tbuckley/cabot-search huggingface dataset:
Abstract 792: ASN002: A novel dual SYK/JAK inhibitor with strong antitumor activity
Authors: Sanjeeva Reddy, Nitin K. Damle, Aranapakam M. Venkatesan, Scott K. Thompson, Niranajan Rao, Roger A. Smith, Sandeep Gupta
Journal: Cancer Research (2015)

Abstract Spleen tyrosine kinase (SYK) and Janus kinase (JAK) play important roles in the pathogenesis of various types of lymphomas, solid tumors, myeloproliferative and inflammation disorders. Inhibition of these targets has been shown to suppress tumor growth in various preclinical and/or clinical studies. Most B-cell malignancies are driven by the B-cell receptor (BCR) pathway, and SYK plays a critical role in this pathway by initiating and amplifying the signal from the receptor. JAK kinases (JAK1, JAK2, JAK3 and TYK2), upon stimulation by various growth factors and cytokines, phosphorylate signal transducers and activators of transcription family proteins (STAT1 -5) which activate various downstream target genes. ASN002 is a novel and potent dual inhibitor of SYK and JAK kinases with IC50 values of 5-46 nM in biochemical assays. In mechanistic cell-based studies involving IgE and cytokine stimulations, ASN002 strongly suppressed the SYK and JAK family kinase signaling pathways measured as pLAT and pSTAT levels, respectively. The compound showed anti-proliferative activity in a broad panel of human cancer cell lines including DHL6, DHL4, OCI-LY10, H929, Pfeiffer, HT-1376, and Lovo, suggesting activity in both solid and hematological tumor types. In a multiple myeloma (H929) xenograft model, ASN002 exhibited significant efficacy in inhibiting tumor growth (&amp;gt;95%). It also significantly delayed the onset of hind limb paralysis in the human erythroleukemia (HEL) mouse model. ASN002 has good oral bioavailability, metabolic stability, is not a Pgp substrate, and shows little to no inhibition of CYP450 isozymes. ASN002 showed a favorable safety profile in rat and dog toxicology studies. A Phase I/II clinical study is being planned for the evaluation of ASN002 in lymphomas (diffuse large B cell lymphoma, mantle cell lymphoma, follicular lymphoma) and solid tumors. Citation Format: Sanjeeva Reddy, Nitin K. Damle, Aranapakam M. Venkatesan, Scott K. Thompson, Niranajan Rao, Roger A. Smith, Sandeep Gupta. ASN002: A novel dual SYK/JAK inhibitor with strong antitumor activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 792. doi:10.1158/1538-7445.AM2015-792
P-255 A randomized, placebo-controlled, double-blind phase II trial of peri-operative cimetidine in early colorectal cancer
Authors: M. Jameson, M. Arendse, M. Findlay, I. Bissett, S. Lolohea, J. Warren, F. Frizelle, J. Keating, G. Jacobson, C. Romano, R. van Dalen
Journal: Annals of Oncology (2015)
Antigen-Specific TH Cell Monitoring by CD154 Expression in Japanese Cedar-Specific SCIT
Authors: T. Nomura, I. Tsuge, C. Inuo, Y. Nakajima, K. Tanaka, N. Naruse, S. Suzuki, H. Ando, Y. Kondo, S. Saitoh, A. Urisu
Journal: Journal of Allergy and Clinical Immunology (2013)
Mechanism of Selectivity of an Angiogenesis Inhibitor From Screening a Genome-Wide Set of Saccharomyces cerevisiae Deletion Strains
Authors: Pierre J. Dilda, Anthony S. Don, Kara M. Tanabe, Vincent J. Higgins, John D. Allen, Ian W. Dawes, Philip J. Hogg
Journal: JNCI Journal of the National Cancer Institute (2005)

The synthetic tripeptide arsenical 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) is an angiogenesis inhibitor that targets the mitochondria of actively dividing but not quiescent endothelial cells, arresting their proliferation and causing apoptosis. Normal endothelial cells are much more sensitive to GSAO than tumor cells. To elucidate the mechanism of tumor cell resistance, we identified yeast genes that are necessary for resistance to GSAO.We screened a genome-wide set of 4546 Saccharomyces cerevisiae deletion strains to identify GSAO-sensitive strains. We then examined GSAO accumulation in and proliferation activity of endothelial cells (BAECs) and tumor cells treated with GSAO and modulators of pathways and proteins identified in the yeast screen. We also examined GSAO effects on proliferation of mammalian cells transfected with transporter protein constructs.Eighty-eight deletion strains were sensitive to GSAO. The most sensitive strains had deletions of genes whose products are involved in vacuolar function (corresponding to drug transport in mammalian cells) and glutathione synthesis. BAECs were more sensitive to GSAO than tumor cells, and cell sensitivity to GSAO was approximately proportional to cellular glutathione levels. Treatment of BAECs and tumor cells with MK-571, an inhibitor of multidrug resistance-associated protein (MRP), or with buthionine sulfoximine, an inhibitor of glutathione synthesis, increased their sensitivity to GSAO. Mammalian cells transfected with MRP1 or MRP2 were resistant to GSAO, whereas cells transfected with MRP3, MRP4, MRP5, P-glypoprotein, or breast cancer resistance protein were not.Differences in MRP activity and cellular glutathione levels contribute to the selectivity of GSAO for endothelial versus tumor cells. MRP1 and/or MRP2 may transport GSAO from resistant cells, with glutathione acting as a cotransporter. Genetic screening in yeast is a powerful tool for understanding drug action in mammalian cells.
Management of Adverse Drug Reactions with Suspected Immune Mechanisms in Latin America
Authors: Mario Sánchez Borges, Ricardo Cardona-Villa, Luis Felipe C. Ensina, Dirceu Sole, Alfredo Arias Cruz, Sandra González Díaz, Alejandra Macias-Weinmann, Maximiliano Gómez, Carlos Serrano, Mabel Noemi Cuello, Paola Toche Pinaud, Ruth Ramirez Giraldo, Miguel Vinuesa, Adolfo Salvatierra, Camila Telles, Djanira Andrade, Alicia De Falco, Gregorio Mercovich, Adriana Weisz, Edgardo J. Jares
Journal: Journal of Allergy and Clinical Immunology (2013)
Pulmonary Epithelial Cell-Derived Cytokine TGF-β1 Is a Critical Cofactor for Enhanced Innate Lymphoid Cell Function
Authors: Laura Denney, Adam J. Byrne, Thomas J. Shea, James S. Buckley, James E. Pease, Gaelle M.F. Herledan, Simone A. Walker, Lisa G. Gregory, Clare M. Lloyd
Journal: Immunity (2015)

Highlights•Epithelial-derived TGF-β drives pulmonary response to allergen•Epithelial TGF-β promotes GATA3-driven cytokine production by suppression of Sox4•TGF-β is chemoactive for innate lymphoid cells that express TGF-βRII•The local pulmonary environmental niche defines the nature of immune reactionsSummaryEpithelial cells orchestrate pulmonary homeostasis and pathogen defense and play a crucial role in the initiation of allergic immune responses. Maintaining the balance between homeostasis and inappropriate immune activation and associated pathology is particularly complex at mucosal sites that are exposed to billions of potentially antigenic particles daily. We demonstrated that epithelial cell-derived cytokine TGF-β had a central role in the generation of the pulmonary immune response. Mice that specifically lacked epithelial cell-derived TGF-β1 displayed a reduction in type 2 innate lymphoid cells (ILCs), resulting in suppression of interleukin-13 and hallmark features of the allergic response including airway hyperreactivity. ILCs in the airway lumen were primed to respond to TGF-β by expressing the receptor TGF-βRII and ILC chemoactivity was enhanced by TGF-β. These data demonstrate that resident epithelial cells instruct immune cells, highlighting the central role of the local environmental niche in defining the nature and magnitude of immune reactions.Graphical abstract
Deciphering the Genetic Complexity of Schizophrenia
Authors: Tyrone D. Cannon
Journal: JAMA Psychiatry (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Part 11: Pediatric Basic Life Support and Cardiopulmonary Resuscitation Quality
Authors: Dianne L. Atkins, Stuart Berger, Jonathan P. Duff, John C. Gonzales, Elizabeth A. Hunt, Benny L. Joyner, Peter A. Meaney, Dana E. Niles, Ricardo A. Samson, Stephen M. Schexnayder
Journal: Circulation (2015)
Nutritional Factors in Cataract
Authors: G E Bunce, J Kinoshita, J Horwitz
Journal: Annual Review of Nutrition (1990)

Age-related cataract is a condition characterized by multiple mechanisms and multiple risk factors. The mechanisms that bring about a loss in transparency include oxidation, osmotic stress, and chemical adduct formation. Risk factors for cataract include diabetes, radiation (ultraviolet B, x-ray), certain pharmaceutical substances, certain nutritional states, and possibly acute episodes of dehydration. Interaction occurs between and among mechanistic factors and risk factors. Thus nutrition must be considered as one part of a tapestry of intertwined events and responses. Certain experimental models for nutritional cataract have been useful for study of the cataractogenic process but are probably not important factors in the human disease. Little current evidence supports significant roles in human senile cataract for imbalances of tryptophan or other amino acids, deficiencies of calcium or selenium, or excessive intake of selenium. Overconsumption of galactose is likely to be hazardous only in subjects with genetic inability to metabolize this sugar. Vitamins with antioxidant potential (riboflavin, vitamin E, vitamin C, carotenoids) deserve further research scrutiny to ascertain their significance in cataract etiology. Excessive caloric intake needs to receive added emphasis as a factor contributing to cataract. Diabetes increases the likelihood of cataract three- to four-fold. Obesity, defined as more than 20% overweight, is considered a major risk factor for non-insulin-dependent, or type II, diabetes (69, 73). Weight control can be recommended as a prudent, safe, economic, and effective means of lowering risk probability for diabetes and the associated complication of cataract.
Reply: “What if . . . the National Heart, Lung, and Blood Institute Considers Tobacco?” and “Smoking Control Is a Priority to Promote Heart, Lung, Blood, and Sleep Health”
Authors: James Kiley, Stephen Mockrin, Michael Lauer, George Mensah, W. Keith Hoots, Yasin Patel, Nakela Cook, Amy Patterson, Gary Gibbons
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

From the Editorialists:

We thank Drs. Soriano and Morera for supporting the National Heart, Lung, and Blood Institute’s (NHLBI’s) recent Strategic Visioning effort to collectively identify the greatest unmet needs in heart, lung, blood, and sleep research (1). They are correct in noting the central role tobacco plays in many diseases that fall within the mission of the NHLBI. We are also grateful to Dr. Jiminez-Ruiz and colleagues from the European Respiratory Society's Tobacco Control Committee for their thoughtful letter and key literature highlighting the importance of strategies for the effective prevention and treatment of tobacco use to foster and preserve human health.

The points made in these letters illustrate the kind of feedback we hope to receive from the research community on this and other topics as we move to shape future research priorities. The NHLBI will certainly consider mission-specific compelling questions and critical challenges identified through this process relating to tobacco and its adverse effects on heart, lung, blood, and sleep health.

The NHLBI’s new Strategic Visioning forum (http://nhlbistrategicvisioning.ideascale.com/) provides the broad stakeholder community an opportunity to engage in real-time conversations around topics for the NHLBI to address over the next decade, including tobacco and many other important issues. We encourage our communities to actively participate in this novel process to shape our future research directions.

We believe that joint efforts by the NHLBI and the research, patient, and provider communities will bring optimal and sustained cardiopulmonary health within reach, with the potential to improve the lives of millions of individuals.
Abstract 5295: Latent class longitudinal modeling of CTCs in ER+ metastatic breast cancer patients
Authors: Terry Hyslop, Xuechan Li, Rui Duan, Mario Giuliano, Antonio Giordano, Marlana Orloff, Hallgeir Rui, James M. Reuben, Massimo Cristofanilli
Journal: Cancer Research (2015)

Abstract The baseline and longitudinal monitoring of circulating tumor cells (CTCs) demonstrated strong prognostic and predictive value in patients with metastatic breast cancer (MBC) irrespective of tumor subtype but particularly in ER+ disease. Utilizing a cohort of ER+ MBC patients, with longitudinal assessments of CTCs, we applied a novel statistical model to identify subgroups of CTC patterns that inform patient prognosis. This is a retrospective analysis of 516 patients with MBC who had CTCs serially enumerated as part of their disease evaluation and monitoring. Two-hundred and six patients with ER+ disease and at least 3 CTC measures were identified and constitute the cohort for this analysis. Peripheral blood samples (7.5 ml) collected within 30 days before starting any systemic treatment were drawn into CellSave tubes and processed within 72 hours of collection. The standardized US Food and Drug Administration-cleared CellSearch System was used to isolate and count CTCs. Two-stage models, consisting of patterns of trajectories of CTCs in stage 1, defined via a latent class zero-inflated Poisson model, followed by a probability weighted Cox model of survival outcomes were employed. Both overall survival (OS) and progression free survival (PFS) were considered separately. Model selection was based on Akaike Information Criteria (AIC). Three classes of CTC trajectories are identified (always low = L, 70.3%, controlled moderate = M, 20.9%, high uncontrolled = H, 8.7%) with significant differential OS (AHR M vs L 5.32, p&amp;lt;0.001, H vs L 10.41, p&amp;lt;0.001, H vs M 1.96, p = 0.039) and PFS (AHR M vs L 2.05, p&amp;lt;0.001, H vs L 4.24, p&amp;lt;0.001, H vs M 2.06, p = 0.015) in multivariable modeling adjusting for bone metastases (Y vs. N), number of metastatic sites, and Her2 status. In summary, longitudinal monitoring of CTCs in patients with ER+ MBC can provide additional prognostic stratification and predictive value compared to standard baseline assessment and could potentially assist in better therapy selection and specific efficacy monitoring. Citation Format: Terry Hyslop, Xuechan Li, Rui Duan, Mario Giuliano, Antonio Giordano, Marlana Orloff, Hallgeir Rui, James M. Reuben, Massimo Cristofanilli. Latent class longitudinal modeling of CTCs in ER+ metastatic breast cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5295. doi:10.1158/1538-7445.AM2015-5295
A comparison of the quality of participation of community affiliates and that of universities in the Northern California Oncology Group.
Authors: M M Koretz, P M Jackson, F M Torti, S K Carter
Journal: Journal of Clinical Oncology (1983)

The quality of participation in the performance of clinical trials of university members and community affiliates of the Northern California Oncology Group is evaluated and compared. The data, based on 738 patients on 33 protocols, were collected during a one year period, July 1, 1980--June 30, 1981. The comparisons are made on three types of criteria: accrual distribution, with respect to study phase and modality multiplicity; data quality, generally reflecting protocol adherence; and data completeness. The performance of the community affiliates was found to equal or surpass that of the university members in most measures. Therefore, it is concluded that the community affiliates are functioning as full and valuable participants in the Northern California Oncology Group.
Papillary and Follicular Thyroid Cancer: A Selective Approach to Diagnosis and Treatment
Authors: E L Mazzaferri
Journal: Annual Review of Medicine (1981)

Thyroid carcinoma comprises a group of widely differing tumors ranging from slow-growing, well-differentiated neoplasms that ordinarily have an excellent prognosis to anaplastic cancers that usually have a dismal out­ come. This review is concerned with differentiated thyroid cancers-papil­ lary and follicular-the most common types encountered clinically and about which the most controversy exists regarding management. Benign thyroid nodules are very common, whereas clinically detectable thyroid cancer is relatively rare. Accordingly, a selective approach to the management of thyroid nodules is necessary to avoid SUbjecting an unac­ ceptably large number of persons to surgery. When a nodule is found to be papillary or follicular thyroid cancer, opinions differ regarding optimal therapy. Indeed, lively debate continues, not only around the extent of surgery required, but also about the indica­ tions for therapeutic 1311 and the efficacy of thyroid hormone in controlling tumor growth. This is in part a consequence of the wide range of'biologic behavior displayed by these tumors, which makes the task of evaluating therapy difficult (1-3). Papillary and follicular thyroid cancers are often indolent neoplasms with a benign course, including many associated with prior head and neck irradiation (4). Even with distant metastases, patients may live for decades (5, 6). On other occasions death from differentiated thyroid cancer may occur within a few years of diagnosis. An understanding of the clinical behavior and prognosis of these tumors can lead to both an
Medroxyprogesterone acetate therapy in advanced breast cancer: the predictive value of androgen receptor expression.
Authors: S N Birrell, D M Roder, D J Horsfall, J M Bentel, W D Tilley
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine the predictive value of androgen receptor (AR) levels in primary tumors of women who undergo medroxyprogesterone acetate (MPA) therapy for advanced breast cancer after relapse on tamoxifen adjuvant therapy. METHODS Between 1984 and 1987 at Flinders Medical Centre, South Australia, 136 postmenopausal women received adjuvant tamoxifen therapy for lymph node-positive breast cancer. Estrogen receptor (ER), progesterone receptor (PgR), and AR levels, tumor size, and degree of axillary node involvement were determined at the time of diagnosis. The median follow-up period was 81 months; 89 women developed metastatic disease, 83 of whom subsequently received MPA (500 mg/d). The objective response rate ([RR] ie, complete response [CR] and partial response [PR]) and progression-free interval (PFI) were assessed in response to MPA therapy. Associations between RR, PFI, and primary tumor characteristics including ER, PgR, and AR levels were examined using the Mann-Whitney U test, Kaplan-Meier product-limit estimator, and Cox proportional hazards regression, as appropriate. RESULTS Thirty-two of 83 patients (38.6%) responded to MPA. RR was significantly associated with the presence of AR (P &lt; .001), but not with other primary tumor characteristics or duration of tamoxifen therapy. After initiation of MPA treatment, PFI increased with increasing concentration of AR in the primary tumor. CONCLUSION Response to MPA after adjuvant tamoxifen treatment for lymph node-positive breast cancer was positively associated with AR level in the primary tumor. This finding suggests that MPA action in breast cancer may be mediated in part by the AR.
Results of initial lymph node biopsy in homosexual men with generalized lymphadenopathy.
Authors: A M Levine, P R Meyer, P S Gill, R L Burkes, M Krailo, S Aguilar, J W Parker
Journal: Journal of Clinical Oncology (1986)

Persistent, generalized lymphadenopathy (PGL) is considered part of the acquired immunodeficiency syndrome (AIDS)-related complex. The clinical course is usually benign, although some patients may evolve to AIDS. Characteristic features on lymph node biopsy have been described. Recently, large series of PGL have been reported in which many study patients have not undergone initial diagnostic biopsy. The value of such biopsy has been questioned. We report the clinical, pathologic, and laboratory findings in six homosexual men initially considered as potential candidates for study of the natural history of PGL. They were excluded by initial lymph node biopsy, which revealed small-cleaved lymphoma in two, focal Kaposi's sarcoma in two, disseminated mycobacterium tuberculosis in one, and histoplasma encapsulatum in one. The clinical and laboratory data from these six patients were compared with those from 34 patients with biopsy-proven PGL; no statistically significant difference in any prebiopsy clinical parameter was found. We conclude that initial lymph node biopsy may reveal changes other than reactive hyperplasia in homosexual men with generalized lymphadenopathy.
Current Aspects of Infections and Diseases Related to Staphylococcus Aureus
Authors: H R Shinefield, J C Ribble
Journal: Annual Review of Medicine (1965)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Subtypes of Receptors for Serotonin
Authors: A Frazer, S Maayani, B B Wolfe
Journal: The Annual Review of Pharmacology and Toxicology (1990)

Interest in the physiological functions of 5-hydroxytryptamine (5-HT; seroto­ nin) has increased steadily since its discovery in the intestine (1) and in serum (2). Its identification in brain in the early 1950s (3), followed a decade later by the initial studies of its distribution in brain by histofluorescence (4), stimulated investigations of the possible behavioral functions of this in­ dolealkylamine. In addition to studies of its function in brain, a steady stream of investigations have described its possible functions in the periphery, particularly in the gastrointestinal tract (see 5) and, more recently, in the cardiovascular system (see 6). Indeed, the initial suggestion that there might be more than one type of receptor for 5-HT came from experiments on the isolated guinea pig ileum. Gaddum & Picarelli (7) demonstrated that only a portion of its contractile response to 5-HT could be blocked by high con­ centrations of morphine but that the remainder of the response could be