Biomedical subjects

S Fan

Publications and source records attributed to S Fan.

At least 55 records · Page 3Linked to original sources

PubMed2000

Inhibitory effects of Indole-3-carbinol on invasion and migration in human breast cancer cells.

Indole-3-carbinol (I3C) is a promising phytochemical agent in chemoprevention of breast cancer. Our present study is the first description of I3C that significantly inhibits the cell adhesion, spreading and invasion associated with an up-regulation of PTEN (a tumor suppressor gene) and E-cadherin (a regulator of cell-cell adhesion) expression in T47-D human breast cancer cells. Therefore, I3C exhibits anti-cancer activities by suppressing breast tumor cell growth and metastatic spread. Metastatic breast cancer is a devastating problem, clinical application of I3C as a potent chemopreventive agent may be helpful in limiting breast cancer invasion and metastasis.

Anticarcinogenic Agents↗

PubMed2000

Influence of chemically modified tetracyclines on proliferation, invasion and migration properties of MDA-MB-468 human breast cancer cells.

Chemically modified tetracyclines (CMTs) are promising anti-cancer agents. In this study, we found that CMT-3 and CMT-8 showed dose-dependent cytotoxicities in MDA-MB-468 human breast cancer cells. Moreover, both CMT-3 and CMT-8 significantly inhibited in vitro cell migration and invasion at non-cytotoxic concentrations. Anti-invasion and migration potentials of the CMTs were associated with an increased expression of E-cadherin/catenins (alpha, beta and gamma-catenin) and tumor suppressor BRCA1. In addition, CMT-3 and CMT-8 abolished or reduced spontaneous and HGF/SF-induced cell invasion and migration in U-373 MG human glioblastoma cells. Our current finding is the first demonstration that CMT-3 and CMT-8 can activate the function of invasion suppressor molecules associated with the suppression of breast cancer cell invasion and migration. Thus, clinical application of CMTs may provide potential benefit for suppression of breast cancer growth, invasion and metastasis.

Antineoplastic Agents↗

PubMed2000

Indole-3-carbinol is a negative regulator of estrogen receptor-alpha signaling in human tumor cells.

Estrogen, via its binding to the estrogen receptor (ER), plays an important role in breast cancer cell proliferation and tumor development. Indole-3-carbinol (I3C), a compound occurring naturally in cruciferous vegetables, exhibits a potent antitumor activity via its regulation of estrogen activity and metabolism. This study was designed to determine the effect of I3C on the potential to inhibit the ER-alpha. Using a reporter gene driven by the estrogen receptor, I3C (10-125 micromol/L) significantly repressed the 17ss-estradiol (E2)-activated ER-alpha signaling in a dose-dependent manner. I3C and breast cancer susceptibility gene 1 (BRCA1) synergistically inhibited transcriptional activity of ER-alpha. Moreover, I3C down-regulated the expression of the estrogen-responsive genes, pS2 and cathepsin-D, and up-regulated BRCA1. The inhibitory effects of I3C did not contribute to its cytotoxic effects because these activities were observed at less than toxic concentrations. These results further suggest that antitumor activities of I3C are associated not only with its regulation of estrogen activity and metabolism, but also its modulation of ER transcription activity.

Breast Neoplasms↗

PubMed2000

Conditioned immunosuppressive effect of cyclophosphamide on delayed-type hypersensitivity response and a preliminary analysis of its mechanism.

In the present study, camphor odor and intraperitoneal (i.p.) injection of cyclophosphamide (CY) were used as conditioned stimulus (CS) and unconditioned stimulus (US), respectively. In the unconditioned group, mice were exposed to camphor odor for 1 h followed by an i.p. injection of CY (75 mg/kg). On the next day, the above CS/US association trial session was repeated followed by smearing dinitrochlorobenzene (DNCB) on mouse abdominal skin for sensitizing the animal for delayed-type hypersensitivity (DTH) response. Five days after DNCB sensitization, mice were exposed to camphor odor (1 h), followed by an i.p. injection of CY, and then DNCB was smeared on the left ear of mice for the challenge of DTH response. Both the left/right ear weight ratio and the activity of leukocyte migration inhibitory factor (LMIF) were used as the index of DTH response, which was done 24 h after DNCB challenge. In the conditioned group, the treatment was the same as that in the unconditioned group, except that normal saline was injected on day 5 instead of CY. Furthermore, in order to analyze the mechanism of the conditioned response (CR), the mouse serum from the conditioned group (CR serum) was injected into normal mice 6 h prior to DNCB challenge. Results showed that in the conditioned group, left/right ear weight ratio and LMIF activity were statistically lower than that in the DTH group, and there was no difference between conditioned and unconditioned groups. Thus, an animal model of conditioned immunosuppressive response had been established. The results also showed that after CR serum was injected into normal mice, DTH response was also significantly suppressed. However, if CR serum was treated with dialysis (10,000 molecular weight cut-off), the suppressive effect of CR serum on DTH response disappeared. Taken together, the data suggested that a chemical compound(s) in serum, with a molecular weight less than 10,000, was important in mediating the conditioned immunosuppressive response. This may be a very important molecule(s) that could be very critical to our understanding of the interaction between the central nervous system and immune function.

Animals↗

PubMed2000

Biological basis of radiation sensitivity. Part 1: Factors governing radiation tolerance.

Local tumor recurrence after radiation therapy is due primarily to the failure to eradicate all of the tumor cells within the treatment fields. Theoretically, all cancers could be controlled locally if a sufficiently high radiation dose could be delivered to a treatment volume that encompassed all of the tumor cells. In practice, however, the administration of a radiation dose high enough to sterilize all of the tumor cells would pose an unacceptably high risk of severe damage to normal tissues. Technologic improvements in the delivery of therapeutic radiation have led to some improvements in the therapeutic ratio (i.e., the ratio of the dose required to eradicate every tumor cell to the dose that produces unacceptable normal tissue toxicity). Further significant improvements in the therapeutic ratio will drive from an understanding of the mechanisms governing the sensitivity of malignant and normal cells to radiation. Part 1 of this two-part article reviews the clinical and tissue kinetic factors that govern the sensitivity of normal tissues and organs to ionizing radiation. Part 2, which will appear in next month's issue, describes recent insights into the cellular and molecular pathways that determine the sensitivity of normal cells and tumor cells to radiation.

Antineoplastic Agents↗

PubMed2000

Biological basis of radiation sensitivity. Part 2: Cellular and molecular determinants of radiosensitivity.

Recent studies have elucidated some of the molecular and cellular mechanisms that determine the sensitivity or resistance to ionizing radiation. These findings ultimately may be useful in devising new strategies to improve the therapeutic ratio in cancer treatment. Despite the rapid advances in knowledge of cellular functions that affect radiosensitivity, we still cannot account for most of the clinically observed heterogeneity of normal tissue and tumor responses to radiotherapy, nor can we accurately predict which individual tumors will be controlled locally and which patients will develop more severe normal tissue damage after radiotherapy. However, several candidate genes for which deletion or loss of function mutations may be associated with altered cellular radiosensitivity (e.g., ATM, p53, BRCA1, BRCA2, DNA-PK) have been identified. Some of the differences in normal tissue sensitivity to radiation may stem from mutations with milder effects, heterozygosity, or polymorphisms of these genes. Finally, molecular mechanisms linking genetic instability, radiosensitivity, and predisposition to cancer are being unraveled.

Apoptosis↗

PubMed2000

Transforming growth factor beta induces mesangial cell apoptosis through NO- and p53-dependent and -independent pathways.

BACKGROUND: Because transforming growth factor beta (TGF-beta) has been shown to have a bimodal effect on mesangial cell (MC) proliferation, we studied its effect on MC apoptosis. METHODS: Cultured mouse MCs were used to evaluate the effect of TGF-beta. Morphologic evaluation of MC apoptosis was performed by staining cells with H-33342 and propidium iodide. To confirm the effect of TGF-beta on MC apoptosis, DNA was extracted from control and TGF-beta-treated MCs and run on gel electrophoresis. We evaluated the effect of NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on TGF-beta-induced MC apoptosis to determine the role of NO and studied the effect of sodium nitroprusside (SNP) and SNAP (S-nitroso-N-acetyl-penicillamine) on MC apoptosis to confirm the effect of NO. We examined the role of p53 by studying the effect of TGF-beta on MCs derived from p53 knockout mice (p53KO-MC) as well as a normogenic strain (N-MC). We also examined the effect of TGF-beta, SNP, and SNAP on apoptosis of p53 mutant (MDAMB-231) and wild-type p53 (MCF-7) breast cancer cell lines. In addition, Western blots were generated from control, TGF-beta-treated, and SNAP-treated MCs and probed for the expression of p53. RESULTS: TGF-beta promoted MC apoptosis. Moreover, TGF-beta-treated MCs displayed integer multiples of 180 base pairs (ladder pattern). L-NAME inhibited TGF-beta-induced MC apoptosis. Furthermore, SNP and SNAP, NO donors, promoted MC apoptosis. TGF-beta also enhanced the MC expression of p53. TGF-beta induced only a moderate degree of apoptosis in MCs derived from p53KO-MC when compared with N-MCs. Similarly, the TGF-beta-induced apoptosis of MDAMB-231 was of a moderate degree when compared with MCF-7 cells. CONCLUSIONS: We hypothesize that TGF-beta promotes MC apoptosis through NO generation and p53-dependent and -independent pathways.

Animals↗

PubMed2000

[Rainfall interception capacity of forest canopy between two different stands].

Based on the observation data, the rainfall interception capacity of the canopy in plantation and natural forest stands and its relation to rainfall were examined using the method of taking maximum under the same rainfall. The results showed that the rainfall interception capacity of plantation forest increased rapidly with the increase of rainfall, because of its even distribution of branches and leaves, which was higher under low rainfall less than 30 mm, and the saturation interception capacity was easily reached, depending on the quantity of branches and leaves in the canopy. Although the interception capacity of natural forest was relatively weak under low rainfall less than 30 mm, compared with plantation forest, it was much stronger under heavy rainfall more than 30 mm. The saturation interception of natural forest was larger than that of plantation forest.

Ecosystem↗

PubMed2000

[A comparative study on nutrient accumulation and distribution of different generations of Chinese fir plantations].

The nutrient accumulations and distribution of different generation of Chinese fir plantations in central production areas of China were studied through the investigation of plantation with different generation(first, second and third), ages (5, 10, 15, 20 years old) and sites(site index 14, 16 and 18). The nutrient accumulations and distribution of Chinese fir plantations were greatly influenced by the number of planting generation. Nutrient accumulation and utilization efficiency in tree layer of Chinese fir plantations declined with the increasing planting generation number, with the first generation > the second > the third; while the nutrient accumulation of understory vegetation was increased with the increasing of planting generation number. Compared with the first generation plantations, nutrient accumulation of tree layer of the second and the third generations decreased by 17.56% and 36.24% respectively, and the third generation platation decreased by 22.65% than the second generation. Meanwhile, successive planting resulted in a decreasing nutrient utilization efficiency of Chinese fir plantation, and an increasing nutrient necessary for dry matter production per unit, which is disadvantageous to the maintaining of soil fertility, but beneficial to the nutrient accumulation of understory vegetation.

Abies↗

PubMed2000

[Inhibitory effects of ligustrazine on the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 in human umbilical vein endothelial cells induced by preeclamptic plasma].

OBJECTIVE: To determine whether plasma from preeclamptic women induces expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on cultured endothelial cells, and the effects of ligustrazine (LTZ) on the expression of ICAM-1, VCAM-1. METHODS: Human umbilical vein endothelial cells (HUVEC) were isolated by collagenase mixed with trypsin. LTZ was added to HUVEC monolayers grown to confluency on 96-well microplates for 30 minutes. Then HUVEC were incubated with medium containing 20% plasma (volume/volume) either from women with preeclampsia or normotensive pregnancy or nonpregnant women. ICAM-1, VCAM-1 expression was determined after 16 hours of exposure by an enzyme-linked immunosorbent assay (ELISA) technique performed on the cell monolayer. RESULTS: There was a statistically significant increase in ICAM-1, VCAM-1 expression in the endothelial cells exposed to preeclamptic and nonpregnant plasma compared with those exposed to normotensive plasma. Pretreatment with LTZ could reduce the expression of ICAM-1 exposed to preeclamptic plasma, and reduce the expression of VCAM-1 exposed to any of the three sources of plasma. CONCLUSIONS: Preeclamptic plasma induces ICAM-1 and VCAM-1 expression in HUVEC in vitro. Ligustrazine may inhibit the upregulation effects of ICAM-1 and VCAM-1 expression induced by preeclamptic plasma.

Adult↗

PubMed2000

Calcitonin gene-related peptide in Langerhans cells in psoriatic plaque lesions.

OBJECTIVE: To study the mechanism of stress exacerbating psoriasis and the involvement effect of neuropeptides in psoriatic pathogenesis, we investigated the expression and secretion of calcitonin gene-related peptide (CGRP) in psoriatic lesions, then identified the target cells of CGRP, the characters of CGRP positive dendrite cells and the source of CGRP in psoriatic plaque lesions. METHODS: Specific radioimmunoassay (RIA) and immunohistochemistry staining methods were used to determine CGRP secretive content and the target cells of CGRP in psoriatic plaque lesion tissue of vulgaris psoriasis. Double immunofluorenscence staining was done on psoriatic plaque lesion sections by first using rabbit anti-human CGRP antibody and mouse anti-human CD1a antibody, second using PE-conjugated anti-mouse immunoglobulin and FITC-conjugated anti-rabbit immunoglobulin. Confocal laser microscope showed the psoriatic lesion sections. Then both digoxigenin labelled anti-sense and sense RNA probe of CGRP were synthesized to make sure the source of CGRP on the dendrite cells. The psoriatic lesion sections were studied by in situ hybridization. RESULTS: The content of CGRP in vulgaris psoriatic plaque lesions was higher than that of normal controls (P < 0.01). CGRP was also found on the dermal microvascular endothelial cells and the epidermal dendrite cells in psoriatic plague lesions. Further study showed that CGRP existed on the surface of epidermal CD1a + Langerhans cell in psoriatic plaque lesion. The CGRP mRNA expressed around the nucleus of the Langerhans cells in psoriatic lesion. CONCLUSIONS: The pathogenesis of psoriatic plaque lesions was closely related to the overexpression of neuropeptide CGRP. The CGRP contacted with the dermal microvascular endothelial cells and epidermal dendrite cells in psoriatic plaque lesion. The CGRP positive epidermal dendrite cell was CD1a + Langerhans cell. The Langerhans cell itself expressed CGRP mRNA.

Adult↗

PubMed2000

[Relations of chemotherapy-induced tumor necrosis to plasma platin concentration and primary tumor temperature in patients with osteosarcoma in the lower extremities treated by hyperthermic isolation limb perfusion with cisplatin].

OBJECTIVES: To study the relations of chemotherapy-induced tumor necrosis to plasma concentration of platin and primary tumor temperature in hyperthermic isolation limb perfusion (HILP) with cisplatin, and to investigate the correlation between the tumor necrosis rate and the relapse-free survival (RFS). METHODS: Fifteen patients with II B osteosarcoma in the lower extremities were treated with neoadjuvant chemotherapy. Among them, 10 were male and 5 female. The average age was 18 years (ranging from 13 to 29). Chemotherapy included a single bonus dose of HILP with cisplatin (CDDP, 15 mg/m(2)). The plasma concentration of platin and the tumor temperature in the affected limb were measured during the course of the HILP with CDDP. Limb salvage surgery was performed in 9 patients and amputation in 6. After surgery, serial sections of the excised tumor specimens were made to determine the tumor necrosis rate. All of the patients were followed up for more than 5 years. RESULTS: The highest attained tumor temperature was between 41.4 degrees C - 43.0 degrees C (mean 42.3 degrees C +/- 0.46 degrees C), and the platin concentration ranged from 4.56 microg/mL to 14.66 microg/mL (mean 8.93 microg/mL +/- 3.16 microg/mL) during the course of HILP with CDDP. Thirteen patients with a necrosis rate of over 90% were well responded, and the remaining two with a necrosis rate 87.2% and 86.3% were poor responded. Eight patients remained tumor-free for 5 years. Primary tumor temperature and platin concentration were significantly related to the tumor necrosis rate (P = 0.001 and P < 0.001, respectively). No significant correlation was noted between the long-term survival rate and the three parameters in the regression analysis. CONCLUSIONS: HILP with CDDP is useful in the treatment of primary osteosarcoma. Increased tumor necrosis ensure a successful surgical excision of tumor. HILP however is still limited to the patients who are not candidates for lime salvage surgery, because the same condition of high temperature and high concentration of platin are not applicable to distant metastasis.

Adolescent↗

PubMed2000

[Liver transplantation for hepatocellular carcinoma: a report of 8 patients].

OBJECTIVE: To evaluate the feasibility of liver transplantation as a treatment for hepatocellular carcinoma (HCC). METHODS: From July 1995 to October 1998, eight liver cancer patients with cirrhosis underwent liver transplantation in Queen Mary Hospital. The liver grafts were obtained from 6 brainstem dead donors and 2 living donors. Five patients had known HCC and 3 had incidental tumor identified in the explanted liver. TNM staging: stage II (5 cases), stage III (2 cases) and stage IV a (1 case). After liver transplantation, the patients were followed up prospectively for a median of 36 months. Except for one patient who had preoperative chemotherapy, no anticancer treatment was given before and after transplantation. RESULTS: Three patients had acute rejection, 5 developed complication in early post transplantation. All were treated promptly and improved. One patient died one year after operation from septicemia. The recurrence-free survival rates of one and three years were 100% and 83.3%, respectively. CONCLUSIONS: Liver transplantation is a feasible method for treatment of HCC in selected patients. Living donor liver transplantation can overcome the problems of donor shortage and tumor growth while waiting for liver transplantation.

Adult↗

PubMed2000

[The mechanism of biological adaptability of peripheral nerves during limb lengthening in rabbits].

OBJECTIVE: To study the mechanism of subclinical damage and repairing process of peripheral nerves during gradual tibial lengthening. METHODS: Histological investigation, electrophysiological examination of tibial nerve and GAP-43 mRNA expression of sciatic nerve related spinal cord and ganglion were observed in 10%, 20%, 30%, 40% lengthening, and at 2, 4, 8 weeks phases after 40% limb lengthening in 80 rabbits. RESULTS: With the increase of elongation, severer and more obvious nerve damage and stronger expression of GAP-43 mRNA happened. However, nerve regeneration occurred synchronously and the changes recovered gradually within 8 weeks. CONCLUSION: Damage of the peripheral nerves is common during limb lengthening. But, it is temporary and recoverable in case the lengthening rate is < 1 mm/d.

Animals↗

PubMed1999

Coordinate alterations in the expression of BRCA1, BRCA2, p300, and Rad51 in response to genotoxic and other stresses in human prostate cancer cells.

BACKGROUND: BRCA1 and BRCA2 participate in cell cycle progression, apoptosis, and DNA repair pathways. The latter role may be mediated by interaction with DNA recombinase Rad51. The purpose of this study was to evaluate the effects of genotoxic and other cytotoxic agents on expression of DNA damage-response genes (BRCA1, BRCA2, p300, and Rad51) in human prostate cancer cells. METHODS: Subconfluent proliferating cultures of Tsu-Prl or DU-145 cells were treated with various stressful agents and assayed 24 hr later for alterations in: 1) mRNA expression (by semiquantitative reverse transcription-PCR); 2) cell viability (by trypan blue dye exclusion); and 3) protein expression (by Western blotting). RESULTS: Of 26 agents screened, BRCA1 and BRCA2 mRNA reductions were observed in both cell lines after exposure to adriamycin (ADR), camptothecin (CPT), sodium selenite (SLN), and ultraviolet radiation (UV), while nitrogen mustard (HN2) caused mRNA reduction in DU-145 but not in Tsu-Prl. Inhibition of BRCA1/2 expression by ADR and HN2 was blocked by cycloheximide, suggesting that this requires new protein synthesis, while inhibition by CPT, SLN, and UV did not require protein synthesis. Reduction of p300 and Rad51 mRNA levels occurred in parallel with that of BRCA1/2, suggesting coordinate regulation of these genes. The ability of an agent to inhibit mRNA expression was not directly correlated with cytotoxicity. ADR, CPT, UV, and SLN also caused reduction of protein levels; but the kinetics of decreases in protein vs. mRNA differed. After ADR treatment, high molecular weight (Mr hyperphosphorylated) BRCA1 decreased more rapidly than the low Mr species. BRCA2 showed a more rapid decrease in protein than mRNA, while Rad51 showed the opposite. By 48 and 72 hr post-ADR, all four mRNAs and proteins were reduced to well below control levels, except for Rad51 protein, which was only moderately decreased. CONCLUSIONS: Selected DNA-damaging agents (ADR, CPT, and UV) and a reducing agent (SLN) inhibited BRCA1/2, p300, and Rad51 expression in prostate cancer cells, although decreases in mRNA vs. protein did not coincide. We postulate that temporal changes in relative protein levels affect different phases of the stress response, and that the ultimate downregulation of all four genes promotes prostate cancer survival.

BRCA2 Protein↗

PubMed1999

BRCA1 inhibition of estrogen receptor signaling in transfected cells.

Mutations of the breast cancer susceptibility gene BRCA1 confer increased risk for breast, ovarian, and prostatic cancers, but it is not clear why the mutations are associated with these particular tumor types. In transient transfection assays, BRCA1 was found to inhibit signaling by the ligand-activated estrogen receptor (ER-alpha) through the estrogen-responsive enhancer element and to block the transcriptional activation function AF-2 of ER-alpha. These results raise the possibility that wild-type BRCA1 suppresses estrogen-dependent transcriptional pathways related to mammary epithelial cell proliferation and that loss of this ability contributes to tumorigenesis.

BRCA1 Protein↗

PubMed1999

Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein.

Previous studies have shown that the cell cycle-regulated E2F transcription factor is subjected to both positive and negative control by phosphorylation. Here we show that in transient transfection experiments, adenovirus E1A activation of the viral E2 promoter is abrogated by coexpression of the viral E4 open reading frame 4 (E4-ORF4) protein. This effect does not to require the retinoblastoma protein that previously has been shown to regulate E2F activity. The inhibitory activity of E4-ORF4 appears to be specific because E4-ORF4 had little effect on, for example, E4-ORF6/7 transactivation of the E2 promoter. We further show that the repressive effect of E4-ORF4 on E2 transcription works mainly through the E2F DNA-binding sites in the E2 promoter. In agreement with this, we find that E4-ORF4 inhibits E2F-1/DP-1-mediated transactivation. We also show that E4-ORF4 inhibits E2 mRNA expression during virus growth. E4-ORF4 has previously been shown to bind to and activate the cellular protein phosphatase 2A. The inhibitory effect of E4-ORF4 was relieved by okadaic acid, which inhibits protein phosphatase 2A activity, suggesting that E4-ORF4 represses E2 transcription by inducing transcription factor dephosphorylation. Interestingly, E4-ORF4 did not inhibit the transactivation capacity of a Gal4-E2F hybrid protein. Instead, E4-ORF4 expression appears to result in reduced stability of E2F/DNA complexes.

Adenovirus E1A Proteins↗

PubMed1999

Self-oriented regular arrays of carbon nanotubes and their field emission properties

The synthesis of massive arrays of monodispersed carbon nanotubes that are self-oriented on patterned porous silicon and plain silicon substrates is reported. The approach involves chemical vapor deposition, catalytic particle size control by substrate design, nanotube positioning by patterning, and nanotube self-assembly for orientation. The mechanisms of nanotube growth and self-orientation are elucidated. The well-ordered nanotubes can be used as electron field emission arrays. Scaling up of the synthesis process should be entirely compatible with the existing semiconductor processes, and should allow the development of nanotube devices integrated into silicon technology.

Journal Article↗