PubMed Health⌕ Search

Biomedical subjects

D Fan

Publications and source records attributed to D Fan.

At least 145 records · Page 8Linked to original sources
PubMed1989

Arrest and retention of multilamellar liposomes in the brain of normal mice or mice bearing experimental brain metastases.

The blood-brain barrier presents a major obstacle to the systemic treatment of malignant brain tumors and brain metastases. We investigated whether the direct injection of liposomes into the internal carotid artery of normal mice or mice with experimental brain-melanoma metastases could allow delivery of anticancer drugs across this barrier. Liposomes of different sizes (greater than 5 microns, less than 1 micron, 40-80 nm) and lipid compositions were injected i.v. or into the internal carotid artery. The retention of liposomes in the brain of normal C3H/HeN mice was similar to that observed in mice with experimental brain cancer metastasis. The highest accumulation of liposomes in the brain occurred with large multilamellar vesicles, which also produced severe toxicity presumably due to embolism. Smaller liposomes were not toxic but did not accumulate in the brain. Liposomes injected i.v. did not accumulate in the brain, either. Thus, neither i.v. nor intracarotid administration of liposomes produce results suitable for therapy of brain tumors/metastases.

Animals↗
PubMed1989

Antiproliferative activity of liposome-encapsulated transforming growth factor-beta against MDA-MB-435 human breast carcinoma cells.

We determined whether transforming growth factor-beta (TGF-beta) could be encapsulated in phospholipid liposomes and then would mediate antiproliferative activity against the sensitive, human breast cancer cell line, MDA-MB-435. TGF-beta was encapsulated in multilamellar liposomes consisting of phosphatidylcholine (PC) or PC and phosphatidylserine (PS) at a 7:3 molar ratio. It was captured in both the aqueous phase and the bilayer lipid (hydrophilic and lipophilic association) and was stable for at least 24 hr of incubation at 37 degrees C in medium that contained 5% fetal bovine serum. In calcium- and magnesium-free Hanks' balanced salt solution, TGF-beta in the internal aqueous compartment was stable for at least five days, even in the presence of trypsin and ethylenediamine tetraacetic acid. TGF-beta (type 1 or 2) in liposomes was active as free-form TGF-beta in mediation of antiproliferative effects. The lipophilic nature of TGF-beta, which resulted in a high capture ratio in liposomes, coupled with exceptional stability, suggested that liposomes could be a carrier for the in vivo use of TGF-beta.

Breast Neoplasms↗
PubMed1989

Clonal stimulation or inhibition of human colon carcinomas and human renal carcinomas mediated by transforming growth factor-beta 1.

We examined various human carcinomas and cells populating a single human neoplasm to determine whether they exhibit a heterogeneous response to the effects of transforming growth factor-beta 1 (TGF-beta). Using recently established human colon carcinoma and renal cell carcinoma under defined in vitro conditions, we observed intertumoral and intratumoral heterogeneity and polarity of responses to TGF-beta (growth inhibition or stimulation) that did not correlate with the metastatic phenotype of the cancer cells as assessed in athymic nude mice. TGF-beta mediated both cytostatic and cytolytic effects against sensitive tumor cells, and these responses were not related to the effects of TGF-beta on the cell-cycle traverse. The human colon carcinoma and renal cell carcinoma, however, exhibited differences in the expression of TGF-beta receptors.

Animals↗
PubMed1989

Potent in situ activation of murine lung macrophages and therapy of melanoma metastases by systemic administration of liposomes containing muramyltripeptide phosphatidylethanolamine and interferon gamma.

Mouse alveolar macrophages (AM) were rendered tumoricidal after the intravenous administration of liposomes containing muramyl tripeptide phosphatidylethanolamine (MTP-PE), a lipophilic derivative of muramyl dipeptide. The addition of recombinant mouse interferon gamma (r-IFN-gamma) to the liposomes significantly potentiated this effect. This potentiation was also observed in therapeutic studies of mice bearing well-established spontaneous lung melanoma metastases. Multiple intravenous injections of liposomes containing both MTP-PE and r-IFN-gamma resulted in 70% survival in one group treated for small lung metastases and 50% in another group treated for large lung metastases. These data demonstrate that the presentation of r-IFN-gamma and MTP-PE in liposomes is more efficient in inducing the destruction of metastases than either agent administered alone.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Antitumor activity against human tumor samples of cis-diamminedichloroplatinum(II) and analogues at equivalent in vitro myelotoxic concentrations.

We compared the antitumor activity of cis-diamminedichloroplatinum(II) (cisplatin; CDDP) with three CDDP analogues: cis-diammine-1,1-cyclobutanedicarboxylateplatinum(II) (CBDCA), N-methyliminodiacetato-1,2-diamino(cyclohexane)platinum(II) (MIDP), and N-(2-hydroxyethyl)-iminodiacetato-1,2-diamino(cyclohexane)platinum (II) (HIDP). Fresh human tumor samples in the adhesive tumor culture system were utilized for this comparison. The equitoxic concentrations of all four drugs were derived based on their inhibitory activity against human bone marrow samples. For these normalized concentrations, CDDP proved to have a higher cytotoxic activity than its analogues. CBDCA's in vitro activity had a significant correlation with CDDP activity (r = 0.67) in vitro. However, the structurally similar substances MIDP and HIDP demonstrated a much greater degree of association (r = 0.90). Our data suggest that CBDCA, HIDP, and MIDP have overall less activity than CDDP when tested at equitoxic in vitro concentrations. Close association between CDDP and CBDCA also reflects known clinical experience with these two drugs, suggesting the method of comparison used here is probably appropriate. These conclusions, however, must be validated by clinical trials.

Bone Marrow↗
PubMed1987

Comparison of antitumor activity of standard and investigational drugs at equivalent granulocyte-macrophage colony-forming cell inhibitory concentrations in the adhesive tumor cell culture system: an in vitro method of screening new drugs.

We compared the in vitro growth inhibition of primary human tumor cells in the adhesive tumor cell culture system (ATCCS), exposed to the investigational agents caracemide, spirogermanium and taxol and to standard chemotherapy agents at equitoxic concentrations for granulocyte-macrophage colony-forming cells (GM-CFC) in vitro. Clinically active standard agents tested at up to GM-CFC 90% inhibitory concentrations (IC90) resulted in in vitro activity (greater than or equal to 50% tumor growth inhibition) in at least 30% of tumors tested. In vitro responses for taxol, caracemide and spirogermanium were 78%, 9% and 7%, respectively. This paper proposes a model that incorporates two hypotheses: (1) myelotoxic drugs which inhibit tumor growth at concentrations equal to or less than equitoxic GM-CFC ICs will demonstrate clinical activity; and (2) both myelotoxic and particular nonmyelotoxic drugs inactive in vitro at these doses will not be active clinically. If this drug screening concept is valid, taxol may be clinically more active than caracemide and spirogermanium.

Alkaloids↗
PubMed1985

Pharmacologic assessment of regimen chemosensitivity in the soft-agar assay: effect of oxygen on human tumors.

The influence of oxygen on the growth and the in vitro chemosensitivity of human tumor cells was studied in the soft-agar assay. Tumor cells of pancreatic and ovarian origin prefer a reduced oxygen atmosphere for colony formation, whereas those of pulmonary origin grow better in 20% oxygen. Depending on the physiologic oxygen tension and the histologic origin of a particular cancer type, the in vitro chemosensitivity of many drug obtained with the conventional culture system could be inadequately assessed. The in vitro responses of tumor cells to combinations of drugs were measured by the regimen efficacy index (REI) method. The REI delineates the possible regimen enhancement or regimen default based on the in vitro chemosensitivity of the individual agents tested in the assay. In vitro regimen enhancement was observed only in ascites incubated in a reduced oxygen atmosphere with two-drug combinations. However, regardless of the oxygen gradients used, regimen default was seen in cancer cells of solid tumors treated with all combinations of drugs tested. This study suggests further investigation on the effects of oxygen in the soft-agar assay, and proposes the novel use of the REI method for evaluating the in vitro regimen chemosensitivity of human tumor cells.

Antineoplastic Agents↗
PubMed1985

Cooperative evaluation of human tumor chemosensitivity in the soft-agar assay and its clinical correlations.

In supporting the human-tumor cloning effort of the Southwest Oncology Group, we conducted an independent retrospective study to evaluate the clinical correlations of the soft-agar colony-forming assay developed by Hamburger and Salmon (1977). This study was made with the cooperation of 76 clinicians and 11 hospitals in Greater New Orleans. In a 10-month trial (July 1982 to May 1983), we received 134 human tumors of 26 classifications and achieved 76% success in colony growth from 122 plated samples. Retrospective correlations between the in vitro chemosensitivity of tumor colonies and clinical drug responses were made possible in 31% of the patients. Evaluation of 45 in vitro and in vivo associations indicated a combined sensitivity of 0.65 and a specificity of 0.68 for the assay. Technical refinements and the selectivity of the assay are discussed.

Antineoplastic Agents↗
PubMed1984

Sectional analysis of tumor colony growth in the soft-agar assay: effects of oxygen.

Soft-agar clonogenicity of L1210 mouse leukemia cells and of xenografts of a human melanoma and a carcinoma of the cervix was studied sectionally by the sizes of the colonies grown under hypoxic gradients and aerobic condition. Soft-agar plating efficiency was increased in cultured L1210 cells with decreasing oxygen concentrations. The growth of both cultured L1210 cells and their BDF1 ascites was better in 5% oxygen than in 20% oxygen. Although soft-agar colony development of both melanoma and cervical carcinoma was significantly better in 5% oxygen, the former has a secondary preference for a hypoxic atmosphere and the latter, for an aerobic condition.

Animals↗
PubMed1984

Phospholipase activity in human tumors: localization by cytochemical staining.

Phospholipase activity was localized for the first time by cytochemical staining at the plasma membrane of malignant cells in gastric adenocarcinomas by electron microscopy. This activity was not found in benign cells of the same tumor, e.g., in components of the connective tissue underlying the glandular epithelium, or in cells beyond the margin of the same tumor. Neither benign nor malignant cells of colorectal tumors, nor those in malignant melanoma, had any phospholipase activity that could be demonstrated by the method.

Adenocarcinoma↗
PubMed1984

Vinblastine-induced formation of annulated lamellae in SV3T3 cells.

SV40-transformed 3T3 cells formed microtubular crystals in the cytoplasm when treated with vinblastine sulfate. Annulated lamellae, an unusual intracellular organelle found in some actively proliferating cell types, appeared concurrently with the formation of microtubular crystals. Although crystals were also seen in non-transformed 3T3 cells treated with vinblastine, annulated lamellae were not found.

Animals↗
PubMed1982

Protein synthesis by attached pulmonary macrophages. Effect of phagocytosis.

We studied the effect of phagocytosis of polystyrene latex beads on protein synthesis by pulmonary macrophages. To do this we determine the specific radioactivity of extracellular and intracellular free phenylalanine and of phenylalanine released from tRNA and used this information in calculating the rates of protein synthesis. Phagocytosis resulted in an increased rate of protein synthesis irrespective of which precursor specific radioactivity was used in the calculation. The rate of protein synthesis was increased per microgram polyribosomal RNA; but there was no increase in the amount of polyribosomal RNA in phagocytizing macrophages. The increase in the rate of protein synthesis (1.4-fold) was almost identical to the increase (1.3-fold) in the rate of ribosome transit in phagocytizing compared to nonphagocytizing macrophages. The decreased ribosome transit time during phagocytosis occurred without a fall in the average molecular weight of macrophage proteins. We conclude that phagocytosis increases the rate of protein synthesis in attached pulmonary macrophages and that this increased rate of synthesis can be accounted for almost completely by an increased rate of polypeptide chain elongation and/or termination.

Animals↗
PubMedDate not supplied

Microbial keratitis in Hong Kong: relationship to climate, environment and contact-lens disinfection.

Microbial keratitis has been studied in Hong Kong as a representative sub-tropical climate of south China. An 18-month investigation in 1997/98 of 223 cases of ulcerative keratitis (presumed microbial) was conducted in the 2 million population of Shatin and Kowloon at the Prince of Wales and Hong Kong Eye Hospitals respectively with comprehensive microbiology. A case-control study was pursued at the same time between 45 contact-lens wearers (CLW) developing microbial keratitis and 135 lens-wearing volunteers matched for age, sex, educational status and visual acuity. Home water supplies were sampled for Acanthamoeba. Previous ocular surface disease and trauma (preventable by wearing goggles for grinding) were common predisposing causes while cosmetic wear of contact lenses was responsible for 26% of cases overall. Pseudomonas aeruginosa was the commonest bacterium isolated, from both CLW and non-CLW, with infection being acquired within the community. These 28 pseudomonads remained fully sensitive to the third-generation cephalosporins, aminoglycosides and quinolone antibiotics, which is very encouraging. Fungi were isolated, predominantly Fusarium sp., but less commonly than expected. A fungal/bacterial ratio was obtained of 1/17, while in comparison, the expected ratio for a tropical climate ranges from 1/5 (Singapore) to 1/2 (South India). Acanthamoeba was the second commonest microbe isolated from keratitis of CLW. The domestic water environment of 8% of homes of both patients and controls wearing contact lenses was colonized with Acanthamoeba. Lack of hygiene, use of tap water for storing lenses, failure to air-dry lens-storage cases or use of one-step hydrogen peroxide disinfectant were identified as risk factors for keratitis in CLW. The study results commend use of multipurpose solutions by CLW in Hong Kong to achieve the lowest expected rates of infection.

Acanthamoeba Keratitis↗
PubMedDate not supplied

Expression of multidrug resistance-related markers in gastric cancer.

BACKGROUND: To detect the expression of glutathione S-transferase Pi(GST-pi), multidrug resistance-associated protein (MRP), lung-resistance protein(LRP), multidrug resistance gene1 (MDR1) and MGr1 antigen(MGr1-Ag) in the patients with primary gastric cancer and without any prior chemotherapy and to evaluate the correlations between them. PATIENTS AND METHODS: The expression of GST-pi, MRP, LRP and MDR1 in cancer tissue and the adjacent non-cancerous tissue from 50 patients was examined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The expression of MGr1-Ag in these tissues was also examined by immunohistochemistry. RESULTS: The positive rate of GST-pi mRNA, MRP mRNA, LRP mRNA, MDR1mRNA and MGr1-Ag in gastric cancer tissue was 36.00%, 12.00%, 10.00%, 10.00% and 18.00% respectively. The overall positive rate of their expression was 58.00%. Clinicopathological factors were not significantly related to their expression. No significant correlation was observed between these markers. CONCLUSION: These MDR markers are differently over-expressed and no coexpression exists in gastric cancer. MGr1-Ag was a novel MDR protein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Phrenic and intercostal repetitive nerve stimulation: a useful electroneurophysiological method to detect the respiratory status of myasthenia gravis patients.

OBJECTIVE: To get a comprehensive recognition about the profile of phrenic repetitive nerve stimulation (PRNS) and intercostal repetitive nerve stimulation (IRNS) in healthy people, to investigate the electrophysiological features about respiratory function of myasthenia gravis (MG) patients, and to detect the predictive value of IRNS and PRNS on the respiratory deterioration of MG patients during the pulse treatment with large dosage of adrenal corticosteroid. SUBJECTS AND METHODS: Bilateral PRNS and IRNS with stimulation frequency of 3 and 5 Hz were tested in 28 healthy people and 113 MG patients; limb and cranial repetitive nerve stimulation (RNS), clinical score and forced vital capacity (FVC) were also recorded from those MG patients. Further more, PRNS and IRNS of 36 MG patients were tested 3 days before the beginning of their adrenal corticosteroid pulse treatment, FVC, clinical score and respiratory changes of the MG patients were simultaneously observed. RESULTS: For healthy people, there were no significant differences in the results of PRNS or IRNS in different age, sex and testing sides. After combining the left result with the right one, the amplitude decrement percentage in PRNS and IRNS was less than 7%. PRNS had more technical difficulty than IRNS. For 113 MG patients, FVC was dependent on the values of PRNS, IRNS and facial RNS. A subclinical respiratory dysfunction was found in patients with type I and II MG. The abnormal rate of PRNS in type IIb MG was similar to that in type III and IV MG, even though a difference in the percentage of amplitude decrement between them was observed. Meanwhile, both the abnormal rate and the percentage of amplitude decrement of IRNS had no difference between type IIb MG and type III and IV MG. The general incidence of abnormal PRNS and abnormal IRNS were higher than those of decreased FVC and clinical dyspnea, and the sensitivity of PRNS in type IIa MG patients was higher than that of IRNS. Among 36 MG patients under the adrenal corticosteroid pulse treatment, 14 showed the newly clinical dyspnea or worsened original one 2 to 13 days after the beginning of the therapy. There were significant difference of the above parameters between the patients with and without respiratory deterioration during the treatment. Logistic regression analysis showed that when the mean value of the bilateral IRNS amplitude decrement was larger than 30%, the odds ratio of the occurrence of the respiratory deterioration was 19.523, for both 3 and 5 Hz stimulation. CONCLUSIONS: It is recommended that PRNS and IRNS will be defined as abnormal when their amplitude reduces more than 15%. PRNS and IRNS are neurophysiological indices reflecting the damage of respiratory muscles in MG, they are helpful in evaluating the clinical condition correctly and making the classification of MG properly. It is necessary to test the PRNS and IRNS in type II MG patients regularly. Although the respiratory damage during the adrenal corticosteroid treatment was correlated with PRNS, IRNS, FVC, MG clinical score and type, only IRNS had predictive value on the respiratory deterioration during the treatment.

Adrenal Cortex Hormones↗