigan.

PURPOSE: Accurate delineation of the mediastinal and hilar lymph node regions is essential for a reproducible definition of target volumes used in conformal irradiation of non-small-cell lung cancer. The goal of this work was to generate a consensus to delineate these nodal regions based on definitions from the American Joint Committee on Cancer. METHODS AND MATERIALS: A dedicated thoracic radiologist, thoracic surgeon, medical physicist, and three radiation oncologists were gathered to generate a three-dimensional radiologic description for the mediastinal and hilar nodal regions on axial CT scans. This paper proposes an atlas of most of the lymph node stations described by Mountain and Dresler. RESULTS: The CT boundaries of lymph node stations 1-2, 3, 4, 5, 6, 7, 8, 10-11 were defined on axial CT, along with image illustrations. CONCLUSION: These CT-based illustrative definitions will provide guidelines for clinical practice and studies evaluating incidental radiation in radiotherapy. Studies are ongoing at the University of Michigan to measure quantitatively the incidental nodal radiation received by patients with non-small-cell lung cancer.

Humans↗
PubMed2004

Distinguishing sources of groundwater nitrate by 1H NMR of dissolved organic matter.

Dissolved organic matter (DOM) originating from a certain source usually carries characteristic marks in its molecular structures that can be recognized by spectroscopic analysis. Sources of water-borne contaminants, such as nitrate, can be identified by recognition of the characteristics of DOM entrained in the water. In this study, DOM in groundwaters sampled from a dairy/crop production area (Chino Basin, CA) was analyzed by 1H nuclear magnetic resonance (1H NMR). Results showed that DOM derived from natural soil organic matter has a characteristic resonance at a chemical shift region of 4.0-4.3 ppm, while DOM derived from dairy wastes has a characteristic resonance at a lower chemical shift region of 3.2-3.6 ppm. These signature resonances were then used to distinguish the origins of nitrate in the groundwater. It was found that disposal of dairy wastes on croplands is the primary source of nitrate contamination in groundwater underlying the Chino Basin dairy area.

California↗
PubMed2002

Diagnostic thoracoscopic lung biopsy: an outpatient experience.

BACKGROUND: Tissue diagnosis of either interstitial lung disease or indeterminate pulmonary nodules can be obtained by either limited thoracotomy or thoracoscopic lung biopsy. Both procedures traditionally have required hospital admission. We report a series of patients undergoing outpatient thoracoscopic lung biopsy to demonstrate the safety and efficacy of this practice. METHODS: Sixty-two ambulatory patients with a clinical diagnosis of either interstitial lung disease or indeterminate pulmonary nodule(s) underwent thoracoscopic lung biopsy between June 2000 and June 2001. All procedures were performed with double-lumen endotracheal anesthesia and stapled wedge resection. Chest tubes were removed if no air leak was present and if chest radiograph demonstrated no residual pneumothorax. RESULTS: Of 62 patients undergoing thoracoscopic lung biopsy, 45 (72.5%) were discharged home within 8 hours of observation on the day of operation. Fourteen (22.5%) were discharged within 23 hours of their operation. Reasons for 23-hour observation included significant comorbidity (8), pain management (4), postoperative air leak (1), and conversion to muscle-sparing thoracotomy (1). Three (5%) required admission for prolonged air leak (2) or conversion to muscle-sparing thoracotomy (1). Diagnoses were obtained in 61 patients, including neoplasm (25), interstitial lung disease (18), granulomatous disease (7), and other (11). One patient was readmitted for pneumothorax. Patients diagnosed with nonbronchogenic pulmonary metastases were more likely to be discharged on the day of operation. No differences in age, smoking status, or preoperative pulmonary function testing were observed between patients requiring short-stay observation and those discharged immediately after operation. CONCLUSIONS: Outpatient thoracoscopic lung biopsy is safe and effective, and has become our procedure of choice for diagnosis of either interstitial or focal lung disease.

Adult↗
PubMed2002

Standardisation of von Willebrand Factor in therapeutic concentrates: calibration of the 1st International Standard for von Willebrand Factor concentrate (00/514).

An international study involving 26 laboratories assayed two candidate von Willebrand Factor (VWF) concentrates (B and C) for VWF:Antigen (VWF:Ag), VWF:Ristocetin Cofactor (VWF:RCo) and VWF:Collagen binding (VWF:CB) relative to the 4th International Standard Factor VIII/VWF Plasma (4th IS Plasma) (97/586). Estimates of VWF:Ag showed good agreement between different methods, for both candidates, and the overall combined means were 11.01 IU/ml with inter-laboratory variability (GCV) of 10.9% for candidate B and 14.01 IU/ml (GCV 11.8%) for candidate C. Estimates of VWF:RCo showed no significant difference between methods for both candidates and gave overall means of 9.38 IU/ml (GCV 23.7%) for candidate B and 10.19 IU/ml (GCV 24.4%) for candidate C. Prior to the calibration of the candidates for VWF:CB it was necessary to calibrate the 4th IS Plasma relative to local frozen normal plasma pools; there was good agreement between different collagen reagents and an overall mean of 0.83 IU per ampoule (GCV 11.8%) was assigned. In contrast, estimates of VWF:CB in both candidates showed large differences between collagen reagents with inter-laboratory GCV's of 40%. Candidate B (00/514) was established as the 1st International Standard von Willebrand Factor Concentrate by the WHO Expert Committee on Biological Standardisation in November 2001 with assigned values for VWF:Ag (11.0 IU/ampoule) and VWF:RCo (9.4 IU/ampoule). Large inter-laboratory variability of estimates precluded the assignment of a value for VWF:CB.

Calibration↗
PubMed2002

[Modeling transfer and partitioning of potentially toxic pollutants in soil-crop system for human food security].

Human exposure to potential toxic pollutants and the associated health risk is a focus of current environmental and medical studies. However, the transfer and partitioning of the pollutants in the soil-crop systems turns to be a key problem for evaluating the food intake of the pollutants. This paper deals with the methodology and the approach of computer modeling of the soil-crop partitioning of the pollutants under agricultural systems for human food security and the elaboration of guidelines for soil protection. Two major models, crop ecological model and soil environmental chemical model, are discussed respectively. These models may be valuable for the research of agricultural environment protection and the development of guidelines for soil protection in China.

Consumer Product Safety↗