tbuckley/cabot-search huggingface dataset:
Trop-2 Induces Tumor Growth Through AKT and Determines Sensitivity to AKT Inhibitors
Authors: Emanuela Guerra, Marco Trerotola, Romina Tripaldi, Anna Laura Aloisi, Pasquale Simeone, Andrea Sacchetti, Valeria Relli, Antonella D'Amore, Rossana La Sorda, Rossano Lattanzio, Mauro Piantelli, Saverio Alberti
Journal: Clinical Cancer Research (2016)

Inhibition of AKT is a key target area for personalized cancer medicine. However, predictive markers of response to AKT inhibitors are lacking. Correspondingly, the AKT-dependent chain of command for tumor growth, which will mediate AKT-dependent therapeutic responses, remains unclear.Proteomic profiling was utilized to identify nodal hubs of the Trop-2 cancer growth-driving network. Kinase-specific inhibitors were used to dissect Trop-2-dependent from Trop-2-independent pathways. In vitro assays, in vivo preclinical models, and case series of primary human breast cancers were utilized to define the mechanisms of Trop-2-driven growth and the mode of action of Trop-2-predicted AKT inhibitors.Trop-2 and AKT expression was shown to be tightly coordinated in human breast cancers, with virtual overlap with AKT activation profiles at T308 and S473, consistent with functional interaction in vivo AKT allosteric inhibitors were shown to only block the growth of Trop-2-expressing tumor cells, both in vitro and in preclinical models, being ineffective on Trop-2-null cells. Consistently, AKT-targeted siRNA only impacted on Trop-2-expressing cells. Lentiviral downregulation of endogenous Trop-2 abolished tumor response to AKT blockade, indicating Trop-2 as a mandatory activator of AKT.Our findings indicate that the expression of Trop-2 is a stringent predictor of tumor response to AKT inhibitors. They also support the identification of target-activatory pathways, as efficient predictors of response in precision cancer therapy. Clin Cancer Res; 22(16); 4197-205. ©2016 AACR.
Unsuspected Urinoma of an Obstructed Kidney Detected in a Bone Scan in a Patient With Lung Cancer
Authors: Aurora Sainz-Esteban, María Isabel Jiménez, Juan Gabriel Villanueva, Amparo Cobo, Roberto Olmos
Journal: Clinical Nuclear Medicine (2014)

A 60-year-old woman with an adenocarcinoma of the lung was referred to our department for a bone scan to assess the extension of the metastatic bone disease. The images showed several foci of radiotracer uptake in the bone consistent with malignant involvement. Besides, a considerable accumulation of tracer was shown in the right perinephric region as well as in the renal pelvis. SPECT/CT images demonstrated a superior perirenal urine leak due to rupture of the collecting system. The leakage was treated by urinary catheter decompression with complete recovery after 4 weeks.
Abstract 2561: IKKα links inflammation and tumorigenesis in a mouse model of lung squamous cell carcinoma
Authors: Qun Jiang, Zuoxiang Xiao, Jami Willette-Brown, Timothy Back, Robert H. Wiltrout, Yinling Hu
Journal: Cancer Research (2012)

Abstract NF-kB plays critical roles in linking inflammation and carcinogenesis. The activation of NF-kB is regulated by the IkB Kinase Complex (IKK), composed of IKKα, IKKα, and NF-κB essential modulator (NEMO). We have established a mouse model of lung squamous cell carcinoma (SCC) by inactivating IKKα in vivo. However, IKKα's attributes relating to linkage between inflammation and lung SCC have not yet been well-defined. We now show that inactivation of IKKα in mice causes systemic chronic inflammation, which consequently promotes lung SCC initiation and progression. In mice with mutated IKKα, CD4 T cells, dendritic cells, and macrophages are all significantly increased in the spleen and lung. Proinflammatory cytokines and chemokines are also remarkably elevated in the lungs of these mice. An M2 macrophage phenotype is observed only in the lungs of old IKKα mutant mice, not in younger mice, suggesting the M1/M2 polarization may be driven by the proinflammatory microenvironment in these mice. Production of Th2 cytokines and IL-10 are elevated in CD4 T cells from the lungs of mice with mutated IKKα, and may contribute to M2 polarization during the chronic inflammation. In addition, depletion of macrophages in these mice can significantly reduce Th2 cytokine production, oxidative DNA damage, and shut down SCC development in the lungs, suggesting their important roles in inflammation-associated lung carcinogenesis. Together, our data suggest that IKKα may play important roles in linking inflammation and lung SCC tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2561. doi:1538-7445.AM2012-2561
Placental Blood as a Source of Hematopoietic Stem Cells for Transplantation into Unrelated Recipients
Authors: Joanne Kurtzberg, Mary Laughlin, Michael L. Graham, Clay Smith, Janice F. Olson, Edward C. Halperin, Gilbert Ciocci, Carmelita Carrier, Cladd E. Stevens, Pablo Rubinstein
Journal: New England Journal of Medicine (1996)

Transplantation of bone marrow from unrelated donors is limited by a lack of HLA-matched donors and the risk of graft-versus-host disease (GVHD). Placental blood from sibling donors can reconstitute hematopoiesis. We report preliminary results of transplantation using partially HLA-mismatched placental blood from unrelated donors.
Kinase Inhibition — A New Approach to the Treatment of Rheumatoid Arthritis
Authors: David A. Fox
Journal: New England Journal of Medicine (2012)

Two placebo-controlled trials reported in this issue of the Journal show the efficacy of an oral Janus kinase (JAK) inhibitor, tofacitinib, in the treatment of rheumatoid arthritis.1,2 If this agent is approved by the Food and Drug Administration (FDA) for use in patients with rheumatoid arthritis, clinicians will confront several complex questions. What is the rationale for targeting this family of kinases? How effective is tofacitinib as compared with other proven agents that are used to treat rheumatoid arthritis? What safety concerns need to be kept in focus? How should JAK inhibition be combined with other medications in the . . .
Impact of Internal Mammary Sentinel Node Imaging in Breast Cancer
Authors: Myriam Benamor, Claude Nos, Paul Fréneaux, Krishna B Clough
Journal: Clinical Nuclear Medicine (2003)

A 28-year-old woman underwent mammary lymphoscintigraphy for evaluation of the sentinel node status of a small infiltrating ductal carcinoma in the central, lower, and outer quadrant of the left breast confirmed by biopsy. The patient was scheduled for lumpectomy and sentinel node biopsy. Lymphoscintigraphy showed increased uptake at two sites of the peritumorally injected tracer (60 MBq; 1.6 mCi rhenium sulfur nanocolloid) in internal mammary nodes, two of which were located most proximal to the tumor and related to the tumor by two distinct lymphatic ducts. An axillary lymph node was also detected. At surgery, the gamma probe confirmed the location of all the hot spots, and four nodes were harvested: one axillary, two first internal mammary nodes in the third intercostal space, and one internal mammary node in the second intercostal space. Histologic analysis revealed that the axillary sentinel node was free of disease, but the two first intramuscular sentinel nodes were metastatic. The second-echelon internal mammary node above the sentinel nodes (second intercostal space) was free of disease. This case shows the benefit of imaging all the drainage pathways of a breast tumor and retrieving nonaxillary lymph nodes, which may be the only positive nodes. As a result of the findings, the patient's prognosis may be altered and the subsequent therapeutic approach may be modified. Although exclusive involvement of the internal mammary chain is well established and relatively rare (occurring in approximately 5% of cases), it is important to remember that the axillary status of a breast tumor is not the only major prognostic factor.
The Use of Molecular Methods in Infectious Diseases
Authors: L S Tompkins
Journal: New England Journal of Medicine (1992)

IN recent years a large number of articles have appeared in clinical journals describing contemporary molecular methods and their applications in clinical medicine. This review addresses four applications of molecular techniques in infectious diseases: they can be used to demonstrate relatedness between strains for epidemiologic investigations, to shed light on the pathogenesis or virulence of a strain, to facilitate the clinical diagnosis, and to identify the agents of syndromes whose causes are unknown.Molecular EpidemiologyTo find the cause of an infectious-disease outbreak, epidemiologists need to determine early on whether a single strain (or type) of microorganism is responsible for . . .
Abstract 542: Inoculated carcinoma associated fibroblasts and hormone independent murine mammary tumor growth
Authors: Ana Sahores, Victoria Fabris, Silvia Vanzulli, Claudia Lanari, Caroline A. Lamb
Journal: Cancer Research (2010)

Abstract Murine mammary carcinomas from the MPA-murine breast cancer model express estrogen and progesterone receptors and transit through different stages of hormone dependence. Hormone dependent (HD) tumors only grow in the presence of medroxyprogesterone acetate (MPA) and hormone independent (HI) variants are those that grow without hormone supply. In co-culture studies we have demonstrated that carcinoma associated fibroblasts (CAF) from HI tumors (CAF HI) can stimulate epithelial cell proliferation better than those from HD tumors (CAF HD). However, in vivo, CAF-HI inoculated together with purified epithelial cells (EPI) only increased tumor growth of EPI HI and they were not able to replace the hormone requirement of EPI HD. Thus, the aim of this study was to investigate the role of CAF HI enhancing HI tumor growth and to elucidate why CAF HI failed to stimulate HD cells in vivo. For this purpose murine C4-HI tumors were transplanted in BALB/c-wt (wt) or in BALB/c-GFP (GFP) mice. Mice were subcutaneously inoculated with EPI HI alone or co-mingled with CAF HI-wt (in GFP mice) or CAF HI-GFP (in wt mice) and the resulting tumors were excised at different time points. Fluorescence analysis of frozen sections indicated that inoculated CAF HI-GFP were detected 7 days after their inoculum in wt mice whereas they were no longer detected at later time points. To elucidate how CAF HI are able to enhance tumor growth when co-inoculated with EPI HI cells, we quantified polymorphonuclear (hematoxilin and eosin) and mast cells (toluidine blue staining) in the EPI HI + CAF HI group and in the EPI HI group and no significant differences were observed. In similar experiments when cells were inoculated intradermically to evaluate angiogenesis, and animals were sacrificed after different time points, we observed that on day 5, there was a significantly higher number of vessels in the co-inoculated group (Control 1.1±0.1; CAF HI 1.8± 0.8; EPI HI 2.0±0.7; EPI HI + CAF HI 3.3±0.5 p&amp;lt;0.05). In summary, we conclude that the inoculated CAF fail to induce HD growth because they do not persist in the tumor mass, although they may participate during the first stages of tumor growth favoring angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 542.
1397 SINGLE NUCLEOTIDE POLYMORPHISMS ASSOCIATED WITH SEROCLEARANCE OF HEPATITIS B SURFACE ANTIGEN IN CHRONIC HEPATITIS B PATIENTS WITH SEROCLEARANCE OF HBV DNA
Authors: H.-I. Yang, M.-H. Lee, J. Liu, C.-Y. Lee, Y.-R. Lin, C.-L. Jen, Y.-C. Chien, T.-N. Ho, C.-H. Chen, C.-J. Chen
Journal: Journal of Hepatology (2012)
THU0476-HPR Perceived influence of health status on sexual activity in ankylosing spondylitis patients:
Authors: K. Hansen Berg, A. Prøven, E. Almås, E.E.P. Benestad, M. Østensen, G. Haugeberg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondylitis (AS) is a chronic, systemic inflammatory rheumatic disease which affects the axial skeleton, but may also affect peripheral joints, tendons and internal organs. The disease which begins in the second or third decade may give rise to significant loss of function and impaired quality of life. Sexuality is an important part of quality of life. Only a few studies have explored this issue in AS patients. In a rheumatoid arthritis (RA) cohort, (74% females, mean (SD) age 56.5 (14.2) years), 1/3 of the patients reported their health statues to have a considerable influence on their sexual activity (1). <h3>Objectives</h3> To examined the impact of perceived influence of health status on sexual activity in AS patients. <h3>Methods</h3> This is a prospective observational study were patients with established AS seen in the outpatient clinic in three hospitals in the southern and eastern part of Norway, were asked to participate. A broad specter of data was collected which included: demographic, clinical (BASDAI, BASFI) and quality of life data (15ED) which also included a question on perceived influence of health status on sexual activity. <h3>Results</h3> Mean (SD) age in the 411 assessed patients, (66.6% men, 33.4% women), was 44.1 (13.9) years and disease duration 16.9 (11.8) years. In the patient cohort 89.8% were HLA-B27 positive, 45.0% reported to be ever users of biologics, 92.7% NSAID and 19.7% to be ever user of DMARD. Mean (SD) values was 3.2 (2.1) for BASDAI, 2.8 (2.2) for BASFI, 3.9 (2.5) for BAS-G, 2.5 (2.0) for BASMI, 0.56 (0.49) for HAQ, 13.7 (12.8) mm/hr for ESR and 8.4 (11.4) mg/l for CRP. 82% reported to have a partner with whom they currently had sex with and 75.8% were reporting to be married or cohabitant. As shown in the table 83% reported their health status to have no or little impact on their sexual activity. A statistically significant (p&lt;0.05) gender difference was observed where 85.3% men and 78.4% women reported no or little impact on their sexuality. <h3>Conclusions</h3> In contrast to what has been reported for RA (1/3) less than 1/5 of the AS patients reported their health status to have considerable influence on their sexual activity. Differences in gender distribution and age may partly explain these differences. <h3>References</h3> Helland Y, Dagfinrud H, Kvien TK. Perceived influence of health status on sexual activity in RA patients: associations with demographic and disease-related variables. Scand J Rheumatol. 2008 May-Jun;37(3):194-9 <h3>Disclosure of Interest</h3> None Declared
HSV-1 Vector-Delivered FGF2 to the Retina Is Neuroprotective but Does Not Preserve Functional Responses
Authors: Brian Spencer, Seema Agarwala, Laura Gentry, Curtis R. Brandt
Journal: Molecular Therapy (2001)

Fibroblast growth factor 2 (bFGF, FGF2) exhibits mitogenic, angiogenic, wound healing, and neuroprotective properties. Infusion of FGF2 in vivo to treat neurodegenerative disorders in animal models results in increased survival of damaged neurons, but these effects are transient. To test the feasibility of HSV vector-delivered FGF2 for neuroprotection, we inserted the FGF2 gene under the control of the HCMV immediate-early promoter into an attenuated avirulent HSV-1 vector. Transduction with FGF2/HSV-1 virus promoted survival of PC12 cells, induced differentiation of these cells to the neuronal phenotype in vitro, and protected PC12 neuronal cells from death induced by nerve growth factor withdrawal. The attenuated FGF2/HSV-1 virus was able to deliver and direct expression of the FGF2 gene in the eye. Delivery prior to light exposure in a rat model of retinal degeneration resulted in significant protection against photoreceptor loss. However, functional ERG responses were not detected. Treatment of normal eyes with the vector alone suppressed ERGs, which were only partially restored in eyes receiving the FGF2 vector. Thus, although the FGF2-HSV-1 virus induced preservation of cell and tissue structure, this was not sufficient to protect photoreceptor function. Fibroblast growth factor 2 (bFGF, FGF2) exhibits mitogenic, angiogenic, wound healing, and neuroprotective properties. Infusion of FGF2 in vivo to treat neurodegenerative disorders in animal models results in increased survival of damaged neurons, but these effects are transient. To test the feasibility of HSV vector-delivered FGF2 for neuroprotection, we inserted the FGF2 gene under the control of the HCMV immediate-early promoter into an attenuated avirulent HSV-1 vector. Transduction with FGF2/HSV-1 virus promoted survival of PC12 cells, induced differentiation of these cells to the neuronal phenotype in vitro, and protected PC12 neuronal cells from death induced by nerve growth factor withdrawal. The attenuated FGF2/HSV-1 virus was able to deliver and direct expression of the FGF2 gene in the eye. Delivery prior to light exposure in a rat model of retinal degeneration resulted in significant protection against photoreceptor loss. However, functional ERG responses were not detected. Treatment of normal eyes with the vector alone suppressed ERGs, which were only partially restored in eyes receiving the FGF2 vector. Thus, although the FGF2-HSV-1 virus induced preservation of cell and tissue structure, this was not sufficient to protect photoreceptor function.
P60 Cannabis Lung Causing Debilitating Emphysema: Are We On The Verge Of An Epidemic?
Authors: N. B. Chinnappa, K. Zalewska, D. Mckeon
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Cannabis (or marijuana) is the world’s most widely-used illicit drug, according to UN drug report 2012 prevalence of cannabis use between 15–64 years of age is around 1.7% in Europe and 2.6% in USA.<sup>1</sup> It is particularly prevalent amongst adolescents and young adults. As societies reconsider the legal status of cannabis, policy makers and clinicians require sound knowledge of the acute and chronic effects of cannabis. There has been surprisingly little research into its effects on respiratory health. In a rural region of North Wales we have noticed an increasing number of young patients presenting with precocious bullous emphysema associated with very high tobacco and cannabis usage. <h3>Methods</h3> A series of 8 patients presenting through the Emergency Department with an exacerbation of COPD were noted to have precocious COPD associated with high cannabis use. The age was between 35–48, all had both physiological and radiological signs of advanced emphysema. All had at least 10–20 years of cannabis usage smoking more than 5 ‘joints’ per day. Of these, 4 patients were significantly impaired to require long term oxygen therapy, and one is actively listed for a single lung transplant. All had normal levels of alpha 1 antitrypsin and chymotrypsin. <h3>Results</h3> We found young patients with debilitating COPD secondary to cannabis use i.e. as less as 10 years of use.<sup>2</sup> We postulate that cannabis smoking leads to severe COPD in young patients independent of genetic susceptibility, which is on the verge of increase. <h3>Conclusions</h3> The addition of cannabis to the tobacco, and high usage at a young age is leading to increase in the incidence of COPD in general and bullous emphysema as a phenotype in particular. We are concerned that the dangers of cannabis inhalation and these risks are not being appreciated by the wider health community. More research is needed to know the mechanisms of the inflammatory response secondary to cannabis smoking. <h3>References</h3> UN drug report 2012, United Nations Office on Drugs and Crime Tashkin DP. Effects of marijuana smoking on the lung.<i> Annals of the American Thoracic Society</i>. 2013;10(3):239–47
INSULIN CONVULSIONS
Authors: JACOB P. FROSTIG, J. SCHREIBER, C. R. BENNETT, G. F. THOMAS
Journal: American Journal of Psychiatry (1941)

1. The frequency of occurrence of the insulin convulsion in the published material, if not prevented, is established as being from 2.4 per cent at the lowest to 4.1 per cent at the highest level, relative to the number of shock days. 2. Convulsions in insulin shock treatment are divided into two groups: The myoclonoid vascular collapse and the epileptoid convulsion. It is contended that the epileptoid convulsion is infrequent and depends either upon an epileptic disposition, or upon previous brain injury. 3. The myoclonoid vascular collapse is preceded by a myoclonoid pre-convulsive phase; the relationship of the occurrence of this phase to the occurrence of the convulsion proper being about 19:1. In order to prevent convulsions of the myoclonoid vascular type the injection of 1⅞ grain sodium amytal during the myoclonoid prodrome is recommended. Such an injection must be repeated in case the myoclonoid twitchings reappear. In 19.4 per cent of all sodium amytal days a second injection was required. 4. By using this method, in 42 cases with a total of 2025 insulin days and 1445 shock days, the incidence of convulsions was reduced to 3 instead of the expected 46, the percentage being 0.2 per cent instead of 2.4 per cent. A comparison of the results of groups treated with the same method, except for the prevention of convulsions, has shown that the absence of convulsions had no effect on the trend of improvement. 5. No complications arose from the use of sodium amytal. On the contrary, a smoother progress of the shock was obtained.
771 SEQUENCE ANALYSIS OF THE HBV PreC/C REGION BY ULTRA-DEEP PYROSEQUENCING AS A PREDICTOR OF ADEFOVIR TREATMENT OUTCOME IN PATIENTS WITH HBeAg-POSITIVE CHRONIC HEPATITIS B
Authors: C. Rodriguez, S. Chevaliez, F. Darthuy, J.-M. Pawlotsky
Journal: Journal of Hepatology (2013)
Perceptual elements in brain mechanisms of acoustic communication in humans and nonhuman primates
Authors: David H. Reser, Marcello Rosa
Journal: Behavioral and Brain Sciences (2014)

Abstract Ackermann et al. outline a model for elaboration of subcortical motor outputs as a driving force for the development of the apparently unique behaviour of language in humans. They emphasize circuits in the striatum and midbrain, and acknowledge, but do not explore, the importance of the auditory perceptual pathway for evolution of verbal communication. We suggest that understanding the evolution of language will also require understanding of vocalization perception, especially in the auditory cortex.
Management of Refractory Fluid Retention with a Combination of L-Arginine Monohydrochloride and Mercurials
Authors: Lazaro I. Gidekel, Paul Sherlock, Ann S. Peterson, Parker Vanamee
Journal: New England Journal of Medicine (1960)

FLUID retention presents a problem in the management of many diverse clinical conditions. It is most commonly associated with congestive heart failure and Laënnec's cirrhosis, but may also be present in patients with diffuse or localized carcinomatosis that manifests as pleural effusion, ascites, lymphedema of extremities or generalized edema, and may be very difficult to mobilize.In many cases the fluid retention can be adequately controlled by the administration of mercurial diuretics,1 chlorothiazide and related compounds2 or carbonic anhydrase inhibitors.3 However, not uncommonly patients with fluid retention may not respond to these agents from the beginning or may become refractory . . .