tbuckley/cabot-search huggingface dataset:
In postmenopausal women with breast cancer treated with aromatase inhibitors, denosumab reduced fractures
Authors: Nicholas Wilcken, Clara Inkyung Lee
Journal: Annals of Internal Medicine (2015)

Source Citation Gnant M, Pfeiler G, Dubsky PC, et al; Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 May 29. Epub ahead of print. 26040499
An unusual cause of upper gastrointestinal haemorrhage
Authors: G D De Palma
Journal: Gut (2005)

Background: Late radiation enteritis in humans is associated with accumulation of extracellular matrix and increased connective tissue growth factor (CTGF) expression that may involve intestinal muscular layers.Aims: We investigated the molecular pathways involved in maintenance of radiation induced fibrosis by gene profiling and postulated that alteration of the Rho pathway could be associated with radiation induced fibrogenic signals and CTGF sustained expression.Patients and methods: Ileal biopsies from individuals with and without radiation enteritis were analysed by cDNA array, and primary cultures of intestinal smooth muscle cells were established.Then, the effect of pharmacological inhibition of p160 Rho kinase, using Y-27632, was studied by real time reverse transcription-polymerase chain reaction, western blot, and electrophoretic mobility shift assay.Results: Molecular profile analysis of late radiation enteritis showed alterations in expression of genes coding for the Rho proteins.To investigate further the involvement of the Rho pathway in intestinal radiation induced fibrosis, primary intestinal smooth muscle cells were isolated from radiation enteritis.They retained their fibrogenic differentiation in vitro, exhibited a typical cytoskeletal network, a high constitutive CTGF level, increased collagen secretory capacity, and altered expression of genes coding for the Rho family.Rho kinase blockade induced a simultaneous decrease in the number of actin stress fibres, a smooth muscle actin, and heat shock protein 27 levels.It also decreased CTGF levels, probably through nuclear factor kB inhibition, and caused decreased expression of the type I collagen gene. Conclusion:This study is the first showing involvement of the Rho/Rho kinase pathway in radiation fibrosis and intestinal smooth muscle cell fibrogenic differentiation.It suggests that specific inhibition of Rho kinase may be a promising approach for the development of antifibrotic therapies.
Current Science on Consumer Use of Mobile Health for Cardiovascular Disease Prevention
Authors: Lora E. Burke, Jun Ma, Kristen M.J. Azar, Gary G. Bennett, Eric D. Peterson, Yaguang Zheng, William Riley, Janna Stephens, Svati H. Shah, Brian Suffoletto, Tanya N. Turan, Bonnie Spring, Julia Steinberger, Charlene C. Quinn
Journal: Circulation (2015)
Transference-Focused Psychotherapy for Borderline Personality Disorder: A Clinical Guideby Frank E. Yeomans, M.D., Ph.D., John F. Clarkin, Ph.D., and Otto F. Kernberg, M.D. Washington, DC, American Psychiatric Publishing, 2015, 427 pp., $75.00.
Authors: Robert E. Feinstein
Journal: American Journal of Psychiatry (2015)
Suicidal Behavior in Schizophrenia: Characteristics of Individuals Who Had and Had Not Attempted Suicide
Authors: Jill M. Harkavy-Friedman, Kathleen Restifo, Dolores Malaspina, Charles A. Kaufmann, Xavier F. Amador, Scott A. Yale, Jack M. Gorman
Journal: American Journal of Psychiatry (1999)

This study compares demographic and clinical characteristics of 52 individuals with schizophrenia or schizoaffective disorder who had attempted suicide with those of 104 individuals with schizophrenia or schizoaffective disorder who had not made a suicide attempt.Participants were interviewed with the Diagnostic Interview for Genetic Studies.Most suicide attempts were of moderate to severe lethality, required medical attention, and involved significant suicidal intent. Individuals who had and had not attempted suicide did not differ with respect to demographic variables, duration of illness, rate of depression, or substance abuse. The two groups are affected differentially when depressed.Biopsychosocial assessments and interventions are essential for reducing the risk for suicidal behavior in individuals with schizophrenia.
Occurrence of Mammary Tumors in Mice Carrying the Mammary Tumor Agent in Diffusion Chambers
Authors: Ruth M. Merwin, Lena W. Redmon, Glenn H. Algire
Journal: JNCI Journal of the National Cancer Institute (1964)

Spontaneous mammary tumor tissue from mice with or without the milk agent was sealed between Millipore membrane filters with pores of various sizes. These diffusion chambers were placed intraperitoneally in agent-free, 4- to 8-week-old mice susceptible to the induction of mammary tumors by the milk agent. Mammary tumors appeared as expected in accordance with present knowledge of the size of the virus, the viral content of tissues, and the susceptibility of mice to the induction of tumors. Many tumors arose when chambers had coarse pores (0.30 or 0.45 μ in diameter), but few were induced when the pores were fine (0.10 μ or less). Tumors were induced whether the donors were strain C3H and the hosts BALB/c or vice versa. The tumor incidence was almost identical, regardless of whether tumor tissue was placed inside or outside coarse-pored diffusion chambers. However, a suspension of an approximately equal amount of tissue injected intraperitoneally induced fewer tumors. Spontaneous mammary tumor tissue obtained from presumably agent-free C3H mice and placed in coarse-pored chambers in BALB/c mice did not induce tumors.
Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib
Authors: F Castagnetti, G Gugliotta, M Breccia, F Stagno, A Iurlo, F Albano, E Abruzzese, B Martino, L Levato, T Intermesoli, P Pregno, G Rossi, F Gherlinzoni, P Leoni, F Cavazzini, C Venturi, S Soverini, N Testoni, G Alimena, M Cavo, G Martinelli, F Pane, G Saglio, G Rosti, M Baccarani
Journal: Leukemia (2015)
Implications of Heterogeneity of Treatment Effect for Reporting and Analysis of Randomized Trials in Critical Care
Authors: Theodore J. Iwashyna, James F. Burke, Jeremy B. Sussman, Hallie C. Prescott, Rodney A. Hayward, Derek C. Angus
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Randomized clinical trials (RCTs) are conducted to guide clinicians' selection of therapies for individual patients. Currently, RCTs in critical care often report an overall mean effect and selected individual subgroups. Yet work in other fields suggests that such reporting practices can be improved. Specifically, this Critical Care Perspective reviews recent work on so-called "heterogeneity of treatment effect" (HTE) by baseline risk and extends that work to examine its applicability to trials of acute respiratory failure and severe sepsis. Because patients in RCTs in critical care medicine-and patients in intensive care units-have wide variability in their risk of death, these patients will have wide variability in the absolute benefit that they can derive from a given therapy. If the side effects of the therapy are not perfectly collinear with the treatment benefits, this will result in HTE, where different patients experience quite different expected benefits of a therapy. We use simulations of RCTs to demonstrate that such HTE could result in apparent paradoxes, including: (1) positive trials of therapies that are beneficial overall but consistently harm or have little benefit to low-risk patients who met enrollment criteria, and (2) overall negative trials of therapies that still consistently benefit high-risk patients. We further show that these results persist even in the presence of causes of death unmodified by the treatment under study. These results have implications for reporting and analyzing RCT data, both to better understand how our therapies work and to improve the bedside applicability of RCTs. We suggest a plan for measurement in future RCTs in the critically ill.
Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from National Surgical Adjuvant Breast and Bowel Project Protocol B-06.
Authors: B Fisher, C Redmond, E R Fisher, R Caplan
Journal: Journal of Clinical Oncology (1988)

This study correlates the disease-free survival (DFS), distant disease-free survival (DDFS), and survival (S) of 1,157 histologically node negative breast cancer patients with the estrogen and/or progesterone receptor (ER, PR) and with the nuclear or histologic grade (NG, HG) of their tumors. All were treated by operation without systemic adjuvant therapy. The DFS, DDFS, and S were significantly greater (P = .005, .004, less than .001) in patients with ER positive than ER negative tumors but the magnitude of the differences after 5 years of follow-up was slight (8% in both DFS and DDFS and 10% in S). Differences of that magnitude are insufficient to discriminate clearly between patients who should or should not receive systemic therapy. As with ER, there were outcome differences in favor of PR positive tumors but only in S was the difference significant (8% at 5 years; P = .002). When combined with ER, PR made no independent contribution in the outcome prediction. Regression analysis indicated that NG was the most important single marker of outcome. The prognosis of women with unknown ER or PR was equivalent to or better than that in those with ER or PR positive tumors. This finding seems to be related to tumor size in that a higher proportion of tumors with unknown receptors were less than 1.0 cm, thus having insufficient tissue for analysis. Our findings disclose that in node negative breast cancer patients, NG is a better marker of prognosis than is tumor ER, and that PR is of little or no value. Tumor NG may also be useful for selecting the type of systemic therapy to be used in these patients.
Differential effects of simvastatin and dexamethasone on TLR3-induced anti-viral cytokines in asthmatic epithelium
Authors: Angelica Brandelius, Irma Mahmutovic Persson, Jenny Calvén, Leif Bjermer, Carl Persson, Morgan Andersson, Lena Uller
Journal: European Respiratory Journal (2013)

Possibly reflecting anti-inflammatory properties, statin treatment may ameliorate viral-induced exacerbations. We have shown that simvastatin but not dexamethasone inhibits viral-induced, potentially pathogenic thymic stromal lymphopoietin production. It is important that treatments of exacerbations spare the host defence to viral infections. IFN-beta, IFN-lambda and IL-32 are major antiviral components of innate immunity.  Objective: Explore effects of simvastatin and dexamethasone on TLR3-induced IFN-beta, IFN-lambda and IL-32 in asthmatic epithelium.  Methods: Primary bronchial epithelial cells, obtained by fibre optic bronchoscopy from allergic asthma patients (n=6) were grown in 12-well plates and treated with simvastatin (0,2-5μg), dexamethasone (1μM) or vehicle control prior to TLR3 stimulation for 3 and 24 h and samples analysed by RTqPCR and ELISA.  Results: TLR3 stimulation induced early (3h) expression of IFN-beta (1000-fold) that was dose-dependently inhibited by simvastatin but not by dexamethasone. IFN-lambda was induced (6000-fold) at 3h and further sustained at 24 h (2000-fold). Only the early IFN-lambda expression was reduced by the highest dose of simvastatin. Dexamethasone was without effect. IL-32 was induced (2-fold) at 3h and further increased at 24h. At both time-points the highest dose of simvastatin reduced IL-32 but dexamethasone was without effect.  Conclusion: Dexamethasone treatment spared TLR3-induced expression of all three anti-viral cytokines in bronchial epithelial cells from asthma donors. Simvastatin completely inhibited TLR3-induced IFN-beta whereas the inducement of IFN-lambda and IL-32 were largely spared by simvastatin.
Genetic Prodrug Activation Therapy for Breast Cancer: A Phase I Clinical Trial of<i>erb</i>B-2–Directed Suicide Gene Expression
Authors: Hardev S. Pandha, Lesley-Ann Martin, Anne Rigg, Helen C. Hurst, Gordon W.H. Stamp, Karol Sikora, Nicholas R. Lemoine
Journal: Journal of Clinical Oncology (1999)

PURPOSE: This trial was designed to test the safety and efficacy of a tumor-specific genetic prodrug activation therapy targeted by use of the human erbB-2 gene promoter. The erbB-2 oncogene is overexpressed in approximately 20% of cases of breast cancer and is associated with poor prognosis. PATIENTS AND METHODS: Twelve breast cancer patients received transcriptionally targeted gene therapy in a phase I clinical trial using direct intratumoral injection of plasmid construct combined with systemic administration of prodrug. The genetic prodrug activation therapy is specifically targeted to erbB-2–overexpressing breast cancer cells by use of a therapeutic cassette that contains the Escherichia coli cytosine deaminase gene driven by the tumor-specific erbB-2 promoter, thus allowing activation of fluorocytosine to the active cytotoxic fluorouracil only within tumor cells that express the oncogene. RESULTS: The approach was shown to be safe and to result in targeted gene expression in up to 90% of cases. Using a number of different assays, we demonstrated that significant levels of expression of the suicide gene were specifically restricted to erbB-2–positive tumor cells, confirming the selectivity of the approach. CONCLUSION: The results of this study, the first targeted gene therapy for breast cancer and the first to use the cytosine deaminase system in human subjects, are encouraging for the development of genetic prodrug activation therapies that exploit the transcriptional profile of cancer cells.
Interactions of Erythropoietin, Granulocyte Colony-Stimulating Factor, Stem Cell Factor, and Interleukin-11 on Murine Hematopoiesis During Simultaneous Administration
Authors: I. Roeder, G. de Haan, C. Engel, W. Nijhof, B. Dontje, M. Loeffler
Journal: Blood (1998)
Investigation of Human Urogenital Tract Tumors for Papovavirus Etiology: Brief Communication 2
Authors: Keerti V. Shah, Richard W. Daniel, Kenneth R. Stone, Arthur Y. Elliott
Journal: JNCI Journal of the National Cancer Institute (1978)

Cells cultured from human urogenital cancer and other cancers as well as cells from noncancerous tissues were examined by immunofluorescent staining with antibodies to Tantigens and capsid antigens of papovaviruses BK virus (BKV), JC virus, and simian virus 40 (SV40), and to capsid antigens of herpes simplex virus types 1 and 2 and human cytomegalovirus (CMV). Cells from early passage cultures of 123 primary tissues and from 14 continuous lines derived from transitional or renal cell carcinoma were tested. None of the cell preparations was specifically stained with any of the antisera. A serologic comparison of patients with bladder cancer, patients with prostate cancer, and normal control groups for BKV hemagglutination-inhibiting and SV40-neutralizing antibodies showed no differences among the 3 groups. None of the sera in the 3 groups had SV40 or BKV T-antlbodies. In tests of supernatants of 35 primary cultures for presence of virus, a single isolation, that of a cytomegalovirus, was made. The study revealed no evidence that infection with papovaviruses of the SV4G-polyoma subgroup has any part in the production of bladder and prostate cancer.
The GOLD domain, a novel protein module involved in Golgi function and secretion
Authors: Vivek Anantharaman, L Aravind
Journal: Genome biology (2002)

Members of the p24 (p24/gp25L/emp24/Erp) family of proteins have been shown to be critical components of the coated vesicles that are involved in the transportation of cargo molecules from the endoplasmic reticulum to the Golgi complex. The p24 proteins form hetero-oligomeric complexes and are believed to function as receptors for specific secretory cargo.Using sensitive sequence-profile analysis methods, we identified a novel beta-strand-rich domain, the GOLD (Golgi dynamics) domain, in the p24 proteins and several other proteins with roles in Golgi dynamics and secretion. This domain is predicted to mediate diverse protein-protein interactions. Other than in the p24 proteins, the GOLD domain is always found combined with lipid- or membrane-association domains such as the pleckstrin homology (PH), Sec14p and FYVE domains.The identification of the GOLD domain could aid in directed investigation of the role of the p24 proteins in the secretion process. The newly detected group of GOLD-domain proteins, which might simultaneously bind membranes and other proteins, point to the existence of a novel class of adaptors that could have a role in the assembly of membrane-associated complexes or in regulating assembly of cargo into membranous vesicles.
Narciclasine as well as other Amaryllidaceae Isocarbostyrils are Promising GTP‐ase Targeting Agents against Brain Cancers
Authors: Gwendoline Van Goietsenoven, Véronique Mathieu, Florence Lefranc, Alexander Kornienko, Antonio Evidente, Robert Kiss
Journal: Medicinal Research Reviews (2012)

Abstract The anticancer activity of Amaryllidaceae isocarbostyrils is well documented. At pharmacological concentrations, that is, approximately 1 μ M in vitro and approximately 10 mg/kg in vivo, narciclasine displays marked proapoptotic and cytotoxic activity, as does pancratistatin, and significant in vivo anticancer effects in various experimental models, but it is also associated with severe toxic side effects. At physiological doses, that is, approximately 50 n M in vitro and approximately 1 mg/kg in vivo, narciclasine is not cytotoxic but cytostatic and displays marked anticancer activity in vivo in experimental models of brain cancer (including gliomas and brain metastases), but it is not associated with toxic side effects. The cytostatic activity of narciclasine involves the impairment of actin cytoskeleton organization by targeting GTP ases, including R hoA and the elongation factor e EF 1 A . We have demonstrated that chronic treatments of narciclasine (1 mg/kg) significantly increased the survival of immunodeficient mice orthotopically xenografted with highly invasive human glioblastomas and apoptosis‐resistant brain metastases, including melanoma‐ and non‐small‐cell‐lung cancer‐ ( NSCLC ) related brain metastases. Thus, narciclasine is a potentially promising agent for the treatment of primary brain cancers and various brain metastases. To date, efforts to develop synthetic analogs with anticancer properties superior to those of narciclasine have failed; thus, research efforts are now focused on narciclasine prodrugs.
Behavior of Intravenously Injected Malignant Lymphoma Cells. A Morphologic Study
Authors: K. P. Dingemans
Journal: JNCI Journal of the National Cancer Institute (1973)

Malignant lymphoma cells of different types were injected intravenously into intact, isologous mice. Cells designated as lymphosarcoma cells were trapped initially in the lungs or the liver after injection into a tail vein and a mesenteric vein, respectively. A few days later, however, they were distributed evenly over both the lungs and the liver, regardless of the site of injection. Within 8 days, all animals had died with greatly enlarged livers and spleens and massive numbers of tumor cells in the lungs. Cells designated as lymphocytic leukemia cells formed sharply demarcated, spherical nodules in virtually every organ investigated, regardless of the site of injection. Only in the lungs were they confined to the capillaries. Despite these differences, the interaction of the cells with the surrounding lung or liver tissue was identical for both types of tumors. In the lung capillaries, the endothelium was never injured; but, in the liver, the tumor cells quickly penetrated the sinusoidal wall by fragmentation of the endothelium over large areas, withoutthe formation of pseudopods. However, after the extravasation, pseudopods were extended into adjacent hepatocytes. The hepatocytes were often greatly distorted by the tumor cells, but they never seemed to be obliterated; the bile canaliculi always remained intact. Although the Kupffer cells were initially in close contact with the tumor cells, no phagocytosis or any other signs of activation of the Kupffer cells developed.
Comparison of Three Isotopic Assays of Cell-Mediated Cytotoxicity Against Mouse Tumor Cells. I. Basic Parameters: Baseline Controls, Target Cells, and Methods of Calculation
Authors: Chou-Chik Ting, Joseph Y. Park, Myrthel E. Nunn, Ronald B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1977)

We compared three different isotopic assays of cell-mediated cytotoxicity under identical test conditions: 51Cr, 125iododeoxyuridine, and [3H]proline release assays. We made these comparisons both in a syngeneic mouse tumor system and an allogeneic system. It was found that several parameters could affect considerably the results obtained with these tests, such as: baseline controls, preparation of target cells, and methods of calculation. In comparison of three different baseline controls, the normal control gave the most consistent results, whereas the other two controls (autologous and medium controls) gave varying results depending upon the condition of the target cells. For use as target cells, established tissue culture cells were usually superior because of a much lower spontaneous release of the isotope, when compared to fresh ascites tumor cells or shortterm tissue culture cells. The advantage of established culture cells was particularly noted in isotopic assays with prolonged incubation (20–40 hr). In addition, the methods used for calculation were also shown to affect the apparent outcome of the results.
Expression of vascular endothelial-cadherin and vascular endothelial growth factor in non-small cell lung cancer and their clinical significances
Authors: Tao Tao, Hong Chen
Journal: European Respiratory Journal (2012)

To investigate the expression of Vascular Endothelial-cadherin(VE-cadherin) and Vascular Endothelial Growth Factor(VEGF) with the association of clinicopathological characteristics and their correlation in non-small cell lung cancer(NSCLC). Expression of them were examined by immunohistochemical staining in 72 cases of NSCLC patients and their adjacent non-neoplastic tissues, 45 of them were measured by RT-PCR.The positive rates of them in cancer cells were 69.4% and 84.7% respectively,which were higher than the normal tissues(0% and 16.7%)(P 0.05). The relative expression intensity of VE-cadherin mRNA in NSCLC tissues and adjacent non-neoplastic tissues were 0.621±0.182 and 0.445±0.052(P<0.05). The relative expression intensity of VEGF mRNA in NSCLC tissues and adjacent non-neoplastic tissues were 0.275±0.103 and 0.050±0.154(P<0.05). The expression of them in lymph node metastasis were higher compared to that in cases without lymph node metastasis(P<0.05).Our results suggest that VE-cadherin may play an important role in angiogenesis and act in a synergistic manner in NSCLC.