Biomedical subjects

K J Pienta

Publications and source records attributed to K J Pienta.

136 records · Page 8Linked to original sources

PubMedDate not supplied

Establishment of an immortalized Copenhagen rat bone marrow endothelial cell line.

Bone marrow endothelial cells are critical mediators in the processes of cell trafficking as well as cancer metastasis, however few established models exist. An immortal cell line of Copenhagen rat bone marrow endothelium was established after infection of primary cultured cells with Adenovirus-12 SV40 hybrid virus and designated YPBE-1. The established cell line has continued to proliferate more than 70 population doublings and has not undergone "crisis". It stains positively for SV40 T-antigen in its nuclei by immunohistochemistry and grows in a monolayer with a cobblestone appearance. It demonstrates Dil-Ac-LDL uptake as an endothelial marker. YPBE-1 does not express Integrin beta 3 or endothelin, but does express Integrin alpha 6 beta 1 on the plasma membrane and demonstrates tube formation in Matrigel. This cell line of rat bone marrow endothelial origin should be useful for studying mechanisms of bone metastasis and cell trafficking.

Animals↗

PubMedDate not supplied

Establishment of immortalized Copenhagen rat prostate endothelial cell lines.

Since the introduction of culture methods for umbilical vein endothelial cells, many successful attempts for culturing endothelial cells have been reported. The successful establishment of immortalized cell lines of organ specific endothelium, however, has been rare. Primary cultured endothelial cells isolated from the Copenhagen rat prostate were immortalized by infection with an Adenovirus-12 SV40 hybrid virus. Two immortal cell lines of Copenhagen rat prostate endothelium were established and designated YPEN-1 and YPEN-2. The established cell lines have continued to proliferate more than 80 population doublings and have not undergone senescence. They stain positively for but are nonproducers of SV4O0 T-antigen and grow in a monolayer with a cobblestone appearance. They demonstrate Dil-Ac-LDL uptake as an endothelial marker. YPEN-1 and YPEN-2 cells exhibit positive staining for endothelin and MRC OX-43 and express Integrin a6 beta 1 and Integrin beta 3 on their plasma membrane and demonstrate tube formation in Matrigel. Doubling times of YPEN-1 and YPEN-2 are 26 hours and 21 hours, respectively. Genetically, YPEN-1 and YPEN-2 are both diploid. These cell lines of rat prostate endothelial origin should be useful for studying angiogenesis and its inhibition.

Animals↗

PubMedDate not supplied

Establishment of an immortalized Copenhagen rat prostate epithelial cell line.

An immortal cell line of Copenhagen rat prostate epithelium was established after transfection of primaly cultured cells with SV4O DNA and designated EPYP-1. The established cells have continued to proliferate more than 70 population doublings, have not undergone senescence, and stain positively for SV40 T-antigen in their nuclei by immunohistochemistry. They grow in a monolayer with an epithelial morphology and exhibit positive staining for cytokeratin. EPYP-1 cells exhibited positive staining with anti-prostatic acid phosphatase antibody and expressed Integrin a6,B1 on their plasma membrane. They did not demonstrate Dil-Ac-LDL uptake as an endothelial marker. Both testosterone and dihydrotestosterone stimulated the growth of EPYP-1. Genetically EPYP-1 was aneuploid, however no tumors formed after subcutaneous and intra-prostatic injection of the cells in Copenhagen rats. This immortalized cell line of Copenhagen rat prostate epithelial origin may be suitable for studying early events in the conversion of cells to tumorigenicity.

Acid Phosphatase↗

PubMedDate not supplied

The effect of castanospermine on the metastatic properties of prostate cancer cells.

BACKGROUND: Most deaths from prostate cancer result from the metastatic spread of the disease. Castanospermine has been shown to inhibit tumor growth and metastasis in mouse and rat models. We hypothesized that castanospermine might inhibit metastasis in the Dunning model of rat prostate adenocarcinoma by interfering with the metastatic properties of tumor cells. MATERIALS AND METHODS: We examined the cytotoxicity of castanospermine toward the metastatic MAT-LyLu and nonmetastatic AT. 1 cell lines and its effects on cell motility and adhesion to endothelial cells. We assessed castanospermine's effects on in vivo metastasis in Copenhagen rats. RESULTS: Castanospermine was not cytotoxic toward the MAT-LyLu and AT. 1 cell lines at concentrations through 10 micrograms/mL, nor did it significantly affect cell motility, adhesion to endothelial cells, or in vivo metastasis. CONCLUSIONS: Within the Dunning model, castanospermine did not appear to significantly affect cell characteristics related to metastatic potential.

Adenocarcinoma↗

PubMedDate not supplied

Development of doxorubicin resistant rat prostate cancer cell lines.

BACKGROUND: One possible mechanism of chemotherapeutic resistance in patients with metastatic prostate cancer is the overexpression of P-glycoprotein. Additional tumor models are necessary to study this phenomenon. MATERIALS AND METHODS: Doxorubicin resistant rat prostate cancer cell lines were developed by increasing doxorubicin levels in cell culture. RESULTS: The MDR lines (AT3B-1, AT3B-2, MLLB-1, and MLLB-2) were more resistant to vinblastine compared to controls. When P-glycoprotein was blocked, the AT3 MDR lines demonstrated efflux activity. Injection of AT3 MDR lines into rats followed by doxorubicin treatment produced larger tumors compared to the parental controls. CONCLUSIONS: MDR rat prostate cancer cells were developed. AT3B-1 and AT3B-2 cell lines have drug efflux pump ability, whereas the MLLB-1 and MLLB-2 may not, suggesting alternative key mechanisms other than P-glycoprotein overexpression. These new cell lines are being used to study chemotherapy resistance in prostate cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Examination of the DNA methylation properties in nontumorigenic and tumorigenic breast epithelial cell lines.

Molecular changes in the progressive state of tumorigenesis often include altered patterns of DNA methylation. Utilizing a series of breast epithelial cell lines, the overall 5-methylcytosine content in genomic DNA demonstrated an overall decrease when comparing two malignant cell lines (MCF-7 and T47D) with a mortal cell line (MCF 1 2M) and several derivative cell lines of the immortalized MCF10 cultures (MCF10A,-2A, -5A, A1neoT2, and 139B6). Further investigation on the methylation status of these cells lines indicated no difference in DNA methyltransferase activity, both at a protein and mRNA levels, in the nontumorigenic cell lines examined while activity was 3-10 fold higher in the tumorigenic lines (MCF7, T47D, SkBr3, MB-MDA-231, -468). Examination of the CpG island in the 5' promoter region of the estrogen receptor gene indicates that this region is unmethylated in the mortal and immortal nontumorigenic lines as well as the tumorigenic lines examined, with the exception of the estrogen receptor negative breast cell line MB-MDA-468 which appears to be partially methylated at this site. These results indicate methylation of this CpG island does not account for the inactivation of the estrogen receptor gene in immortalized nontumorigenic breast cells, suggesting another mechanism of transcriptional inactivation of ER in this environment.

Breast↗

PubMedDate not supplied

A high-fat diet does not influence the growth of the Dunning R3327-H transplantable prostate adenocarcinoma.

BACKGROUND: The etiology of prostate cancer is currently a mystery. Several epidemiological studies suggest a link between dietary fat and prostate cancer. In vitro and in vivo studies support this evidence. Using the Dunning model of rat prostate cancer we hypothesized that a high-fat diet (20%) would increase the growth of the R3327-H tumor. MATERIALS AND METHODS: R3327-H tumors were implanted subcutaneously into male Copenhagen rats which were fed diets with 5 or 20% total fat. Tumors were allowed to grow for 16 weeks; they were then excised and weighed. The initial and final weights of the rats were also recorded. RESULTS: Statistical analysis revealed the level of dietary fat was a positive predictor of weight gain (p < 0.01). No effect on tumor growth was seen when compared to dietary fat, fiber type, or the interaction of fat and fiber. DISCUSSION: Growth of the R3327-H tumor, when implanted subcutaneously, is not affected by the level of dietary fat.

Animals↗

PubMedDate not supplied

Carboplatin-induced cell death in model prostate cancer systems.

BACKGROUND: Many chemotherapeutic agents are believed to kill cancer cells by inflicting cellular damage which triggers the cell to enter apoptosis (programmed cell death). We investigated the means by which carboplatin induces cell death in three model cancer systems: the human prostate carcinoma cell lines PC-3 and LNCaP and the human cervical carcinoma cell line HeLa. MATERIALS AND METHODS: Drug cytotoxicity, cell cycle effects, bcl-2 deactivation, and multiple markers for apoptosis were utilized to examine carboplatin activity within these cell lines. RESULTS: In HeLa cells, carboplatin appears to induce an S-phase block followed by apoptosis. In contrast, PC-3 and LNCaP cells show no cell cycle phase block and die from necrosis rather than apoptosis. The effects of carboplatin contrast sharply with the effects of paclitaxel, which induces an M-phase block and apoptosis in all three cell lines. CONCLUSIONS: These results show that PC-3 and LNCaP cells are relatively resistant to carboplatin and suggest two causes of resistance: bypassing the cell cycle checkpoints which serve as points of entry into apoptosis, and incomplete execution of the effector mechanisms of apoptosis. Carboplatin resistance in the prostate cancer cell lines fits into the developing scheme of apoptosis-necrosis and raises valuable questions about the root causes of cancer resistance to chemotherapeutic agents.

Apoptosis↗

PubMedDate not supplied

The isolation and characterization of epithelial cells from canine prostate.

BACKGROUND: Prostate cancer causes approximately 40,000 deaths in the United States annually (1,2). Adenocarcinoma of the prostate occurs primarily in two species: human and dog (3,4). Although less common in dogs, the etiologic factors responsible for spontaneous canine prostate cancer are presumably the same as for humans. Given the similar etiology and epidemiology of the disease among the two species, a model of canine prostate epithelial cells would be a powerful tool to study the disease. METHODS: Prostate epithelial cells were isolated from a sexually intact, adult beagle, and primary cultures established. Epithelial clones were immortalized by transfection with the Simian Virus 40 large T-antigen cDNA. Cells were characterized using immunohistochemical techniques. RESULTS: The immortal prostate epithelial cell line expresses cytokeratin-18, and prostatic acid phosphatase, markers specific for prostate epithelial cells. K-9PE-I, a stable, fast growing, canine prostate epithelial cell line is available for further study. CONCLUSIONS: A cell based model of canine prostate epithelium was isolated, immortalized, and characterized. The cell line will be available for further study of prostate disease.

Acid Phosphatase↗

PubMedDate not supplied

Quality-of-life evaluation in patients receiving treatment for advanced prostate cancer.

PURPOSE/OBJECTIVES: To evaluate the quality-of-life (QOL) experience in patients who are receiving treatment for advanced prostate cancer and the relationship between response to that treatment and QOL. DESIGN: Descriptive comparative study, repeated measures. SETTING: Medical oncology clinic in a comprehensive cancer center. SAMPLE: 33 patients receiving treatment for advanced prostate cancer. METHODS: Patient self-administered questionnaires and chart review. MAIN RESEARCH VARIABLES: Response to therapy and QOL. FINDINGS: No significant differences were seen in patients at the baseline evaluation. Patients who demonstrated response to therapy based on declining prostate specific antigen levels, however, demonstrated a significant increase in their QOL scores compared to those patients who were not responding to treatment. CONCLUSIONS: Although significant differences in survival at this stage of prostate cancer in patients who receive therapeutic treatment versus those who do not have yet to be demonstrated, there appears to be a benefit in QOL for those patients who respond to therapy. IMPLICATIONS FOR NURSING PRACTICE: These data support the use of QOL measurements in patients undergoing treatment for advanced prostate cancer. This information can be used in discussions with patients who are facing treatment decisions and who are concerned about the impact of treatment on their overall QOL. The data also stimulate questions for future research on QOL in this population, such as the difference in QOL in those patients who choose therapeutic treatment versus those who do not.

Aged↗