1,721,058 research outputs found
Examining Cell Polarity Differences in Classical and Basal-Subtypes of Pancreatic Ductal Adenocarcinoma
Full text linkPancreatic ductal adenocarcinoma (PDAC) remains a difficult challenge in oncology, with an average 5-year survival rate of 12%. Two subtypes of PDAC have been identified, a classical subtype and a basal subtype, in which the basal subtype tends to have worse clinical outcomes. This study aimed to elucidate the differences in apicobasal cell polarity between classical and basal PDAC patient-derived xenograft (PDX) organoids that could explain the difference in clinical outcomes between the two subtypes. The loss of apicobasal cell polarity and cell-cell adhesion can be a hallmark of cancer progression to invasive and metastatic disease. In this project, I first optimized the protocol for immunofluorescence to ensure reliable staining for subsequent analysis. Specifically targeting the fixing duration, antibody dilution, and blocking buffer solution. With the optimized protocol, the study explored cell polarity differences, focusing on tight junctions and apicobasal cell polarity. Classical organoids displayed a more organized distribution of tight junctions compared to basal organoids. Apicobasal polarity staining revealed that classical organoids exhibited a distinct, well-preserved organization, whereas basal organoids displayed less defined polarity, potentially influencing metastatic outcomes. Furthermore, cancer-associated fibroblasts (CAFs) are essential in PDAC and can influence cell polarity or tumor organization. To study this interaction, I first tested whether human fibroblasts persist in in-vivo tumors when co-injected with PDAC cells using immunofluorescence staining of CAF markers. It was found that human fibroblasts remain in tumors, which demonstrates that co-culture with tumor cells is a valid mouse injection model. Thus, this co-culture model can be used to further study the role that CAFs play in cell polarity between the two subtypes. The study provides a foundation for future investigations into the genetic underpinnings of these differences and their potential impacts on tumor behavior and response to therapy, shedding light on novel avenues for targeted treatments in PDAC.Bachelor of Scienc
Inhibiting JNK in combination with FOLFOX chemotherapy shows potential as pancreatic cancer treatment
Full text linkPancreatic cancer is the 3rd leading cause of cancer deaths in the United States. A combination regimen of folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) has an established efficacy in treating pancreatic ductal adenocarcinoma (PDAC) and is amenable to further drug combination, but the cellular signaling response to FOLFOX has not been determined.Bachelor of Scienc
Evaluating cingulin expression in classical and basal subtypes of pancreatic ductal adenocarcinoma by immunofluorescence
Full text linkPancreatic Ductal Adenocarcinoma (PDAC) comprises 90% of pancreatic cancers and has a 5-year survival rate of only 11%. PDAC was discovered to have a classical and basal subtype based on similar gene expression profiles. The classical subtype of pancreatic ductal adenocarcinoma (PDAC) is associated with a more defined cell polarity and has a better prognosis and response to current treatments than the basal tumor subtype. We hypothesize that classical tumors have a more defined cell polarity, based on cingulin localization pattern and expression, compared to basal tumors Through this research, we hope to establish a link between cingulin expression and PDAC subtype. This link could help open new potential treatment targets based on cell polarity in the future. We conducted immunofluorescence staining and confocal imaging for cingulin using 3 lines of cryosectioned classical tumor tissue, 3 lines of basal tumor tissue, and 3 lines of classical organoids. Our results after visually comparing fluorescence levels showed no significant difference in cingulin expression between the classical versus basal PDAC tumors.Bachelor of Science in Public Healt
Identification of Potential Biomarkers in PDAC
Full text linkPancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, with a 5-year survival rate of approximately 6%. The poor prognosis associated with PDAC emphasizes the need to improve detection and screening, therefore we aimed to identify new biomarkers associated with PDAC progression. 137 cancer associated genes identified from our microarray data were screened for gene expression using 13 PDAC cell lines and 42 samples isolated from the blood of 21 PDAC and 4 control patients. 56 genes were found to have expression in >70% of PDAC cell lines and low expression in control buffy coat samples. 16 of these genes showed significant survival differences in patients with low expression when analyzed in our microarray data. Two of these genes, GJB3 and MFI2, showed a trend of higher expression in metastatic PDAC patients compared to benign or local PDAC patients. GJB3 and MFI2 may have clinical relevance for patient survival and be useful as metastatic biomarkers for PDAC, but improved sample isolation techniques and screening of more samples is needed to determine their significance.Master of Scienc
Identifying biomarkers of response to modified FOLFIRINOX regimens using patient derived xenograft mouse models of pancreatic ductal adenocarcinoma
Full text linkPancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective therapies. FOLFIRINOX is a chemotherapeutic regimen for patients with metastatic disease that provides an unprecedented median overall survival of 11.1 months. However, significant toxicities necessitate dose reductions and limit the number of patients eligible for FOLFIRINOX treatment. I used patient derived xenograft (PDX) mouse models of PDAC to assess efficacy of modified regimens and determine if intra-tumoral heterogeneity plays a role in response. I also used RNA sequencing of PDX tumors to identify potential biomarkers of response. No significant differences in response to standard and modified FOLFIRINOX regimens were observed; however, intra-tumoral heterogeneity affected responses of one PDX tumor line to modified regimens. Biomarkers associated with differential responses could not be identified by RNA sequencing. RNA sequencing data confirmed previously identified PDAC subtypes, classical and basal-like.Master of Scienc
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Data Management and Sharing Plan for: Targeting EGFR for basal subtype cancer
No full textThe Data Management and Sharing Plan describes the scientific data to be generated and/or used in the research and outlines a strategy for managing and sharing project data
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
- …
