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Janet E. Price

Bio: Janet E. Price is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Metastasis & Cancer. The author has an hindex of 48, co-authored 122 publications receiving 8221 citations. Previous affiliations of Janet E. Price include University of Texas at Austin & University of Texas Health Science Center at Houston.


Papers
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Journal Article
TL;DR: The results suggest that the estrogen receptor-negative MDA-MB-435 cell line injected into nude mice is a favorable site for the growth of human breast carcinomas and could be a valuable tool for analysis of the cellular and molecular basis of the metastasis of advanced breast cancer.
Abstract: There are few reports describing experimental models of the growth and metastasis of human breast carcinomas. This article discusses the tumorigenic and metastatic properties of two estrogen receptor-negative breast carcinomas injected into nude mice. Tumor growth in the mammary fatpad (m.f.p.) and the subcutis was compared in female nude mice. The injection of 10(5) viable cells of two human breast carcinoma cell lines (MDA-MB-231 and MDA-MB-435) gave a 100% tumor take rate in the m.f.p., whereas only 40% of the s.c. injections produced tumors and these occurred several weeks after the appearance of the m.f.p. tumors. Thus, the m.f.p. of nude mice is a favorable site for the growth of human breast carcinomas. MDA-MB-435 tumors produced distant metastases in 80% to 100% of recipients. The most common sites for metastasis were the lymph nodes and lungs, with a lower incidence of metastases in muscle (chest wall and thigh), heart, and brain. New variant cell lines were isolated from metastases in the lungs, brain, and heart. All the cell lines were tumorigenic in the m.f.p., and the lung- and heart-derived metastasis lines produced slightly more lung metastases than the original cell line. However, the brain metastasis variant produced significantly fewer lung metastases. Intravenous inoculation of the spontaneous metastasis-derived cell lines produced few lung colonies. Only cell variants isolated from experimental lung metastases showed enhanced lung colonization potential when reinjected i.v. Our results suggest that the estrogen receptor-negative MDA-MB-435 cell line injected in the m.f.p. of nude mice could be a valuable tool for analysis of the cellular and molecular basis of the metastasis of advanced breast cancer.

653 citations

Journal ArticleDOI
TL;DR: Dietary administration of curcumin significantly decreased the incidence of breast cancer metastasis to the lung and suppressed the expression of NF-κB, cyclooxygenase 2, and matrix metalloproteinase-9 in a human breast cancer xenograft model.
Abstract: Currently, there is no effective therapy for metastatic breast cancer after surgery, radiation, and chemotherapy have been used against the primary tumor. Because curcumin suppresses nuclear factor-kappaB (NF-kappaB) activation and most chemotherapeutic agents activate NF-kappaB that mediates cell survival, proliferation, invasion, and metastasis, we hypothesized that curcumin would potentiate the effect of chemotherapy in advanced breast cancer and inhibit lung metastasis. We tested this hypothesis using paclitaxel (Taxol)-resistant breast cancer cells and a human breast cancer xenograft model. As examined by electrophoretic mobility gel shift assay, paclitaxel activated NF-kappaB in breast cancer cells and curcumin inhibited it; this inhibition was mediated through inhibition of IkappaBalpha kinase activation and IkappaBalpha phosphorylation and degradation. Curcumin also suppressed the paclitaxel-induced expression of antiapoptotic (XIAP, IAP-1, IAP-2, Bcl-2, and Bcl-xL), proliferative (cyclooxygenase 2, c-Myc, and cyclin D1), and metastatic proteins (vascular endothelial growth factor, matrix metalloproteinase-9, and intercellular adhesion molecule-1). It also enhanced apoptosis. In a human breast cancer xenograft model, dietary administration of curcumin significantly decreased the incidence of breast cancer metastasis to the lung and suppressed the expression of NF-kappaB, cyclooxygenase 2, and matrix metalloproteinase-9. Overall, our results indicate that curcumin, which is a pharmacologically safe compound, has a therapeutic potential in preventing breast cancer metastasis possibly through suppression of NF-kappaB and NF-kappaB-regulated gene products.

556 citations

Journal ArticleDOI
TL;DR: The expression of various genes that regulates angiogenesis in human ovarian carcinomas is associated with the pattern of the disease and its progression, and targeting specific genes that regulateAngiogenesis could offer new approaches to the treatment of ovarian cancer.
Abstract: Background: By the time patients are diagnosed with ovarian carcinoma peritoneal dissemination of the tumor often has occurred. The progressive growth and spread of ovarian carcinoma depend, in part, on the formation of an adequate blood supply. We determined whether the expression of genes that regulate distinct steps in angiogenesis (i.e., the formation of new blood vessels) was associated with the pattern and progressive growth of human ovarian carcinomas implanted in the peritoneal cavity of nude mice. Methods: Five different human ovarian carcinomas were injected individually into the peritoneal cavity of female NCr-nu/nu nude mice. The expression of basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), interleukin 8 (IL-8), and collagenase type IV (MMP-2 [matrix metalloproteinase-2] and MMP-9) was determined by northern blot analysis, in situ hybridization of messenger RNA, and immunohistochemical analysis. Blood vessel distribution and density, macrophage infiltration pattern, and stromal reaction were determined by immunohistochemical analysis with specific antibodies. Results: Three of the carcinomas produced both solid lesions and ascitic tumors, whereas the remaining two produced only solid lesions. Two of the carcinomas produced rapidly progressive disease, two produced slow disease, and one produced intermediate disease. The formation of ascites was directly associated with expression of VEGF/ VPF, and survival was inversely associated with expression of IL-8. In rapidly growing tumors, the number of blood vessels was high throughout the lesion; in contrast, in slow-growing tumors, most vessels (and infiltrating macrophages) were located at the periphery. Conclusions: The expression of various genes that regulate angiogene-sis in human ovarian carcinomas is associated with the pattern of the disease and its progression. Therefore, targeting specific genes that regulate angiogenesis could offer new approaches to the treatment of ovarian cancer.

389 citations

Journal Article
TL;DR: The technique of peritoneovenous shunting, which returns the fluid to the circulation via a one-way, valved, anastomosis between the peritoneum and the jugular vein, has unrivaled power and interest for those seeking to understand mechanisms underlying tumor metastasis in humans.
Abstract: The technique of peritoneovenous shunting for the alleviation of abdominal pain and distension in malignant ascites due to inoperable cancer, returns the fluid to the circulation via a one-way, valved, anastomosis between the peritoneum and the jugular vein. Surprisingly, although the patients treated with this technique receive direct infusions of malignant tumor cells into the blood, this study of 29 patients, 15 of whom came to autopsy, shows that they did not all develop metastases, some being completely free of such lesions despite long survival. Even when metastases do form, they are small and clinically asymptomatic, and the technique is therefore not hazardous. In some patients, inert tumor cells identifiable by natural markers were recognized in the tissues, but no growing metastases were observed. In others, the distribution of secondary deposits was unexpected in that metastases did not form in the organ containing the first capillary bed encountered, although hematogenous metastases had formed in other organs. Despite the fact that various factors such as (a) the small numbers of patients treated with the technique; (b) the sensitive nature of studies on terminally ill patients; and (c) the absence of consistency in the sample population with regard to factors such as length of survival and site of neoplasm, combine to reduce the number of suitable cases for study, the approach has unrivaled power and interest for those seeking to understand mechanisms underlying tumor metastasis in humans.

304 citations

Journal Article
TL;DR: E1A is a tumor suppressor gene for c-erbB-2/neu-overexpressing human ovarian cancer cells and may be useful in developing therapeutic reagents for these human cancers.
Abstract: Amplification or overexpression of c-erbB-2/neu protooncogene, or both, occur frequently in many different types of human cancers and have been shown to correlate with decreased survival in ovarian cancer patients. We have previously found that the ovarian carcinoma cell line SK-OV-3 overexpresses c-erbB-2/neu mRNA. To further study the biological effect of c-erbB-2/neu overexpression in SK-OV-3 cells, we injected such cells i.p. into female nu/nu mice and found that this cell line forms extensive abdominal tumors and ascites. From the ascites in an injected mouse, we established the SKOV3.ip1 cell line and found that it expressed 2-fold more c-erbB-2/neu-encoded p185 proteins than the parental SK-OV-3 cells. When transformation phenotypes of SK-OV-3 and SKOV3.ip1 cells were compared, SKOV3.ip1 cells showed higher cell growth and DNA synthesis rates, formed more colonies in soft agar, produced larger s.c. tumors, and resulted in shorter survival of nu/nu mice after i.p. injection. These data indicate that the level of c-erbB-2/neu overexpression may correlate with the degree of malignancy in these ovarian carcinoma cells. Since we had previously shown that the adenovirus 5 E1A gene product can suppress transformation and metastatic properties induced by mutation-activated rat neu oncogene in mouse embryo fibroblast cells, we further examined whether E1A can abrogate malignancy in c-erbB-2/neu-overexpressing human ovarian cancer cells. We introduced the E1A gene into c-erbB-2/neu-overexpressing SKOV3.ip1 cells and found that the E1A-expressing ovarian cancer cell lines had decreased c-erbB-2/neu-encoded p185 expression and reduced malignancy, including a decreased ability to induce tumors in nu/nu mice. Therefore, we concluded that E1A is a tumor suppressor gene for c-erbB-2/neu-overexpressing human ovarian cancer cells and may be useful in developing therapeutic reagents for these human cancers.

287 citations


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Journal ArticleDOI
TL;DR: Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion.
Abstract: Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion. Intratumoral hypoxia and genetic alterations can lead to HIF-1alpha overexpression, which has been associated with increased patient mortality in several cancer types. In preclinical studies, inhibition of HIF-1 activity has marked effects on tumour growth. Efforts are underway to identify inhibitors of HIF-1 and to test their efficacy as anticancer therapeutics.

6,024 citations

Journal ArticleDOI
TL;DR: It is now known that the potential of a tumour cell to metastasize depends on its interactions with the homeostatic factors that promote tumour-cell growth, survival, angiogenesis, invasion and metastasis.
Abstract: Researchers have been studying metastasis for more than 100 years, and only recently have we gained insight into the mechanisms by which metastatic cells arise from primary tumours and the reasons that certain tumour types tend to metastasize to specific organs. Stephen Paget's 1889 proposal that metastasis depends on cross-talk between selected cancer cells (the 'seeds') and specific organ microenvironments (the 'soil') still holds forth today. It is now known that the potential of a tumour cell to metastasize depends on its interactions with the homeostatic factors that promote tumour-cell growth, survival, angiogenesis, invasion and metastasis. How has this field developed over the past century, and what major breakthroughs are most likely to lead to effective therapeutic approaches?

4,319 citations

Journal ArticleDOI
17 Nov 2006-Cell
TL;DR: Understanding of the origins and nature of cancer metastasis and the selection of traits that are advantageous to cancer cells is promoted.

3,863 citations

Journal ArticleDOI
TL;DR: Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might lead to new therapeutic targets and better anticancer strategies.
Abstract: The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. For example, the ATP-binding cassette (ABC) drug transporters have been shown to protect cancer stem cells from chemotherapeutic agents. Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anticancer strategies.

3,480 citations

Journal ArticleDOI
14 Oct 2011-Cell
TL;DR: The invasion-metastasis cascade is a multistep cell-biological process that involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments as mentioned in this paper.

3,150 citations