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Biomedical subjects

S Fu

Publications and source records attributed to S Fu.

At least 109 records · Page 6Linked to original sources
PubMed1995

Resistance to taxol chemotherapy produced in mouse marrow cells by safety-modified retroviruses containing a human MDR-1 transcription unit.

We used an animal model system to transplant lethally-irradiated mice with one million marrow cells which had been: (1) collected from 5-fluorouracil (5-FU) treated mice; and (2) transduced with retroviruses containing a multiple drug resistance-1 (MDR-1) gene transcription unit. Following recovery from the transplant, we exposed these mice to doses of taxol ranging from 7 mg/kg to 30 mg/kg, which corresponds to doses of 68 to 268 mg/m2 in man. The median white blood cell count by 5 days after taxol (expressed as the percentage of the white blood cell count before taxol) was 83% (range 46-100%) in 11 courses of taxol in mice transplanted once with MDR-1 transduced marrow immediately after transplant, whereas the median white blood cell count by 5 days after taxol in mice not transplanted with MDR-1 marrow was 41% in nine courses of taxol (range 11-66%). This difference is statistically different at the P < 0.001 level (Wilcoxon test). One million marrow cells from the MDR-1 transplanted mice were harvested and serially transplanted through five additional cohorts of mice, and tested with taxol after each cohort. The white blood cell count (expressed as the percentage of pre-taxol white blood cell count) after each cohort ranged from 94-146% in the 29 mice transplanted with the transduced MDR-1 marrow, which had been through more than one transplant. This is statistically different from the median white blood cell count recovery after taxol in mice which have no human MDR-1 modified marrow (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Chemotherapy resistance to taxol in clonogenic progenitor cells following transduction of CD34 selected marrow and peripheral blood cells with a retrovirus that contains the MDR-1 chemotherapy resistance gene.

A retrovirus containing the multiple drug resistance (MDR-1) cDNA, was used to transduce cultures of CD34 selected human marrow cells, on stromal monolayers in the presence of hematopoietic growth factors IL-3 and IL-6, following collection from patients recently recovered from chemotherapy-induced myelosuppression. In one experiment, these CD34 selected cells were grown in Dexter cultures for 35 days or more following MDR-1 transduction, and then plated in methylcellulose. Polymerase chain reaction (PCR) analysis of colonies picked after 10-14 days of methylcellulose culture, using a set of primers that are specific for the endogenous or the retrovirally transduced MDR-1, showed that the long-term culture initiating cells (LTCICs) were transduced by the MDR-1 virus. Analysis of the colonies from the CD34 selected MDR-1 transduced cells, with a reverse transcription (RT) PCR assay that could distinguish viral MDR-1 mRNA from endogenous MDR-1 mRNA, showed that the viral MDR-1 mRNA levels were much higher than that of the MDR-1 mRNA from the endogenous MDR-1 gene in the transduced CD34 selected cells. Fluorescence activated cell sorting (FACS) analysis of the CD34 selected transduced marrow cells within 48 h after the transduction, using the C219 and UIC2 monoclonal antibodies for p-glycoprotein, showed that the transduction frequency under these conditions varied from 7 to 20%. Rhodamine efflux studies showed that this additional p-glycoprotein was functional and that the frequency of cells with high p-glycoprotein levels was higher in the transduced cells than in the non-transduced cells. The resistance to taxol of the CD34 selected transduced cells, as judged by the plating efficiency of clonogenic progenitor cells derived from these cells by growth in methylcellulose supplemented with taxol was much higher in the transduced cells than in untransduced cells. In order to test the reproducibility of the transduction frequency of the retroviral supernatants from PA317 MDR-1 viral producer cells on CD34 selected cells, the virus produced from 12 different lots of supernatants from the PA317 MDR-1 producer cell line was used to transduce CD34 selected marrow cells from four different patients, and to transduce the peripheral blood cells of two additional patients collected following chemotherapy-induced myelosuppression. The supernatant lots used for these transduction experiments were tested by Microbiological Associates (Rockville, MD, USA), by the Mus dunni co-cultivation and amplification tests in the S+L-assay and found to be negative for replication-competent retrovirus, and later approved for human use by the Food and Drug Administration.(ABSTRACT TRUNCATED AT 400 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Suppression of tumorigenesis by transcription units expressing the antisense E6 and E7 messenger RNA (mRNA) for the transforming proteins of the human papilloma virus and the sense mRNA for the retinoblastoma gene in cervical carcinoma cells.

Human cervical carcinoma cell lines that harbor human papilloma virus (HPV) have been reported to express HPV E6 and E7 proteins at least in the beginning stages if not at all stages of the disease. The HPV E6 and E7 proteins bind to and inactivate the products of the p53 and retinoblastoma (Rb) tumor suppressor genes, which thereby allow the cervical carcinoma cells to circumvent the action of these tumor suppressor genes. We observed that the introduction of the antisense HPV 18 E6 and E7 sequences, as well as a sense cDNA for the human wild-type Rb gene into a human cervical carcinoma cell line (HeLa), which is positive for the HPV 18 provirus, decreased the in vitro and in vivo growth rate of the transfected cells if both antisense transcripts for the HPV 18 E6 and E7 and sense transcripts for human Rb were expressed. In addition, overexpression of a complementary DNA (cDNA) for the Rb messenger RNA was sufficient to slow the proliferation of HeLa cells, and the level of Rb cDNA expression was correlated with the degree to which the rate of growth of the tumor was slowed. The results of our experiments show that the presence of HPV E6 and E7 proteins and the resultant inactivation of Rb in cervical carcinoma cells contributes to the neoplastic phenotype even in highly evolved cervical carcinoma cell lines such as HeLa, which have been derived from a cervical carcinoma patient at an advanced stage of the disease process. These data suggest that the HPV proteins play a role not only at the beginning of cervical cancer, but also at advanced stages of this disease. These experiments may lead to genetic approaches to the control of this disease that involve antisense sequences that downregulate the E6 and E7 genes or lead to expression of the Rb gene.

Animals↗
PubMed1995

[The experimental observation on the procedure of atherosclerotic restenosis following PTCA].

Angioplasty of stenotic iliac artery was performed in 23 Japanese white rabbits. Angiography and histopathology examinations were performed one day (6 rabbits), 3 days (5 rabbits), one week (5 rabbits) and one month (7 rabbits) after dilation. TXB/PGF in blood was analyzed with radio-immunologic method. TXB/6-K-PGF increased at 1st day, began to reduce at 3rd day, became almost normal after one week and returned to normal level week after one month. Restenosis occurred in all animals. Platelet aggregation and mural thrombi were observed at 1st and 3rd day. New endothelial cells covered the surface of denuded endothelium at 3rd day. At 7th day, repairing of endothelium was completed and proliferation of smooth muscle cells were prominent in new intimia. Stenosis of lumen occurred again after 1 month. The results suggested that intimia injury during the procedure initiates the process of restenosis and aggregation of platelets, imbalance of between TXA and PGI is and proliferation of smooth muscle cells play important roles in the formation of restenosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Clinical and pathologic studies on idiopathic uveal effusion.

In order to investigate the clinical features, pathology and treatment of idiopathic uveal effusion syndrome, ten eyes of seven patients with the syndrome had been studied. In addition to general clinical examinations, indirect opthalmoscopy, fundus fluorescein angiography and (FFA) ultrasonography were used to make definite diagnoses. The findings of these examinations indicate four key features of the idiopathic uveal effusion syndrome. They are: annular cilio-choroidal detachment, shifting non-rhegmatogenous retinal detachment, unremarkable inflammation in the anterior segment, and normal intraocular pressure. The fundus change is characterized by the "leopard-spot". All patients were treated by sclerectomy and sclerotomy, ciliochoroidal detachments disappeared soon after surgery, and retinal detachments resolved later on. Patients' visual acuity recovered well. The histochemical and electron microscopic examinations of excised tissues from five eyes showed thickened sclera, a general increase of the scleral fibril width compared to normal scleral, the disruption of normal lamellar arrangement of the scleral fibers and the deposition of glycosaminoglycans in the interfibrillar spaces. All these indicate that a congenital scleral abnormality seems to be the basic pathophysiology of the idiopathic uveal effusion syndrome.

Adult↗
PubMed1995

PML/RARalpha, a fusion protein in acute promyelocytic leukemia, prevents growth factor withdrawal-induced apoptosis in TF-1 cells.

A unique mRNA produced by the t(15;17) (q22-24;q11-21) translocation in the leukemic cells of acute promyelocytic leukemia patients encodes a chimeric protein, PML/RARalpha, which is formed by the fusion of the retinoic acid receptor alpha (RARalpha) and the promyelocytic locus gene (PML). This translocation is often the only visible karyotypic aberration present which is detected in almost 100% of acute promyelocytic leukemia patients. As an initial step to study the role of PML/RARalpha in leukemogenesis, we attempted to express the fusion protein in hematopoietic cells through retrovirus-mediated gene transfer of the retroviral vector, pGPRCHT, which contains the PML/RARalpha cDNA. Transduction of the PML/RARalpha cDNA fragment used in this vector, which extends from the position 31 bp to the position 2638 bp in a transcription unit driven by the Moloney murine sarcoma virus LTR, was found to abrogate the growth factor dependence of TF-1 cells. In addition, introduction of PML/RARalpha into TF-1 cells can protect these cells from the apoptosis usually induced in TF-1 cells by growth factor withdrawal, as measured by three assays for apoptosis: morphology, DNA ladder formation, and end labeling of nicked DNA with fluorescent-conjugated nucleotide precursors followed by a fluorescence-activated cell sorting assay. These data suggest that the PML/RARalpha fusion protein may inhibit programmed cell death in myeloid cells.

Apoptosis↗
PubMed1994

Differential effects of thermal injury on circulating insulin-like growth factor binding proteins in burn patients.

The results of this report provide evidence that insulin-like growth factor-1 binding proteins (IGFBPs) in human sera are differentially regulated as a result of severe burn injury. Using the ligand binding technique, 125I-IGF-1 visualizes 5 different protein bands corresponding to those previously reported for IGFBP-1 to 4 with apparent sizes of 23-42 kd in serum samples prepared from severely burned patients and healthy individuals. The level of IGFBP-3 was significantly decreased within 3-5 days of injury and remained depressed for up to 20 days post injury. The average level of this binding protein reached its lowest value within 3-5 days of the injury (3.8 +/- 1.48% relative to day 0-1 value, n = 4, p < 0.01). Serum samples from 3 of 4 patients showed no recovery within 20 days post injury and the level of IGFBP-3 remained significantly depressed (p < 0.01). In contrast, the levels of IGFBP-2 and IGFBP-4 increased 2 and 3 fold in the same serum samples within 3-5 days of the burn injury, respectively. This increase returns to normal (day 0-1 value) within 7-10 days for IGFBP-2, but the level of IGFBP-4 remained elevated 4 fold relative to the day 0-1 (p < 0.01). However, the abundance of IGFBP-1 in these serum samples was not significantly altered by the burn injury. By controlling for protein loading, these apparent alterations of IGFBPs in the sera of burned patients were not due to hemodilution. Similarly, significant reductions in IGFBP-3 were not likely due to IGFBP-3 specific protease activity in the sera of burn patients since incubation of sera from burn patients and normal individuals at 37 degrees C did not alter the pattern of IGFBPs in sera obtained from normal individuals. Of interest, the level of IGF-1 protein in these samples was also markedly reduced following severe burn injury similar to IGFBP-3. The results of this study suggest that a marked reduction of serum IGF-1 seen in burn patients is associated with a significant reduction of IGFBP-3, a major IGF-1 binding protein in human serum.

Adult↗
PubMed1994

Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML.

Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures.

Antigens, CD↗
PubMed1994

[Hyperfractionated irradiation for non-small cell lung cancer (NSCLC)--a phase III clinical trial].

From Dec. 1990 to Aug. 1991, 109 patients with NSCLC were randomized into two groups. The first was treated by hyperfractionated irradiation (HF) with 1.15-1.25Gy per fraction, twice daily (interval > or = 6 hrs between fractions), and total doses of 69.6 +/- 2.1Gy. The other was conventional irradiation (CF) with 1.8-2.0Gy per fraction, once a day, and total doses of 63.9 +/- 1.1Gy. All but 11 was included in the analysis. The results showed that HF, compared to CF, could improve immediate response rates in patients with squamous cell carcinoma or with tumor size of 3-6cm (P < 0.05). The comparison of 1 and 2 year survivals did not show significant difference, but 1 year local control rate was 47.3% in HF and 29.1% in CF, P < 0.05. Further stratified analysis showed that the 1 and 2 year local control rates in patients of HF in stage I-IIIa were 54%, 28%; 39%, 13% in patients of CF in stage I-IIIa, P < 0.05. The 1 and 2 year survival rates in patients in stage I-IIIa were 64%, 32% in HF; 18%, 6% in CF, (P < 0.05). An assessment of acute and late toxicity showed no significant difference in incidences between the two groups. It is concluded that HF, compared to CF, can improve 1 and 2 year survival and local control rates of patients in stage I-IIIa.

Adult↗
PubMed1993

Molecular approaches to the diagnosis and treatment of cancer.

We have used autologous bone marrow transplantation (ABMT) as a setting to develop the genetic therapy of cancer in hematopoietic neoplasms based on the use of the bone marrow as a conduit through which to introduce regulatory molecules into the patient. This has involved three developmental phases: 1) learning how to develop genetic modification techniques; 2) learning how to develop in vivo selection techniques for the genetically modified cells; and 3) developing molecular vectors for modification of hematopoietic cells for therapy of cancer. These programs will be summarized in terms of their progress at the conference.

Bone Marrow Transplantation↗
PubMed1993

Genetic therapy of human neoplastic disease.

Molecular biology has provided clinical investigators and basic scientists with the tools to identify those changes present within neoplastic hematopoietic and epithelial cells that lead to the evolution of unregulated patterns of cell growth. This information has made possible the development of therapy that involves genetic modification of either the normal hematopoietic cells (for chemoprotection), or the tumor cells themselves to suppress the growth of these cells. This article will summarize the clinical and laboratory data that is evolving in this area.

Animals↗
PubMed1993

The effect of laminin on molecular motion in the cell membrane and on cell motility.

We have studied the variation of lateral diffusion of proteins in the cell membrane, of membrane lipid fluidity and of the electrophoretic motility (EPM) of macrophages after treatment with extrinsic laminin. The results showed that the lateral diffusion coefficient D value of membrane proteins, the fluidity of membrane lipids and the EPM of macrophages were decreased after laminin had bound to its membrane receptor on the macrophages. These results are important for developing an understanding of the early reaction of plasma membranes and cells in the presence of laminin.

Animals↗
PubMed1992

Molecular cytogenetic study of short arm aberrations in human D, G group chromosomes.

Six cases of Dp+/Gp+, 10 cases of D/G translocation, 1 case of supernumerary marker chromosome, and 1 case of Yqs were studied using molecular and cytogenetic techniques. The Ag-NOR frequencies of the Dp+ and Gp+ groups were found to be higher than those of normal controls, while their satellite association frequencies were lower. Autoradiographic silver grains were not significantly distributed along the p+ part of the marker chromosome as revealed by chromosomal in situ hybridization using an rRNA probe. This result differs from our previous report. It is suggested that there might be different mechanisms for the formation of p+ on acrocentric chromosomes. D/G translocation cases were found to have lost their NOR. A study of supernumerary marker chromosomes and Yqs cases suggested that the marker chromosome and Yqs exerted no phenotypic effect. The mechanism of their formation is discussed.

Adolescent↗
PubMed1992

[Molecular cytogenetic study of an extra small chromosome].

An extra small chromosome was observed in a three-generation family. Eight members of this family were involved, but their phenotypes were normal. Molecular cytogenetic study was carried out, using cytogenetic methods and chromosome in situ hybridization with 3H-labelled rDNA probe. The results showed that this chromosome was from the short arm of chromosome of D/G group. The origin and genetic effects of this chromosome and fertility of the carriers were also discussed were also discussed briefly.

Adult↗
PubMed1991

Pyronaridine: A new antimalarial drug.

The worldwide spread of strains of Plasmodium falciparum that are resistant to chloroquine has highlighted the urgent need for new antimalarial drugs, particularly in less developed tropical countries. However, in the current economic climate the pharmaceutical giants in the developed world are withdrawing from tropical disease research. Consequently, the following article from Fu Sui and Xiao Shuhuo is of particular interest, not only because it summarizes work on on alternative antimalarial drug that is efficacious against multiply resistant Plasmodium but also because this drug has been developed primarily from Chinese research efforts, the results of which have largely only been published in the Chinese scientific literature. The drug under scrutiny is pyronaridine, and is the product of 30 years of chemistry that began with the mepacrine nucleus. This nucleus was selected as the starting point in the search for a chloroquine alternative because the various derivatives synthesized were active against chloroquine-resistant parasites. However, mepacrine itself also needed replacing as it is too toxic for mass use. After synthesizing and screening a huge series of substitutions, the addition of an amodiaquine side-chain to this nucleus was found to give the greatest activity for fewest adverse effects. Being aware of the rapid selection of pyronaridine-resistant Plasmodium strains that occurs in the laboratory, the Chinese efforts have also investigated the use of drug combinations to circumvent or delay the development of drug resistance. In addition to the triple combination described here, pyronaridine and primaquine combinations are under trial against both P. vivax and P. falciparum. Pyronaridine is a highly active blood schizonticide like chloroquine and amodiaquine. It has already undergone extensive trials in humans against both P. falciparum and P. vivax. However, nothing is known of its mode of action, nor the basis for the development of resistance and although it is active against chloroquine-resistant strains of parasite, paradoxically, pyronaridine-resistant Plasmodium is resistant to chloroquine.

Journal Article↗
PubMed1991

A modified electrode plate for low energy electric conversion of atrial fibrillation.

Fifty-six patients with atrial fibrillation associated with heart disease were treated with a modified electrode plate for low energy electric conversion. Fifty-four (96%) of these cases were successfully converted into sinus rhythm using the modified electrode plates, a new site and low energy discharge (an average of about 50 J). To construct the new-style electrode plates, a 2 cm arc segment was cut from each of two electrodes (10 cm in diameter each). As for the site of application, the cut-edge of the anterior chest electrode, which has a concave diameter of 150 cm, is placed close to the right of the sterum over the fourth to sixth intercostal spaces, and the cut-edge of the other electrode is placed to the left of the spinal column at the level of the seventh to ninth thoracic vertebrae. The safe-effective period for the appearance of the first post-discharge QRS complex was found to be 1.4-5.0 s.

Adult↗