tbuckley/cabot-search huggingface dataset:
Abstract B32: TGF-β blockade improves the distribution and efficacy of chemotherapeutic agent in breast carcinoma
Authors: Jieqiong Liu, Shan Liao, Yuhui Huang, Rakesh K. Jain, Lei Xu
Journal: Clinical Cancer Research (2010)

Abstract In its journey from blood vessels to cancer cells, a therapeutic agent must overcome the transport barrier posed by the interstitial matrix. In contrast to our understanding of blood vessels, our understanding of the formation and function of the tumor interstitial matrix is still in its infancy. A primary component of the interstitial matrix, collagen type I, has been shown to inversely correlate with diffusive transport in solid tumors. TGF-β can stimulate production of collagen by stromal cells in tumors. Thus, we studied the effect of blocking TGF-β pathway in breast carcinoma progression and response to chemotherapy. To this end, we used a soluble Fc:TGF-β type II receptor fusion protein (sTβRII) to block TGF-β pathway in two breast cancer models (human MDA-MB-231 cells and mouse 4T1 cells). TGF-β blockade significantly impaired the growth and metastasis of orthotopic tumors in both tumor models. The recruitment of myofibroblasts and interstitial matrix content was determined by immunohistochemistry, TGF-β blockade significantly decreased the recruitment of myofibroblast and the level of collagen I. Next, to determine the effect of TGF-β blockade on interstitial transport, we injected fluorescent doxorubicin into the tail vein of mice and observed the intratumoral distribution of doxorubicin autofluorescence by confocal microscopy. We found that TGF-β blockade increased the transvascular flux of fluorescent doxorubicin. As a result, doxorubicin liposome (DOXIL) treatment was significantly more effective in inhibiting tumor progression in TGF-β blocked tumors compared to parental tumors. In summary, our study characterized the functional role of TGF-β in modulating tumor interstitial matrix in breast cancer xenografts and suggested that blocking TGF-β signaling pathway may represent a testable therapeutic approach to be combined with conventional chemotherapy in breast cancer treatment. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B32.
Blood Lead, Blood Pressure, and Hypertension in Perimenopausal and Postmenopausal Women
Authors: Denis Nash, Laurence Magder, Mark Lustberg, Roger W. Sherwin, Robert J. Rubin, Rachel B. Kaufmann, Ellen K. Silbergeld
Journal: JAMA (2003)

Context Lead exposures have been shown to be associated with increased blood pressure and risk of hypertension in older men. In perimenopausal women, skeletal lead stores are an important source of endogenous lead exposure due to increased bone demineralization. Objective To examine the relationship of blood lead level with blood pressure and hypertension prevalence in a population-based sample of perimenopausal and postmenopausal women in the United States. Design, Setting, and Participants Cross-sectional sample of 2165 women aged 40 to 59 years, who participated in a household interview and physical examination, from the Third National Health and Nutrition Examination Survey conducted from 1988 to 1994. Main Outcome Measures Associations of blood lead with blood pressure and hypertension, with age, race and ethnicity, cigarette smoking status, body mass index, alcohol use, and kidney function as covariates. Results A change in blood lead levels from the lowest (quartile 1: range, 0.5-1.6 µg/dL) to the highest (quartile 4: range, 4.0-31.1 µg/dL) was associated with small statistically significant adjusted changes in systolic and diastolic blood pressures. Women in quartile 4 had increased risks of diastolic (&amp;amp;gt;90 mm Hg) hypertension (adjusted odds ratio [OR], 3.4; 95% confidence interval [CI], 1.3-8.7), as well as moderately increased risks for general hypertension (adjusted OR, 1.4; 95% CI, 0.92-2.0) and systolic (&amp;amp;gt;140 mm Hg) hypertension (adjusted OR, 1.5; 95% CI, 0.72-3.2). This association was strongest in postmenopausal women, in whom adjusted ORs for diastolic hypertension increased with increasing quartile of blood lead level compared with quartile 1 (adjusted OR, 4.6; 95% CI, 1.1-19.2 for quartile 2; adjusted OR, 5.9; 95% CI, 1.5-23.1 for quartile 3; adjusted OR, 8.1; 95% CI, 2.6-24.7 for quartile 4). Conclusions At levels well below the current US occupational exposure limit guidelines (40 µg/dL), blood lead level is positively associated with both systolic and diastolic blood pressure and risks of both systolic and diastolic hypertension among women aged 40 to 59 years. The relationship between blood lead level and systolic and diastolic hypertension is most pronounced in postmenopausal women. These results provide support for continued efforts to reduce lead levels in the general population, especially women.
Benign stricture of the oesophagus: role of non-steroidal anti-inflammatory drugs.
Authors: W E Wilkins, M G Ridley, A L Pozniak
Journal: Gut (1984)

The medication history of patients presenting with benign oesophageal stricture is compared with an age and sex matched control population selected from the community. Fifty five out of 151 consecutive admissions to a dysphagia clinic were found to have benign oesophageal stricture. Twenty six out of 53 (49%) had been prescribed non-steroidal anti-inflammatory drugs in the year preceding their clinic appointment. Ten patients (19%) had been prescribed other drugs implicated in oesophageal disease over the same period. In the control population, 20 out of 165 (12%) had been prescribed non-steroidal anti-inflammatory drugs, and 31 out of 165 had been prescribed 'other' drugs in the preceding year. The difference between numbers on non-steroidal anti-inflammatory drugs in the patient and control groups was highly significant (X2 = 23.87, p less than 0.1%). This study has shown an association between the prescribing of non-steroidal anti-inflammatory drugs and benign stricture of the oesophagus.
Incidence, outcomes, and cost of foot ulcers in patients with diabetes.
Authors: S D Ramsey, K Newton, D Blough, D K McCulloch, N Sandhu, G E Reiber, E H Wagner
Journal: Diabetes Care (1999)

OBJECTIVE: To determine the incidence of foot ulcers in a large cohort of patients with diabetes, the risk of developing serious complications after diagnosis, and the attributable cost of care compared with that in patients without foot ulcers. RESEARCH DESIGN AND METHODS: Retrospective cohort study of patients with diabetes in a large staff-model health maintenance organization from 1993 to 1995. Patients with diabetes were identified by algorithm using administrative, laboratory, and pharmacy records. The data were used to calculate incidence of foot ulcers, risk of osteomyelitis, amputation, and death after diagnosis of foot ulcer, and attributable costs in foot ulcer patients compared with patients without foot ulcers. RESULTS: Among 8,905 patients identified with type 1 or type 2 diabetes, 514 developed a foot ulcer over 3 years of observation (cumulative incidence 5.8%). On or after the time of diagnosis, 77 (15%) patients developed osteomyelitis and 80 (15.6%) required amputation. Survival at 3 years was 72% for the foot ulcer patients versus 87% for a group of age- and sex-matched diabetic patients without foot ulcers (P &amp;lt; 0.001). The attributable cost for a 40- to 65-year-old male with a new foot ulcer was $27,987 for the 2 years after diagnosis. CONCLUSIONS: The incidence of foot ulcers in this cohort of patients with diabetes was nearly 2.0% per year. For those who developed ulcers, morbidity, mortality, and excess care costs were substantial compared with those for patients without foot ulcers. The results appear to support the value of foot-ulcer prevention programs for patients with diabetes.
Expression of a cyclin E1 isoform in mice is correlated with the quiescent cell cycle status of hepatocytesin vivo
Authors: Nils-Holger Zschemisch, Christian Liedtke, Uta Dierssen, Yulia A. Nevzorova, Torsten Wüstefeld, Jürgen Borlak, Michael P. Manns, Christian Trautwein
Journal: Hepatology (2006)

Cyclin E1 controls G1/S phase transition of the eukaryotic cell cycle. We report the impact of alternative spliced cyclin E1 isoforms on cell cycle regulation in hepatocytes. We show that expression of new cyclin E1 mRNA variants IN3, Δ4, and Δ5 is associated with retarded proliferation in murine hepatocellular carcinoma. Additionally, we demonstrate that a new cyclin E1 isoform Δ3/8 lacking the central part of wild-type mRNA is expressed predominantly in nonproliferating murine hepatocytes. Following partial hepatectomy, Δ3/8 is downregulated when hepatocytes enter the cell cycle from quiescence. The Δ3/8 protein does not exhibit any cyclin box motif but binds cyclin-dependent kinase 2 without stimulating kinase activity. We demonstrate that Δ3/8 lacks any nuclear localization signal and is exclusively located in the cytoplasm. Overexpression of Δ3/8 in cultured cells leads to a delayed G0-G1 transition, indicating that this splice variant helps to maintain a quiescent state of hepatocytes. In conclusion , we identified an isoform of cyclin E1 involved in G0 maintenance and suggest an additional mechanism for cell cycle control.
Abstract 1086: The role of HEF1 protein in stabilization and activation of AurA kinase in metastatic breast cancer
Authors: Elena N. Pugacheva, Sarah McLaughlin, Bridget Hindman, Erica A. Golemis
Journal: Cancer Research (2010)

Abstract AurA kinase expression is linked to human disease since the extent of AurA up-regulation was significantly associated with advanced tumor stage and the occurrence of metastasis. AurA inhibitors have recently entered phase II clinical trials for cancer treatment, but application of these inhibitors for treatment of advanced human cancers has demonstrated limited efficacy. The reasons why potent in vitro inhibitors of AurA are inefficient under these conditions are unknown. In our current study, we define the mechanisms by which AurA is upregulated in breast tumor cells and what impact HEF1 expression has on AurA-associated occurrence of metastasis. Our hypothesis is that over-expression of HEF1 protein in breast cancer cells will protect AurA from proteolytic degradation, resulting in activation of AurA kinase. Here we demonstrate that direct binding of HEF1 stabilizes AurA by blocking the cdh1 binding site and limiting AurA ubiquitination. HEF1 binding decreases the efficacy of AurA inhibitors in cell culture. Deletion of HEF1 by gene knockout and depletion by siRNA in cell lines cause dramatic decreases in AurA protein level and kinase activity - indicating HEF1 is the major AurA regulator in vivo. We further show that deletion of HEF1 reduces tumor cell proliferation and invasion in mouse mammary tumor models. These data provide insights into the potential development of small molecule inhibitors that could be used therapeutically to target the HEF1/AurA pathway and thereby inhibit tumor formation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1086.
Environmental Oxidant Pollutant Effects on Biologic Systems
Authors: Carroll E. Cross, Giuseppe Valacchi, Bettina Schock, Malinda Wilson, Stefan Weber, Jason Eiserich, Albert van der Vliet
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Section:ChooseTop of pageAbstract <<THE PLANT WORLDTHE INSECT WORLDTHE SKIN WORLDTHE RESPIRATORY TRACT WOR...ReferencesCITING ARTICLES
Effect of sulphide on short chain acyl-CoA metabolism in rat colonocytes.
Authors: J W Moore, W Babidge, S Millard, W E Roediger
Journal: Gut (1997)

BACKGROUND: It has been proposed that the diminished n-butyrate oxidation observed in ulcerative colitis may be the result of sulphide induced inhibition of short chain acyl-coenzyme A (acyl-CoA) dehydrogenase activity. AIM: To examine the acyl-CoA ester profiles in isolated rat colonic epithelial cells treated in vitro with sodium hydrogen sulphide (NaHS). METHODS: Isolated rat colonic epithelial cell suspensions were incubated for 10 minutes in the presence of [1-14C] n-butyrate (5 mM), with and without NaHS (1.5 mM). Incubations were carried out both in the presence and the absence of exogenous CoA and ATP. Metabolic performance was assessed by 14CO2 production and by acyl-CoA ester production measured by HPLC with ultraviolet detection. RESULTS: Results are given as mean (SEM). For colonocytes incubated in the presence of exogenous CoA and ATP, treatment with NaHS significantly diminished 14CO2 production (control 0.97 (0.06) mumol/g dry weight cells/min, treated 0.26 (0.09) mumol/g dry weight cells/min, p = 0.0019), was associated with an increase in butyryl-CoA concentrations in the final reaction mixture at 10 minutes (control 2.55 (0.28) mumol/g dry weight cells, treated 3.32 (0.32) mumol/g dry weight cells, p = 0.002), and a reduction in crotonyl-CoA concentrations (control 0.274 (0.02) mumol/g dry weight cells, treated 0.120 (0.04) mumol/g dry weight cells, p = 0.008). The mean concentration of acetyl-CoA in the reaction mixture at 10 minutes was not significantly different between control and sulphide treated incubations. There were no significant differences in acyl-CoA ester profiles observed when cells were incubated in the absence of exogenous CoA and ATP. CONCLUSIONS: These results support the view that sulphides inhibit n-butyrate oxidation in colonic epithelial cells by inhibiting short chain acyl dehydrogenation of activated fatty acids.
Separating Wheat From Chaff of Nutrition Information
Authors: Andrew A. Skolnick
Journal: JAMA (1997)

TO HELP health reporters separate the wheat from the chaff of nutrition information, the American Heart Association (AHA) served a hearty helping of nutrition science at its 24th Health and Science Journalists Forum in Seattle, Wash. And to give them a taste of the difficulties of translating the latest research findings into dietary guidelines, one authority explained why Americans need to reduce their high salt consumption while another explained why they don't. <h3>Saline Solution?</h3> "Based on all the available experimental, epidemiologic, and clinical evidence, it seems prudent to include avoidance of a high salt intake as one component of a population-based, comprehensive nutritional strategy for the prevention of cardiovascular disease," said Theodore A. Kotchen, MD, professor and chair of the Department of Medicine at the Medical College of Wisconsin in Milwaukee. "New clinical trials call into question the benefits of salt restriction, in comparison with other dietary interventions—calorie restriction
Argon Plasma Endoscopic Section of Biliary Metallic Prostheses
Authors: J. F. Demarquay, R. Dumas, E. P. Peten, P. Rampal
Journal: Endoscopy (2001)

We report our recent experience of using argon plasma to endoscopically cut biliary Wallstent prostheses in these patients. The first patient had a bleeding duodenal ulceration caused by the impaction of the prosthesis meshes whereas the second patient had an ill-positioned biliary stent with impaction into the opposite duodenal wall. Both prostheses were shortened using argon plasma. In the third patient, the lower extremity of a obstructed biliary Wallstent was positioned in the third duodenum preventing its endoscopic catheterization. After shortening using argon plasma, a new plastic stent could be inserted to allow drainage. The outcomes in these cases demonstrate the feasibility of endoscopically shortening metallic Wallstents after release using argon plasma.
Tyrosine deficiency and retardation?
Authors: May Annexton
Journal: JAMA (1978)

To add to the confusion about phenylketonuria (PKU), there is a new wrinkle. According to a report published in March of this year in the<i>Proceedings of the National Academy of Sciences</i>(75:1562), deficiency of the nonessential amino acid tyrosine may be just as responsible for the mental retardation in PKU as high levels of phenylalanine. A study by Samuel Bessman, MD, Malcolm Williamson, MD, and Richard Koch, MD, of the University of Southern California School of Medicine, attempted to correlate the mean IQ of siblings of known PKU children (67% of PKU siblings are heterozygous for PKU and 33% are normal, according to Mendelian predictions) with their ability to convert phenylalanine to tyrosine. Results showed a 10 point mean IQ difference between those siblings least able and those most able to convert phenylalanine to tyrosine. According to the investigators, since the mothers of PKU children are always heterozygous for
Serum alkaline phosphatase determination. Value in the staging of advanced breast cancer
Authors: Douglas R. White, John J. Maloney, Hyman B. Muss, Richard P. Vance, Paula Barnes, Virginia Howard, Leonard Rhyne, Robert J. Cowan
Journal: JAMA (1979)

A retrospective study of 146 patients with metastatic disease was undertaken to verify the clinical impression that radionuclide scanning rarely, if ever, discloses hepatic metastases in breast cancer patients with normal serum alkaline phosphatase (AP) levels. Only two of 39 patients with abnormal liver scans had normal AP levels, and we conclude that liver scans are not necessary as a routine screening method for liver metastases when the AP level is normal. In contrast AP levels were not predictive of bone scan results. All patients with a twofold or greater elevation of the AP level had abnormal bone, liver, or bone and liver scans. Routine AP determinations provide accurate staging information, and their proper use can decrease the cost of initial and follow-up examination of patients with breast cancer.
Innovations in Program and Funding of Mental Health Services for Blue-Collar Families
Authors: JUDSON L. STONE, VIRGINIA CROWTHERS
Journal: American Journal of Psychiatry (1972)

A public mental health clinic formerly serving only children and seeking to broaden its service and financial base joined with a consumer advocate, the United Auto Workers, to provide treatment to underserved blue-collar workers. Comprehensive outpatient mental health service to adults on a prepaid basis was made possible through an innovative financial arrangement with Blue Cross. The authors discuss various problems in implementing this program, which they offer as a possible model for financing community mental health services.
Sensitizing Effect of Galectin-7 in Urothelial Cancer to Cisplatin through the Accumulation of Intracellular Reactive Oxygen Species
Authors: Yoshiyuki Matsui, Shugo Ueda, Jun Watanabe, Ichiro Kuwabara, Osamu Ogawa, Hiroyuki Nishiyama
Journal: Cancer Research (2007)

Abstract To improve chemotherapeutic efficacy in urothelial cancer, it is important to identify predictive markers for chemosensitivity as well as possible molecules accelerating cell killing mechanisms. In this study, we assessed the possibility of galectin-7 to accelerate cis-diamminedichloroplatinum (CDDP)–induced cell killing in vitro and also to predict chemosensitivity against CDDP in urothelial cancer patients. The expression of galectin-7 was analyzed in five bladder cancer cell lines with different p53 status after treatment with CDDP. The roles of galectin-7 in chemosensitivity against CDDP were analyzed by transfection of the galectin-7 gene into several of these cell lines. Furthermore, the relationship between the expression of galectin-7 and the response to neoadjuvant chemotherapy was analyzed in 17 human bladder cancer specimens. Exposure to CDDP induced galectin-7 in cell lines with wild-type p53 but not in those with mutated p53. When the galectin-7 gene was transfected into cell lines with mutated p53, the sensitivity to CDDP increased compared with control transfectants. In addition, galectin-7–transfected cells exhibited more accumulation of intracellular reactive oxygen species and activation of c-Jun NH2-terminal kinase (JNK) and Bax than control transfectants. SP600125, an inhibitor of JNK, or antioxidant N-acetyl-l-cysteine inhibited the enhancement of chemosensitivity against CDDP by galectin-7 transfection. In clinical samples, the expression levels of galectin-7 were significantly lower in urothelial carcinomas compared with normal urothelium. When chemosensitivity was tested, its expression levels were higher in the chemosensitive group than in the chemoresistant group. Galectin-7 is a candidate for a predictive marker of chemosensitivity against CDDP, and the targeted expression of galectin-7 might overcome the chemoresistance of urothelial cancer. [Cancer Res 2007;67(3):1212–20]
A 13-item score predicted survival to discharge with good neurologic status after CPR for in-hospital cardiac arrest
Authors: KoKo Aung
Journal: Annals of Internal Medicine (2013)

Source Citation Ebell MH, Jang W, Shen Y, Geocadin RG; Get with the Guidelines–Resuscitation Investigators. Development and validation of the Good Outcome Following Attempted Resuscitation (GO-FAR) score to predict neurologically intact survival after in-hospital cardiopulmonary resuscitation. JAMA Intern Med. 2013 Sep 9. [Epub ahead of print]. 24018585
Low-Molecular-Weight Heparinoid Orgaran Is More Effective Than Aspirin in the Prevention of Venous Thromboembolism After Surgery for Hip Fracture
Authors: M. Gent, J. Hirsh, J.S. Ginsberg, P.J. Powers, M.N. Levine, W.H. Geerts, R.M. Jay, J. Leclerc, J.A. Neemeh, A.G.G. Turpie
Journal: Circulation (1996)

Background The study objective was to determine the relative efficacy and safety of a low-molecular-weight heparinoid (Orgaran) compared with aspirin for the prevention of postoperative venous thromboembolism in patients undergoing surgery for fractured hips. A double-blind, randomized, controlled trial was used to study 251 consecutive eligible and consenting patients undergoing surgery for hip fracture in seven participating hospitals. Methods and Results Patients received either fixed-dose Orgaran by subcutaneous injection every 12 hours in a dose of 750 anti–Factor Xa units or aspirin 100 mg orally twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. All patients had postoperative 125 I-fibrinogen leg scanning and impedance plethysmography. If the results of one or both tests were positive, then venography was performed. Otherwise, venography was done at day 14, or sooner if the patient was ready for discharge. Pulmonary embolism in symptomatic patients was diagnosed on the basis of a high probability perfusion/ventilation lung scan, a positive angiogram, or a clinically significant embolism detected at autopsy. Evaluable venograms were obtained in 90 of the 125 patients randomly assigned to receive Orgaran and in 87 of the 126 patients assigned to receive aspirin. Venous thromboembolism was detected in 25 (27.8%) patients in the Orgaran group and in 39 (44.3%) patients in the aspirin group. Thus, there was a relative risk reduction of 37% with Orgaran ( P =.028; 95% confidence interval, 3.7% to 59.7%). Six (6.8%) of 88 patients in the Orgaran group and 12 (14.3%) of 84 patients in the aspirin group developed proximal deep vein thrombosis or pulmonary embolism, a relative risk reduction of 52% with Orgaran ( P =.137; 95% confidence interval, −30.7% to 84.6%). Hemorrhagic complications occurred in 2 (1.6%) patients given Orgaran and 8 (6.4%) patients given aspirin ( P =.10). There was one major bleed in the Orgaran group compared with four in the aspirin group. Conclusions This study demonstrates that Orgaran is significantly more efficacious than aspirin in preventing postoperative venous thromboembolism in patients undergoing surgery for fractured hips, with no evidence of any increase in hemorrhagic complications.