PubMed Health⌕ Search

Biomedical subjects

Susan K Lutgendorf

Publications and source records attributed to Susan K Lutgendorf.

At least 19 recordsLinked to original sources
PubMed2026

Hope is linked with more favorable tumor molecular signatures in serous ovarian cancer.

INTRODUCTION: Hope has been associated with improved quality of life and lower mortality in cancer, but the underlying biological mechanisms are poorly characterized. We previously reported that hope was associated with less inflammation and more normalized diurnal cortisol pre-treatment among women with ovarian cancer. We also reported associations of socio-environmental factors with pro-metastatic processes. Here, we used genome-wide transcriptional profiling to quantify associations between hope and tumor molecular signatures reflecting invasiveness, inflammation, and cellular immunity. METHOD: Participants were 74 women with serous ovarian cancer who provided demographic information and completed surveys pre-surgery. Hope was assessed using a face-valid item from the Center for Epidemiological Studies Depression Scale (CES-D). Depression was assessed using the full CES-D without the hope item. Illumina HT12 microarrays were used to assay tumor RNA, and associations between hope and tumor gene expression were quantified, adjusting for depression, age, BMI, grade, and stage. RESULTS: Adjusting for covariates, hope was associated with multiple favorable differences in RNA expression, including lower levels of mesenchymal differentiation (p&#x202f;=&#x202f;0.008) and pro-inflammatory gene regulation (NF-&#x3ba;B: p&#x202f;<&#x202f;0.001; IRF1: p&#x202f;=&#x202f;0.024; STAT: p&#x202f;=&#x202f;0.018), elevated epithelial differentiation (p&#x202f;=&#x202f;0.011), and elevated activity of the IRF7 transcription factor which promotes cellular immunity (p&#x202f;=&#x202f;0.016). CONCLUSIONS: These data suggest that hope is associated with an ovarian tumor gene expression profile characterized by reduced epithelial-mesenchymal transition (EMT) and inflammatory activity, and increased activity of a transcription factor promoting cellular immunity. These findings highlight potential biological implications of a resilience factor such as hope, but need replication with more robust assessments of hope.

Epithelial mesenchymal transition↗
PubMed2006

Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy.

PURPOSE: Focal adhesion kinase (FAK) plays a critical role in ovarian cancer cell survival and in various steps in the metastatic cascade. Based on encouraging in vitro results with FAK silencing, we examined the in vivo therapeutic potential of this approach using short interfering RNA (siRNA) in the neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). EXPERIMENTAL DESIGN: Therapy experiments of FAK siRNA with or without docetaxel were done using human ovarian cancer cell lines SKOV3ip1, HeyA8, and HeyA8MDR in nude mice. Additional experiments with a cisplatin-resistant cell line (A2780-CP20) were also done. Assessments of angiogenesis (CD31), cell proliferation (proliferating cell nuclear antigen), and apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) were done using immunohistochemical analysis. RESULTS: A single dose of FAK siRNA-DOPC was highly effective in reducing in vivo FAK expression for up to 4 days as assayed by Western blot and immunohistochemical analysis. Therapy experiments were started 1 week after injection of the ovarian cancer cells. Treatment with FAK siRNA-DOPC (150 mug/kg twice weekly) reduced mean tumor weight by 44% to 72% in the three cell lines compared with the control group (Ps < 0.05 for HeyA8, A2780-CP20, and SKOV3ip1). When FAK siRNA-DOPC was combined with docetaxel, there was even greater reduction in mean tumor weight in all models (all Ps < 0.05). Similar results were observed in combination with cisplatin. Treatment with FAK siRNA-DOPC plus docetaxel resulted in decreased microvessel density, decreased expression of vascular endothelial growth factor and matrix metalloproteinase-9, and increased apoptosis of tumor-associated endothelial cells and tumor cells. CONCLUSIONS: Taken together, these findings suggest that FAK siRNA-DOPC plus docetaxel or platinum might be a novel therapeutic approach against ovarian cancer.

Animals↗
PubMed2006

Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma.

Stress can alter immunological, neurochemical and endocrinological functions, but its role in cancer progression is not well understood. Here, we show that chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden and more invasive growth of ovarian carcinoma cells in an orthotopic mouse model. These effects are mediated primarily through activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway by the beta(2) adrenergic receptor (encoded by ADRB2). Tumors in stressed animals showed markedly increased vascularization and enhanced expression of VEGF, MMP2 and MMP9, and we found that angiogenic processes mediated the effects of stress on tumor growth in vivo. These data identify beta-adrenergic activation of the cAMP-PKA signaling pathway as a major mechanism by which behavioral stress can enhance tumor angiogenesis in vivo and thereby promote malignant cell growth. These data also suggest that blocking ADRB-mediated angiogenesis could have therapeutic implications for the management of ovarian cancer.

Animals↗
PubMed2006

Symptoms and cystoscopic findings in patients with untreated interstitial cystitis.

OBJECTIVES: To examine the relationships between symptoms and cystoscopic findings in women newly diagnosed with interstitial cystitis who had not previously received treatment. METHODS: Twelve newly diagnosed and not previously treated women with interstitial cystitis completed a bladder symptom questionnaire the day before undergoing cystoscopy, hydrodistension, and biopsy. The daily voiding frequency was reported. Cystoscopic findings were converted to a numerical scale, and the data were analyzed using Pearson correlations. RESULTS: Pain symptoms had consistent positive correlations with the cystoscopic findings. An increase in pain with bladder filling was associated with inflammation (P = 0.011), ulceration, and smaller bladder capacity. Pain relief after voiding correlated with smaller bladder capacity (P = 0.019), hematuria, and total cystoscopic score. Pain intensity in the urethra was related to ulceration and hematuria, and pain in the lower abdomen was related to a smaller bladder capacity (P = 0.047), glomerulations, and a larger total cystoscopic score. Daytime frequency correlated negatively with most cystoscopic findings, and nocturnal frequency had a positive relationship with most cystoscopic findings and was significantly associated with a smaller bladder capacity (P = 0.010). Urgency showed no strong associations with any cystoscopic findings. CONCLUSIONS: In patients with untreated interstitial cystitis, a strong correlation between pain and cystoscopic findings was observed. The differences between our results and those of previous studies that found no relationship between symptom reports and cystoscopic findings suggest possible effects of treatment on pain perception and therapeutic influence on cystoscopic findings.

Adult↗
PubMed2006

Coping and quality of life among women extensively treated for gynecologic cancer.

The current study examined the use of engagement and avoidant coping strategies among advanced-stage gynecologic cancer patients who were facing the long-term stressors of extensive chemotherapy and advanced disease. Patients were compared to a reference group of early-stage patients who had received more limited treatment. Compared to the reference group, extensively-treated women more frequently utilized both engagement and avoidant strategies including active coping, seeking social support, and mental disengagement. Use of engagement coping strategies such as active coping and seeking social support were not significantly related to quality of life or mood. However, avoidant coping strategies, including disengagement and cognitive avoidance, were strongly associated with poorer well-being and more distressed mood. Moreover, relationships between coping and quality of life differed between the extensively-treated patients and patients in the limited treatment reference group. The use of avoidance and seeking instrumental support were associated with poorer outcomes among extensively-treated patients but not among the limited treatment group. Results of the current study suggest that coping patterns and outcomes may be more pronounced among cancer patients contending with severe disease and extensive treatment and that avoidant coping strategies may be particularly detrimental with respect to these patients' mood and quality of life.

Adaptation, Psychological↗
PubMed2006

Interleukin-6, histamine, and methylhistamine as diagnostic markers for interstitial cystitis.

OBJECTIVES: To examine the specificity and sensitivity of the inflammatory markers histamine, methylhistamine, and interleukin-6 (IL-6) in the urine of patients with interstitial cystitis compared with that in healthy controls. METHODS: A total of 40 women with interstitial cystitis and 29 healthy controls collected 24-hour urine samples. During the 24 hours before urine collection, all participants refrained from consuming foods and medications that could contain bioactive amines. Methylhistamine and histamine were measured using radioimmunoassay kits and were normalized to urinary creatinine levels; IL-6 was measured using enzyme-linked immunosorbent assay. The data were analyzed by t tests, logistic regression analysis, and receiver operating characteristics. RESULTS: IL-6 and histamine were significantly greater in the patients with interstitial cystitis than in the controls (P = 0.0003 and P = 0.038, respectively). The methylhistamine levels were also greater in the patients with interstitial cystitis than in the controls, but the results did not reach significance (P = 0.063). Using a combination of IL-6 and methylhistamine/creatinine, cutoff points were established. Using these cutoff points, the sensitivity was 70.0%, specificity 72.4%, positive predictive value 77.8%, and negative predictive value 63.6%. CONCLUSIONS: All three markers--histamine, methylhistamine, and IL-6--were greater in the patients with interstitial cystitis than in the controls. A combination of methylhistamine and IL-6 could be used as a sensitive and specific marker for interstitial cystitis.

Adult↗
PubMed2006

The assessment and validity of stress-related growth in a community-based sample.

In an investigation of the assessment and construct validity of stress-related growth, community-dwelling women (N = 163) wrote essays about the impact of a stressful life event that had occurred in the previous few years and completed the Posttraumatic Growth Inventory (PTGI). Independent ratings of growth in the essays were positively correlated with PTGI scores, suggesting that endorsement of growth on questionnaires can be substantiated by personal accounts. There was no relation between reports of growth on the PTGI and socially desirable responding or negative mood. Higher PTGI scores were associated with greater positive mood and greater depth of processing in the essays. These findings support the validity of stress-related growth as a construct and its assessment via questionnaire.

Adaptation, Psychological↗
PubMed2006

The influence of bio-behavioural factors on tumour biology: pathways and mechanisms.

Epidemiological studies indicate that stress, chronic depression and lack of social support might serve as risk factors for cancer development and progression. Recent cellular and molecular studies have identified biological processes that could potentially mediate such effects. This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.

Animals↗
PubMed2005

Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells.

OBJECTIVE: Docetaxel causes cell death through induction of apoptosis; however, cell death characteristics for docetaxel have not yet been fully elucidated. We examined the role of focal adhesion kinase (FAK) cleavage in docetaxel-mediated apoptosis. METHODS: FAK degradation after treatment with docetaxel was determined in both taxane-sensitive (HeyA8 and SKOV3) and taxane-resistant (HeyA8-MDR and SKOV3-TR) ovarian cancer cell lines by Western blot analysis. Cell growth was determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. FAK-targeting small interfering RNA (siRNA) was used to decrease FAK expression. Apoptosis and caspase activity were determined using commercially available kits. RESULTS: SKOV3 and HeyA8 cell lines were both sensitive to docetaxel (IC50 levels, 1-6.2 nmol/L), whereas the SKOV3-TR and HeyA8-MDR cells were resistant (IC50>or=250 nmol/L for both). Docetaxel induced high rates of apoptosis in SKOV3 and HeyA8 cells (84% and 66% apoptosis, respectively) but minimal apoptosis (5-8%) in SKOV3-TR and HeyA8-MDR cells. Similarly, FAK was cleaved in SKOV3 and HeyA8 cells in response to docetaxel treatment but unchanged in the resistant cells. Caspase-3 and caspase-8 activity also increased significantly in docetaxel-treated SKOV3 and HeyA8 cells but not in the taxane-resistant cells. DEVD-fmk (caspase-3 blocker) was able to block both FAK cleavage and apoptosis mediated by docetaxel in SKOV3 and HeyA8 cells. FAK siRNA transfection resulted in 70% to 90% decrease in FAK levels in all cell lines within 72 hours. FAK silencing augmented docetaxel-mediated growth inhibition (5- to 8-fold increase) and apoptosis in both of the taxane-sensitive and taxane-resistant cell lines. CONCLUSIONS: Docetaxel induces FAK cleavage, mediated through activation of caspase-3, in taxane-sensitive ovarian cancer cells but not in taxane-resistant cells. The absence of FAK degradation may contribute to cell survival in taxane-resistant cells. FAK silencing promotes the in vitro efficacy of docetaxel in both taxane-sensitive and taxane-resistant cell lines and may serve as a novel therapeutic approach.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Social support, psychological distress, and natural killer cell activity in ovarian cancer.

PURPOSE: Psychosocial stress has been related to impaired immunity in cancer patients. However, the extent to which these relationships exist in immune cells in the tumor microenvironment in humans has not been explored. We examined relationships among distress, social support, and natural killer (NK) cell activity in ovarian cancer patients in peripheral-blood mononuclear cells (PBMC), ascitic fluid, and tumor-infiltrating lymphocytes (TIL). PATIENTS AND METHODS: Patients awaiting surgery for a pelvic mass suspected of being ovarian cancer completed psychological questionnaires and gave a presurgical sample of peripheral blood. Samples of tumor and ascites were taken during surgery, lymphocytes were then isolated, and NK cytotoxicity and percentage were determined. The final sample, which was confirmed by surgical diagnosis, included 42 patients with epithelial ovarian cancer and 23 patients with benign masses. RESULTS: Peripheral NK cell activity was significantly lower among ovarian cancer patients than in patients with benign masses. Among ovarian cancer patients, NK cytotoxicity in TIL was significantly lower than in PBMC or ascitic fluid. Social support was related to higher NK cytotoxicity in PBMC and TIL, adjusting for stage. Distress was related to lower NK cytotoxicity in TIL. A multivariate model indicated independent associations of both distress and social support with NK cell activity in TIL. CONCLUSION: Psychosocial factors, such as social support and distress, are associated with changes in the cellular immune response, not only in peripheral blood, but also at the tumor level. These relationships were more robust in TIL. These findings support the presence of stress influences in the tumor microenvironment.

Adult↗
PubMed2005

Psychosocial factors and interleukin-6 among women with advanced ovarian cancer.

BACKGROUND: Relations among psychological stress, depression, social support, and interleukin-6 (IL-6, a proinflammatory cytokine) have been documented in humans and animals. Because elevated IL-6 is associated with a poorer prognosis among ovarian cancer patients and has been implicated in the metastasis of ovarian cancer, the current study examined relations between psychosocial factors and IL-6 among women with advanced-stage ovarian cancer. METHODS: Sixty-one ovarian cancer patients completed assessments of social support, distressed mood, and quality of life before surgery. Peripheral blood was drawn preoperatively, and the plasma was assayed for IL-6. Ascites samples were also assayed for IL-6 for a subset of patients. RESULTS: Both IL-6 levels and distressed mood were elevated among patients. After statistically adjusting effects of age and disease stage, social attachment was associated with lower levels of IL-6 in peripheral blood (P = 0.03), whereas poorer health-related quality of life was associated with higher IL-6 (P values ranged from 0.01 to 0.03 on different measures). This pattern of relations was also found in the ascites. Moreover, IL-6 levels in peripheral blood plasma correlated significantly with IL-6 in the ascites (P < 0.001), suggesting that peripheral IL-6 reflects IL-6 levels at the site of the tumor. CONCLUSIONS: Results suggest that social support may play a protective role with respect to IL-6 elevations, and IL-6 may be an independent marker of health-related quality of life among ovarian cancer patients. Processes involving IL-6 represent possible pathways by which behavioral factors may contribute to disease outcomes among women with ovarian cancer.

Ascitic Fluid↗
PubMed2005

Reciprocal age related change in natural killer cell receptors for MHC class I.

Natural killer (NK) cells are essential for healthy aging. NK cell activation is controlled by MHC class I-specific CD94/NKG2 receptors and killer immunoglobulin-like receptors (KIR). To assess NK cytotoxic function in isolation from MHC receptor engagement, we measured the ability of purified NK cells to kill mouse P815 target cells in the presence of anti-CD16 mAb. CD16-mediated cytotoxicity did not change with age, indicating that NK activation and cytotoxic granule release remained functional. We then investigated MHC class I receptor expression on NK cells. There was an age related decrease in CD94 and NKG2A expression and a reciprocal age related increase in KIR expression. NKG2A expression also declined with age on CD56(+) T cells. CD94/NKG2A receptor function was proportional to expression, indicating that NK cell inhibitory signaling pathways were intact. NKG2A and KIR expression were complementary, suggesting that CD94/NKG2A function could substitute for inhibitory KIR function during polyclonal NK cell development in both young and elderly adults. The distinct roles of CD94/NKG2A and KIR receptors suggest that shifting MHC class I receptor expression patterns reflect age related changes in NK cell and CD56(+) T cell turnover and function in vivo.

Adult↗
PubMed2005

Distress and expression of natural killer receptors on lymphocytes.

Chronic distress has been associated with alterations in natural killer (NK) cell and T cell percentages and function. NK cells express inhibitory and stimulatory receptors that regulate cytotoxicity and cytokine secretion. T cells and T cells expressing CD56 (NKT cells) also express these NK-associated receptors, which are thought to serve the same function. The objective of this study was to examine the relationship between distress and expression of NK-associated receptors on NK cells, T cells, and NKT cells. Using multicolor flow cytometry and validated questionnaires, we studied twenty-nine healthy adults with a bimodal age spread. Whereas distress was related to significantly lower percentages of CD3(+) T cells, it was related to significantly higher percentages of NKT cells. Distress was associated with significantly higher percentages of T cells expressing NK-associated receptors including CD94 and KIR. In contrast, distress was associated with significantly lower percentages of NK cells bearing KIR (GL183) receptors. Our findings suggest a possible role for NK-associated receptors in distress-related alterations in lymphocyte maturation, trafficking, or activity.

Adult↗
PubMed2004

Effects of acute stress, relaxation, and a neurogenic inflammatory stimulus on interleukin-6 in humans.

Effects of three experimental manipulations: mental stress, relaxation, and a nociceptive inflammatory stimulus, capsaicin, on levels of interleukin-6 (IL-6) were examined. Fifty subjects were pre-trained in relaxation and then randomized to a stress (Stroop test), relaxation (tape), or control (video) manipulation. Subjects participated in an evening reactivity session including 20 min of stress, relaxation, or control followed by a capsaicin injection in the forearm. Cardiovascular variables and levels of IL-6 were measured before and after the manipulation, and at regular intervals up to 60 min post-capsaicin. Group assignment did not differentially affect change in IL-6 over time, either before or after capsaicin. Small but significant increases in IL-6 were seen at 60 min post-capsaicin. These findings suggest that an acute stress manipulation does not modulate IL-6 within this time frame. Although IL-6 did increase following a neurogenic inflammatory stimulus, it did so subsequent to the maximum flare, suggesting that flare mechanisms are independent of IL-6.

Adult↗
PubMed2004

Religious participation, interleukin-6, and mortality in older adults.

This study prospectively examined the relationship between religious attendance, interleukin-6 (IL-6) levels, and mortality rates in a community-based sample of 557 older adults. Attending religious services more than once weekly was a significant predictor of lower subsequent 12-year mortality and elevated IL-6 levels (> 3.19 pg/mL), with a mortality ratio of.32 (95% confidence interval [CI] = 0.15,0.72; p <.01) and an odds ratio for elevated IL-6 of.34 (95% CI = 0.16, 0.73, p <.01), compared with never attending religious services. Structural equation modeling indicated religious attendance was significantly related to lower mortality rates and IL-6 levels, and IL-6 levels mediated the prospective relationship between religious attendance and mortality. Results were independent of covariates including age, sex, health behaviors, chronic illness, social support, and depression. Findings are consistent with a role for IL-6 in processes mediating the relationship between religious attendance and mortality.

Activities of Daily Living↗
PubMed2004

Mood and cytokine response to influenza virus in older adults.

BACKGROUND: Previous research has indicated that older adults with severe life stress show attenuated immune responses to influenza vaccination. Associations among mood, optimism, stress, and the in vitro cytokine response to influenza virus and vaccine were evaluated in 18 healthy older adults with low to moderate life stress. METHODS: Peripheral blood mononuclear cells were stimulated in cultures with 1999-2000 influenza vaccine viruses (A/Beijing/262/95, A/Sydney/5/97, and B/Yamanashi/166/98) and the 2000-2001 trivalent vaccine (containing A/New Caledonia/20/99, A/Panama/2007/99, and B/Yamanashi/166/98). The levels of T-helper type 1 (interleukin-2 and interferon-gamma) and type 2 (interleukin-10) cytokines were measured in culture supernatants. RESULTS: Stress, age, and current health practices were unrelated to cytokine production. Older adults reporting greater anger, fatigue, confusion, and total mood disturbance had poorer cytokine responses to live virus and vaccine stimulation. In contrast, older adults who reported greater vigor and those who were more optimistic had greater cytokine responses to both live virus and vaccine. These relationships were largely unaffected by medications or health conditions. CONCLUSIONS: These findings suggest that among older adults, even mild to moderate mood disturbance is associated with an attenuated cellular immune response to live influenza virus and vaccine.

Aged↗