tbuckley/cabot-search huggingface dataset:
Phase II study of weekly docetaxel and capecitabine in patients with metastatic gastric cancer (GC)
Authors: G. Catalano, M. Orditura, M. R. Diadema, G. Aurilio, F. Ciardiello, F. de Vita
Journal: Journal of Clinical Oncology (2005)

4207 Background: Docetaxel (T) and Capecitabine (X) are active drugs in GC with synergistic antitumor effects. This synergy is thought to occur from D-mediated upregulation of thymidine phosphorilase (dThdPhase). A recent phase I study suggested that weekly T would result in sustained dThdPhase expression and that X administration at times of maximum dThdPase upregulation would increase the activity of the combination (Nadella P, JCO, 2002). Based on this background, we conducted a phase II trial to assess the activity and toxicity of combination TX in metastatic GC pts. Methods: Eligibility required no prior CT, measurable disease, ECOG PS 0–2, adequate bone marrow, hepatic and renal functions. According to Nadella schedule, treatment consisted of T 36 mg/m2 IV on days 1,8 and 15 and X 625 mg/m2 PO BID on days 5–18 of a 4-week cycle for a minimum of 6 cycles. According to minimax two-stage design of Simon and evaluating a minimum activity of 30% with an alternative hypothesis of 50%, the accrual will be stopped if less than 6 major responses were obtained among the first 16 pts. Results: From 11/2003 to 11/2004,21 pts (M/F: 14/7; median age:60,range 45–68; ECOG PS 0/1/2: 10/6/5) were enrolled. A total of 94 cycles were given, with a median of 5 (range 1–8) per patient. Primary analysis of activity according to intention to treat, showed a RR of 37% (CR:6%) and SD in 25%, with a disease control in 62% of pts. The median response duration was 6.6 months (range 3.2–9.1 months).Toxicity according to NCI criteria was evaluated for all pts. Grade 3 / 4 neutropenia and stomatitis occurred in 5% of pts; grade 1/2 hand-foot syndrome was recorded in 14% of pts. Because of the mild toxicity, a dose reduction was required only in 6.1% of cycles. Conclusions: TX is active and tolerated as first-line outpatient treatment in metastatic GC. Furthermore the safety profile suggests that TX regimen could be considered a potential therapeutic option especially for pts with poor PS. Accrual to final sample (46 pts) is in progress. No significant financial relationships to disclose.
Top-down versus bottom-up perspectives on clinically significant memory reconsolidation
Authors: Terry Marks-Tarlow, Jaak Panksepp
Journal: Behavioral and Brain Sciences (2015)

Lane et al. are right: Troublesome memories can be therapeutically recontextualized. Reconsolidation of negative/traumatic memories within the context of positive/prosocial affects can facilitate diverse psychotherapies. Although neural mechanisms remain poorly understood, we discuss how nonlinear dynamics of various positive affects, heavily controlled by primal subcortical networks, may be critical for optimal benefits.
Abstract 17199: Platelet ROCK2 is an Important Mediator of Thrombotic Stroke
Authors: Hyung-Hwan Kim, Seo-Kyoung Hwang, Yong-Joo Ahn, Goo Taeg Oh, Lea M. Beaulieu, Jane E. Freedman, James K. Liao
Journal: Circulation (2011)

Background: The activation of platelets is the final common pathway for most ischemic strokes. However, the signaling pathways that lead to platelet activation are not well understood. The Rho-associated coiled-coil forming kinases (ROCKs) are important mediators of the actin cytoskeleton. Because changes in the actin cytoskeleton underlie platelet activation and aggregation, we hypothesize that ROCKs in platelets may play an important role in thrombus-mediated ischemic stroke. Methods and Results: Platelets from global ROCK2-deficient (ROCK2 -/- ) mice showed decreased thrombin-induced pseudopodia formation, collagen adhesion, and homo- and heterotypic aggregation compared with platelets from wild-type (WT) mice. To determine the role of platelet ROCK2 in thrombosis-mediated ischemic stroke, we generated a mouse strain with platelet-specific ROCK2 deficiency (ROCK2 Plt-/- ) using conditional ROCK2 flox/flox mice and platelet-specific PF4-Cre mice. ROCK2 Plt-/- mice were born at expected Mendelian ratios and did not show any obvious developmental or phenotypic abnormalities. One day before ischemic onset, arterial blood was withdrawn from donor mice (WT or ROCK2 Plt-/- mice), into PE-50 tubing, stored at room temperature for 2 hrs, and then kept at 4 °C for 22 hrs. Middle cerebral artery (MCA) occlusion was induced by injection of the coagulated blood into recipient WT mice. Laser Doppler flowmetry was used to confirm successful MCA occlusion. Following clot injection, an embolus of varying size was found in the proximal MCA of all mice at 24 hrs. Compared to WT→WT mice, ROCK2 Plt-/- →WT exhibited greater improvement in relative cerebral blood flow (rCBF) (19% vs. 92% reduction, p =0.0026). This correlated with decreased cerebral infarct size (67.6 ± 18.9 mm 3 vs. 126.3 ± 17.0 mm 3 , p&lt;0.05, n=6-9) and improved neurological deficit score (2.3 ± 0.4 vs. 3.5 ± 0.5, p =0.037, n=6-9). Conclusion: These finding indicate that ROCK2 in platelets is critical for thrombus formation and in mediating MCA occlusion in the clot-embolic model of stroke. These results suggest that inhibition of platelet ROCK2 may have therapeutic benefits in ischemic stroke.
PSA-activated proaerolysin as a prostate specific cancer therapy
Authors: Jeff L. Browning, Ralph Abi-Habib, Ravibhushan Singh, Carol Carter, Janelle Ortiz, Rosemina Merchant, J. Thomas Buckley, Samuel R. Denmeade, Arthur E. Frankel
Journal: Cancer Research (2006)

2178  Native proaerolysin is a channel-forming bacterial protoxin that is activated upon cleavage by host proteases such as furin. PRX302 is an engineered form of proaerolysin in which the furin cleavage site has been replaced with a sequence known to be preferred by the protease, prostate specific antigen (PSA). The goal of this study was to examine the suitability of PRX302 for use as a therapeutic agent in prostate cancer and benign prostatic hyperplasia as assessed by comparing proteolytic activation of PRX302 and native proaerolysin and their cytotoxicity towards PSA-producing and non-producing cell lines. Modification of native proaerolysin to PRX302 markedly altered the activity of each of the proteases (chymotrypsin, trypsin, furin, and thrombin) tested toward this protein. Activity toward proaerolysin was decreased 10-100 fold for each of the proteases tested except PSA, which showed a 4-fold increase in activity against the modified protein. Of all enzymes tested, only PSA cleaved more PRX302 than proaerolysin. Indeed the ratio of PRX302 to proaerolysin cleavage by PSA was more than 40 times that of any other protease tested. As expected, native proaerolysin was effectively cytotoxic at low pM concentrations in all cells tested (LNCaP, DU145, CWR22Rvi, PC3, PrEC, and RWPE2-W99). However, PRX302 was cytotoxic at low pM concentration only in normal (PrEC) and papilloma- transfected (RWPE2-W99) prostate cells, both of which produce active PSA. In conclusion, PRX302 appears to be preferentially activated by PSA and selectively kills PSA producing cells. PRX302 deserves further study for possible treatment of prostate cancer and benign prostatic hyperplasia.
Biological Antagonism: The Theory of Biological Relativity.
Authors: Gustav J. Martin
Journal: JAMA (1952)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Biologic Response to Intracavitary Interleukin-2/Lymphokine Activated Killer (IAK) Cells in the Treatmemt of Primary Malignant Brain Tumors
Authors: R. L. Hayes, M. Koslow, E. M. Hiesiger, H. Hochster, K. Hymes, E. Moore, D. M. Pierz, A. Wise, J. Ransohoff
Journal: Neuro-Oncology (1991)

A Phase I trial of intracavitary recombinant Cetus IL-2 and lymphokine-activated killer (IAK) cells was performed in 9 adult patients (pts) with recurrent glioma with Karnofsky scores ≦ 60; 8 pts Grade IV, 1 pt Grade III. Following leukapheresis, lymphocytes were activated ex vivo. Activated IAK and IL-2 were infused via an Ommaya reservoir implanted in the tumor cavity during reqperation. Repetitive bolus IL-2 was given MWF for two weeks (wks). This cycle was repeated 2 wks later and in similar 4 wk courses every 12 wks for pts with anti-tumor response or stable disease. Corticosteroid therapy was limited to treatment of IL-2 related CNS toxicity. There was no evidence of systemic toxicity, nor were changes observed in peripheral immunophenotypes. The reservoirs were aspirated prior to each infusion and analyzed. A progressive eosinophilia was noted in the aspirates in a cumulative IL-2 dose-dependent manner, with apparent priming between cycles. Lumbar CSF punctures obtained in two cases also demonstrated eosinophilia. Similarly, IL-2 levels increased in the aspirates in a cumulative dose related manner. Tissue specimens, obtained in 5 pts after therapy, demonstrated pericavitary necrosis with an eosinophilic infiltrate and perivascular mononuclear cells. There were two partial responses. The median survival for 8 pts with Grade IV tumors was >50 wks, with 3 pts still alive.
Disaster at Buffalo Creek. Loss of communality at Buffalo Creek
Authors: Kai T. Erikson
Journal: American Journal of Psychiatry (1976)

The survivors of the Buffalo Creek disaster suffered both individual and collective trauma, the latter being reflected in their loss of communality. Human relationships in this community had been derived from traditional bonds of kinship and neighborliness. When forced to give up these long-standing ties with familiar places and people, the survivors experienced demoralization, disorientation, and loss of connection. Stripped of the support they had received from their community, they became apathetic and seemed to have forgotten how to care for one another. This was apparently a community that was stronger than the sum of its parts, and these parts--the survivors of the Buffalo Creek flood--are now having great difficulty finding the personal resources to replace the energy and direction they had once found in their community.
Targeting glycogen synthase kinase-3 (GSK-3) in human melanoma
Authors: Roger Lo, Ramin Nazarian, Yang Zong, Anthoni Ribas, Owen Witte
Journal: Clinical Cancer Research (2008)

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA

A18 

In our functional survey of specific melanoma-associated alterations, we found a surprising anti-oncogenic role of beta-catenin signaling. Introduction of a protein-stabilized form of beta-catenin antagonized oncogene (activated Ras and c-Met)-driven transformation of human epidermal melanocytes (HEMs). Tracing the canonical beta-catenin pathway identified GSK-3, a negative regulator of beta-catenin, as a potential molecular target amenable to pharmacologic inhibition in melanoma cells. Treatment of oncogene-transformed HEMs with a small molecular GSK-3 inhibitor, BIO phenocopied the inhibitory effect of beta-catenin overexpression. Whereas the growth of primary HEMs and oncogene-transduced derivatives is exquisitely sensitive to inhibition by BIO treatment, the growth of patient-derived melanoma cell lines, in contrast, showed variable sensitivities (over two orders of magnitude) to pharmacologic GSK-3 inhibition. BIO synergized with the p53-MDM2 inhibitor, Nutlin-3, in the growth inhibition of susceptible melanoma cells. In addition, cell lines harboring NRAS mutations, compared to those with BRAF mutations or WT NRAS/BRAF alleles, are associated with increased resistance to GSK-3 inhibition. Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) of genomic mRNA profiles revealed enhanced cellular autophagy to be correlated with increased resistance to BIO-mediated growth inhibition. Relative BIO-resistance correlated with increased GFP-LC3 subcellular punctate localization, a reporter for enhanced autophagolysosomal flux. Additionally, pharmacologic inhibition of the autophagolysosomal pathway enhanced BIO-mediated growth inhibition. Thus, the growth of melanoma cells displays variable sensitivities to GSK-3 inhibition, and survival of melanoma cells in response to acute GSK-3 inhibition may be partially mediated by enhanced cellular autophagy.
The Aetiology and Pathology of Rickets from an Experimental Point of View.
Authors: V. Korenchevsky
Journal: JAMA (1923)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The Natural History of Asymptomatic Ventricular Pre-Excitation
Authors: Vincenzo Santinelli, Andrea Radinovic, Francesco Manguso, Gabriele Vicedomini, Simone Gulletta, Gabriele Paglino, Patrizio Mazzone, Giuseppe Ciconte, Stefania Sacchi, Simone Sala, Carlo Pappone
Journal: Journal of the American College of Cardiology (2009)
Attempted suicide among living co-twins of twin suicide victims
Authors: A Roy, N L Segal, M Sarchiapone
Journal: American Journal of Psychiatry (1995)

The authors hypothesized that significantly more living monozygotic than dizygotic co-twins of twin suicide victims would themselves have attempted suicide.They determined the absence or presence of an attempt at suicide at any time among 26 living monozygotic co-twins and nine living dizygotic co-twins of twins who had committed suicide.They found that 10 of the 26 surviving monozygotic co-twins but none of the nine surviving dizygotic co-twins had themselves attempted suicide.Although monozygotic and dizygotic twins may have some differing developmental experiences, these results contribute to findings of previous studies of suicide in twins in suggesting that genetic factors may play a role in suicidal behavior.
The Technic of Local Anesthesia.
Authors: Arthur E. Hertzler
Journal: JAMA (1925)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract MP044: Prediction of 10-year and Lifetime Risk for Cardiovascular Disease in Mexico: Results from a National Representative Survey in 2006
Authors: Andres Catzin-Kuhlmann, Rosalba Rojas, Ruy Lopez-Ridaura, Clicerio Gonzalez, Aida Jimenez-Corona, Martin Lajous
Journal: Circulation (2012)

Introduction: Mexico is undergoing a fast-paced epidemiologic transition, yet little is known about its cardiovascular risk. In the absence of Mexican prediction tools algorithms developed for other populations may be informative and a first step in the development of risk calculation tools specific to this population. Methods: We applied two US-based algorithms based on the Framingham Heart Study data to stratify 5,074 cardiovascular disease-free Mexican adults by 10-year and lifetime cardiovascular risk. We used data from the 2006 Mexican National Health and Nutrition Survey (ENSANUT), a publicly available complex multistage, stratified nationally representative survey. Participants were aged 20 to 82 years and represent 42 million Mexican adults. Ten-year and lifetime predicted risks were combined to define the following groups: low 10-year (&lt;10%)/low lifetime (&lt;39%) predicted risk, low 10-year (&lt;10%)/high lifetime (≥39%) predicted risk and high 10-year (≥10%) predicted risk or diagnosed diabetes. Results: While we estimated that according to these tools a slight majority of Mexican adults (56% or 24 million) are at low short-term/low lifetime predicted risk for cardiovascular disease, there are 10 million Mexican adults (24%) that despite a low short-term risk have a high lifetime predicted cardiovascular risk, while 20% (8 million) are at a high short-term risk for cardiovascular disease. Women had a higher prevalence of low short-term/low lifetime predicted risk (64 vs 46%), while men had a high short term predicted risk that was twice that of women (26 vs 14%). The prevalence of low short-term either with low or high lifetime predicted cardiovascular risk was somewhat higher in rural areas, but there was no substantial difference between participants from urban and rural areas in the prevalence of high short-term risk for cardiovascular disease. Conclusion: Half of Mexican adults have an elevated risk for developing cardiovascular disease during their lifetimes, but less than a half of those are identified using traditional short-term risk calculation tools only. This is the first exercise of this kind in Mexico, risk stratification was based on algorithms that may not be entirely applicable to Mexican population and require refinement.
Phase I trial of CT-2106 (polyglutamated camptothecin) administered weekly in patients (pts) with advanced solid tumors
Authors: A. Daud, C. Garrett, G. R. Simon, P. Munster, D. Sullivan, S. Stromatt, C. Allevi, B. Bernareggi
Journal: Journal of Clinical Oncology (2006)

2015 Background: CT-2106, a camptothecin (CPT) conjugate, is a topoisomerase I inhibitor. Covalent binding through the hydroxyl group of CPT to polyglutamate, a biodegradable polymer of glutamic acid, enhances CPT aqueous solubility and prevents opening of the lactone ring and subsequent CPT binding to albumin. Responses were observed in a Q3 week dosing study in which the maximum tolerated dose (MTD) was 75 mg/m 2 . Objectives of this study are to determine the MTD and pharmacokinetics (PK) of CT-2106 given weekly to pts with advanced cancer. Methods: Pts received CT-2106 (10 min IV infusion) on days 1, 8, and 15 of each 28 day cycle. Toxicity (NCI CTC v3) and tumor response (RECIST) were assessed. Plasma was analyzed for conjugated and unconjugated CPT by liquid chromatography and tandem mass spectrometry. Results: Enrollment is complete with 21 evualuable pts. Dose limiting toxicities (DLT) are shown in the table . Median age = 60 years (range 36–83), median doses = 6 (1–9), median prior therapies = 3 (1–6). Most pts (12) had melanoma. In a Q3 week study assessments of conjugated and unconjugated CPT demonstrated that CT-2106 provides prolonged exposure to conjugated CPT and slow, progressive release of active CPT from the polymeric backbone. The PK of unconjugated CPT is dependent on the disposition profile of conjugated CPT; unconjugated CPT elimination is formation rate limited. The distribution of conjugated CPT appears to be restricted to extracellular body fluids. Total clearance includes renal excretion documented by substantial urinary excretion levels and CPT cleavage via metabolic pathways. Accumulation of conjugated or unconjugated CPT was not observed with repeated Q3 week dosing. PK in this weekly dosing study will be presented. Conclusions: CT-2106 is generally well tolerated without the toxicities normally associated with CPT, specifically hemorrhagic cystitis and severe diarrhea. The MTD is 25–35 mg/m 2 in these heavily pretreated pts. [Table: see text] [Table: see text]
Tinnitus: Diagnosis/Treatment
Authors: Abraham Shulman
Journal: Annals of Internal Medicine (1991)

History of tinnitus research the origin of tinnitus common errors in the use of masking for relief of tinnitus tinnitus models - a basis for the evaluation of the pathophysiology of tinnitus psychophysical and psycho-acoustic correlations of tinnitus electrophysiology of the auditory system auditory brain stem response and tinnitus efferent auditory system pathways and tinnitus neurotransmitters conclusions epidemiology of tinnitus classification of tinnitus medical evaluation tinnitus evaluation medical audiologic tinnitus patient protocol steps in the medical-audiologic tinnitus patient protocol clinical types of tinnitus specific etiologies of tinnitus computer data analysis - tinnitus data registry impairment, handicap, disability, and tinnitus significance, prognosis, and prevention of tinnitus medical methods, drug therapy, and tinnitus control strategies diet surgical methods instrumentation electrical stimulation acupuncture psychological issues of tinnitus biofeedback hypnotherapy combined treatment methods and strategies for tinnitus control speculations and conclusions auditory brain stem response and tinnitus - case studies.