Dentists’ Leadership‐Related Educational Experiences, Attitudes, and Past and Current Behavior

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153576/1/jddj002203372014786tb05741x.pd

Oral health‐related concerns, behavior, and communication with health care providers of patients with breast cancer: impact of different treatments

AimThe objectives are to compare responses of breast cancer (BCa) treatment groups (chemotherapy, tamoxifen, and aromatase inhibitors (AIs) to each other and a control regarding (a) subjective oral health, (b) oral health‐related behaviors, (c) oral health‐related concerns, and (d) communication with health care providers.MethodsSurvey data were collected from 140 postmenopausal BCa patients and 41 healthy postmenopausal control respondents.ResultsBCa patients reported on average more frequent mouth sores/mucositis (5‐point scale with 1 = never: 1.63 vs. 1.14; p < .01), glossadynia (1.60 vs. 1.07; p < .01), xerostomia (2.48 vs. 1.40; p < .01), and dysgeusia (2.10 vs. 1.46; p < .01) than the control respondents. Patients undergoing chemotherapy were more aware that cancer treatment can affect their oral health than patients on tamoxifen/AI (93% vs. 55%/56%; p < .001). BCa patients reported being more frequently informed by oncologists about oral health‐related effects of cancer treatment than by dentists. Oncologists/nurses were more likely to communicate about oral health‐related treatment effects with patients undergoing chemotherapy than patients on tamoxifen or AIs. Few BCa patients perceived dentists as knowledgeable about cancer treatment‐related oral concerns and trusted them less than oncologists.ConclusionsBCa treatments impact oral health. Low percentages of BCa patients had received specific information about impacts of BCa treatments on oral health from their dentists.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141444/1/scd12266.pd

Periodontal health, perceived oral health, and dental care utilization of breast cancer survivors

ObjectivesThis population‐based analysis examined the prevalence of periodontal diseases along with the self‐perceived oral health and patterns of dental care utilization of breast cancer survivors in the United States.MethodsData from the 1999‐2004 National Health and Nutrition Surveys were utilized, examining information from 3,354 women between 50 and 85 years of age. Primary outcomes were gingivitis and periodontitis, self‐perceived oral health, and dental care utilization. Logistic regression analyses were used to estimate relationships of breast cancer diagnosis and primary outcomes while controlling for confounding factors.ResultsBreast cancer survivors were more likely to be older than 55 years, white, nonsmokers, have higher levels of education and income, and a higher prevalence of osteoporosis. Breast cancer survivors were significantly less likely to have dental insurance (P = 0.04). Utilization of dental services and reason for last dental visit did not significantly differ between groups. A history of a breast cancer diagnosis did not increase the odds of gingivitis [odds ratio (OR):  1.32; 95 percent confidence interval (CI): 0.53‐3.63], periodontitis (OR: 1.82; 95 percent CI:  0.89‐4.01), or poor self‐perceived oral health (OR: 0.89; 95 percent CI: 0.61‐1.33) after adjusting for age, race, education, dental care utilization, and smoking status.ConclusionsIn this sample, a history of breast cancer does not significantly impact periodontal health, self‐perceived oral health, and dental care utilization. However, efforts should be made to assure that breast cancer survivors have dental insurance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111973/1/jphd12084.pd

Expression and activation of Α v Β 3 integrins by SDF-1/CXC12 increases the aggressiveness of prostate cancer cells

BACKGROUND Stromal cell-derived factor-1 (SDF-1 or CXCL12) and CXCR4 are key elements in the metastasis of prostate cancer cells to bone—but the mechanisms as to how it localizes to the marrow remains unclear. METHODS Prostate cancer cell lines were stimulated with SDF-1 and evaluated for alterations in the expression of adhesion molecules using microarrays, FACs, and Western blotting to identify Α v Β 3 receptors. Cell–cell adhesion and invasion assays were used to verify that activation of the receptor is responsive to SDF-1. RESULTS We demonstrate that SDF-1 transiently regulates the number and affinity of Α v Β 3 receptors by prostate cancer cells to enhance their metastatic behavior by increasing adhesiveness and invasiveness. SDF-1 transiently increased the expression of Β 3 receptor subunit and increased its phosphorylation in metastatic but not nonmetastatic cells. CONCLUSIONS The transition from a locally invasive phenotype to a metastatic phenotype may be primed by the elevated expression of Α v Β 3 receptors. Activation and increased expression of Α v Β 3 within SDF-1-rich organs may participate in metastatic localization. Prostate 67:61–73, 2007. © 2006 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55878/1/20500_ftp.pd

Human papillomavirus 16 L2 inhibits the transcriptional activation function, but not the DNA replication function, of HPV-16 E2

In this study we analysed the outcome of the interaction between HPV-16 L2 and E2 on the transactivation and DNA replication functions of E2. When E2 was expressed on its own, it transactivated a number of E2-responsive promoters but co-expression of L2 led to the down-regulation of the transcription transactivation activity of the E2 protein. This repression is not mediated by an increased degradation of the E2 protein. In contrast, the expression of L2 had no effect on the ability of E2 to activate DNA replication in association with the viral replication factor E1. Deletion mutagenesis identified L2 domains responsible for binding to E2 (first 50 N-terminus amino acid residues) and down-regulating its transactivation function (residues 301–400). The results demonstrate that L2 selectively inhibits the transcriptional activation property of E2 and that there is a direct interaction between the two proteins, although this is not sufficient to mediate the transcriptional repression. The consequences of the L2–E2 interaction for the viral life cycle are discussed

Mer Tyrosine Kinase Regulates Disseminated Prostate Cancer Cellular Dormancy

Many prostate cancer (PCa) recurrences are thought to be due to reactivation of disseminated tumor cells (DTCs). We previously found a role of the TAM family of receptor tyrosine kinases TYRO3, AXL, and MERTK in PCa dormancy regulation. However, the mechanism and contributions of the individual TAM receptors is largely unknown. Knockdown of MERTK, but not AXL or TYRO3 by shRNA in PCa cells induced a decreased ratio of Pâ Erk1/2 to Pâ p38, increased expression of p27, NR2F1, SOX2, and NANOG, induced higher levels of histone H3K9me3 and H3K27me3, and induced a G1/G0 arrest, all of which are associated with dormancy. Similar effects were also observed with siRNA. Most importantly, knockdown of MERTK in PCa cells increased metastasis free survival in an intraâ cardiac injection mouse xenograft model. MERTK knockdown also failed to inhibit PCa growth in vitro and subcutaneous growth in vivo, which suggests that MERTK has specificity for dormancy regulation or requires a signal from the PCa microenvironment. The effects of MERTK on the cell cycle and histone methylation were reversed by p38 inhibitor SB203580, which indicates the importance of MAP kinases for MERTK dormancy regulation. Overall, this study shows that MERTK stimulates PCa dormancy escape through a MAP kinase dependent mechanism, also involving p27, pluripotency transcription factors, and histone methylation. J. Cell. Biochem. 118: 891â 902, 2017. © 2016 Wiley Periodicals, Inc.Escape from cellular dormancy is the process where previously dormant single disseminated tumor cells reactivate to form cancer microâ metastases, which continue to grow and ultimately make the disease incurable. Here, were show that Mer tyrosine kinase is important for prostate cancer dormancy escape through a mechanism involving MAP kinases, cell cycle inhibitors, epigenetics, and transcription factors associated with pluripotent cells.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136285/1/jcb25768_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136285/2/jcb25768.pd

Prostate Carcinoma Skeletal Metastases: Cross-talk between Tumor and Bone

The majority of men with progressive prostate cancer develop metastases with the skeleton being the most prevalent metastatic site. Unlike many other tumors that metastasize to bone and form osteolytic lesions, prostate carcinomas form osteoblastic lesions. However, histological evaluation of these lesions reveals the presence of underlying osteoclastic activity. These lesions are painful, resulting in diminished quality of life of the patient. There is emerging evidence that prostate carcinomas establish and thrive in the skeleton due to cross-talk between the bone microenvironment and tumor cells. Bone provides chemotactic factors, adhesion factors, and growth factors that allow the prostate carcinoma cells to target and proliferate in the skeleton. The prostate carcinoma cells reciprocate through production of osteoblastic and osteolytic factors that modulate bone remodeling. The prostate carcinoma-induced osteolysis promotes release of the many growth factors within the bone extracellular matrix thus further enhancing the progression of the metastases. This review focuses on the interaction between the bone and the prostate carcinoma cells that allow for development and progression of prostate carcinoma skeletal metastases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44522/1/10555_2004_Article_402865.pd

Papillomavirus Capsid Binding and Uptake by Cells From Different Tissues and Species

The inability of papillomaviruses (PV) to replicate in tissue culture cells has hampered the study of the PV life cycle. We investigated virus-cell interactions by the following two methods: (i) using purified bovine PV virions or human PV type 11 (HPV type 11) virus-like particles (VLP) to test the binding to eukaryotic cells and (ii) using different VLP-reporter plasmid complexes of HPV6b, HPV11 L1 or HPV11 L1/L2, and HPV16 L1 or HPV16 L1/L2 to study uptake of particles into different cell lines. Our studies showed that PV capsids bind to a broad range of cells in culture in a dose-dependent manner. Binding of PV capsids to cells can be blocked by pretreating the cells with the protease trypsin. Penetration of PV into cells was monitored by using complexes in which the purified PV capsids were physically linked to DNA containing the gene for beta-galactosidase driven by the human cytomegalovirus promoter. Expression of beta-galactosidase occurred in < 1% of the cells, and the efficiency of PV receptor-mediated gene delivery was greatly enhanced (up to 10 to 20% positive cells) by the use of a replication-defective adenovirus which promotes endosomal lysis. The data generated by this approach further confirmed the results obtained from the binding assays, showing that PV enter a wide range of cells and that these cells have all functions required for the uptake of PV. Binding and uptake of PV particles can be blocked by PV-specific antisera, and different PV particles compete for particle uptake. Our results suggest that the PV receptor is a conserved cell surface molecule(s) used by different PV and that the tropism of infection by different PV is controlled by events downstream of the initial binding and uptake

Hepatocyte Growth Factor Increases Osteopontin Expression in Human Osteoblasts through PI3K, Akt, c-Src, and AP-1 Signaling Pathway

BACKGROUND: Hepatocyte growth factor (HGF) has been demonstrated to stimulate osteoblast proliferation and participated bone remodeling. Osteopontin (OPN) is a secreted phosphoglycoprotein that belongs to the SIBLING family and is present during bone mineralization. However, the effects of HGF on OPN expression in human osteoblasts are large unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that HGF induced OPN expression in human osteoblasts dose-dependently. HGF-mediated OPN production was attenuated by c-Met inhibitor and siRNA. Pretreatment of osteoblasts with PI3K inhibitor (Ly294002), Akt inhibitor, c-Src inhibitor (PP2), or AP-1 inhibitor (curcumin) blocked the potentiating action of HGF. Stimulation of osteoblasts with HGF enhanced PI3K, Akt, and c-Src activation. In addition, incubation of cells with HGF also increased c-Jun phosphorylation, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the OPN promoter. HGF-mediated AP-1-luciferase activity and c-Jun binding to the AP-1 element was reduced by c-Met inhibitor, Ly294002, Akt inhibitor, and PP2. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the interaction between HGF and c-Met increases OPN expression in human osteoblasts via the PI3K, Akt, c-Src, c-Jun, and AP-1 signaling pathway

Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process

Prostate cancer has a predilection to metastasise to the bone marrow stroma (BMS) by an as yet uncharacterised mechanism. We have defined a series of coculture models of invasion, which simulate the blood/BMS boundary and allow the elucidation of the signalling and mechanics of trans-endothelial migration within the complex bone marrow environment. Confocal microscopy shows that prostate epithelial cells bind specifically to bone marrow endothelial-to-endothelial cell junctions and initiate endothelial cell retraction. Trans-endothelial migration proceeds via an epithelial cell pseudopodial process, with complete epithelial migration occurring after 232±43 min. Stromal-derived factor-1 (SDF-1)/CXCR4 signalling induced PC-3 to invade across a basement membrane although the level of invasion was 3.5-fold less than invasion towards BMS (P=0.0007) or bone marrow endothelial cells (P=0.004). Maximal SDF-1 signalling of invasion was completely inhibited by 10 μM of the SDF-1 inhibitor T140. However, 10 μM T140 only reduced invasion towards BMS and bone marrow endothelial cells by 59% (P=0.001) and 29% (P=0.011), respectively. This study highlights the need to examine the potential roles of signalling molecules and/or inhibitors, not just in single-cell models but in coculture models that mimic the complex environment of the bone marrow