UMLS:C0006142 - FACTA Search

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Query: UMLS:C0006142 (breast cancer)
160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood progenitor harvests of breast cancer patients are contaminated with tumor cells, suggesting a potential role for these cells in the relapse after high-dose chemotherapy. Whereas physical purging methods do not eliminate contaminating tumor cells completely, pharmacological purging, although highly efficient, is hampered by a strong nonspecific toxicity toward hematopoietic progenitor cells. Taking advantage of the high efficiency of adenovirus-mediated gene transfer to epithelial cells, we selectively loaded breast cancer cells in vitro with a cytotoxic drug by gene transfer of the prodrug-converting enzyme cytosine deaminase (AdCMV.CD) and 5-fluorocytosine (5-FC). Despite the low dose of vector administered, limited exposure to 5-FC, and transplantation only of viable tumor cells into SCID mice, all animals that received cells treated in vitro with AdCMV.CD plus 5-FC were completely free of tumor development. These data show that the selective loading of tumor cells with AdCMV.CD/5-FC might be useful for purging of autografts.
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PMID:Ex vivo breast cancer cell purging by adenovirus-mediated cytosine deaminase gene transfer and short-term incubation with 5-fluorocytosine completely prevents tumor growth after transplantation. 979 11

In the present study, we developed an antitumor immunoconjugate that appears to be promising as a novel curative antitumor agent against a variety of human solid tumors. We generated a new antihuman endoglin (EDG) monoclonal antibody (mAb) K4-2C10 (or termed SN6f) that cross-reacts with mouse endothelial cells. Such cross-reactive anti-EDG mAbs have not been reported previously. This mAb was used to target tumor-associated vasculature in SCID mice inoculated with human tumors. No anti-EDG mAb or its immunoconjugates have previously been successfully used for targeting vasculature in vivo. In this study, MCF-7 human breast cancer cells were inoculated s.c. into SCID mice. K4-2C10 did not react with the MCF-7 cells but showed a weak reactivity with mouse endothelial cells. The mAb reacted with the proliferating endothelial cells more strongly than with the quiescent endothelial cells. The mAb exhibited much stronger reactivity (>10-fold) with human endothelial cells than with mouse endothelial cells and reacted strongly with vascular endothelium of tumor-associated blood vessels in a variety of human malignant tissues. Conjugates of K4-2C10 with ricin A chain (RA) and deglycosylated ricin A chain (dgRA) showed a weak but specific cytotoxic activity against murine endothelial cells in vitro; the 50% inhibitory dose of the RA and dgRA conjugates was 54 nm and 29 nm, respectively. Remarkable antitumor efficacy was observed when a small amount (a total of 60 microgram corresponding to 24% of the LD50 dose) of the dgRA conjugate was administered i.v. into SCID mice that had been inoculated s.c. with MCF-7. Unconjugated mAb K4-2C10 was not significantly effective in the inhibition of the tumor growth. The immunotoxin (IT) completely inhibited growth of the tumor in all of the treated mice (n = 8). Furthermore, similar antitumor efficacy was observed when the IT was administered i.v. into the tumor-inoculated SCID mice that had been pretreated with unconjugated K4-2C10 to block the potentially available weak binding sites of normal tissues. The strong therapeutic effects of the IT were reproduced in another set of therapeutic experiments. No significant side effects were observed in the mice. The differences in the tumor growth between the control group and the IT-treated groups were statistically significant. The IT showed antiangiogenic activity in the dorsal air sac method. The results indicate that K4-2C10 IT effectively treated the tumor-bearing mice by selectively inhibiting the tumor-associated blood vessels and by disrupting tumor-associated angiogenesis. The strong antitumor efficacy of the K4-2C10 IT is remarkable in view of the fact that K4-2C10 and its IT showed only a weak reactivity with mouse endothelial cells, and a relatively small amount of the IT was administered i.v. to treat s.c. tumors. We anticipate that the K4-2C10 IT will show much stronger antitumor efficacy and antiangiogenic activity in patients with solid tumors and other angiogenesis-associated diseases. The present results demonstrate for the first time that an anti-EDG mAb or its immunoconjugate can effectively target tumor-associated vasculature in vivo.
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PMID:Long-lasting complete inhibition of human solid tumors in SCID mice by targeting endothelial cells of tumor vasculature with antihuman endoglin immunotoxin. 981 81

Sestamibi is known to be a substrate for P-glycoprotein, the membrane transporter which confers multidrug resistance by pumping certain chemotherapeutic agents out of tumour cells. In this study, the utility of sestamibi imaging for detecting inhibition of P-glycoprotein (Pgp) function by two potent, second-generation chemosensitizers, PSC833 and GG918, was assessed in a mouse xenograft model of multidrug-resistant human breast cancer, MCF7-AdrR. Preliminary in vitro studies confirmed that MCF7-AdrR cells accumulate only low levels of sestamibi and that both sensitizers inhibit transporter function to a similar extent, resulting in 20-fold higher accumulation of sestamibi. MCF7-AdrR cells were grown as a xenograft in SCID mice and sestamibi kinetics in the tumour were analysed by dynamic imaging (30 frames at a rate of one frame per minute). Administration of either chemosensitizer produced a dose-dependent slowing of the efflux rate of sestamibi compared to untreated tumours. The same effect was evident in two additional parameters: percent activity remaining at 30 min determined by imaging and sestamibi levels measured in excised tissues. These results show that sestamibi imaging can detect inhibition of Pgp function and suggest that this approach could be used clinically to document effective delivery of chemosensitizers.
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PMID:99Tcm-sestamibi imaging of inhibition of the multidrug resistance transporter in a mouse xenograft model of human breast cancer. 1008 59

CD40 is present on B cells, monocytes, dendritic cells, and endothelial cells, as well as a variety of neoplastic cell types, including carcinomas. CD40 stimulation by an antibody has previously been demonstrated to induce activation-induced cell death in aggressive histology human B-cell lymphoma cell lines. Therefore, we wanted to assess the effects of a recombinant soluble human CD40 ligand (srhCD40L) on human breast carcinoma cell lines. Human breast carcinoma cell lines were examined for CD40 expression by flow cytometry. CD40 expression could be detected on several human breast cancer cell lines and this could be augmented with interferon-gamma. The cell lines were then incubated with a srhCD40L to assess effects on in vitro growth. srhCD40L significantly inhibited the proliferation of the CD40(+) human breast cancer cell lines. This inhibition could also be augmented with interferon-gamma. Viability was also affected and this was shown to be due to increased apoptosis of the cell lines in response to the ligand. Treatment of tumor-bearing mice was then performed to assess the in vivo efficacy of the ligand. Treatment of tumor-bearing SCID mice with the ligand resulted in significant increases in survival. Thus, CD40 stimulation by its ligand directly inhibits human breast carcinoma cells in vitro and in vivo. These results suggest that srhCD40L may be of clinical use to inhibit human breast carcinoma growth.
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PMID:Inhibition of human breast carcinoma growth by a soluble recombinant human CD40 ligand. 1021 96

Endoglin (CD105), which is a component of the TGF-beta receptor complex, is highly expressed at the surface of proliferating human endothelial cells such as those of tumor vessels. In the present study, we tested the antitumor efficacy of (125)I-labeled anti-endoglin monoclonal antibodies (MAbs), SN6f and SN6j, against s. c. tumors of MCF-7 human breast cancer cells in SCID mice by i.v. administration. SN6f and SN6j cross-react weakly with mouse endothelial cells, but show no significant reactivity with MCF-7 tumor cells. These MAbs are effectively internalized into the cells after binding to the cell surface antigen of endothelial cells. Four groups of SCID mice (n = 10 or 9 in each group) inoculated s.c. with 8 x 10(6) MCF-7 cells were treated with (125)I-SN6f (10 microCi), (125)I-SN6j (10 microCi), a (125)I-labeled isotype-matched control IgG (10 microCi) or PBS. The systemic therapy was performed in 2 series, i.e., on days 3, 5, 7 and days 58, 60, 62. Both (125)I-SN6f and (125)I-SN6j showed significant growth suppression of the tumors, whereas the (125)I-labeled control IgG did not show any significant antitumor efficacy. No significant toxicity or weight loss was observed in mice treated with either (125)I-SN6f or (125)I-SN6j. After 100 days of observation, autopsies revealed no significant organ damage. Our results show the possible usefulness of antiangiogenic radioimmunotherapy using (125)I-labeled anti-endoglin MAbs.
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PMID:Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using (125)I-labeled anti-endoglin monoclonal antibodies. 1041 73

Increased expression of the epithelial mucin MUC1 has been linked to tumor aggressiveness in human breast carcinoma. Recent studies have demonstrated that overexpression of MUC1 interferes with cell-substrate and cell-cell adhesion by masking cell surface integrins and E-cadherin. Additionally, the cytoplasmic tail of MUC1 is involved in signal transduction and interactions with catenins. In the present study, we have examined the in vitro expression of MUC1 mRNA and protein in a panel of 14 human breast cancer cell lines using northern blotting, western blotting, immunocytochemistry, and flow cytometry. Considerable variability of expression was noted not only between cell lines but also within several individual lines. Many cell lines such as BT 20, KPL-1, and T47D expressed abundant MUC1 whilst others such as MDA-MB-231 and MCF-7 showed intermediate expression, and MDA-MB-435 and MDA-MB-453 expressed very low levels. Low levels of MUC1 expression were associated with decreased expression of cytokeratin and increased expression of vimentin. Additionally, 12 of the cell lines were established as xenografts in immunocompromised (SCID) mice, and MUC1 expression in both the primary tumors as well as metastases was assessed immunohistochemically. In general, in vivo expression mirrored in vitro expression, although there was reduced in vivo expression in T47D and ZR-75-1 xenografts. Although we showed no correlation between tumorigenicity or metastasis and MUC1 expression, this study will assist development of experimental models to assess the influence of MUC1 of on breast cancer progression.
Breast Cancer Res Treat 1999 Dec
PMID:Heterogeneity of MUC1 expression by human breast carcinoma cell lines in vivo and in vitro. 1071 87

2-Methoxyestradiol. 2-Methoxyestradiol (2-ME) is an endogenous estradiol metabolite that disrupts microtubule function, suppresses murine tumors, and inhibits angiogenesis. Since some microtubule inhibitors have been shown to alter radiosensitivity, we have evaluated 2-ME as a radiation enhancer in vitro. H460 human lung cancer cells were plated, treated with 2-ME for 24 h, and irradiated; then colony-forming ability was assessed. The radiation dose enhancement ratios (DERs) using this protocol were 1.3, 1.8 and 2.1 for 1, 1.5 and 2 microM 2-ME, respectively. Using a single-cell plating protocol, the respective DERs were 1.2, 1.5 and 1.8. The parent compound of 2-ME, beta-estradiol, did not enhance radiation effects at equally cytotoxic doses. Isobologram analysis showed that 1 microM 2-ME was additive with radiation, but that 1.5 and 2 microM were synergistic. Cell cycle analysis showed a dose-dependent increase in the percentage of cells in the radiosensitive G(2)/M phase after a 24-h treatment with 2-ME; a threefold increase in the percentage of cells in G(2)/M phase was observed using 2 microM 2-ME. Treatment with 2 microM 2-ME almost completely inhibited repair of sublethal damage (SLD) as shown using split-dose recovery. Radiosensitive, repair-deficient murine SCID (severe combined immunodeficient) cells did not show enhancement of radiation effects with 2 microM 2-ME, but enhancement was observed in the wild-type parental cells (CB-17). SCID cells complemented with human DNA-dependent protein kinase restored radioenhancement by 2-ME. In addition, MCF-7 breast cancer cells were also radiosensitized by 2 microM 2-ME (DER = 2.1). These data suggest that 2-ME is a potential radiation sensitizer, in addition to its previously reported antitumor and antiangiogenic properties. We have verified the antiangiogenic activity of 2-ME in vitro using human endothelial cells. Based on these results, we hypothesize that the mechanism of radiation enhancement may involve redistribution of cells into G(2)/M phase by 2-ME, and that the resulting population of cells is repair-deficient and thus radiosensitive.
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PMID:Enhancement of radiation effects in vitro by the estrogen metabolite 2-methoxyestradiol. 1076 Sep 97

GAP31 (Gelonium protein of 31 kDa) and MAP30 (Momordica protein of 30 kDa) are agents isolated from the medicinal plants Gelonium multiflorum and Momordica charantia, respectively. The current study was conducted to investigate the efficacy of GAP31 and MAP30 on estrogen-independent and highly metastatic human breast tumor MDA-MB-231 both in vitro and in vivo. The effect of these agents on the expression of breast tumor antigen HER2 (also known as neu or as c-erbB 2) was also examined. Treatment of MDA-MB-231 breast cancer cells with GAP31 and MAP30 resulted in inhibition of cancer cell proliferation as well as inhibition of the expression of HER2 gene in vitro. When MDA-MB-231 human breast cancer cells were transferred into SCID mice, the mice developed extensive metastases and all mice succumbed to tumor by day 46. Treatment of the human breast cancer bearing SCID mice with GAP31 or MAP30 at 10 micrograms/injection EOD for 10 injections resulted in significant increases in survival, with 20-25% of the mice remaining tumor free for 96 days. Thus, anti-tumor agents GAP31 and MAP30 are effective against human breast cancer MDA-MB-231 in vitro and in vivo. These agents may therefore be a potential therapeutic use against breast carcinomas.
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PMID:Inhibition of MDA-MB-231 human breast tumor xenografts and HER2 expression by anti-tumor agents GAP31 and MAP30. 1081 Mar 36

The objective of the present study was to investigate the effect of dietary phytosterols on the growth and metastasis of the human breast cancer MDA-MB-231 cell line xenografted in SCID mice. Two groups of animals were fed AIN-93G diet supplemented with 0.2% cholic acid and 2% sterol (cholesterol or phytosterol mixture) for 15 days before inoculation of the tumor into the right inguinal mammary fat pad. Tumor growth and food consumption were recorded weekly throughout the 8 weeks of the experiment. At the end of the experiment, the animals fed phytosterol had a 40% lower serum cholesterol and 20 and 30 fold higher serum beta-sitosterol and campesterol, respectively as compared to those fed cholesterol. There was no difference between the two groups in body weight and food consumption. However, the tumor size in animals fed phytosterols was 33% smaller (P < 0.03) and had 20% fewer metastases to lymph nodes and lungs than the cholesterol group. At termination, the tumor weight of the animals fed the phytosterol diet was also less (P < 0.07) than that of the cholesterol group. It is concluded that dietary phytosterols retard the growth and spread of breast cancer cells.
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PMID:Dietary phytosterol inhibits the growth and metastasis of MDA-MB-231 human breast cancer cells grown in SCID mice. 1081 Mar 60

Because adenocarcinoma of the breast expresses receptors for alpha-fetoprotein (AFP), we studied Tc-99m AFP as a radiopharmaceutical to detect breast cancer. The biodistribution of Tc-99m radiolabeled natural human AFP (full length) and recombinant domain III (DIII) of human AFP was compared to Tc-99m sestamibi and Tl-201 in a murine model of human breast cancer. Estrogen receptor positive (MCF7, T-47D) and estrogen receptor negative (MDA-MB-231, BT-20) human breast cancer xenografts were grown subcutaneously in the lateral thorax region of immunosuppressed mice (ICR SCID). Quantitative comparisons of percent-injected dose per gram of tissue (%ID/gram) and tumor to thigh ratio (T/Th) were performed at 0-60 minutes and at 24 hours following injection. For most tumors, T/Th for AFP and DIII was significantly greater than T/Th for Tc-99m sestamibi and Tl-201. In all breast cancers (BT-20, MCF7, MDA-MB-231, T-47D), Tc-99m AFP T/Th increased from 60 minutes to 24 hours, suggesting good tumor retention of this radiopharmaceutical. DIII and AFP had significantly higher %ID/gram than either Tl-201 or Tc-99m sestamibi when considered across all tumor types at both 60 minutes and 24 hours. The data suggests that localization of Tc-99m AFP in human breast cancer xenografts is initially rapid, increases with time, and is superior to Tc-99m sestamibi and Tl-201. Given its high uptake by breast cancer cells, its low non-tumor localization and its rapid renal excretion, these Tc-99m AFP preparations may be useful agents to detect human breast carcinoma.
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PMID:Scintigraphic detection of breast cancer xenografts with Tc-99m natural and recombinant human alpha-fetoprotein. 1085 Mar 35

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