tbuckley/cabot-search huggingface dataset:
MK2 inhibitory peptide delivered in nanopolyplexes prevents vascular graft intimal hyperplasia
Authors: Brian C. Evans, Kyle M. Hocking, Michael J. Osgood, Igor Voskresensky, Julia Dmowska, Kameron V. Kilchrist, Colleen M. Brophy, Craig L. Duvall
Journal: Science Translational Medicine (2015)

Nanopolyplexes formulated from a pH-responsive, endosomolytic polymer with a peptide inhibitor of MAPKAP kinase 2 block inflammatory and migratory signaling in vascular smooth muscle cells and prevent intimal hyperplasia in human saphenous vein grafts.
Trapping the intruder — immune receptor domain fusions provide new molecular leads for improving disease resistance in plants
Authors: Simon G. Krattinger, Beat Keller
Journal: Genome biology (2016)

A new study uses genomics to show that fusions of plant immune receptors and other protein domains occur in significant numbers. This finding will generate many new research hypotheses and provide new opportunities for breeding resistant plant varieties. Please see related Research article: http://dx.doi.org/10.1186/s12915-016-0228-7
The significance of SUV of 18-FDG PET for the diagnosis and treatment of lung cancer
Authors: H. Guo, X. Hu, Z. Li
Journal: Journal of Clinical Oncology (2006)

17032 Background: To explore the possibility that the standardized uptake value(SUV) of positron emission tomography(PET) could be a prognostic factor for lung cancer and whether it holds more significance than clinical stage,the current predominant prognostic factor for NSCLC patients. To assess the possible connection between the SUV and clinical and histopathologic characteristics of lung cancer patients(especially the histology), in order to build a comprehensive picture for the potential application of SUV. Methods: Eighty-two patients taking PET examination before receiving any treatment were analysed, the majority of which(fifty) consisted of patients treated with multiple modality treatment where surgery played a central role. 1-year and 3-year survival(OS) Rate, Progress Free Survival(PFS) Rate were calculated by Kaplan-Meier method and evaluated with the log-rank test.The prognostic significance was assessed by univariate and multivariate analyses.Nonparametric tests were performed to determine whether there was valuable difference amid each SUV group classified by certain clinical or histopathologic characteristic. Results: A SUV cutoff of 5.0 for the primary tumor showed the greatest discriminative value for overall survival.As for the PFS,the cufoff is 4.0. The SUV for the primary tumor was a significant predictor for both overall survival and PFS, based on the result that the relative risk was 7.075 and 2.719 respectively. As a result of multivariate analyse,the prognostic value of SUV and Clinical Staging was independent of each other, and the value of the SUV was considerably higher than the latter. The SUV for the small-cell lung cancer group was statistically higher than the non-small-cell lung cancer group. And there was significant overall discrepancy across the groups sorted by the degree of differentiation. Conclusions: The SUV of the primary tumor has the potential to be the leading prognostic factor for patients treated by multiple modality treatment, leading to substantially improved management for lung cancer patients. And there could be close connection between SUV and histopathologic or differentiation feature of lung cancer tissue, although it is still open to discussion. Analysis for larger number of cases could settle the issue. No significant financial relationships to disclose.
Radiosensitization with Carotid Arterial Infusion of Bromodeoxyuridine (BUdR) ± 5 Fluorouracil (5FU) Biomodulation with Focal External Beam Radiation (FEBT) for Malignant Gliomas
Authors: H. S. Greenberg, W. F. Chandler, W. D. Ensminger, L. Junck, A. Thornton, H. Sandler, M. A. Page, P. Mckeever, S. Gebarski, B. Liang, R. Tankanow
Journal: Neuro-Oncology (1991)

A permanently implantable pump system has been developed for safe continuous intraarterial (IA) carotid BUdR ± 5FU infusion.[l] BUdR ± 5 FU is delivered IA because of its regional advantage (Rd). Fifty-four patients (41 Grade IV, 13 Grade III) were entered on one of two studies for the treatment of malignant gliomas with IA BUdR ± 5FU infused continuously for 8 1/2 weeks with FEBT to 5940 cGy the last 6 1/2 weeks. Twenty-three patients (18 Grade IV, 5 Grade III) were treated with BUdR alone with the maximum tolerated dose of 400 mg/m2/day for 8 1/2 weeks. The median survival was 20 months (2.4 S.E.). In the second trial, 31 patients were entered on IA BUdR + 5FU with a Kaplan Meier estimated median survival of 20.5 (4.5 SE.) months. The maximum tolerated dose of IA BUdR/5FU was 400 mg/m2/day of BUdR and 5 mg/m2/day of 5FU. The Kaplan Meier estimated median survival of all patients in trials 1 and 2 (total 54) is 20.5 (1.9 S.E.) months. The Kaplan Meier estimated median survival of the 41 Grade IV and 13 Grade III was 14 (2.9 S.E.) and 50 months (14 S.E.), respectively. The only vascular complication has been one transient episode of amaurosis fugax. The dose limiting toxicity in both trials has been a reversible self limited unilateral focal forehead dermatitis, iritis, conjunctivitis and blepharitis. Continuous IA infusion of BUdR ± 5 FU is feasible, safe, and represents a potential means of enhancing the effectiveness of FEBT in the treatment of malignant gliomas.
Use of adrenal androgen levels to predict response to ketoconazole in patients with androgen independent prostate cancer: Results from CALGB 9583
Authors: C. J. Ryan, S. Halabi, E. Kaplan, N. Vogelzang, P. Kantoff, E. J. Small
Journal: Journal of Clinical Oncology (2004)

4558 Background Adrenal androgens can activate the androgen receptor and stimulate prostate cancer growth. Because of its adrenolytic properties, ketoconazole (keto) is active as a secondary hormonal therapy in men with androgen-independent prostate cancer (AiPCa). The relationship between pre-treatment adrenal androgen levels and outcome after therapy with keto was therefore evaluated. Methods 260 patients with AiPCa were enrolled on CALGB 9583, a randomized trial of antiandrogen withdrawal (AAWD) compared to AAWD plus keto. 133 patients received initial keto, of which 103 had available baseline adrenal androgen levels, performed by a central laboratory. Androstedione (AON), dehydroepiandrostendione (DHEA) and DHEA-sulfate levels were measured. All patients were treated with antiandrogen withdrawal, keto 400 mg po tid, and hydrocortisone 40 mg po qd. Regression models (logistic and proportional hazard) were used to assess the prognostic significance of baseline adrenal androgen levels in predicting overall survival and PSA response defined by Consensus Criteria. Results In patients with available adrenal androgen levels, PSA response rate was 28% and median response duration was 4.76 months (Interquartile range 2.76–9.07). The median baseline AON level was 640 mcg/mL. The median AON for patients with and without a PSA response was 880 mcg/mL vs. 530 mcg/mL, Wilcoxon p = .034; and for patients with a duration of PSA response ≥ median vs. < median was 1080 vs. 550 mcg/dL, Wilcoxon p = .007. Conversely, elevation of baseline AON levels was predictive of PSA response (odds ratio = 2.26 [95% CI = 1.03–5.00, p = 0.043]). In a multivariate analysis, patients with AON levels > median had improved survival (hazard ratio for death 0.62, [95% CI = 0.39–0.96, log rank p = 0.032]). Conclusions AiPCa patients with higher baseline AON levels have a higher likelihood of response to keto, a longer duration of response, and improved survival compared with patients with lower AON levels. These data support a risk adapted approach to ketoconazole therapy based on baseline AON levels. No significant financial relationships to disclose.
Quercetin, an Artificial Regulator of the High Aerobic Glycolysis of Tumor Cells 1 2
Authors: Else-Maj Suolinna, Dennis R. Lang, Efraim Racker
Journal: JNCI Journal of the National Cancer Institute (1974)

We showed that the high aerobic glycolysis observed in several tumor cells was caused by high ATPase activity. In some tumors, the ATPase activity of the Na+K+ pump was responsible; in some, the mitochondrial ATPase; and in others, an unidentified ATPase generated ADP and Pi required for glycolysis. In the cells analyzed thus far, the increased ATPase activity was not due to an increased function of the pump but to a loss of the control mechanism responsible for tight coupling. Some bioflavonoids inhibit the aerobic glycolysis by specifically repairing the defective control mechanism.
Abstract P051: Inflammation is Significantly Associated With High Blood Pressure in Females Only
Authors: Jenny Eckner, Charlotte A Larsson, Lennart Rastam, Ulf Lindblad
Journal: Circulation (2012)

INTRODUCTION The causes of high blood pressure are complex and based on an interaction between multiple biological factors and behaviours. Insulin resistance and inflammation are commonly acknowledged mechanisms in the development of CVD, while insulin resistance and relative body weight correspondingly predict the development of high blood pressure. HYPOTHESIS We aimed to compare insulin resistance, relative body weight, and inflammation in the association with SBP. METHODS In 2001-2005 a random sample of residents aged 30-74 years in the municipalities of Vara and Skövde, South-western Sweden, were invited to a survey of cardiovascular risk factors. In all 1811 participants in Vara (participation rate 81%) and 1005 participants in Skövde (70%) were enrolled. Subjects with a known history of hypertension were excluded for the current study. Specially trained nurses saw all subjects in the morning after a 10 hours over night fast, and venous blood samples were taken. A physical examination included body height and body weight (light cloths and no shoes), blood pressure was measured twice in a supine position after a 5 minutes rest (arm in heart level). The mean of the 2 measurements was used for statistical analyses. Hs-CRP and plasma insulin were analysed, and BMI and HOMA-index were calculated using standard algorithms. The log form of HOMA-ir was used in statistical analyses. Associations were explored in males and females separately using multivariate linear regression. RESULTS In all 2538 subjects, 1266 men (50%) and 1272 women (50%) without known hypertension were included. BMI and HOMA-ir were both significantly associated with SBP in both males and females, while hs-CRP was associated with SBP in women only. These factors were accordingly entered into a multivariate linear regression model also including age. In men HOMA-ir [regression coefficient, (95% confidence interval), and p-value] [5.4 (2.5-8.4), p&lt;0.001], was significantly associated with SBP, while BMI [0.2 (-0.3-0.5), p=0.087], and CRP was not [0.02 (-0.1-0.1), p=0.138]. In women all three mechanisms came out significantly; HOMA-ir [5.4 (2.2-8.6), p&lt;0.001], BMI [0.4 (0.2-0.5), p&lt;0.001], and CRP [0.2 (0.02-0.4), p=0.031]. There were statistically significant interaction terms between gender and CRP (p=0.037), and gender and HOMA-ir (P=0.045), respectively, while no corresponding interaction was found for BMI. CONCLUSIONS Our study confirms a strong impact of insulin resistance and relative body weight on blood pressure levels in both men and women. However, a significant association between hs-CRP and systolic blood pressure in women was not seen in men. Gender differences in insulin resistance and inflammation were statistically confirmed by interaction terms. These findings have implications for future research and for development of clinical practice.
A prospective study of adjuvant anastrozole and gene promoter methylation in the contralateral breast of high-risk women
Authors: T. M. Prowell, M. Fackler, P. Argani, N. F. Khouri, A. L. Blackford, K. Shahverdi, A. C. Wolff, N. E. Davidson, S. Sukumar, V. Stearns
Journal: Journal of Clinical Oncology (2008)

1514 Background: Women with breast cancer are at increased risk to develop a contralateral breast (CLB) cancer. Adjuvant aromatase inhibitor (AI) trials have reported a significantly decreased incidence of CLB cancer. We hypothesized that 12 months of anastrozole would decrease breast density, circulating estrogens, and cumulative gene promoter methylation in breast tissue. Methods: We conducted a prospective, single-arm study in 50 evaluable patients to assess the effect of anastrozole on CLB density and circulating estrogens (primary), and CLB gene methylation (secondary). Eligible patients were postmenopausal women with hormone receptor-positive stage 0-III breast cancer who had completed local therapy, had an intact CLB, and would receive an AI as their sole adjuvant therapy. Subjects received anastrozole 1 mg daily for 12 months. Mammograms and estrogens were assessed at 0, 6, and 12 months, with optional CLB core biopsies at 0 and 6 months. Investigators blinded to patients and time point performed quantitative multiplex methylation-specific PCR (QM- MSP) for Cyclin D2, RAR-beta, Twist, RASSF1a, APC1, and HIN1. Results: From March 2004 to September 2006, 54 women were enrolled, and we collected 33 paired 0/6 month CLB core biopsies. With QM-MSP, all 6 genes were amplifiable for 25/33 paired samples; in total, 28/33 samples at baseline and 30/33 at 6 months were assessed. At baseline, 84% of paired samples had measurable cumulative methylation of the 6 genes; among single genes, Twist (33%), RASSF1a (28%), and RAR-beta (35%) were most frequently methylated. After 6 months of anastrozole, we observed significant decreases in methylation for Twist (p<0.001), RASSF1a (p=0.01), and RAR-beta (p=.03), among patients who were positive for methylation at baseline. Analysis of changes in CLB density and circulating estrogens is underway. Conclusions: Studies using the CLB as a high-risk model are feasible. Hypermethylation is common in the breasts of high-risk women, and, in 3 of 6 genes studied, decreased significantly after 6 months of anastrozole. A prospective study of the relationship between changes in methylation and incidence of breast cancer in high-risk women is needed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Oncomethylome Sciences, Inc Novartis, Pfizer
The meanings of “hope” to patients with cancer, nearing the end of their lives
Authors: I. N. Olver, J. A. Eliott
Journal: Journal of Clinical Oncology (2006)

18567 Background: In two studies of the speech of patients with cancer about end-of-life decision-making, the word hope was often spontaneously used. In 23 patients earlier in their disease there was a difference between hope used as a noun, often objective, outside the patient’s control, and presented as “no hope”, or as a verb which was directed by patients and facilitated imagining a positive future (Qual Health Res 2002, 12: 173–193). In a second study 28 patients judged within 3 months of dying, following unprompted use of hope during interview, were specifically prompted to talk about hope. Methods: Discourse analysis was used to analyze the speech from the semi-structured interviews of the patients. The sample size was determined by data saturation. Results: All in the second study were Caucasian, average age 61, 15 males, 18 had partners and 19 were Christian, 1 Druid, and 8 listing no religion. Ten patients made reference to hope as variable in amount. In general the more the better, but even 1%, while trivial scientifically, may be important personally. The problem with quantifiable hope is that it is perceived to dwindle with the medical prognosis with which “no hope” is most often identified. Twenty patients hoped for a longer life although 19 had specifically indicated that they were dying, suggesting that this hope was not death denying. Most wanted more time to achieve tasks and be with family. Hoping recognized uncertainty yet attested to the value patients placed on various activities. Eight talked of hoping for a cure, although this was not overwhelming in the present. Some mentioned the possibility of a miracle cure, reinforced by the construction that medicine gives hope. Hope sometimes shifted from life to either an acceptable dying in 8 patients or to focus on others. The legacy to others could be objects or life lessons. Hopes can be shared by partners and can change. Two patients spoke of hope sourced from God and as enduring beyond death. Conclusions: Patients found it challenging to talk of hope in the abstract. Hope can be positive and sustaining or disillusioning when not attained. No significant financial relationships to disclose.
Transversus Abdominis Release as an Alternative Component Separation Technique for Ventral Hernia Repair
Authors: Jeffrey A. Blatnik, David M. Krpata, Yuri W. Novitsky
Journal: JAMA Surgery (2016)

What Is the Innovation? The use ofmyofascial advancement flaps, or component separation technique,datesbackmorethan25years.Themostcommonlymentioned approach is that of Ramirez et al1 from 1990 in which the external abdominal oblique (EO)musculature isdividedasamethodof providingmidlineabdominalmuscle advancementofup to 10cmbilaterally. Although effective in rectusmusclemedialization, anterior componentseparationtechniquerequirescreationof large,oftenmorbid, lipocutaneousflaps.TheRives-Stopparetromuscular reconstruction is effective, but it is not applicable for larger defects. Transversus abdominis release (TAR) is themost recent technique to address limitations of traditional reconstructive options. Incontrast tocreating largeskin flaps toaccessanddividetheEO muscle, TARbeginsbyentering theposterior rectus sheath (Figure). Thisdissection iscarried laterally to 1cmmedialof the lineasemilunaris.Theposterior rectussheath is thendivided justmedial to theneurovascularperforatorsand lineasemilunaris.Theunderlying fibersof the transversusabdominismuscleare identifiedanddividedtoenter aretromuscular/preperitonealplane.Thisdissectionisthencarriedout lateral to thepsoasmuscle.Once this is repeatedbilaterally, theposterior rectussheath is thenclosed in themidline, completely isolating thevisceral contents fromanyprostheticmesh.At this stage, there is aspace for theplacementofa largepieceofmesh, reinforcing theentirevisceral sac.Thetypeofmeshvariesdependingonthetypeofhernia repair.Midweightmacroporousmesh is typicallyselectedformidlinedefectswheremuscleclosurecanbeobtained.Flankherniasand those for which fascial closure is difficult may benefit from a heavyweightmesh.However,dataonhowthisaffectsoutcomesareunavailable.Drainsareplacedover themeshtominimizeseromaformation. Thedrainsareremovedafter theoutputhasdecreasedto lessthan30
What do redox metabolism, printers/lithographers, and hip replacements have to do with the prevention of melanoma?
Authors: F. Meyskens
Journal: Journal of Clinical Oncology (2007)

8583 Our studies of the properties of reactive oxygen species(ROS) in melanomagenesis led us to explore the role of heavy metals in this process. A systematic experimental exploration of the effect of ROS on melanin and melanosomes in melanocytes and melanoma cells using biophysical techniques including electroparamagnetic resonance to measure free radicals and electron microscopy suggests that the conversion of melanin from an anti-oxidant and reducing agent to a pro-oxidant and photoreactive compound is an early pathogenic event that is accompanied by melanosomal disruption that serves as an ongoing organelle source of free radical generation. The involvement of selected heavy metals enhances this process and in conjunction with ultraviolet light can lead to phenotypic changes in normal human melanocytes that resemble dysplatic nevi melanocytes in culture. A re-examination of the non-genetic risk factors for melanoma has identified a large(and neglected) epidemiology that implicates heavy metals and includes markedly increased risks for melanoma in printers/lithographers(4 large studies), electrical industry workers (3 large studies), and hip replacements patients(a large meta-analyses and 2 cohort studies). High levels of cobalt are present in this latter group post-replacement that lasts for years (?indefinitely) Clinical observations (imaging studies) and studies that document the importance of metallothionein expression in primary melanoma and prognosis also offers ancillary support for the involvement of metals in the pathogenesis of melanoma Based on these considerations and the role of copper in the melanin synthesis pathway and the binding characteristics of metals to melanin we propose that the most likely culprits that accounts for a significant contribution to the etiology and pathogenesis of melanoma are Cu+2 and Co+2 and suggests that chelation may be a reasonable strategy for the prevention of melanoma. No significant financial relationships to disclose.
Determining familial risk of multiple myeloma
Authors: E. A. Coleman, H. Lynch, C. Enderlin, C. B. Stewart, R. Kennedy, B. Barlogie
Journal: Journal of Clinical Oncology (2007)

8111 Background: The etiology of multiple myeloma (MM) remains unknown although genetic and environmental factors have been implicated. Familial MM has been reported; however, whether this familial tendency is due to genetic factors or environmental exposures or both is not known. Analysis of SEER data showed that Iowa, an agricultural state, had the highest incidence of MM; however, once we adjusted for race, sex, age, and year of diagnosis, the effect of geographic area was small and the main effect was race. This project aims to build a Familial MM Registry of families and investigate the families’ pedigrees and environmental factors to determine the familial risk of MM. The long term goal is to identify myeloma susceptibility loci which ultimately could lead to finding myeloma prone germline mutations. Methods: Patients (n = 67) from the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences and their family members with MM or a related malignancy (amyloidoses, lymphoma, chronic lymphocytic leukemia, chronic myelogenous leukemia, Waldenstrom's macroglobulinemia, Hairy cell leukemia, acute myelogenous leukemia, acute lymphocytic leukemia, Hodgkin's disease) were interviewed for environmental factors associated with MM and for family history data to complete pedigrees. Pedigrees were analyzed to determine the patterns of inheritance. Results: Data show that 26 patients (39%) have family members with MM (one having five family members with MM) and 34 patients (51%) have family members with related malignancies. Eighteen families (27%) have a putative autosomal dominant mode of genetic transmission of MM. Pancreatic cancer, malignant melanoma, breast cancer and lymphoma may be part of a myeloma syndrome. Pesticide/insecticide exposure, raising cattle or growing cotton were the most prevalent environmental risk factors. Conclusions: The pedigrees suggest the existence of genetic traits affecting MM susceptibility. This work will be part of the efforts to create an international consortium to study familial MM. Research in the area of molecular epidemiology is needed to discover the genetic and environmental determinants of this disease and the reasons for the racial and gender differences. No significant financial relationships to disclose.