tbuckley/cabot-search huggingface dataset:
What Is the Impact of Shared Decision Making on Treatment and Outcomes for Older Women With Breast Cancer?
Authors: Jeanne Mandelblatt, Barbara Kreling, Melissa Figeuriedo, Shibao Feng
Journal: Journal of Clinical Oncology (2006)

Purpose Shared decision making (SDM) has been recommended as a standard of care, especially when there are treatment alternatives or uncertainty in outcomes. However, we know little about use of SDM in cancer care, and even less is known about SDM in older patients. We describe patient and physician determinants of SDM in older women with breast cancer and evaluate whether SDM is associated with treatment patterns or short-term outcomes of care. Patients and Methods Women age 67 or older treated for early stage breast cancer in 29 sites from five geographic regions comprise the study sample (N = 718). Data were obtained from patients by in-person and telephone interviews. Physician data were collected via survey, and medical records were reviewed to ascertain comorbidity and tumor characteristics. Random effects and logistic regression models were used to assess associations between SDM and other factors. Results Women who were age 67 to 74 years (v 75 or older) were accompanied to consultation and who sought information reported the highest SDM, after considering covariates. While SDM was not associated with surgical treatment, greater SDM was associated with higher odds of having adjuvant treatment, controlling for clinical factors. Greater SDM was also associated with improved short-term satisfaction. Conclusion SDM plays an important role in the process of care for older women with breast cancer. Physicians treating this growing population have a simple, but powerful tool for improving outcomes within their grasp—spending time to engage and involve older women in their breast cancer care.
Airway epithelium as an effector of inflammation: molecular regulation of secondary mediators
Authors: LD Martin, LG Rochelle, BM Fischer, TM Krunkosky, KB Adler
Journal: European Respiratory Journal (1997)

Deleterious environmental stimuli cause the airway epithelium to respond with increased secretions of mucus, reaction of oxygen/nitrogen species, changes in ciliary beating, and the influx of inflammatory cells. The epithelium is a target for factors released by infiltrating inflammatory cells, and has recently been shown to serve as an effector of such inflammation. Molecular mechanisms regulating production of secondary inflammatory mediators (cytokines, lipid mediators, and reactive oxygen/nitrogen species) have yet to be fully described. This report reviews the production of secondary mediators by epithelial cells and by airway epithelium. Lipid mediators are enzymatically produced by the airway epithelium in response to primary mediators. Molecular mechanisms regulating the production of cyclo-oxygenase, lipoxygenase and prostaglandin synthase are discussed, along with the potential of lipid mediators to produce inflammation. The molecular regulation of nitric oxide production is also described in the context of its role as a signalling molecule in pathways regulating secretion of mucus, ciliary motion, and intercellular adhesion molecule-1 (ICAM-1) expression. The production of cytokines by the airway epithelium is shown to play a role in causing inflammation associated with respiratory diseases. Particular attention is paid to molecular mechanisms governing the expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8).
Staying true to our roots
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2007)

T cells tell macrophages when to start making the toxic soup of lysosomal enzymes, reactive oxygen species, and nitric oxide that destroys intracellular pathogens. In 1983, Carl Nathan proved that this start signal comes in the form of the secreted cytokine IFNgamma.
Responsiveness of Growth Hormone-Deficient Children to Human Growth Hormone EFFECT OF REPLACEMENT THERAPY FOR ONE YEAR
Authors: Daniel Rudman, Joseph H. Patterson, Donna L. Gibbas
Journal: Journal of Clinical Investigation (1973)

Previous studies have shown that growth hormone (GH)-deficient children are more responsive to exogenous human growth hormone (HGH) than non-GH-deficient children. In six GH-deficient children, velocity of linear growth was less than 2.5 cm/yr. By the metabolic balance study technique, anabolic responses (increments in elemental balances) were measured to a 7 day course of 0.0532 U HGH/kg body weight (BW)(3/4) per day (dose B) and to 0.168 U/kg BW(3/4) per day (dose C). They were then treated for 1 yr with HGH at a dose intermediate between B and C. Velocity of linear growth accelerated to 15-25 cm/yr for the first 4-7 mo, then declined to 0-8 cm/yr. At 12 mo, responsiveness to doses B and C was measured again; the responses were only 20-60% as great as before treatment. After 3 mo without HGH treatment, responsiveness to the anabolic effects of doses B and C returned to the magnitudes observed before treatment. A low titer of plasma antibodies to HGH was detected in two of the six children at the end of the year's treatment; these titers showed little change after 3 mo without HGH. Thus the hyperresponsiveness of GH-deficient subjects to exogenous HGH, compared to non-GH-deficient individuals, declines during long-term HGH treatment and is restored by 3 mo interruption of treatment. These changes in peripheral responsiveness may be related to the decline in velocity of linear growth which occurs after 4-7 mo of continuous treatment. When HGH was withdrawn after 12 mo, all six patients exhibited negative balances of N, P, Na, and K and loss of BW. Ratios of elemental balances showed about half the weight loss to represent protoplasm, and about half extracellular fluid. These observations indicate a role of GH in the continuing regulation of nitrogen and mineral metabolism in addition to its function as a growth-promoting hormone.
The Systemic Capillary Leak Syndrome: A Case Series of 28 Patients From a European Registry
Authors: Marie Gousseff
Journal: Annals of Internal Medicine (2011)

Background: The systemic capillary leak syndrome (SCLS) is a rare disease characterized by life-threatening attacks of capillary hyperpermeability. Objective: To describe the clinical characteristics, laboratory findings, treatments, and outcomes of patients with SCLS who were not previously reported in the literature. Design: Case series. Setting: Patients referred to a European multicenter SCLS registry between January 1997 and July 2010. Patients: 28 patients with SCLS. Measurements: Frequency, severity of attacks, and vital status were assessed every 6 months, from diagnosis to the end of the study. Results: 13 men and 15 women referred to the registry who were not previously reported in the literature had 252 attacks. Median age at disease onset was 49.1 years (range, 5.4 to 77.7 years), and median annual frequency of attacks was 1.23 (range, 0.13 to 21.18) per patient. Monoclonal IgG gammopathy was observed in 25 patients (89%). Preventive treatment included intravenous immunoglobulin (n = 18), terbutaline (n = 9), and aminophylline (n = 10). Eight patients died (29%); 1-year survival was 89%, and 5-year survival was 73%. Death was directly related to SCLS attacks in 6 of 8 cases (75%). In 10 patients with a prediagnosis period greater than 6 months who received preventive treatment, the annual frequency of attacks after diagnosis decreased by a median of 1.55 (range, 0.14 to 8.84) per patient. Five years after diagnosis, survival was 85% in 23 patients who had received prophylactic treatment and 20% in 5 patients who had not. Limitation: The benefits of preventive treatment could not be precisely ascertained because of the small sample size and because most patients received several treatments. Conclusion: Clinical experience with these 28 patients with SCLS suggests that prophylactic treatment with β2-agonists or intravenous immunoglobulin may reduce the frequency and severity of attacks and may improve survival. Primary Funding Source: Université Pierre et Marie Curie, Paris, France.
Glycemic Control Impact on Body Weight Potential to Reduce Cardiovascular Risk
Authors: Giorgio Sesti
Journal: Diabetes Care (2011)

The prevalence and incidence of type 2 diabetes are progressively increasing because of a concomitant rise in the prevalence of obesity. Intentional weight loss in patients with type 2 diabetes has been associated with a 25% reduction in total mortality and a 28% reduction in cardiovascular disease and diabetes mortality (1).

Weight gain is not only a risk factor for development of type 2 diabetes, but it is also the undesirable feature of several current antidiabetic treatments such as thiazolidinediones, sulfonylureas, and insulin, with an estimated 2-kg weight gain for every 1% decrease in HbA1c (2,3). Reasons for this include defensive snacking to treat or prevent hypoglycemia, decreased glucosuria, decreased basal metabolic rate, and expansion in adipose tissue and fluid retention.

Recently, novel therapeutic agents were developed for the treatment of type 2 diabetes. Among these are the incretin-based therapies, which include glucagon-like peptide (GLP)-1 receptor agonists and inhibitors of the protease dipeptidyl peptidase (DPP)-4. Both classes of drugs use the antidiabetic properties of GLP-1, an incretin hormone that potentiates insulin secretion in a glucose-dependent manner (4). In addition, GLP-1 exerts many beneficial effects on pancreatic islet function, including stimulation of (pro)-insulin biosynthesis, reduction in β-cell apoptosis induced by toxic agents, and suppression of glucagon release from the α-cells, resulting in reduced hepatic glucose output (5). GLP-1 also decreases the rate of gastric emptying, which slows the entry of nutrients into the circulation after meals, reduces appetite, and promotes satiety, leading to weight loss upon chronic exposure (6). However, GLP-1 has a short half-life (∼1–2 min), since it is rapidly degraded through NH2-terminal cleavage by the protease DPP-4; therefore, a continuous infusion would be required to achieve a clinical effect in diabetic patients (7). Two approaches were used to overcome these limitations: 1 ) GLP-1 …
Transplantation of Woodchuck Hepatocellular Carcinoma in Nude Mice
Authors: Kenichi Kobayashi, Kenichi Fukuoka, Fumiaki Matsushita, Hideo Morimoto, Yoshinobu Hinoue, Hideo Honjo, Nobuyoshi Tanaka, Tatsuho Sugimoto, Yasuhiro Kato, Nobu Hattori, Shigeharu Ueda, Shiro Kato
Journal: Hepatology (1983)

Woodchuck hepatocellular carcinoma has been successfully transplanted into nude (athymic) mice. The morphology of heterotransplanted tumor is similar to that of naturally occurring hepatocellular carcinoma before transplantation. The growth rate of transplanted tumor was very slow compared with those of other transplanted tumors. During the first month, only two tumors appeared. However, definitive tumor growth was noted in 6 of 20 nude mice about 3 months later. Seventeen of 20 nude mice exhibited sustained tumor growth after 6 months. The woodchuck hepatocellular carcinoma in nude mice provides an in vivo model for the study of oncogenesis of human hepatocellular carcinoma related to hepatitis B virus.
Tetranucleotide Microsatellite Instability in Surgical Margins for Prediction of Local Recurrence of Head and Neck Squamous Cell Carcinoma
Authors: Stephane Temam, Odile Casiraghi, Jean-Baptiste Lahaye, Jacques Bosq, Xian Zhou, Morbize Julieron, Gerard Mamelle, J. Jack Lee, Li Mao, Bernard Luboinski, Jean Benard, Francois Janot
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Postoperative radiotherapy is used to prevent local recurrence of head and neck squamous cell carcinoma in patients with positive surgical margins. We sought to determine whether tetranucleotide microsatellite instability could be detected in surgical margins and used to predict local recurrence. Experimental Design: We prospectively collected tumor and surgical margin specimens from patients with head and neck squamous cell carcinoma who had undergone surgical resection at Institut Gustave-Roussy during a 1-year period. Margins were considered positive if extensive pathological examination revealed either carcinoma within 5 mm or dysplasia. We tested five tetranucleotide microsatellite markers (UT5085, L17686, D9S753, ACTBP2, and CSF1R) in the tumor specimens and paired surgical margins of the patients whose margins were negative on pathological examination. Results: Pathological examination revealed that among the 76 patients, 22 had positive margins; therefore, these patients were excluded. Of the 54 remaining patients, 26 (48%) had tumors informative for markers UT5085, L17686, or both; the other 3 markers were not informative. Seven (27%) of the 26 informative tumors had the same instability pattern in the surgical margins. At a median follow-up of 26 months, 5 of the 7 local recurrences occurred in patients with molecularly positive surgical margins. A strong, independent association was found between positive surgical margins and local recurrence (P = 0.01; hazard ratio, 6.49). Conclusions: Tetranucleotide microsatellite instability in surgical margins may be a useful biomarker to predict local recurrence of head and neck squamous cell carcinoma in patients with apparently disease-free margins.
Of Spiders and Crabs: The Emergence of Lysophospholipids and Their Metabolic Pathways as Targets for Therapy in Cancer
Authors: Mandi Murph, Tamotsu Tanaka, Shuying Liu, Gordon B. Mills
Journal: Clinical Cancer Research (2006)

Abstract Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), two small lysophospholipids, are potent inducers of many of the hallmarks of cancer including cell proliferation, survival, migration, invasion, and neovascularization in in vitro and in vivo tumor models. Furthermore, the enzymes metabolizing LPA and S1P and their receptors are aberrant in multiple cancer lineages and exhibit transforming activity altering patterns and targets for metastasis. Several recent studies show the remarkable activity of new chemical genomics and/or potential novel drugs in preclinical models. Combined with the physiologic and pathophysiologic activities of LPA and S1P, these studies suggest the implementation of preclinical and clinical evaluation of LPA and S1P as therapeutic targets.
Cancer Survivorship: A New Challenge in Delivering Quality Cancer Care
Authors: Julia H. Rowland, Maria Hewitt, Patricia A. Ganz
Journal: Journal of Clinical Oncology (2006)

“After my very last radiation treatment for breast cancer, I lay ona cold steel table hairless, half-dressed and astonished by the tearsstreaming down my face. I thought I would feel happy about ﬁnallyreaching the end of treatment, but instead I was sobbing. At the time,Iwasn’tsurewhatemotionsIwasfeeling.Lookingback,IthinkIcriedbecause this body had so bravely made it through 18 months ofsurgery, chemotherapy, and radiation. Ironically, I also cried be-cause I would not be coming back to that familiar table where I hadbeen comforted and encouraged. Instead of joyous, I felt lonely,abandoned and terriﬁed. This was the rocky beginning of cancersurvivorship for me.”—Elizabeth D. McKinley, MD, MPH
Regulation of Excision Repair Cross-Complementation Group 1 by Snail Contributes to Cisplatin Resistance in Head and Neck Cancer
Authors: Dennis Shin-Shian Hsu, Hsin-Yi Lan, Chi-Hung Huang, Shyh-Kuan Tai, Shyue-Yih Chang, Tung-Lung Tsai, Cheng-Chi Chang, Cheng-Hwai Tzeng, Kou-Juey Wu, Jung-Yie Kao, Muh-Hwa Yang
Journal: Clinical Cancer Research (2010)

We investigated the mechanism and clinical significance of the epithelial-mesenchymal transition (EMT)-induced chemoresistance in head and neck squamous cell carcinoma (HNSCC).The correlation between the expression of different EMT regulators and chemoresistance genes, such as excision repair cross complementation group 1 (ERCC1), was evaluated in cancer cell lines from the NCI-60 database and four human HNSCC cell lines. Ectopic expression of Snail or short-interference RNA-mediated repression of Snail or ERCC1 was done in HNSCC cell lines. Cell viability was examined for cells after cisplatin treatment. A luciferase reporter assay and chromatin immunoprecipitation were used to identify the transcriptional regulation of ERCC1 by Snail. Immunohistochemical analysis of Snail, Twist1, ERCC1, hypoxia inducible factor-1 α (HIF-1α), and NBS1 were done in samples from 72 HNSCC patients receiving cisplatin-based chemotherapy.The correlation between the expression of Snail and ERCC1 was confirmed in different cell lines, including HNSCC cells. In HNSCC cell lines, overexpression of Snail in the low endogenous Snail/ERCC1 cell lines FaDu or CAL-27 increased ERCC1 expression, and hypoxia or overexpression of NBS1 also upregulated ERCC1. Knockdown of Snail in the high endogenous Snail/ERCC1 cell line OECM-1 downregulated ERCC1 expression and attenuated cisplatin resistance. Furthermore, suppression of ERCC1 in Snail- or NBS1-overexpressing HNSCC cells enhanced sensitivity to cisplatin. Snail directly regulated ERCC1 transcription. In patients with HNSCC, coexpression of Snail and ERCC1 correlated with cisplatin resistance and a poor prognosis.Activation of ERCC1 by Snail is critical in the generation of cisplatin resistance of HNSCC cells.
Anchors Aweigh!
Authors: Paul B. Bennett
Journal: Circulation Research (2000)

enomics, proteomics, transgenics, molecular medicine: these are some of the scientific catch phrases of the 1990s.The hard work and high expectations of the past decade are beginning to influence reality.Results have accrued to the point that we can begin applying molecular knowledge to therapeutics.Although still in the formative stages, one cannot help but see the vast potential of the exponentially growing molecular knowledge base for understanding physiology and pathophysiology.
The isolation of functionally heterogeneous hepatocytes of the proximal and distal half of the liver acinus in the rat
Authors: Jorge J. Gumucio, Maryann May, Caroline Dvorak, Jose Chianale, Veronica Massey
Journal: Hepatology (1986)

The objective of this study was to isolate hepatocytes of the proximal half (Zones 1 and 2) or distal half (Zones 2 and 3) of the liver acinus. The zonal origin of the isolated hepatocytes was recognized by: (a) the presence in hepatocytes of a fluorescent marker, acridine orange, selectively delivered to either the proximal or the distal half of the acinus by in situ perfusion prior to cell isolation and (b) the measurement of the induction of cytochrome P-450 by phenobarbital, an induction known to occur predominantly in the distal half of the acinus. Following the selective labeling of the acinus with acridine orange, livers were perfused with collagenase in either the portal to hepatic vein direction (anterograde) or in the retrograde direction. Hepatocytes isolated by either an anterograde or a retrograde perfusion were separated by centrifugation in a Percoll density gradient. This procedure isolated populations of proximal or distal hepatocytes, respectively, which were intact and 90% fluorescent. In an effort of assessing the heterogeneity of the separated proximal and distal hepatocytes, each population was further fractionated by centrifugal elutriation. This resulted in the arbitrary separation of proximal or distal hepatocytes into five fractions. Total cytochrome P-450 was determined spectrophotometrically in each of the fractions isolated from controls and after 3 days of the in vivo administration of phenobarbital. On the basis of the pattern of fluorescence in isolated hepatocytes and on the cytochrome P-450 inductive response to phenobarbital administration, it is proposed that: (a) the anterograde or retrograde perfusion of the liver with collagenase separated hepatocytes predominantly of the proximal or distal half of the liver acinus, respectively and (b) that hepatocytes of the distal half of the liver acinus responded to phenobarbital administration with the highest level of cytochrome P-450 induction, indicating that the isolated hepatocytes conserved the functional heterogeneity observed in vivo.
Anticoagulant-Induced Thrombosis
Authors: J. O. Ballard
Journal: JAMA (1999)

EACH YEAR THROMBOEMBOLISM affects millions of individuals worldwide. As a result, anticoagulants are among the most commonly prescribed drugs in clinical practice. Heparin sodium and warfarin sodium are used alone or sequentially for primary and secondary prophylaxis in the management of a variety of thrombotic diseases. Bleeding complications associated with these agents are well-known; however, the risks and causes of paradoxical venous or arterial thrombosis occurring during anticoagulant therapy have only recently been elucidated. This article reviews the current understanding of serious acquired-prothrombotic states that can occasionally develop during treatment with anticoagulants. As background, a brief description of each drug’s mechanism of action is first presented.
Hormone replacement therapy and the prevention of cardiovascular disease
Authors: H. J. Teede
Journal: Human Reproduction Update (2002)

Cardiovascular disease (CVD) is the primary killer of both men and women in Western societies. The implementation of preventive strategies has led to a fall in the rate of CVD, but there is still much to be achieved. Proven interventional strategies are largely under-utilized, and the search continues for further promising interventions. HRT appears to reduce CVD in post-menopausal women, based on observational data supported by plethora of evidence for the beneficial cardiovascular effects of estrogen. However, a recent controlled trial in post-menopausal women with established CVD has shown that a specific combined oral HRT regimen did not reduce, and may even contribute to, an early increase in cardiovascular events, suggesting that HRT is inappropriate in secondary prevention. HRT may be useful in the primary prevention of CVD, yet observational data that suggested cardiovascular benefit with HRT also suggests that 80% of CVD in women could be eliminated by lifestyle modification, without the attendant risks of HRT including thrombosis and (potentially) breast cancer. At present, it is arguable that the evidence is inadequate to recommend HRT solely for the purpose of CVD prevention, and that the challenge for the health professional should be appropriate utilization of established preventative therapies, with further research into the potential role of HRT and estrogen-receptor modulators.
Dynamical Systems Approach to Endothelial Heterogeneity
Authors: Erzsébet Ravasz Regan, William C. Aird
Journal: Circulation Research (2012)

Endothelial cells display remarkable phenotypic heterogeneity. An important goal is to elucidate the scope and mechanisms of endothelial heterogeneity and to use this information to develop vascular bed-specific therapies. We reexamine our current understanding of the molecular basis of endothelial heterogeneity. We introduce multistability as a new explanatory framework in vascular biology. We draw on the field of nonlinear dynamics to propose a dynamical systems framework for modeling multistability and its derivative properties, including robustness, memory, and plasticity. Our perspective allows for both a conceptual and quantitative description of system-level features of endothelial regulation.