PubMed Health⌕ Search

Biomedical subjects

E Cheng

Publications and source records attributed to E Cheng.

At least 73 records · Page 4Linked to original sources

Flow cytometry as a predictive indicator in patients with operable gastric cancer.

Adenocarcinoma of the proximal portion of the stomach (gastroesophageal [GE] junction and cardia) is increasing in incidence. The inferior survival of patients with GE-cardia lesions as compared with patients with tumors located in the body and antrum has been attributed to anatomic features. To determine if a biological difference could explain the varying prognosis, flow cytometric studies were performed prospectively in 50 patients with operable gastric cancer and analyzed for association with site, histology, gender, age, stage, and disease-free survival. DNA aneuploidy significantly correlated with tumor location: 96% of GE-cardia carcinomas were aneuploid as compared with 48% of body-antrum tumors (P = .0008). Nodal involvement was more common in aneuploid tumors (P = .0548), and women were more likely to have diploid tumors than were men (P = .0233). The median disease-free survival for patients with diploid tumors was 18.5 months as compared with 5.4 months for patients with aneuploid carcinomas (P = .076). Furthermore, within the body-antrum of the stomach, patients with diploid tumors had a significantly better disease-free survival than did those with aneuploid tumors from the same site (18.4 v 4.7 months, P = .0185). These results indicate there is a difference in the DNA content of gastric tumors located in different sites within the stomach and that DNA content correlates with prognosis.

Adenocarcinoma↗

A phase II trial of streptozotocin and adriamycin in advanced APUD tumors.

Thirty-three patients with advanced carcinoid tumors, islet cell carcinomas, or medullary carcinomas of the thyroid were entered into a phase II trial combining streptozotocin (STZ) and Adriamycin. Thirty-one patients are evaluable for response, and 29 are evaluable for survival. Six (19%) patients achieved objective partial responses (95% confidence limits: 5.4-33). The median duration of response for partial responders was 282 days. The median survival for responders and nonresponders was 16.2 months and 7.8 months, respectively, with an overall median survival of 10.9 months. At 10.9 months median follow-up, 4 (14%) of 29 patients are surviving. Toxicity was mild, except that nausea or vomiting occurred in 25 of 31 patients evaluable for toxicity. With this dose and schedule of administration, STZ and Adriamycin produce modest response rates with objective palliation of disease in patients with advanced amine precursor uptake and decarboxylation (APUD) tumors.

Adenoma, Islet Cell↗

Aging-associated changes in murine intestinal immunoglobulin A and M secretions.

The aging effect on the quantity of intestinal IgA and IgM class-specific immunoglobulins secreted and the quality of intraluminal intestinal IgA was studied in 5- to 6-month-old and 24- to 28-month-old male BALB/c mice. The level of IgA increased in the intestinal juice from the aged mice, while the IgM level remained unchanged. These alterations were similar to those found in serum, but the effect of age on serum IgA was profound, almost a threefold increase, in contrast to an increase of just under 35% in intestinal secretions. The ratio of dimeric to total IgA in the small intestine decreased in the older mice, though that of serum was unchanged. In contrast, the total amounts of dimeric IgA in the small intestinal lavage fluid did not change between the two age groups, while the dimeric IgA in serum in older mice were 4.5 times as high as those of young mice. The binding of purified intestinal dimeric IgA to antigens from normal habitant enteric bacteria (gamma streptococci and Enterobacter agglomerans) declined in the old mice. In the immunochemical studies, using SDS-PAGE and isoelectric focusing, the purified intestinal IgA from the young and old mice showed no major differences. Thus, the findings in aged small intestinal perfusates that the increased content of intraluminal IgA is due to an increased monomeric IgA, but not to a reduced dimeric IgA, which remains unchanged, and that the binding capacity of the dimeric IgA to the bacterial antigens is diminished, suggest that the level of the natural secretory IgA antibody is decreased. These altered quantitative and functional features of intraluminal intestinal IgA observed in the aged mice appear to be due to the complex heterogeneous effects of senescence on gut-associated lymphoid tissues, and may contribute to age-related impairment in gut humoral immune function.

Aging↗

Thermolysin and alpha-chymotrypsin mediated synthesis of tripeptides containing proline.

The tripeptides Z-Pro-Leu-Gly-OEt, Z-Pro-Leu-Gly-NH2 and Z-Pro-Leu-Gly-OBzl were synthesized by thermolysin and alpha-chymotrypsin catalysis. The optimum conditions for the couplings between Z-Pro-OH and H-Leu-OEt or H-Leu-Gly-OEt catalysed by thermolysin were determined by a systematic study involving analysis of pH effect, ammonium sulfate concentration, reaction time, enzyme concentration, and relative proportion of the carboxyl and amine components. The best yield obtained for Z-Pro-Leu-OEt was 77% and for Z-Pro-Leu-Gly-OEt, 100%. Z-Pro-Leu-OEt was coupled to H-Gly-OEt, H-Gly-NH2 and H-Gly-OBzl. The best conditions to obtain Z-Pro-Leu-Gly-OEt and Z-Pro-Leu-Gly-NH2 were determined by the study of some factors that affect the reaction yield, such as organic solvent presence, substrate ratio and aqueous and organic solvent ratio. The yield obtained under optimum synthesis conditions was 55% for Z-Pro-Leu-Gly-OEt and 61% for Z-Pro-Leu-Gly-NH2. Z-Pro-Leu-Gly-OBzl was synthesized with 42% yield.

Chymotrypsin↗

Cell calcium levels of normal and cystic fibrosis nasal epithelium.

To determine whether epithelial ion transport abnormalities in cystic fibrosis (CF) might reflect abnormal regulation of intracellular Ca2+ levels, cytosolic free calcium (Cai2+) was measured using fura-2 or quin2 in suspensions of normal or CF nasal epithelial cells derived from primary cell culture. The basal Cai2+ level measured with fura-2 in CF nasal epithelia was 155 +/- 9 nM (n = 5), a value not significantly different from normal nasal epithelia (143 +/- 16 nM, n = 5). Total cell calcium was measured by atomic absorption spectroscopy and no differences were observed between CF (6.3 +/- 0.5 nmol/mg protein; n = 3) and normal (6.2 +/- 1.2 nmol/mg protein; n = 3) nasal epithelial cells. Placing Na+ loaded cells in a low (10 mM) extracellular Na+ solution resulted in a rapid increase in Cai2+ consistent with Ca2+ uptake via a plasmalemmal Na+-Ca2+ exchanger. The level of Cai2+ achieved by this low Na+ maneuver was not significantly different in CF cells compared to normal cells. Neither isoproterenol (10(-5) M) nor forskolin (10(-6) M) had any effect on Cai2+ in normal or CF nasal epithelial cells. Thus, it appears that differences in cell Cai2+, as measured by fluorescent chelators in suspensions of cultured cells, do not account for the abnormalities in basal or isoproterenol stimulated ion transport in CF tissues.

Adolescent↗

Maternal serum alpha-fetoprotein and fetal trisomy-21 in women 35 years and older: implications for alpha-fetoprotein screening programs.

A retrospective study of 3,411 women who underwent midtrimester amniocentesis for fetal chromosome analysis between June 1979 and August 1984 was performed to evaluate an association between low maternal serum alpha-fetoprotein (AFP) concentrations and Down syndrome (DS) pregnancies. A total of 71 pregnancies was found with abnormal fetal chromosomes; of these, 26 cases were trisomy-21 and 10 cases were trisomy-18. The maternal serum AFP in women with DS fetuses was relatively lower than levels in women with fetuses that had normal chromosomes. In addition, the AFP concentrations in amniotic fluid were decreased in cases involving DS fetuses. We have estimated the risks for DS pregnancy at all maternal ages and most serum AFP concentrations. Using these calculations, genetic counselors will be able to provide more accurate risk estimates for trisomy-21 following maternal serum AFP testing.

Adult↗

Evaluation of new anticancer agents against human pancreatic carcinomas in nude mice.

Heterotransplantation of human cancers in nude mice has provided an in vivo model for studying the biologic characteristics of human tumors, particularly their response to chemotherapy. In an effort to identify cytotoxic agents effective against pancreatic carcinoma, this model was used to evaluate the efficacy of three new anticancer agents--menogarol, 4'-epirubicin, and taxol--against two human transplanted pancreatic tumors. Relative area (tumor length X width) differed significantly between menogarol-treated and control groups (p = 0.034). A marked response was also observed in the tumors to 4'-epirubicin (p = 0.01). Taxol was ineffective in controlling tumor growth; by the fourth week, the size of treated tumors was similar to that of the control group (p = 0.55). No toxicity was observed in either the menogarol- or taxol-treated animals. Animals bearing the P2 tumor, and treated with 4' epirubicin displayed severe toxicity by day 18 with death by day 21 in most animals. For the second tumor, Capan-1, relative area differed significantly between the menogarol-treated and the control group (p = 0.003). In animals given 4'-epirubicin, a smaller difference was observed when comparing the relative areas (p = 0.09). Animals treated with taxol again showed no difference in the tumors when compared with controls (p = 1.0). The use of the nude mouse system has evolved so that tumor-oriented trials are now feasible with the hope of clinical applicability. This study illustrates that at least two agents--menogarol and 4'-epirubicin--may have some antitumor activity against pancreatic carcinoma in this system.

Adult↗

Phase II trial of etoposide in APUD tumors.

Thirty-three patients with advanced, metastatic APUD tumors (islet cell, carcinoid, or medullary carcinomas of the thyroid) were treated with etoposide as a single agent. Of 29 evaluable patients, four (14%) had partial responses (95% confidence limits, 1%-26%). Toxic effects seen were those previously reported for etoposide as a single agent. Etoposide has activity in APUD tumors; further studies with this agent are indicated.

Adenoma, Islet Cell↗

Chloride uptake into cultured airway epithelial cells from cystic fibrosis patients and normal individuals.

The chloride permeability of airway and sweat ductal epithelium of cystic fibrosis (CF) patients is decreased. This abnormality could represent an intrinsic characteristic of the epithelial cell or the response to a tonic extrinsic stimulus, in vivo. We cultured airway epithelial cells derived from CF and non-CF individuals under identical conditions that were free from donor-specific factors. Differences in the characteristics of cells that multiplied under these circumstances are unlikely to reflect the effects of extrinsic modulation present in the host. After 8-12 days in culture, the cells of CF and non-CF patients were similar in morphology and intracellular electrolyte content, but the CF cultures took up chloride at a reduced rate. The difference could not be attributed to a higher intracellular potential in CF cells or to the presence of a stilbene anion-sensitive chloride-chloride exchange in non-CF cells. We conclude that epithelial cells from CF patients grown in the absence of extracellular factors of the host express reduced cellular chloride permeability, a defect similar to that found in vivo and in freshly excised nasal epithelium.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Growth and differentiation of human nasal epithelial cells in culture. Serum-free, hormone-supplemented medium and proteoglycan synthesis.

Ham's F12 medium supplemented with insulin (Ins), transferrin (Tf), epidermal growth factor (EGF), hydrocortisone (HC), T3, cholera toxin (CT), and bovine hypothalamus extract (BHE) was developed for in vitro growth of human nasal epithelial (HNE) cells. The HNE cells were dissociated from freshly excised nasal polyps or turbinates with protease. Colony-forming efficiency of primary HNE cells was approximately 5%. Growth studies showed Ins, BHE, and CT were essential for growth; HC, EGF, Tf, and T3 were also stimulatory for growth. The growth rate in this serum-free, hormone-supplemented medium was 24 h per population doubling. Up to 20 population doublings and 3 passages of dissociated HNE cells could be achieved. Addition of serum to this culture medium inhibited epithelial cell growth. Vitamin A had no apparent effect on cell growth but induced an alteration in the morphologic characteristics of the cell. The epithelial nature of cultured cells was confirmed by positive staining with antihuman keratin antibody, ultrastructural studies, and by formation of a columnar, ciliated epithelium in denuded tracheal grafts repopulated by these cultured HNE cells. Biochemical analyses of glycoproteins (labeled with 3H-glucosamine and/or 35S-sulfate) secreted by cultured HNE cells were unable to demonstrate the secretion of mucinlike glycoproteins in culture. Instead, major secretory products of cultured cells were hyaluronate and heparan sulfate. These results were in agreement with morphologic observations that showed no mucus-secreting granules in cultured cells. Dome formation was observed in high cell density cultures. We conclude that HNE cells can be cultured in well-defined culture media. As indicated by formation of domes, these cells may be useful for in vitro ion transport studies. Further differentiation, however, may be required for studies of mucin synthesis.

Adolescent↗

Adenocarcinoma of unknown primary origin: treatment with vindesine and doxorubicin.

Adenocarcinoma of unknown primary origin (ACUP) is a common oncologic problem for which there is no standard therapy. Forty-two patients with metastatic tumor were identified as having ACUP after extensive evaluation failed to reveal a primary site of disease. They were treated with an investigational chemotherapy regimen consisting of vindesine and doxorubicin. Of the 38 evaluable patients, six (16%) had major responses to chemotherapy. The median duration of response was 4 months. The median survival of the responding patients has not been reached, but is greater than 8 months. The median survival of the nonresponding patients was 6 months. Vindesine and doxorubicin were well tolerated. The major toxicity was leukopenia, with a median wbc count nadir of 2600/mm. We conclude that the combination of vindesine and doxorubicin has some activity in ACUP, but does not improve the response rate seen with other regimens.

Adenocarcinoma↗

Phase II trial of 1,2-diaminocyclohexane-(4-carboxyphthalato) platinum(II) (DACCP) in colorectal carcinoma.

In an effort to investigate the antitumor activity of new cisplatin analogues, 1,2-diaminocyclohexane-(4-carboxyphthalato) platinum (II) (DACCP) was administered in a phase II disease-oriented trial to patients with advanced colorectal carcinoma. Six patients had not received prior chemotherapy, while four had received one drug, and two had received more than one drug. Primary sites of disease were in the liver only (8 patients), liver and lung (2 patients), and intra-abdominal (2 patients). Liver radionuclide scans and CT scans were the main parameter for evaluation. The drug was administered intravenously every 4 weeks at a dose of 640 mg/m2. There were no responses in 12 adequately treated patients. One patient had stable disease for 5 months. Nausea and vomiting was milder than that seen with cisplatin. A peripheral neuropathy was seen in four patients. Fever occurred in two patients and urticaria in one patient. No patient had significant drug-induced anemia, and renal dysfunction was not observed. DACCP at this dose and schedule demonstrated no efficacy as a single agent in the treatment of colorectal carcinoma.

Adult↗

Effect of human saliva and serum on ion transport by dog tracheal mucosa. Comparison of normal subjects with cystic fibrosis patients.

It has been proposed that cystic fibrosis (CF) saliva or serum contains factors that alter ion transport in various tissues. Since CF frequently affects the lungs, and disturbances in epithelial ion transport has been proposed to contribute to the pathophysiology of pulmonary disease in CF, we investigated whether saliva or serum from CF patients could alter ion transport across airways epithelium. Canine tracheal mucosae were mounted in lucite chamber and perfused on both sides with Krebs-Henseleit solution at 37 degrees C and pH 7.4. Unidirectional fluxes of 22Na and 36Cl were measured in pairs of mucosal tissues under short circuit conditions. Saliva from 5 CF patients stimulated short circuit current (SCC) by 33 +/- 8 microA/cm2 and net Cl secretion by 1.10 +/- 0.33 muEq/cm2 X h (mean +/- SE; p less than 0.05). No change occurred in net Na absorption. Saliva from normal subjects raised SCC by 34 +/- 7 microA/cm2 and increased net Cl secretion by 1.29 +/- 0.46 muEq/cm2 X h (n = 9; p less than 0.02). Serum from both CF patients and control subjects briefly stimulated SCC. Exposure of tracheal mucosa to normal as well as CF saliva, such as by aspiration, or to serum, such as by transudation, stimulates Cl secretion, and therefore water secretion into airway lumen. There appears to be no difference in the effect exerted by CF saliva or serum and that of normal subjects. These findings argue against the presence of a specific circulating or secreted CF factor that could alter ion transport across respiratory epithelia in a way that might contribute to lung disease in CF.

Adolescent↗