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N Choi

Publications and source records attributed to N Choi.

At least 19 recordsLinked to original sources
PubMed2001

Atomic force microscopy of RecA--DNA complexes using a carbon nanotube tip.

We report high resolution images of RecA-double stranded (ds) DNA complexes obtained by atomic force microscopy (AFM). When a carbon nanotube (CNT) tip was used, AFM images visualized the 10-nm pitch of RecA-dsDNA complexes and RecA filaments as three-dimensional surface topography without reconstruction analysis. The depth of the notch between two pitches was less than 1 nm. When adsorbed on a soft surface covered with proteins, naked DNA, RecA monomers, RecA hexamers, and short RecA filaments were all clearly resolved in one image. The high resolution images with a CNT tip provided valuable information on the initiation process of RecA-dsDNA complex formation.

DNA↗
PubMed2001

Predictive factors in radiotherapy for non-small cell lung cancer: present status.

PURPOSE: To evaluate the predictive factors for radiation response in non-small cell lung cancer (NSCLC) and the role of such factors in guiding high dose radiation therapy. METHODS: The first International Workshop on Prognostic and Predictive Factors in Lung Cancer was organized by the Hellenic Cooperative Oncology Group and held in Athens, Greece under the auspices of the International Association for the Study of Lung Cancer. Presentations at this meeting provided the outline of this report, which has also been supplemented with available data from the current literature. RESULTS: The predictive factors for both the natural history and the therapy outcome of NSCLC are grouped as follows: (1) tumor related factors (anatomic factors); the extent of tumor (tumor stage) is one of most important prognostic factors affecting the therapy outcome. Tumor size (T stage), anatomical structures involved (T4 vs. T3 lesion), and the presence of regional lymph node metastasis have a significant impact on both prognosis and response to appropriate therapy; (2) host-related factors (clinical factors) that are important in therapy response include performance status, weight loss of more than 10% of body weight in the previous 6 months, and associated co-morbidities, i.e. pulmonary and cardiac diseases; (3) technical factors of radiation therapy which play a decisive role in successful outcome. The target volume should be defined accurately using modern imaging studies. The radiation dose fractionation schedule, in terms of the dose intensity and total dose, should be high enough to provide local tumor control in the majority of patients. Three-dimensional (3-D) conformal planning is an essential tool in dose escalation studies to determine the maximum tolerated dose of radiation; (4) biological/radiobiological/metabolic factors. Biologic markers resulting from genetic lesions in lung cancer are grouped as follows: (a) oncogene amplification and overexpression (aberrant gene expression) and mutated tumor suppressor genes -- ras gene, myc gene, HER-2/neu and survivin gene, p53 and mutated beta-tubulin gene; (b) tumor biologic/radiobiologic factors -- tumor cell proliferation kinetics, hypoxia, intrinsic cellular radiosensitivity, gamma factor, and DNA content; (c) enzymes and hormones: neuron-specific enolase, serum lactate dehydrogenase, and enhanced glucose metabolic rate supported by increased glucose transporter protein. The surviving fraction of tumor cells at 2.0 Gy of radiation (SF2) as a measure of intrinsic tumor cell radiosensitivity, potential doubling time (T(Pot)) as a measure of the rate of tumor cell proliferation and gamma factor representing the slope of the survival curve at 50% survival rate are being investigated as potential predictors for therapy response. Enhanced glucose utilization, a hallmark of malignant transformation, is being studied as a potential monitor for therapy response by using PET-FDG. CONCLUSION: Current data indicate that there is a dose-response relationship between radiation dose and local tumor control, and also between local tumor control and survival in stage III NSCLC. Therapeutic factors, i.e. total radiation dose, fractionation schedule and dose intensity, and use of 3-D conformal radiation to secure the optimum therapeutic ratio are important for improved local tumor control and survival. Future research should be directed towards radiation dose escalation using 3-D conformal therapy to determine the maximum tolerated dose (MTD) of radiation in chemo-radiotherapy, and the use of this MTD for improved local tumor control and survival. Radiobiological, molecular, and metabolic markers may have potential for monitoring tumor response and optimizing radiation therapy.

Biomarkers, Tumor↗
PubMed1999

The First Bismuth Phosphide Complex:

Thermally unstable crystals of the title compound-the first bismuth phosphide complex to be structurally characterized (see picture)-are obtained by the reaction of [Bi(NMe(2))(3)] with [tBuPHLi] (1:3) in THF/hexane. Berry pseudorotation of the pseudo-trigonal-bipyramidal [{(tBuP)(3)}(2)Bi](-) ion is prevented for steric reasons.

Journal Article↗
PubMed1998

Low-temperature synthesis of zintl compounds with a single-source molecular precursor

Thermolysis of the heterobimetallic phosphinidene complex [Sb(PCy)3]2- Li6.6HNMe2 (Cy = C6H11) at 303 to 313 kelvin gives Zintl compounds containing (Sb7)3- anions. The complex thus constitutes a stable molecular single-source precursor to Zintl compounds and provides a potential low-temperature route to photoactive alkali metal antimonates. The new chemical reaction involved, which is driven thermodynamically by the formation of P-P bonds, has implications in the low-temperature synthesis of other technologically important materials (such as gallium arsenide).

Journal Article↗
PubMed1998

Dynamic T1-weighted magnetic resonance imaging and positron emission tomography in patients with lung cancer: correlating vascular physiology with glucose metabolism.

The management of primary lung cancer relies on sophisticated imaging methods to assist in the diagnosis, staging, and evaluation of tumor regression during treatment. The information provided is generally anatomical in nature, except for that provided by positron emission tomography with [18F]fluorodeoxyglucose, a modality that yields physiological data that have been shown to be useful in identifying neoplasia, based on an elevated glucose metabolic rate. Because the metabolism of malignant tissue depends intimately on neovascularization to provide oxygen and glucose in sufficient quantities to allow tumor growth, the characterization of tumor vascular physiology could be an important tool for assessing and predicting the likely effectiveness of treatment. Our goal was to show the feasibility and practical value of parameters of tumor vascular physiology obtained using dynamic T1-weighted magnetic resonance imaging (MRI), to correlate them with glucose metabolism and to demonstrate changes in these parameters during and after treatment in patients with lung cancer. Parameters of vascular physiology [permeability-surface area (PS) product and extracellular contrast agent distribution volume] and glucose metabolism were assessed in 14 patients with lung cancer. Glucose metabolism was measured by using [18F]fluorodeoxyglucose-positron emission tomography. Vascular physiology was assessed by dynamic T1-weighted, contrast-enhanced MRI. The mean PS product in tumor was 0.0015 +/- 0.0002 s(-1) (n = 13) before, 0.0023 +/- 0.0003 s(-1) (n = 3, P = 0.053) midway through, and 0.00075 +/- 0.0002 s(-1) (n = 5, P < 0.03) 2 weeks after treatment. Values for the extracellular contrast distribution space were 0.321 +/- 0.03 before, 0.289 +/- 0.02 midway through, and 0.195 +/- 0.02 (P < 0.01) 2 weeks after therapy. The glucose metabolic rate was significantly correlated with the PS product (P < 0.01) but not with the extracellular contrast distribution space. Our results demonstrate that tumor PS product correlates with glucose metabolism, that chemo- and radiotherapy induce observable and quantifiable changes in these parameters, and that such changes can be measured by in vivo dynamic MRI. Quantitative dynamic T1-weighted MRI of tumor vascular physiology may have a useful role in the clinical management of lung cancer.

Aged↗
PubMed1997

5-HT1A receptor mRNA expressions differ in the embryonic spinal cord of male and female rats.

During critical periods of development, the effects of testosterone (T) on promoting androgenization of the central nervous system (CNS) are reflected not only by behavior, morphology, and hormone secretion but also by gene expression. The mechanisms involved in sexual differentiation of the CNS, however, remain incompletely defined. The current set of experiments examined with in situ hybridization the dimorphism in 5-HT1A receptor mRNA expression in the embryonic rat spinal cord and the possible role of T in the dimorphism. We found sex-related differences in expression of 5-HT1A mRNA in the spinal cord, which were altered by a single injection of T. The results suggest that this gonadal steroid is responsible for the sexual dimorphism in 5-HT1A mRNA expression occurring during the critical period.

Animals↗
PubMed1996

Assessment of preoperative accelerated radiotherapy and chemotherapy in stage IIIA (N2) non-small-cell lung cancer.

Forty patients with N2 non-small-cell lung cancer (stage IIIA), as determined by mediastinoscopy, were entered into a preoperative neoadjuvant study of chemotherapy (platinum, 5-fluorouracil, vinblastine) and accelerated radiotherapy (150 cGy twice per day for 7 days) for two cycles. Surgical resection was then performed and followed up with an additional cycle of chemotherapy and radiotherapy. All patients completed preoperative therapy. A major clinical response was seen in 87% of patients. Thirty-five patients underwent resection (one preoperative death, one refused operation, one had deterioration of pulmonary function, and two had pleural metastases). Operative mortality rate was 5.7% (2/35). Sixty percent of patients had no complications. Major complications included pulmonary emboli (three), pneumonia (two), and myocardial infarction (one). Down-staging was seen in 46% of patients, with two patients (5.7%) having no evidence of tumor in the specimen, five patients having sterilization of all lymph nodes, and nine patients having sterilization of mediastinal nodes but positive N1 nodes. Median survival of 40 patients was 28 months, with a projected 5-year survival of 43%. Patients with downstaged disease had statistically significant improved survival compared with patients whose disease was not downstaged.

Antineoplastic Agents↗
PubMed1996

Cell kinetic study of thymic epithelial tumors using PCNA (PC10) and Ki-67 (MIB-1) antibodies.

We performed an immunohistochemical cell kinetic study with monoclonal antibodies to proliferating cell nuclear antigen (PCNA)-PC10-and Ki-67-MIB-1-on 62 thymic epithelial tumors, to evaluate whether there is correlation between the proliferation indices of the neoplastic epithelial cells and histological subtype, stage, and risk of relapse. The 62 cases of thymic epithelial tumors were classified as medullary thymoma (4 cases), composite (mixed) thymoma (17 cases), organoid thymoma (predominantly cortical) (11 cases), cortical thymoma (10 cases), well-differentiated thymic carcinoma (18 cases), and poorly differentiated thymic carcinoma (2 cases). Labeling indices were expressed as percentage of epithelial cells with positive nuclear immunostaining by random counting of 1,000 epithelial tumor cells, using an oil immersion 100 x objective. PCNA labeling indices were consistently higher than those of Ki-67, and they correlated with each other. Well-differentiated thymic carcinoma showed higher labeling indices (3.11% +/- 3.53%) by Ki-67 antibody compared with the medullary type (0.60% +/- 0.07%) (P < .05) but there were no statistically significant differences between the other histological subtypes. Stage IV cases showed higher PCNA labeling indices (PCNA: 11.07% +/- 7.35%, Ki-67: 6.86% +/- 5.87%) than cases of the other stages (P < .05), but there were no statistically significant differences in either labeling index between the other stages. The number of patients who relapsed was too small to permit meaningful correlation between labeling indices and relapse. Our results indicate that the differences in biological behavior of the different histological subtypes of thymic epithelial tumors may be in part explained by differences in tumor growth fraction. Analysis of a larger group of patients will be required to determine whether proliferation fraction as determined by this method can be used to predict outcome in individual cases.

Adult↗
PubMed1994

Thymoma. Histologic subclassification is an independent prognostic factor.

BACKGROUND: Several histologic classifications of thymomas have been proposed, and attempts have been made to correlate the different histologic subtypes to clinical behavior and prognosis. Recently, Marino and Müller-Hermelink and Kirchner et al. proposed a new morphologic classification of thymomas based on the resemblance of the neoplastic cells to subtypes of the normal thymic epithelial cells. In this classification, six categories of thymic epithelial tumors are recognized. They define four categories of thymoma: medullary, mixed, organoid (predominantly cortical), and cortical, and two subgroups of thymic carcinomas: well differentiated thymic carcinoma and high grade carcinomas. METHODS: The authors studied 116 patients with thymic epithelial tumors classified according to the proposals of Marino and Müller-Hermelink and Kirchner et al. to assess the effect of histologic classification and other factors (stage, size of tumor, lymphoid hyperplasia, myasthenia gravis, age, sex, and treatment) on survival, and freedom from relapse. RESULTS: Eight cases (7%) were medullary, 32 cases (28%) mixed, 20 cases (17%) organoid (predominantly cortical), 21 cases (18%) cortical, 29 cases (25%) well differentiated carcinoma (WDTC), two cases (2%) high grade carcinoma, and four cases (3%) unclassifiable. Fifty-two patients were in stage I, 32 stage II (16 IIA, 16 IIB), 28 stage III, and four Stage IVA. Only stage (P = 0.0001; hazard ratio = 5.36) and histology (P = 0.0019; hazard ratio = 8.010) were significant in predicting recurrence. Histology was highly correlated with stage, but by multivariate analysis was an independent factor in predicting relapse (P = 0.0281; hazard ratio = 5.92). None of the medullary or mixed thymomas recurred, even though 30% were invasive. Patients with WDTC recurred more often and earlier than patients with organoid and cortical thymoma (log rank, P = 0.0001). The actuarial freedom from relapse for patients with WDTC was 58% at 5 years and 46% at 10 years compared with 100% for other subtypes. Both advanced stage (III and IV) and the WDTC histologic subtype significantly increased the risk of death from thymoma (log rank, P = 0.0001). The actuarial survival of patients with WDTC was 80% at 5 years and 54% at 10 years, whereas that of patients with the other subtypes was 100% at 5 and 10 years. Five of seven relapses and six of seven deaths from thymoma occurred in patients with WDTC. In Stage II patients, one of 16 minimally invasive (Stage IIA) tumors recurred, compared with 3 of 16 grossly invasive (Stage IIB) tumors, indicating that microscopic assessment of invasion is important in staging. CONCLUSIONS: The histologic classification of Marino and Müller-Hermelink has prognostic significance, independent of tumor stage. Medullary and mixed thymomas were benign tumors with no risk of recurrence, even when capsular invasion was present. Organoid and cortical thymoma showed intermediate invasiveness and a low, but significant, risk of late relapse, even with minimal invasion. WDTC were always invasive and had a significantly increased risk of relapse and death, even for Stage II patients. Adjuvant therapy appears unnecessary for medullary and mixed thymomas, even when invasive.

Adolescent↗
PubMed1991

Gastrin-releasing peptide gene expression in small cell and large cell undifferentiated lung carcinomas.

Gastrin-releasing peptide (GRP; mammalian bombesin) is present in the neuroendocrine cells of human fetal lung and in small cell lung carcinomas (SCLCs), where it may act as a growth factor. Considering the potential importance of GRP as a tumor marker, we have conducted a retrospective immunohistochemical analysis of 176 lung tumors for markers of GRP gene expression, as well as several other markers of neuroendocrine cell differentiation: chromogranin A, neuron-specific enolase, and calcitonin. The majority of carcinoids contained mature GRP, in contrast to only a minority of SCLCs and large cell lung carcinomas (LCLCs). However, a majority of SCLCs and LCLCs contained proGRP immunoreactivity. In situ hybridization did not add any information beyond what was obtained using proGRP antisera. In spite of sharing these neuroendocrine cell markers, SCLCs are associated with a graver prognosis than LCLCs. No prognostic significance was associated with immunostaining for GRP or several other markers of neuroendocrine cell differentiation.

Adult↗
PubMed1987

A phase II trial of cyclophosphamide, etoposide, and cisplatin with combined chest and brain radiotherapy in limited small-cell lung cancer: a Cancer and Leukemia Group B Study.

Limited-extent small-cell lung carcinoma (SCLC) remains a therapeutic problem with little improvement in complete response (CR) rates and long-term survival in the past 5 years. From June 1984 through January 1985, 56 patients with limited-extent SCLC were enrolled in a Cancer and Leukemia Group B (CALGB) phase II study using five cycles of cyclophosphamide (500 mg/m2 intravenously [IV] day 1), etoposide (80 mg/m2 IV days 1 to 3), and cisplatin (33 mg/m2 IV days 1 to 3) administered at 3-week intervals (CEP), with radiation therapy (50 Gy to chest and 30 Gy to brain) administered concomitant with cycles 4 and 5, followed by three cycles of cyclophosphamide (500 mg/m2 IV day 1), etoposide (80 mg/m2 IV days 1 to 3), and doxorubicin (50 mg/m2 IV day 1). Of 49 patients evaluable for response, the overall response rate was 88%, with 57% CRs. The median overall survival was 14 months; the median duration of CR was 10 months, and nine CRs remain disease free at a median follow-up of 23 months. Toxicity was significant: 56% patients experienced WBC less than 1,000 microL, 32% platelets less than 25,000 microL and 10% hemoglobin less than 7 g/dL. There was one treatment-related septic death. These results are as good as the best previous CALGB study of SCLC, despite a reduction in duration of treatment from 18 to 5 months. We are currently using a variant of this multimodality treatment approach as our standard management for patients with limited-extent SCLC.

Adult↗