tbuckley/cabot-search huggingface dataset:
Abstract 2550: Combination of the KSP inhibitor ARRY-520 with bortezomib causes sustained tumor regressions and significantly increased time to regrowth in bortezomib sensitive and resistant models of multiple myeloma
Authors: Richard Woessner, Brian Tunquist, Duncan Walker, Sumeet Rana, Robert Orlowski, Deborah Kuhn
Journal: Cancer Research (2011)

Abstract The allosteric kinesin spindle protein (KSP) inhibitor ARRY-520 has potent antitumor activity as a single agent in xenograft models of multiple myeloma, with complete response rates as high as 100%. It has shown promising signs of activity in a phase 1 trial in patients with advanced / refractory multiple myeloma, and a phase 2 study in this patient population is in progress. We report here on the striking activity of ARRY-520 in combination with bortezomib in multiple myeloma xenograft models. We investigated the activity of the combination of ARRY-520 with bortezomib in several xenograft models of multiple myeloma that are sensitive (Kas-6, ANBL-6, and H929) and resistant (RPMI8226, JJN3, a subline of ANBL-6 made resistant to bortezomib by in vitro treatment, and a subline of RPMI8226 that acquired a PI3K activating mutation) to bortezomib. The combination of ARRY-520 with bortezomib showed additive or superadditive activity, compared to either drug alone, in 6 of the 7 models tested. Complete responses and cures were observed in several models. The Kas-6 model was particularly sensitive, with a 100% cure rate (complete response through day 100). Since previous work from our lab (Mol. Cancer Ther. 9(7), 2046, 2010) implicates MCL1 status as a predictor of response to ARRY-520 in multiple myeloma cell lines, we evaluated the effect of the ARRY-520 + bortezomib combination on MCL1 and other markers of apoptosis. Treatment with the combination resulted in elevation of the cleaved / full length PARP ratio (up to 15X), compared to tumors treated with the single agents, along with a decline in MCL1 levels that coincided with elevation of the level of a 28kd fragment of MCL1 (up to 17X). This shortened form of MCL1 has been reported to be pro-apoptotic. Thus, the cleavage of MCL1 to a proapoptotic form, leading to a decrease in survival signaling and an increase in apoptotic signaling, may play a role in the activity of the ARRY-520 + bortezomib combination. The observation that the combination remained highly active even in models that were poorly responsive to single agent bortezomib suggests that the mechanisms underlying resistance to bortezomib may be distinct from those that contribute to activity of the combination. These results support ARRY-520 + bortezomib as a rational combination for clinical evaluation, including in patients with bortezomib-refractory disease. A phase 1 trial to evaluate the combination of ARRY-520 + bortezomib + dexamethasone is in progress. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2550. doi:10.1158/1538-7445.AM2011-2550
A comparative study of the effects of insulin/glucagon infusions, parenteral amino acids and high dose corticosteroids on survival in a rabbit model of acute fulminant hepatitis
Authors: Gerald Y. Minuk.M.D., Thomas A. Sherman, Eldon A. Shaffer, Seamus K. Kelly
Journal: Hepatology (1986)

Acute fulminant hepatitis was induced in 55 healthy adult male rabbits with the potent hepatotoxin galactosamine hydrochloride (3.75 mmoles per kg i.v.). Control rabbits (n = 27) were divided into three groups: Group I (n = 10) underwent sham surgery for placement of an indwelling central venous catheter; Group II (n = 9) received 5% dextrose and water via an indwelling central venous catheter, and Group III (n = 8) received daily intramuscular injections of 0.9% sodium chloride. Treated rabbits (n = 28) also consisted of three groups: Group IV (n = 9) received 12-hr intravenous infusions of insulin (0.029 units per kg per hr) and glucagon (2.86 μg per kg per hr) daily; Group V (n = 10) received a continuous infusion of parenteral amino acids (Travasol), and Group VI (n = 9) received daily intramuscular methylprednisolone (0.69 mg per kg). In each case, treatment was initiated 16 hr following galactosamine injection. Serum aminotransferase activity was determined on Days 0, 1, 4 and 10 of the 10-day study. Liver histology was obtained immediately after death and graded under code on a scale of 1 to 4 for severity of hepatitis. Rabbits surviving 10 days were sacrificed on Day 10 for histologic examination. The extent of galactosamine-induced hepatic injury was similar in all six groups as manifest by peak mean SGPT(range: 2,662 to 3,568 IU per liter), SGOT (range: 4,435 to 5,625 IU per liter) levels and hepatic histologic findings. The overall survival rate in controls was 6/27 (22%); in insulin/glucagon-treated animals 2/9 (22%), and in the amino acid-treated group 2/10 (20%). The corticosteroid-treated group, however, had significantly improved survival: 6/9 (67%, p < 0.05, Fisher's exact test). No difference between groups was observed in the mean survival times of animals dying prior to Day 10 (range: 30.7 ± 2.7 — 55.5 ± 13.0 hr, mean ± S.E., p > 0.05). In conclusion, the results of this study indicate that in this animal model of acute fulminant hepatitis and withthese doses, insulin/glucagon infusions and parenteral amino acids have no beneficial effect, while high dose corticosteroids significantly enhance survival. On the basis of these results, a reappraisal of the use of high dose corticosteroidsin the treatment of nonviral forms of acute fulminant heptitis in humans would appear to be indicated.
Blood pressures that fall on rechecking.
Authors: P M Gaylarde
Journal: BMJ (1982)

mercury is of little or no consequence.We cannot on the one hand condone inaccuracy of technique while on the other we make management decisions based on small differences in blood pressure.We stand by our conclusion that the LSH sphygmomanometer, being inaccurate because of a calibration error and an interpretative tendency to underestimate blood pressure, is unsuitable for studies of blood pressure and should not be used as a reference standard.
Evaluate the antiviral treatment responses in patients with chronic hepatitis C virus infection by third generation anti-HCV assay
Authors: Tung Hung-Da, Lu Sheng-Nan, Lee Chuan-Mo, Wang Jing-Houng, Chen Tsung-Ming, Hung Chao-Hung, Huang Wu-Siung, Changchien Chi-Sin
Journal: Journal of Hepatology (2002)
New techniques in assisted conception Consultation document incomprehensible
Authors: V McDonald, D Axworthy, S Golombok, R Cook, A Bish, C Murray
Journal: BMJ (1994)

EDITOR, - The Human Fertilisation and Embryology Authority has recently published a public consultation document, Donated Ovarian Tissue in Embryo Research and Assisted Conception.1,2 This document discusses the “issues surrounding the use in research and treatment of ovarian tissue obtained from mature women, from girls or women who have died or from aborted fetuses” (para 1). Comments on these issues are invited from “members of the public, interested bodies and organisations” (para 42).

To respond to the document the public must first be able to understand its contents. We have assessed this formally using a readability formula. This provides an estimate of the proportion of the population likely to understand a piece of text, based on the lengths of sentences and …
Predictors of Death, Local Recurrence, and Distant Metastasis in Completely Resected Pathological Stage-I Non–Small-Cell Lung Cancer
Authors: Jung-Jyh Hung, Wen-Juei Jeng, Wen-Hu Hsu, Teh-Ying Chou, Biing-Shiun Huang, Yu-Chung Wu
Journal: Journal of Thoracic Oncology (2012)
Transnational Surrogacy and the Justice Condition of Nonexploitation
Authors: Vida Panitch
Journal: The American Journal of Bioethics (2014)

Click to increase image sizeClick to decrease image size NotesWilkinson (Citation2003) identifies the Consent Condition and the Justice Condition as I employ them here. I refer to them as “components” of exploitation rather than as conditions so as to differentiate them from the three conditions of Kirby's heuristic.Kirby provides little argumentation for his claim that TGS arrangements are coercive on the grounds that LMIC surrogates cannot but choose otherwise. This definition is contentious, and although Kirby cites Wertheimer's (Citation1996) alternative account, according to which coercion depends on the commissioning parents threatening to make the surrogate worse off than she otherwise would have been, he does not address whether this type of coercion occurs in TGS arrangements.
Tumor Quantification in Clinical Positron Emission Tomography
Authors: Bing Bai, James Bading, Peter S Conti
Journal: Theranostics (2013)

Positron emission tomography (PET) is used extensively in clinical oncology for tumor detection, staging and therapy response assessment.Quantitative measurements of tumor uptake, usually in the form of standardized uptake values (SUVs), have enhanced or replaced qualitative interpretation.In this paper we review the current status of tumor quantification methods and their applications to clinical oncology.Factors that impede quantitative assessment and limit its accuracy and reproducibility are summarized, with special emphasis on SUV analysis.We describe current efforts to improve the accuracy of tumor uptake measurements, characterize overall metabolic tumor burden and heterogeneity of tumor uptake, and account for the effects of image noise.We also summarize recent developments in PET instrumentation and image reconstruction and their impact on tumor quantification.Finally, we offer our assessment of the current development needs in PET tumor quantification, including practical techniques for fully quantitative, pharmacokinetic measurements.
Abstract C14: Loss of haptotaxis facilitates invasion in LKB1-deficient melanoma
Authors: Keefe T. Chan, Sreeja B. Asokan, Tao Bo, Matthew E. Berginski, Wenjin Liu, Shelly D. Cochran, Norman E. Sharpless, James E. Bear
Journal: Cancer Research (2013)

Abstract Germline mutations in the serine/threonine kinase STK11/LKB1 are associated with Peutz-Jehgers Syndrome, which is characterized by hyperpigmentation of the oral mucosa. Inactivating somatic mutations occur in approximately 10-20% of melanomas; however, how the loss of LKB1 facilitates melanoma invasion remains poorly understood. Using cell lines derived from simultaneous activation of KRas and inactivation of LKB1 in melanocytes, we have investigated melanoma migration upon reconstitution with LKB1. Reexpression of LKB1 diminishes migration during wound healing, spheroid outgrowth into 3D collagen, and overall single cell speed in random motility assays. Furthermore, the formation of invadopodia is independent of LKB1 status in both human and mouse melanomas. Interestingly, using microfluidic devices we have found that loss of LKB1 abrogates the ability of cells to respond to gradients of extracellular matrix (haptotaxis) but does not impair their ability to chemotax to EGF. We have also recently developed a model of orthotopic implantation of multicellular tumor spheroids into the dermis of the mouse ear skin and have validated this approach by recapitulating the finding that LKB1 limits tumorigenesis. We are using this model to image local invasion in vivo by multiphoton microscopy and are currently examining the intriguing hypothesis that loss of extracellular matrix sensing is one aspect that contributes to metastatic migration. Citation Format: Keefe T. Chan, Sreeja B. Asokan, Tao Bo, Matthew E. Berginski, Wenjin Liu, Shelly D. Cochran, Norman E. Sharpless, James E. Bear. Loss of haptotaxis facilitates invasion in LKB1-deficient melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C14.
Virological Studies in Chronic Bronchitis
Authors: M. B. Eadie, E. J. Stott, N. R. Grist
Journal: BMJ (1966)

Though there is not likely to be one single cause for the com plex disease of chronic bronchitis, the hypothesis that viruses play an important part in the initiation or progression of this condition is at least tenable (Scottish Standing Medical Advisory Committee, 1963 ; Stuart-Harris, 1965) and the serious effect of influenza A infections on chronic bronchitics is well established (Stuart-Harris et al., 1953, Stuart-Harris and Hanley, 1957). Of the reported attempts to demonstrate a viral cause for acute exacerbations of chronic bronchitis those of Jack and Gandevia (1960) and Hennessy (1962) gave negative results. Serological studies have suggested an association between exacerbations and infections with respiratory syncytial virus (Sommerville, 1963) and influenza B, and possibly with para-influenza viruses (Stark et al., 1965). Carilli et al. (1964), using both serological and isolation techniques, showed a high incidence of virus infections in exacerbations of chronic bron chitis. Infections with rhinoviruses were not detected in any of these studies. The present investigation was designed to seek evidence of virus infections by observing a group of patients with chronic bronchitis in their homes for several years and studying episodes of respiratory illness by serological and isolation techniques designed to detect infections with most of the known respiratory viruses.
International trials registry is missing important information, study finds
Authors: J. Wise
Journal: BMJ (2009)

Researchers have found that important information is missing from many trials recorded on the international register of clinical trials ClinicalTrials.gov, a publicly accessible database of clinical trials managed by the US National Library of Medicine.

Joseph Ross, assistant professor of geriatrics at the Mount Sinai School of Medicine, New York, and colleagues sampled a cross section of trials on the registry. After excluding phase I safety trials, they identified 7515 trials that were registered within ClinicalTrials.gov after 31 December 1999 and whose record indicated trial completion by 8 June 2007. 

All of the trials reported the essential information required by the registry, but optional data including the primary outcome of …
Role of technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis. A comparative study.
Authors: J M Nolla-Sole, L Mateo-Soria, A Rozadilla-Sacanell, J Mora-Salvador, J Valverde-Garcia, D Roig-Escofet
Journal: Annals of the Rheumatic Diseases (1992)

The tumor suppressor protein p53 is a transcription factor that regulates apoptotic responses produced by genotoxic agents. Previous studies have reported that 7,12-dimethylbenz[<i>a</i>]anthracene (DMBA)-induced bone marrow toxicity is p53-dependent in vivo. Our laboratory has shown that DMBA-induced splenic immunosuppression is CYP1B1- and microsomal epoxide hydrolase (mEH)-dependent, demonstrating that the DMBA-3,4-dihydrodiol-1,2-epoxide metabolite (DMBA-DE) is probably responsible for DMBA-induced immunosuppression. DMBA-DE is known to bind to DNA leading to strand breaks. Therefore, we postulated that a p53 pathway is required for DBMA-induced immunosuppression. In the present studies, our data show that activated p53 accumulated in the nuclei of spleen cells in WT and AhR-null mice after DMBA treatment, but not in CYP1B1-null or mEH-null mice. These results suggest that DMBA activates p53 in a CYP1B1- and mEH-dependent manner in vivo but is not AhR-dependent. Ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein (ATR) are sensors for DNA damage that signal p53 activation. Increased ATM, phospho-ATM (Ser<sup>1987</sup>), and ATR levels were observed after DMBA treatment in WT, p53-null, and AhR-null mice but not in CYP1B1-null or mEH-null mice. Therefore, ATM and ATR seem to act upstream of p53 as sensors of DNA damage. Ex vivo immune function studies demonstrated that DMBA-induced splenic immunosuppression is p53-dependent at doses of DMBA that produce immunosuppression in the absence of cytotoxicity. High-dose DMBA cytotoxicity may be associated with p53-independent pathways. This study provides new insights into the requirement of genotoxicity for DMBA-induced immunosuppression in vivo and highlights the roles of ATM/ATR in signaling p53.
Immunohistochemical characterization of elastofibroma and exclusion of ABCC6 as a predisposing gene
Authors: M. Naouri, P. Michenet, N. Chassaing, L. Martin
Journal: British Journal of Dermatology (2007)

Journal Article Immunohistochemical characterization of elastofibroma and exclusion of ABCC6 as a predisposing gene Get access M. Naouri, M. Naouri Departments of Dermatology and Pathology, Hôpital Porte‐Madeleine, CHR d'Orléans, BP 2439, F‐45032 Orléans cedex, France Search for other works by this author on: Oxford Academic Google Scholar P. Michenet, P. Michenet Departments of Dermatology and Pathology, Hôpital Porte‐Madeleine, CHR d'Orléans, BP 2439, F‐45032 Orléans cedex, France Search for other works by this author on: Oxford Academic Google Scholar N. Chassaing, N. Chassaing Department of Genetics, CHU Purpan, Toulouse, France Search for other works by this author on: Oxford Academic Google Scholar L. Martin L. Martin Departments of Dermatology and Pathology, Hôpital Porte‐Madeleine, CHR d'Orléans, BP 2439, F‐45032 Orléans cedex, France Correspondence: L. Martin. E‐mail: ludovic.martin@chr‐orleans.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 4, 1 April 2007, Pages 755–758, https://doi.org/10.1111/j.1365-2133.2006.07735.x Published: 01 April 2007
Poly(N-isopropylacrylamide) hydrogels with interpenetrating multiwalled carbon nanotubes for cell sheet engineering
Authors: Yu-Shuan Chen, Pei-Chun Tsou, Jem-Mau Lo, Hsieh-Chih Tsai, Yan-Zhen Wang, Ging-Ho Hsiue
Journal: Biomaterials (2013)
SPRAIN OF CERVICAL SPINE CAUSING THROMBOSIS OF ANTERIOR SPINAL ARTERY
Authors: ROY R. GRINKER
Journal: JAMA (1927)

Trauma or excessive muscular activity may produce dislocation, fracture or fracture dislocation of a vertebra. Distortion of the vertebral column may also occur momentarily, the vertebrae quickly returning into normal alinement. According to Oppenheim, 1 in the very short period of temporary vertebral displacement, contusion, compression or tearing of the cord may take place.  Frazier 2 states that the mechanism of such vertebral sprains is an overstretching or laceration of the spinal ligaments, and according to the extent of ligamentous injury there may be more or less transitory disarrangement of the normal relationship of one vertebral body to the other. Only when the bodies do not return to their original relationship is the lesion converted into a true dislocation. In cases of localized cord injury without evidence of fracture or dislocation, the assumption is that the cord has been subjected to pressure by a temporary luxation.  Frazier gives, as the
Comrades in arms
Authors: D. Spence
Journal: BMJ (2009)

We weren’t totally convinced that the action was necessary or even that it would work—we cursed this interventionist, US style of attack. The standard issue equipment, the multi-vials and the syringes, were substandard and flimsy, and the syringes had too narrow a needle. I had decided to use my own equipment. But just like every practice across the county we obeyed our orders, rounded up suspects, and went on the vaccination offensive. 

We called up the reservists, pulled on …
A British Medical Association Lecture on CEREBRAL TUMOURS
Authors: H. S. Souttar
Journal: BMJ (1929)

CrEREBRAXL tuml-lours are unique in the nature and the variety of the symnptomns they lodluce, in the diagnostic problems they present, and in the difficulties which miiust be over- come by the surgeon who endeavours to approach them.Moreover, thLey are by no means uncommiion in every class of practice, and the general physiciani, the ophthlmaliiic surgeon, and the aural specialist must all be preparedi to m,eet them; they are more destructive to the patienit than any other class of tumour, and thev affect personality in a manner which must always arrest our interest and arouse our sympathy.There can be feew conditionis which make a more widespread appeal.In the short time at my disposal I propose to glance at cerebral tumours from tlhree points of view-tlhose of the phvsiologist, the physiciani, anid the sur geoni-anid to reply briefly to three questions: How do these tumourlis produce symptoms?lhat symiiptoms -do they produce?How nay they be approached?Naturally a full replv to these qiuestions would involve ani elaborate treatise, but even tteir brief consideration gives some insight into the problem-ls which confronit the cerebral surgeon.THE PRODUCTION OF SYMPTOMS.Thle brain differs from all the other organs of the body In the fect that it is enclosed in a rigid case, which entirely modifies the conditions of its circulationi, and in the existeince within and arounid it of a sewoodar v anid independenit circulation, that of the cerebro-spinal fluid.Tumours produce their effects not, as might be supposed, from the pressure they exert on the cerebral tissue, b)ut from the interference they produce with the arterio-venouis and the cerebro-spinal ciirculations.Let us first consider the latter.The cerebro-spinal fluid is contintuouslv secreted bv the choroid plexuses, chiefly in the lateral ventricles, and from these it flows through the foraml-ina of Monro into the thiifd ventricle, from which it is conveved by the aqueduct of Sylvius to the fourth ventricle, escaping by the foramina
Endoscopic Tumor Therapy
Authors: H. Neuhaus
Journal: Endoscopy (1989)

In palliative biliary tumor treatment, various methods achieve relief of symptoms owing to adequate bile drainage. Endoscopically placed endopros-theses are suitable for the majority of patients with malignant biliary stenoses. However, migration and clogging of stents frequently impair the success of therapy. Tumor debulking by laser therapy or intraluminal irradiation and endoscopically controlled implantation of self-expanding biliary stents with a large diameter and a small surface area may improve the long-term results. Peroral or percutaneous cholangioscopy facilitate the application and the follow-up checks of these recently developed methods. Endoscopy of the biliary tree is warranted to determine the future role of the various strategies in biliary tumor therapy.
Selenium may act as cancer inhibitor
Authors: Phil Gunby
Journal: JAMA (1981)

Mysterious, metallic selenium—17th in abundance among the earth's elements, potentially poisonous in some compounds, yet apparently essential to human health—has been cast over the years as both "hero" and "villain" among the trace substances. Now, another heroic role seems to be in the offing. Recent research reports spotlight selenium as a likely inhibitor of preneoplastic changes. One of the latest of these reports is from Daniel Medina, PhD, professor of cell biology, Baylor College of Medicine, Houston. He told an American Cancer Society seminar in Daytona Beach, Fla, that if introduced early in the process, selenium can inhibit virally or chemically induced tumorigenesis in animals. Medina cautions that until more is known about selenium toxicity levels in humans, "it is not recommended that people buy and consume this mineral as a prophylactic measure without any idea of how much they are taking. Chronic toxicity is possible because selenium is widely
Effect of oral fluticasone on refractory peptic esophageal stricture - a new therapeutic method
Authors: Q. Cai, S. Yarandi, R. Kung, J. Brown, H. Xu, Q. Cai
Journal: Endoscopy (2012)

Corrected by:Effect of oral fluticasone on refractory peptic esophageal stricture – a new therapeutic methodEndoscopy 2012; 44(S 02): E442-E442DOI: 10.1055/s-0034-1367649