tbuckley/cabot-search huggingface dataset:
Molecular Pathways: Clinical Applications and Future Direction of Insulin-like Growth Factor-1 Receptor Pathway Blockade
Authors: Wade T. Iams, Christine M. Lovly
Journal: Clinical Cancer Research (2015)

The IGF1R signaling pathway is a complex and tightly regulated network that is critical for cell proliferation, growth, and survival. IGF1R is a potential therapeutic target for patients with many different malignancies. This brief review summarizes the results of clinical trials targeting the IGF1R pathway in patients with breast cancer, sarcoma, and non-small cell lung cancer (NSCLC). Therapeutic agents discussed include both monoclonal antibodies to IGF1R (dalotuzumab, figitumumab, cixutumumab, ganitumab, R1507, AVE1642) and newer IGF1R pathway targeting strategies, including monoclonal antibodies to IGF1 and IGF2 (MEDI-573 and BI 836845) and a small-molecule tyrosine kinase inhibitor of IGF1R (linsitinib). The pullback of trials in patients with breast cancer and NSCLC based on several large negative trials is noted and contrasted with the sustained success of IGF1R inhibitor monotherapy in a subset of patients with sarcoma. Several different biomarkers have been examined in these trials with varying levels of success, including tumor expression of IGF1R and its pathway components, serum IGF ligand levels, alternate pathway activation, and specific molecular signatures of IGF1R pathway dependence. However, there remains a critical need to define predictive biomarkers in order to identify patients who may benefit from IGF1R-directed therapies. Ongoing research focuses on uncovering such biomarkers and elucidating mechanisms of resistance, as this therapeutic target is currently being analyzed from the bedside to bench.
Phaeochromocytomas of the Bladder
Authors: O Khan, G D Chisholm, Gordon Williams, R B Welbourn
Journal: Journal of the Royal Society of Medicine (1982)

Phaeochromocytomas of the bladder are rare, only about 100 cases having been reported previously. Four adults with these lesions have been managed at Hammersmith Hospital in the past 10 years. Three patients had hypertension, together with syncopal attacks and/or headaches, induced by micturition. The fourth patient presented with haematuria. After control of blood pressure and localization of the tumours by various combinations of cystoscopy, intravenous urography, venous sampling, ultrasound, angiography and computerized coaxial tomography (CT scanning), 3 patients underwent partial cystectomy, and the fourth pelvic exenteration. Two patients were apparently cured of the disease, but 2 were not. One developed nodal metastases and recurrence of hypertension after 18 months and one rapidly developed metastases in the lungs and elsewhere. Effective therapy probably requires a high index of suspicion in diagnosing the condition and possibly an aggressive surgical and radiotherapeutic policy.
G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in Obesity and Diabetes
Authors: Xiaoxin X. Wang, Michal Herman Edelstein, Uzi Gafter, Liru Qiu, Yuhuan Luo, Evgenia Dobrinskikh, Scott Lucia, Luciano Adorini, Vivette D. D’Agati, Jonathan Levi, Avi Rosenberg, Jeffrey B. Kopp, David R. Gius, Moin A. Saleem, Moshe Levi
Journal: Journal of the American Society of Nephrology (2015)

Obesity and diabetes mellitus are the leading causes of renal disease. In this study, we determined the regulation and role of the G protein-coupled bile acid receptor TGR5, previously shown to be regulated by high glucose and/or fatty acids, in obesity-related glomerulopathy (ORG) and diabetic nephropathy (DN). Treatment of diabetic db/db mice with the selective TGR5 agonist INT-777 decreased proteinuria, podocyte injury, mesangial expansion, fibrosis, and CD68 macrophage infiltration in the kidney. INT-777 also induced renal expression of master regulators of mitochondrial biogenesis, inhibitors of oxidative stress, and inducers of fatty acid β-oxidation, including sirtuin 1 (SIRT1), sirtuin 3 (SIRT3), and Nrf-1. Increased activity of SIRT3 was evidenced by normalization of the increased acetylation of mitochondrial superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2) observed in untreated db/db mice. Accordingly, INT-777 decreased mitochondrial H2O2 generation and increased the activity of SOD2, which associated with decreased urinary levels of H2O2 and thiobarbituric acid reactive substances. Furthermore, INT-777 decreased renal lipid accumulation. INT-777 also prevented kidney disease in mice with diet-induced obesity. In human podocytes cultured with high glucose, INT-777 induced mitochondrial biogenesis, decreased oxidative stress, and increased fatty acid β-oxidation. Compared with normal kidney biopsy specimens, kidney specimens from patients with established ORG or DN expressed significantly less TGR5 mRNA, and levels inversely correlated with disease progression. Our results indicate that TGR5 activation induces mitochondrial biogenesis and prevents renal oxidative stress and lipid accumulation, establishing a role for TGR5 in inhibiting kidney disease in obesity and diabetes.
Geriatric Pharmacology: Basic and Clinical Considerations*
Authors: N Tumer, P J Scarpace, D T Lowenthal
Journal: The Annual Review of Pharmacology and Toxicology (1992)

After a traumatic childhood in Europe during the Second World War, I found that scientific research in Israel was a pleasure beyond my expectations. Over the last 65 year, I have worked on the chemistry and pharmacology of natural products. During the ...Read More
Prenatal Diagnosis by Amniocentesis
Authors: A Robinson, G P Henry
Journal: Annual Review of Medicine (1985)

One of the major applications of somatic cell genetics to clinical medicine is in the area of prenatal diagnosis by genetic amniocentesis, which permits the accurate prediction of fetal disease and allows pregnant women to selectively maintain unaffected fetuses. The more recent developments in recombinant DNA research promise to expand tremendously the potential of this technique.
Pilot randomised trial of a healthy eating behavioural intervention in uncontrolled asthma
Authors: Jun Ma, Peg Strub, Nan Lv, Lan Xiao, Carlos A. Camargo, A. Sonia Buist, Philip W. Lavori, Sandra R. Wilson, Kari C. Nadeau, Lisa G. Rosas
Journal: European Respiratory Journal (2015)

Rigorous research on the benefit of healthy eating patterns for asthma control is lacking. We randomised 90 adults with objectively confirmed uncontrolled asthma and a low-quality diet (Dietary Approaches to Stop Hypertension (DASH) scores &lt;6 out of 9) to a 6-month DASH behavioural intervention (n=46) or usual-care control (n=44). Intention-to-treat analyses used repeated-measures mixed models. Participants were middle-aged, 67% female and multiethnic. Compared with controls, intervention participants improved on DASH scores (mean change (95% CI) 0.6 (0, 1.1) versus −0.3 (−0.8, 0.2); difference 0.8 (0.2, 1.5)) and the primary outcome, Asthma Control Questionnaire scores (−0.2 (−0.5, 0) versus 0 (−0.3, 0.3); difference −0.2 (−0.5, 0.1)) at 6 months. The mean group differences in changes in Mini Asthma Quality of Life Questionnaire overall and subdomain scores consistently favoured the intervention over the control group: overall 0.4 (95% CI 0, 0.8), symptoms 0.5 (0, 0.9), environment 0.4 (−0.1, 1.0), emotions 0.4 (−0.2, 0.9) and activities 0.3 (0, 0.7). These differences were modest, but potentially clinical significant. The DASH behavioural intervention improved diet quality with promising clinical benefits for better asthma control and functional status among adults with uncontrolled asthma. A full-scale efficacy trial is warranted.
Oxidative Stress in Neurodegenerative Diseases
Authors: N A Simonian, J T Coyle
Journal: The Annual Review of Pharmacology and Toxicology (1996)

The pathophysiologies of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD), are far from being fully explained.Oxidative stress (OS) has been proposed as one factor that plays a potential role in the pathogenesis of neurodegenerative disorders.Clinical and preclinical studies indicate that neurodegenerative diseases are characterized by higher levels of OS biomarkers and by lower levels of antioxidant defense biomarkers in the brain and peripheral tissues.In this article, we review the current knowledge regarding the involvement of OS in neurodegenerative diseases, based on clinical trials and animal studies.In addition, we analyze the effects of the drug-induced modulation of oxidative balance, and we explore pharmacotherapeutic strategies for OS reduction.
Current Issues in Central Venous Catheter Infection
Authors: P Toltzis, D A Goldmann
Journal: Annual Review of Medicine (1990)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Aging—Causes and Defenses
Authors: George R. Martin, David B. Danner, Nikki J. Holbrook
Journal: Annual Review of Medicine (1993)

Recent studies have shown that chromosomes shorten as cells divide and become senescent. Also, deletions in mitochondrial DNA increase markedly with advancing age, presumably secondary to damage from oxygen radicals. Since host defenses against environmental factors also become attenuated, the molecular damage associated with aging may increasingly perturb normal homeostasis and increase the susceptibility to disease and disability. Such age-associated dysfunctions can be targeted and interrupted.
Antibiotic Therapy for Chronic Infection of Pseudomonas in the Lung
Authors: N. Høiby
Journal: Annual Review of Medicine (1993)

Chronic Pseudomonas aeruginosa lung infection is an endobronchiolitis characterized by the microcolony mode of growth (biofilm). Early colonization is treated with oral ciprofloxacin combinedw ith colistin inhalation. Chronic infection is treated with “maintenance chemotherapy” consisting of β-lactam antibiotics and tobramycin intravenously in combination with colistin inhalation four times yearly.
ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease
Authors: Jilu Zhang, Abdulraouf M. Ramadan, Brad Griesenauer, Wei Li, Matthew J. Turner, Chen Liu, Reuben Kapur, Helmut Hanenberg, Bruce R. Blazar, Isao Tawara, Sophie Paczesny
Journal: Science Translational Medicine (2015)

Graft-versus-host disease (GVHD) remains a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We previously identified high plasma soluble suppression of tumorigenicity 2 (sST2) as a biomarker of the development of GVHD and death. sST2 sequesters interleukin-33 (IL-33), limiting its availability to T cells expressing membrane-bound ST2 (mST2) [T helper 2 (TH2) cells and ST2(+)FoxP3(+) regulatory T cells]. We report that blockade of sST2 in the peritransplant period with a neutralizing monoclonal antibody (anti-ST2 mAb) reduced GVHD severity and mortality. We identified intestinal stromal cells and T cells as major sources of sST2 during GVHD. ST2 blockade decreased systemic interferon-γ, IL-17, and IL-23 but increased IL-10 and IL-33 plasma levels. ST2 blockade also reduced sST2 production by IL-17-producing T cells while maintaining protective mST2-expressing T cells, increasing the frequency of intestinal myeloid-derived suppressor cells, and decreasing the frequency of intestinal CD103 dendritic cells. Finally, ST2 blockade preserved graft-versus-leukemia activity in a model of green fluorescent protein (GFP)-positive MLL-AF9 acute myeloid leukemia. Our findings suggest that ST2 is a therapeutic target for severe GVHD and that the ST2/IL-33 pathway could be investigated in other T cell-mediated immune disorders with loss of tolerance.
Prospectively randomized clinical trial of three intensive chemotherapy regimens for the treatment of advanced unfavorable histology non-Hodgkin's lymphoma.
Authors: M J O'Connell, D P Harrington, J D Earle, G J Johnson, J H Glick, P P Carbone, R H Creech, R S Neiman, R B Mann, M N Silverstein
Journal: Journal of Clinical Oncology (1987)

Three hundred thirty-two eligible patients with advanced (Ann Arbor stage III or IV) non-Hodgkin's lymphoma of aggressive histologic subtype (Rappaport classification diffuse histiocytic [DH], diffuse poorly differentiated lymphocytic [DPDL], diffuse mixed [DM], or diffuse undifferentiated [DU]) were randomly assigned to receive induction chemotherapy with one of three intensive regimens in a clinical trial conducted by the Eastern Cooperative Oncology Group (ECOG) between 1978 and 1983. Chemotherapy regimens consisted of cyclophosphamide, vincristine, prednisone, and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (COPA) administered in 3-week cycles; cyclophosphamide plus doxorubicin plus prednisone beginning day 1, with vincristine plus bleomycin day 15 of each 3-week cycle (COPA + Bleo); or cyclophosphamide plus doxorubicin plus procarbazine beginning day 1, and bleomycin plus vincristine plus prednisone beginning day 15 of each 4-week cycle (CAP-BOP). The median patient follow-up from study entry for patients still alive is 5 years. The three regimens were not significantly different with respect to complete response (CR) rates (43% to 46%), time to progression of malignant disease (median, 1.0 to 1.7 years), or survival (5-year survival, 34% to 45%), although duration of complete remission appeared to be shorter in patients receiving COPA (P = .03). COPA + Bleo and CAP-BOP were significantly more toxic than the COPA regimen. This study did not demonstrate any substantial therapeutic advantage associated with the addition of a fifth or sixth chemotherapy drug, or with treatment administered on a more frequent administration schedule, compared with the COPA regimen in this population of patients with advanced diffuse non-Hodgkin's lymphoma. The relatively small proportion of long-term disease-free survivors treated with COPA underscores the need for prospective clinical trials of new and more effective treatments for patients with these potentially curable tumors.
Soundings: Judgment day
Authors: Trisha Greenhalgh
Journal: BMJ (2004)

Conference centre in Amsterdam. I'm in the press room, being briefed by an attractive hostess in a sash. She hands me a map marked with a cross. You will find the treasure here. Outside, 4000 delegates are networking in a purpose built informal space with endless corridors of glossy posters. They are vying, variously, for Best Oral Presentation, Best Poster, Most Innovative Quality Improvement Project, and Patient Communication Award. I'm here to judge Young Researcher of the Year.

Regular readers of this column will know that I can't read maps. I'm one floor too high but don't know it. I blunder into the pharmaceutical industry corner and start judging. The lad beside the poster—he's young all right—offers me a freshly squeezed raspberry juice and starts a spiel about a new contraceptive. The poster is surreal—lovers entwined, bound by a rubbery halo. So small you don't know it's there, he explains. But no cost effectiveness studies that he knows of. We exchange business cards.

The next guy—bald and wrinkled, but I presume he has a syndrome—offers a plate of petits fours and a free first aid kit for my car. We admire his poster. I note creative use of imagery and sexual innuendo, but sadly the small print is unreadable. Have I ever prescribed Something-o-sartan, he asks. I rack my brain. Yes, once, against my better judgment, and the patient developed mouth ulcers. I talk him through my Yellow Card report.

The next “poster” is a free medical check from a company selling an anti-obesity drug. I'm game. I complete a questionnaire about my personal habits, stand on the scales, and have my fat content estimated by an infra-red machine. Reassuringly, I fail to qualify for a free sample pack, but am awarded an apple in a takeaway bag.

Eventually, I am rescued and escorted to the lift. The real Young Researcher of the Year display stands proud in a draughty hall, conspicuous by the absence of freebies, sales pitch, and delegates. These shortlisted dozen are the names—mostly unpronounceable and double barrelled—to watch for the future. Their posters, comprising simple printouts glued on to card, present solid, original research with direct messages for patient care. I struggle to pick a winner, and slink guiltily back upstairs to queue for my free lunch.
Airway epithelial dual oxidase 1 mediates allergen-induced IL-33 secretion and activation of type 2 immune responses
Authors: Milena Hristova, Aida Habibovic, Carmen Veith, Yvonne M.W. Janssen-Heininger, Anne E. Dixon, Miklos Geiszt, Albert van der Vliet
Journal: Journal of Allergy and Clinical Immunology (2015)
Impact of high-dose cytarabine and asparaginase intensification on childhood acute myeloid leukemia: a report from the Childrens Cancer Group.
Authors: R J Wells, W G Woods, B C Lampkin, M E Nesbit, J W Lee, J D Buckley, C Versteeg, G D Hammond
Journal: Journal of Clinical Oncology (1993)

PURPOSE The purpose of this review was to determine the impact of high-dose cytarabine and asparaginase intensification, administered shortly after remission induction, on the outcome of childhood acute myeloid leukemia (AML). MATERIALS AND METHODS Three consecutive Childrens Cancer Group (CCG) trials of acute myeloid leukemia, CCG 251 (1979 to 1983), CCG 213P (1983 to 1985), and CCG 213 (1985 to 1989) with a total of 1,294 patients, were reviewed and provide the basis of this report. RESULTS CCG 213P demonstrated the importance of dose interval, in that two courses of cytarabine and asparaginase administered at 7-day intervals gave superior 5-year survival rates (58% v 41% from the end of induction, P &lt; .04) to the same therapy administered at 28-day intervals. CCG 213 showed that there was no advantage to the maintenance therapy used for patients who received two courses of cytarabine and asparaginase at 7-day intervals (5-year survival, 68% [no maintenance] v 44% [maintenance] from the end of consolidation, P &lt; .01). Inclusion of the 7-day interval cytarabine/asparaginase intensification was accompanied by an overall improvement in 5-year survival rates from diagnosis when compared with historical controls (CCG 213, 36% v CCG 251, 29%, P &lt; .02) although other differences between these studies could also be responsible for the improvement seen. CONCLUSION High-dose cytarabine and asparaginase intensification eliminated the benefit of prolonged maintenance therapy in childhood AML and was accompanied by an overall improvement in survival.
Multiple Myeloma, Version 2.2016
Authors: Kenneth C. Anderson, Melissa Alsina, Djordje Atanackovic, J. Sybil Biermann, Jason C. Chandler, Caitlin Costello, Benjamin Djulbegovic, Henry C. Fung, Cristina Gasparetto, Kelly Godby, Craig Hofmeister, Leona Holmberg, Sarah Holstein, Carol Ann Huff, Adetola Kassim, Amrita Y. Krishnan, Shaji K. Kumar, Michaela Liedtke, Matthew Lunning, Noopur Raje, Seema Singhal, Clayton Smith, George Somlo, Keith Stockerl-Goldstein, Steven P. Treon, Donna Weber, Joachim Yahalom, Dorothy A. Shead, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2015)

Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Recent statistics from the American Cancer Society indicate that the incidence of MM is increasing. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) included in this issue address management of patients with solitary plasmacytoma and newly diagnosed MM.
3′ hexameric deoxyguanosine run (dG6 run) enhances immunogenecity of phosphodiester CpG-ODN without increasing the risk of splenomegaly in murine model of asthma
Authors: Y. Chang, T. Kim, H. Kang, S. Kim, J. Bahn, Y. Kim, K. Min, S. Cho, Y. Chang
Journal: Journal of Allergy and Clinical Immunology (2003)
Sparse Reconstruction Challenge for diffusion MRI: Validation on a physical phantom to determine which acquisition scheme and analysis method to use?
Authors: Lipeng Ning, Frederik Laun, Yaniv Gur, Edward V.R. DiBella, Samuel Deslauriers-Gauthier, Thinhinane Megherbi, Aurobrata Ghosh, Mauro Zucchelli, Gloria Menegaz, Rutger Fick, Samuel St-Jean, Michael Paquette, Ramon Aranda, Maxime Descoteaux, Rachid Deriche, Lauren O’Donnell, Yogesh Rathi
Journal: Medical Image Analysis (2015)
Cancer diagnosis as a risk factor for personal bankruptcy.
Authors: S. D. Ramsey, C. R. Fedorenko, K. S. Snell, A. C. Kirchhoff, W. Hollingworth, D. K. Blough
Journal: Journal of Clinical Oncology (2011)

6007 Background: The risk of bankruptcy for cancer patients is not well characterized and may vary by cancer type, treatment, and personal factors. Linking the Washington State SEER registry with Western District of Washington bankruptcy court records, we measured the rate of bankruptcy after cancer and identified factors that increased risk among common cancers. Methods: We included adults age >20 with newly diagnosed first primary cancers between 1995-2009, excluding cancers in situ or diagnosed at death. We calculated the conditional probability of personal bankruptcy (chapters 7 and 13), i.e., probability conditional on survival to the time point. For cancers with the highest risk, we used competing risks regression to identify patient- and treatment-related factors associated with bankruptcy. Results: There were N=231,799 cancer cases; after a mean follow-up of 4.3(sd=4.1) years, N=4,805 (2.1%) filed for bankruptcy. Median time to bankruptcy was 2.5 years. Lung, thyroid, and leukemia/lymphoma cancers had the highest conditional probabilities at 1 year (1.5%, 0.9%, and 0.6%, respectively), 2 years (3.1%, 2.0%, and 1.4%, respectively), and 5 years (7.7%, 4.8%, and 3.6%, respectively) from diagnosis. In regression analysis (Table), age ≥65 at diagnosis was associated with a decreased risk of bankruptcy for all cancers (Hazard Ratio [HR] 0.3-0.5). Bankruptcy risk was higher for lung, colorectal and breast cancer cases receiving surgery (HR 2.0-4.1) and chemotherapy (HR 1.4-1.5). Conclusions: Bankruptcy risk is highest for lung, thyroid, and leukemia/lymphoma cancer patients. Patients over age 65, who are typically on Medicare, have a much lower risk of bankruptcy than younger patients. Certain cancers face additional risks due to surgery and chemotherapy. Lung Thyroid Leukemia/ lymphoma Uterine Colorectal Melanoma Breast Prostate Conditional probability of bankruptcy at 5 years 7.7% 4.8% 3.6% 3.2% 3.1% 3.0% 2.9% 1.7% Hazard ratios* Age ≥65 – – – – – – – – Female – n/a + n/a n/a Married + – Regional** – – Distant** – – – Surgery + + + Radiation Chemotherapy + + + White – – – * Indicates a higher (+) and lower (–) bankruptcy risk; significant at α=.05. Models adjusted for year of diagnosis and rural/urban residence. **Reference = localized stage at diagnosis.
Quantitative Magnetic Resonance Imaging of Bronchopulmonary Dysplasia in the Neonatal Intensive Care Unit Environment
Authors: Laura L. Walkup, Jean A. Tkach, Nara S. Higano, Robert P. Thomen, Sean B. Fain, Stephanie L. Merhar, Robert J. Fleck, Raouf S. Amin, Jason C. Woods
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Bronchopulmonary dysplasia (BPD) is a prevalent yet poorly characterized pulmonary complication of premature birth; the current definition is based solely on oxygen dependence at 36 weeks postmenstrual age without objective measurements of structural abnormalities across disease severity.
Amphetamine: Effects on Catecholamine Systems and Behavior
Authors: L S Seiden, K E Sabol, G A Ricaurte
Journal: The Annual Review of Pharmacology and Toxicology (1993)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More