Project description:Chemotherapy may cause DNA damage within the oral mucosa of cancer patients leading to mucositis, a dose-limiting side effect for effective cancer treatment. We used whole genome gene expression analysis to identify cellular damage to the mucosal tissue occuring two days post induction chemotherapy and identified gene expression patterns that may or may not be predictive of oral mucositis. Keywords: Treatment effect
Project description:Chemotherapy may cause DNA damage within the oral mucosa of cancer patients leading to mucositis, a dose-limiting side effect for effective cancer treatment. We used whole genome gene expression analysis to identify cellular damage to the mucosal tissue occuring two days post induction chemotherapy and identified gene expression patterns that may or may not be predictive of oral mucositis. Experiment Overall Design: Punch buccal biopsies from healthy controls (HC, samples BRENC1, BRENC2, BRENC3, n=3) and five AML patients pre-chemotherapy (Pre-C, samples BREN11, BREN21, BREN41, BREN51, n=4) and (Post-C, samples BREN22, BREN32, BREN42, BREN52, n=4)(Ntotal=11) gave suitable RNA integrity to perform microarray analysis. Samples Pre-C:BREN31 and post-C:BREN12 were not suitable for microarray analysis. Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) was used to conduct gene expression profiling.
Project description:Cytotoxic chemotherapy is used to treat many thousands of patients across many cancer types annually. Recent studies have demonstrated that chemotherapy causes systemic response that can be exploited to promote cancer cell survival and dissemination, termed “chemotherapy-induced metastasis. However, there have been no studies investigating how chemotherapy alters the extracellular matrix of breast tumors, or if those changes might help to support metastatic dissemination. Here, we report the first characterization of the chemotherapy-treated breast cancer matrisome using the MMTV-PyMT transgenic mouse model of breast cancer. We identify distinct changes induced by different cytotoxic chemotherapies. In particular, we identify collagen IV as significantly associated with taxane-based chemotherapy treatment. Biological validation confirmed collagen IV as chemotherapy-associated and identified collagen IV-driven Src and FAK signaling as important mediators of invasion in the post-chemotherapy tumor microenvironment.
Project description:Collectively, viruses are the principal cause of cancers arising in patients with immune dysfunction, including HIV+ patients. Kaposi’s Sarcoma (KS) etiologically linked to KSHV continues to be the most common AIDS-associated tumor. The involvement of oral cavity represents one of the most common clinical manifestations of this tumor. HIV infection incurs an increased risk for periodontal diseases and oral carriage from a variety of pathogenic bacteria. In the current study, by using 16S rRNA based pyrosequencing, we found that oral shedding of KSHV altered oral microbiota signature in HIV+ patients which may contribute to virus-associated malignancies development.
Project description:Metastasis accounts for 90% of cancer-related deaths, yet the mechanisms by which cancer cells colonize secondary organs remain poorly understood. For breast cancer patients, metastasis to the liver is associated with poor prognosis and a median survival of 6 months. Standard of care is chemotherapy, but recurrence occurs in 30% of patients. Systemic chemotherapy has been shown to induce hepatotoxicity and fibrosis, but how chemotherapy impacts the composition of the liver extracellular matrix (ECM) remains unknown. Individual ECM proteins drive tumor cell proliferation and invasion, features that are essential for metastatic outgrowth in the liver. Here, we characterize the liver ECM of tumor-bearing mice treated with and without chemotherapy using the MMTV-PyMT transgenic model of breast cancer. We identify distinct drug-specific changes induced by commonly used cytotoxic chemotherapies. We identify Collagen V as an ECM protein that is more abundant in livers isolated from paclitaxel-treated mice and identify mechanisms of Collagen V driven invasion via ECM organization and signaling through α1β1 integrins.
Project description:The purpose of this study is to describe the effects of allogeneic stem cell transplant on oral microbiota and to examine differences in those patients who acquired respiratory complications. Forty-five patients were consented for the study and followed for 100 days post-transplant. Eleven patients represented by 115 speciment had specimens collected before and after transplant were subjected to further analysis. The Human Oral Microbe Identification Microarray was used for this analysis. In these 11 patients, five developed respiraotry complications after transplant and six did not develop this complication. Cluster analysis was used to identify patterns in the data. 115 specimens are included from 11 patients. These specimens were collected before and after transplant. There are no duplicate samples.
Project description:Changes in cellular lipid metabolism are a common feature in most solid tumors, which occur already in early stages of the tumor progression. However, it remains unclear if the tumor-specific lipid changes can be detected at the level of systemic lipid metabolism. The objective of this study was to perform comprehensive analysis of lipids in breast cancer patient serum samples. Lipidomic profiling using an established analytical platform was performed in two cohorts of breast cancer patients receiving neoadjuvant chemotherapy. The analyses were performed for 142 patients before and after neoadjuvant chemotherapy, and the results before chemotherapy were validated in an independent cohort of 194 patients. The analyses revealed that in general the tumor characteristics are not reflected in the serum samples. However, there was an association of specific triacylglycerols (TGs) in patients' response to chemotherapy. These TGs containing mainly oleic acid (C18:1) were found in lower levels in those patients showing pathologic complete response before receiving chemotherapy. Some of these TGs were also associated with estrogen receptor status and overall or disease-free survival of the patients. The results suggest that the altered serum levels of oleic acid in breast cancer patients are associated with their response to chemotherapy.
Project description:The purpose of this study is to describe the effects of allogeneic stem cell transplant on oral microbiota and to examine differences in those patients who acquired respiratory complications. Forty-five patients were consented for the study and followed for 100 days post-transplant. Eleven patients represented by 115 speciment had specimens collected before and after transplant were subjected to further analysis. The Human Oral Microbe Identification Microarray was used for this analysis. In these 11 patients, five developed respiraotry complications after transplant and six did not develop this complication. Cluster analysis was used to identify patterns in the data.
Project description:When locally advanced breast cancer is treated with neoadjuvant chemotherapy, the recurrence risk is significantly higher if no complete pathologic response is achieved. Identification of the underlying resistance mechanisms is essential to select treatments with maximal efficacy and minimal toxicity. Here we employed gene expression profiles derived from 317 HER2-negative treatment-naïve breast cancer biopsies of patients who underwent neoadjuvant chemotherapy, deep whole exome and RNA-sequencing profiles of 22 matched pre- and post-treatment tumors, and treatment outcome data to identifiy biomarkers of response and resistance mechanims. Molecular profiling of treatment-naïve breast cancer samples revealed that expression levels of proliferation, immune response and extracellular matrix (ECM) organization combined predict response to chemotherapy. Triple negative patients with high proliferation, high immune response and low ECM expression had a significantly better treatment response and survival benefit (HR 0.29, 95% CI 0.10-0.85; p=0.02), while in ER+ patients the opposite was seen (HR 4.73, 95% CI 1.51-14.8; 0=0.008). The characterization of paired pre-and post-treatment samples revealed that aberrations of known cancer genes were either only present in the pre-treatmane sample (CDKN1B) or in the post-treatment sample(TP53, APC, CTNNB1). Proliferation-associated genes were frequently down-regulated in post-treatment ER+ tumors, but not in triple negative tumors. Genes involved in ECM were upregulated in the majority of post-chemotherapy samples. Genomic and transcriptomic differences between pre- and post-chemotherapy samples are common and may reveal potential mechanisms of therapy resistance. Our results show a wide range of distinct, but related mechanisms, with a prominent role for proliferation- and ECM-related genes.