Biomedical subjects

C I Lee

Publications and source records attributed to C I Lee.

At least 19 recordsLinked to original sources

PubMed2005

HIV-1-derived lentiviral vectors and fetal route of administration on transgene biodistribution and expression in rhesus monkeys.

The gene transfer efficiency of lentiviral vectors pseudotyped with vesicular stomatitis virus-glycoprotein (VSV-G) driven by the MND or CMV promoters and expressing the enhanced green fluorescent protein (EGFP) was investigated in fetal rhesus monkeys (Macaca mulatta) (N=21). Fetuses (50+/-10 days gestation; term 165+/-10 days) were injected under ultrasound guidance using an intraperitoneal (i.p.) or intrahepatic (i.h.) approach with a range of 1 x 10(7)-2 x 10(8) infectious particles/fetus. Analysis of transgene biodistribution and expression was performed in multiple tissues at 3-7 months postgene delivery using quantitative techniques. Overall, results indicated the following: (1) i.p. gene transfer at 40 days gestation resulted in a more diffuse distribution of the vector compared to administration at 60 days gestation; (2) vector biodistribution was similar after administration by the i.p. or i.h. routes; and (3) gene expression analysis in transduced tissues showed the presence of mRNA transcripts that correlated with the level of gene transfer. These studies suggest that fetal gene transfer using the i.p. and i.h. routes results in prolonged transduction and expression of the transgene in multiple tissues.

Animals↗

PubMed2005

Heavy metal removal from aqueous solution in sequential fluidized-bed reactors.

In this study, the sequential fluidized bed reactors (FBRs), were used to remove heavy metals including, Cu, Pb, and Ni, from synthetic wastewater. Heavy metals were removed through crystallization of metal carbonate and hydroxide precipitates on the surface of sand grains. The results showed that the influent metal concentration limits in the sequential FBRs were higher than those in the vertical FBRs. The removal efficiency for Cu, Pb, and Ni reached 96%, 93%, and 98% when the influent concentrations were 250 mg l(-1), 130 mg l(-1) and 130 mg l(-1), respectively. The pH value in the effluent of the FBR ranged from 8.7 to 9.1. The amount of metal coated onto the sand surface was determined and it was found that most of the metal ions were collected in the first reactor. The mechanism of heavy metal removal in the sequential FBRs concluded crystallization and filtration.

Carbonates↗

PubMed2002

Development of the Korean versions of WHO Quality of Life scale and WHOQOL-BREF.

The purpose of this study was to develop the Korean version of World Health Organization Quality of Life study assessment instrument (WHOQOL) and WHOQOL-BREF, an abbreviated version of WHOQOL and to identify contributing factors in the quality of life of Koreans. The WHOQOL and WHOQOL-BREF were translated into colloquial Korean according to instructions of the WHOQOL study group. Then the Korean questionnaire was applied to 538 subjects, composed of 171 medical patients and 367 healthy subjects who volunteered to rate the scale. Finally, 486 subjects completed the rating. Collected data were analyzed statistically. The Korean version of WHOQOL and WHOQOL-BREF domain scores demonstrated good test-retest reliability, internal consistency, criterion validity, content validity and discriminant validity. The physical, psychological, social and environmental domains made a significant contribution to explaining the variance in the quality of life while the independence and spiritual domains made a lesser contribution. The domain scores produced by the WHOQOL-BREF correlated highly with the WHOQOL. The physical health domain contributed most in overall quality of life, while the social domain made the least contribution. These results suggest that the Korean version of WHOQOL and WHOQOL-BREF are valid and reliable in the assessment of quality of life and that physical domain is contributing most and social and spiritual factors are contributing least to the quality of life in Koreans.

Adult↗

PubMed2001

Oxygen radical-mediated reduction in basal and agonist-evoked NO release in isolated rat heart.

Oxygen free radicals (OFR) play a primary role in ischemia-reperfusion-mediated vascular dysfunction and this is paralleled by a loss of endothelial nitric oxide synthase (eNOS) activity. The authors tested whether a direct exposure to OFR may affect vascular relaxation by altering nitric oxide (NO) release. Effects of electrolysis(EL)-generated OFR on basal and agonist-evoked NO release were monitored in isolated rat hearts by oxyhemoglobin assay. Electrolysis-induced changes were compared with those obtained after 30 min perfusion with NOS and cyclooxygenase (COX) inhibitors NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) and indomethacin (INDO, 1 m M). Electrolysis-generated hydroxyl radical (.OH) formed by.O2-and H2O2 via the Fenton reaction as revealed by Electron Paramagnetic Resonance (EPR). After EL, basal NO release declined by 60% and coronary perfusion pressure (CPP) increased by approximately 70%. L-NAME/INDO perfusion similarly lowered NO release (-63%) but increased CPP less than EL (56+/-3%P<0.03 v post-EL). In presence of excess substrates and cofactors eNOS activity was not affected by EL. Both acetylcholine (ACh; 1 microM) and bradykinin (BK; 10 n M) had minimal effect in reversing EL-induced vasoconstriction, whereas both partially reversed L -NAME/INDO-mediated constriction. Sodium nitroprusside (SNP, 1 microM) completely reversed L-NAME/INDO constriction and partly countered that after EL (-38+/-2.5, P<0.001). Acetylcholine-evoked NO release was nearly abolished by both treatments whereas BK still elicited partial NO release after eNOS/cyclooxygenase inhibition (P<0.001) but not after EL. In conclusion, OFR severely impair NO-mediated coronary vasorelaxation affecting both basal and agonist-evoked NO release but not eNOS activity. However, EL also significantly blunts NOS/COX-independent vasodilation suggesting alteration of other vasodilatative pathways.

Acetylcholine↗

PubMed2001

Rhesus monkey model for fetal gene transfer: studies with retroviral- based vector systems.

Many life-threatening conditions that can be diagnosed early in gestation may be treatable in utero using gene therapy. In order to determine in utero gene transfer efficiency and safety, studies were conducted with fetal rhesus monkeys as a model for the human. Included in these studies were Moloney murine leukemia virus (MLV)-based amphotropic retrovirus, vesicular stomatitis virus-G (VSV-G) pseudotyped MLV, and a VSV-G pseudotyped HIV-1-based vector, all expressing the enhanced green fluorescent protein (EGFP) as a reporter gene and driven by a cytomegalovirus-immediate early promoter (N = 16). Rhesus monkey fetuses were administered viral vector supernatant preparations by the intraperitoneal (ip) (N = 14) or intrahepatic (ih) (N = 2) routes via ultrasound guidance at 55 +/- 5 days gestation (late first trimester; term 165 +/- 10 days). Fetuses were monitored sonographically, specimens were collected prenatally and postnatally, and tissue harvests were performed at birth or 3 or 6 months postnatal age (3-10 months post-gene transfer). PCR analyses demonstrated that transduced cells were present at approximately 1.2% in peripheral blood mononuclear cells from fetuses administered amphotropic MLV, <0.5% in fetuses receiving MLV/VSV-G, and approximately 4.2% for the lentiviral vector, which decreased to 2% at birth. Hematopoietic progenitors showed that overall (mean of all time points assessed), approximately 25% of the collected colonies were positive for the EGFP transgene with the lentiviral vector, which was significantly greater than results achieved with the MLV-based vector systems (4-9%; P < or = 0.001-0.016). At necropsy, 0.001-10% of the total genomic DNA was positive for EGFP in most tissues for all groups. EGFP-positive fluorescent cells were found in cell suspensions of thymus, liver, spleen, lymph nodes, cerebral cortex, and bone marrow (0.5-6%). Overall, the results of these studies have shown: (1) healthy infants expressing vector sequences up to 10 months post-gene transfer, (2) fetal primate administration of retroviral vectors results in gene transfer to multiple organ systems, (3) the highest level of gene transfer to hematopoietic progenitors was observed with the lentiviral vector system, and (4) there was no evidence of transplacental transfer of vector sequences into the dams. The rhesus monkey is an important preclinical primate model system for exploring gene transfer approaches for future applications in humans.

Animals↗

PubMed2001

Lentiviral vector gene transfer into fetal rhesus monkeys (Macaca mulatta): lung-targeting approaches.

We previously reported the efficiency of gene transfer in fetal monkeys using retroviral vectors and an intraperitoneal (IP) approach. Here, we explored intrapulmonary administration to determine whether gene transfer can be limited to the developing lung. The HIV-1-derived lentiviral vector (VSV-G pseudotyped; 1 x 10(7) infectious particles/fetus), using the enhanced green fluorescent protein (EGFP) as a reporter, was directly injected into fetal lung with ultrasound guidance (n=4; 55 or 70 days gestation; term 165+/-10 days). Fetuses were monitored sonographically, fetal/maternal blood samples collected during gestation, and four of four healthy newborns were delivered at term. All lung lobes were positive for the transgene (< or = 1%) when assessed by PCR, and transgene expression was observed by direct fluorescence microscopy and flow cytometry. The results of this study show the following: (1) successful gene transfer in fetal monkeys using an intrapulmonary approach; (2) less transduction of non-pulmonary tissues with gene transfer at 70 days gestation compared with 55 days gestation or use of an IP approach; (3) that the pulmonary epithelium was EGFP-positive by immunohistochemistry; and (4) no evidence of transplacental transport of vector sequences or antibody responses in the dams. The results of these investigations indicate the efficiency of fetal gene transfer by intrapulmonary delivery, and emphasize the importance of the fetal monkey as a preclinical model system for exploring in utero genetic treatment strategies for pulmonary disorders.

Animals↗

PubMed2001

IGF-II and IGF binding protein (IGFBP-1, IGFBP-3) gene expression in fetal rhesus monkey tissues during the second and third trimesters.

The IGF system is a key modulator of somatic fetal growth. Studies with human fetal tissues have shown a specific spatial and temporal pattern of expression of IGF and IGF binding protein (IGFBP) mRNAs, but have been limited to defined periods during gestation (i.e. 8-20 wk gestation) because of tissue availability. To fully assess the role of these peptides in the primate growth process, a longitudinal study was conducted that focused on the expression of IGF-II and IGFBP-1 and IGFBP-3 genes in the rhesus monkey (Macaca mulatta). Liver, kidney, brain, and lung were collected from rhesus monkey fetuses approximately every 2 wk from 65 (early second trimester) through 150 d gestation (term 165 +/- 10 d) (n = 50), then processed for in situ hybridization using radiolabeled human cDNAs. IGF-II mRNA was abundantly expressed in fetal kidney (maturing glomerulus, supporting mesenchyme, cells of the developing nephrons), liver (hepatocytes), cerebral cortex (choroid plexus, capillaries), and lung (blood vessels, connective tissues, lamina propria, cartilage framework). IGFBP-1 was expressed only in the hepatocytes and IGFBP-3 mRNA was modestly expressed within the kidney (developing nephrons, collecting system mesenchyme), and liver (hepatocytes). These studies have shown that (1) IGF-II, IGFBP-1, and IGFBP-3 are expressed in specific cell types of the fetal monkey indicating a paracrine/autocrine role during development; (2) changes in IGF-II and IGFBP mRNA expression occur with advancing gestation; and (3) fetal monkey tissues express IGF-II and IGFBPs in a similar manner when compared with the human fetus.

Animals↗

PubMed2000

Differential sensitivity to hydroxyl radicals of pre- and postjunctional neurovascular transmission in the isolated canine mesenteric vein.

In some pathophysiological conditions, the first target of reactive oxygen intermediates is the vascular system. Superoxide anions, when generated in the vascular circulation, may then escape into the extracellular space via an anion channel and, following dismutation to hydrogen peroxide (H(2)O(2)), form hydroxyl radicals (HO(*)). In an attempt to understand the role of HO(*) in the regulation of transmission at the sympathetic neurovascular junction, the effect of HO(*) at nerve terminals was examined by measuring the amount of noradrenaline (NA) released from isolated, spirally cut, superfused canine mesenteric vein during basal and electrical stimulation (ES; 5Hz, 2ms, 9V); tension development evoked by ES was also recorded simultaneously. HO(*) was generated from Fenton's reagent (1. 5x10(-4)M H(2)O(2) plus 10(-4)M FeSO(4)); generation of HO(*) from H(2)O(2)/FeSO(4) in the superfusate was monitored by electron spin resonance spectroscopy using the spin-trap 5, 5-dimethyl-1-pyrroline-N-oxide throughout the experimental time course. Exposure to HO(*) of the helical strips produced an irreversible decrease in tension development evoked by ES with no effect on NA release, suggesting that the observed effect is elicited postjunctionally. The susceptibility of the processes of NA-mediated contraction to HO(*) may differ greatly from that of the NA release mechanism at the prejunctional site. Exposure of the strip preparation to HO(*) leads to a substantial stimulation of basal release of NA without affecting ES-evoked NA release, possibly due to enhanced non-exocytotic Ca(2+)-independent release elicited by HO(*). A direct demonstration of this concept was obtained by showing a significant increase in the basal response of NA release in Ca(2+)-free solution. The major conclusion of the present study is that HO(*) can damage NA-mediated contraction of the vascular preparations at the postjunctional site, and may selectively induce a non-exocytotic release of NA from the prejunctional site of sympathetic neurotransmission.

Animals↗

PubMed2000

Regulation of xanthine oxidase by nitric oxide and peroxynitrite.

Xanthine oxidase (XO) is a central mechanism of oxidative injury as occurs following ischemia. During the early period of reperfusion, both nitric oxide (NO(*)) and superoxide (O-*(2)) generation are increased leading to the formation of peroxynitrite (ONOO(-)); however, questions remain regarding the presence and nature of the interactions of NO(*) or ONOO(-) with XO and the role of this process in regulating oxidant generation. Therefore, we determined the dose-dependent effects of NO(*) and ONOO(-) on the O-*(2) generation and enzyme activity of XO, respectively, by EPR spin trapping of O-*(2) using 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide and spectrophotometric assay. ONOO(-) markedly inhibited both O-*(2) generation and XO activity in dose-dependent manner, while NO(*) from NO(*) gas in concentrations up to 200 microM had no effect. Furthermore, we observed that NO(*) donors such as NOR-1 also inhibited O-*(2) generation and XO activity; however, these effects were O-*(2)-dependent and blocked by superoxide dismutase or ONOO(-) scavengers. Finally, we found that ONOO(-) totally abolished the Mo(V) EPR spectrum. These changes were irreversible, suggesting oxidative disruption of the critical molybdenum center of the catalytic site. Thus, ONOO(-) formed in biological systems can feedback and down-regulate XO activity and O-*(2) generation, which in turn may serve to limit further ONOO(-) formation.

Electron Spin Resonance Spectroscopy↗

PubMed1999

Inhibition of skeletal sarcoplasmic reticulum Ca2+-ATPase activity by deferoxamine nitroxide free radical.

Deferoxamine is an inhibitor of iron-dependent free radical reactions. Despite the antioxidant roles, prolonged clinical use of the chelator is far from benign, and paradoxically, deferoxamine has been shown to promote lipid peroxidation. The possible toxicity of the drug's metabolites, such as deferoxamine nitroxide free radical, deserves attention. We, therefore, tested the hypothesis that deferoxamine nitroxide radicals produced as a result of enzymatic one-electron oxidation of deferoxamine by horseradish peroxidase in the presence of H2O2 are capable of inactivating Ca2+-ATPase of skeletal sarcoplasmic reticulum microsomes as a model system with which to explore the effect of the radical on a biological membrane. Ca2+-ATPase activity of sarcoplasmic reticulum was depressed by exposure to Fenton's reagent (H2O2/FeSO4); the observed effect was significantly enhanced by deferoxamine. We found that the Fenton reaction produced hydroxyl radical, as determined by electron spin resonance spectroscopy. The formation of hydroxyl radical was completely inhibited by deferoxamine; instead, under the same experimental conditions (in the presence of sarcoplasmic reticulum vesicles with or without FeSO4 but without spin trap 5, 5-dimethyl-1-pyrroline N-oxide), the spectral shape and hyperfine coupling constants of electron spin resonance signals confirmed to be long-lived deferoxamine radical were obtained. Furthermore, exposure of sarcoplasmic reticulum vesicles to deferoxamine radical formed by horseradish peroxidase via reaction with H2O2 caused an inhibition of the Ca2+-ATPase activity. The findings show that the sarcoplasmic reticulum vesicles can act as peroxidases and suggest that deferoxamine enhances the decreased Ca2+-ATPase activity afforded by H2O2/FeSO4 due to formation of its metabolites, possibly deferoxamine nitroxide free radical.

Animals↗

PubMed1999

Nonparametric estimation of bounded survival functions with censored observations.

Stochastic ordering of survival functions is a useful concept in many areas of statistics, especially in nonparametric and order restricted inferences. In this paper we introduce an algorithm to compute maximum likelihood estimates of survival functions where both upper and lower bounds are given. The algorithm allows censored survival data. In a simulation study, we found that the proposed estimates are more efficient than the unrestricted Kaplan-Meier product limit estimates both with and without censored observations.

Algorithms↗

PubMed1998

Phase I clinical trial: pharmacokinetics of a novel anthracycline, DA-125 and metabolites. Single dose study.

Single dose of DA-125, 20 (n = 3), 40 (n = 3), 60 (n = 3), 80 (n = 6), or 100 (n = 6) mg/m2 body surface area, was administered intravenously in 5 min to 21 patients with various types of cancer as phase I clinical trial. The main side-effects of DA-125 were nausea, vomiting, leukopenia (especially neutropenia), and thrombocytopenia. Among those, hematological side-effects increased with increased doses of DA-125. No patient developed side-effects equal to or higher than grade III up to DA-125 dose of 60 mg/m2. However, at DA-125 dose of 80 mg/m2, 1 out of 3 patients developed grade III leukopenia and grade IV neutropenia. Therefore, 3 additional patients participated taking the dose of 80 mg/m2; no patient developed side-effects equal to or higher than grade III. Hence, DA-125 dose increased to 100 mg/m2. At DA-125 dose of 100 mg/m2, 2 out of 3 patients developed side-effects equal to or higher than grade III and, therefore, 3 additional patients participated taking this dose. Among the 3 additional patients, 1 patient developed both grade III leukopenia and neutropenia. Therefore, further accrual was stopped at this dose (100 mg/m2). The maximally tolerated dose (MTD) of DA-125 was determined to be 100 mg/m2, and the dose-limiting factor for DA-125 was bone marrow suppression. DA-125 dose of 80 mg/m2, 80% of MTD of DA-125, was recommended as the dose for phase II clinical trial. Cardiotoxicity was not observed in any of the 21 patients according to the ECG and RVG. Neither fever, stomatitis, diarrhea, and renal and nervous system toxicity, nor abnormality in blood coagulation was observed in any of the patients, and death or life-threatening side-effects due to DA-125 were also not observed. Antitumor effects of DA-125 were evaluated from the 21 patients; 6 progressive disease, 14 stable disease, and 1 partial response. Pharmacokinetic parameters of M1, such as AUC, t1/2, CL, VSS, and MRT, seemed to be independent of i.v. doses of DA- 125, 20-100 mg/m2 and less than 0.75% of M1 were excreted in 96 h urine when expressed in terms of DA-125 i.v. dose. M2 was the main metabolite of DA-125 among M1-M4 excreted in urine; 10.1 approximately 22.3% of M2 was excreted in 96 h urine when expressed in terms of DA-125 i.v. dose. Bile was collected via the T-tube in 1 additional patient at the dose of 100 mg/m2. Biliary excretion of M1 and M2 was negligible; less than 0.320 and 4.76% of M1 and M2, respectively, were excreted in 96 h bile when expressed in terms of DA-125 i.v. dose.

Adult↗

PubMed1997

DNA analysis by flow cytometry in early gastric cancer.

OBJECTIVES: Flow cytometric analysis of a paraffin-embedded block of tissue provides rapid and accurate means of analyzing the DNA content of a tumor. The aim of this study was to clarify the clinical significance of flow cytometric findings in early gastric cancer(EGC). Thus we conducted this study to investigate whether DNA contents of tumor cells can correlate with known prognostic indices in patients with EGC. METHODS: The flow cytometric DNA analysis was performed with paraffin-embedded specimens from tumors of 107 patients with EGC. Flow cytometric analysis was performed using a FACScan (Becton Dickinson). In constructing the histogram, 30,000 cells were scanned from each section and results were scored. The S-phase fraction was obtained according to the CellFit cell cycle analysis (Becton Dikinson). Frequencies of aneuploidy in tumors with various clinical and pathologic parameters were compared using the chi-square test. Mean SPF/PI valuse were compared by the student t-test. RESULTS: Diploidy pattern was observed in 80 (75%) cases while aneuploidy was seen in 27(25%) cases. Aneuploidy was more frequently detected in tumors with submucosal involvement (32.7%) and lymph node (+) group (30.8%) than in the mucosal tumor (17.3%) and lymph node (-) group (24.5%), but the differences were not significant. Frequency of aneuploidy was not affected by either the histologic type or morphologic classification. On the other hand, high proliferative activities (SPF/PI) significantly correlated with the submucosal tumor invasion (66.7% vs. 45%; p < 0.05) and lymph node metastasis (28.6% vs. 7.5%; p < 0.05). CONCLUSION: Tumor aggressiveness is not directly related to DNA aneuploidy but proliferative activities are responsible for the aggressive nature of early gastric cancer. The results of this study show that DNA analysis by flow cytometry in considered to be one method of determining the biological activity of gastric cancer cells.

Adult↗

PubMed1996

Skeletal sarcoplasmic reticulum dysfunction induced by reactive oxygen intermediates derived from photoactivated rose bengal.

We investigated the role of reactive oxygen intermediates generated from photoactivation of xanthene dye rose bengal on skeletal sarcoplasmic reticulum (SR) function, which plays a major role in the regulation of intracellular Ca++ and thereby in the generation of force. We used SR microsomes of canine masseter muscle as a model system in which to explore the effect of oxidation by determining oxalate-supported Ca++ uptake, Ca++, Mg++-adenosine triphosphatase (Ca++-ATPase) activity and Ca++ permeability of the SR vesicles. Skeletal SR vesicles exposed to rose bengal (50 nM) illuminated at 560 nm resulted in significant inhibition of Ca++ uptake velocity and Ca++-ATPase activity and in stimulation of Ca++ permeability. The observed effect afforded by illuminated rose bengal was dependent on intensity of light. Most reactive oxygen species scavengers tested had no protective effect; histidine (a powerful quenching agent for singlet oxygen), however, significantly protected the effect of illuminated rose bengal on Ca++ uptake velocity and Ca++-ATPase activity. The illumination of rose bengal also caused histidine-inhibitable loss of total sulfhydryl groups of SR. The increased Ca++ permeability elicited by illuminated rose bengal was blunted by a cocktail of histidine-catalase, but not by histidine alone. Generation of reactive oxygen species (singlet oxygen, superoxide and hydroxyl radical) from photoactivation of rose bengal was studied by electron spin resonance spectroscopy by use of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2,2,6,6-tetramethylpiperidine (TEMP). We found that illumination of rose bengal formed a 1:2:2:1 quartet, characteristic of the hydroxyl radical-DMPO spin adduct, which was effectively blunted by hydroxyl radical scavenger, dimethyl sulfoxide, and by superoxide scavenger, superoxide dismutase. The results of electron spin resonance study also showed that singlet oxygen was produced by photoactivation of rose bengal was detected as singlet oxygen-TEMP product (TEMPO); 2,2,6,6-tetramethylpiperidine-N-oxyl). The formation of TEMPO signal was strongly inhibited by histidine. Similarly, we could detect hydrogen peroxide production from illuminated rose bengal. It is suggested that photoactivation of rose bengal generated singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radical, and the data obtained from the present study indicate that singlet oxygen, rather than superoxide, hydrogen peroxide and hydroxyl radical, to be the active agent in the Ca++ transport system of SR; the observed effect of singlet oxygen may be due to sulfhydryl group oxidation. Our results are also consistent with the view that singlet oxygen does not appear to be an exclusive species that increases Ca++ permeability of SR vesicles, but the increased Ca++ permeability may be caused in part by hydrogen peroxide as well as singlet oxygen.

Animals↗

PubMed1993

Metastatic involvement of the stomach secondary to lung carcinoma.

Blood-borne metastatic involvement of the stomach by cancer is a rare entity. According to the number of reports in the literature, the most common tumors that spread to the stomach through the blood stream are malignant melanoma, breast carcinoma and lung carcinoma. Recently, two cases of metastatic involvement of the stomach secondary to lung carcinoma were diagnosed by gastroscopy. The first patient was a 66-year-old man who had primary lung carcinoma with multiple bone and subcutaneous metastases. Gastroscopy showed multiple submucosal tumors with central umbilications in the fundus and in the upper body of the stomach. Pathologic examination revealed massive submucosal infiltration and conical shaped and scanty deep mucosal infiltration of undifferentiated small cell carcinoma suggestive of metastatic involvement. The second patient was a 68-year-old man who had primary lung carcinoma with brain metastasis. Gastroscopy showed a large fungating mass in the greater curvature side of the stomach. Pathologic examination revealed poorly differentiated squamous cell carcinoma. We report the two cases of metastatic gastric cancer from lung carcinoma with the literature review.

Aged↗

PubMed1993

Immunohistochemical detection of p53 protein, c-erbB-2 protein, epidermal growth factor receptor protein and proliferating cell nuclear antigen in gastric carcinoma.

There is increasing evidence that genes involved in normal cell growth and differentiation (oncogenes) or genes that encode for growth factors are important in determining the development and biologic aggressiveness of gastric carcinoma. This study was undertaken to define the prognostic value of the overexpression of p53 protein, c-erbB-2 protein, EGFr protein and PCNA in gastric carcinomas. Using monoclonal antibodies, immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections from 84 primary gastric carcinomas. Overall, 34% of gastric carcinomas had nuclear-staining for p53 protein, 34% of carcinomas membrane staining for the c-erbB-2 and 74% of carcinomas membrane and cytoplasmic staining for EGFr, showing distribution in a heterogeneous fashion. PCNA was expressed as Grade 2 and 3 in 75% of patients with gastric carcinomas. Both c-erbB-2 and p53 staining was significantly associated with high grade expression of PCNA. p53 staining tended to be associated with positive nodal status and metastasis, and c-erbB-2 staining with positive nodal status only. Multivariate analysis using the Cox model showed that overexpression of p53 protein, c-erbB-2 protein and PCNA was not an independent prognostic variable in gastric carcinoma. These results suggest that expressions of p53 and c-erbB-2 protein are heterogeneous and that p53 and c-erbB-2 overexpressions are significantly associated with high proliferative activity in gastric carcinoma.

Antigens, Neoplasm↗

PubMed1991

[Clinical and cellular biologic diagnosis of Cockayne syndrome: a case report].

We report a case of Cockayne syndrome. A 6-year-old boy presented with a progeroid face, dwarfism, psychomotor retardation, skin photosensitivity and retinal pigmented degeneration. Neurological study disclosed slowed nerve conduction velocities and a brain CT showed calcification in the basal ganglia. Auditory brain stem evoked potential showed prolonged interpeak latency of wave I to wave V. Laboratory evaluation revealed mild liver dysfunction and peripheral eosinophilia. Fibroblast cultures from the patient and his family were exposed to ultraviolet (UV) light of 254 nm, ranging from 1 to 10 J/m2. Under 1 J/m2 irradiation, the surviving fraction of the fibroblasts from the patient, his mother, and a control subject were 40%, 50%, 90% respectively. If the fibroblasts of these subjects were exposed to 2 J/m2 and 3 J/m2 irradiation, the surviving fraction changed to 10%, 22%, 80% and 1.5%, 9%, 68%, respectively. However, fibroblasts from his sister and father showed the same surviving fraction as the control. The study showed that fibroblasts from the patient and his mother were extremely sensitive to UV light irradiation. We also study the concentration of the pyrimidine dimer of DNA in the patient and the control subject. Pyrimidine dimer showed no difference between the patient and the normal subject before and after 24-hour UV irradiation. These results suggest that the sensitivity to UV of Cockayne fibroblasts may be due to a ligase deficiency or to a replicon initiation disturbance in Cockayne cells.

Cell Survival↗

PubMed1981

Use of human prostate-specific antigen in monitoring prostate cancer.

The newly reported human prostate-specific antigen (PA) is a specific histiotypic product of human prostate. With the use of a sensitive enzyme immunoassay, the circulating PA in prostatic cancer patients has been evaluated clinically. In 96 patients with advanced stage of disease (D2) and receiving chemotherapies, the pretreatment serum PA levels were found to be of prognostic value with regard to the patient survival. Ten patients with metastatic prostate cancer were monitored for more than 32 weeks by 183 serial PA values and were found generally to respond to the treatment. Additionally, in another group of 32 patients who underwent curative therapies for localized prostate cancer, 161 serum samples were evaluated during periods of 12 to 114 weeks (average 56 weeks). Of these patients, five developed metastases during follow-up, and all were shown to exhibit increasingly elevated PA values, either corresponding to or preceding the clinical diagnosis of disease recurrence. These results suggest that PA is a new marker with potential value to merit further clinical study.

Antigens, Neoplasm↗