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You searched for +publisher:"Penn State University" +contributor:("David Feith, Committee Member"). Showing records 1 – 2 of 2 total matches.

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Penn State University

1. Cleary, Allison Shea. Heterogeneity in Mammary Cancer: Using Mouse Models to Investigate Tumor Subtype Origins and Interclonal Interactions.

Degree: 2014, Penn State University

Breast cancer is a heterogeneous disease on two levels. First, breast cancers display inter-tumor heterogeneity evidenced by the diversity of clinically and molecularly defined tumor subtypes that differ with respect to disease progression and drug sensitivity. Second, individual breast cancers display remarkable intra-tumor heterogeneity evidenced by the diversity of component tumor cell subtypes co-residing within each cancer that differ with respect to cell morphology, proliferation rate, metastatic potential, drug sensitivity, and capacity for tumor reconstitution. The cellular mechanisms that generate and maintain breast cancer heterogeneity, both at the level of tumor subtype and tumor cell subtype, remain poorly understood. Using mouse models of human breast cancer, this dissertation examines whether and how breast cancer heterogeneity derives from the diverse and highly interactive cell subtypes that comprise the normal mammary gland, breast cancer’s tissue-of-origin. In one set of experiments directed at uncovering the origin of tumor subtypes, we examined why transgenic mouse models of breast cancer nearly always yield a hormone receptor (HR)-negative mammary cancer subtype. In the mammary gland, mature ducts consist of basal and luminal mammary epithelial cell (MEC) subtypes. The luminal epithelial compartment can be further subdivided into hormone receptor (HR)-positive and HR-negative subsets. While human breast cancers frequently express HRs and depend on ovarian hormones for growth, transgenic mouse models of breast cancers show an unexplained bias toward HR-negative disease. Since the majority of mouse breast cancer models use the mouse mammary tumor virus long terminal repeat (MMTV-LTR) as a mammary-specific promoter element, we examined whether MMTV targets transgene expression to a specific MEC compartment. Using the MMTV-LTR to drive expression of a nuclear H2BGFP reporter transgene, we observed nuclear labeling restricted to HR-negative cells within the luminal compartment. Combining this labeling strategy with MMTV-directed expression of the Neu oncogene, we found Neu transgene expression was similarly enriched within HR-negative luminal MECs. Further, Neu-initiated neoplasias were comprised entirely of HR-negative cells from the carcinoma-in-situ stage onward. Thus, MMTV-driven Neu expression targets HR-negative luminal cells, culminating in HR-negative tumors. We propose that the HR-negative phenotype of many mouse breast cancer models can be explained by MMTV-driven transgene expression in HR-negative MECs. In another set of experiments, we sought to study interactions between tumor cell subtypes. To do this, we developed a novel experimental platform for culturing chimeric mammary organoids which permits analysis of both the cell-autonomous and non-autonomous effects of oncogene expression. By combining primary MECs from two different transgenic donors, chimeric mammary organoids were assembled consisting of intermingled populations of genetically distinct donor MECs that could each be… Advisors/Committee Members: Edward Joseph Gunther, Dissertation Advisor/Co-Advisor, Edward Joseph Gunther, Committee Chair/Co-Chair, David Feith, Committee Member, Leslie Joan Parent, Committee Member, Todd Schell, Committee Member, Raghu Sinha, Committee Member.

Subjects/Keywords: tumor heterogeneity; interclonal cooperation; breast cancer; mammary gland; transgenic mice; 3D organoid culture; FACS

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Cleary, A. S. (2014). Heterogeneity in Mammary Cancer: Using Mouse Models to Investigate Tumor Subtype Origins and Interclonal Interactions. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/22628

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Cleary, Allison Shea. “Heterogeneity in Mammary Cancer: Using Mouse Models to Investigate Tumor Subtype Origins and Interclonal Interactions.” 2014. Thesis, Penn State University. Accessed February 25, 2021. https://submit-etda.libraries.psu.edu/catalog/22628.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Cleary, Allison Shea. “Heterogeneity in Mammary Cancer: Using Mouse Models to Investigate Tumor Subtype Origins and Interclonal Interactions.” 2014. Web. 25 Feb 2021.

Vancouver:

Cleary AS. Heterogeneity in Mammary Cancer: Using Mouse Models to Investigate Tumor Subtype Origins and Interclonal Interactions. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Feb 25]. Available from: https://submit-etda.libraries.psu.edu/catalog/22628.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cleary AS. Heterogeneity in Mammary Cancer: Using Mouse Models to Investigate Tumor Subtype Origins and Interclonal Interactions. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/22628

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Penn State University

2. Chin-quee, Karis P. Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look .

Degree: 2013, Penn State University

ABSTRACT Successful metastasis requires some degree of hospitality from the host organ that is metastasized. In recent years, evidence has been mounting that the primary tumor contributes to adapting this remote organ to increase this hospitality. Interestingly, many in vitro experiments have shown that conditioned media from cancer cells produce physical changes which theoretically could facilitate invasion. These include perturbations in extracellular matrix and of cell to cell adhesions. The conditioned media in these in vitro experiments could be interpreted to be a proxy for either paracrine or endocrine effects, however, when these observations are coupled with evidence from in vivo experiments, it seems possible that primary tumors have remote effects on un-metastasized organs that can elicit changes in them which are pro-metastatic. We have performed a series of experiments designed to characterize and describe changes in osteoblasts (hFOB) which occur as a result of exposure to conditioned medium from breast cancer cells (MDA-MET). Functional experiments aimed at investigating whether these changes are pro-metastatic were included as a means of this characterization. Thus cell to cell adhesions, as well as the ability of the osteoblastic environment to attract MDA-MET cells were both assessed. Further, we investigated mechanistically the bases behind the observations from the functional experiments. Methods Confluent hFOB cells were treated with conditioned media from either MDA-MET, MDA-MB-231 HTERT-HME1 or hFOB cells 24 hrs. This treatment conditioned medium was removed, the cells washed and serum-free medium added to the hFOB cells. hFOB-conditioned medium was collected after 18hrs. This medium was then used in in vitro migration assays measuring number of MDA-MET migratory cells by labeling the cells with DNA-binding dye Cyquant; in establishing presence of collagen by western blot; in collagenase assays and in a cytokine array where antibodies to 74 cytokines were embedded on a membrane. The presence of Type 1 collagen receptors was shown by immunocytochemistry. The data were analyzed using one way ANOVA and the Student’s T test. Results We found that conditioned medium from hFOB cells that had been treated with MDA-MET-conditioned medium attracted more MDA-MET cells than hFOB cells pre-exposed to its own medium only. We hypothesized that Type 1 collagen fragments of specific length were the chemoattractants responsible for our observed effect. This was evidenced by an increase in collagenase in the conditioned medium of hFOB cells which had been exposed to MDA-MET-conditioned medium. The definitiveness of this evidence was aided by the inherent fidelity of the collagenase enzymes and its Type 1 collagen substrate and the distinctiveness of the product of this enzyme substrate interaction. We also showed that bacterial collagenase, which creates short collagen fragments of non-specific length removed the ability of hFOB -conditioned medium to attract MDA-MET cells. In addition, we showed that at… Advisors/Committee Members: Henry Joseph Donahue, Dissertation Advisor/Co-Advisor, Henry Joseph Donahue, Committee Chair/Co-Chair, Andrea Manni, Committee Member, Andrea Marie Mastro, Committee Member, David Feith, Committee Member, Lisa M Shantz, Committee Member, Ralph Lauren Keil, Committee Member.

Subjects/Keywords: breast cancer metastasis; pre-metastatic niche; bone; collagen fragments; collagenase

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Chin-quee, K. P. (2013). Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/17496

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Chin-quee, Karis P. “Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look .” 2013. Thesis, Penn State University. Accessed February 25, 2021. https://submit-etda.libraries.psu.edu/catalog/17496.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Chin-quee, Karis P. “Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look .” 2013. Web. 25 Feb 2021.

Vancouver:

Chin-quee KP. Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look . [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Feb 25]. Available from: https://submit-etda.libraries.psu.edu/catalog/17496.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chin-quee KP. Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look . [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/17496

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.