Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A major incentive for the development of the synthetic retinoids has been their potential for the treatment and prevention of cancer. Early studies demonstrated that treatment with isotretinoin or etretinate alone could result in the regression of some existing skin cancers. However, even at high doses the response rates were poor. Greater efficacy has been observed with retinoids used in the prevention of cancer of the skin and oral cavity in high-risk patients. The potential for retinoids as chemopreventive agents is being further explored as selected retinoids are being targeted to specific malignancies, such as fenretinide for breast cancer chemoprevention. The effectiveness of tretinoin as a treatment for promyelocytic leukemia has raised enthusiasm for retinoids as cancer therapeutic agents. Furthermore, evidence of synergy between the retinoids and a variety of cytokines as enhances of differentiation chart a bright future for retinoids in oncology.
 ...
PMID:Retinoids for the future: oncology. 146 Jan 23

Triptolide (Tri) is a diterpenoid triepoxide isolated from Tripterygium wilfordii Hook F. The effects of Tri on the colony formation of breast cancer cell lines MCF-7 and BT-20, stomach cancer cell lines MKN-45, MKN-7, and KATO-III, and promyelocytic leukemia cell line HL-60 were reported. Using Hamburger-Salmon's double layer agar technique with certain modifications, cancer cells were cultured in 0.3% agar in a highly humidified atmosphere of 5% CO2 at 37 degrees C for 14-21 d. Colonies were counted on d 14 (occasionally d 21) with the colony analyzer system CA-7A. Of the 5 solid tumor cell lines tested, 4 showed diminished colony formation in soft agar by greater than 70% of control value in Tri 10(-8) mol.L-1 (continuous exposure). The magnitudes of the inhibitory effect of Tri on most breast and stomach cancer cell lines were similar to that on the leukemia cell line HL-60. IC50 were 0.504-1.22 micrograms.L-1. The clinically achievable peak plasma concentration (PPC) of Tri was estimated as 0.15 mg.L-1, being 72-126 times higher than the IC70 of the cancer cell lines except KATO-III. The results suggest that Tri might have a potential therapeutic effect on some types of solid tumors, e.g., breast and stomach cancers.
 ...
PMID:Inhibitory effect of triptolide on colony formation of breast and stomach cancer cell lines. 181 94

The cytotoxic activity of 5'-deoxy-5-fluorouridine (5'-ddFUrd) was established in six cultured human tumor lines: 47-DN and MCF-7 breast carcinomas, MG-63 osteosarcoma, HCT-8 colon carcinoma, Colo-357 pancreatic carcinoma, and HL-60 promyelocytic leukemia. Cells were exposed to a wide range of 5'-dFUrd concentrations (from 0.1 microM to 1.0 mM) for 3, 6, or 24 hrs, and then cloned using standard in vitro clonogenic assays. 5'-dFUrd exhibited its best activity in the 47-DN and MCF-7 breast cell lines and in the MG-63 osteosarcoma line (3-hr LD50 values of 32, 34, and 38 microM, respectively). Less activity was observed in the HCT-8 colon (LD50 = 195 microM) and Colo-357 pancreatic (LD50 = 155 microM) tumor lines, and ver poor activity was noted in the HL-60 leukemia cell line (LD50 = 465 microM). The metabolism of 5'-dFUrd to 5-FU (FUra) and FUra-nucleotides was determined and found to directly correlate with the potency of 5'-FUrd in these cell lines. These results suggest that: (a) there is a marked variation in sensitivity of human cancer cells of different tissue origin to 5'-dFUrd, (b) there is a direct relationship between the sensitivity of human cells to 5'-dFUrd and the ability of the cell to metabolize 5'-dFUrd to FUra, and (c) increasing exposure period of cells to 5'-dFUrd did not markedly alter 5'-dFUrd potency in all human cancer cells examined, with the exception of the 47-DN breast cancer cells.
 ...
PMID:Cytotoxic activity of 5'-deoxy-5-fluorouridine in cultured human tumors. 622 89

The decay of nitroxide spin label electron paramagnetic resonance (EPR) absorption intensity was used to investigate the doxorubicin-mediated intracellular generation of free radicals. The effects of 50-500 micrograms/ml doxorubicin on human tumor cells (MCF-7, breast cancer cells, and HL-60, promyelocytic leukemia, cells) were studied by measuring 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) absorption intensity decay (TAID) at a TEMPO concentration of 10 microM. Doxorubicin accelerated the TAID in both cell lines with a detection limit of 50 micrograms/ml for MCF-7 cells and 500 micrograms/ml doxorubicin for HL-60 cells. Preincubation of cells with the iron chelating agent, deferoxamine (5 mM), partially prevented the effects of doxorubicin on the TAID. Catalase and copper, zinc-superoxide dismutase (Cu,Zn-SOD) had no influence on the effects of doxorubicin on the TAID in intact cells. However, Cu,Zn-SOD completely abolished the effects of doxorubicin on the TAID in a MCF-7 cell-free system. Our findings suggest that doxorubicin mediates the intracellular generation of O2.- and that iron is involved in this process.
 ...
PMID:Doxorubicin-mediated free radical generation in intact human tumor cells enhances nitroxide electron paramagnetic resonance absorption intensity decay. 841 98

Lung cancer in women has replaced uterine cancer among the cancers causing the highest mortality in women. However, breast cancer remains a leading cause of death because of increasing incidence. Potential causes for the increase in both these diseases in women will be explored. An exciting development in recent years has been the clarification of the role of oncogenes in carcinogenesis. It appears that some cancers require multiple sequential mutations for malignant transformation to occur. This may be the model for the study of carcinogenesis. These developments in molecular genetics have important implications in screening, diagnosis, prevention, and in treatment strategies. We may be witnessing the beginning of the era of cell differentiation therapy. Retinoids have a potential for impacting on the treatment of neoplasms such as promyelocytic leukemia and oropharyngeal cancers. Understanding of the mechanism of cell differentiation may be forthcoming although molecular genetic studies.
 ...
PMID:The past, the present, the future. 843 74

9-cis retinoic acid (9-cis RA) is a retinoid receptor pan-agonist that binds with high affinity to both retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Using a variety of in vivo and in vitro cancer models, we present experimental data that 9-cis RA has activity as a potential chemotherapeutic agent. Treatment of the human promyelocytic leukemia cell line HL-60 with 9-cis RA decreases cell proliferation, increases cell differentiation, and increases apoptosis. Induction of apoptosis correlates with an increase in tissue transglutaminase (type II) activity. In vivo, 9-cis RA induces complete tumor regression of an early passage human lip squamous cell carcinoma xenograft. Finally, 9-cis RA inhibits the anchorage-independent growth of the human breast cancer cell lines MCF-7 and LY2 (an antiestrogen-resistant MCF-7 variant). Transient co-transfection assays indicate that 9-cis RA inhibits estrogen receptor transcription of an ERE-tk-LUC reporter through RAR or RXR receptors. These data suggest that retinoid receptors can antagonize estrogen-dependent transcription and provides one possible mechanism for the inhibition of cell growth by 9-cis RA in breast cancer cell lines. In summary, these findings present evidence that 9-cis RA has a wide range of activities in human cancer models.
Breast Cancer Res Treat 1996
PMID:The efficacy of 9-cis retinoic acid in experimental models of cancer. 882 26

Our previous studies demonstrated that the promyelocytic leukemia gene, PML which involved in the 15;17 translocation in acute promyelocytic leukemia (APL) is a growth and transformation suppressor. In this study, recombinant PML adenovirus, Ad-PML was constructed and used to infect human breast cancer cells in vitro and in vivo, the anti-oncogenic function of PML and its mechanism of growth suppressing effect in breast cancer cells were examined. We showed that Ad-PML effectively infected the MCF-7 and SK-BR-3 cells. A high level of PML protein was expressed within 24 h post-infection and a detectable level remained at day 16. Ad-PML significantly suppressed the growth rate, clonogenicity, and tumorigenicity of breast cancer cells. Intratumoral injections of MCF-7-induced tumors by high titer Ad-PML suppressed tumor growth in nude mice by about 80%. The injection sites expressed high level of PML and associated with a massive apoptotic cell death. To elucidate the molecular mechanism of PML's growth suppressing function, we examined the effect of Ad-PML on cell cycle distribution in MCF-7 and SK-BR-3 cells. We found that Ad-PML infection caused a cell cycle arrest at the G1 phase. We further showed that G1 arrest of MCF-7 cells is associated with a significant decrease in cyclin D1 and CDK2. An increased expression of p53, p21 and cyclin E was found. The Rb protein became predominantly hypophosphorylated 48 h post-infection. These findings indicate that PML exerts its growth suppressing effects by modulating several key G1 regulatory proteins. Our study provides important insight into the mechanism of tumor suppressing function of PML and suggests a potential application of Ad-PML in human cancer gene therapy.
 ...
PMID:Recombinant PML adenovirus suppresses growth and tumorigenicity of human breast cancer cells by inducing G1 cell cycle arrest and apoptosis. 958 81

1alpha,25-dihydroxyvitamin D(3) (VD) is a pleiotropic nuclear hormone that also has effects on cell cycle regulation. VD and its synthetic analogues are known inhibitors of cellular growth and inducers of apoptosis, however, the primary mediator genes of these effects largely remain unknown. In order to identify novel targets for VD, that may be involved in the regulation of the cell cycle, a differential display PCR (ddPCR) approach was applied to the MCF-7 human breast cancer cell line, which provided the gene for cyclin C as an interesting candidate. Quantitative assessment of cyclin C expression showed that the gene was significantly upregulated by VD and its analogues, EB1089 and CB1093 both on the level of mRNA expression and more so on the level of protein expression in MCF-7 cells. Upregulation of cyclin C protein expression could also be confirmed in MeWo human melanoma and in U937 human promyelocytic leukemia cells. This observation adds a new gene candidate to the list of primary VD responding genes. Cyclin C is not a typical cyclin, as it apparently modulates the activity of the RNA polymerase II complex, which provides fresh insight into the mechanisms of cell cycle and general transcriptional regulation by VD and its analogues.
 ...
PMID:Cyclin C is a primary 1alpha,25-dihydroxyvitamin D(3) responding gene. 1067 18

The promyelocytic leukemia (PML) gene encodes a putative tumor suppressor gene involved in the control of apoptosis, which is fused to the retinoic acid receptor alpha (RARalpha) gene in the vast majority of acute promyelocytic leukemia (APL) patients as a consequence of chromosomal translocations. The PMLRARalpha oncoprotein is thought to antagonize the function of PML through its ability to heterodimerize with and delocalize PML from the nuclear body. In APL, this may be facilitated by the reduction to heterozygosity of the normal PML allele. To determine whether PML acts as a tumor suppressor in vivo and what the consequences of deregulated programmed cell death in leukemia and epithelial cancer pathogenesis are, we crossed PML(-/-) mice with human cathepsin G (hCG)-PMLRARalpha or mammary tumor virus (MMTV)/neu transgenic mice (TM), models of leukemia and breast cancer, respectively. The progressive reduction of the dose of PML resulted in a dramatic increase in the incidence of leukemia, and in an acceleration of leukemia onset in PMLRARalpha TM. By contrast, PML inactivation did not affect neu-induced tumorigenesis. In hemopoietic cells from PMLRARalpha TM, PML inactivation resulted in impaired response to differentiating agents such as RA and vitamin D3 as well as in a marked survival advantage upon proapoptotic stimuli. These results demonstrate that: (a) PML acts in vivo as a tumor suppressor by rendering the cells resistant to proapoptotic and differentiating stimuli; (b) PML haploinsufficiency and the functional impairment of PML by PMLRARalpha are critical events in APL pathogenesis; and (c) aberrant control of programmed cell death plays a differential role in solid tumor and leukemia pathogenesis.
 ...
PMID:Role of promyelocytic leukemia (PML) protein in tumor suppression. 1118 7

The effect of high-frequency ultrasound on doxorubicin (DOX) release from Pluronic micelles and intracellular DOX uptake was studied for promyelocytic leukemia HL-60 cells, ovarian carcinoma drug-sensitive and multidrug-resistant (MDR) cells (A2780 and A2780/ADR, respectively), and breast cancer MCF-7 cells. Cavitation events initiated by high-frequency ultrasound were recorded by radical trapping. The onset of transient cavitation and DOX release from micelles were observed at much higher power densities than at low-frequency ultrasound (20-100 kHz). Even a short (15-30 s) exposure to high-frequency ultrasound significantly enhanced the intracellular DOX uptake from PBS, RPMI 1640, and Pluronic micelles. The mechanisms of the observed effects are discussed.
 ...
PMID:Drug delivery in pluronic micelles: effect of high-frequency ultrasound on drug release from micelles and intracellular uptake. 1239 66


1 2 3 4 5 6 7 Next >>