Biomedical subjects

D Fan

Publications and source records attributed to D Fan.

150 records · Page 9Linked to original sources

PubMedDate not supplied

Stable expression of a cDNA encoding rat brain protein kinase C-beta I confers a multidrug-resistant phenotype on rat fibroblasts.

Protein kinase C (PKC) is a Ca++- and phospholipid-dependent protein kinase that plays an important role in signal transduction pathways that regulate cell growth. Tumor cells selected for a multidrug resistant (MDR) phenotype often express elevated levels of PKC activity. To directly test whether PCK overexpression can produce an MDR phenotype, we studied rat embryo fibroblasts that were infected with the full-length cDNA clone RP58 encoding the beta I form of rat brain PKC. The PKC-beta I gene recipient R6-PKC3 cells are stable, overproduce PKC, and express an elevated level of PKC activity. R6-PKC3 cells exhibited significant resistance to adriamycin, actinomycin D, vinblastine, and vincristine but not to 5-fluorouracil. Intracellular accumulation of adriamycin, vinblastine, and vincristine was decreased in the R6-PKC3 cells, but this was not associated with an altered level of P-glycoprotein expression. Moreover, the reduction in drug accumulation appeared to be a consequence of a decreased rate of drug uptake. The data indicate that overexpression of PKC in rat fibroblasts produces an MDR phenotype without altering P-glycoprotein expression.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMedDate not supplied

Granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of cancer.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the four major colony-stimulating factors (CSFs) that regulate hematopoiesis. GM-CSF can stimulate a single bone marrow stem cell to proliferate and differentiate into mature neutrophils, eosinophils, granulocytes or macrophages. The outcome of recent clinical trials indicates that GM-CSF has the prospect of being clinically effective in augmenting the recovery of hematopoiesis in recipients of autologous bone marrow transplantation, in cancer patients suffering from the hematopoietic toxicity associated with chemotherapy and radiation therapy, and in patients with acquired immunodeficiency syndrome (AIDS).

Colony-Stimulating Factors↗

PubMedDate not supplied

[5-Fluorouracil in trabeculectomy: preliminary report].

Subconjunctival 5-FU injections were used as an adjunctive therapy in trabeculectomy for high risk glaucoma patients. We injected 5 mg once a day for five to seven days as a routine treatment. For the first 10 eyes, the injections were started immediately after the operation. However, for the remaining 9 eyes, the injections began 24 to 48 hours postoperative. If the appearance of the bleb was not prominent or enriched in vascularity, the duration of the injections should be extended to 10 to 14 days. At least 8 months of follow-up were available for 19 eyes, including aphakic glaucoma, 8 eyes; neovascular glaucoma, 2 eyes; previous failed filter, 6 eyes; total collapse of the anterior chamber with leucoma adherence, 1 eye; glaucoma due to mesodermal dysgenesis, 1 eye; and juvenile glaucoma, 1 eye (whose fellow eye had received twice failed filtering procedures). The results revealed a success rate of 79% (intraocular pressure below 22mmHg with or without topical medication). The success rate for aphakic glaucoma was 63% (5/8), for neovascular glaucoma 100% (2/2) and for the failed filters 83% (5/6). We also presume that 5-FU injections would be effective in the treatment of to abnormally marked fibrous proliferations caused by age factors. The complications related to the use of 5-FU include corneal epithelial defect 4/9 (21%), conjunctival leak 3/9 (16%), subconjunctival hematoma 1/19 (5%), and conjunctival sterile ulcer 1/19 (5%).

Adolescent↗

PubMedDate not supplied

Accelerated growth of human colon cancer cells in nude mice undergoing liver regeneration.

The purpose of this study was to determine whether liver regeneration induced by partial hepatectomy (PH) influences the growth of human colon cancer (HCC) cells implanted into athymic nude mice. HCC KM12C cells were injected subcutaneously into nude mice and then the mice were randomized to undergo PH, laparotomy, or no surgery. The latent period to development of measurable tumors was shorter and the growth rate of HCC tumors was significantly faster in hepatectomized mice. Accelerated tumor growth directly coincided with liver regeneration. Peak mitotic activity in both the regenerating liver and HCC occurred on the second day following PH. No enhancement in growth of tumors occurred in mice implanted with HCC cells 3 weeks after PH (i.e. 2 weeks after completion of liver regeneration). The accelerated tumor growth was specific to HCC. We base this conclusion on results of control experiments where cells from human melanoma, colon, breast, prostate, and renal cancer were injected into nude mice that were then randomized to undergo PH or laparotomy. Only HCC grew faster in hepatectomized mice. No significant differences in expression of epidermal growth factor receptor (EGF-R) and c-met were found between HCC tumors in mice with PH or laparotomy, suggesting that over-expression of EGF-R or c-met is not an essential component of this phenomenon. The accelerated growth of HCC cells at a site distant from surgical trauma suggests that circulating growth factors involved in liver regeneration can specifically stimulate the growth of HCC cells.

Animals↗

PubMedDate not supplied

Adoptive immunotherapy of advanced renal cell cancer using PHA-stimulated autologous lymphocytes.

Patients with advanced renal cell carcinoma, previously failed maximal treatment with standard chemo-hormonal-radiation therapies, were treated with plant lectin phytohemagglutinin (PHA)-stimulated autologous peripheral blood lymphocytes in a 10-year study with a 16-year follow up period. In a phase I-II setting, 52 patients were given subcutaneously 40-80 x 10(6) PHA-stimulated lymphocytes weekly for 3 weeks and then escalated to a maximum number of 80 x 10(9) lymphocytes over the next 9 weeks at 3 week intervals. In vitro blastogenesis under study conditions (10 micrograms/ml PHA for 72 hr) measured by [3H]thymidine uptake was optimal with lymphocyte stimulating indexes approaching 300. Lymphocytes obtained from patients with breast cancer, melanoma and renal cell carcinoma responded to PHA similarly to those from normal volunteers. All patients that responded developed erythematous reactions at the sites of injection; malaise, joint paint and chill-fever for 24-48 hr. The patients that responded the best were those with at least 1 positive reaction out of 4 skin tests (tuberculosis, yeast, dermatophytin, mumps) prior to therapy. All toxicity was transient and did not exceed Grade I based on criteria of the Southwest Oncology Group. The majority of patients developed a lymphopenia in the first 24 hr followed by a lymphocytosis 48-72 hr later. For some patients the lymphocytosis was as much as 30% atypical lymphocytes. Of 41 evaluable patients, there were 5 complete responses, 8 partial responses, 3 stable diseases, and 25 progressive disease. The overall response rate was 32% and the median survival was 2.8 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Renal Cell↗

PubMedDate not supplied

Comparative preclinical toxicology and pharmacology of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) in vitro and in rodents and primates.

4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) is being evaluated for its anticancer activities. Acute, subacute and chronic oral, dermal, opthalmic and dermal LD50 and acceptance studies in adult mice, rats, rabbits and monkeys demonstrated some vomiting at 5 g/kg doses in monkeys but otherwise no unacceptable toxicities. In vitro, T.I. for A-007 were calculated using murine bone marrow GM-CFC and human cancer cell lines. A relative oral bioavailability factor of 2% was calculated for rats and monkeys for plasma A-007. Non-compartmental pharmacokinetic analysis suggests enterohepatic circulation. Plasma A-007 could not be detected after applying a 0.25% gel topically. Generally, A-007 is well tolerated.

Administration, Oral↗